Orthopaedic Knowledge

Update® OKU®14
Editor

Leesa M. Galatz MD, MBA, FAAOS

Mount Sinai Professor and System Chair, Leni and Peter W. May
Department of Orthopedic Surgery, Icahn School of Medicine at
Mount Sinai, Mount Sinai Health System, New York, New York

Assistant Editor

Frederick M. Azar MD, FAAOS

Chief of Staff, Campbell Clinic, Professor and Sports Medicine
Fellowship Director, University of Tennessee-Campbell, Department
of Orthopaedic Surgery and Biomedical Engineering, Memphis,
Tennessee
Copyright

Board of Directors, 2021-2023

Felix H. Savoie III, MD, FAAOS
President

Kevin J. Bozic, MD, MBA, FAAOS

First Vice President
Paul Tornetta III, MD, FAAOS
Second Vice President
Michael L. Parks, MD, FAAOS
Treasurer

Daniel K. Guy, MD, FAAOS

Past President
Claudette M. Lajam, MD, FAAOS
Chair, Board of Councilors

Alfonso Mejia, MD, MPH, FAAOS

Chair-Elect, Board of Councilors
Joel L. Mayerson, MD, FAAOS
Secretary, Board of Councilors

Alexandra E. Page, MD, FAAOS

Chair, Board of Specialty Societies

Armando F. Vidal, MD, FAAOS

Chair-Elect, Board of Specialty Societies
Adolph J. Yates, Jr, MD, FAAOS
Secretary, Board of Specialty Societies

Lisa N. Masters
Lay Member
Chad A. Krueger, MD, FAAOS
Member at Large

Valerae O. Lewis, MD, FAAOS

Member at Large

Toni M. McLaurin, MD, FAAOS

Member at Large
Karen M. Sutton, MD, FAAOS
Member at Large

Thomas E. Arend, Jr, Esq, CAE

Chief Executive Officer (ex-officio)

Staff

American Academy of Orthopaedic Surgeons

Anna Salt Troise, MBA, Chief Commercial Office

Hans Koelsch, PhD, Director, Publishing

Lisa Claxton Moore, Senior Manager, Editorial

Steven Kellert, Senior Editor

Wolters Kluwer Health

Brian Brown, Director, Medical Practice

Tulie McKay, Senior Content Editor, Acquisitions

Stacey Sebring, Senior Development Editor
Sean Hanrahan, Editorial Coordinator

Erin Cantino, Portfolio Marketing Manager

Alicia Jackson, Senior Production Project Manager

Stephen Druding, Manager, Graphic Arts & Design

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The material presented in the Orthopaedic Knowledge Update ® ,

Fourteenth Edition has been made available by the American Academy of
Orthopaedic Surgeons (AAOS) for educational purposes only. This material
is not intended to present the only, or necessarily best, methods or
procedures for the medical situations discussed, but rather it is intended to
represent an approach, view, statement, or opinion of the author(s) or
producer(s), which may be helpful to others who face similar situations.
Medical providers should use their own, independent medical judgment, in
addition to open discussion with patients, when developing patient care
recommendations and treatment plans. Medical care should always be based
on a medical provider’s expertise that is individually tailored to a patient’s
circumstances, preferences and rights. Some drugs or medical devices
demonstrated in AAOS courses or described in AAOS print or electronic
publications have not been cleared by the Food and Drug Administration
(FDA) or have been cleared for specific uses only. The FDA has stated that
it is the responsibility of the physician to determine the FDA clearance status
of each drug or device he or she wishes to use in clinical practice and to use
the products with appropriate patient consent and in compliance with
applicable law. Furthermore, any statements about commercial products are
solely the opinion(s) of the author(s) and do not represent an Academy
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ISBN 978-1-9751-9746-9
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Published 2024 by the American Academy of Orthopaedic Surgeons

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Copyright 2024 by the American Academy of Orthopaedic Surgeons
Acknowledgments

Editorial Board
Orthopaedic Knowledge Update® 14
Leesa M. Gala , MD, MBA, FAAOS
Mount Sinai Professor and System Chair
Leni and Peter W. May Department of Orthopedic Surgery
Icahn School of Medicine at Mount Sinai
Mount Sinai Health System
New York, NY
Frederick M. Azar, MD, FAAOS
Chief of Staff, Campbell Clinic
Professor and Sports Medicine Fellowship Director
University of Tennessee-Campbell Clinic
Department of Orthopaedic Surgery and Biomedical
Engineering
Memphis, Tennessee
Martin I. Boyer, MD, FAAOS
Carol B. and Jerome T. Loeb Professor
Department of Orthopaedic Surgery
Washington University School of Medicine
Saint Louis, Missouri
Wesley H. Bronson, MD, MS
Assistant Professor
Department of Orthopaedic Surgery
Mount Sinai Hospital and Health System
New York, New York
Aaron M. Chamberlain, MD, MSc, MBA, FAAOS
Associate Professor
Department of Orthopaedic Surgery
Washington University School of Medicine
Barnes Jewish Hospital
Center of Advanced Medicine
Orthopedic Center in Chesterfield, Missouri
Saint Louis, Missouri
Cara A. Cipriano, MD, FAAOS
Chief, Orthopaedic Oncology
Associate Professor
Department of Orthopaedic Surgery
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania
David Joseph Ciufo, MD
Assistant Professor
Department of Orthopaedics and Physical Performance
University of Rochester
Rochester, New York
Jonah Hebert-Davies, MD, FRCSC, FAAOS
Associate Professor
Department of Orthopedics and Sports Medicine
Harborview Medical Center
University of Washington
Seattle, Washington
Kenneth J. Hunt, MD, FAAOS
Associate Professor
Chief of Foot and Ankle Surgery
Vice Chair—Quality, Patient Safety and Outcomes
Department of Orthopedics
University of Colorado School of Medicine
Aurora, Colorado
Francis Young-In Lee, MD, PhD, Hon MBA, FAAOS
Wayne O. Southwick Professor
Departments of Orthopaedics and Rehabilitation, Pathology,
and Biomedical Engineering
Yale School of Medicine, Yale University
Yale New Haven Hospital
New Haven, Connecticut
William M. Mihalko, MD, PhD, FAAOS
Professor and JR Hyde Chair of Excellence
Campbell Clinic Department of Orthopaedic Surgery and
Biomedical Engineering
The University of Tennessee Health Science Center
Chair, Joint Graduate Program in Biomedical Engineering
University of Tennessee Health Science Center
Chair, Department of Orthopaedic Surgery
Methodist LeBonheur Hospitals
Memphis, Tennessee
Calin Stefan Moucha, MD, FAAOS
Professor
Department of Orthopaedic Surgery
Icahn School of Medicine at Mount Sinai
Chief, Joint Replacement Surgery
Mount Sinai Health System
New York, New York
Bradford O. Parsons, MD, FAAOS
Professor of Orthopaedic Surgery
Vice-Chair of Education at the Leni and Peter W. May
Department of Orthopaedic Surgery
Director of Orthopedic Residency Program
Director of Mount Sinai Shoulder Fellowship
Icahn School of Medicine at Mount Sinai
Chief of Shoulder Surgery
Department of Orthopedics
Mount Sinai Hospital
New York, New York
Jonathan G. Schoenecker, MD, PhD, FAAOS
Professor and Jeffrey W. Mast Chair, Orthopaedics Trauma and
Hip Surgery
Department of Orthopaedics
Vanderbilt University Medical Center
Monroe Carell Jr. Children’s Hospital at Vanderbilt
Nashville, Tennessee
Beth Shubin Stein, MD, FAAOS
Associate Professor
Weill Cornell Medical College
Co-Director, Women’s Sports Medicine Center
Co-Founder, Patellofemoral Center
Hospital for Special Surgery
New York, New York
Jeffrey G. Stepan, MD, MSc
Assistant Professor
Department of Orthopaedic Surgery and Rehabilitative
Medicine
University of Chicago
Chicago, Illinois
Sabrina Strickland, MD, FAAOS
Associate Professor
Department of Orthopaedic Surgery
Weill Cornell Medical College
Attending Orthopaedic Surgeon
Department of Sports Medicine and Shoulder Service
Hospital for Special Surgery
New York, New York
Contributors

Timothy Achor, MD, FAAOS Associate Professor, University of

Texas Health Science Center at Houston, McGovern Medical School,
Memorial Hermann Hospital, Houston, Texas

Neel Anand, MD, FAAOS Medical Director, Spine Center,

Professor of Orthopaedics, Department of Orthopaedics, Cedars-
Sinai Medical Center, Los Angeles, California

Alexandre Arkader, MD, FAAOS Associate Professor of

Orthopedic Surgery, Pediatric Orthopedics and Orthopedic
Oncology, Perelman School of Medicine at University of
Pennsylvania, The Children’s Hospital of Philadelphia,
Philadelphia, Pennsylvania

Blair S. Ashley, MD Orthopaedic Surgeon, Main Line Health

Orthopaedics and Spine, Lankenau Medical Center, Wynnewood,
Pennsylvania

Kendrick Au, MD, MSc Department of Orthopaedic Surgery,

Health Sciences Centre, St. John’s, Newfoundland

Mohamed Awad, MD, MBA Research Services Professional,

Orthopedic Trauma and Fracture Surgery, Limb Restoration
Program, Department of Orthopedics, University of Colorado,
Anschu Medical Campus, Denver, Colorado

Aaron M. Baessler, MD Orthopaedic Surgeon, American Health

Network, Indianapolis, Indiana
Cristian A. Balcescu, MD Orthopaedic Spine Surgeon, Department
of Orthopaedic Surgery, Sheridan Orthopaedic Associates PC,
Sheridan, Wyoming

Keith D. Baldwin, MD, MSPT, MPH, FAAOS Associate Professor,

Division of Orthopaedic Surgery, Children’s Hospital of
Philadelphia, University of Pennsylvania, Philadelphia,
Pennsylvania

Raveendhara R. Bannuru, MD, PhD Assistant Professor, Division

of Rheumatology, Tufts Medical Center, Tufts University School of
Medicine, Boston, Massachuse s

Abhiram R. Bhashyam, MD, PhD Assistant Professor, Department

of Orthopaedic Surgery, Harvard Medical School, Boston,
Massachuse s

Gideon Blumstein, MD, MS Orthopaedic Spine Surgeon, Watkins

Spine Group, Cedars-Sinai Marina Del Rey Hospital, Marina Del
Rey, California

Barre Boody, MD Orthopedic Spine Surgeon, Indiana Spine

Group, Carmel, Indiana, Assistant Professor, Department of
Clinical Orthopedic Surgery, Indiana University School of
Medicine, Indianapolis, Indiana

Martin I. Boyer, MD, FAAOS Carol B. and Jerome T. Loeb

Professor of Orthopedic Surgery, Department of Orthopaedic
Surgery, Washington University in St. Louis, St. Louis, Missouri

Kendall Bradley, MD Assistant Professor, Department of

Orthopaedic Surgery, Duke University, Durham, North Carolina

Jacqueline M. Brady, MD, FAAOS, FAOA Associate Professor,

Department of Orthopaedics and Rehabilitation, Oregon Health
and Science University, Portland, Oregon
Robert L. Brochin, MD A ending Orthopedic Surgeon, Chicago
Hand and Orthopedic Surgery Centers, Schaumburg, Illinois

James A. Browne, MD Alfred R Shands Professor of Orthopaedic

Surgery, Department of Orthopaedic Surgery, University of
Virginia, Charlo esville, Virginia

Jessica Burns, MD, MPH Assistant Professor, Department of Child

Health, The University of Arizona College of Medicine - Phoenix,
Phoenix, Arizona

Alexandra K. Callan, MD Assistant Professor, Director of

Musculoskeletal Oncology, Department of Orthopaedic Surgery, UT
Southwestern Medical Center, Dallas, Texas

Jose A. Canseco, MD, PhD Assistant Professor, Spine Surgery,

Department of Orthopaedic Surgery, Rothman Orthopaedics at
Thomas Jefferson University Hospital, Philadelphia, Pennsylvania

James E. Cassat, MD, PhD Associate Professor, Departments of

Pediatrics; Pathology, Microbiology, and Immunology, and
Biomedical Engineering, Vanderbilt University Medical Center,
Nashville, Tennessee

Christina M. Nypaver Cebulko, MD Orthopaedic Hand Surgery

Fellow, Department of Orthopaedic Surgery and Rehabilitation
Medicine, University of Chicago, Chicago, Illinois

Peter N. Chalmers, MD, FAAOS Assistant Professor, Department

of Orthopaedics, University of Utah, Salt Lake City, Utah

Ferdinand J. Chan, MD, FAAOS Assistant Professor, Department

of Orthopaedic Surgery, Albert Einstein College of Medicine at
Montefiore Medical Center, Bronx, New York

Andrea H.W. Chan, MD, MA, FRCSC Assistant Professor,

Divisions of Plastic and Orthopaedic Surgery, Toronto Western
Hospital, The Hospital for Sick Children, University of Toronto,
Toronto, Ontario, Canada

Darwin Chen, MD, FAAOS Associate Professor, Department of

Orthopaedic Surgery, Icahn School of Medicine at Mount Sinai,
New York, New York

Frank E. Chiarappa, MD Chief, Orthopaedic Oncology, Department

of Orthopaedic Surgery, University of California - San Diego, San
Diego, California

Bonnie Y. Chien, MD Assistant Professor, Department of

Orthopedic Surgery, Columbia University, New York, New York

Samuel K. Cho, MD, FAAOS Chief of Spine Surgery, Mount Sinai

West, Professor, Department of Orthopaedics, Icahn School of
Medicine at Mount Sinai, New York, New York

R. Carter Clement, MD, MBA Associate Professor, Department of

Orthopaedic Surgery, Louisiana State University Health Sciences
Center, New Orleans, Louisiana

David Clever, MD, PhD Resident Physician, Department of

Orthopaedic Surgery, Washington University in St. Louis, St. Louis,
Missouri

Wayne Cohen-Levy, MD, MS Assistant Professor, Department of

Orthopaedic Surgery, Case Western Reserve School of Medicine,
University Hospitals/Cleveland Medical Center, Cleveland, Ohio

Ma hew Colman, MD, FAAOS, FAOA Spine Surgery and

Musculoskeletal Oncology, Associate Professor, Department of
Orthopedic Surgery, Rush University Medical Center, Chicago,
Illinois

Anna R. Cooper, MD, MPH, FAAOS Assistant Professor,

Department of Orthopaedic Surgery, Westchester Medical Center
Health Network / New York Medical College, Valhalla, New York

Roger Cornwall, MD, FAAOS Professor, Department of

Orthopaedic Surgery and Developmental Biology, Cincinnati
Children’s Hospital Medical Center, University of Cincinnati
College of Medicine, Cincinnati, Ohio

Kevin J. Cronin, MD, MS Assistant Professor, Florida Orthopaedic

Institute, Department of Orthopaedic Surgery and Sports Medicine,
University of South Florida, Tampa, Florida

Jason M. Cuéllar, MD, PhD, FAAOS Assistant Professor,

Department of Orthopaedic Surgery, Cedars-Sinai Medical Center,
Los Angeles, California

Vinod Dasa, MD, FAAOS Professor, Department of Orthopedic

Surgery, Louisiana State University Health Sciences Center, New
Orleans, Louisiana

Constantine A. Demetracopoulos, MD, FAAOS Assistant

Professor, Department of Orthopaedic Surgery, Hospital for Special
Surgery, New York, New York

Jaime R. Denning, MD, MS, FAAOS Associate Professor,

Department of Orthopaedic Surgery, Cincinnati Children’s
Hospital, University of Cincinnati, Cincinnati, Ohio

John A. deVries, MD, MS Assistant Professor, Kerk Kerkorian

School of Medicine, Department of Orthopaedic Surgery, University
of Nevada, Orthopaedic Surgeon, Orthopaedics and Spine Institute,
University Medical Center, Las Vegas, Nevada

Srikanth N. Divi, MD Assistant Professor, Department of

Orthopaedic Surgery, Northwestern University Feinberg School of
Medicine, Chicago, Illinois
Hicham Drissi, PhD Professor, Department of Orthopaedics,
Emory University, Atlanta, Georgia

Ian M. Duensing, MD Assistant Professor, Department of

Orthopaedic Surgery, University of Virginia, Charlo esville,
Virginia

Eric W. Edmonds, MD, FAAOS Professor of Orthopaedic Surgery,

University of California, San Diego, Rady Children’s Hospital San
Diego, San Diego, California

Andrew S. Fang, MD, FAAOS Chief of Orthopedics, Department

of Orthopedics, Musculoskeletal Oncology and Podiatry, Kaiser
South San Francisco, South San Francisco, California

Lacey Favazzo, PhD Instructor, Department of Orthopedics,

University of Colorado Anschu Medical Campus, Aurora,
Colorado

Yale A. Fillingham, MD, FAAOS Assistant Professor, Rothman

Orthopaedic Institute, Thomas Jefferson University, Philadelphia,
Pennsylvania

Jill C. Flanagan, MD, FAAOS Adjunct Assistant Professor,

Department of Orthopeadic Surgery, Children’s Healthcare of
Atlanta, Emory University, Atlanta, Georgia

Veronica Fleck, MS, RAC Director, Regulatory Affairs, MCRA, LLC,

Washington, DC

James H. Flint, MD, FACS, FAAOS Chief, Musculoskeletal

Oncology, Associate Professor, Department of Orthopedic Surgery,
Naval Medical Center San Diego, San Diego, California

Jeanne M. Franzone, MD, FAAOS Assistant Professor, Assistant

Professor of Orthopaedic Surgery and Pediatrics, Thomas Jefferson
University, Philadelphia, Pennsylvania
Ma hew R. Garner, MD, FAAOS Associate Professor, Department
of Orthopaedics and Rehabilitation, Penn State College of
Medicine, Hershey, Pennsylvania

Elizabeth B. Gausden, MD, MPH, FAAOS Department of Adult

Reconstruction and Joint Replacement, Hospital for Special
Surgery, New York, New York

Qingnian Goh, PhD Instructor of Orthopaedic Surgery, Cincinnati

Children’s Hospital Medical Center, University of Cincinnati
College of Medicine, Cincinnati, Ohio

S. Raymond Golish, MD, PhD, MBA, FAAOS Chief Medical

Officer, HCA Healthcare, JFK Medical Center, Palm Beach, Florida

L. Henry Goodnough, MD, PhD Assistant Professor, Orthopaedic

Trauma, Department of Orthopaedic Surgery, Stanford Medicine,
Stanford, California

Christina J. Gutowski, MD, MPH, FAAOS Assistant Professor,

Department of Orthopaedic Surgery, Cooper Medical School of
Rowan University and Cooper University Healthcare, Camden, New
Jersey

Hani Haider, PhD Professor, Director of Orthopaedic Biomechanics

and Advanced Surgical Technologies Laboratory, Department of
Orthopaedic Surgery and Rehabilitation, University of Nebraska
Medical Center, Omaha, Nebraska

Eni Halilaj, PhD Associate Professor, Mechanical Engineering,

Biomedical Engineering, and the Robotics Institute, Carnegie
Mellon University, Pi sburgh, Pennsylvania

William G. Hamilton, MD, FAAOS Adult Reconstruction

Fellowship Director, Anderson Orthopaedic Clinic, Alexandria,
Virginia
Warren C. Hammert, MD Professor of Orthopaedic Surgery and
Plastic Surgery, Department of Orthopaedic Surgery, Duke
University Medical Center, Durham, North Carolina

Erik N. Hansen, MD, FAAOS Associate Professor Clinical

Orthopaedic Surgery, Department of Orthopaedic Surgery,
University of California, San Francisco, California

Alicia K. Harrison, MD, FAAOS Associate Professor, Department

of Orthopaedic Surgery, University of Minnesota, Minneapolis,
Minnesota

Bre L. Hayden, MD Assistant Professor, Department of

Orthopaedic Surgery, Icahn School of Medicine at Mount Sinai,
New York, New York

Rex Haydon, MD, PhD, FAAOS Simon and Kalt Families Professor
of Orthopaedic Surgery, Associate Director, Molecular Oncology
Laboratory, U Chicago Medicine, Chicago, Illinois

Jensen K. Henry, MD Instructor in Orthopaedic Surgery,

Department of Orthopaedic Surgery, Hospital for Special Surgery,
New York, New York

Jessica H. Heyer, MD Assistant Professor of Orthopaedic Surgery,

Department of Pediatric Orthopaedic Surgery, Hospital for Special
Surgery, New York, New York

Jaclyn F. Hill, MD, FAAOS Associate Professor, Department of

Orthopaedic Surgery, Baylor College of Medicine, Houston, Texas

Alan S. Hilibrand, MD, MBA, FAAOS The Joseph and Marie Field
Professor of Spinal Surgery, Vice Chairman, Academic Affairs and
Faculty Development, Department of Orthopaedic Surgery,
Rothman Orthopaedics at Thomas Jefferson University Hospital,
Philadelphia, Pennsylvania
Jason C. Ho, MD Assistant Professor, Department of Orthopaedic
Surgery, Cleveland Clinic, Cleveland, Ohio

Joshua B. Holt, MD Assistant Professor, Department of

Orthopedics and Rehabilitation, University of Iowa Hospitals and
Clinics, Iowa City, Iowa

Jerry I. Huang, MD, FAAOS Professor, Department of

Orthopaedics and Sports Medicine, Program Director, UW
Combined Hand Fellowship, University of Washington Medical
Center, Sea le, Washington

Jessica L. Hughes, MD Assistant Professor, Department of

Orthopaedic Surgery, University of Pi sburgh, Children’s Hospital
of Pi sburgh, Pi sburgh, Pennsylvania

Marissa D. Jamieson, MD Assistant Professor, Department of

Orthopaedic Surgery, Foot and Ankle Division, University of
Colorado School of Medicine, Denver, Colorado

Eugene S. Jang, MD, MS Associate Physician, Department of

Musculoskeletal Oncology, Kaiser Permanente, Oakland, California

Nichole A. Joslyn, MD Reno Orthopedic Center, Reno, Nevada

Lisa A. Kafchinski, MD, FAAOS, FAOA Assistant Professor,

Department of Orthopaedic Surgery, University of Alabama at
Birmingham, Birmingham, Alabama

Sanjeev Kakar, MD, FAAOS, FAOA Professor, Department of

Orthopaedic Surgery, Mayo Clinic, Rochester, Minnesota

Brian A. Karamian, MD Instructor, Spine Surgery, Department of

Orthopaedic Surgery, University of Utah, Salt Lake City, Utah

Mehdi Kazemzadeh-Narbat, PhD, PMP, CQA Associate Director,

Regulatory Affairs, MCRA, LLC, Washington, DC
Meghan Kelly, MD, PhD Assistant Professor, Department of
Orthopaedic Surgery, Mount Sinai Icahn School of Medicine, New
York, New York

Beau J. Kildow, MD Assistant Professor, Department of

Orthopaedic Surgery and Rehabilitation, University of Nebraska
Medical Center, Omaha, Nebraska

Tae Won B. Kim, MD, CPE, FAAOS Assistant Professor,

Department of Orthopaedic Surgery, Cooper Medical School of
Rowan University and Cooper University Healthcare, Camden, New
Jersey

T. Jay Kleeman, MD, FAAOS Assistant Professor, Department of

Orthopedic Surgery, Foot and Ankle Division, University of
Colorado School of Medicine, Denver, Colorado

Christian Klemt, PhD Research Fellow, Bioengineering Laboratory,

Massachuse s General Hospital, Harvard Medical School, Boston,
Massachuse s

Conor P. Kleweno, MD, FAAOS Associate Professor, Department

of Orthopaedic Surgery, Harborview Medical Center, University of
Washington, Sea le, Washington

Michael L. Knudsen, MD Assistant Professor of Orthopedic

Surgery, Department of Orthopedic Surgery, Division of Shoulder,
Elbow and Sports Medicine, Columbia University Medical Center,
New York-Presbyterian Hospital, New York, New York

Young-Min Kwon, MD, PhD, FAAOS Professor, Harvard Medical

School, Vice Chair, Department of Orthopedic Surgery,
Massachuse s General Hospital, Director, Bioengineering
Laboratory, Massachuse s General Hospital, Harvard Medical
School, Boston, Massachuse s
Lisa La anza, MD, FAAOS Professor and Chair, Department of
Orthopaedics and Rehabilitation, Yale University, New Haven,
Connecticut

Samuel J. Laurencin, MD, PhD Adult Reconstruction Orthopaedic

Surgeon, Neurosurgery, Orthopaedics and Spine Specialists, PC,
Department of Orthopaedic Surgery, Waterbury Hospital,
Waterbury, Connecticut

Cassandra A. Lee, MD, FAAOS Professor, Department of

Orthopaedic Surgery, UC Davis School of Medicine, Sacramento,
California

Francis Young-In Lee, MD, PhD, Hon MBA, FAAOS Wayne O.

Southwick Professor, Departments of Orthopaedics and
Rehabilitation, Pathology, and Biomedical Engineering, Yale School
of Medicine, Yale University, Yale New Haven Hospital, New Haven,
Connecticut

Jonathan Lee, MD Orthopedic Spine Surgeon, Englewood Hospital,

Englewood, New Jersey

Nathaniel Lempert, MD Assistant Professor, Department of

Orthopaedics, Vanderbilt University Medical Center, Nashville,
Tennessee

Gregory S. Lewis, PhD Associate Professor, Department of

Orthopaedics and Rehabilitation, Mechanical Engineering, and
Biomedical Engineering, Pennsylvania State University, Hershey,
Pennsylvania

Kevin J. Li le, MD, FAAOS, FAOA Professor, Department of

Orthopaedic Surgery, Cincinnati Children’s Hospital Medical
Center, University of Cincinnati School of Medicine, Cincinnati,
Ohio
Milton T.M. Li le, MD, FAAOS, FAOA Assistant Professor,
Cedars-Sinai Orthopaedic Trauma Fellowship Director,
Orthopaedic Surgery Department, Cedars-Sinai Medical Center,
Los Angeles, California

Raymond W. Liu, MD, FAAOS Victor M. Goldberg Professor,

Department of Orthopaedic Surgery, Case Western Reserve
University, Rainbow Babies and Children’s Hospital, Cleveland,
Ohio

Stephanie L. Logterman, MD A ending Surgeon, Department of

Pediatric Orthopedic Surgery, Orlando Health Arnold Palmer
Hospital for Children, Orlando, Florida

Craig R. Louer, MD Assistant Professor, Department of

Orthopaedic Surgery, Vanderbilt University Medical Center,
Nashville, Tennessee

W.G. Stuart Mackenzie, MD, FAAOS Associate Fellowship

Director, Department of Orthopaedic Surgery, Nemours Children’s
Hospital - Delaware, Wilmington, Delaware

Bilal Mahmood, MD Assistant Professor of Orthopaedic Surgery,

Department of Orthopaedics and Physical Performance, University
of Rochester, Rochester, New York

Geoffrey S. Marecek, MD, FAAOS, FAOA Associate Professor,

Department of Orthopaedic Surgery, Cedars-Sinai Medical Center,
Los Angeles, California

Ryan Mayer, MD Orthopaedic Trauma Surgeon, Premier

Orthopaedic and Trauma Specialists, Los Angeles, California

Michael McDonald, DO Orthopaedic Trauma Fellow Emory at

Grady Orthopaedic Trauma Fellowship, Department of
Orthopaedic Surgery, Emory University, Atlanta, Georgia
Thomas Moore, JrMD Assistant Professor, Program Director,
Emory at Grady Orthopaedic Trauma Fellowship, Associate
Program Director, Emory University, Department of Orthopaedic
Surgery Residency, Atlanta, Georgia

Stephanie N. Moore-Lotridge, PhD Assistant Professor,

Department of Orthopaedics, Vanderbilt University Medical Center,
Nashville, Tennessee

Nicole Montgomery, MD, FAAOS Assistant Professor,

Department of Orthopaedic Surgery, Texas Children’s Hospital /
Baylor College of Medicine, Houston, Texas

Kevin A. Morash, MD, MEd, FRCSC Assistant Professor,

Department of Surgery, Western University, London, Ontario,
Canada

Lee Jae Morse, MD Chief of Orthopaedics and Sports Surgery,

Department of Musculoskeletal Oncology, Kaiser Oakland and
Richmond Medical Centers, Oakland, California

Anand M. Murthi, MD, FAAOS Chief, Shoulder & Elbow Surgery,

MedStar Union Memorial Hospital, Baltimore, Maryland Professor,
Department of Orthopaedic Surgery, Georgetown University School
of Medicine, Washington, DC

Surena Namdari, MD, MSc, FAAOS Professor, Rothman

Orthopaedic Institute, Department of Orthopaedic Surgery,
Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania

Sreeharsha V. Nandyala, MD Orthopaedic Surgeon, Adult and

Pediatric Spine Surgery/Robotic Spine Surgery, Nevada Orthopedic
and Spine Center, Las Vegas, Nevada

Regis O’Keefe, MD, PhD, FAAOS Fred C. Reynolds Professor and

Chair, Department of Orthopaedic Surgery, Washington University
School of Medicine, St. Louis, Missouri
Kamil T. Okroj, MD Spine Surgery Fellow, Department of
Orthopaedic Surgery, Northwestern University, Chicago, Illinois

Melissa Orr, BS Analyst, Department of Orthopaedics, Cleveland

Clinic, Cleveland, Ohio

Andrew Park, MD Surgeon, Department of Orthopaedic Surgery,

Kaiser Permanente, Panorama City, California

Cecilia Pascual-Garrido, MD, PhD Associate Professor,

Department of Orthopaedic Surgery, Washington University School
of Medicine in St. Louis, St. Louis, Missouri

Alpesh A. Patel, MD, MBA, FAAOS Vice Chair of Strategy,

Professor, Departments of Orthopedic Surgery and Neurosurgery,
Northwestern University Feinberg School of Medicine, Chicago,
Illinois

Karan S. Patel, MD Spine Surgery Fellow, Department of

Orthopaedic Surgery, Rush University, Chicago, Illinois

Karin A. Payne, PhD Associate Professor, Department of

Orthopaedics, University of Colorado Anschu Medical Campus,
Aurora, Colorado

Kevin J. Perry, MD, DPT Assistant Professor, Department of

Orthopaedic Surgery, LSU Health Shreveport, Shreveport,
Louisiana

Nicolas S. Piuzzi, MD Adult Joint Reconstruction Surgery,

Associate Staff, Adult Joint Reconstruction, Director of Research,
Cleveland Clinic, Orthopaedic and Rheumatologic Institute,
Cleveland, Ohio

Frank Johannes Plate, MD, PhD Associate Professor, Director of

Adult Reconstruction Research, Department of Orthopaedic
Surgery, University of Pi sburgh, Pi sburgh, Pennsylvania
Samuel Pollard, RAC General Manager, Vorpal Technologies, K.K,
Tokyo, Japan

Themistocles Protopsaltis, MD, FAAOS Chief, Division of Spine

Surgery, NYU Grossman School of Medicine, New York, New York

Noah J. Quinlan, MD Shoulder and Elbow Fellow, Department of

Orthopaedics and Sports Medicine, University of Washington,
Sea le, Washington

Benjamin F. Ricciardi, MD, FAAOS Assistant Professor,

Department of Orthopaedic Surgery, University of Rochester
School of Medicine, Rochester, New York

Kathleen D. Rickert, MD, FAAOS Assistant Professor,

Orthopaedic Surgery, University of California - San Diego, Rady
Children’s Hospital, San Diego, California

Jessica C. Rivera, MD, PhD, FAAOS Clinical Associate Professor,

Department of Orthopaedic Surgery, Louisiana State University
Health Science Center, New Orleans, Louisiana

Jesse L. Roberts, MD Assistant Professor, Department of

Orthopedics, University of Washington, Sea le, Washington

Augustine M. Saiz, JrMD Assistant Professor, Department of

Orthopaedic Surgery, University of California, Davis, Sacramento,
California

Khaled J. Saleh, MD, MPH, MHCM (Harv), FRCSC, CPE Clinical

Professor, Department of Surgery, Michigan State University, East
Lansing, Michigan, Clinical Professor Surgical Sciences, College of
Medicine at Central Michigan University, Mount Pleasant,
Michigan, Lifetime Associate National Research Council, National
Academies of Science, Washington, DC
Mara Schenker, MD, FAAOS Associate Professor, Chief of
Orthopaedics, Grady Memorial Hospital, Director of Orthopaedic
Trauma, Emory University, Department of Orthopaedics, Atlanta,
Georgia

Jonathan G. Schoenecker, MD, PhD, FAAOS Professor and Jeffrey

Mast Chair of Trauma and Hip Surgery, Department of
Orthopaedics, Vanderbilt University Medical Center, Nashville,
Tennessee

Lew C. Schon, MD, FAAOS Director of Orthopedic Innovation,

Institute for Foot and Ankle Reconstruction, Mercy Medical Center,
Baltimore, Maryland Professor, Department of Orthopedic Surgery,
NYU Grossman School of Medicine, New York, New York

Andrew M. Schwar , MD Assistant Professor, Department of

Orthopaedics and Rehabilitation, University of Iowa, Iowa City,
Iowa

Edward M. Schwarz, PhD Professor, Department of Orthopaedics,

University of Rochester, Rochester, New York

Thorsten M. Seyler, MD, PhD, FAAOS Assistant Professor,

Division of Adult Reconstruction, Co-Director, Adult
Reconstruction Fellowship, Associate Residency Director, Director,
Orthopaedic Biofilm Laboratory, Department of Orthopaedic
Surgery, Durham, North Carolina

Benjamin Shore, MD, MPH, FRCSC Co-Director, Cerebral Palsy

and Spasticity Center, Cerebral Palsy Endowed Chair, Director,
Pediatric Orthopaedic Fellowship, Associate Professor of
Orthopaedic Surgery, Harvard Medical School, Boston Children’s
Hospital, Boston, Massachuse s

Sean E. Slaven, MD Adult Reconstruction Fellow, Anderson

Orthopaedic Clinic, Alexandria, Virginia
Nicholas T. Spina, MD Assistant Professor, Orthopaedic Surgery,
University of Utah, Salt Lake City, Utah

Jeffrey G. Stepan, MD, MSc Assistant Professor, Department of

Orthopaedic Surgery and Rehabilitation Medicine, University of
Chicago, Chicago, Illinois

Joseph F. Styron, MD, PhD, FAAOS Associate Professor,

Department of Orthopaedic Surgery, Cleveland Clinic, Cleveland,
Ohio

Nina Suh, MD, FAAOS Assistant Professor, Department of

Orthopaedic Surgery, Emory University, Atlanta, Georgia

Narayan Sundaram, MD, MBA Assistant Professor, Department of

Radiology, University of Chicago, Chicago, Illinois

Ishaan Swarup, MD Assistant Professor Clinical Orthopaedic

Surgery, Department of Orthopaedic Surgery, University of
California, San Francisco, California

Eric W. Tan, MD, FAAOS Associate Professor, Department of

Orthopaedic Surgery, University of Southern California, Los
Angeles, California

Thomas W. Throckmorton, MD, FAAOS Professor, Campbell

Clinic Department of Orthopaedic Surgery and Biomedical
Engineering, The University of Tennessee Health Science Center,
Memphis, Tennessee

Gregory R. Toci, MD Resident, Orthopaedic Surgery, Department

of Orthopaedic Surgery, Rothman Orthopaedics at Thomas
Jefferson University Hospital, Philadelphia, Pennsylvania

Alison Toth, MD, FAAOS Associate Professor, Department of

Orthopaedic Surgery, Duke University, Durham, North Carolina
Vidyadhar V. Upasani, MD, FAAOS, FAOA Associate Professor of
Clinical Orthopedic Surgery, Department of Orthopedic Surgery,
University of California San Diego, Rady Children’s Hospital San
Diego, San Diego, California

Kenneth L. Urish, MD, PhD, FAAOS Associate Professor,

Department of Orthopaedic Surgery, University of Pi sburgh,
Pi sburgh, Pennsylvania

Colyn Watkins, MD Instructor in Orthopaedic Surgery,

Department of Orthopaedic Surgery, Harvard Medical School,
Boston Children’s Hospital, Boston, Massachuse s

David A. Weiner, MD Assistant Professor, Department of

Orthopaedic Surgery, Medstar Georgetown University Hospital,
Washington, DC

Mitchell C. Weiser, MD, MEng, FAAOS Assistant Professor,

Department of Orthopaedic Surgery, Albert Einstein College of
Medicine at Montefiore Medical Center, Bronx, New York

Jocelyn Wi stein, MD, FAAOS Associate Professor, Department of

Orthopaedic Surgery, Duke University, Durham, North Carolina

Daniel H. Wiznia, MD, FAAOS Assistant Professor, Department of

Orthopaedics and Rehabilitation, Yale University, New Haven,
Connecticut

Stephanie E. Wong, MD Assistant Professor Clinical Orthopaedic

Surgery, Department of Orthopaedic Surgery, University of
California, San Francisco, California

Melissa A. Wright, MD Department of Orthopaedic Surgery,

MedStar Union Memorial Hospital, Baltimore, Maryland

Vonda J. Wright, MD, MS, FAAOS Associate Professor of

Orthopaedic Surgery, University of Central Florida School of
Medicine, President, Hughston Orthopaedics Southeast, Orlando,
Florida

Gord Guo Zhu, MD, PhD Assistant Professor, Department of

Pathology, Cooper Medical School of Rowan University and Cooper
University Healthcare, Camden, New Jersey

Benjamin Zmistowski, MD Assistant Professor, Shoulder and

Elbow Division, Department of Orthopaedics, Washington
University, St. Louis, Missouri

Michael Zuscik, PhD Professor, Department of Orthopaedics,

University of Colorado Anschu Medical Campus, Aurora,
Colorado
Preface

It is our distinct pleasure to present to you the 14th edition of

Orthopaedic Knowledge Update ® . This textbook builds on the
fundamental principles set forth in previous editions, with
revisions and updates based on new evidence, outcomes, and
innovations in the recent literature. Every orthopaedic topic, from
principles and basic science to sports medicine, total joint
replacement, trauma, pediatrics, pathology, and oncology, is
represented and serves to enhance education not only of resident
physicians but of all orthopaedic surgeons seeking to remain
current in the literature and on developments in their subspecialty.
As in all the previous editions, OKU ® 14 is divided into easily
identifiable sections, which allows for quick reference. Annotation
of the bibliographic citations published within the past 5 years
assists readers and future authors in their literature searches. The
overall text is concise and easy to understand, which is largely
because of the collaborative effort between the authors, section
editors, and editorial staff, all of whom helped to collect,
synthesize, and condense vast amounts of information into one
updated, reader-friendly resource.
As with any publication of this quality, the true credit goes to the
contributing authors. We are indebted to these leaders, our
colleagues, for sharing their skills and knowledge and for
contributing their valuable time and effort to this worthwhile
project. They worked determinedly to ensure that the text would
continue to offer the newest and most important information that is
available. I believe OKU ® will remain the go-to text for residents
preparing for a new rotation or an examination as well as for
seasoned orthopaedic surgeons who need to stay abreast of the
most recent advances in the field. I am also grateful to our section
editors for their indispensable work. Each chapter had to pass their
scrutiny, not once but often two or three times, until each topic was
discussed to their expert satisfaction. Their dedication to the
accuracy of information ensures the robustness necessary for a
resource of this magnitude.
And, last but certainly not least, we would like to thank our
editorial and production teams that have proven to be the
powerhouses behind this very successful publication. To keep this
high-quality textbook as current as possible, they worked against
stringent publication deadlines, yet they managed to keep the
project moving smoothly forward through the entire production
process. Without these individuals working behind the scenes, such
an endeavor would never be possible.
It is our hope that residents, fellows, and surgeons alike will find
this edition beneficial. We are confident that it will uphold the high
standards of all the previous editions and will continue to provide
orthopaedic surgeons and surgeon trainees with essential
knowledge to support their practices.
Leesa M. Gala , MD, MBA, FAAOS
Editor
Frederick M. Azar, MD, FAAOS
Assistant Editor
Contents

Section 1: General Topics

SECTION EDITOR: William M. Mihalko, MD, PhD, FAAOS

Chapter 1
Orthopaedic Research
Vinod Dasa, MD, FAAOS, Raveendhara R. Bannuru, MD, PhD,
Jessica C. Rivera, MD, PhD, FAAOS

Chapter 2
Biostatistics
Melissa Orr, BS, Nicolas S. Piuzzi, MD

Chapter 3
Orthopaedic Patient Safety: Core Competencies and Communication
Skills
Aaron M. Baessler, MD, Thomas W. Throckmorton, MD, FAAOS

Chapter 4
Regulation of Orthopaedic Products
Veronica Fleck, MS, RAC, Mehdi Kazemzadeh-Narbat, PhD, PMP,
CQA, Samuel Pollard, RAC, S. Raymond Golish, MD, PhD, MBA,
FAAOS

Chapter 5
Health Policy
Mohamed E. Awad, MD, MBA, Khaled J. Saleh, MD, MPH, MHCM
(Harv), FRCSC, CPE
Chapter 6
Preoperative Evaluation and Postoperative Care of the Orthopaedic
Patient
Ian M. Duensing, MD, James A. Browne, MD

Chapter 7
Coagulation and Blood Management
William G. Hamilton, MD, FAAOS, Sean E. Slaven, MD

Chapter 8
Musculoskeletal Biomechanics and Biomaterials
Kenneth L. Urish, MD, PhD, FAAOS, Gregory S. Lewis, PhD, Eni
Halilaj, PhD

Chapter 9
Musculoskeletal Imaging Principles
John A. deVries, MD, MS, Narayan Sundaram, MD, MBA, Rex
Haydon, MD, PhD, FAAOS

Chapter 10
Patient Optimization
Frank Johannes Plate, MD, PhD, Andrew M. Schwartz, MD,
Thorsten M. Seyler, MD, PhD, FAAOS

Chapter 11
New Technology in Orthopaedic Surgery: Robotics, Artificial
Intelligence, and Machine Learning
Hani Haider, PhD, Beau J. Kildow, MD

Section 2: Translational Science and Emerging Technologies

SECTION EDITOR: Francis Young-In Lee, MD, PhD, Hon MBA,
FAAOS

Chapter 12
Structure and Biology of Normal and Diseased Bone
David Clever, MD, PhD, Cecilia Pascual-Garrido, MD, PhD, Regis
O’Keefe, MD, PhD, FAAOS

Chapter 13
Biomaterials and Implants: Regenerative Engineering Approaches for
Orthopaedics
Samuel J. Laurencin, MD, PhD, Wayne Cohen-Levy, MD, MS

Chapter 14
Musculoskeletal Mechanics and Kinesiology
Christian Klemt, PhD, Young-Min Kwon, MD, PhD, FAAOS

Chapter 15
Normal and Abnormal Fracture Healing
Francis Y. Lee, MD, PhD, Hon MBA, FAAOS, Hicham Drissi, PhD

Chapter 16
Articular Cartilage Biology, Osteoarthritis, Biologics, and Stem Cell
Therapy
Karin A. Payne, PhD, Lacey Favazzo, PhD, Michael Zuscik, PhD

Chapter 17
Muscle and Nerve Disorders
Qingnian Goh, PhD, Roger Cornwall, MD, FAAOS

Chapter 18
Orthopaedic Infections and Microbiology
James E. Cassat, MD, PhD

Chapter 19
Applications of Three-Dimensional Technologies in Orthopaedic
Surgery
Daniel H. Wiznia, MD, FAAOS, Lisa Lattanza, MD, FAAOS

Chapter 20
Inflammation and Immunology
Benjamin F. Ricciardi, MD, FAAOS, Edward M. Schwarz, PhD
Section 3: Trauma
SECTION EDITOR: Jonah Hebert-Davies, MD, FRCSC, FAAOS

Chapter 21
Polytrauma Care
Milton T. M. Little, MD, FAAOS, FAOA, Geoffrey S. Marecek, MD,
FAAOS, FAOA

Chapter 22
Management of Open Fractures
Kevin J. Perry, MD, DPT, Matthew R. Garner, MD, FAAOS

Chapter 23
Upper Extremity Trauma
Mara Schenker, MD, FAAOS, Michael McDonald, DO, Thomas
Moore Jr, MD

Chapter 24
Lower Extremity Trauma
Augustine M. Saiz Jr, MD, Ryan Mayer, MD, Timothy Achor, MD,
FAAOS

Chapter 25
Pelvic Trauma
L. Henry Goodnough, MD, PhD, Conor P. Kleweno, MD, FAAOS

Chapter 26
Spinal Trauma
Sreeharsha V. Nandyala, MD, Nicholas T. Spina, MD

Section 4: Shoulder
SECTION EDITOR: Bradford O. Parsons, MD, FAAOS

Chapter 27
Shoulder Anatomy, Biomechanics, Clinical Evaluation, and Imaging
Alicia K. Harrison, MD, FAAOS, Michael L. Knudsen, MD
Chapter 28
Rotator Cuff Disease, Calcific Tendinitis, Adhesive Capsulitis,
Throwing Shoulder, and Instability
Kevin J. Cronin, MD, MS, Surena Namdari, MD, MSc, FAAOS

Chapter 29
Shoulder Arthritis and Arthroplasty
Melissa A. Wright, MD, Anand M. Murthi, MD, FAAOS

Section 5: Elbow
SECTION EDITOR: Aaron M. Chamberlain, MD, MSc, MBA, FAAOS

Chapter 30
Anatomy, Biomechanics, Physical Examination, and Imaging of the
Elbow
Benjamin Zmistowski, MD

Chapter 31
Elbow Degenerative Conditions and Nerve Disorders
Robert L. Brochin, MD, Joseph F. Styron, MD, PhD, FAAOS, Jason
C. Ho, MD

Chapter 32
Tendinopathy, Throwing Injuries, and Elbow Ligament Reconstruction
Noah J. Quinlan, MD, Peter N. Chalmers, MD, FAAOS

Section 6: Hand and Wrist

Section Editors: Jeffrey G. Stepan, MD, MSc, Martin I. Boyer, MD,
FAAOS

Chapter 33
Anatomy, Clinical Examination, and Imaging of the Hand and Wrist
Martin I. Boyer, MD, FAAOS, Jeffrey G. Stepan, MD, MSc

Chapter 34
Bone and Soft-Tissue Infections and Vascular Conditions of the Hand
and Wrist
Bilal Mahmood, MD, Warren C. Hammert, MD

Chapter 35
Neuropathies and Hand Arthritis
Jeffrey G. Stepan, MD, Msc, Christina M. Nypaver Cebulko, MD

Chapter 36
Ligament Injuries of the Wrist
Nichole A. Joslyn, MD, Sanjeev Kakar, MD, FAAOS, FAOA

Chapter 37
Tendon Injuries and Tendinopathies of the Hand and Wrist
Kendrick Au, MD, MSc, Nina Suh, MD, FAAOS

Chapter 38
Hand and Wrist Injuries, Fractures, and Reconstruction: Microsurgery
and Replantation
Abhiram R. Bhashyam, MD, PhD, Jerry I. Huang, MD, FAAOS

Section 7: Hip and Femur

SECTION EDITOR: Calin Stefan Moucha, MD, FAAOS

Chapter 39
Anatomy and Biomechanics, Evaluation, Clinical Examination, and
Imaging of the Hip
Mitchell C. Weiser, MD, MEng, FAAOS, Ferdinand J. Chan, MD,
FAAOS

Chapter 40
Early Degenerative Conditions of the Hip
Erik N. Hansen, MD, FAAOS, Stephanie E. Wong, MD, Ishaan
Swarup, MD

Chapter 41
Muscular, Neurovascular, and Soft-Tissue Conditions of the Hip
Blair S. Ashley, MD, Yale A. Fillingham, MD, FAAOS
Chapter 42
End-Stage Hip Degeneration and Hip Reconstruction
Brett L. Hayden, MD, Darwin Chen, MD, FAAOS

Section 8: Knee
Section Editors: Sabrina Strickland, MD, FAAOS, Beth Shubin Stein,
MD, FAAOS

Chapter 43
Ligament Injuries to the Knee
Jacqueline M. Brady, MD, FAAOS, FAOA

Chapter 44
Articular Cartilage of the Knee: Defects, Degeneration, and
Preservation
Cassandra A. Lee, MD, FAAOS

Chapter 45
Meniscal Pathology, Repair, and Transplant
Jocelyn Wittstein, MD, FAAOS, Kendall Bradley, MD, Alison Toth,
MD, FAAOS

Chapter 46
Knee Arthritis and Reconstruction
Vonda J. Wright, MD, MS, FAAOS, Elizabeth B. Gausden, MD,
MPH, FAAOS

Section 9: Foot and Ankle

Section Editors: David Joseph Ciufo, MD, Kenneth J. Hunt, MD,
FAAOS

Chapter 47
Foot and Ankle Anatomy and Biomechanics
Marissa D. Jamieson, MD, T. Jay Kleeman, MD, FAAOS
Chapter 48
Degenerative Conditions and Osteonecrosis of the Foot and Ankle
Jensen K. Henry, MD, Constantine A. Demetracopoulos, MD,
FAAOS

Chapter 49
The Diabetic Foot
Bonnie Y. Chien, MD, Lew C. Schon, MD, FAAOS, Eric W. Tan, MD,
FAAOS

Chapter 50
Foot and Ankle Reconstruction
Meghan Kelly, MD, PhD

Section 10: Spine

SECTION EDITOR: Wesley H. Bronson, MD, MS

Chapter 51
Spine Anatomy
Samuel K. Cho, MD, FAAOS, David A. Weiner, MD, Jonathan Lee,
MD

Chapter 52
Spine Evaluation, Clinical Examination, and Imaging
Themistocles S. Protopsaltis, MD, FAAOS, Karan S. Patel, MD

Chapter 53
Cervical Degenerative Conditions
Jose A. Canseco, MD, PhD, Brian A. Karamian, MD, Gregory R.
Toci, MD, Alan S. Hilibrand, MD, MBA, FAAOS

Chapter 54
Thoracolumbar Conditions
Srikanth N. Divi, MD, Kamil T. Okroj, MD, Alpesh A. Patel, MD,
MBA, FAAOS
Chapter 55
Thoracolumbar Minimally Invasive Surgical Techniques
Jason M. Cuéllar, MD, PhD, FAAOS, Neel Anand, MD, FAAOS

Chapter 56
Spinal Column Infections
Barrett Boody, MD, Cristian A. Balcescu, MD

Chapter 57
Current Concepts in Primary Benign, Primary Malignant, and
Metastatic Tumors of the Spine
Gideon Blumstein, MD, MS, Matthew W. Colman, MD, FAAOS,
FAOA

Section 11: Pediatrics

SECTION EDITOR: Jonathan G. Schoenecker, MD, PhD, FAAOS

Chapter 58
Pediatric Shoulder, Upper Arm, and Elbow Trauma
Jessica H. Heyer, MD, Alexandre Arkader, MD, FAAOS

Chapter 59
Pediatric Forearm, Wrist, and Hand Trauma
Kathleen D. Rickert, MD, FAAOS, Jessica Burns, MD, MPH

Chapter 60
Pediatric Upper Extremity Disorders
Andrea H.W. Chan, MD, MA, FRCSC, Kevin J. Little, MD, FAAOS,
FAOA

Chapter 61
Pediatric Pelvis, Hip, and Femur Trauma
Stephanie L. Logterman, MD, Keith D. Baldwin, MD, MSPT, MPH,
FAAOS

Chapter 62
Pediatric Knee, Lower Extremity, and Ankle Fractures
Jaime R. Denning, MD, MS, FAAOS

Chapter 63
Pediatric Hip Disorders
Vidyadhar V. Upasani, MD, FAAOS, FAOA, Jessica L. Hughes, MD

Chapter 64
Pediatric Lower Extremity and Foot Disorders
Jill C. Flanagan, MD, FAAOS, Jaclyn F. Hill, MD, FAAOS, Raymond
W. Liu, MD, FAAOS

Chapter 65
Pediatric Athletic Injuries
Eric W. Edmonds, MD, FAAOS

Chapter 66
Pediatric Spine Disorders and Trauma
Craig R. Louer, MD, R. Carter Clement, MD, MBA, Joshua B. Holt,
MD

Chapter 67
Pediatric Skeletal Dysplasias, Connective Tissue Disorders, and
Other Genetic Conditions
W. G. Stuart Mackenzie, MD, FAAOS, Kevin A. Morash, MD, MEd,
FRCSC, Jeanne M. Franzone, MD, FAAOS

Chapter 68
Pediatric Neuromuscular Disorders
Colyn Watkins, MD, Benjamin J. Shore, MD, MPH, FRCSC

Chapter 69
Pediatric Musculoskeletal Infection, Inflammatory Conditions, and
Nonaccidental Trauma
Stephanie N. Moore-Lotridge, PhD, Nathaniel Lempert, MD,
Jonathan G. Schoenecker, MD, PhD, FAAOS

Section 12: Musculoskeletal Oncology and Pathology

SECTION EDITOR: Cara A. Cipriano, MD, FAAOS

Chapter 70
Evaluation and Management of Musculoskeletal Tumors
Anna R. Cooper, MD, MPH, FAAOS, Nicole Montgomery, MD,
FAAOS

Chapter 71
Benign Tumors and Tumorlike Conditions of Bone
Frank E. Chiarappa, MD, James H. Flint, MD, FACS, FAAOS

Chapter 72
Sarcomas of Bone
Alexandra K. Callan, MD, Jesse L. Roberts, MD, Andrew Park, MD

Chapter 73
Metastatic Tumors of Bone
Eugene S. Jang, MD, MS, Lee Jae Morse, MD, Andrew S. Fang,
MD, FAAOS

Chapter 74
Benign Soft-Tissue Tumors and Masses
Lisa A. Kafchinski, MD, FAAOS, FAOA

Chapter 75
Soft-Tissue Sarcomas
Tae Won B. Kim, MD, CPE, FAAOS, Christina J. Gutowski, MD,
MPH, FAAOS, Gord Guo Zhu, MD, PhD

Index
S E CT I ON 1
General Topics
SECTION EDITOR
William M. Mihalko, MD, PhD, FAAOS
C H AP T E R 1

Orthopaedic Research
Vinod Dasa MD, FAAOS, Raveendhara R. Bannuru MD, PhD,
Jessica C. Rivera MD, PhD, FAAOS

Dr. Dasa or an immediate family member is a member of a speakers’ bureau or has made paid presentations
on behalf of Bioventus and Pacira Biosciences; serves as a paid consultant to or is an employee of Bioventus,
Cymedica, and Pacira Biosciences; has stock or stock options held in Cymedica, Doc Social, Goldfinch
Consulting, mymedicalimages.com, Ortho Lazer, and SIGHT Medical; and has received research or
institutional support from Cartiheal and Cymedica. Dr. Rivera or an immediate family member is a member of a
speakers’ bureau or has made paid presentations on behalf of NuVasive and serves as a board member,
owner, officer, or committee member of American Academy of Orthopaedic Surgeons, Limb Lengthening and
Reconstruction Society, and Orthopaedic Research Society. Neither Dr. Bannuru nor any immediate family
member has received anything of value from or has stock or stock options held in a commercial company or
institution related directly or indirectly to the subject of this chapter.

ABSTRACT
Evaluating the quality and relevance of research is a foundational principle
of any healthcare provider. It is important to review the tools and
mechanisms to evaluate the various types of research and their quality.
There are multiple types of publications, with open access articles becoming
more and more popular. Orthopaedic surgeons must be aware of the
benefits and pitfalls of these new options. Clinical practice guidelines are an
important part of clinical management and are important in healthcare
policy; orthopaedic surgeons must be able to evaluate the development and
interpretation of guidelines.
Keywords: basic science; clinical practice guidelines; clinical science;
translational research

Introduction
Basic science data in their fundamental state would seem to be universally
understood and appreciated, yet it has been shown that what are thought of
as objective and unbiased data can be interpreted through a variety of
perspectives and paradigms. There has never been a more pressing time for
scientists, clinicians, and the general public to appreciate the complexity and
fragility of science. It must be understood that methodology, design,
analysis, and interpretation across all disciplines in a manner that serves the
public good will allow advancement along a meaningful and unbiased path.

Importance of Clinical and Basic Science Research

in the Field of Orthopaedics
The notion of transferring knowledge gained in the laboratory to the bedside
is a foundational component of medical research. 1 Orthopaedic surgery has
seen tremendous advances based on laboratory and bench science. Examples
range from the development of new biomaterials, including ceramic to
polyethylene with implant survivorship lasting 35 years, to the elucidation of
mechanisms of tissue healing that has informed best practices for
rehabilitation. 2 More recently, increasing interest in the biologic aspects of
the musculoskeletal system has informed the development of novel
therapeutic advances focused on enhancing the biologic properties of
healing. From platelet-rich plasma to gene therapy for chronic conditions
such as arthritis and basic and translational research, these new approaches
will pave the way for modern biologic treatments for conditions that have
long been prevented from robust nonsurgical treatments. 3

Clinical Translation of Basic Science to the Bedside

There are many types of research involved in understanding a clinical
disorder, developing and evaluating possible therapeutic agents,
implementing a new therapy, studying the outcomes, and even compiling
guidelines for prevention and treatment. This concept is termed benchtop to
bedside. Basic science research starts at the benchtop, using laboratory
methods to study fundamental mechanisms of a disease. Genetic, molecular,
and cellular pathways may be elucidated using basic science methods.
Underlying knowledge gained from basic science informs understanding of
disease pathophysiology and therapeutic design.
Preclinical research is often also considered basic science but links
fundamental laboratory findings with clinical disease. In vitro models, such
as cell and tissue cultures, small animal models, and even simulated
modeling all are types of preclinical research that link benchtop findings to
be er understand how diseases can be managed. Preclinical research also
includes studying disease and therapies in large animals. Both in vitro or
small animal models and large animal models are required to study a new
therapy, including new drugs, prior to human testing. Once preclinical
research results in a new therapy that is well tested in these models, early
clinical research can begin.
Each of these steps from very basic research to study of human subjects
must be linked toward a common goal to advance the treatment of a human
disease or improve public health. This is the essence of clinical translation or
translational science. The National Institutes of Health National Center for
Advancing Translational Sciences defines translational science as the “field
of investigation focused on understanding the scientific and operational
principles underlying each step of the translational process.” 4 By focusing
on translation, basic and clinical researchers avoid performing research for
the sake of research, but instead for an end goal toward improving human
and public health.

Knowing the Specifics of How Research is

Conducted and How to Read and Interpret Clinical
Studies
Reviewing and synthesizing research is critical for any medical professional
to not only remain aware of current trends but to ensure a proper
understanding of foundational principles within orthopaedics. For potential
researchers, understanding historical work and current practices points to
knowledge gaps and frames new questions and areas of investigation to
support the translation of basic science to clinical care.
Healthcare professionals may read studies for a variety of reasons but
require competencies for lifelong learning. These include critical and
creative thinking, problem analysis, gathering and organizing information,
abstract reasoning, interpretive and assessment skills, insight and intuition
in generating knowledge, effective communication, and information literacy.
5

Reading and interpreting scientific literature requires a deliberate and

methodologic approach. The type of literature sought will depend on
whether the learner is looking for research ideas, enhancing knowledge on a
given topic, or looking for answers to a particular problem. Each reader has a
different goal in mind; thus, understanding how research is structured and
organized is important to the ultimate goal. Most clinical studies are divided
into a common organizational scheme starting with a title, abstract,
introduction, materials/methods, results, discussion/conclusion, and
references. Although the introduction and discussion contain the authors’
perspective of the current state of science and how the presented research
adds to it, readers must be critical of the research methods and results to
make their own conclusions and determine how the research applies to their
own practice. Understanding the components of each section and what they
include will be important to an efficient and thorough review of information.
6

Importance of Bias and Level of Evidence to

Interpret Study Conclusions
Classifying scientific studies by level of quality, or level of evidence, allows
be er evaluation of the potential for bias. 7 Bias is often introduced in
methodologically weak studies such as case reports and expert opinion. As
study design and rigor improve, the risk of bias diminishes. Biases can occur
at all stages of research from trial design to data analysis; therefore, it is
important to appreciate the potential for bias and its effect on interpretation
of the results. 8

Levels of Evidence
Medical science has evolved well beyond examining an experimental
treatment compared with a placebo control. As big data, health economics,
and many other new investigational disciplines become increasingly
important, a framework to judge the quality and strength of the research is
needed. Table 1 outlines the complexity of research categories and lists the
levels of evidence based on the type and goals of the research endeavor. 9

Table 1
Oxford Centre for Evidence-Based Medicine: Levels of Evidence (March
2009)

Economic
Differential
Therapy/Prevention, and
Level Prognosis Diagnosis Diagnosis/Symptom
Etiology/Harm Decision
Prevalence Study
Analyses
 Economic
Differential
Therapy/Prevention, and
Level Prognosis Diagnosis Diagnosis/Symptom
Etiology/Harm Decision
Prevalence Study
Analyses
1a SR (with homogeneity SR (with SR (with SR (with SR (with
*
) of RCTs homogeneity * homogeneity * ) homogeneity * ) of homogeneity
) of inception of level 1 prospective cohort *
) of level 1
cohort diagnostic studies economic
studies; CDR studies; CDR ” studies
”
validated in with 1b studies
different from different
populations clinical centers
1b Individual RCT (with Individual Validating ** Prospective cohort Analysis
narrow confidence inception cohort study study with good based on
interval ”! ) cohort study with good ” ” ” follow-up **** clinically
with > 80% reference sensible
follow-up; standards; or costs or
CDR ” CDR ” tested alternatives;
validated in a within one systematic
single clinical center review(s) of
population the
evidence;
and
including
multiway
sensitivity
analyses
1c All or none § All or none Absolute All or none case Absolute
case series SpPins and series better value
SnNouts ” ” or worse-
value
analyses ” ” ” ”
2a SR (with homogeneity SR (with SR (with SR (with SR (with
*
) of cohort studies homogeneity * homogeneity * ) homogeneity * ) of 2b homogeneity
) of either of level >2 and better studies *
) of level >2
retrospective diagnostic economic
cohort studies studies
studies or
untreated
control
groups in
RCTs
 Economic
Differential
Therapy/Prevention, and
Level Prognosis Diagnosis Diagnosis/Symptom
Etiology/Harm Decision
Prevalence Study
Analyses
2b Individual cohort study Retrospective Exploratory ** Retrospective cohort Analysis
(including low-quality cohort study cohort study study, or poor follow- based on
RCT; eg, <80% follow- or follow-up with good ” ” ” up clinically
up) of untreated reference sensible
control standards; or costs or
patients in an CDR ” after alternatives;
RCT; derivation, or limited
derivation of validated only review(s) of
CDR ” or on split-sample the
validated on §§§
or databases evidence;
split-sample single
§§§
only studies; and
including
multiway
sensitivity
analyses
2c Outcomes research; Outcomes — Ecological studies Audit or
ecological studies research outcomes
research
3a SR (with homogeneity — SR (with SR (with SR (with
*
) of case-control homogeneity * ) homogeneity * ) of 3b homogeneity
studies of 3b and better and better studies *
) of 3b and
studies better
studies
3b Individual case-control — Nonconsecutive Nonconsecutive Analysis
study study; or cohort study, or very based on
without limited population limited
consistently alternatives
applied or costs,
reference poor quality
standards estimates of
data, but
including
sensitivity
analyses
incorporating
clinically
sensible
variations
4 Case series (and poor Case series Case-control Case series or Analysis with
quality cohort and (and poor study, poor or superseded no sensitivity
case-control studies §§ quality nonindependent reference standards analysis
) prognostic reference
cohort standards
studies *** )
 Economic
Differential
Therapy/Prevention, and
Level Prognosis Diagnosis Diagnosis/Symptom
Etiology/Harm Decision
Prevalence Study
Analyses
5 Expert opinion without Expert Expert opinion Expert opinion Expert
explicit critical opinion without explicit without explicit opinion
appraisal, or based on without critical critical appraisal, or without
physiology, bench explicit critical appraisal, or based on physiology, explicit
research or first appraisal, or based on bench research or critical
principles based on physiology, first principles appraisal, or
physiology, bench research based on
bench or first economic
research or principles theory or
first principles first
principles
CDR = clinical decision rule, RCT = randomized controlled trial, SR = systematic review
Notes:
Users can add a minus-sign “-” to denote the level of that fails to provide a conclusive answer because:
EITHER a single result with a wide confidence interval
OR a Systematic Review with troublesome heterogeneity.
Clinical Decision Rule. (These are algorithms or scoring systems that lead to a prognostic estimation or a
”

diagnostic category.)
An “Absolute SpPin” is a diagnostic finding whose Specificity is so high that a Positive result rules-in the
””

diagnosis. An “Absolute SnNout” is a diagnostic finding whose Sensitivity is so high that a Negative result
rules-out the diagnosis.
Good reference standards are independent of the test, and applied blindly or objectively to all patients.
”””

Poor reference standards are haphazardly applied, but still independent of the test. Use of a non-
independent reference standard (where the ‘test’ is included in the ‘reference’, or where the ‘testing’ affects
the ‘reference’) implies a level 4 study.
Better-value treatments are clearly as good but cheaper, or better, at the same or reduced cost. Worse-
””””

value treatments are as good and more expensive or worse and equally or more expensive.
By homogeneity we mean a systematic review that is free of worrisome variations (heterogeneity) in the
*

directions and degrees of results between individual studies. Not all systematic reviews with statistically
significant heterogeneity need be worrisome, and not all worrisome heterogeneity needs be statistically
significant. As noted above, studies displaying worrisome heterogeneity should be tagged with a “-” at the
end of their designated level.
Validating studies test the quality of a specific diagnostic test based on prior evidence. An exploratory
**

study collects information and trawls the data (e.g. using a regression analysis) to find which factors are
‘significant’.
By poor quality prognostic cohort study we mean one in which sampling was biased in favour of patients
***

who already had the target outcome, or the measurement of outcomes was accomplished in <80% of
study patients, or outcomes were determined in an unblinded, non-objective way, or there was no
correction for confounding factors.
Good follow-up in a differential diagnosis study is >80%, with adequate time for alternative diagnoses to
****

emerge (for example 1-6 months acute, 1 – 5 years chronic).§Met when all patients died before the Rx
became available, but some now survive on it; or when some patients died before the Rx became
available, but none now die on it.
§§
By poor quality cohort study we mean one that failed to clearly define comparison groups and/or failed to
measure exposures and outcomes in the same (preferably blinded), objective way in both exposed and
non-exposed individuals and/or failed to identify or appropriately control known confounders and/or failed to
carry out a sufficiently long and complete follow-up of patients. By poor quality case-control study we mean
one that failed to clearly define comparison groups and/or failed to measure exposures and outcomes in
the same (preferably blinded), objective way in both cases and controls and/or failed to identify or
appropriately control known confounders.
Split-sample validation is achieved by collecting all the information in a single tranche, then artificially
§§§

dividing this into “derivation” and “validation” samples.

See note above for advice on how to understand, rate, and use trials or other studies with wide confidence
”!

intervals.
Reproduced from Howick J, Chalmers I, Glasziou P, et al. Explanation of the 2011 Oxford Centre for
Evidence-Based Medicine (OCEBM) Levels of Evidence (Background Document). Oxford Centre for
Evidence-Based Medicine. https://www.cebm.ox.ac.uk/resources/levels-of-evidence/explanation-of-the-
2011-ocebm-levels-of-evidence/

Systematic Reviews and Meta-analyses

An estimated 2.5 million new scientific papers are published annually. 10 The
resulting overflow of information means that most professionals cannot stay
up to date in their fields simply by reading journals. Systematic reviews and
meta-analyses offer the opportunity to evaluate summary statistics of large
amounts of data. In a well-done meta-analysis, resources are rigorously
reviewed and screened for quality, filtering out data that may be unreliable
or inaccurate.
Meta-analysis is a complex and powerful statistical procedure that
combines the results of different eligible studies to generate a single
estimate of the major effect with enhanced precision. Some applications of
systematic review and meta-analyses are as follows: (1) Up-to-date meta-
analyses provide a comprehensive summary of existing clinical evidence and
can lay a groundwork for future research. (2) Clinical practice guideline
development is dependent on meta-analytic data. (3) Meta-analytic data are
often used in the FDA approval process. (4) Meta-analytic data can result in
the removal of a treatment from the market. Systematic reviews and meta-
analyses that include high level studies are considered level I evidence.

Randomized Controlled Trials

Another study that yields a high level of evidence is the randomized
controlled trial. In this type of research, of which there are many design
variations, research subjects are randomly assigned a treatment group or
intervention so that comparisons can be made between groups. The
randomization is an important method for avoiding bias. Examples of
comparisons that might be studied by way of randomization include
comparing two different implants used to treat a similar fracture for rates of
bone healing or comparing two types of rehabilitation after a sports injury to
determine time to return to sport. However, many clinical questions in
orthopaedic surgery are not appropriate for randomization. For example,
injuries that are typically managed with surgery may not be appropriate for
research that might allocate a patient to a nonsurgical treatment. Although
randomized controlled trials allow researchers to carefully design research,
other study designs are needed to address real-life clinical scenarios.
Randomized trials, depending on the rigor of the trial design, are level I or II
evidence.

Cohort Studies
Cohort studies are prospective or retrospective studies that begin with the
exposure of interest. The study design then involves a cohort of subjects
with the exposure of interest, which is then compared with a cohort without
the exposure. Tests of association may then be used statistically to determine
whether the exposure is associated with one or more outcomes of interest.
Cohort studies may be enrolled prospectively and subjects followed for
outcomes for a specified period of time. Alternatively, the exposures and
outcomes can be identified retrospectively. Prospective studies that are well
controlled can be very powerful and offer ways to effectively study
conditions with multiple variables or treatments that cannot be randomized.
Cohort studies are considered level III evidence. Inception, well-controlled
prospective cohort studies may be considered level II evidence.

Case-Control Studies
Case-control studies are retrospective studies that begin with a certain
outcome of interest. Cases are subjects in the study who have the outcome
and control subjects do not. The study procedures then a empt to identify
whether exposures of interest are or are not related to the eventual outcome.
In this way, a statistical comparison can be made between cases and control
subjects. These types of studies are helpful for rare outcomes because
acquiring large numbers of subjects for more complex study designs may be
prohibitive. They are relatively inexpensive and can be completed with small
subject numbers. Disadvantages of case-control design include being limited
to study of one outcome variable at a time, and sampling and recall bias can
influence how exposures and sequence of events are interpreted. Because of
these limitations, case-control studies are considered level IV evidence.

Case Series
Case series are reports on a small collection of patients who have a particular
diagnosis or are undergoing a specific intervention. The purpose of the case
series is to describe the topic diagnosis or intervention. These may be
informative, particularly for unusual presentations or rare conditions.
However, a case series does not permit conclusions to be drawn about a
treatment or diagnosis. Case series are considered level IV evidence.

Expert Opinion
Expert opinion comprises the experience and judgment of the opinion
author or authors. Although certain knowledgeable individuals in the
profession may be able to offer helpful insight, expert opinion does not
equate to the high level of evidence that results from systematic research.
Expert opinion is considered level V evidence.

How to Perform a Systematic Review and Meta-

analysis
Performing a systematic review involves several steps (Figure 1). After a
topic or clinical question is chosen, a research question is generated using
PICO (Patient, Intervention, Comparison, and Outcome) format. Table 2
demonstrates components of a PICO question.
 Figure 1 Flowchart shows steps to perform a systematic review and meta-analysis.

Table 2
PICO Question
Clinical Question: How useful is acetaminophen for treating osteoarthritis?
Question Components Constructing a PICO Question
P—Population/Patient/Diagnosis/Condition Adults with primary knee
Describe the most important characteristics of the condition being osteoarthritis with no
investigated (patient age, diagnosis, disease severity) comorbidities
I—Intervention/Exposure Oral acetaminophen 3,000 mg
Describe the intervention (drug, dose, frequency, route of per day
administration)
C—Comparison Placebo
Describe the alternative being considered (placebo, no treatment,
usual care, gold standard)
O—Outcome Pain, function
Describe the outcome of interest (death, total joint replacement,
pain, function)
The PICO research question: What are the benefits and harms of acetaminophen [I] compared
to placebo [C] for adults with knee osteoarthritis [P] in terms of change in pain and function
scores [O]?

Following PICO question development, inclusion and exclusion criteria

are defined before embarking on a literature search. Research protocol is
developed in accordance with the Preferred Reporting Items for Systematic
Review and Meta-Analyses Protocols (PRISMA-P) 11 and is registered at the
International Prospective Register of Systematic Reviews—PROSPERO. 12
The literature search must be performed in at least two electronic databases
(Pubmed, Medline, Embase, or Cochrane databases) and supplemented by
hand searching the article bibliographies. The retrieved studies are screened
based on the inclusion and exclusion criteria by at least two reviewers.
Methodologic and reporting quality of the included studies is important to
produce unbiased results. High-quality studies are less prone to bias and
thus more likely to report results that are true. Quality of the included
randomized controlled trials is assessed using the Cochrane risk of bias tool.
13
Parameters that are usually assessed include allocation concealment
(selection bias), blinding of participants and personnel (performance bias),
blinding of outcome assessment (detection bias), withdrawals (a rition
bias), and accuracy of the reporting (reporting bias). Proper randomization,
standardized prospective data collection, patient and provider blinding, and
active follow-up measures can limit the aforementioned biases. Studies
reporting negative results and small studies are less likely to be published,
leading to publication bias.
The most commonly used meta-analysis models are described in Table 3.
Systematic review and meta-analysis results should be presented in
accordance with the Preferred Reporting Items for Systematic Review and
Meta-Analyses (PRISMA) statement. 14 Adherence to Meta-analysis of
Observational Studies in Epidemiology (MOOSE) guidelines is preferred for
reporting systematic review of observational studies. 15

Table 3
Overview of Different Meta-analysis Models

Fixed-Effect Meta-analysis Model Random-Effects Meta-analysis Model

Assumes that the population effect sizes Assumes that the selected studies are
are the same for all studies random samples from a larger population

Accounts for within-study error only Accounts for both within-study error and
between-study variation

More weight is attributed to studies with Study weights are assigned to minimize both
higher precision sources of variation

Appropriate only to draw inferences on the Attempts to generalize findings beyond the
studies included in the meta-analysis included studies

Like any other research study, systematic reviews are also prone to bias. It
is crucial to differentiate high-quality systematic reviews from low-quality
systematic reviews. The Assessment of Multiple Systematic Reviews
(AMSTAR) index is a tool that allows for the reproducible assessments of the
quality of systematic reviews. 16 , 17

Clinical Practice Guidelines

The National Academy of Medicine (formerly the Institute of Medicine)
defined clinical practice guidelines as: “statements that include
recommendations, intended to optimize patient care, that are informed by a
systematic review of evidence and an assessment of the benefits and harms
of alternative care options.” 18 Professional societies are well positioned to
identify the needs and gaps in their field, collect and analyze the data on a
scale impractical to the individual practitioner, and disseminate that
information to the people most likely to use it. Using best available evidence,
clinical practice guidelines aim to provide a condensed and ve ed resource
for the clinical practitioners. In accordance with National Academy of
Medicine guidelines, clinical practice guideline creation should involve the
following: defining the clinical problem and patient population; assembling
a guideline development group; appraising the best available evidence; and
creating and disseminating the clinical practice guideline.
The process that the American Academy of Orthopaedic Surgeons
(AAOS) undertakes to produce clinical practice guidelines is generally as
follows. Once a topic is identified, PICO questions are generated. To answer
those PICO questions, systematic reviews and meta-analyses are performed.
Based on the appraisal of the best available evidence, a recommendation
with an associated strength or grade is made. 19 This is followed by a period
of peer review and community review prior to publication.

Grades of Recommendations
Grading of Recommendations, Assessment, Development and Evaluation
(GRADE) outlines a transparent and structured process that rates the quality
of the available scientific evidence to develop guidelines. 20 The steps
involved in developing recommendations specified by GRADE are presented
in Figure 2.

Figure 2 Flowchart shows an overview of the GRADE (Grading of Recommendations,

Assessment, Development and Evaluation) process for developing evidence-based
guidelines.(Reproduced with permissions from Guyatt G, Oxman AD, Akl EA, et al. GRADE
guidelines: 1. Introduction—GRADE evidence profiles and summary of findings tables. J Clin
Epidemiol. 2011;64[4];383-394.)

After an evidence-based literature review is completed, the workgroup

will summarize their findings as recommendations graded by the quality
and number of studies included in the analysis using consistent language.
The summary of findings and grade of recommendation may support or
refute a certain intervention. There are typically four grades of
recommendation: strong, moderate, limited, or consensus. Strong
recommendations would come from synthesis of two or more studies of high
level of evidence, whereas consensus may be generated when no studies are
available but expert opinion allows for some guidance.

Open Access Articles

Subscription print journals have been the mainstay for dissemination of
research studies. Over the years, a growing trend of open access journals has
emerged; for example, journals where the model shifts the burden of cost to
the authors and allows for access to content for no additional cost. This
emerging model allows for rapid dissemination and lowers the barrier of
knowledge transfer by avoiding costly journal subscriptions. As of 2021,
there were more than 16,000 journals in the Directory of Open Access
Journals (h p://www.doaj.org). Unfortunately, this model lends itself to
predatory behaviors from journals trying to take advantage of authors, such
as large article processing charges shifting the cost burden away from the
publisher. In this model, readers must be sensitive to conflicts and
motivations of the publishers and authors. 21
Many traditional subscription journals have created open access partner
journals, which allow authors to switch submission to the open access
partner typically if the manuscript is rejected from the first submission and
offered an automatic evaluation in the open access journal without having to
resubmit the manuscript. 22 Although many think this may be the future of
knowledge dissemination, authors and readers should be aware of the
conflicts and challenges with the new model.

Summary
Evaluating research can be challenging. As the tools and ability to collect
data improve, new types of research such as big data create new
opportunities to understand biologic processes. These fundamentals are
important and can influence population and policy as seen by the effect of
clinical practice guidelines. Understanding how to interpret and judge
research in all its forms is an important foundational skill for practicing
orthopaedic surgeons.
Key Study Points
Understanding bias in research enables the reader to properly assess results.
Defining levels of evidence will help the reader understand the strength of the results.
Understanding various types of research allows for improved data interpretation.
Clinical practice guidelines and how they are created are important for managing a clinical
practice.

Annotated References
1. Summary of Report of the Graylyn Development Consensus Conference,
November 1998, From Report 13 of the Council on Scientific Affairs (I-99),
Update on Clinical Research. h p://www.ama-
assn.org/ama/pub/article/2036-2392.html. Accessed June 5, 2021.
2. Warth LC, Callaghan JJ, Liu SS, Klaassen AL, Goe DD, Johnston RC:
Thirty-five-year results after Charnley total hip arthroplasty in patients
less than fifty years old. A concise follow-up of previous reports. J Bone
Joint Surg Am 2014;96(21):1814-1819.
3. Watson Levings RS, Broome TA, Smith AD, et al: Gene therapy for
osteoarthritis: Pharmacokinetics of intra-articular self-complementary
adeno-associated virus interleukin-1 receptor antagonist delivery in an
equine model. Hum Gene Ther Clin Dev 2018;29(2):90-100.
4. The National Center for Advancing Translational Science: Emerging Field
of Translational Science 2021. Available at: h ps://ncats.nih.gov/training-
education/emerging- field-translational-science. Accessed June 5, 2021.
NIH authority on managing and enhancing translational research across
all government funded projects.
5. Durbin CGJr: How to read a scientific research paper. Respir Care
2009;54(10):1366-1371.
6. Subramanyam R: Art of reading a journal article: Methodically and
effectively. J Oral Maxillofac Pathol 2013;17(1):65-70.
7. Wright JG, Swiontkowski MF, Heckman JD: Introducing levels of
evidence to the journal. J Bone Joint Surg 2003;85(1):1-3.
8. Pannucci CJ, Wilkins EG: Identifying and avoiding bias in research. Plast
Reconstr Surg 2010;126(2):619-625.
9. Howick J, Chalmers I, Glasziou P, et al: Explanation of the 2011 Oxford
Centre for Evidence-Based Medicine (OCEBM) Levels of Evidence
(Background Document). Oxford Centre for Evidence-Based Medicine.
 Accessed June 5, 2021. Available at:
h ps://www.cebm.ox.ac.uk/resources/levels-of-evidence/explanation-of-
the-2011-ocebm-levels-of-evidence/.
10. Bell RJ: What is wrong with the medical literature? Climacteric
2017;20(1):22-24.
11. Shamseer L, Moher D, Clarke M, et al: Preferred reporting items for
systematic review and meta-analysis protocols (PRISMA-P) 2015:
Elaboration and explanation. Br Med J 2015;349:g7647.
12. National Institute for Health Research: PROSPERO: International
prospective register of systematic reviews.
Available at: h ps://www.crd.york.ac.uk/PROSPERO/. Accessed June 2,
2022. This is an international database of prospectively registered
systematic reviews.
13. Sterne JAC, Savović J, Page MJ, et al: RoB 2: A revised tool for assessing
risk of bias in randomised trials. BMJ 2019;366:l4898.
14. Page MJ, Moher D, Bossuyt PM, et al: PRISMA 2020 explanation and
elaboration: Updated guidance and exemplars for reporting systematic
reviews. Br Med J 2021;372:n160. Updated guidance on reporting of
systematic reviews is provided.
15. Brooke BS, Schwar TA, Pawlik TM: MOOSE reporting guidelines for
meta-analyses of observational studies. JAMA Surg 2021;156(8):787-788.
Updated guidance on reporting of meta-analyses of observational studies
is provided.
16. Shea BJ, Grimshaw JM, Wells GA, et al: Development of AMSTAR: A
measurement tool to assess the methodological quality of systematic
reviews. BMC Med Res Methodol 2007;7:10.
17. Shea BJ, Reeves BC, Wells G, et al: AMSTAR 2: A critical appraisal tool
for systematic reviews that include randomised or non-randomised
studies of healthcare interventions, or both. Br Med J 2017;358:j4008.
18. Institute of Medicine: Clinical Practice Guidelines We Can Trust. The
National Academies Press, 2011.
19. The American Academy of Orthopaedic Surgeons: Understanding
Guideline Language. Available at:
h ps://www.orthoguidelines.org/definitions. Accessed March 15, 2022.
20. GRADE series in the Journal of Clinical Epidemiology. Available at:
h ps://www.jclinepi.com/content/jce-GRADE-Series. Accessed June 5,
2021.
21. Moher D, Moher E: Stop predatory publishers now: Act collaboratively.
Ann Intern Med 2016;164(9):616-617.
22. Ganesh Kumar N, Meador KG, Drolet BC: Challenges in open access
publishing. JAMA Surg 2018;153(10):875-876.
C H AP T E R 2

Biostatistics
Melissa Orr BS, Nicolas S. Piuzzi MD

Dr. Piuzzi or an immediate family member serves as a paid consultant to or is an employee of

RegenLab and Stryker; has received research or institutional support from Regeneron and
Zimmer; and serves as a board member, owner, officer, or committee member of American
Association of Hip and Knee Surgeons and ISCT. Neither Melissa Orr nor any immediate family
member has received anything of value from or has stock or stock options held in a commercial
company or institution related directly or indirectly to the subject of this chapter.

ABSTRACT
It is important for orthopaedic surgeons to have a basic overview of
research methodology, basic statistical principles, and a review of
the current literature regarding biostatistics in orthopaedic
research. The practice of evidence-based medicine requires
orthopaedic surgeons to keep abreast of the latest clinical studies,
with the ability to critically appraise research relevant to their
individual practice.
Keywords: clinical relevance; evidence-based medicine; patient-
reported outcome measures; statistical significance; study design

Introduction
It is imperative for orthopaedic surgeons to have a basic
understanding of biostatistics and comprehension of research
methodology, specifically (1) how to evaluate the validity of
evidence; (2) the basics of clinical study design and common
statistical tests; (3) interpretation of clinical relevance versus
statistical significance; and (4) patient-reported outcome measures
(PROMs) commonly used in orthopaedics.

Evidence-Based Medicine
Although higher levels of statistical methods are being included in
medical literature, investigations have demonstrated that
disparities often exist in the correct understanding and
interpretation of results among the medical community. 1 , 2 In
surgery, specifically, descriptive studies predominate and the
statistical methods chosen for a given study affect interpretation
and application to practice. 3 Evidence-based medicine (EBM) is
defined as “the conscientious, explicit, and judicious use of the
current best evidence in making decisions about the care of
individual patients.” 4 This translates to a process of integrating
individual clinical expertise with external clinical evidence.
Individual expertise refers to judgment acquired by clinical
practice, and external clinical evidence refers to relevant patient-
centered clinical research. 5 Clinical evidence should inform but not
replace individual clinical expertise. In practice, EBM involves
applying knowledge from clinical trials, meta-analyses, and reviews
to patient care for which an understanding of biostatistics is of key
importance. 6 Thus, for EBM to promote consistent treatment
strategies and to establish standards of orthopaedic surgery
practice, surgeons should have an understanding of study design
and methodology along with biostatistics. The cycle of EBM 7 , 8 is
depicted in Figure 1.
 Figure 1 Diagram shows the cycle of evidence-based medicine.Ask:
formulating an answerable question. Acquire: a thorough search of relevant
literature. Appraise: critical evaluation of evidence and application to current
question. Apply: translating conclusions in the context of the current clinical
problem. Act: evaluating the process by integrating the physician’s clinical
judgment with the patient’s perspective.

Evaluating the Validity of Evidence

All health care professionals should deliver care based on the best
available evidence to ensure outcomes. However, it is also the
responsibility of practitioners to understand how external evidence
can be applied to their clinical practices. Evaluating evidence occurs
on both an internal (within the study) and external (outside of the
study) level. Questions that can be used to evaluate clinical
evidence are provided in Table 1.

Table 1
Questions to Evaluate Relevant Literature

Internal External
Internal External

Does the study measure what it says? How meaningful are the results?
Was randomization done? Do the results translate to my
Was blinding done? practice?
Were the randomized groups similar Are the study patients different from
at baseline? my patients?
What was the follow-up period? How can I apply these results to my
How many patients dropped out of the patient?
study?
Were the benefits worth the risks and
costs?

Evidence-Based Orthopaedic Surgery

The application of EBM to orthopaedic surgery is not without
challenges. In surgery, on-the-spot decisions are made and often
affected by socialized knowledge within this specialized
community. 8 Although randomized controlled trials (RCTs) are the
highest level of evidence (Table 2), surgery is a complex
intervention with variability often unsuited to RCT regulations,
including placebo (sham surgery) and double blinding of
treatment, resulting in lower percentage of RCT in orthopaedics
compared with other fields. 9 To adopt EBM to surgical practice, the
health care practitioner needs to have appropriate knowledge to
best interpret and understand the application of the literature to
the question at hand. Furthermore, the development of large
databases of prospective cohort studies can present high-quality
evidence with more diverse patient populations.

Table 2
Levels of Evidence

Level Study Type

I Randomized controlled trial, systematic reviews of randomized controlled trials
II Prospective cohort
III Case-control, retrospective cohort
IV Case series
V Expert opinion
Proper Study Design

Hypothesis
When relying on EBM to guide decision making in clinical practice,
a research hypothesis is tested by investigators. The null hypothesis
(H0) states that there is no statistical difference between groups.
The null hypothesis is deemed true until a study presents
significant data to support its rejection. The alternative hypothesis
(H1) is the presence of an effect.
Example H0: Body mass index has no effect on complication rate
after total hip arthroplasty
Example H1: Body mass index has an effect on complication rate
after total hip arthroplasty
Consider the example of probing the association of body mass
index (BMI) with complication rate after total hip arthroplasty. A
2020 study compared the rate of surgical complications between
patients undergoing total hip arthroplasty and found a significantly
higher rate of complications for patients with BMI outside of the
normal to overweight range. 10 Thus, researchers are able to reject
the null hypothesis in favor of the alternative.

Dependent and Independent Variables

Independent variables are what are expected to influence
dependent variables; change in a dependent variable is the effect of
change in the independent variable. For the aforementioned
example, the independent variable is BMI and the dependent
variable is complication rate. It is important to note that the
relationship between independent and dependent variables is not
always linear. In the aforementioned example, BMI both higher and
lower than a normal-to-overweight range was associated with
increased complications.
 When designing a clinical study, deciding if the goal is to
describe events or to study a treatment is categorized into two
distinct study designs: analytic and descriptive studies 11 (Figure 2).

Figure 2 Diagram shows the study designs and categories.

Descriptive Studies
Descriptive, or observational, studies describe a situation or events.
No explanations of the relationship between any variables are
offered. However, evidence from descriptive studies can prompt a
hypothesis for additional studies. Examples of descriptive studies
include cross-sectional, correlational (or ecologic), case series, and
case reports (Table 3).
Table 3
Examples of Descriptive Studies

Descriptive
Definition Example in Orthopaedics
Studies
Cross- Incidence or prevalence of Patient characteristics and preoperative
sectional event in a specified expectation of pain relief groups are reported
population
Correlational Potential relationship The association between preoperative drug
between two variables use and length of stay is reported
Case series Detailed description of The treatment of large traumatic chondral
patients, usually more than fragments is controversial. Ten young
10 patients undergo repair and clinical results
are described
Case Detailed description of A 71-year-old woman presents with unusual
reports patients with rare diseases, postoperative skin lesion after knee
complications, less than 10 replacement
patients

Cross-sectional studies involve collecting data from many

individuals at a single point in time. For example, a study gave a
questionnaire to patients about to undergo a knee replacement
asking if they expected the surgery to benefit their pain level and
improve function and examined associations between preoperative
characteristics (eg, age, sex, comorbidities) with these expectations.
12
Such studies can examine the relationship between patient
variables and health outcomes as well as provide information on
the prevalence of a given event. Advantages of cross-sectional
studies include being low in cost and time commitment.
Disadvantages include not being able to explain the event.
Case reports or case series are made by clinicians on patients.
Generally they describe rare events (eg, diseases, complications) or
generate new hypotheses (ie, diagnostic methods or treatment
strategies). 11 A case report should present novelty, 13 including
unexpected presentation of a disease, unexpected associations
between a disease and symptoms, adverse events, new or emerging
diseases, or unusual adverse effects of medications. As described in
a 2021 study, an example of a case report would be a postoperative
skin lesion (sca ered pruritic bullae) around the incision site 7
weeks after total knee arthroplasty. 14 A case series exists in a
research study that tracks subjects with a known exposure, such as
patients who have received a similar treatment, or examines their
medical records for exposure and outcome. An example of a case
series, as described in a 2019 study, is an evaluation of 10 male
patients with an age range of 10 to 25 years who all had a diagnosed
traumatic displaced pure chondral fracture of the knee and
underwent internal fixation. 15 Within the orthopaedic literature,
case series are the most commonly reported research. 16
Disadvantages of case series include selection bias and lack of a
control group.
Correlational studies determine a potential relationship between
two variables and represent average exposure levels within a given
population. The disadvantage of correlational studies is that
correlation does not imply causation, and the correlation does not
imply valid statistical association. Furthermore, relationships
observed at the group level may not always apply to individuals as
well as potential confounding variables that are not taken into
account. An example of a correlational study, as described in a 2021
study, is examining the association of preoperative prescription
drug use with length of stay after total hip arthroplasty. 17 In such a
study, confounding factors of age, race, BMI, smoking status, and
insurance are controlled. Although the results would not claim that
preoperative drug use causes an increased length of stay, such a
study would highlight an association and make clinicians aware of
an increased risk within a patient population.

Analytic Studies
Analytic studies answer a scientific hypothesis and use a sample to
make inferences about the target population as a whole. The main
categories of analytic studies are RCTs, cohort studies, and
retrospective case-control trials.
 RCTs constitute the gold standard of EBM. 18 Participants are in a
defined population and randomized into a treatment or control
group. For example, a trial in which patients undergoing a revision
total knee arthroplasty who are identified to be at risk for wound
complications are randomized to receive either standard of care or
closed incision negative-pressure therapy. 19 Treatment groups can
be a new or existing treatment, and the control group could be an
existing treatment or no treatment at all (placebo). 20 Participants
are followed prospectively and treatment groups are compared. The
disadvantages of RCTs are that they can be costly, time intensive,
and not always feasible or ethical in a surgery discipline. Finally,
because of selection bias, the results may not be generalizable to
the entire population. For the aforementioned example, it would be
unknown if the results could be applied to all revision cases or only
those identified as high risk for complication. Application of RCTs
to the population can be improved when they occur multi-
institutionally. Because of the challenges involved with RCT and
surgery, RCTs made up only 8% of the original research published
in The Bone & Joint Journal between 2012 and 2017. 9
Cohort studies are used to compare groups with similar baseline
characteristics such as demographics, but who have undergone
different exposures. These groups are followed either
retrospectively or prospectively. Such studies can be used to
approximate incidence or the proportion of new cases of a disease
within a certain period of time. Cohorts are typically stratified by
specific risk factors, which allow them to be followed prospectively
to observe outcomes. As a result, inferences can be made about the
prognosis of a risk factor.
Cases, or patients with a disease of interest, and control patients
(patients without the disease) can be compared with retrospective
case-control studies. The comparison is made across the level of
exposure to a risk factor. Unlike cohort studies that select groups
based on exposure status, case-control studies select groups based
on disease status. The differences in exposure between cases and
control patients help to find protective factors and risks associated
with outcomes of interest. A challenging part of this study design is
defining the base population and in the selection of control
patients. These studies tend to be longitudinal in nature and
provide an odds ratio as the primary outcome measurement. The
odds ratio is defined as the odds of disease in exposed individuals
compared with odds of disease in unexposed individuals. When
examining rare diseases or events, this provides a good
approximation of relative risk. Overall, if the odds ratio is less than
1, odds are decreased for a given outcome, and if odds ratio is
greater than 1, the odds are increased for a given outcome.

Functional Outcome Scores

Value-based healthcare has shifted focus on metrics of patient
value, determined with functional outcomes and patient-reported
outcomes (PROs). 21 PROs are health conditions, behaviors, and
experiences directly from a patient and without interpretations.
PROMs are survey-based instruments that measure these patients’
symptoms and can be used to estimate benefits of surgical
procedures and quantify the quality of care. 22 The Patient-Reported
Outcome Measurement Information System is a National Institutes
of Health initiative to obtain data on mental, physical, and social
health to develop valid and reportable outcome measures for
patients. 23
Common PROMs in orthopaedic journals include the Knee
Society Score, Hip Society Score, Western Ontario and McMaster
Universities Index, Oxford Knee Score, Oxford Hip Score, Short
Form-36, Short Form-12, University of California at Los Angeles
Score, and visual analog scale score. 24 , 25 The Hip Disability and
Osteoarthritis Outcome Survey and Knee Injury and Osteoarthritis
Outcome Survey were determined to be the most well-validated
joint-specific PROMs and adopted in the Comprehensive Care for
Joint Replacement model. 26 There does not currently exist one
reliable, validated, PROM index for cross-study comparison, 25
although currently different PROMs may be beneficial depending
on the disease, site, or outcome.
Functional outcome scores can also be determined by
performance testing and involve a patient performing a specific test
for a predetermined amount of time. In performance testing, a
clinician or physical therapist is assessing and scoring the
performance. An example of a performance test includes the
Activity Measure for Post-Acute Care Instrument developed by
Boston University researchers. This test evaluates patients on how
much help is needed in completing basic mobility tests such as
climbing stairs or rolling over. 27

Patient-Reported Outcomes
Patient-reported outcome-based performance measures (PRO-PMs)
are the numerical quantification of PROMs. PRO-PMs are the
reported values, often aggregated between patients and validated
for a given procedure or treatment group. The use of these PROs
addresses the quality portion in a value-based health care equation,
by quantifying the degree to which a health service provides care to
enhance a patient’s physical and mental health, function, and
quality of life. PRO-PMs are being increasingly included in payment
programs and being used to launch further quality improvement
initiatives and the aggregation of PRO-PMs in local and nationwide
clinical data registries including the American Joint Replacement
Registry, 28 which can allow for the comparison of providers and
centers.

Minimal Clinically Important Difference

Although values of P are used to determine whether a result is
statistically significant, patients perceive treatment effects rather
than values of P, and a statistically significant result may not
translate to a patient perceiving a meaningful effect. 29 Therefore,
metrics of clinical significance have been established. The minimal
clinically important difference (MCID), the smallest change in the
treatment outcome that a patient perceives as beneficial, 26 has been
correlated to PROM scores in establishing clinically significant
treatment effects. However, the minimal acceptable level for which
a patient would choose to undergo a procedure may be above the
MCID. 30 The MCID can be defined as distribution based, with 0.5
standard deviation (SD) considered as a clinically detectable
difference, or as anchor based, with the change in score tied to an
inquiry on overall improvement. When MCID is defined as a
distribution, the clinical benefit may be overestimated. 26
Furthermore, as nonresponse has been associated with poorer
outcomes, 31 with increased follow-up time and decreased patient
follow-up, outcomes may be overestimated. The Patient Acceptable
Symptom State is calculated by a dichotomous PRO as an anchor to
identify cutoff points in numerical PROM scores. 32 A list of
commonly used metrics of clinical significance is provided in Table
4. Although there is currently no standard for calculating clinically
significant changes in outcomes, in orthopaedics, metrics of clinical
relevance have been recommended, 33 and it is suggested to use
metrics established in similar patient populations.

Table 4
Terms Used to Define Clinical Relevance

Minimal important change (MIC): the change relative to the baseline for the cohort to
report improvement in quality of life
Minimal important difference (MID): the smallest difference in score in the outcome of
interest that informed patients perceive as important
Minimal clinically important difference (MCID): the difference in the mean change
between patients with no improvement and patients with little improvement (also called the
minimum clinically important change [MCIC] or the minimal clinically important improvement
[MCII] if referring only to benefit)
Minimal detectable change (MDC): the smallest change for an individual to experience
improvement in quality of life
Clinically important difference (CID): the difference in an outcome measure that is
considered clinically important
The patient acceptable symptom state: calculated by a dichotomous patient-reported
outcome as an anchor to identify cut-off points in numerical PROM scores
 In evaluating statistical significance, some have advocated for a
shift away from solely reporting on value of P, which is the
probability of observing the event (or series of events) in the data if
the null hypothesis is true, to including other calculations to
evaluate the robustness of an outcome and compare with other
journals. 34 The Fragility Index, 35 created for RCTs, uses an iterative
method of moving one patient outcome from event to nonevent, or
vice versa, and demonstrates how easily statistical significance
based on a value of P can be overturned, recognizing that much of
the published literature is based on statistically fragile trials. 36
Interpretation of the Fragility Index is subjective, with no defined
limit of robustness. However, robustness has been assessed by
reporting the following: Fragility Quotient, the Fragility Index
divided by total sample size, 37 and the number of patients lost to
follow-up, with trials labeled as less robust if number of patients
lost to follow-up is greater than the Fragility Index. 38 The Clinical
Relevance Ratio 39 relies on establishing a clinical relevance
threshold to dichotomize outcomes and reports on the number of
patients achieving clinical importance at a time point over the
number of patients at the start of the study. The Clinical Relevance
Ratio takes into account patients lost to follow-up throughout the
study.

Power Analyses
Power estimations are used to determine how many subjects are
needed to answer the research question. Although clinical studies
entail studying a sample population to make inferences about the
population as a whole, increasing the number of subjects would
more accurately answer the research question. However, studies
can be time intensive and cost intensive, and some trials may pose
risk to study participants. Therefore, finding the minimum number
of participants to support a study is crucial. 40 A power analysis
provides an estimate of the smallest number of observations
needed to statistically support the primary outcome of a study.
Types of Errors
Two types of errors can be made (Table 5). A type I error occurs
when the null hypothesis is rejected incorrectly (false positive). A
type II error is the failure to reject a false null hypothesis (false
negative).

Table 5
Type I and Type II Errors

Actual Truth Reported

Type I error True False
There is a difference in treatment
Type II error False True
There is no difference in treatment

Power Calculations
Power refers to the number of patients required to avoid a type II
error in a comparative study. The chance of a type II error is
referred to as β and power is 1-β. Alpha is the chance of a type I
error and commonly referred to as the significance of a test. A
sample size estimation looks at more than just the type II error and
is more encompassing and applicable to all types of studies. Factors
affecting a power calculation include previsions of measurements,
magnitude of clinically significant difference, how certain the
health care practitioner needs to be of avoiding type I error, and the
type of statistical test. 40 Finding the clinically important difference
is key to the sample size calculation, as small differences may be
statistically significant but not clinically relevant.
Following the determination of the outcome measure and MCID,
the statistical test that will be used for power analysis is identified.
This test is ideally the one that will be used for the final analysis of
the study. The test chosen reflects the relationships among the data
and the expected effect sizes and can be one-sample, two-sample, or
paired tests. Commonly these include the t-test or analysis of
variance (ANOVA) for continuous variables with two or multiple
groups, respectively, and chi-square tests for categorical variables.
More rigorous tests can also be used such as survival curves,
simulation-based approaches, and regressions.
In estimating sample sizes, levels of alpha and beta are
determined. Alpha is generally set at 5% and power (1-β) is
generally 80%. If a higher power is desired, a larger sample size
would be needed. The value of beta can be modified by the effect of
type II errors on the research. For the power calculation to be
performed, values for SDs and means should be assumed for the
primary outcomes. Often this is obtained from literature analysis or
from preliminary or pilot data. Larger effect sizes and smaller SDs
can reduce the sample size needed. The power analysis is an
estimate that improves or worsens depending on the quality of the
assumptions provided. Thus, if a parameter such as SD is not very
accurate, it may be beneficial to be more conservative in the power
calculation. Different values for the parameters can be a empted as
well to understand the effect of changing each parameter on the
outcome. In addition, when planning for a given study, it is
important to account for potential loss to follow-up among patients.

Principles of Statistical Testing

Testing for Hypothesis Acceptance/Rejection

Most common statistical techniques in current use depend on
hypothesis testing that relies on the statement of null and
alternative hypotheses that reflect the goals of research. The null
hypothesis is the default statement and reflects an absence of effect
and thus no statistically significant difference between two groups
in the outcome of interest. The alternative hypothesis reflects the
presence of an effect or that the difference is not equal to zero.
When the alternative hypothesis is not equal to zero, this is a two-
sided alternative hypothesis, which is the most common. Thus, a
two-sided test would be most appropriate.
 Hypothesis testing allows it to be stated that an observed
difference is greater than expected by probability. This is
represented visually with two bell-shaped curves. One curve
represents the probability distribution for the null hypothesis and
the other for the alternative hypothesis. The value of P is the
probability that the difference observed would occur by random
chance if the null hypothesis is true. Values of P are calculated by
taking the underlying probability distribution and finding the
critical value, which is the point on the distribution beyond which
the rejection region is found. If the probability is too small, the
difference is deemed unlikely to be due to random chance. Thus,
the null hypothesis is rejected and a statistically significant
difference is asserted.
The null hypothesis is accepted if there is insufficient evidence
for its rejection. It does not prove equivalence just that the effect in
question is not there. Thus, if the value of P is greater than the
threshold required for rejection, it is stated that the practitioner
fails to reject the null hypothesis and to accept the alternative
hypothesis. An alternative approach that be er supports the
assertion of equivalence is the two, one-sided tests approach. In
literature, it is common to find reported only the statistical test that
was used to test a hypothesis and the value of P obtained, as the
conditions behind hypothesis testing are implied. Statistical tests
should be chosen to reflect the underlying distributions of the data,
the research question being asked, and the type of the data that are
under analysis.
Although most medical research currently focuses on hypothesis
testing, growing trends include more estimation to be er gauge the
result as effect or no effect. These include confidence intervals,
effect size, and treatment effects.

Minimizing Bias and Error

Bias is any departure of results from truth. As the results of
research can be used to guide clinical practice guidance, it is crucial
to minimize bias in clinical research. Forms of bias in research
include conflicts of interest, industry-related bias, wrong sample
size, and positive results. 41
For RCT, the Consolidated Standards of Reporting Trials, or
CONSORT, 42 provides a checklist and flow diagram to encourage
transparent reporting. For reporting in systematic reviews and
meta-analysis, Preferred Reporting Items for Systematic Reviews
and Meta-Analyses, or PRISMA, provides evidence-based minimum
set of items for reporting as discussed in a 2019 study. 43

Bonferroni Correction
One of the most common corrections used when multiple
comparisons are performed is the Bonferroni correction. It is
performed to control for the increased chance of finding a
statistically significant observation when performing multiple
comparisons. When multiple comparisons or statistical tests are
performed simultaneously, the risk of type I error increases. The
Bonferroni correction compensates for this by testing each
individual hypothesis at a significance level of alpha divided by the
number of hypotheses or comparisons performed. Thus, for a given
value of P to be considered significant, it must now be smaller than
this new threshold.

Multivariate Data
When three or more variables are present in data, it is classified as
multivariate. This is opposed to two variables in bivariate data, and
one variable in univariate data. Multivariate data contain more than
one dependent variable. Multivariate analysis encompasses an
entire range of statistical techniques. Techniques used for
multivariate analysis can be divided into dependence and
interdependence. Dependence methods look at cause and effect
and ask whether one variable can be used to explain or predict
other variables. Predictive models used in machine learning make
use of dependence techniques. Interdependence methods are used
to understand pa erns in data without looking for causal
relationships. These methods group together variables in
meaningful ways without assigning cause and effect to them.
Commonly used interdependence techniques include regression
analysis, factor analysis, path analysis, and multivariate ANOVA.

Data Types
When performing statistical analysis, data are categorized into
quantitative or categorical, which affects what type of statistical test
can be used. Quantitative data, also known as numerical data, can
be grouped into categorical, also known as nominal, data to make
use of different tests. Before deciding on a statistical test,
descriptive statistics and plo ing of the data should be performed
to assess the distribution of the data. Nonparametric tests are
performed when data significantly differ from the requisite
distributions. Observations should be independent of one another
for many different tests. Linked observations, when one value is
similar or related to another, can affect the validity of statistical
tests. Thus, great care must be taken to design the study and
sampling of data to avoid unintentional nonindependence. Sources
of nonindependence can occur from observations on similar
samples in relatively close time frames.
Nonindependent observations can also be intentional in studies
such as longitudinal studies on the same subject at different time
points. Clustered data are data that have one observation for each
subject, but all are grouped in a way such as being patients of a
single surgeon or hospital. Repeated-measures are data that are
measured more than once, but the effect that separates the
measurements is not time, but another effect. Independence is
crucial for many statistical models and tests and thus must be
accounted for when analyzing.
Examples of commonly used statistical methods from surgical
literature 3 are presented in Table 6.
Table 6
Commonly Used Statistical Methods and Terms in Orthopaedic
Literature

Test Application Example

Student t- Parametric test, used to compare means between Comparing ages
test groups in normally distributed data between groups
(two
groups)
Analysis of
variance
(more than
two groups)
Chi-square Nonparametric, used to compare frequencies Comparing
test between groups percentage of
Fisher female participants
exact test between groups
(if
frequencies
are small)
Mann- Nonparametric, used to compare population Comparing PROMs
Whitney U distributions between groups using medians in (often reported as
test nonnormally distributed data median values)
(two between groups
groups)
Kruskal-
Wallis test
(more than
two groups)
Kaplan- Nonparametric, used for time-to-event data or survival Implant survival rate
Meier analysis
curve
Competing Survival analysis that takes into account the Implant survival rate
risk probability of a competing event in the elderly
analysis (competing risk of
mortality)
Logistic Model used to determine the odds of a binary event. Assessing the odds
regression Can be univariate or multivariate depending on of revision surgery
number of predictors among those who
smoke
Area under Receiver operator characteristic (ROC) curve graphs Reporting the
the curve the performance of a classification model. AUC or c- goodness of fit of a
(AUC) statistic provide a value of goodness of fit for logistic predictive tool
regression model
 Parametric tests require making assumptions about the
parametric of the population distribution; often it is assumed the
data are to be normally distributed.

Quantitative Data Testing

A Student t-test is an appropriate test when the variable compared
between two samples is a measured quantity and a comparison of
the mean is desired. This is known as a two-sample t-test and
compares a numerical variable across two groups. Commonly the
groups are divided by a categorical variable such as a treatment
group. Thus, the means of a measurable outcome are compared in
groups of patients that each received one of two treatments. A one-
sample t-test can be used to compare a mean of a sample with a
known or expected population mean. A paired t-test compares
aforementioned longitudinal data in patient’s preintervention and
postintervention.
For a valid Student t-test, certain assumptions must be met. The
data being compared must be independent, follow a normal
distribution, and have the same variance, which is known as
homoscedasticity. These assumptions can be tested with statistical
tests and are more likely to be met in larger samples because of the
central limit theorem. Nonparametric tests are used when
distributional assumptions are not met, such as grossly impaired
normality. An example of a nonparametric test for comparing two
unpaired means is a Mann-Whitney U test. In place of a paired t-
test, a Wilcoxon signed-rank test can be performed. However, even
with smaller sample sizes, or small departures in normality or
equality of variance, t-tests are superior to nonparametric tests.
A t-test is used when means are compared across two groups.
When more than two groups are compared, ANOVA can be used. A
one-way ANOVA is best used when a continuous variable is
compared for groups across a single categorical variable. A two-way
ANOVA compares continuous variables across two categorical
variables such as when an outcome is compared between three
treatments in two sexes. As with t-tests, ANOVA requires certain
assumptions be met, which are similar for both tests: independent
observations, normal distribution of observations, and
homoscedasticity. A statistically significant ANOVA test rejects the
null hypothesis of there being no difference between treatment
groups and asserts that a difference exists. An ANOVA will not
state which groups differ from one another, but merely that a
difference exists. To determine which pair is different, post hoc
tests that make pairwise comparisons are used. Two-sample t-tests
or Tukey-Kramer tests are two examples. However, because of the
likelihood of finding a statistically significant difference between
pairs merely by chance, a correction for multiple comparisons
should be considered. One example is the Bonferroni correction
mentioned previously.

Categorical Data Testing

When comparing proportional equality across two categorical
variables, a chi-square test is often used. An example would be
testing number of successes in two treatment groups across a
categorical variable. This information can be recorded in a 2 × 2
contingency table, but larger tables can also be assessed. If any of
the expected values in a contingency table is less than 5, a Fisher
exact test would be more appropriate. Both chi-square and Fisher
exact tests assume independent observations. In cases of paired
data, a McNemar test should be considered. Three categorical
variables can also be compared, such as when stratifying a cohort
and comparing two variables in each cohort. This results in the
generation of multiple 2 × 2 tables. In this scenario, a Cochran-
Mantel-Haenszel test should be considered and McNemar test is
only used for paired data. An example would be comparing two
nominal variables across repeated measurements in time or
location.

Confounding Factors
A confounding factor is a third variable that affects the relationship
of interest between two primary variables. An example would be if
the age of patients affects the effect of treatment on an outcome
variable. If age between the two compared groups is not similar,
and age affects the outcome of the treatment, age would be a
confounding factor to the outcome of interest. Confounding factors
are controlled via study design that minimizes bias such as
properly randomizing to cohorts or by matching characteristics
across cohorts. Confounding factors can be controlled for using
multivariable regression by including them in the model.
Controlling for confounding is essential to the validity of studies
and thus must be considered both when designing the study and
when performing analysis.

Summary
The amount of literature available to orthopaedic surgeons is
rapidly growing. 44 It is necessary for orthopaedic surgeons to be
able to critically appraise this literature to make well-informed
decisions in the practice of EBM.

Key Study Points

EBM is the process of integrating individual clinical expertise with external clinical
evidence.
Level I evidence includes RCT and systematic reviews of randomized controlled
trials.
Statistical significance indicates the reliability of a study’s results, and clinical
significance indicates the relevance of results on clinical practice.
CONSORT and PRISMA provide reporting guidelines to minimize bias.

Annotated References
1. Windish DM, Huot SJ, Green ML: Medicine residents’
understanding of the biostatistics and results in the medical
literature. J Am Med Assoc 2007;298(9):1010.
 2. Msaouel P, Kappos T, Tasoulis A, et al: Assessment of cognitive
biases and biostatistics knowledge of medical residents: A
multicenter, cross-sectional questionnaire study. Med Educ Online
2014;19(1):23646.
3. Williams PJ, Murphy P, Van Koughne JAM, et al: Statistical
techniques in general surgery literature: What do we need to
know? J Am Coll Surg 2018;227(4):450-454.e1.
4. Sacke DL, Rosenberg WMC, Gray JAM, Haynes RB, Richardson
WS: Evidence based medicine: What it is and what it isn’t. Br Med
J 1996;312(7023):71-72.
5. Archdeacon MT, Papp SR, Bernstein M, Giannoudis PV,
Bhandari M, Harvey EJ: How does orthopaedic research affect
patient care? J Orthop Trauma 2018;32(suppl 1):S25-S28.
6. Lewis SJ, Orland BI: The importance and impact of evidence-
based medicine. J Manag Care Pharm 2004;10(5 suppl A):S3-S5.
7. Bhandari M, Giannoudis PV: Evidence-based medicine: What it
is and what it is not. Injury 2006;37(4):302-306.
8. Emara AK, Klika AK, Piuzzi NS: Evidence-based orthopedic
surgery – From synthesis to practice. JAMA Surg
2020;155(11):1009. The authors present viewpoint and case
example on applying evidence-based surgery in orthopaedic
practice. Level of evidence: V.
9. Robinson AHN, Johnson-Lynn SE, Humphrey JA, Haddad FS:
The challenges of translating the results of randomized
controlled trials in orthopaedic surgery into clinical practice. Bone
Joint J 2019;101-B(2):121-123. Editorial describes obstacles in
translating RCTs in orthopaedic surgery to clinical practice. Level
of evidence: V.
10. Scully W, Piuzzi NS, Sodhi N, et al: The effect of body mass
index on 30-day complications after total hip arthroplasty. Hip Int
2020;30(2):125-134. The authors present a large database study
associating BMI with outcomes after total hip arthroplasty. Level
of evidence: III.
11. Jolles BM, Martin E: In Brief: Statistics in brief – Study designs
in orthopaedic clinical research. Clin Orthop Relat Res
2011;469(3):909-913.
12. Razmjou H, Finkelstein JA, Yee A, Holtby R, Vidmar M, Ford M:
Relationship between preoperative patient characteristics and
expectations in candidates for total knee arthroplasty. Physiother
Can 2009;61(1):38-45.
13. Roland CG: The case report. J Am Med Assoc 1968;205(5):281.
14. Fang CJ, Lester BW, Hollenbeck BL: Postoperative skin lesion
after knee replacement. J Am Med Assoc 2021;326(2):181. This is a
case report of a 71-year-old woman presenting with skin lesion
after knee replacement. Level of evidence: IV.
15. Churchill JL, Krych AJ, Lemos MJ, Redd M, Bonner KF: A case
series of successful repair of articular cartilage fragments in the
knee. Am J Sports Med 2019;47(11):2589-2595. This is a
retrospective clinical and radiographic evaluation of 10 patients
who underwent articular cartilage fragment repair. Level of
evidence: IV.
16. Lefaivre KA, Shadgan B, O’Brien PJ: 100 Most cited articles in
orthopaedic surgery. Clin Orthop Relat Res 2011;469(5):1487-1497.
17. Emara AK, Grits D, Klika AK, et al: NarxCare scores greater
than 300 are associated with adverse outcomes after primary
THA. Clin Orthop Relat Res 2021;479(9):1957-1967. The authors
associate preoperative prescription drug use with adverse
outcomes after total hip arthroplasty using an institutional
database. Level of evidence: III.
18. Castillo RC, Scharfstein DO, MacKenzie EJ: Observational
studies in the era of randomized trials: Finding the balance. J
Bone Joint Surg 2012;94(suppl 1):112-117.
19. Higuera-Rueda CA, Emara AK, Nieves-Malloure Y, et al: The
effectiveness of closed-incision negative-pressure therapy versus
silver-impregnated cressings in mitigating surgical site
complications in high-risk patients after revision knee
arthroplasty: The PROMISES randomized controlled trial. J
 Arthroplasty 2021;36(7):S295-S302.e14. This RCT compares closed-
incision negative-pressure therapy versus standard of care in
mitigating surgical site complications after revision knee
arthroplasty. Level of evidence: I.
20. Noordzij M, Dekker FW, Zoccali C, Jager KJ: Study designs in
clinical research. Nephron Clin Pract 2009;113(3):c218-c221.
21. Cizmic Z, Novikov D, Feng J, Iorio R, Meftah M: Alternative
payment models in total joint arthroplasty under the Affordable
Care Act. JBJS Rev 2019;7(3):e4. Various alternative payment
models applicable for orthopaedic surgeons are reviewed.
22. Squitieri L, Bozic KJ, Pusic AL: The role of patient-reported
outcome measures in value-based payment reform. Value Health
2017;20(6):834-836.
23. Baumhauer JF, Bozic KJ: Value-based healthcare: Patient-
reported outcomes in clinical decision making. Clin Orthop Relat
Res 2016;474(6):1375-1378.
24. Siljander MP, McQuivey KS, Fahs AM, Galasso LA, Serdahely
KJ, Karadsheh MS: Current trends in patient-reported outcome
measures in total joint arthroplasty: A study of 4 major
orthopaedic journals. J Arthroplasty 2018;33(11):3416-3421.
25. Ramkumar PN, Harris JD, Noble PC: Patient-reported outcome
measures after total knee arthroplasty: A systematic review. Bone
Joint Res 2015;4(7):120-127.
26. Lyman S, Lee YY, McLawhorn AS, Islam W, MacLean CH: What
are the minimal and substantial improvements in the HOOS and
KOOS and JR versions after total joint replacement? Clin Orthop
Relat Res 2018;476(12):2432-2441.
27. Je e DU, Stilphen M, Ranganathan VK, Passek SD, Frost FS,
Je e AM: AM-PAC “6-Clicks” functional assessment scores
predict acute care hospital discharge destination. Phys Ther
2014;94(9):1252-1261.
28. Wilson I, Bohm E, Lübbeke A, et al: Orthopaedic registries with
patient-reported outcome measures. EFORT Open Rev
 2019;4(6):357-367. This is a review of PROMs and practical
considerations of their implementation in orthopaedic surgery.
29. Clement ND, Bardge M, Weir D, Holland J, Gerrand C, Deehan
DJ: What is the minimum clinically important difference for the
womac index after TKA? Clin Orthop Relat Res 2018;476(10):2005-
2014.
30. Carragee EJ, Cheng I: Minimum acceptable outcomes after
lumbar spinal fusion. Spine J 2010;10(4):313-320.
31. Hutchings A, Neuburger J, Grosse Frie K, Black N, van der
Meulen J: Factors associated with non-response in routine use of
patient reported outcome measures after elective surgery in
England. Health Qual Life Outcomes 2012;10:34.
32. Connelly JW, Galea VP, Rojanasopondist P, et al: Patient
acceptable symptom state at 1 and 3 years after total knee
arthroplasty: Thresholds for the Knee Injury and Osteoarthritis
Outcome Score (KOOS). J Bone Joint Surg Am 2019;101(11):995-
1003. The authors used an international, multicenter cohort to
determine clinically relevant thresholds for Knee Injury and
Osteoarthritis Outcome Score. Level of evidence: IV.
33. Maltenfort M, Díaz-Ledezma C: Statistics in brief: Minimum
clinically important difference – Availability of reliable estimates.
Clin Orthop Relat Res 2017;475(4):933-946.
34. Leopold SS, Porcher R: Editorial: The minimum clinically
important difference – The least we can do. Clin Orthop Relat Res
2017;475(4):929-932.
35. Ridgeon EE, Young PJ, Bellomo R, Mucche i M, Lembo R,
Landoni G: The fragility index in multicenter randomized
controlled critical care trials. Crit Care Med 2016;44(7):1278-1284.
36. Tignanelli CJ, Napolitano LM: The fragility index in randomized
clinical trials as a means of optimizing patient care. JAMA Surg
2019;154(1):74-79. The authors identify median Fragility Index
and Fragility Quotient values for clinical trials and recommend
reporting these values for future RCTs.
37. Checke s JX, Sco JT, Meyer C, Horn J, Jones J, Vassar M: The
robustness of trials that guide evidence-based orthopaedic
surgery. J Bone Joint Surg Am 2018;100(12):e85.
38. Evaniew N, Files C, Smith C, et al: The fragility of statistically
significant findings from randomized trials in spine surgery: A
systematic survey. Spine J 2015;15(10):2188-2197.
39. Orr MN, Klika AK, Gagnier JJ, Bhandari M, Piuzzi NS: A call for
a standardized approach to reporting patient-reported outcome
measures: Clinical relevance ratio. J Bone Joint Surg
2021;103(22):e91. The authors propose a statistical concept and a
standardized reporting form for understanding PROs in clinical
trials.
40. Jones SR, Carley S, Harrison M: An introduction to power and
sample size estimation. Emerg Med J 2003;20(5):453-458.
41. Lewis SC: How to spot bias and other potential problems in
randomised controlled trials. J Neurol Neurosurg Psychiatry
2004;75(2):181-187.
42. Moher D, Schulz KF, Altman DG: The CONSORT statement:
Revised recommendations for improving the quality of reports of
parallel-group randomised trials. Lancet 2001;357(9263):1191-1194.
43. Sco J, Checke s JX, Cooper CM, Boose M, Wayant C, Vassar M:
An evaluation of publication bias in high-impact orthopaedic
literature. JBJS Open Access 2019;4(2):e0055. The authors assess
publication bias in the top 10 orthopaedic journals.
44. Poolman RW, Kerkhoffs GM, Struijs PAA, Bhandari M,
International Evidence-Based Orthopedic Surgery Working
Group: Don’t be misled by the orthopedic literature: Tips for
critical appraisal. Acta Orthop 2007;78(2):162-171.
C H AP T E R 3

Orthopaedic Patient Safety

Aaron M. Baessler MD, Thomas W. Throckmorton MD,
FAAOS

Dr. Throckmorton or an immediate family member has received royalties from Exactech, Inc.,
Responsive Arthroscopy, and Zimmer; is a member of a speakers’ bureau or has made paid
presentations on behalf of Pacira; serves as a paid consultant to or is an employee of
OsteoCentrics and Zimmer; has stock or stock options held in Exactech, Inc., Gilead, and
Responsive Arthroscopy; and serves as a board member, owner, officer, or committee member of
the American Academy of Orthopaedic Surgeons, the American Shoulder and Elbow Surgeons,
and ASES Foundation. Neither Dr. Baessler nor any immediate family member has received
anything of value from or has stock or stock options held in a commercial company or institution
related directly or indirectly to the subject of this chapter.

ABSTRACT
Patient safety is of utmost importance in healthcare. Multiple
compliance organizations ensure appropriate training and
oversight in patient safety, including the Accreditation Council for
Graduate Medical Education and The Joint Commission. The
Accreditation Council for Graduate Medical Education has
developed milestones that all orthopaedic surgeons and trainees
must achieve, whereas The Joint Commission has developed
institutional protocols that health care facilities must adopt.
Central to patient safety is effective communication in the patient-
surgeon relationship, which ensures that patients become educated
in their care and become involved in the shared decision-making
process. All cultures represent unique experiences and viewpoints,
and surgeons must consider cultural values and biases in the
treatment of patients to provide the best care possible.
Keywords: communication skills; cultural competence; informed
surgical consent; patient-centered care; shared decision-making

Introduction
To promote patient and physician safety in orthopaedic surgery,
multiple entities, including the Accreditation Council for Graduate
Medical Education (ACGME) and the American Board of
Orthopaedic Surgery (ABOS), have developed core competencies
for residents and a ending physicians. These oversight bodies also
emphasize clear, effective communication that allows for shared
decision-making between patients and physicians.

Core Competencies and Patient-Centered

Care

ACGME and Clinical Learning Environment

Review
In 2012, the ACGME introduced the Clinical Learning Environment
Review (CLER) program as part of the Next Accreditation System,
with the goal of improving safety and quality of care in teaching
hospitals, given the history of concerns regarding resident work
hours and patient safety. 1 CLER focuses on six areas: patient safety,
quality improvement, transition of care, appropriate resident
supervision, duty-hour oversight and fatigue management, and
professionalism. 1 The ACGME conducts an on-site visit every 18 to
24 months. 1 - 3 The purpose of the visits is to evaluate the role of
residents and fellows in each of the six CLER areas. The evaluation
commi ee, which is separate from ACGME review commi ees,
then provides the institution formal feedback based on each of the
six areas. The CLER also provides resources to aid in faculty
support and leadership development.
 From 2012 to 2015, the ACGME visited participating CLER
institutions and obtained surveys from designated institutional
officials. Surveys revealed that participating institutions increased
focus on patient safety, quality improvement, and resident
supervision, and improved in assessment of procedural
competency. 4 Most of the responding institutions (72%)
implemented changes to individual programs to address one or
more of the six CLER focus areas, with a positive, high-value CLER
experience reported by leadership. 5 A study independent of the
ACGME revealed similar findings in that almost two-thirds of
executive leaders view CLER as a positive experience, and
approximately one-third of all institutions added additional
resources to improve their respective programs, even in the
absence of formal ACGME requirements. 6 The CLER program
strives to continually improve the quality and safety of teaching
institutions, with the next data set from ACGME site visits to be
published in the near future. 7

Core Competencies for Orthopaedic Surgery

Trainees
Part of the ACGME Next Accreditation System involved milestones
for residents to achieve as they progress through training. 8 Specific
orthopaedic milestones were later reviewed in 2015, with the goal to
supplement resident evaluations with a common set of core
competencies that should be achieved. 9 The ACGME and the ABOS
have formally defined overall and subspecialty milestones in
several documents. 10 - 18 The milestones include patient care and
medical knowledge for common pathologies, systems-based
practice, practice-based learning and improvement,
communication, teamwork, and professionalism. A level from 1 to 5
is set for each milestone, with level 1 representing a ributes of an
incoming resident and level 5 representing a resident who has
advanced beyond expectations, nearing the level of an expert (Table
1). It should be noted that graduating residents do not necessarily
meet level 5 milestones, as this level is based on exceeding
expectations of a graduating resident. Level 4 is the target for
graduating residents. There is variability in training among
residency programs, and efforts continually seek to improve
milestone assessment. 19

Table 1
Milestone Evaluation Levels

Level Description Example: Rotator Cuff Injury—Patient Care

1 Milestones expected of an
incoming resident Obtains history and performs basic
physical examination
Lists surgical complications

2 Advancing appropriately but not

performing as well as a resident Obtains focused history and performs
in midresidency physical examination
Orders basic imaging studies
Performs basic surgical approaches and
portal placement
Performs simple shoulder procedures
Prescribes nonsurgical treatment
Provides basic postoperative
management
Diagnosis surgical complications

3 Advancing appropriately and

consistently meeting most Interprets basic imaging studies
targeted milestones Completes preoperative planning with
instrumentation and implants
Capable of performing diagnostic
arthroscopy, subacromial
decompression, distal clavicle resection,
biceps tenotomy
Level Description Example: Rotator Cuff Injury—Patient Care
4 Advancing appropriately and
substantially demonstrating all Able to order and interpret advanced
milestones for residency imaging studies
Completes comprehensive preoperative
planning and alternatives
Capable of performing rotator cuff repair
Appropriately interprets postoperative
imaging studies/implant positioning
Modifies and adjusts postoperative
rehabilitation plan as needed
Treats complications both intraoperatively
and postoperatively

5 Advanced beyond milestone

target Capable of performing complex
arthroscopic rotator cuff repairs, revision
rotator cuff repair, tendon transfers
Surgically manages complex
complications

Currently, orthopaedic surgery trainees are assessed by multiple

individual faculty members. The Clinical Competency Commi ee
at each training institution meets every 6 months to generate
milestone evaluations for each resident. As discussed in a 2020
study, the milestone ratings not only are used by individual
institutions but are also delivered to the ACGME, creating a
summative assessment of resident performance. 20

Core Competencies for the Practicing

Orthopaedic Surgeon
Practicing orthopaedic surgeons also must meet competency
requirements. The ABOS wri en examination test question writers
and oral board examiners, along with the General Orthopaedic
Competency Task Force, combined the medical knowledge and
patient care competencies mentioned previously into two broad
categories: assessment and management. 21 Generally, assessment
competency refers to the ability to appropriately initially evaluate,
investigate, and develop a management plan for conditions.
Management competency refers to the ability to provide initial or
emergency care, surgical or nonsurgical care, and appropriate
follow-up. Management of patients also includes the ability of
physicians to assess their own ability and to either provide
definitive care or transfer care to a qualified individual. There is a
set of six general orthopaedic surgery evaluation competencies and
several sets of individual management competencies that include
adult reconstruction, acute orthopaedic care, sports medicine and
sports surgery, pediatrics, spine, and foot and ankle. Similar to
trainee competencies, there are competencies for office-based
practice, communication, systems and culture, and professionalism.

Communication Skills and Cultural

Competence
Communicating effectively with patients has been shown to
improve quality of patient care. 22 Historically, orthopaedic
surgeons have been considered “high tech, low touch” by patients,
meaning that although orthopaedic surgeons’ technical skills are
excellent, compassion, listening, and overall communication skills
are poor compared with other physicians. 23 Empathy, in particular,
has been thought to be lacking in surgeon-patient communications
during office visits. 24 A retrospective review of all orthopaedic
patient complaints during a 16-year period at a tertiary referral
hospital showed that 14% of all complaints were related to
communication. However, the subcategories of
humaneness/disrespect and expectation of care and treatment
comprised 20% of all complaints. 25 Demeanor and empathy are
part of effective communication, and effective communication is
paramount in meeting patients’ expectations and achieving optimal
outcomes after treatment. Because 54% of all complaints were
communication related, this finding suggests that orthopaedic
surgeons need to improve communication skills.
Developing communication skills can improve outcomes and
overall patient satisfaction. A 2021 retrospective cohort study in
patients with lumbar spine surgery revealed that, after adjusting
for potential confounding variables, patient satisfaction scores were
directly related to physician communication. 26 The authors of a
2020 study demonstrated a correlation between patient ratings of
poor surgeon communication with increased postoperative pain
intensity after total hip arthroplasty. 27
Not only is effective communication important to patients, but it
is also important among health care workers. Effective
communication with patients and health care colleagues has been
shown to improve outcomes and satisfaction while decreasing
adverse event occurrences and length of stay. 28 However, effective
communication is not a diffusion of responsibility and physicians
should directly communicate care to patients and not rely on
support or nursing staff to relay information. One study evaluated
patients in a trauma center who had a canceled orthopaedic surgery
procedure for any reason, most commonly inadequate operating
room time. Nurses alone delivered more than half of all
explanations for surgery cancellation (54.7%) to patients. When an
explanation for the surgery cancellation was provided by a nurse
only, patients were much more likely to be dissatisfied than if the
explanation came directly from the treating physician. If the
physician notified the patient, 96% of patients were satisfied with
the communication. 29

CanMEDS Physician Competency

Framework Project
The Royal College of Physicians and Surgeons of Canada developed
The CanMEDS 2005 Physician Competency Framework Project,
which promotes physician communication skills. 30 Building on this
framework, the American Academy of Orthopaedic Surgeons
(AAOS) regularly promotes communication workshops. 31
However, proper development of communication skills is still
lacking in many residency programs. 32 Assessing residents early in
training with unannounced, standardized patient encounters allows
objective assessment of their communication, patient education,
counseling, and professionalism and can aid institutions in
developing a plan to improve these skills in trainees. 33
Furthermore, personality traits are correlated with communication
skills and, when observed, can be used to identify individual
residents who may need additional training. According to a 2019
study, stress-related personality traits, such as excitable, skeptical,
and imaginative negatively correlate with communication skills,
whereas day-to-day personality traits, such as emotional stability,
agreeability, and conscientiousness correlate with positive
communication skills. 34

The Four E’s: Engagement, Empathy,

Education, Enlistment
An inherent problem within the physician-patient relationship is
the gap in knowledge between the physician and patient about a
disease process, which makes it difficult to understandably convey
a diagnosis and treatment plan. For this reason, the four E’s model
was created to aid in the development of successful communication
skills. 30 The model uses four key actions that physicians may use
for effective communication with patients: engagement, empathy,
education, and enlistment (Table 2). Overall, the model fosters a
human connection between physician and patient, creating trust by
showing understanding of the patient’s condition, reducing patient
anxiety by educating the patient on the condition, and enlisting the
patient into the decision-making process. This promotes patient
adherence to treatment plans and overall satisfaction.

Table 2
The Four E’s Model for the Physician-Patient Relationship

Engagement Create a personal connection. Use welcoming body language. Allow the
patient to speak without interruption. Translate medical terms and knowledge
to simple words and explain in easy-to-learn ways.
Empathy Verbally explain understanding of the patient’s situation. Garner the patient’s
 feelings and concerns.
Education Allow a discussion to occur about the patient’s diagnosis and treatment. Do
not lecture one-sided to patients. Always ask for questions or concerns
regarding the diagnosis and treatment.
Enlistment Explain all risks, benefits, alternatives, and goals of treatment. Allow and
motivate the patient to participate in making a decision.

Cultural Competency

Awareness, Attitude, Knowledge, and Skills

A model of cultural competence has been published that includes
four major components: awareness, a itude, knowledge, and skills.
35
Conceptually, awareness relates to the fact that cultures have
different values and beliefs. A itude allows introspection into
personal beliefs and views toward cultural differences. Knowledge
relates to the understanding that other people or cultures may lack
particular knowledge or contain additional knowledge unknown to
oneself. Cross-cultural skills allow interpersonal interaction across
cultures and the practice of other competencies.
For professionals, cultural competence is achieved after
understanding that individuals have different needs-based cultural
(ie, language, thoughts, communication, actions, customs, beliefs,
values) and institutional (ie, racial, ethnic, religious, social)
structures. 36 Greater cultural awareness and competence by
physicians will help patients be er understand diagnoses and
treatment, which ultimately will lead to be er adherence to
treatment protocols and improved patient outcomes.
From a practical standpoint, the aforementioned cultural
competence concepts are limited in the patient-physician
relationship by several obstacles. Cultural differences, along with
language barriers and literacy differences, may prevent information
from being exchanged or understood. 37 As the US population
continues to become more diverse, efforts are being focused on
understanding cultural differences and biases. A review of cultural
biases highlights the disparity among cultures, using total joint
arthroplasty as an example. 38 Cultural lifestyle and perceived
dysfunction or pain need to be taken into context for each patient.
For instance, a patient who kneels to pray daily may have more
knee pain after total knee arthroplasty than a patient who does not.
In another example of two patients with hip osteoarthritis, the first
patient has severe radiographic changes and is functionally limited
but does not want to have surgery, whereas the second patient has
mild radiographic changes with only minimal symptoms but
expects hip arthroplasty. These differences may result from life
experiences or cultural perceptions of diseases and treatments.

Shared Decision-Making
It is paramount to include patients in the treatment decision-
making process. Much of this chapter has been dedicated to
discussing physician-patient communication, and effective
communication is required to involve patients in shared decision-
making. Shared decision-making is simply the idea that decisions
should be shared with patients and not made for them by the
treating physician. 39 Surgeons alone poorly predict patient
treatment preferences. 40 By involving the patient in the decision-
making process, the surgeon will have a be er idea of patient ideals
and preferences for treatment. 41 Shared decision-making should be
part of every patient encounter, but patients particularly appreciate
shared decision-making when a surgical procedure is an option or
when more than one reasonable treatment option exists. 42
A number of methodologies exist for shared decision-making
between physician and patient; however, all contain the following
steps. (1) Invite the patient to engage in the decision-making
process. A patient may fear being labeled as difficult and may not
initiate conversation. 43 (2) Provide all treatment options, including
risks and benefits of each. Decision aids are helpful in this step,
educating and increasing the patient’s knowledge, which leads to
more productive conversations between the physician and the
patient. 44 , 45 Examples of decision aids are a wri en list of pros and
cons, pamphlets, a video, or a web-based interface on a particular
topic. (3) During the discussion with the patient, leave no question
or concern unanswered. 41 The physician must provide guidance,
and the patient must provide preferences.
Interestingly, the way in which a physician presents treatment
choices can affect a patient’s treatment choice. In one study,
patients with tibial plateau fractures in five different clinical
scenarios were offered two or three treatment choices for each
particular scenario; the patients returned 4 weeks later to repeat the
same scenarios with a slight modification in the way the physician
had presented it. 46 Each scenario tested for a unique bias, and
patients in each scenario changed their preferred treatment to a
statistically significant degree when the treatment options were
presented slightly differently than the index visit. To test for an
emotional bias, for example, patients were offered a prophylactic
fasciotomy to prevent compartment syndrome as opposed to only
having a fasciotomy performed if compartment syndrome signs
appeared after surgery (higher risk of failure but potentially avoids
unnecessary surgery). During the first presentation, the
complications and odds were verbally discussed with the patient,
whereas in the second presentation 4 weeks later, photographs of
an unsuccessfully managed compartment syndrome were added to
the same verbal discussion. Forty-three percent of patients chose
prophylactic fasciotomy after the first presentation, whereas 70% of
patients chose to have the procedure after the second presentation.
There are several benefits to shared decision-making. Involving
patients leads to be er adherence to treatment plans, be er health
outcomes, and improved patient satisfaction. 47 Shared decision-
making ensures that more patients who desire an intervention
actually receive that intervention; it also ensures that patients who
do not want an intervention do not receive that intervention. This
may reduce cost by avoiding unnecessary procedures. 48
Barriers exist in the shared decision-making process. The average
American patient reads at the eighth-grade level. 49 Any wri en or
spoken information needs to be clear and concise, without using
technical jargon. Health literacy tends to be lower in patients with
lower income, no insurance, advanced age, and speaking a primary
language other than English. 50 Therefore, it may be useful to assess
health literacy prior to the decision-making process. Some cultures
or ethnic groups may have beliefs and preferences of which
physicians may be unaware. This is where step 1 (invite the patient
to engage) becomes an important component in the process.
Religious beliefs, for example, may be a significant concern for
some patients but not others.
For physicians, one concern with shared decision-making is that
the additional time required may lead to decreased clinic efficiency.
51
Few studies address this directly; however, long-term benefits
such as fewer postoperative questions and fewer office visits or
phone calls may compensate for the initial time deficit. 52 , 53 A 2021
study was conducted on a web-based interactive patient-provider
software platform for communication, but no benefit was noted
over direct patient-physician communication. 54
Shared decision-making should be incorporated by every
orthopaedic surgeon. Patients benefit by becoming knowledgeable
about their condition and potentially reduced unwanted costs, and
surgeons benefit from having satisfied patients who adhere to
treatment plans and goals.

Informed Surgical Consent

The idea of informed consent recognizes that capable adults have
the right to determine treatment that will affect their bodies. 55 For
surgery, obtaining informed consent is part of the shared decision-
making process. It includes a document that informs a patient
about the procedure to be performed along with the related risks.
Both the patient and surgeon sign the document, indicating that
both understand and accept the procedure to be performed. The
consent serves as a legal document to both the state and surgical
facility as regulated by the proper organization such as The Joint
Commission. 56 There are multiple important pieces of information
contained on a surgical informed consent (Table 3). These include
correct identification of the patient, surgical site, laterality, level (if
indicated), procedure, and implant (if applicable). 55

Table 3
Elements of an Informed Orthopaedic Surgery Consent

Element Needs to Include Example

Correct patient Two identifiers Name, DOB, MRN
Surgical site Location on body Shoulder
Laterality Right, left, or bilateral Right
Level (if applicable) Vertebral level number L5
Procedure Exactly what will be done Total shoulder arthroplasty
Implant Type of implant that will be used Reverse (total shoulder)
DOB = date of birth, MRN = medical record number

In elective surgery, surgical consent is not a single document or

event. The consent process includes a thorough discussion of the
surgery, risks, alternatives, goals, and expected postoperative
course during the preoperative visit, along with accurate medical
record documentation during the visit. The consent process needs
to be performed by the treating surgeon without relying on others
to provide consent to avoid confusion. The physical informed
consent document needs to be completed prior to bringing the
patient into the operating room, ideally in the preoperative holding
area or even the day before surgery. Both the discussion and wri en
language on the form need to be accurate, legible, and
understandable, avoiding confusing medical terminology that can
limit patient comprehension. 57 The final component of informed
consent ensures adequate time for any questions the patient may
have. 55 Despite knowing the components and process of obtaining
informed consent, preventable consent errors still occur. Wrong
surgery still occurs and remains in the top five of commonly
reviewed sentinel events by The Joint Commission. 58
 Minors also have limited rights to make personal health care
decisions. The age at which a minor is considered an adult and able
to provide informed consent depends on the state, but most
commonly it is 18 years. Even before this age, minors need to be
included in discussions regarding their care. A parent or legal
guardian must be present for the discussion and must sign the
consent form. However, minors are protected by law in their right
to receive limb-saving or life-saving treatment, even if a parent or
guardian refuses treatment. 59
For patients who do not speak or understand English, and if the
surgeon does not speak or sign in the patient’s native language, a
proficient translator must be provided to the patient. Health
literacy and reading comprehension also tend to decrease with
increasing age, so all communication must be clear and concise,
and the surgeon must ensure the patient understands the consent.
60
Asking the patient to repeat important aspects of the consent is
useful and may improve the consent process and patient
satisfaction. 61
Decisional capacity also may affect the surgical informed consent
process, such as when another person needs to make treatment
decisions on behalf of a patient who lacks the ability to do so. Each
state has a hierarchy of surrogate decision-makers for patients
lacking decisional capacity. Generally, the patient’s family serves on
this hierarchy and is listed as follows, in descending order: the
spouse (unless divorced or legally separated), an adult child, a
parent, and an adult sibling. 62 In some circumstances, a durable
power of a orney can be appointed by the patient ahead of time.
The power of a orney acts as the designated person, or surrogate,
who is legally responsible to make medical decisions on the
patient’s behalf. When no family or designated power of a orney is
available to provide informed consent for a life-threatening or limb-
threatening issue, two-physician consent may be used. 63 In
complicated cases without any decision makers available, the
hospital ethics commi ee may become involved.
Summary
Multiple entities exist to provide appropriate education in core
competencies and patient-centered care to orthopaedic surgery
trainees and surgeons. A central goal of these training programs is
to promote the safety of patients. Arguably, the most important
aspect of medicine and surgery is communication. Effective
communication increases patient satisfaction and outcomes in
addition to promoting patient safety. Communication skills differ
among trainees and surgeons, and specific methods should be
learned and used, all while taking patient cultural differences into
account. In orthopaedic surgery, effective communication is
paramount in the shared decision-making process and while
obtaining informed consent.

Key Study Points

The ACGME and ABOS have described core competencies for both orthopaedic
surgery trainees and orthopaedic surgeons.
Effective communication relies on specific skills developed by the surgeon, while
understanding that patients’ backgrounds may affect communication styles.
Shared decision-making improves patient knowledge, adherence to treatment,
outcomes, satisfaction.
Informed surgical consent requires patient understanding, and there are rules for
obtaining consent when a patient lacks the ability to understand.

Annotated References
1. Weiss KB, Wagner R, Nasca TJ: Development, testing, and
implementation of the ACGME Clinical Learning Environment
Review (CLER) program. J Grad Med Educ 2012;4(3):396-398.
2. Weiss KB, Bagian JP, Nasca TJ: The clinical learning
environment: The foundation of graduate medical education. J
Am Med Assoc 2013;309(16):1687-1688.
3. Weiss KB, Wagner R, Bagian JP, Newton RC, Patow CA, Nasca
TJ: Advances in the ACGME Clinical Learning Environment
 Review (CLER) program. J Grad Med Educ 2013;5(4):718-721.
4. Koh NJ, Wagner R, Sun H, Newton R, Casey BR, Weiss KB: Early
impressions of the CLER program: A survey of the designated
institutional official community. J Grad Med Educ 2016;8(3):478-
482.
5. Wagner R, Patow C, Newton R, Casey BR, Koh NJ, Weiss KB: The
overview of the CLER program: CLER national report of findings
2016. J Grad Med Educ 2016;8(2 suppl 1):11-13.
6. Long TR, Doherty JA, Frimannsdo ir KR, Rose SH: An early
assessment of the ACGME CLER program: A national survey of
designated institutional officials. J Grad Med Educ 2017;9(3):330-
335.
7. Wagner R, Newton RC, Casey BR, Weiss KB: The continuous
quality improvement of CLER. J Grad Med Educ 2017;9(3):336-337.
8. Nasca TJ, Philibert I, Brigham T, Flynn TC: The next GME
accreditation system-rationale and benefits. N Engl J Med
2012;366:1051-1056.
9. Van Heest AE, Dougherty PJ: CORR curriculum-orthopaedic
education: Operative assessment and the ACGME milestones –
Time for change. Clin Orthop Relat Res 2015;473:775-778.
10. Accreditation Council for Graduate Medical Education,
American Board of Orthopaedic Surgery: The Orthopaedic Surgery
Milestone Project. 2015, pp i-48. Available
at: h ps://www.acgme.org/Portals/0/PDFs/Milestones/Orthopaedi
cSurgeryMilestones.pdf?ver=2015-11-06-120524-887. Accessed
June 8, 2021.
11. Accreditation Council for Graduate Medical Education,
American Board of Orthopaedic Surgery: The Adult Reconstructive
Surgery Milestone Project. 2015, pp i-26. Available at:
h ps://www.acgme.org/Portals/0/PDFs/Milestones/AdultReconstr
uctiveSurgeryMilestones.pdf?ver=2015-11-06-120534-290.
Accessed June 8, 2021.
12. Accreditation Council for Graduate Medical Education,
American Board of Orthopaedic Surgery: The Foot and Ankle
 Milestone Project. 2015, pp i-22. Available at: h ps://www.
acgme.org/Portals/0/PDFs/Milestones/FootandAnkle
Milestones.pdf?ver=2015-11-06-120531-160. Accessed June 8, 2021.
13. Accreditation Council for Graduate Medical Education,
American Board of Orthopaedic Surgery: The Hand Surgery
Milestone Project. 2015, pp i-18. Available at:
h ps://www.acgme.org/Portals/0/PDFs/Milestones/HandSurgery
Milestones.pdf?ver=2015-11-06-120530-627. Accessed June 8, 2021.
14. Accreditation Council for Graduate Medical Education,
American Board of Orthopaedic Surgery: The Musculoskeletal
Oncology Milestone Project. 2015, pp i-18. Available at:
h ps://www.acgme.org/Portals/0/PDFs/Milestones/Musculoskelet
alOncologyMilestones.pdf?ver=2015-11-06-120526-940. Accessed
June 8, 2021.
15. Accreditation Council for Graduate Medical Education,
American Board of Orthopaedic Surgery: The Orthopaedic Sports
Medicine Milestone Project. 2015, pp i-13. Available
at: h ps://www.acgme.org/Portals/0/PDFs/Milestones/Orthopaedi
cSportsMedicineMilestones.pdf?ver=2015-11-06-120525-030.
Accessed June 8, 2021.
16. Accreditation Council for Graduate Medical Education,
American Board of Orthopaedic Surgery: The Orthopaedic Trauma
Milestone Project. 2015, pp i-18. Available at:
h ps://www.acgme.org/Portals/0/PDFs/Milestones/Orthopaedic
TraumaMilestones.pdf?ver=2015-11-06-120524-810. Accessed June
8, 2021.
17. Accreditation Council for Graduate Medical Education,
American Board of Orthopaedic Surgery: The Pediatric Orthopaedic
Surgery Milestone Project. 2015, pp i-20. Available at:
h ps://www.acgme.org/Portals/0/PDFs/
Milestones/PediatricOrthopaedicsMilestones.pdf? ver=2015-11-
06-120523-327. Accessed June 8, 2021.
18. Accreditation Council for Graduate Medical Education,
American Board of Orthopaedic Surgery: The Spinal Orthopaedic
 Surgery Milestone Project. 2015, pp i-15. Available
at: h ps://www.acgme.org/Portals/0/PDFs/Milestones/
SpinalOrthopeadicSurgeryMilestones.pdf?ver=2015-11-06-120519-
840. Accessed June 8, 2021.
19. Dougherty PJ: CORR curriculum – Orthopaedic education:
Reconsidering the ACGME orthopaedic milestones. Clin Orthop
Relat Res 2018;476:2142-2145.
20. Ames SE, Ponce BA, Marsh JL, Hamstra SJ: Orthopaedic surgery
residency milestones: Initial formulation and future directions. J
Am Acad Orthop Surg 2020;28(1):e1-e8. Orthopaedic Milestones 1.0
provides a guide to uniformly track competence training in
residency programs. The tracked data will be shared and will aid
in identifying gaps in learning to ensure competency and a more
uniform orthopaedic curriculum.
21. Kellam JF, Archibald D, Barber JW, et al: The core competencies
for general orthopaedic surgeons. J Bone Joint Surg Am
2017;99:175-181.
22. Klein ER: Effective communication with patients. Pa Nurse
2005;60:14-15.
23. Tongue JR, Epps HR, Forese LL: Communication skills. Instr
Course Lect 2005;54:3-9.
24. Levinson W, Hudak P, Tricco AC: A systematic review of
surgeon-patient communication: Strengths and opportunities for
improvement. Patient Educ Couns 2013;93:3-17.
25. King JD, van Dijk PAD, Overbeek CL, et al: Patient complaints
emphasize non-technical aspects of care at a tertiary referral
hospital. Arch Bone Joint Surg 2017;5(2):74-81.
26. Rabah NM, Khan HA, Winkelman RD, et al: Key drivers of
patient satisfaction with spine surgeons in the outpatient se ing.
J Neurosurg Spine 2021;34(6):871-878. This study sought key
drivers of patient satisfaction in office-based spine surgery and
found that communication between surgeons and patients was
the strongest predictor of satisfaction in patients. Level of
evidence: V.
27. Mohamed NS, Castrodad IMD, Gwam CU, et al: Pain intensity
in total hip arthroplasty patients: How communication influences
satisfaction. Hip Int 2020;30(6):690-694. Using the Press Ganey
survey responses of 302 patients, the authors found that scores
specifically related to communication with doctors and
communication about medicine correlated with true pain
intensity levels postoperatively in patients undergoing total hip
arthroplasty. Be er staff communication to improve patient
satisfaction was emphasized. Level of evidence: IV.
28. Epstein NE: Multidisciplinary in-hospital teams improve patient
outcomes: A review. Surg Neurol Int 2014;5:S295-S303.
29. Mehta SS, Bryson DJ, Mangwani J, Cutler L: Communication
after cancellations in orthopaedics: The patient perspective.
World J Orthop 2014;5:45-50.
30. Keller VF, Carroll JG: A new model for physician-patient
communication. Patient Educ Couns 1994;23:131-140.
31. Institute for Health Care Communication: The American
Academy of Orthopaedic Surgeons. Available at:
h ps://healthcarecomm.org/case-studies/american-academy-of-
orthopaedic-surgeons/. Accessed August 5, 2021. The American
Academy of Orthopaedic Surgeons (AAOS) developed a national
physician-patient communication skills program. Coinciding
with other medical specialties adding physician communication
skills to their curricula, the AAOS began a 3-year pilot program
that entailed 4.5-hour training workshops on physician-patient
interaction, which is a permanent offering. They partnered with
the Institute for Healthcare Communication that has trained over
90,000 physicians in the clinical model known as the 4Es (engage,
empathize, educate, and enlist). Insurance companies now offer
discounts to physicians who participate in these CME
communication workshops.
32. Lundine K, Buckley R, Hutchison C, Lockyer J: Communication
skills training in orthopaedics. J Bone Joint Surg Am 2008;90:1393-
1400.
33. Taormina DP, Zuckerman JD, Karia R, Zabar S, Egol KA,
Phillips DP: Clinical skills and professionalism: Assessing
orthopaedic residents with unannounced standardized patients. J
Surg Educ 2017;75(2):427-433.
34. Holmes KS, Zuckerman JD, Maculatis MC, Friedman AM,
Lawrence E, Phillips DP: Personality predictors of
communication skills among orthopedic surgery residents. J Surg
Educ 2019;77(1):202-212. This retrospective analysis assessed
resident personality traits and found that certain stress traits
negatively influenced their communication skills, whereas
emotional stability traits had a positive influence on
communication skills. Level of evidence: III.
35. Pederson PB: The making of a culturally competent counselor,
in Lonner WJ, Dinnel DL, Hayes SA, Sa ler DN, eds: Online
Readings in Psychology and Culture. Center for Cross-Cultural
Research, Western Washington University, 2002. Available at:
h ps://scholarworks.gvsu.edu/orpc/vol10/iss3/4/. Accessed July 9,
2021.
36. Donahue L: What is cultural competence? PSJS 250 Social
Change through Service 2013. Available at:
h ps://www.vanderbilt.edu/oacs/wp-
content/uploads/sites/140/CulturalCompetence.pdf. Accessed
August 5, 2021. This article defines cultural competence and
communication. Cultural competence is the knowledge that
patients and staff have different needs, based on their language,
thoughts, customs, ethnic and religious beliefs. It discusses how
to build cross-cultural skills and enable work in cross-cultural
situations.
37. Schyve PM: Language differences as a barrier to quality and
safety in health care: The Joint Commission perspective. J Gen
Intern Med 2007;22(suppl 2):360-361.
38. Etienne G, Pierce TP, Khlopas A, et al: Cultural biases in current
medical practices with a specific a ention to orthopedic surgery:
A review. J Racial Ethn Health Disparities 2018;5:563-569.
39. Politi MC, Dizon DS, Frosch DL, Kuzemchak MD, Stiggelbout
AM: Importance of clarifying patients’ desired role in shared
decision making to match their level of engagement with their
preferences. Br Med J 2013;347:f0766.
40. Elwyn G, Frosch D, Thomson R, et al: Shared decision making:
A model for clinical practice. J Gen Intern Med 2012;27:1361-1367.
41. Wilson CD, Probe RA: Shared decision-making in orthopaedic
surgery. J Am Acad Orthop Surg 2020;28:e1032-e1041. This article
explored the models of shared decision-making, including the
benefits and barriers of implementation into practice. They
discuss in depth the role of decision aids and the effect of
technology on this process.
42. Chewning B, Bylund CL, Shah B, Arora NK, Gueguen JA,
Makoul M: Patient preferences for shared decisions: A systematic
review. Patient Educ Couns 2012;86:9-18.
43. Frosch DL, May SG, Rendle KA, Tietbohl C, Elwyn G:
Authoritarian physicians and patients’ fear of being labeled
“difficult” among key obstacles to shared decision making.
Health Aff 2012;31(5):1030-1038.
44. Stacey D, Légaré F, Lewis K, et al: Decision aids for people
facing health treatment or screening decisions. Cochrane Database
Syst Rev 2017;4:CD001431.
45. Hsu C, Liss DT, Frosch DL, Westbrook EO, Arterburn D:
Exploring provider reactions to decision aid distribution and
shared decision making: Lessons from two specialties. Med Decis
Making 2017;37:113-126.
46. Bernstein J, Kupperman E, Kandel LA, Ahn J: Shared decision
making, fast and slow: Implications for informed consent,
resource utilization, and patient satisfaction in orthopaedic
surgery. J Am Acad Orthop Surg 2016;24:495-502.
47. Sepucha KR, Atlas SJ, Chang Y, et al: Informed, patient-centered
decisions associated with be er health outcomes in orthopedics:
Prospective cohort study. Med Decis Making 2018;38:1018-1026.
48. Trenaman I, Stacey D, Bryan S, et al: Decision aids for patients
considering total joint replacement: A cost-effectiveness analysis
alongside a randomised controlled trial. Osteoarthritis Cartilage
2017;25:1615-1622.
49. Eltorai AE, Sharma P, Wang J, Daniels AH: Most American
Academy of Orthopaedic Surgeons’ online patient education
material exceeds average patient reading level. Clin Orthop Relat
Res 2015;473:1181-1186.
50. Menendez MR, Mudgal CS, Jupiter JB, Ring D: Health literacy in
hand surgery patients: A cross-sectional survey. J Hand Surg Am
2015;40:798-804.e2.
51. Braddock CIII, Hudak PL, Feldman JJ, Bereknyei S, Frankel RM,
Levinson W: “Surgery is certainly one good option”: Quality and
time-efficiency of informed decision-making in surgery. J Bone
Joint Surg Am 2008;90:1830-1838.
52. Warlick CA, Berge JM, Ho YY, Yeazel M: Impact of a prostate
specific antigen screening decision aid on clinic function. Urol
Pract 2017;4:448-453.
53. Reid R, Puvanesarajah V, Kandil A, et al: Factors associated with
patient-initiated telephone calls after spine surgery. World
Neurosurg 2017;98:625-631.
54. Visperas AT, Greene KA, Krebs VE, Klika AK, Piuzzi NS,
Higuera-Rueda CA: A web-based interactive patient-provider
software platform does not increase patient satisfaction or
decrease hospital resource utilization in total knee and hip
arthroplasty patients in a single large hospital system. J
Arthroplasty 2021:S0883-S5403. This prospective clinical trial
involved 399 patients undergoing elective total hip or knee
arthroplasty. Patients were randomized to test a patient-provider
software program or undergo standard of care for
communication with their provider. No statistical differences
were found in satisfaction between the two communication
platforms. The authors recommended that the software program
 be used to supplement traditional office follow-up visits. Level of
evidence: I.
55. Orthopaedic Surgical Consent – Information Statement. American
Academy of Orthopaedic Surgeons, 2014. Available at:
h ps://www.aaos.org/globalassets/about/bylaws-
library/information-statements/1038-orthopaedic-surgical-
consent.pdf. Accessed June 8, 2021.
56. The Joint Commission: Universal Protocol. Available at:
h ps://www.jointcommission.org/standards/universal-protocol/.
Accessed June 8, 2021. Wrong-site surgery remains a sentinel
event by the Joint Commission. This website through the Joint
Commission provides guidance and a protocol for preventing
surgery on the wrong site, wrong procedure, or wrong person.
The protocol consists of three key steps: the pre-procedure
verification process, marking the procedure site, and performing
a time-out.
57. Ga ellari M, Butow PN, Ta ersall MH: Informed consent: What
did the doctor say? Lancet 1999;353(9165):1713.
58. The Joint Commission: Most Commonly Reviewed Sentinel Event
Types. The Joint Commission, 2021. Available at:
h ps://www.jointcommission.org/-/media/tjc/documents/resource
s/patient-safety-topics/sentinel-event/most-frequently-reviewed-
event-types-2020.pdf. Accessed June 8, 2021. An update and
review of sentinel events in patient safety that can result in harm
or death is presented. The top five events reviewed by The Joint
Commission were falls, unintended retention of a foreign object,
suicide, wrong surgery, and delay in treatment, the reasons for
which are described in detail.
59. Information Statement – Patient-Physician Communication.
American Academy of Orthopaedic Surgeons, 2017. Available at:
h ps://www.aaos.org/globalassets/about/bylaws-
library/information-statements/1017-patient-
physiciancommunication.pdf. Accessed June 8, 2021.
60. Gazmararian JA, Baker DW, Williams MV, et al: Health literacy
among Medicare enrollees in a managed care organization. J Am
Med Assoc 1999;281:545-551.
61. Prochazka AV, Fink AS, Bartenfeld D, et al: Patient perceptions
of surgical informed consent: Is repeat back helpful or harmful? J
Patient Saf 2014;10(3):140-145.
62. Decisions by Surrogates: An Overview of Surrogate Consent Laws
in the United States. American Bar Association, 2014. Available
at:
h ps://www.americanbar.org/groups/law_aging/publications/bifo
cal/vol_36/issue_1_october2014/default_surrogate_consent_statut
es/. Accessed June 8, 2021.
63. DeMartino ES, Dudzinski DM, Doyle CK, et al: Who decides
when a patient can’t? Statutes on alternate decision makers. N
Engl J Med 2017;376(15):1478-1482.
C H AP T E R 4

Regulation of Orthopaedic
Products
Veronica Fleck MS, RAC, Mehdi Kazemzadeh-Narbat PhD,
PMP, CQA, Samuel Pollard RAC, S. Raymond Golish MD,
PhD, MBA, FAAOS

Dr. Kazemzadeh-Narbat or an immediate family member serves as a paid consultant to or is an

employee of Abbott and Acumed, LLC. Samuel Pollard or an immediate family member has stock
or stock options held in Gilead Sciences, Johnson & Johnson, and Novo Nordisk. Dr. Golish or
an immediate family member serves as a paid consultant to or is an employee of Bio2Tech,
Centinel Spine, Icotec, Intrinsic Therapeutics, Kuros Biosciences, Paradigm Spine, Simplify
Medical, Spine BioPharma, and Wright Medical Technology, Inc.; serves as an unpaid consultant
to Cytonics; has stock or stock options held in Cytonics and Cytonics, Inc.; and serves as a
board member, owner, officer, or committee member of AAOS Biomedical Engineering Committee,
ASTM, and North American Spine Society. Neither Veronica Fleck nor any immediate family
member has received anything of value from or has stock or stock options held in a commercial
company or institution related directly or indirectly to the subject of this chapter.

ABSTRACT
For medical products, the FDA’s primary goal is to protect public
health by ensuring the safety, efficacy, and security of drugs,
biologic products, and medical devices. Medical devices constitute
most products used in orthopaedic procedures and are regulated by
the Center for Devices and Radiological Health, which classifies
devices into three groups according to the degree of risk and level
of control necessary to ensure safety and effectiveness. A medical
device’s classification determines the statutory requirements and
necessary evidence needed to legally market the product. The FDA
has developed independent requirements for custom devices
designed to address an unmet clinical need. The FDA regulates
drug and biologic products under the Center for Drug Evaluation
and Research and the Center for Biologics Evaluation and Research,
respectively, with markedly distinct requirements compared with
medical devices. Combination products that incorporate a
combination of a drug, biologic product, and device are reviewed in
a multicenter manner with a lead center assigned based on the
primary mode of action. The FDA monitors postmarket product
performance through postmarket surveillance of adverse event
reporting and recall actions to correct or remove products that
present a threat to patient safety. Through these measures, the
FDA regulates products used in the orthopaedic industry to ensure
safety and effectiveness.
Keywords: custom device exemption; FDA regulation; medical
device classification; postmarket surveillance; premarket review
pathway

Introduction
It is important to outline the policies and regulations by which the
FDA protects public health by ensuring the safety, efficacy, and
security of drugs, biologic products, and medical devices. The FDA
uses distinct statutory requirements for these three product types,
with each being overseen by dedicated review centers. Medical
devices and the associated premarket and postmarket regulatory
requirements also are prevalent in the orthopaedic industry. In
addition, orthopaedic surgeons should be knowledgeable about
combination products and the various biologic and drug
regulations.

FDA History and Mission

The FDA is a subsidiary of the Department of Health and Human
Services and is responsible for the regulation of foods, dietary
supplements, cosmetics, veterinary products, drugs, medical
devices, and biologics intended for human use. The FDA’s mission
is to protect public health by ensuring the safety, efficacy, and
security of human and veterinary drugs, biologic products, and
medical devices. The centers that primarily focus on medical
products include the Center for Drug Evaluation and Research
(CDER), the Center for Biologics Evaluation and Research (CBER),
and the Center for Devices and Radiological Health (CDRH).

Medical Devices

History of Medical Device Legislation

Despite an increased scrutiny on food, drugs, and biologic products
in the early 19th century, medical devices remained largely
unregulated until Congress enacted the Medical Device
Amendments to the Federal Food, Drug, and Cosmetic Act in 1976
to provide reasonable assurance of the safety and effectiveness of
medical devices. This act laid the foundation of the medical device
regulation framework currently used, creating a risk-based
classification system for all medical devices and establishing the
regulatory pathways for new medical devices, including premarket
approval (PMA), premarket notification (510(k)), and
Investigational Device Exemption (IDE).
The Safe Medical Devices Act of 1990 expanded the prior medical
device regulation to include improved postmarket surveillance of
devices. In addition, this Act authorized recalls and civil penalties
for violations, developed substantial equivalence for the 510(k)
program, and created the Humanitarian Use Device
(HUD)/Humanitarian Device Exemption (HDE) program for the
development of devices targeting rare diseases.
In 1997, legislation was passed under the FDA Modernization
Act, which provided additional updates to the regulatory
framework, including the creation of the least burdensome
provisions for premarket review and establishing the de novo
program. Additional legislation has since been passed to grant the
FDA the authority to collect user fees, enact the Small Business
Determination program, establish a Unique Device Identification
system, and create the Breakthrough Device Designation program
to expedite the review of novel technologies intended to treat
serious or life-threatening diseases or conditions. 1

Medical Device Classification

The term medical device refers to an instrument, apparatus,
implement, machine, contrivance, implant, in vitro reagent, or other
similar or related article, including any component, part, or
accessory, that is (1) recognized in the official National Formulary,
or the United States Pharmacopeia or any supplement to them; (2)
intended for use in the diagnosis of disease or other conditions, or
in the cure, mitigation, treatment, or prevention of disease; or (3)
intended to affect the structure or any function of the human body,
and that does not achieve its primary intended purposes through
chemical action within or on the body and is not dependent on
being metabolized for the achievement of its primary intended
purposes.

Risk Classifications
FDA classifies medical devices into one of three classes according
to the degree of risk and the level of control necessary to ensure the
safety and effectiveness of the device. 2 The three classes are as
follows:

Class I—Lowest risk requiring general controls, for example,

surgical instruments, medical gloves, elastic bandages, and
scalpels. Most class I devices are exempt from 510(k)
submissions.
Class II—Moderate risk requiring special controls, for example,
intervertebral cages, intramedullary nails, fracture fixation
plating systems, and most total joint arthroplasties. Most class
II devices require 510(k) clearance with applicable special
 q pp p
controls and demonstration of substantial equivalence to a
predicate device. Benchtop biomechanical testing in alignment
with standards-se ing organizations (eg, American Society for
Testing and Materials, International Organization for
Standardization) is typical for 510(k) orthopaedic devices, and
most do not require supporting clinical trial data.
Class III—Greatest potential risk requiring PMA, for example,
total disk arthroplasties and other motion-preserving spinal
implants, novel joint arthroplasty systems such as some mobile
and hard-on-hard bearings, recombinant osteobiologic bone
graft substitutes, and hyaluronic acid products regulated as
devices. Class III devices support or sustain human life, are of
substantial importance in preventing impairment of human
health, present an unreasonable risk of illness or injury, or are
not substantially equivalent to a legally marketed predicate.

Any device that does not fall under an existing class I, II, or III
regulation and is not considered a preamendment device, as
previously defined, is automatically classified as class III under
section 513(f). This automatic classification occurs without any FDA
rulemaking process and regardless of the risk. Device
manufacturers can submit a request for a formal device
determination or classification from the FDA through a 513(g)
request before submi ing a marketing application.

General and Special Controls

General controls are the basic provisions that provide the FDA the
means of ensuring the safety and effectiveness of medical devices,
and they apply to all medical devices regardless of class. These
include provisions related to adulteration, misbranding, device
registration and listing, premarket notification, banned devices,
records and reports, and Good Manufacturing Practices. The term
special controls refers to the additional controls necessary to
provide a reasonable assurance of safety and effectiveness for a
specific device type where general controls alone have been
determined to be insufficient. Special controls have been
established for some class II devices based on device-specific
considerations and include adherence to guidance documents,
performance standards, postmarket surveillance, patient registries
or guidelines, and other appropriate actions as identified by the
CDRH. 3

Reclassification Process
As the FDA’s experience and knowledge of a device type increases,
a device’s classification can be updated through the reclassification
process. Devices may be reclassified through the 513(e) or 513(f)
processes if new information is provided demonstrating that a
lower classification is sufficient or a higher classification is
necessary to ensure safety and effectiveness. The 513(f) process
includes de novo submissions for novel medical devices that have a
risk profile of a class I or II device. The FDA may initiate or
industry may petition to reclassify a device, and a panel meeting
can be convened for the FDA to solicit expert feedback. 4 One
example is the FDA proposing the reclassification of bone growth
stimulators from class III to class II and convening a panel meeting
to elicit feedback in September 2020. 5

Medical Device Approval Processes

Overview of Regulatory Requirements
FDA regulatory requirements for medical devices encompass the
entire product life cycle, including premarket, postmarket,
inspection, compliance, and enforcement. General controls are the
fundamental regulatory requirements with which all manufacturers
of medical devices distributed in the United States must comply 3 , 6
(Table 1).

Table 1
Overview of General Controls for Medical Devices
General Control Description
Establishment registration Facilities that are involved in the production and distribution
and medical device listing of medical devices intended for the United States are
required to register annually with the FDA and list the
devices manufactured and activities performed on these
devices.
Quality System Regulation Manufacturers of all finished devices and accessories must
(QSR) adhere to QSR requirements per 21 CFR 820 unless the
device is exempt.
Labeling requirements Device must be appropriately labeled to inform the patient
and user of key design aspects (eg, description, materials,
sterility) of the device and its intended use.
Medical Device Reporting User facilities must report MDR for death and serious injury
(MDR) within 10 working days after first becoming aware of the
event, importers within 30 calendar days (21 CFR 803).
Recalls/corrections/removals Manufacturers are required to report any recall, correction,
or removal undertaken to reduce a risk to health within 10
working days of initiating a recall, with some exceptions
granted (21 CFR 806).
Premarket Marketing submissions allow for distribution in the United
notification/approval States for class II and III devices (unless exempt).
Investigational device Allows exemption to the premarket requirements for
exemption for clinical studies distribution of an investigational device for a clinical study.

Premarket Approval
Class III devices are reviewed through the PMA pathway, which
constitutes the most rigorous and stringent device marketing
application required by the FDA. PMA is based on valid scientific
evidence that demonstrates reasonable assurance of safety and
effectiveness with a positive benefit-risk profile. PMA submissions
most often require clinical data and a quality system review, and
the review may involve FDA inspections and/or a public-facing
expert panel vote. The PMA pathway can be significantly longer and
more expensive than alternative pathways and may result in
additional postmarket commitments for the lifetime of the device,
such as reporting, surveillance, or postapproval clinical studies. The
review time for a PMA is typically 180 days, with the FDA issuing a
request for additional information at the 100-day timepoint. The
sponsor (submi er) will have 180 days to respond to this request
but can request an extension. For orthopaedic devices, IDE clinical
studies are rigorous and often have the following features: two-arm
randomized controlled trial; noninferiority study compared with an
active control; 1- or 2-year primary end point with mandatory 5-year
follow-up; minimal loss to follow-up (target 85% follow-up or
higher); and a composite primary end point that incorporates
multiple safety and efficacy measures, all of which must be met
patient-wise for a clinical success. Typical components of the
composite primary outcome measure include a patient-reported
outcome instrument; absence of secondary surgical intervention;
absence of neurologic symptoms (clinical worsening); radiographic
outcomes; and/or absence of device-related severe adverse events.
Including the clinical study activities and regulatory processes,
PMA approval typically requires a time commitment of more than 5
years and the requisite capital to run a major clinical trial and
conduct regulatory actions over a protracted period. Post-PMA
modifications are implemented through various supplements such
as panel-track supplement, 180-day supplement, real-time
supplement, 30-day notice, special PMA supplement, and annual
reports. 7

Investigational Device Exemption

An IDE allows a device intended for investigational use to be
shipped lawfully across the United States and used in a clinical
study to collect safety and effectiveness data. Devices that are
deemed to pose significant risk to the patient must have an
approved IDE before initiation of the clinical study. Nonsignificant
risk devices (defined in 21 CFR 812) do not require an IDE, but
must follow abbreviated requirements including labeling,
institutional review board approval, informed consent, and
monitoring. IDEs are reviewed by the FDA within 30 days, with the
review focused on evaluating device safety. For reference, the FDA
will provide any comments, referred to as study design
considerations, on effectiveness end points and/or the ability of a
study to support a future marketing application during the IDE
review. Study design considerations should not impede approval of
the IDE. Sponsors are not required to submit a PMA or 510(k),
register their establishment, or list the device while the device is
under investigation. Sponsors of IDEs are also exempt from the
Quality System Regulation requirements except for the
requirements pertaining to design controls. 8

Premarket Notification (510(k))

A premarket notification (ie, a 510(k) submission) is used to obtain
clearance of a class II medical device by demonstrating substantial
equivalence to a legally marketed predicate device. The 510(k)
devices are required to demonstrate that they are expected to be as
safe and as effective as a previously cleared class II device with the
same intended use. Class III devices, drugs/biologics, or
uncleared/unapproved devices may not serve as predicate devices.
The differences in technology between the subject and predicate
device should not be so significant that there are new risks
presented by the subject device not relevant to the predicate
technology. Devices may be found not substantially equivalent to
the predicate device if they do not meet one of these high-level
criteria or if the performance testing does not demonstrate
substantial equivalence. A 510(k) is subject to a 90-day review from
the FDA, with the FDA typically issuing an Additional Information
Request around the 60-day timepoint, placing the review clock on
hold. The sponsor will have an additional 180 days to respond to
this request, after which the 90-day review clock is resumed. The
510(k)s are typically considered the lowest barrier to entry in terms
of both time and cost compared with other premarket pathways. 9

De Novo
The De Novo process is a risk-based classification process designed
to allow for the classification of novel medical devices that can
reasonably be considered low-medium risk class I or class II, but
for which there is no predicate device. This process creates a new
classification regulation for the device, after which the device can
serve as a predicate for future, similar products through the 510(k)
pathway. The De Novo review is twofold and first includes a review
of current regulations, predicate devices, and the subject
technology to determine whether the device is eligible for this type
of submission. Second, the device is reviewed to ensure a
reasonable assurance of safety and effectiveness and that the
benefits of the technology outweigh the risks. De Novo review
clocks are 150 days for the FDA review and may include substantial
additional hold time to correct any deficiencies after the first 75
days of review. Although an important pathway, few orthopaedic
devices have been granted a De Novo to date, though its use may
be increasing.

Humanitarian Device Exemption

FDA has created programs to facilitate the development of medical
products intended to manage rare diseases including the Orphan
Drug Designation and the HUD. An HUD is defined as a medical
device intended to manage or diagnose a disease or condition that
is manifested in no more than 8,000 individuals in the United States
per year. These products must submit a marketing application
called a Humanitarian Device Exemption (HDE). The FDA
implemented further profit-limiting regulations on HUDs to
encourage the development of these products for the pediatric
population. Unlike PMAs, there is no user fee or panel-track for
HDEs. Before submi ing an HDE, an applicant must first obtain
HUD designation from the Office of Orphan Products
Development. An HDE application involves a 75-day review from
FDA, in which the sponsor must demonstrate that the product will
not expose patients to an unreasonable or significant risk and
demonstrate a probable benefit (ie, exempt from demonstrating
effectiveness). Following approval of an HDE, only facilities that
have institutional review board oversight may use the device. 10 , 11

Product Development Protocol

The product development protocol (PDP) process is designed for
devices with well-established technologies and allows for
marketing approval, whereby the clinical evaluation of a device and
the development of necessary information for approval are merged
into a single regulatory mechanism. The PDP is a contract that
describes the agreed-on details of design and development
activities and the necessary acceptance criteria for these activities.
This offers the manufacturer the advantage of predictability by
coming to an early agreement with the FDA on the necessary
evidence needed to demonstrate safety and effectiveness. A PDP
that is determined to be completed by the FDA is considered to
have an approved PMA. 12

Custom Devices
Criteria for Custom Device Exemption
A device may qualify for the custom device exemption per 520(b) of
the Federal Food, Drug, and Cosmetic Act if the following criteria
apply:

The device is not generally available in the United States in

finished form and cannot be classified under a generic device
type, which is a group of devices that do not differ significantly
in purpose, design, materials, energy source, function, or any
other feature related to safety and effectiveness, and for which
similar regulatory controls are sufficient to provide reasonable
assurance of safety.
The device necessarily deviates from generic device types,
meaning that the device is sufficiently unique so that clinical
investigations would be impractical and could not be
performed to demonstrate conformance to applicable
performance standards and/or support premarket review.
The device is requested via an order of a physician or dentist.

In guidance, the FDA gives examples of potential custom devices

for which a population could not be studied (eg, total hip
arthroplasty in a patient with diminutive anatomy, total disk
arthroplasty in a patient who is 7 feet, 2 inches tall, occipital
condyle fixation in a toddler). In orthopaedics, one critical
distinction is that patient-matched or patient-specific devices,
including three-dimensional printed devices or patient-specific
cu ing jigs, do not necessarily qualify as custom devices. Although
patient-matched or patient-specific orthopaedic devices can be
three-dimensionally printed according to an individual patient’s
anatomy, this does not automatically qualify the device as a custom
implant because patient-matched devices can be manufactured
using device history records and have developed device
specifications. These are so-called envelope submissions. Of note,
total joint arthroplasties with a large number of sizes chosen by
preoperative imaging and sometimes labeled customized are not
truly custom in the FDA’s view. Accordingly, customized, patient-
matched, or patient-specific devices typically require premarket
review via 510(k) or PMA pathways. 13 , 14

Requirements for Custom Devices

Custom devices may be requested by a physician or a dentist to
meet a special need related to the unique pathology or a unique
physiologic condition of either a patient or a physician. Qualifying
as a custom device indicates that the device is exempt from
premarket review. However, custom devices are notably not exempt
from Quality System regulation (21 CFR Part 820). Custom devices
should also meet regulatory requirements for registration and
listing (21 CFR Part 807), adverse event reporting (21 CFR Part 803),
recalls (21 CFR Part 806), and labeling (21 CFR Part 801). 13 , 14

Notable Changes to Custom Devices Under the FDA

Safety and Innovation Act
In 2012, the FDA Safety and Innovation Act required the
implementation of several changes to custom device exemption.
One notable change was the allowance for multiple units of a device
type to qualify for custom device exemption, with the stipulation
that there should be no more than five allotments per year. One
allotment typically entails one patient or one physician, and one
device unit. In addition, the FDA Safety and Innovation Act
implemented a requirement for manufacturers of custom devices to
submit an annual report by March 31 of each calendar year. The
required contents of the annual report are outlined in FDA
guidance documents and are dependent on whether the custom
device is patient centric or physician centric. 13 , 14

Custom Devices Versus Compassionate Use

Devices that do not meet all of the requirements of a custom device
exemption may qualify for compassionate use, which allows for an
unapproved or uncleared medical device to be used on human
subjects when the device is the only option available for a patient
with a serious condition. In a compassionate use case, the probable
risk to the patient should not be greater than the probable risk
from the disease. Compassionate use cases require prior FDA
approval. A surgeon interested in pursuing a compassionate use
case should request authorization from the sponsor, and the
sponsor should submit the compassionate use request to the FDA.
The compassionate use request should justify why the device meets
the specific needs of the patient and present a strategy for patient
monitoring. Additional considerations exist for compassionate use
requests related to a product under an ongoing IDE investigation.
Any compassionate use request submi ed when there is an existing
IDE for the device will have the same 30-day review cycle similar to
other IDE submissions. All other compassionate use requests are
typically reviewed within 15 days of receipt. Compassionate use
requests also require a follow-up report to the FDA within 45 days
of using the compassionate use device. 15 , 16 Of note, this is a
narrow exception, including devices undergoing IDE studies for
another indication; physician-directed use (so-called off-label use),
which is frequently directed by clinical judgment, is common by
contrast.
Regulation of Orthopaedic Combination,
Drugs, and Biologic Products
Combination Products
According to 21 CFR 3.2(e), orthopaedic combination products are
therapeutic products that are composed of a combination of drugs,
devices, and/or biologic constituents combined into a single entity.
They can be packaged together or separately but are specifically
labeled to be used together. Common orthopaedic combination
products include bone cements containing antibiotics or bone
grafts containing biologics, such as bone morphogenetic protein
(eg, INFUSE [Medtronic] or OP-1 [Stryker]). Combination products
are reviewed in multiple centers (ie, CBER, CDER, and CDRH) and
assigned a lead center selected based on the primary mode of
action (PMOA), defined as “the single mode of action of a
combination product that provides the most important therapeutic
action of the combination product.” 17
The product classification and lead center are determined by the
product PMOA and intended use, as well as regulatory precedence
and scientific knowledge within each center. An official Request for
Designation may be submi ed to the Office of Combination
Products to determine the appropriate product classification. 18 , 19
The Office of Combination Products provides formal feedback to
assign the product a lead center for the premarket review within 60
days. Alternatively, sponsors may obtain informal, nonbinding
feedback on the classification through a Pre-Request for
Designation submission. 20
The lead center for a combination product will have primary
jurisdiction over its premarket review and regulation. For example,
if an orthopaedic combination product includes a device (such as
metallic hardware) and a biologic (such as cells, blood, tissues), and
the PMOA is a ributable to the biologic product, the CBER will
have primary jurisdiction for the combination product and the
CDRH will be the consulting center. The lead center will dictate the
review policy that is used (ie, the CDRH-lead products will follow
the device review policy). 8 Notably, the CBER also regulates
medical devices related to licensed blood and cellular products by
applying appropriate medical device laws and regulations. 21

Biologics and Drugs

The major difference between biologic products and drugs is the
manufacturing process. Although drugs are chemically synthesized
with well-defined chemical structure, biologics usually involve a
complex mixture and are not easily identified or characterized.
Biologics are manufactured through a biologic process or through
biotechnology and tend to be heat sensitive and susceptible to
microbial contamination. 22

Human Cell and Tissue Products

The FDA has issued a guidance document as of July 2020 regarding
the regulations of human cells, tissues, and cellular and tissue-
based products (HCT/Ps) defined in 21 CFR 1271.10(a). According
to this guidance document, some HCT/Ps are not required to obtain
premarket approval/clearance from FDA if they meet the criteria of
section 361 of the Public Health Service Act (PHS Act) (42 U.S.C.
264), whereas others are regulated as drugs, devices, and/or biologic
products under section 351 of the PHS Act (42 U.S.C. 262) and/or
the Federal Food, Drug, and Cosmetic Act. For a product to be
eligible for section 361, the HCT/P should be minimally
manipulated (ie, not altering relevant characteristics of the tissue),
intended for homologous use only (ie, performs the same basic
function as the donor tissue), and the cells or tissues should not be
combined with another article, except water, crystalloid, or a
sterilizing, preserving, or storage agent, which raise new clinical
safety concerns.
Specific examples of some 361 HCT/Ps that meet the criteria in 21
CFR 1271.10(a) and are commonly used in orthopaedic products
include bone, adipose, amnion, skin, fascia, cartilage, and bone
marrow, which are minimally manipulated, intended for
homologous use only, and not combined with another article, with
some exceptions. Milling, grinding, and other methods for shaping
and sizing bone marrow are considered minimal manipulation
when they do not alter bone’s original relevant characteristics
relating to its utility to support the body and protect internal
structures. Human demineralized bone matrix combined with other
components intended to make the bone matrix easier to handle by
turning it into a pu y or paste (such as sodium hyaluronate,
glycerol, or calcium phosphate) does not qualify for regulation
solely under section 361 of the PHS Act. These products are placed
in bone voids or defects and are regulated under the device
provisions of the Federal Food, Drug, and Cosmetic Act. 23
If an HCT/P does not meet the aforementioned criteria, the
HCT/P will be regulated as a drug, device, and/or biologic product
under the Federal Food, Drug, and Cosmetic Act, and/or section 351
of the PHS Act. 24 An example of an orthopaedic product not
subject to section 361 is cultured cartilage cells. From a regulatory
perspective, any culture steps are typically considered to be more
than minimal manipulation, as culture typically changes
phenotypes including surface markers.

Biologics License Application Versus New Drug

Application
The HCT/P products considered under section 351 of the PHS Act
are reviewed in CBER under a Biologics License Application (BLA).
BLA issuance is based on the determination of continued safety,
purity, and potency of the product. Products reviewed under BLA
are subject to US PHS requirements for systemic control over all
aspects of the manufacturing process. Orthopaedic or bone tissue
engineered constructs, which include drug constituents responsible
for the PMOA, are considered as drug/device combination products
assigned to the CDER as the lead center with consultation with the
CDRH. The regulatory pathway associated with drugs reviewed
under the CDER is a new drug application.
Clinical Studies for Biologics and Drugs
Regardless of whether a product requires a BLA or new drug
application for the marketing application, to initiate a clinical study
of the biologic or drug product, an investigational new drug (IND)
application is needed. Data from IND studies are submi ed as part
of a BLA or new drug application marketing application. Unlike
medical device studies in which some preclinical studies are often
allowed to occur in conjunction with clinical studies under an IDE,
preclinical testing of biologic substances must be completed before
initiating an IND clinical study, with all animal studies performed
under Good Laboratory Practice standards per 21 CFR 58. The IND
generally includes three clinical study phases: phase I is designed
to evaluate safety and adverse effects; phase II is designed to
evaluate efficacy and dose ranging; and phase III is designed to
provide additional information on efficacy and safety. 25

Adverse Event Reporting

FDA monitors postmarket device performance through postmarket
surveillance tools including Medical Device Reporting (MDR),
which is a tool for the FDA to identify and triage any problems with
products from individual manufacturers as well as identify and
analyze larger trends for general product types. Manufacturers,
importers, and device user facilities (hospitals, nursing homes,
outpatient facilities) are mandatory reporters of MDRs as per 21
CFR Part 803. MDR information is publicly available in the
Manufacturer and User Facility Device Experience database. 26 , 27

Mandatory Reporting
Manufacturers and importers must report any time one of their
devices may have caused or contributed to death or serious injury,
or when a device has malfunctioned and would be likely to cause or
contribute to a death or serious injury on recurrence. These reports
from manufacturers should be submi ed to the FDA within 30
calendar days of becoming aware of the event. 28 User facilities must
report to the manufacturer when there is a suspected medical
device–related death or serious injury. User facilities should also
report any device-related deaths to the FDA directly, but are only
required to report device-related serious injury directly to the FDA
when the device manufacturer is unknown. These reports from user
facilities should be submi ed within 10 working days of becoming
aware of the event. User facilities also have a requirement to submit
an annual report to FDA by January 1 of each year using FDA Form
3419 to provide a full summary of death and serious injury reports
from the prior calendar year. 28

Voluntary Reporting (MedWatch)

Although not mandated, the FDA also encourages health care
professionals and patients to submit voluntary reports. These
voluntary reports are submi ed to MedWatch, which is the FDA’s
Safety Information and Adverse Event Reporting Program.
Reporting through MedWatch can be done through the online
reporting portal or by submi ing the FDA Form 3500 (Health
Professional) or 3500B (Consumer/Patient) to MedWatch. Problems
with drugs, biologics, devices, combination products, nutritional
products, cosmetics, and food all can be reported through the
MedWatch program. Information that is encouraged to be reported
to MedWatch includes unexpected adverse effects or adverse
events, product quality problems, product use/medication errors
that could be prevented, or therapeutic failures. 29

Device Recalls
Recall Definition and Classification
If there is a problem with a medical device that is being marketed, a
company may propose either a correction or a removal from the
market. The correction aims to address a problem with a device in
the place where it is used, whereas a removal addresses a problem
by removing a device from where it is used. Recall may refer to
either a correction or a removal action. Recalls are typically initiated
by the manufacturer of the device as a voluntary action, but recalls
may also be required by the FDA in rare circumstances.
Once a recall has been initiated, a Health Hazard Evaluation is
completed to determine the appropriate recall classification, which
can be one of the following: class I—A situation in which there is a
reasonable probability that the use of, or exposure to, a violative
product will cause serious adverse health consequences or death;
class II—A situation in which use of, or exposure to, a violative
product may cause temporary or medically reversible adverse
health consequences or where the probability of serious adverse
health consequences is remote; class III—A situation in which use
of, or exposure to, a violative product is not likely to cause adverse
health consequences.
Following the Health Hazard Evaluation and resulting
classification of the recall, a company is then charged with
developing a recall strategy. The recall strategy includes identifying
the depth of the recall, administering public warnings and other
relevant communications, and checking for effectiveness of the
recall. Recalls can be searched and monitored through the public
Medical Device Recalls Database on the FDA website. 30 - 32

Surgeon Guidelines for Recalls

During the execution of a recall strategy, hospitals or surgeons may
be directly notified of a device recall, or patients may be notified
and reach out to surgeons for guidance. The American Academy of
Orthopaedic Surgeons (AAOS) asserts that patient safety must be
the highest priority in cases of recalled devices. For implanted
devices, the AAOS recommends that surgeons carefully evaluate
the risk of device failure against revision surgery or reoperation and
notes that revision surgery as a preventative measure against
possible malfunction is rarely recommended. Although the
manufacturer of the device maintains responsibility for
orchestrating a product recall, the AAOS provides the following
guidelines specific to orthopaedic surgeons: (1) Be aware of device
recalls and potential health problems associated with them. (2)
Report incidents of adverse events related to medical products via
MedWatch (online at www.fda.gov/medwatch/index.html or by
calling 1-800-FDA-1088). (3) Cooperate with hospitals and implant
manufacturers in notifying patients of the recall and its related
concerns in cases where patient safety may be at risk. (4) Pursue a
course of shared decision-making with the patient. (5) Maintain the
appropriate level of surveillance to inform future activity (revision,
monitoring). 33

Summary
The FDA regulates medical products, including devices, drugs,
biologics, and combination products, to ensure their safety, efficacy,
and security on the US market. Medical devices are regulated by the
CDRH and are classified based on the degree of risk and level of
control necessary to ensure safety and effectiveness, with class I
devices representing the lowest risk and class III devices
representing the highest risk. Class I devices typically do not
require premarket submissions, whereas class II and class III
devices are commonly reviewed through the 510(k) pathway and
PMA pathway, respectively. Medical devices can also be reclassified
through the 513(e) or 513(f) (de novo) pathways. Alternative
premarket pathways for medical devices include HDE, PDPs, and
custom device exemptions. FDA regulates drug and biologic
products under the CDER and the CBER, respectively, with
markedly distinct requirements compared with medical devices.
Combination products that incorporate a combination of a drug,
biologic, and device are reviewed in a multicenter manner with a
lead center assigned based on the PMOA. The FDA monitors
postmarket product performance through postmarket surveillance
of adverse event reporting and recall actions to correct or remove
any product that presents a threat to patient safety. Health care
professionals can contribute to postmarket surveillance of medical
products through the voluntary MedWatch program.
Key Study Points
The FDA regulates medical devices, drugs, biologics, and combination products
through distinct regulatory pathways under the CDRH, CDER, and CBER,
respectively, with combination products being assigned a lead center based on the
PMOA.
Most products in the orthopaedic space are medical devices, which are classified
into three risk-based classes. Class I devices typically only require general controls,
class II devices typically require special controls and 510(k) premarket notification
based on comparison with a predicate device, and class III devices typically require
an IDE clinical study and PMA.
The FDA requires adverse event reporting for death and serious injury or
malfunctions that could result in death or serious injury. Device recalls allow for the
correction or a removal of a malfunctioned product from the market.

Annotated References
1. A History of Medical Device Regulation & Oversight in the United
States. U.S. Food & Drug Administration. Updated June 24, 2019.
Available at: h ps://www.fda.gov/medical-devices/overview-
device-regulation/history-medical-device-regulation-oversight-
united-states. Accessed October 15, 2021. This FDA webpage
outlines the history of drug and medical device regulation in the
United States and key laws defining relevant regulations.
2. Pierma eo K: How is My Medical Device Classified? U.S. Food &
Drug Administration. CDRH Learn Web site. Available at:
h ps://www.fda.gov/media/131270/download. Accessed October
15, 2021. This FDA presentation outlines the classification system
of medical devices and key considerations related to these
classifications, including regulatory pathway and evidence
requirements.
3. General Controls for Medical Devices. U.S. Food & Drug
Administration. Updated March 22, 2018. Available at:
h ps://www.fda.gov/medical-devices/regulatory-controls/general-
controls-medical-devices. Accessed October 15, 2021.
4. Reclassification U.S. Food & Drug Administration. CDRH
Transparency Web site. Updated July 7, 2021. Available at:
h ps://www.fda.gov/about-fda/cdrh-transparency/reclassification.
Accessed October 15, 2021. This FDA webpage outlines the
reclassification process described in section 513(e) of the FD&C
Act.
5. Koutsoumbelis S: Orthopaedic and Rehabilitation Devices Panel
September 8-9, 2020 - Koutsoumbelis le er, in Garcia P, ed: Re:
FDA Medical Devices Advisory Commi ee Panel Meeting on
Reclassification of Noninvasive Bone Growth Stimulators ed.
FDA.gov. U.S. Food & Drug Administration, 2020. This article
provides FDA Advisory Panel Meeting Information related to the
reclassification of bone growth stimulators.
6. Overview of Device Regulation. U.S. Food & Drug Administration.
Updated September 4, 2020. Available at:
h ps://www.fda.gov/medical-devices/device-advice-
comprehensive-regulatory-assistance/overview-device-regulation.
Accessed October 15, 2021. This FDA webpage outlines
requirements and regulations associated with medical devices
including medical device listing, establishment registration, and
required submissions.
7. Premarket Approval (PMA). U.S. Food & Drug Administration.
Updated May 16, 2019. Available at: h ps://www.fda.gov/medical-
devices/premarket-submissions/premarket-approval-pma.
Accessed October 15, 2021. This FDA webpage outlines the PMA
process for class III devices.
8. Investigational Device Exemption (IDE). U.S. Food & Drug
Administration. How to Study and Market Your Device Web site.
Updated December 13, 2019. Available at:
h ps://www.fda.gov/medical-devices/how-study-and-market-
your-device/investigational-device-exemption-ide. Accessed
October 15, 2021. This FDA webpage outlines IDE requirements
for investigational studies of unapproved medical devices.
 9. Premarket Notification 510(k). U.S. Food & Drug
Administration. How to Study and Market Your Device Web site.
Updated March 13, 2020. Available at:
h ps://www.fda.gov/medical-devices/premarket-
submissions/premarket-notification-510k. Accessed October 15,
2021. This FDA webpage outlines the premarket notification
requirements for medical devices with predicate devices
requirement 510(k)s.
10. Ge ing a Humanitarian Use Device to Market. U.S. Food &
Drug Administration. How to Study and Market Your Device Web
site. Updated December 12, 2019. Available
at: h ps://www.fda.gov/medical-devices/humanitarian-device-
exemption/ge ing-humanitarian-use-device-market. Accessed
October 15, 2021. This FDA webpage outlines the humanitarian
use device regulation for products with limited market potential,
including an overview of designation requirements.
11. Humanitarian Device Exemption. U.S. Food & Drug
Administration. How to Study and Market Your Device Web site.
Available at: h ps://www.fda.gov/medical-devices/premarket-
submissions/humanitarian-device-exemption. Accessed October
15, 2021. This FDA webpage outlines the HDE pathway for
humanitarian use devices, including submission requirements
and considerations.
12. PMA Application Methods. U.S. Food & Drug Administration.
How to Study and Market Your Device Web site. Updated September
27, 2018. Available at: h ps://www.fda.gov/medical-
devices/premarket-approval-pma/pma-application-methods#pdp.
Accessed October 15, 2021.
13. NathanS, IveyP: Custom Device Exemption. U.S. Food & Drug
Administration. Available at:
h ps://www.fda.gov/media/89996/download. Accessed October
15, 2021. This is an FDA PowerPoint presentation outlining
custom device exemption and considerations, including the five
per year allotment limits and annual reporting requirements.
14. Custom Device Exemption: Guidance for Industry and Food and
Drug Administration Staff, in Health CfDaR, ed: FDA.gov. U.S.
Food & Drug Administration, 2014.
15. Expanded Access for Medical Devices. U.S. Food & Drug
Administration. Updated June 21, 2019. Available at:
h ps://www.fda.gov/medical-devices/investigational-device-
exemption-ide/expanded-access-medical-devices#compassionate.
Accessed October 15, 2021. This FDA webpage outlines the
expanded access programs for medical devices, including
emergency use, compassionate use, and treatment IDEs.
16. Santel F: Emergency Use and Compassionate Use of
Unapproved Devices. U.S. Food & Drug Administration.
Available at: h ps://www.fda.gov/media/77477/download.
Accessed October 15, 2021. This FDA PowerPoint presentation on
emergency use and compassionate use of unapproved devices
includes an overview of key considerations and roles and
responsibilities of physicians and IRB.
17. Frequently Asked Questions About Combination Products. U.S.
Food & Drug Administration. Available at:
h ps://www.fda.gov/combination-products/about-combination-
products/frequently-asked-questions-about-combination-
products#CP. Accessed October 15, 2021. This FDA webpage
covers FAQs pertaining to combination products.
18. How to Write a Request for Designation (RFD): Guidance for
Industry, in Products OoC, ed: FDA.gov. U.S. Food & Drug
Administration, 2011.
19. Combination Products Policy Council. U.S. Food & Drug
Administration. Updated June 18, 2019. Available at:
h ps://www.fda.gov/combination-products/about-combination-
products/combination-products-policy-council. Accessed October
15, 2021. This FDA webpage provides an overview of FDA’s
Combination Products Policy Council, including representatives
and roles.
20. How to Prepare a Pre-Request for Designation (Pre-RFD):
Guidance for Industry, in Services HaH, ed: FDA.gov. U.S. Food &
Drug Administration, 2018.
21. Devices Regulated by the Center for Biologics Evaluation and
Research. U.S. Food & Drug Administration. Updated March 22,
2018. Available at: h ps://www.fda.gov/vaccines-blood-
biologics/510k-process-cber/devices-regulated-center-biologics-
evaluation-and-research. Accessed October 15, 2021.
22. What Are “Biologics” Questions and Answers. U.S. Food & Drug
Administration. Updated February 6, 2018. Available at:
h ps://www.fda.gov/about-fda/center-biologics-evaluation-and-
research-cber/what-are-biologics-questions-and- answers.
Accessed October 15, 2021.
23. Jurisdictional Update: Human Demineralized Bone Matrix. U.S.
Food & Drug Administration. Updated February 16, 2018.
Available at: h ps://www.fda.gov/combination-
products/jurisdictional-updates/jurisdictional-update-human-
demineralized-bone-matrix. Accessed October 15, 2021.
24. Regulatory Considerations for Human Cells, Tissues, and
Cellular and Tissue-Based Products: Minimal Manipulation and
Homologous Use – Guidance for Industry and Food and Drug
Administration Staff, in Health CfBEaRaCfDaR, ed: FDA.gov. U.S.
Food & Drug Administration, 2020. This FDA guidance
document outlines considerations related to HCT/Ps and tissue-
based products, clarifying the regulations of minimal
manipulation and homologous use as they pertain to section 361
regulations.
25. Investigational New Drug (IND) Application. U.S. Food & Drug
Administration. Updated February 24, 2021. Available at:
h ps://www.fda.gov/drugs/types-applications/investigational-
new-drug-ind-application. Accessed October 15, 2021. This FDA
webpage outlines IND considerations and requirements.
26. Medical Device Reporting (MDR): How to Report Medical Device
Problems. U.S. Food & Drug Administration. Updated October 2,
 2020. Available at: h ps://www.fda.gov/medical-devices/medical-
device-safety/medical-device-reporting-mdr-how-report-medical-
device-problems. Accessed October 15, 2021. This FDA webpage
outlines MDR considerations and how to report medical device
complaints and adverse events.
27. MAUDE - Manufacturer and User Facility Device Experience. U.S.
Food & Drug Administration, 2021. Available at:
h ps://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfmaude/sear
ch.cfm. Accessed October 15, 2021. This is an FDA MAUE
database search portal.
28. Mandatory Reporting Requirements: Manufacturers, Importers
and Device User Facilities. U.S. Food & Drug Administration.
Updated May 22, 2020. Available at: h ps://www.fda.gov/medical-
devices/postmarket-requirements-devices/mandatory-reporting-
requirements-manufacturers-importers-and-device-user-facilities.
Accessed October 15, 2021. This FDA webpage outlines the
mandatory reporting requirements for medical device
manufacturers, importers, and end users, including an overview
of timing requirements and appropriate forms.
29. MedWatch Online Voluntary Reporting Form. U.S. Food & Drug
Administration. Available at:
h ps://www.accessdata.fda.gov/scripts/medwatch/index.cfm?
action=reporting.home. Accessed October 15, 2021. This is the
FDA webpage for voluntary reporting for health professionals,
consumers, and patients.
30. What is a Medical Device Recall? U.S. Food & Drug
Administration. Updated September 26, 2018. Accessed.
Available at: h ps://www.fda.gov/medical-devices/medical- -
device-recalls/what-medical-device-recall. Accessed October 15,
2021.
31. Recalls, Corrections and Removals (Devices). U.S. Food & Drug
Administration. Updated September 29, 2020. Available at:
h ps://www.fda.gov/medical-devices/postmarket- requirements-
devices/recalls-corrections-and-removals-devices. Accessed
 October 15, 2021. This FDA webpage outlines considerations for
device recalls, corrections, and removals, including definitions,
classification summaries, and appropriate strategies.
32. Medical Device Recalls. U.S. Food & Drug Administration,
2021. Available at: h ps://www.accessdata.fda.gov/scripts/cdrh/cfd
ocs/cfRES/res.cfm. Accessed October 15, 2021. This is the FDA’s
medical device recalls database search portal.
33. American Academy of Orthopaedic Surgeons. Informa tion
Statement 1019: Implant Device Recalls. American Academy of
Orthopaedic Surgeons (AAOS). Published 2002. Updated 02,
2016. Available at:
h ps://www.aaos.org/globalassets/about/bylaws-
library/information-statements/1019-implant-device-recalls1.pdf.
Accessed October 15, 2021.
C H AP T E R 5

Health Policy
Mohamed E. Awad MD, MBA, Khaled J. Saleh MD, MPH,
MHCM (Harv), FRCSC, CPE

Dr. Saleh or an immediate family member has received royalties from Aesculap/B.Braun; serves as
a paid consultant to or is an employee of Aesculap/B.Braun, John Dingell VAMC, Legend Health,
PLC, Saleh Medical Innovation Consulting, PLC, Sphere Orthopaedics and Regeneration, and
VAMC - Surgical Institute of Excellence in Health Services & Research; serves as an unpaid
consultant to Central Michigan University-College of Medicine and Michigan State University;
has stock or stock options held in Right Mechanics; and has received research or institutional
support from 3M/KCI. Neither Dr. Awad nor any immediate family member has received anything
of value from or has stock or stock options held in a commercial company or institution related
directly or indirectly to the subject of this chapter.

ABSTRACT
Over the past decade, orthopaedic practice and healthcare policies
have been rapidly changing for be er value. It is important to have
an understanding of the cornerstones of the US healthcare system,
such as Medicare, Medicaid, private payer reimbursement models
and alternative payment models, patient protection, and the
Affordable Care Act. There have been recent changes in healthcare
policies that have affected orthopaedic care. These include the 2020
Hospital Outpatient Prospective Payment System, the Hospital-
Acquired Condition Reduction Program, the Centers for Medicare
& Medicaid Services CMS Star Rating system, regulations for
ambulatory surgical centers, and price transparency.
Keywords: Affordable Care Act; insurance; Medicare; Medicare
Access and CHIP Reauthorization Act; policy
Introduction
The US healthcare system is a unique and complicated
collaboration between many different entities, all participating in
the provision of patient care. The interplay between these entities
continues to evolve dramatically over time, with practices and
policies continually being repealed, adapted, or newly established
in order to continue striving to provide optimal care at reduced
cost. In the United States, per-capita gross domestic product costs
of health care remain the highest of any developed country in the
world 1 (Figure 1), with an estimated $1 trillion of waste costs spent
annually. 2 National healthcare expenditures reached $3.8 trillion in
2018, accounting for 17.7% of the US gross domestic product. 3

Figure 1 Graph illustrates the health consumption expenditures as a

percentage of gross domestic product.(Courtesy of Kaiser Family Foundation
Analysis of OECD and National Health Expenditures Data. Available at:
https://www.healthsystemtracker.org/indicator/spending/health-expenditure-gdp/.
Accessed May 1, 2021.)

Orthopaedic surgery care is a large driver of healthcare costs. 4 In

2018, total hip arthroplasty (THA) and total knee arthroplasty
(TKA) were two of the four most common inpatient surgeries
performed in the United States and were the two most commonly
performed nonmaternal inpatient procedures. 5 Spine fusions,
femur fixations, and vertebral diskectomies were also among the
top 10 surgical procedures performed during inpatient stays. In a
2019 analysis conducted by Blue Cross Blue Shield, expenditures for
the management of orthopaedic pain conditions represented 14%
of all health expenditures among their members, accounting for
more than $54 billion in costs. 6 Utilization of health services
increased by 17% for knee replacements and 33% for hip
replacements from 2010 to 2017. 6
The Centers for Medicare & Medicaid Services (CMS) projected
that by 2028, healthcare spending would reach $6.19 trillion and
would account for 19.7% of gross domestic product. Private health
insurance is projected to remain the largest source of healthcare
expenditures in 2028. 7 However, Medicare’s share is expected to
grow as the population continues to age. Although Medicare paid
for $1 of every $5 of healthcare spending in 2018, CMS projects that
it will pay for $1 of every $4 of healthcare spending in 2028. 3 The
proportion of spending by third-party payers, public health
activities, and investment is projected to decrease slightly from
2018 to 2028 from 15% to 13.5% of all health expenditures 7 (Figure
2).
 Figure 2 Graph illustrates the projected change in US healthcare expenditures,
2018 to 2028.(Data from (NHE) Table 3 National Health Expenditures; Aggregate
and per Capita Amounts, Percent Distribution and Annual Percent Change by
Source of Funds: Calendar Years 2012-
2028. Available at: https://www.cms.gov/Research-Statistics-Data-and-
Systems/Statistics-Trends-and-Reports/NationalHealthExpendData/NHE-Fact-
Sheet#:∼:text=Because%20national%20health%20expenditures%20are,to%201
9.7%20percent%20in%202028.)

Over the past decade, the United States set forth an effort to
address these costs and issues in access by addressing the quality,
efficiency, and safety of health care. Passage of the Patient
Protection and Affordable Care Act and the Medicare Access and
Children’s Health Insurance Program (CHIP) Reauthorization Act
(MACRA) 8 revolutionized health care and were both implemented
to promote increased quality of care, while also improving patient
outcomes and reducing healthcare expenses. An understanding of
the history and intricacies of healthcare policies is crucial in
continuing to provide patients with excellent care and being able to
adapt to a changing healthcare environment.

Federally Funded Health Care

The United States first developed a privatized healthcare system
after it lacked the necessary funding after World War II to create an
often-discussed universal health plan. 9 However, the need to
ensure health services for a large portion of the population was
undeniable. Under the leadership of President Lyndon B. Johnson,
the US Congress impelled a radical change to healthcare coverage
by adopting the Social Security Amendments of 1965, establishing
both the Medicare and Medicaid programs. 10 Although both
programs vary and have undergone several different iterations over
the years, they currently represent the predominant form of
government-funded health care in the United States.
Since the creation of these programs, the federal oversight has
also shifted over the years. The Bureau of Health Insurance, under
the Social Security Administration, first oversaw Medicare. The
Social and Rehabilitation Service was responsible for the
administration of Medicaid. At the inception of these programs,
these branches were both treated as individual arms within the
Department of Health, Education, and Welfare. However, in 1976,
the federal government established the Health Care Financing
Administration, which became the first branch of government to
manage both Medicaid and Medicare. The Health Care Financing
Administration was renamed the Centers for Medicare & Medicaid
Services (CMS) in 2001, persisting as the existing governing body
for federally funded health care.

Medicare
The passage of the Social Security Amendments of 1965 ushered in
the development of Medicare, providing insurance for all US adults
at least 65 years of age. Prior to establishment of Medicare, only an
estimated 60% of adults older than 65 years had access to medical
care. Since its inception in 1965, Medicare has expanded to cover
three primary populations: (1) people age 65 years or older, (2)
people younger than 65 years with certain disabilities, and (3) all
people with end-stage renal disease. Approximately 20% of
Medicare beneficiaries age 65 years or older are covered solely by
traditional Medicare, whereas 80% are enrolled in another form of
additional insurance coverage to supplement Medicare. 11

Original Coverage
At its creation, Medicare was composed of two parts: Part A and
Part B. Part A provides coverage for inpatient hospital visits, skilled
nursing facilities, some home healthcare services, and hospice care.
Medicare Part A is funded by mandatory payroll deductions.
Furthermore, 99% of beneficiaries do not pay any deductible for
care. For the 1% of patients with less than 10 years of Medicare-
covered employment, inpatient hospital visits require an annually
adjusted deductible, which the Social Security Administration has
set at $1,484 as of the 2021 calendar year. 11 Those with less than 40
quarters of covered employment must also pay a monthly premium
that is also adjusted annually by the Social Security Administration.
Medicare Part B is a supplementary insurance that covers
physician services, outpatient services, certain home health
services, durable medical equipment, and other specific medical
and health services not covered by Medicare Part A. Durable
medical equipment may include canes, walkers, wheelchairs,
mobility devices, and prosthetic devices. Part B is financed through
a combination of premiums paid by enrollees and appropriations
from the federal budget. After the annual deductible is met, Part B
enrollees are subject to a 20% coinsurance rate. However, Part B
covers 100% of preventive services that the US Preventive Services
Task Force designated as grade A or B types of preventive
screenings such as yearly mammograms and osteoporosis
screening. 11

Medicare Expansion
Rising healthcare costs in the 1990s became a major concern for the
federal government. Maintaining the Medicare program, however,
was a major priority, and in 1997, Congress passed the Balanced
Budget Act in an effort to balance the federal budget in 5 years. To
accomplish this goal, Medicare was expanded. New policies allowed
for the coordination between private insurers and Medicare
administrators to provide alternatives to the traditional Medicare,
thereby placing more of the costs on the individuals.
 Medicare Part C, also known as the Medicare Advantage plan,
offers beneficiaries a combination of Part A and Part B benefits—
commonly along with Part D—through approved private insurance
entities. Part C offers beneficiaries the flexibility of enrolling in a
health maintenance organization (HMO) or preferred provider
organization (PPO), while still receiving traditional Medicare
benefits. Enrollment in Medicare Advantage has steadily grown
over time and in 2019, approximately one-third of people enrolled
in Medicare were enrolled in the Medicare Advantage plan.
Specifically, more than 60% of those enrolled in Medicare
Advantage select a generally more affordable HMO plan, which can
lead to barriers to obtaining specialist care and restrictions to
obtaining certain medications.
Entities receive rebates from the federal government for offering
Medicare Advantage plans. They are, however, required to use a
portion of the rebates to reduce premiums, offer additional
benefits, or lower cost sharing for enrollees. Furthermore, enrollees
in Medicare Advantage often tend to receive benefits not covered
by traditional Medicare, including but not limited to fitness
benefits, dental benefits, and eye examinations.
The government further expanded Medicare with the Medicare
Prescription Drug, Improvement, and Modernization Act of 2003,
creating Part D. Part D provides coverage of prescription drugs to
all Medicare beneficiaries through private sponsors regulated by
Medicare. Enrollees may voluntarily elect to enroll in Part D, paying
a monthly premium and deductible to shield themselves from
increasing drug costs.

Current Cost and Sustainability

When Medicare was first established, it covered 19 million US
adults. As of 2020, Medicare serves as health insurance for an
estimated 61.2 million US adults, a number projected to steadily
grow to 80 million in 2030 as the Baby Boomer generation (those
born between 1946 and 1964) continues to age into Medicare.
Despite many of the changes to increase cost sharing, spending is
projected to grow from $750.2 billion in 2018 to over $1.5 trillion in
2028, 3 , 7 although these projections are less certain after the effects
of the SARS-CoV-2 pandemic. Calls for Medicare expansion have
grown in recent years. Policy changes that are possible in the near
future include reduction of the Medicare eligibility to age 60 years
and including coverage for dental and vision plans. Medicare
expansion would also dramatically increase projected future
Medicare expenditures.

Medicaid
The US government established Medicaid under Section XIX of the
Social Security Amendments of 1965 as a collaborative effort
between federal and state governments to provide a public health
support system for low-income Americans. 10 At its inception,
Medicaid eligibility was tied to welfare assistance from the
government. The scope of Medicaid has evolved dramatically since
1965 as it now encompasses coverage for many pregnant women,
people with disabilities, and children in low-income families.
Medicaid is structured as a federal and state government
partnership. This partnership is jointly financed, and the federal
government matches state Medicaid spending. Each state has the
flexibility to set its own Medicaid spending budget and establish
guidelines, in accordance with certain federal requirements, of
eligible populations, covered services, and physician and healthcare
institution reimbursement models.
Federal guidelines establish that states must cover four
mandatory populations to be eligible for federal funding: (1)
children in families with income below 138% of the federal poverty
line, (2) pregnant women living below 138% of the federal poverty
line, (3) certain parents and caregivers with low income, and (4)
most seniors and people with disabilities receiving cash assistance
through the Supplemental Security Income program. The rate of
federal matching may vary from 50% to 75% depending on state
per-capita income levels. In addition, the federal government
provided up to 100% matching for 2014 to 2016 and now 90%
matching beyond 2020 to support Medicaid expansion at the state
level, as outlined in the Affordable Care Act.
Because of its support of low-income individuals, Medicaid is a
countercyclical program with a dynamic number of enrollees. In
times of economic downturn and economic uncertainty, many
Americans lose their jobs and, thus, their employer-based
insurance coverage. During the financial crisis of 2008 and its
aftermath, Medicaid enrollment increased by more than 10 million
people 12 to support the burgeoning need of health care in these
newly uninsured people. Federal matching helps to reduce the
financial pressure on state governments facing constrained budgets
during periods of financial uncertainty. Medicaid currently covers
approximately one in five Americans and accounts for 16% of
healthcare spending in the United States. In fiscal year 2019,
Medicaid spending totaled approximately $604 billion, with an
additional $22 billion in expenditures for administrative costs and
accounting adjustments.
The State CHIP was established under the Balanced Budget Act
of 1997 to provide health insurance to millions of children who are
born into families with incomes above the Medicaid threshold but
too low to afford traditional private health insurance plans. This
program is designed similar to Medicaid as a federal-state
partnership but is characterized by an enhanced federal match rate.
States have the ability to design their State CHIP independently of
Medicaid, but many elect to combine this program with Medicaid.

Private Health Insurance

Private health insurance plans accounted for 34% of all US health
insurance expenditures in 2018, representing the largest single
source of insurance coverage. 13 Individuals may either directly
purchase or receive private health insurance coverage from their
employers. Prior to the effects of the coronavirus pandemic on the
economy, in 2019, private health insurance covered 67.3% of the US
population. 14

Health Maintenance Organizations

HMOs are a type of managed care organization that provides
integrated care for a patient among an integrated group of
providers within the insurer’s system for a certain set payment rate
for their services. These providers generally are either employed
directly by the HMO or work with a separate group contracted by
the HMO. These plans generally offer less expensive health
premiums and lower out-of-pocket costs than other types of private
insurance; however, these are much more restrictive, providing no
out-of-network coverage.
HMOs generally underscore the importance of preventive
medicine in their plans, requiring primary care physicians (PCPs) to
act as gatekeepers to the medical system. These PCPs only
authorize specialty referrals if the HMO guidelines deem them as
medically necessary. Moreover, these plans may delay access to
specialty care for some patients. If patients decide to visit a
healthcare provider out of their network, they may face
considerable out-of-pocket costs in nonemergency situations.

Preferred Provider Organization

A PPO, akin to an HMO, is another type of managed care
organization, with a few critical differences. In a PPO, covered
populations are encouraged to visit in-network providers for a
lower fee. However, patients have the flexibility to seek out-of-
network care at a slightly higher cost. Patients in PPO plans may
also seek in-network specialty care without a referral from a PCP,
and many may elect not to have any consistent PCP. However, these
plans are associated with slightly higher premiums and cost
sharing than HMO plans.
Point-of-Service Plans and Exclusive
Provider Organizations
Point-of-service plans and exclusive provider organizations offer
different blends of the traditional HMO and PPO plans. Point-of-
service plans allow for the flexibility to seek out-of-network care
while still encouraging in-network visits through reduced costs.
However, these plans still require patients to first obtain
authorization from a PCP to access specialty services, as with
HMOs. Exclusive provider organizations restrict all out-of-network
care but do not require a PCP to authorize access to healthcare
specialists.

Other Private Insurance Plans

Catastrophic or high-deductible health plans offer exceptionally low
monthly premiums in exchange for remarkably high monthly
deductibles. These plans are designed to offer health insurance for
younger, healthier people who may not use health services often
but still require protection from high-cost emergency or worst-case
situations. To be eligible for these plans, enrollees must either be
younger than 30 years or receive an exemption from the
government. These plans offer insurance after the deductible is met
each year and cover the 10 essential benefits covered by other
marketplace plans. As of 2020, the deductible for all catastrophic
plans is $8,150. 15
Health savings accounts (HSAs) and flexible spending accounts
allow for employers and/or employees to contribute a portion of
pretax earnings to healthcare expenditures. By paying for services
with pretax income, individuals may be able to reduce overall
healthcare costs. Premiums are not usually eligible for coverage by
these plans, but deductibles, copayments, and some other expenses
are covered. To qualify for an HSA, an individual must be enrolled
in a high-deductible health plan, because HSAs act to help mitigate
the high deductibles. HSAs can be beneficial for users in that any
funds in the HSAs that are unused can be rolled over to the
following calendar year annually. Flexible spending accounts
function as a line of credit, allowing the user to pay for services
beyond what they currently can afford as long as they are expected
to be able to obtain the funding by the end of the calendar year.
Flexible spending accounts can be used to cover a wider variety of
services than an HSA. One such benefit can be coverage of
childcare expenses. However, unlike an HSA, any funds not used by
the end of the year are lost.

Care Reimbursement

Revenue Cycle Management

From a patient’s initial encounter with the healthcare system to the
final payment of balances, hospital systems around the world
engage in basic revenue cycle management to track all revenue
from patients. Revenue cycle management can provide key insights
to a healthcare institution’s performance and expose barriers to
driving improved financial results. Failure to adequately track all
patients may often result in delayed payments or instances where
no payment is received. Furthermore, health systems may often
outsource these responsibilities to specialized companies. Often
strategies for a particular health system may involve staffing
changes, risk mitigation, cost reduction, and a ainment of key
performance indicators.

Diagnosis-Related Groups
First conceptualized through a multidisciplinary team at Yale
University, diagnosis-related groups (DRGs) were introduced to
classify products that a patient receives for a care episode. 16 The US
government established the Medicare Inpatient Prospective
Payment System in October 1983 to use DRGs for Medicare
reimbursement in efforts to control rising care costs. Healthcare
providers around the United States use diagnostic codes for any
patient diagnoses. CMS then reclassifies patients via their assigned
primary diagnostic code, up to 24 additional diagnoses, and up to
25 procedures during a hospital stay into one specific Medicare
Severity Diagnosis-Related Group (MS-DRG). MS-DRGs are distinct
from DRGs because many groups are subdivided into those with or
without complications or comorbidities. CMS establishes payment
using the average cost of all patients within the same MS-DRG. The
total number of MS-DRGs may change annually to incorporate
newly defined diagnoses and new technologies, but all are intended
to be clinically coherent cohorts wherein all patients have similar
conditions. As of 2021, CMS recognizes 767 approved MS-DRGs, of
which 75 comprise most orthopaedic surgery care episodes. 17
Importantly, MS-DRG 470, major joint replacement or rea achment
of the lower extremity without major complication or comorbidity,
represented the fourth most common primary diagnosis among all
DRGs. 18

Physician Fee Schedule

CMS uses a Medicare physician fee schedule to reimburse
providers for services rendered through a measurement of relative
value units (RVUs). RVUs are determined based on the complexity
of a service and resource use with geographical adjustment on a
common scale. Changes to the high-deductible health plans must
not exceed $20 million in expenditures annually. Moreover, annual
updates to increase payments in one area are met with decreases in
other areas. Orthopaedic surgery practices, along with other
specialty providers, are bracing for drastic cuts in the high-
deductible health plans over the coming years. Recently CMS
proposed cuts of 5% across all orthopaedic surgery RVUs, with an
additional 5.4% reduction in RVUs for hip and knee arthroplasty
procedures. The federal government faced increased pressure from
all orthopaedic surgery societies and postponed payment cuts
because of the effects of the COVID-19 pandemic. However, access
to orthopaedic surgery care may be threatened over the coming
years if proposed cuts are implemented.

Hospital-Acquired Condition Reduction

Program
In 2008, CMS implemented the Hospital-Acquired Conditions
(HACs) Initiative, aiming to increase emphasis on value-based care.
19
A HAC is defined as a medical condition or complication not
present at admission that develops in a patient during a hospital
stay. This initiative identified 14 incidences as HAC-defining
events, listed in Table 1. Eight conditions are serious reportable
events, including foreign object retained after surgery, air
embolism, and ABO incompatibility. Five are harmful conditions
that occur more often yet are believed to be reasonably preventable
if accepted standards of care are followed: stage III and IV pressure
ulcer; falls and trauma leading to fractures, dislocations, head
injuries, burns, or other trauma; catheter-associated urinary tract
infection; vascular catheter-associated infection; and surgical site
infection (SSI).

Table 1
The 14 Hospital-Acquired Conditions as Defined by the Centers
for Medicare & Medicaid Services

Foreign object accidentally retained Surgical site infection, mediastinitis, following

after surgery coronary artery bypass graft
Air embolism Surgical site infection following bariatric surgery for
obesity
ABO blood incompatibility Surgical site infection following certain orthopaedic
procedures
Stage III and IV pressure ulcers Surgical site infection following cardiac implantable
electronic device
Falls and trauma Manifestations of poor glycemic control
Catheter-associated urinary tract Deep vein thrombosis /pulmonary embolism
infection
Vascular catheter–associated Iatrogenic pneumothorax with venous catheterization
infection
 The HAC for SSIs was expanded in the fiscal year 2009 rules to
include those following specific orthopaedic procedures and
infections following bariatric procedures. An 11th and 12th HAC
were also identified: one for serious complications of diabetes
acquired during a stay (manifestations of poor glycemic control)
and one for deep vein thrombosis or pulmonary embolism
following certain orthopaedic procedures.
The HAC Reduction Program became effective in October 2014,
aimed at penalizing hospitals experiencing high rates of the
aforementioned complications. Hospital systems with HAC scores
in the bo om 25th percentile would see reduced payments of 1%
over the fiscal year. 20 Aside from reduction in payments as a result
of poor HAC scores, these adverse events have direct economic
effects. The concept behind linking these adverse events with
financial penalty was to create an added layer of institutional
incentive, in addition to providing higher quality of care, in an
a empt to reduce, or even eliminate, these HACs. In the United
States, the incidence of HACs across an inpatient sample of 351
million admissions was 4%, or 1 in 25 inpatient stays. 21 This rate
might vary depending on multiple factors including patient-
specific, surgical-specific, and hospital-specific risk factors. By
defining some of the risks associated with the most common HACs
in common orthopaedic procedures, payers can more appropriately
risk-stratify patients prior to surgery. This can be of benefit to both
the patient and the provider. There will be less risk associated with
surgery performed on a more high-risk patient, leading to more
opportunities of care for the patient and less risk of penalty to
providers.

Hospital-Acquired Condition Reduction Act

and Orthopaedic Care
The four most prevalent inpatient orthopaedic procedures in the
United States are TKA (752,900 procedures), THA (522,800
procedures), spinal fusion (463,200 procedures), and laminectomy
(438,200 procedures). 22 The annual volume of TKA and THA
performed in the United States has been steadily increasing and
this is projected to continue. It has been reported that patients who
underwent TKA and THA experienced HACs at a rate of 1.3%.
These HACs following TKA involved thromboembolism events
(deep vein thrombosis/pulmonary embolism) (0.8%), followed by
in-hospital falls and traumas (0.4%), and SSIs (0.2%). 23 However, in-
hospital falls and trauma were higher (0.9%) in patients who
underwent THA, followed by deep vein thrombosis/pulmonary
embolism (0.3% of cases), and SSI (0.1%). 23 These HACs were
stratified into HACs into catheter-associated urinary tract infection
(1.9%), followed by SSI (1.5%), and venous thromboembolism
(1.3%). Similar to TKA and THA, rates of spinal fusion have steadily
increased. The rate of elective fusions increased 62.3% from 122,679
cases in 2004 to 199,140 cases in 2015. This increased volume was
most accounted for by patients age 65 years and older. The largest
increases were for spondylolisthesis (111%) and scoliosis (186.6%).
However, disk degeneration, herniation, and stenosis accounted for
42.3% of all elective fusions in 2015.
Following spinal fusions, the rate of HAC incidence is often
dependent on the specifics of the performed procedures. In those
undergoing cervical fusions, the incidence of HACs was 4.6%, with
most of these (95.2%) being falls and trauma, followed by SSIs with
a 3.7% incidence rate. Following thoracolumbar fusions, the HAC
frequency increases to 5.2%, with most similarly composed of falls
and trauma (87%). SSI accounted for the second most prevalent
HAC at 11%. 23 In a 2019 study of those undergoing any type of
spinal fusion secondary to deformity, it was noted that HACs occur
at a rate of 5.4%. 24 In this study, the leading cause of HAC was
catheter-associated urinary tract infection (2.1%), followed by SSI
(1.8%) and venous thromboembolism (1.8%).
It is appropriate to discuss laminectomies and fusions together,
as these two procedures often are performed simultaneously. These
incidents resulted in an excess cost of more than $2 billion, which
translates to approximately $40,000 per patient per HAC. Along
with this direct fiscal burden, enduring a HAC added on average
8.17 days to each patient’s hospital stay, which can lead to indirect
hidden costs, such as occupying beds that can be used for other
patients or delaying return to work. 7 These costs can vary according
to the nature and severity of HAC a patient experiences.

Patient Protection and Affordable Care Act

The landscape of American health care and political discourse
changed dramatically in 2010, when the federal government, led by
President Barack Obama, pushed forward the Patient Protection
and Affordable Care Act (PPACA, or ACA). 25 This new legislation
aimed to expand health insurance coverage to all Americans,
offered new patient protections, and established the individual
mandate, a provision requiring individuals to either obtain a
minimum level of health insurance or pay a fine. 25

Key Reforms
Passage of the ACA led to a massive reduction in the uninsured
population. Increased coverage was primarily due to expansion of
Medicaid eligibility but also to changes in the private insurance
market. Several US population groups had been positively affected
by ACA legislation, especially those who have been at the greatest
risk for lacking insurance, including African Americans, Latinos,
and economically disadvantaged groups. As a result, CMS
commi ed to an iterative approach for widespread quality
initiatives by implementing several value-based programs, and
quality measurement and quality payment programs. The four
value-based programs authorized by the ACA include the Hospital
Readmissions Reduction Program, the Hospital Value-Based
Purchasing Program, the HAC Reduction Program, and Physician
Value-Based Modifier. These programs primarily aim for be er care
with low costs as well as linking the provider payment to their
performance. Accordingly, CMS adopted some programs to assess
the performance (quality measurement) and determine the
payment (quality payment). The quality measurement programs
include Physician Quality Reporting System, Hospital Outpatient
Quality Reporting, and Hospital Inpatient Quality Reporting
Program.
By compelling everyone to enroll in a health insurance plan, the
ACA helped offset many of the worries associated with its broader
requirements. Moreover, adding more young and healthy people to
an insurer’s population helps mitigate the risks faced by insurers
and spread the costs more evenly. Since the ACA’s original
passage, the individual mandate was eliminated by President
Donald Trump in the Tax Cuts and Jobs Act of 2017.
To allow those without employers to purchase insurance plans
and abide by the individual mandate, the ACA established the
health insurance exchange. This exchange serves as a marketplace
where consumers can compare insurance plans and purchase
private insurance directly. These exchanges are regulated and
administered by either federal or state governments. 26
The ACA also set forth a sweeping expansion of Medicaid
coverage. With this legislation, the federal government eliminated
the differing levels of Medicaid eligibility in different states and
instead mandated a unified expansion across the country with an
eligible income of 133% of the federal poverty line. 27 To support
states in this expansion, the federal government provided 100%
monetary support to offset the increased costs of the expansion.

Constitutional Challenges
The legal status of the PPACA has been challenged multiple times
at the level of the Supreme Court and remains a contentious topic
across the political spectrum. With continued challenges, the
PPACA has become a dynamic legislation, often facing changes
that either chip away at or build upon its original provisions.
Opponents of the legislation began questioning its legality almost
immediately after its passage. During the following year, in
November 2011, two provisions quickly came into question,
specifically regarding the mandated Medicaid expansion and the
status of the individual mandate. 25
After hearing arguments, on July 28, 2012, there was a ruling
against federally mandated state Medicaid expansion. The Supreme
Court deemed withholding federal Medicaid funds to be coercive.
Furthermore, as the law currently stands, states are able to decide
whether to expand Medicaid per the ACA. The Supreme Court
ruled that the constitutionality of the individual mandate resided in
the federal government’s power to tax and that the penalty of the
individual mandate ultimately amounts to a tax on the uninsured
population. 28
In 2014, the ACA faced another key judicial ba le. In two
separate cases of Halbig v Burwell and King v Burwell, plaintiffs filed
lawsuits suggesting that provisions of the policies purchased on the
federal exchange were unconstitutional because of specific wording
in the ACA that stated provisions be allocated to individuals
enrolled through an exchange established by the State. 29
Ultimately, Chief Justice Roberts of the Supreme Court issued a
majority decision siding with the Obama administration favoring
the contextual definition and stating that the clause in question
ultimately did not establish legality over federal exchanges. This
decision proved fundamental in ensuring coverage for millions of
Americans purchasing policies on the federal exchange. 29
In the most recent threat to the ACA, a group of Republican-led
states challenged its constitutionality after passage of the Tax Cuts
and Jobs Act of 2017. 30 In February 2018, a Texas District Court
ruled in favor of the plaintiffs in Texas v Azar, stating that the
individual mandate is a core provision of the ACA and elimination
of the penalty rendered the law an unconstitutional use of the
government’s taxation power. 31 This ruling upheld the ACA,
however, and did not address the question of the individual
mandate’s constitutionality. 31
The Implications of the ACA on Orthopaedic
Care
The PPACA allowed expansion by individual states of Medicaid
eligibility to individuals younger than 65 years with income at or
with incomes up to 138% of the federal poverty level. As of January
2017, 31 states and the District of Columbia had adopted Medicaid
expansion and the other 19 states had not. Although the ACA has
increased coverage, it may not have increased access to specialty
outpatient health services. 24 In New York State, a 2020 study
evaluated access to the 10 most common elective orthopaedic
surgeries. The authors found that ACA-supported Medicaid
expansion was associated with an increase in Medicaid enrollment
and a concomitant increase in the utilization of orthopaedic care by
Medicaid beneficiaries. 32
In 2016, Louisiana expanded its Medicaid program. This
expansion has increased the number of Medicaid enrollees by more
than 400,000, increasing its Medicaid population from
approximately 20% to 30% of Louisiana residents, one of the
highest Medicaid populations per capita in the country. 24 The
limitations and burdens placed on patients because of their type of
insurance are not yet fully understood. Therefore, it is necessary to
study the correlation between the different types of insurance and
the access to orthopaedic services.

Political Activity and Future of the ACA

The Republican Party has stood in sharp opposition to the ACA.
Currently, the legislation is generally well received by the public,
with many provisions specifically receiving overwhelming public
support. The executive branch has played a crucial role in the
implementation of the ACA. The administration of President Joe
Biden over the years of 2021 to 2025 is expected to be much more
favorable to the ACA and is expected to continue building support
for expansion of coverage. Without bipartisan agreement, the
future of the ACA remains unclear, and implementation of its
provisions will likely continue to shift back and forth based on the
controlling political party.

Alternative Payment Models

Passage of the ACA set the stage for the development of
fundamentally new quality improvement initiatives to promote
value-based care and reduce rising healthcare system costs and
waste. The US healthcare system was historically characterized by a
fee-for-service (FFS) model under which providers are reimbursed
directly by insurers for claims submi ed on an itemized basis for
each service administered. Moreover, hospitals and providers have
been incentivized based on the quantity of services provided, with
li le to no penalty for poor quality or overused services.
The National Quality Strategy was first enacted in 2011 as part of
the ACA to improve patient care. This strategy encompasses the
broader healthcare movement in the United States to incentivize
providers to deliver quality care instead of high-quantity care. The
National Quality Strategy adopted a set of three aims and six
priorities to address the health concerns plaguing Americans. The
triple aim centered around improving quality of care for patients,
considering population needs and social determinants of health,
and promoting affordable care by reducing costs of health care.
To track its goal of achieving affordable care while balancing
spending, the Department of Health and Human Services
established a goal that at least 30% of all Medicare FFS payments
should be linked to quality or value through an alternative payment
model (APM) by the end of 2016, and 50% by the end of 2018. 33 The
Department of Health and Human Services also set a goal to tie
85% of FFS payments to quality or value by the end of 2016 and 90%
by the end of 2018. Although the Department of Health and Human
Services has seen continued improvement in alternative-payment
model alignment, it has failed to hit its target goals since 2017.
From 2014 to 2018, the percentage of Medicare FFS payments linked
to APMs nearly doubled, from 22% to 41%. Measuring quality and
creating a program that can effectively promote quality and value-
based care has proved to be difficult. However, multiple programs
have been created to enact this change.

Bundled Payments
CMS launched the Bundled Payments for Care Improvement (BPCI)
initiative in January 2013 to facilitate the value-based care transition
as the first form of APM. Bundled payments conceptually render a
single payment for a predefined episode of care over a specified
time period. The total value of a care episode is predetermined by
CMS and the length of time that defines a single care episode is
also determined by CMS but varies by BPCI model. 34
Under a bundled payment plan, the insurer shifts much of the
risk to the provider of care. The provider must be able to cover not
only the costs of the acute care visit, but also the costs of any
complications or readmissions within a specified time frame.
Conversely, the provider benefits in a bundled payment model if
they are able to provide high-quality care at a cost lower than the
agreed-upon payment.
Bundled payment models were designed for 49 various episodes
of care termed DRGs, many of which encompass orthopaedic
surgery procedures including TKA and THA, 35 upper extremity
joint replacement, and spinal fusion. Positive early results have
been reported across orthopaedic specialties in both adult
reconstructive and spine surgeries. BPCI deployment has often
resulted in reduced cost of care, lower utilization rates, and reduced
complications and readmissions.
However, the BPCI model has raised alarming concerns among
practitioners. Currently, the BPCI lacks a strong method of
accurately risk-stratifying patients based on factors including older
age, frailty, lower socioeconomic status, and comorbidities. These
factors all may be associated with increased surgical risk. As
providers aim to reduce their costs and improve their outcomes, the
BPCI may also incentivize some providers not to perform surgery
on patients with a greater risk of readmission or surgical
complications. Moreover, early research suggests that bundled
payment programs may exacerbate health disparities.

Comprehensive Care for Joint Replacement

TKA and THA remain the two most common surgical procedures in
inpatient hospital stays among Medicare beneficiaries. Moreover,
these often serve as targets for healthcare innovation. The
Comprehensive Care for Joint Replacement (CJR) model was
created to mandate bundled-care payment for lower extremity joint
replacements in certain geographic areas around the United States
beginning April 1, 2016. Under the CJR model, hospitals carry most
of the risk for the value of care, as opposed to the previous BPCI
initiative, where management firms, hospitals, and physician
practices all are evaluated by the CMS. 36 The CJR model defines an
episode of care as beginning during the admission for major joint
replacement or rea achment of the lower extremity and ending 90
days after discharge.
Initially, participation in the CJR model of care for lower
extremity joint replacements was mandatory in all 67 metropolitan
statistical areas, as determined by the CMS. Metropolitan statistical
areas are counties that are associated with an urban area with a
population of at least 50,000 people. 36 After 2 years of the initial
program, CJR experienced several policy and term updates.
Currently, participation in CJR is voluntary for all the providers in
33 of the 67 metropolitan statistical areas along with for all low-
volume and rural providers. Benchmark pricing for the cost of care
was initially established through a combination of the practice’s
own historic pricing and that of their region. After multiple years of
participation in the CJR model, pricing for a hospital or provider
then shifts to the regional cost of care for the lower extremity joint
replacement episode. 36
BPCI Advanced
BPCI Advanced was launched beginning in October 2018 as a new
iteration of the CMS voluntary episodic payment models. 37 BPCI
Advanced is an episodic payment model that allocates a single
bundled payment for an episode of care for specified DRGs
covering an episode for up to 90 days after discharge. As in the
original BPCI, participants in this model receive payments if they
achieve costs below their target price. Up to 10% of payments in
this model are adjusted based on quality performance. 37 Centers
around the country are participating in this model (Figure 3).

Figure 3 Map of centers participating in the current Bundled Payments for

Care Improvement Advanced model.(Courtesy of Centers for Medicare and
Medicaid Services. https://innovation.cms.gov/innovation-
models/map#model=bpci-advanced. Accessed May 1, 2021.)

Medicare Access and CHIP Reauthorization

Act
Congress passed MACRA of 2015, fundamentally transforming the
traditional physician payment system. 38 At its core, the legislation
shifted health care from a volume-based to a value-based system
where practitioners benefit only when patients are ensured quality
health care. In practice, this was facilitated by repealing the
sustainable growth rate model for Medicare payments and instead
using two alternative Medicare payment pathways.
The first pathway that exists is the merit-based incentive pathway
system (MIPS). MIPS adapts a traditional FFS model into one that
can be adjusted based on quality of care. Payment under MIPS is
furthermore adjusted based on a combination of performance in
quality, cost, promoting interoperability (eg, using electronic health
records), and establishing improvement activities. To maintain high
reimbursement under MIPS, providers must be able to not only
maximize the quality of care patients receive, but also maximize the
coordination of care. MIPS is mandatory for all practices except for
(1) new practices in their first year accepting Medicare patients, (2)
practices seeing fewer than 100 Medicare patients or billing
Medicare less than $30,000 annually, and (3) practices that are
qualified participants in an APM.
MACRA also established a secondary payment pathway, the
Advanced APM track. Participants shift all or most of their Part B
payments to one of 23 approved advanced APMs. In addition to
normal payments that are received under an APM, this model
offers participants a 5% incentive payment for achieving threshold
levels of payments or patients through a given APM. Two such
advanced APMs are the CJR and BPCI Advanced, whereas the
original BPCI models do not qualify as an approved APM. These
two MACRA payment models, MIPS and APMs, provide the
participants with performance-based payment adjustment
(reimbursements) and an incentive payment for the participation,
respectively. These programs use a combination of incentive
payments and payment adjustments to promote reporting of
quality information by eligible providers and hospitals. These
legislations shifted US health care from a volume-based to a value-
based payment system. MACRA is intended to advance the goals of
ACA by creating a system where practitioners only benefit when
patients are ensured quality health care. Medicare’s payment
reimbursement to hospitals is based not only on the services
provided to Medicare patients, but also for the quality of the
services provided. Hospitals are rewarded for providing a higher
quality and value of service. 39

CMS Hospital Quality Star Rating Program

As hospitals and healthcare providers began undertaking quality
improvement initiatives and participating in various models of care,
consumers were faced with difficulty assessing the status of a given
center. The government therefore sought new methods to increase
public transparency, launching the CMS’s Hospital Inpatient
Quality Reporting Program in 2003. 40 Using the Hospital Compare
website, consumers could compare different institutions directly
using different quality metrics. 41 Reporting under this program
incentivized clinicians to improve the quality and cost of inpatient
care for all patients. To support hospitals in reporting designated
quality measures in inpatient quality reporting, CMS offered a 0.4%
reduction in the measure of inflation and goods used by hospitals.
CMS sought to collate reported measures of quality into a single
score and on July 27, 2016, launched the Overall Hospital Quality
Star Ratings program. This rating, as it was given by the federal
government, played a major role in affecting patient selection of
sites of care, hospitals contracting with one another, and payers
se ing payments to hospitals. In this program’s inception, a star
rating was created through the combination of 64 reported hospital
quality measures into measure groups: mortality, safety of care,
readmission, patient experience, effectiveness of care, timeliness of
care, and efficient use of medical imaging. 42
Initial rating methods were met with widespread concern after
the exposure of many flaws, leading to a suspension of the program
in 2020. 42 In the initial iteration, small hospitals were compared
with large tertiary care centers even though smaller centers were
mandated to report fewer measure groups. As a result, in 2016, the
relative proportion of community hospitals receiving four-star or
five-star ratings was double that of major teaching hospitals. 42
Additionally, measure groups were calculated through a
complicated and opaque latent variable model weighting approach.
In one example, one measure in the Safety of Care accounted for
almost 90% of the rating, whereas the other measures collectively
accounted for the rest of the measure.
After collating feedback from hospitals and conducting a
rigorous review with technical experts, CMS relaunched the Overall
Hospital Quality Star Ratings program in April 2021 with three
major improvements. 42 In the first major improvement, measure
groups were scored as simple averages of their components so that
all individual items were equally weighted, clarifying ratings for all
involved parties. The second major change created a guideline that
hospitals must report at least three measure groups to receive a star
rating. Under the new approach, five measure groups exist:
mortality, safety of care, readmission, patient experience, and
timely and effective care. Fewer hospitals received a star rating as a
result of this change, but comparisons could be drawn between
those that did with greater accuracy. The final major change in the
updated program involved stratifying hospitals for comparison
based on the number of measure groups reported, either three,
four, or five. In 2021, this resulted in 931 hospitals that did not
satisfy all 5 measure groups to be compared with another in either
3 or 4 measure groups. 42 This stratification of hospitals allowed for
improved comparisons between one another, preventing hospitals
that report more data from being penalized. However, the accuracy
of this star rating system in predicting the outcome of surgical care
is still controversial or even unknown.

Limitations and Issues With the Overall

Hospital Quality Star Ratings Program
Critics are concerned that patients will be misled to believe a five-
star-rated hospital will provide superior quality of health care.
Concern has been voiced that the overall star rating does not
accurately represent each hospital’s performance. The validity of
the star rating has been questioned based on many major referral
centers in the country not receiving a five-star rating, and some
receiving one or two stars. This highlights how clinical experts
recognize that large referral centers provide superior specialty care,
even if the overall star rating of that specific institution does not
reflect the center’s reputation. Moreover, few measures for elective
procedures are included in the overall star rating. Medical
conditions such as fractures, congestive heart failure, stroke, acute
myocardial infarction, and pneumonia are usually urgent
circumstances. Each hospital may not be able to report data on all
measures, based on the type and number of patients treated. More
complex procedures and services may not be included in the
Hospital Compare calculation and therefore will not influence the
star rating of the hospital. Future updates to the calculation should
include more measures that patients value when comparing
hospitals.

How to Achieve a Better CMS Rating and

Improve a Practice’s Performance
One of the most challenging tasks in orthopaedic practice is
performance measurement and improvement. The performance
measurement is not only a data collection process but rather it is a
process to improve efficiency of operations. Performance
measurement systems can be based on either financial or
nonfinancial data. As a contemporary approach, the balanced
scorecard (BSC) provides a comprehensive set of financial and
nonfinancial performance measures for orthopaedic practices to be
strategy focused. The BSC is a management tool that was developed
in the 1990s. 43 The four original BSC categories are finance; internal
business processes; learning and growth; and customer. 43 Aside
from vision and mission, orthopaedic practices need to consider
redesigning their organizational structure because of the
requirements from the BSC. Inserting the function of internal audit
and risk management units is crucial to perform daily evaluation
basis. The CMS recommendations have been reviewed and
summarized to achieve be er rating and improve the facility’s
performance and these recommendations are presented in the BSC
chart (Figures 4 and 5).

Figure 4 Diagram shows the balanced scorecard for better implementation of

the New Overall Star Rating System.
 Figure 5 Diagram shows four balanced scorecard categories of main Centers
for Medicare & Medicaid Services performance measures.

Other Recent Changes Affecting Orthopaedic

Surgery

Outpatient Total Joint Replacement

Advances in medical technology and surgical techniques have made
a transition to outpatient TKA and THA possible in a safe and
efficacious manner. CMS released the calendar year 2020 Hospital
Outpatient Prospective Payment System, which includes payment
updates to total joint arthroplasties. The calendar year 2020
Hospital Outpatient Prospective Payment System proposed
removing THA from the inpatient-only list, making it eligible to be
reimbursed by hospital outpatient departments. 44 CMS removed
the current procedural terminology codes for TKA from its
inpatient-only list in 2018 and THA in 2020. Historically, both
procedures were only performed in the inpatient se ing. After the
CMS announcement, Medicare was allowed to provide payments for
these patients regardless of their hospital admission status,
ushering in a change to the status quo.
Increasing numbers of providers are adopting outpatient TKA
and THA techniques for higher value care. In 2017, the average
price for a TKA was $30,249 in the inpatient se ing compared with
$19,002 in the outpatient se ing. 6 Similarly, average prices of hip
replacements were $30,685 and $22,078 in inpatient and outpatient
se ings, respectively. 6 Although these procedures may be
performed on an outpatient basis, orthopaedic surgeons must
ensure that patients are proper candidates for outpatient
procedures. In the near future, many lower extremity joint
replacements will continue to be performed on an inpatient level
except for a select group of healthier patients with low comorbidity.

Ambulatory Surgical Centers

In the United States, ambulatory surgical centers (ASCs) have been
increasing since the early 1980s as a result of changes in
reimbursement arrangements and advances in medical technology.
Over the past 2 decades, orthopaedic surgery, similar to other
surgical disciplines, has shifted from the inpatient to the outpatient
se ing in association with a rapid growth in the number of ASCs.
In the early 1980s, the Medicare program was expanded to cover
care in ASCs, and a prospective payment system based on DRGs
was adopted for hospital inpatient care that created strong financial
incentives for hospitals to shift less complex surgery to outpatient
se ings. The CMS developed the Ambulatory Surgical Center
Quality Reporting Program to provide a uniform set of quality
measures for the ASC se ing. The primary purpose of these
measures is to promote high-quality care for patients receiving
services in ASC se ings. The Ambulatory Surgical Center Quality
Reporting Program uses a variety of tools to stimulate and support
a significant improvement in the quality of ASC care. Moreover,
this initiative aims to refine and standardize ASC data collection,
data transmission, and performance measures to construct a
prioritized and standard quality outpatient measure set for ASCs.
The CMS announced that ASCs that do not meet program
requirements, which include reporting of quality measure data for
the Ambulatory Surgical Center Quality Reporting Program, may
receive a 2% reduction in their ASC payment update. In the se ing
of rotator cuff repairs, the prevalence of outpatient procedures at
ASCs has increased by 272% from 1996 to 2006. 45 The same trends
were exemplified in other procedures such as the percentage of
carpal tunnel releases (CTRs) and knee arthroscopies performed at
ASCs. Outpatient CTRs and knee arthroscopies increased from 16%
to 49% and 15.3% to 50.7%, respectively. 46 One study demonstrated
that ASCs provide faster surgical times and achieve greater
efficiency as a result of having consistent and experienced surgical
teams who are familiar with the procedures, as well as surgical
room setups, and protocols. 47 These data have prompted some
insurers to adopt payment models that encourage patients to select
ASC-based surgery over hospital outpatient department–based
surgery, contributing to an increased utilization of ASC services by
approximately 14.3% over the past several years, which is estimated
to save insurers 17% to 17.6% in annual payouts. 48

Price Transparency
Under the Trump administration, a bipartisan group of legislators
approved new legislation requiring all hospitals in the United
States to provide accessible information online displaying pricing
information for all services provided. Further expansion mandated
hospitals to disclose not only gross charges, but also discounted
cash prices, payer-specific negotiated charges, and de-identified
maximum and minimum charges at negotiated rates.
Across the country and even within the same geographic area,
the cost of many procedures can vary significantly. For example,
within Dallas, Texas, the highest charge for a hip replacement is
fourfold greater than the lowest priced hip replacement in the same
city. 6
 Price transparency is intended to provide consumers the option
to compare the cost of care between hospitals and thereby drive
down the price of healthcare services by allowing consumers to
shop for the best price. Advocates argue that this in turn will
incentivize competition among providers to reduce their costs. 49
Opponents argue that health care is an inelastic good and that
transparency may drive an increase in negotiated rates because the
drive to access health care may be more important than the choice
of shopping around. 50 Opponents also believe that consumers may
be confused by and make decisions based on the overinflated gross
charges listed on a hospital chargemaster although they would not
be paying those rates.
The effects of price transparency on access to care, particularly
across orthopaedic surgery practices, remain yet to be seen. As of
June 2021, ASCs and private practices are not yet required to
publish the costs of their services. It remains unclear whether
publishing rates may be difficult. Concerns also exist as to whether
small practices can remain competitive should price transparency
further drive down reimbursements and negotiated rates.

Summary
The US healthcare system is a complex system interwoven with
consumers, government, and the private market. As the
government continues to play a larger role in revolutionizing and
enforcing healthcare transformation, understanding the history of
many policies can be important in the practice of medicine. The
ever-changing nature of health care also necessitates that surgeons
remain well informed of the effect of new policies and their future
trajectory. Orthopaedic surgeons should master understanding this
network of policies facing not only their patients, but also their own
institutions and practices. Orthopaedic surgeons should embrace
activism to ensure improved access to musculoskeletal care for
patients while also defending the future of the practice.
Key Study Points
When Medicare was first established, it covered 19 million US adults. As of 2020,
Medicare serves as health insurance for an estimated 61.2 million US adults, a
number projected to steadily grow to 80 million in 2030.
Recently, the CMS proposed cuts of 5% across all orthopaedic surgery RVUs, with
an additional 5.4% reduction in RVUs for hip and knee arthroplasty procedures.
Under the CJR model, hospitals carry most of the risk for the value of care, as
opposed to the previous BPCI initiative.
In 2018, CMS released BPCI Advanced, which is an episodic payment model that
allocates a single bundled payment for an episode of care for specified diagnostic-
related groups covering an episode for up to 90 days postdischarge.
Calendar year 2020 Hospital Outpatient Prospective Payment System proposed
removing THA from the inpatient-only list, making it eligible to be reimbursed by
hospital outpatient departments.

Annotated References
1. Papanicolas I, Woskie LR, Jha AK: Health care spending in the
United States and other high-income countries. J Am Med Assoc
2018;319(10):1024-1039.
2. Shrank WH, Rogstad TL, Parekh N: Waste in the US health care
system: Estimated costs and potential for savings. J Am Med Assoc
2019;322(15):1501-1509. This study estimated the levels of waste in
the US health system. The estimated cost of waste ranged from
$760 to $935 billion. Implementation of effective measures to
eliminate waste represents an opportunity to reduce the
continued increases in US healthcare expenditures. Level of
evidence: I.
3. Centers for Medicare and Medicaid Services: National Health
Expenditure Data Facts Sheet 2020. h ps://www.cms.gov/Research-
Statistics-Data-and-Systems/StatisticsTrends-and-
Reports/NationalHealthExpendData/NHE-Fact-Sheet. Accessed
June 15, 2021. In 2020, CMS released a data fact sheet that showed
the national healthcare expenditures reached $3.8 trillion in 2018,
accounting for 17.7% of the US gross domestic product. Level of
evidence: III.
4. Kaye DR, Luckenbaugh AN, Oerline M, et al: Understanding the
costs associated with surgical care delivery in the Medicare
population. Ann Surg 2020;271(1):23-28. This retrospective study
aimed to quantify the costs of inpatient and outpatient surgery in
the Medicare population. The findings highlight not only the
magnitude of spending on surgery but also the areas of greatest
growth, which could be targeted by future payment reforms.
Level of evidence: II.
5. The United States Healthcare Cost and Utilization Project
(HCUP-US): HCUP Fast Stats - Most Common Operations During
Inpatient Stays 2018. h ps://www.hcup-
us.ahrq.gov/faststats/NationalProceduresServlet. Accessed June
15, 2021.
6. Blue Cross Blue Shield: Planned Knee and Hip Replacement
Surgeries are on the Rise in the U.S 2019. h ps://www.bcbs.com/the-
health-of-america/reports/planned-knee-and-hip-replacement-
surgeries-are-the-rise- the-us#F2. Accessed June 15, 2021.
According to the data sheet released by Blue Cross Blue Shield
Insurance, the utilization of health services increased by 17% for
knee replacements and 33% for hip replacements from 2010 to
2017. Level of evidence: III.
7. Sisko AM, Keehan SP, Poisal JA, et al: National health
expenditure projections, 2018-27: Economic and demographic
trends drive spending and enrollment growth. Health Aff
2019;38(3):491-501. This economic analysis showed that
healthcare expenditures are projected to grow at an average
annual rate of 5.5% for 2018 to 2027 and represent 19.4% of gross
domestic product in 2027. Among the major payers, average
annual spending growth in Medicare (7.4%) is expected to exceed
that in Medicaid and private health insurance. Level of evidence:
II.
8. Cheng J, Kim J, Bieber SD, Lin E: Four years into MACRA: What
has changed? Semin Dial 2020;33(1):26-34. This literature review
presented a critical analysis and evaluation of the changes during
4 years into the MACRA. MACRA offers two tracks for
 participation, the Merit- based Incentive Payment System and
the Advanced APMs. Level of evidence: V.
9. Masterson A: The National Health Service: A Political History by
Charles Webster. Oxford University Press, 1998
10. Corning PA: The Evolution of Medicare: From Idea to Law. US
Social Security Administration, Office of Research and Statistics,
1969.
11. Keehan SP, Cuckler GA, Poisal JA, et al: National health
expenditure projections, 2019-28: Expected rebound in prices
drives rising spending growth. Health Aff 2020;39(4): 704-714.
Price growth for medical goods and services is projected to
accelerate, averaging 2.4% per year for 2019 to 2028, which partly
reflects faster expected growth in health-sector wages. The
insured share of the population is expected to fall from 90.6% in
2018 to 89.4% by 2028. Level of evidence: II.
12. Holahan J: The 2007-09 recession and health insurance coverage.
Health Aff 2011;30(1):145-152.
13. Hartman M, Martin AB, Espinosa N; The National Health
Expenditure Accounts Team: National health care spending in
2016: Spending and enrollment growth slow after initial coverage
expansions. Health Aff 2018;37(1):150-160.
14. United States Census Bureau: Health Insurance Coverage in the
United States: 2018 2019.
h ps://www.census.gov/content/dam/Census/library/-
publications/2019/demo/p60-267.pdf. Accessed June 20, 2021. This
data fact sheet from the US Census Bureau showed that, in 2019,
private health insurance covered 67.3% of the US population.
15. HealthCare.gov: Catastrophic Health Plans 2020.
h ps://www.healthcare.gov/choose-a-plan/catastrophic-health-
plans/. Accessed June 20, 2021. This webpage describes the
catastrophic health plans in detail. These plans are designed to
offer health insurance for younger, healthier people who may not
use health services often but still require protection from high-
 cost emergency or worst-case situations. As of 2020, the
deductible for all catastrophic plans is $8,150.
16. Fe er RB: Diagnosis related groups: Understanding hospital
performance. Interfaces 1991;21(1):6-26.
17. Centers for Medicare and Medicaid Services: FY 2021 Inpatient
Prospective Payment System (IPPS) Final Rule Home Page 2021.
h ps://www.cms.gov/medicare/acuteinpatient-pps/fy-2021-ipps-
final-rule-home-page. Accessed July 2021. CMS established
payment using the average cost of all patients within the same
MS-DRG. The total number of MS- DRGs may change annually
to incorporate newly defined diagnoses and new technologies,
but all are intended to be clinically coherent cohorts wherein all
patients have similar conditions. As of 2021, CMS recognizes 767
approved MS- DRGs, of which 75 comprise most orthopaedic
surgery care episodes. Level of evidence: III.
18. Centers for Medicare and Medicaid Services: Major Joint
Replacement (Hip or Knee) 2020. h ps://www.cms.gov/Outreach-
and-Education/Medicare-Learning-Network-
MLN/MLNProducts/Downloads/jointreplacement-
ICN909065Printfriendly.pdf. Accessed June 20, 2021. This data
fact sheet from CMS showed that MS-DRG 470, major joint
replacement or rea achment of the lower extremity without
major complication or comorbidity, represented the fourth most
common primary diagnosis among all DRGs.
19. Waters TM, Daniels MJ, Bazzoli GJ, et al: Effect of Medicare’s
nonpayment for hospital-acquired conditions: Lessons for future
policy. JAMA Intern Med 2015;175(3):347-354.
20. Cassidy A: Medicare’s Hospital-Acquired Condition Reduction
Program. Project HOPE, 2015.
21. A enello FJ, Wen T, Cen SY, et al: Incidence of “never events”
among weekend admissions versus weekday admissions to US
hospitals: National analysis. Br Med J 2015;350:h1460.
22. McDermo KW, Freeman WJ, Elixhauser A: Overview of
operating room procedures during inpatient stays in US
 hospitals, 2014: Statistical brief# 233, in Healthcare Cost and
Utilization Project (HCUP) Statistical Briefs. Agency for Healthcare
Research and Quality, 2017.
23. Crespi Z, Ismail A: Hospital-acquired conditions: A review of
classical and novel risk factors following total hip and knee
arthroplasties. JBJS Rev 2021;9(7). This review determines the risk
factors of HACs and assesses the extent of their economic
implications following two of the most prevalent inpatient
orthopaedic procedures in the United States: TKA and THA. The
authors outlined the current guidelines that are aimed at
reducing the incidence of the HACs. Level of evidence: III.
24. Marrero CE, Igbokwe LI, Leonardi C: Access to orthopedic care
post Medicaid expansion through the affordable care act. J Natl
Med Assoc 2019;111(2):148-152. Through a simulated patient
telephone survey, this study aimed to evaluate access to
orthopaedic surgeons for Medicaid patients in Louisiana. The
results suggest that although Medicaid expansion has decreased
the uninsured rate, access to outpatient orthopaedic care for
Medicaid patients in Louisiana is still significantly limited. Level
of evidence: II.
25. Reisman M: The affordable care act, five years later: Policies,
progress, and politics. P T 2015;40(9):575-600.
26. Jones DK, Greer SL: State politics and the creation of health
insurance exchanges. Am J Public Health 2013;103(8):e8-e10.
27. Wiley L: Medicaid for All?: State-Level Single-Payer Health Care.
Ohio State Law Journal, 2018.
28. CRS Report for Congress: Medicaid and Federal Grant Conditions
After NFIB v. Sebelius: Constitutional Issues and Analysis 2012.
29. King et al: v Burwell, Secretary of Health and Human Services, et al.
576 U.S. 473 (2015). Certiorari to the United States Court of
appeals for the fourth circuit, Supreme Court of the United
States. 2015.
30. Weinzierl M, Scherf R: Donald Trump and the Tax Cuts and Jobs
Act. Harvard Business School Case 719-002. Harvard Business
 School, 2018.
31. Kirkner RM: Sessions leaves the ACA undefended. Manag Care
2018;27(8):7-8.
32. Williamson TR, Paoli AR, Hu ler L, Zuckerman J, Bosco J:
Access to elective orthopaedic surgery after the affordable care
act Medicaid expansion: The New York State experience. J Am
Acad Orthop Surg 2020;28(4): e158-e163. This retrospective study
queried the New York Statewide Planning and Research
Cooperative System database and identified all patients who
underwent the 10 most common elective orthopaedic surgeries.
ACA–supported Medicaid expansion was associated with an
increase in Medicaid enrollment and a concomitant increase in
the utilization of orthopaedic surgery. Level of evidence: III.
33. Burwell SM: Se ing value-based payment goals — HHS efforts
to improve U.S. Health care. N Engl J Med 2015;372(10):897-899.
34. Barinaga G, Chambers MC, El-Othmani MM, Siegrist RB, Saleh
KJ: Affordable care organizations and bundled pricing: A new
philosophy of care. Orthop Clin North Am 2016;47(4):707-716.
35. El-Othmani MM, Sayeed Z, Ramsey JnA, Abaab L, Li le BE,
Saleh KJ: The joint utilization management program-
implementation of a bundle payment model and comparison
between year 1 and 2 results. J Arthroplasty 2019;34(11):2532-2537.
Under the BPCI program, the Joint Utilization Management
Program model demonstrates higher efficiency of care in the
post–acute care se ing through reduced length of stay, inpatient
rehabilitation admission rates, and 30-day readmission rate.
Level of evidence: II.
36. Sood N, Shier VL, Nakata H, Iorio R, Lieberman JR: The impact
of comprehensive care for joint replacement bundled payment
program on care delivery. J Arthroplasty 2019;34(4):609-612.e1.
This study examines whether hospital participation in CJR is
associated with having programs focused on improving
posthospitalization care or reducing costs using a survey of
orthopaedic surgeons. There were no statistically significant
 differences in implementation of having programs to reduce
costs or improve care during hospitalization. Level of evidence:
II.
37. Liao JM, Martinez JR, Shan EZ, et al: Medicare’s new voluntary
bundled payment program: Episode selection and participant
characteristics. Healthcare (Amsterdam, Netherlands) 2019;7(2):26-
30. This study offers the first evidence that some new types of
physician group practices and hospital types are being a racted
to Medicare bundled payments, an important insight for other
healthcare organizations without previous experience in
Medicare’s APMs. Level of evidence: III.
38. Hussey PS, Liu JL, White C: The Medicare access and CHIP
reauthorization act: Effects on Medicare payment policy and
spending. Health Aff 2017;36(4):697-705.
39. Sayeed Z, El-Othmani M, Shaffer WO, Saleh KJ: The Medicare
access and CHIP reauthorization act (MACRA) of 2015: What’s
new? J Am Acad Orthop Surg 2017;25(6):e121-e130.
40. Centers for Medicare & Medicaid Services. Hospital Inpatient
Quality Reporting Program. Accessed June 20, 2021.
h ps://www.cms.gov/Medicare/Quality-Initiatives- Patient-
Assessment-
Instruments/HospitalQualityInits/HospitalRHQDAPU.html
41. “Hospital compare” gets official rollout by CMS. Qual Le
Healthc Lead 2005;17(5):11-12.
h ps://pubmed.ncbi.nlm.nih.gov/16045104/
42. Bilimoria KY, Barnard C: An evolving hospital quality star rating
system from CMS: Aligning the stars. J Am Med Assoc
2021;325(21):2151-2152. In 2016, the CMS introduced the Overall
Hospital Quality Star Ratings program in an a empt to provide a
single public measure of hospital quality, summarizing dozens of
metrics on Hospital Compare. The star ratings carry considerable
credibility, given that they are issued by the federal government,
the single largest healthcare payer in the United States. Level of
evidence: V.
43. Kaplan RS, Norton DP: The balanced scorecard – measures that
drive performance. Harv Bus Rev 1992;70(1):71-79.
44. Centers for Medicare & Medicaid Services (CMS), HHS:
Medicare program: Hospital outpatient prospective payment and
ambulatory surgical center payment systems and quality
reporting programs; organ procurement organization reporting
and communication; transplant outcome measures and
documentation requirements; electronic health record (EHR)
incentive programs; payment to nonexcepted off-campus
provider-based department of a hospital; hospital value-based
purchasing (VBP) program; establishment of payment rates
under the Medicare physician fee schedule for nonexcepted items
and services furnished by an off-campus provider-based
department of a hospital. Final rule with comment period and
interim final rule with comment period. Fed Regist
2016;81(219):79562-79892.
45. Colvin AC, Egorova N, Harrison AK, Moskowi A, Flatow EL:
National trends in rotator cuff repair. J Bone Joint Surg Am
2012;94(3):227-233.
46. Kim S, Bosque J, Meehan JP, Jamali A, Marder R: Increase in
outpatient knee arthroscopy in the United States: A comparison
of national surveys of ambulatory surgery, 1996 and 2006. J Bone
Joint Surg Am 2011;93(11):994-1000.
47. Avery DM III, Matullo KS: The efficiency of a dedicated staff on
operating room turnover time in hand surgery. J Hand Surg Am
2014;39(1):108-110.
48. Robinson JC, Brown TT, Whaley C, Bozic KJ: Consumer choice
between hospital-based and freestanding facilities for
arthroscopy: Impact on prices, spending, and surgical
complications. J Bone Joint Surg Am 2015;97(18):1473-1481.
49. Miller BJ, Mandelberg MC, Griffith NC, Ehrenfeld JM: Price
transparency: Empowering patient choice and promoting
provider competition. J Med Syst 2020;44(4):80. In light of recent
health policy efforts to promote price transparency, this study
 reviews the challenges and benefits of price transparency. These
price transparency efforts include the recent executive order and
associated rulemaking directing providers to disclose negotiated
and out-of-pocket costs for shoppable healthcare services. Level
of evidence: V.
50. Esmaeilzadeh P: The impacts of the perceived transparency of
privacy policies and trust in providers for building trust in health
information exchange: Empirical study. JMIR Med Inform
2019;7(4):e14050. This retrospective study aimed to study the
health information exchange (HIE) adoption using a trust-
centered model. When patients trust in healthcare providers, and
they are aware of HIE security measures, HIE sharing procedures,
and privacy terms, they feel more in control, more assured, and
less at risk. Moreover, trust in providers has a significant
moderating effect on building trust in HIE efforts (P < 0.05). Level
of evidence: II.
C H AP T E R 6

Preoperative Evaluation and

Postoperative Care of the
Orthopaedic Patient
Ian M. Duensing MD, James A. Browne MD

Dr. Browne or an immediate family member has received royalties from DJ Orthopaedics; serves
as a paid consultant to or is an employee of DJ Orthopaedics, Kinamed, and OsteoRemedies; has
stock or stock options held in Radlink; and serves as a board member, owner, officer, or
committee member of American Association of Hip and Knee Surgeons, American Joint
Replacement Registry (AAOS), and Southern Orthopaedic Association. Neither Dr. Duensing nor
any immediate family member has received anything of value from or has stock or stock options
held in a commercial company or institution related directly or indirectly to the subject of this
chapter.

ABSTRACT
Careful preoperative evaluation and thoughtful postoperative
treatment of orthopaedic surgical candidates is essential to
successfully minimizing intraoperative and postoperative
complications while maximizing postoperative improvement and
function. This starts with meticulous preoperative assessment to
identify comorbidities that often are not readily apparent in
asymptomatic patients but may affect surgical success and risk
profiles. Cardiac and frailty risk indices provide objective data that
can help surgeons navigate patients through appropriate
stratification and preoperative testing, which occasionally leads to
specialist consultation and advanced workup. Cardiac risk
assessment is based heavily on patients’ prior history of cardiac
disease and/or myocardial infarction. Treatment of patients who
have undergone cardiac stent placement can be nuanced and
requires collaboration with a cardiologist. A broader understanding
of unique risks and management challenges faced with nonelective
and emergent cases allows for comprehensive care of all
orthopaedic patients. An understanding of individualized
perioperative pain management strategies and utilization of
multimodal pain regimens can lead to improved treatment of
patients with postoperative pain and help minimize narcotic use
and abuse.
Keywords: multimodal pain regimen; orthopaedic triage;
postoperative management; preoperative optimization; risk index

Introduction
Rising numbers of orthopaedic procedures and an aging population
create a demand for careful perioperative management, particularly
with a trend toward enhanced recovery pathways and same-day
discharges. Preoperative care before elective procedures can be
complex and requires a multidisciplinary approach to ensure
appropriate risk stratification, patient education, and optimization.
This includes preoperative screening tests and risk index
calculations as well as optimization of medical comorbidities.

Importance of Optimization
Personal subjection to risk has always been associated with surgery,
with historically poor predictability leaving patients and surgeons
with a sense of uncertainty. The evolution of formal risk prediction
has allowed for quantifiable risk assessment and informed surgical
decision making. Surgical risk is individualized from patient to
patient and influenced by a number of static and dynamic factors;
some of these are modifiable, some are not. The care team should
work to influence variables that are modifiable to ensure risk to the
patient is as low as possible and the likelihood of success is high.
This is important not only for patient success, satisfaction, and
quality of life but also for improving the value and cost of care in an
already strained health care system.

Pairing Risk With the Surgical Intervention

Perioperative risk spans a spectrum of severity ranging from minor
setbacks to devastating complications up to and including death or
permanent disability. Each case must be evaluated independently
as the complication profile is uniquely different and influenced by
individual patient risk and is compounded by complexity of
surgery. Most orthopaedic procedures are typically considered to be
intermediate risk (>1% but <3% risk for major cardiac events);
however, this level can vary. 1 High-risk surgery is typically seen as a
binary variable, yes or no, based on the aforementioned cutoff value
of 3% risk. 2 This knowledge, supported with quantitative risk
scoring systems and prediction models, helps patients and families
set realistic expectations related to mobility, expected recovery,
discharge timing, morbidity, and mortality rates. A more
comprehensive understanding of the potential for harm allows
patients to make be er decisions regarding their willingness to
proceed with elective surgery.

Preoperative Assessment
Historically, individual risk has been evaluated by surgeons’ gut
feeling or clinical gestalt and relied heavily on surgeon experience,
comfort level, and the ability to manage complications or escalate
care including critical care support. 3 Objective risk scoring systems
provide/augment/support physicians with quantifiable, evidence-
based data for informed decision making. There are many risk
calculators available that simplify the process of quantifying risk
assessment and allow for immediate data return.

Evaluation/Predictors of Risk
Cardiac Risk Indices
Major adverse cardiac events (MACEs) are prognostically important
in patients not undergoing cardiac surgery and frequently occur in
asymptomatic individuals. In a 2020 study of more than 2,000 high-
risk patients undergoing noncardiac surgical procedures, MACE
rates were 15.2% at 30 days and 20.6% within 1 year, 4 with a
cardiovascular death rate in this group of 1.2% at 30 days and 3.7%
at 1 year. The original Cardiac Risk Index (CRI), the CRI in non-
cardiac surgery or Goldman Risk Index, weighed patient
demographic data, general medical conditions and comorbidities,
clinical signs of heart failure, electrocardiographic manifestations,
and procedural risk to assign a risk class to these patients. 5 This
tool has become antiquated with more recent iterations of risk
indices and is now of historic relevance only.

Revised Cardiac Risk Index

The Revised Cardiac Risk Index (RCRI) was developed more than 20
years after the original CRI. It is simple, easy to use, and brief,
consisting of only six equally weighted components. 6 The input
variables are specifically centered around a history of cardiac
comorbidities and those caused by microvascular and
macrovascular disease. 7 Table 1 details the components of the
RCRI. According to the original description of this risk index, a
score of 0 carries a major cardiac event risk of 0.4%, whereas a score
of 3 or greater carries a risk of greater than 10%.

Table 1
Revised Cardiac Risk Index

Revised Cardiac Risk Index Variables Points Allocated

Ischemic heart disease 1
Cerebrovascular disease 1
Diabetes mellitus (insulin-dependent) 1
Chronic kidney disease (serum Cr 2.0 mg/dL or greater) 1
Congestive heart failure 1
High-risk surgery 1
Adapted from Feely MA, Collins CS, Daniels PR, et al: Preoperative testing before noncardiac
surgery: Guidelines and recommendations. Am Fam Physician 2013;87(6):414-418.

Acute Coronary Syndrome, Postmyocardial Infarction,

and Cardiac Risk
A prior cardiovascular event elevates the risk of recurrent acute
coronary syndrome, particularly in those with multiple prior
myocardial infarctions, yielding a recurrence rate of 24.4% within 2
years. 8 Survivors of myocardial infarction undergo a transition of
risk magnitude as they progress from the acute phase to a more
stable chronic phase. Although still at increased risk in comparison
with control patients who have not experienced myocardial
infarction, there is a well-documented risk regression seen in those
with multiple myocardial infarctions, with increasing length of time
from event, with risk normalization at around 3 to 4 months. 9 The
increasing population of patients who have experienced a cardiac
event has led to the development of secondary prevention risk
indices such as the Thrombolysis in Myocardial Infarction Risk
Score for Secondary Prevention, which evaluates nine clinical
variables that can predict up to a fivefold gradient of risk of
recurrent acute coronary syndrome, can stratify by magnitude of
risk (low, intermediate, and high), and has been validated in large
cohort studies. 10

Total Joint Arthroplasty CRI

General noncardiac risk prediction models may not be as accurate
as procedure-specific and population-specific tools. The total joint
arthroplasty CRI, which consists of three equally weighted variables
(age older than 80 years, history of cardiac disease, and history of
hypertension), was developed to be er stratify undergoing elective
joint replacement, 11 with a score of 3 equating to an adjusted odds
ratio of 11.19 and 16.27 for cardiac complication after total knee
arthroplasty and total hip arthroplasty, respectively. Recently,
experts have expressed concerns over this model’s simplicity, citing
the importance of sex, family history, ejection fraction, dyspnea,
anemia, dialysis, and cardiac and pulmonary comorbidities, which
have been independently associated with a postoperative cardiac
event after total joint arthroplasty. 12 Although validation and
further study is needed, identification of these variables should be
recognized and potentially included in future prediction models.

Modified Frailty Index

Objective cardiac risks identified by predictive modeling fail to
adequately represent a complete picture of total patient risk.
Frailty, or a state of vulnerability secondary to accumulation of
physiologic deficits and loss of reserve, 13 has become an area of
interest across surgical specialties and has been heavily studied in
orthopaedics as a potential negative modifier of outcomes. 13 Two
variations of the Modified Frailty Index (mFI) have been validated,
the older 11-point model (mFI-11) and a newer 5-point model (mFI-
5). The variables included were based on preoperative conditions
registered in the American College of Surgeons National Surgical
Quality Improvement Program database and extrapolated to fit a
more concise model. 13 The mFI-5 is a simple tool that looks at five
domains which are listed in Table 2. 14 Both the mFI-11 and the mFI-
5 have been useful across many of the orthopaedic subspecialties
and have been shown to be equally effective in predicting 30-day
morbidity, postoperative complications, and mortality with
excellent concordance in orthopaedics as a whole. 14 , 15

Table 2
Five-Factor Modified Frailty Index

Five-Factor Modified Frailty Index (mFI-5) Points Allocated

Chronic obstructive pulmonary disease/pneumonia 1
Diabetes mellitus 1
Nonindependent functional status 1
Congestive heart failure 1
Hypertension requiring medical treatment 1
Adapted from Traven SA, Reeves RA, Althoff AD, Slone HS, Walton ZJ: New five-factor
modified frailty index predicts morbidity and mortality in geriatric hip fractures. J Orthop
Trauma 2019;33(7):319-323.

American College of Surgeons National Surgical Quality

Improvement Program Surgical Risk Calculator
The American College of Surgeons National Surgical Quality
Improvement Program Surgical Risk Calculator was created in 2013
as a means to use data collected from the National Surgical Quality
Improvement Program database to facilitate decision making in the
preoperative se ing by assessing surgical appropriateness and
safety based on a number of preoperative risk factors. 16 The index
was formed based on variables from more than 1.4 million patients
and include a number of binary variables (yes or no) including
presence of diabetes, dyspnea, steroid use, hypertension,
congestive heart failure, and smoking (Table 3). Validation of this
model has shown high concordance with excellent predictive
probability for morbidity, mortality, and surgical and nonsurgical
complications. 16 An online tool to complete this risk assessment is
available at h ps://riskcalculator.facs.org/RiskCalculator/.

Table 3
The American College of Surgeons National Surgical Quality
Improvement Program Surgical Risk Calculator

Variables Response
Age (quartiles) <65, 65-75, 75-85, >85
Sex Male or Female
BMI class <18.5, 18.5-24.9, 25-29.9, 30-34.9, 35-39.9, >40
Emergency case Yes or No
Functional status Independent, requires assistance, dependent
ASA class 1-5
Diabetes mellitus Yes or No (+/− insulin)
Hypertension (requiring treatment) Yes or No
Congestive heart failure Yes or No
History of cardiac event Yes or No
Tobacco use (within 1 year) Yes or No
Dyspnea Yes or No
Ventilator Yes or No
Chronic steroid use Yes or No
 Variables Response
Preoperative ascites (within 1 month) Yes or No
Malignancy (metastatic) Yes or No
Chronic obstructive pulmonary disease Yes or No
Acute kidney failure Yes or No
Dialysis Yes or No
Preoperative sepsis (within 48 hr) Yes or No
CPT-specific risk Based on 2805 CPT codes
ASA = the American Society of Anesthesiologists, BMI = body mass index, CPT = Current
Procedural Terminology
Adapted from Bilimoria KY, Liu Y, Paruch JL, et al: Development and evaluation of the
universal ACS NSQIP surgical risk calculator: A decision aid and informed consent tool for
patients and surgeons. J Am Coll Surg 2013;217(5):833-842.e1-3.

Preoperative Testing: American College of

Cardiology/American Heart Association
Guidelines
Presurgical screening frequently yields identification of discrete
comorbid conditions that require medical workup and
optimization, but more often identifies high-risk individuals in
whom further testing may be beneficial. Orthopaedic surgeons and
other noncardiac, nonvascular surgeons often rely on the guidance
of the 2014 American College of Cardiology/American Heart
Association (ACC/AHA). 17 Utilization trends of preoperative
cardiac testing over the past decade have shown a decline because
of increased focus on appropriate use criteria and greater
awareness of cost-containment issues. 18

Electrocardiogram
Preoperative electrocardiogram (ECG) is a supplemental,
noninvasive test that has been heavily relied on perioperative
testing for its simplicity and utility in identification of potentially
threatening rhythm abnormalities. Current recommendations for
obtaining preoperative resting 12-lead ECG are based on urgency of
surgery and functional capacity of the patient, which is expressed as
metabolic equivalent tasks (METs), 17 or the basal oxygen
consumption for a 70-kg male; a MET of greater than 10 implies
excellent functional capacity, whereas a MET of less than 4 suggests
poor functional capacity. 17 This stratification allows determining
which patients should proceed with preoperative testing.

Who Needs It
ECG is thought to be of li le use and rarely indicated for
asymptomatic patients without cardiac history, those undergoing a
low-risk procedure, or those who can perform greater than 4 METs 1
because it has a low likelihood of changing management. It should,
however, be considered for all other groups, including those with
known coronary artery disease, peripheral arterial disease, clinically
significant arrhythmia, cerebrovascular disease, or other structural
heart disease and for any patient undergoing any high-risk
procedure. 17

When to Seek Cardiac Clearance

Referral restriction and resource preservation is important in
patients for whom cardiology referral is necessary. Concerns about
ECG findings or appropriateness may be answered through
telephone consultation with cardiology to appropriately stratify
patients while limiting traffic through heavily sought-after
specialists. Reasonable referrals according to the ACC/AHA
guidelines 17 include:

Patients with cardiac history and new findings on screening

ECG if comparison is available or any abnormal findings if
prior studies are not available. This is particularly important
for patients who are undergoing major or high-risk procedures.
A history of coronary artery disease with ST segment changes
translates to greater than 11% chance of myocardial infarction
or death postoperatively compared with a rate of 2.6% in those
without ST segment changes
 Patients with clinically significant sustained arrhythmias
especially with hemodynamic fluctuations
Patients with conduction abnormalities such as high-grade
heart blocks
Patients of any age with family history of sudden cardiac death

Exceptions include a known history of atrial fibrillation that is

hemodynamically stable and unchanged from prior assessments or
single premature ventricular tachycardia events and nonsustained
tachyarrhythmias without hemodynamic compromise. 17

Effectiveness as a Screening Tool

Although unlikely to change management significantly most of the
time, it meets many of the criteria for a useful screening tool. It is
simple to administer, inexpensive, and noninvasive and has the
potential to identify high-risk patients. Adherence to the
ACC/AHA guidelines for those who should undergo preoperative
ECG and appropriate consultation criteria can maximize the utility
of the ECG while minimizing inappropriate referral pa erns.

Echocardiogram
Heart failure remains a significant cause of perioperative morbidity
and mortality. Transthoracic echocardiogram (TTE) is the study of
choice when evaluating structural heart disease, specifically, left
ventricular morphology assessment (wall thickness and chamber
size), ventricular function (filling pressures and ejection fraction),
and valvular abnormalities (stenosis versus regurgitation). 19

Preoperative Left Ventricular Function

2014 ACC/AHA guidelines recommend 17 preoperative assessment
of left ventricular function in the following conditions:
 New onset dyspnea of unknown etiology in patients without
history of heart failure
Presence of clinical signs and symptoms of heart failure
Worsening dyspnea or clinical deterioration in patients with
known heart failure
History of valvular heart disease or heart failure without a TTE
in the past year
Clinical suspicion of moderate to severe valvular dysfunction

Identification of structural heart problems is critical because left

ventricular systolic dysfunction, severe mitral regurgitation, and
aortic stenosis were strongly associated with perioperative MACE 1
although adherence to ACC/AHA guidelines can be variable.

Specialist Driven
Information guiding the necessity of additional testing is
contradictory and often confusing with discrepancies seen even
among cardiologists, a subset of whom are culpable of ordering
rarely appropriate TTEs with no difference in clinical outcomes. 20
The decision for additional cardiac workup and further testing is
often identified on preoperative screening by orthopaedic surgeons
and anesthesiologists. These visits may prompt referral
emphasizing the need for knowledge of these guidelines.

Stress Test
The purpose of the cardiac stress test performed before elective
noncardiac surgery is to identify and optimize high-risk patients,
particularly those who have abnormal initial screening tests (ECGs
or TTEs). 18 According to ACC/AHA 2014 guidelines for
preoperative evaluation, 17 routine screening exercise ECG/TTE or
dobutamine stress echo testing is not recommended but is deemed
reasonable for patients who are at elevated risk and have poor or
unknown functional capacity if it will either change management or
help in the assessment for underlying myocardial ischemia.
Chest Radiograph
There is a lack of supportive evidence guiding the use of
preoperative chest radiograph before noncardiac surgery because
results frequently do not change clinical course. The 2016 updates
to the National Institute for Health and Care Excellence guidelines
as well as other guidelines recommend against routine preoperative
chest radiographs. 21 Preoperative chest radiograph may be
indicated in patients who are at risk of postoperative pulmonary
complications, including individuals older than 60 years, chronic
lung disease, American Society of Anesthesiologists class 2 or
greater, functional dependence, and hypoalbuminemia (<35 g/L). 22

Pulmonary Testing
Pulmonary function testing can identify patients with poor
pulmonary reserve and therefore may be useful in detecting those
at risk of postoperative pulmonary compromise. However, many of
these tests are dependent on patient effort and are difficult to
interpret. National Institute for Health and Care Excellence
guidelines based on low-quality evidence recommend against
routine testing in healthy patients or those undergoing low-risk
surgery. 21 Pulmonary testing may be indicated in patients with a
history of known respiratory disease or those undergoing major or
complex surgery with greater risk. 21

Use of Beta Blockers

Despite early support in the late 1990s and early 2000s,
unacceptably high rates of perioperative hypotension, bradycardia,
stroke, and death have resulted in waning enthusiasm for the use of
beta blockers. 23 Most recent ACC/AHA guidelines 17 reflect a much
more cautious approach toward the preoperative administration of
beta blockers. According to these guidelines, perioperative beta
blockers should be avoided in patients within 24 hours of
noncardiac surgery if not already taking these medications but
should be continued in patients taking these medications
chronically. Initiation of beta-blocker therapy may be favored in
patients at high or intermediate risk of MACE or in those with
three or more risk factors on the RCRI, but should be initiated
more than 48 hours before surgery to assess safety and tolerability
of the medication. 17

Patients With Cardiac Stents

Percutaneous coronary intervention and revascularization has
shown tremendous success in the management of coronary artery
disease. 24 Risks of postoperative complications vary with stent type
and timing from percutaneous coronary intervention. 17 A balance
must be struck when managing risk in these patients influenced by
urgency of surgery, length of time from stent placement, bleeding
risk while on dual antiplatelet therapy (APT), and thrombosis risk
when ceasing APT for procedures. Bare metal stents have shorter
requirements for dual APT than do drug-eluting stents, which is
advantageous to mitigate bleeding risk; however, there is still
substantial risk to these patients undergoing surgery in the acute
poststent period. 17 Current recommendations are to delay elective
noncardiac surgery until after the completion of dual APT for at
least 1 month and ideally 4 to 6 weeks. 17
Bare metal stents–related intimal hyperplasia and restenosis led
to the development of drug-eluting stents, which elute an
antiproliferative agent to prevent restenosis. 25 Drug-eluting stents
have been shown to be superior to bare metal stents in terms of
risk reduction of cumulative incidence of MACE but carry a
substantially greater risk of stent thrombosis than bare metal
stents, 25 necessitating a greater need for APT and a greater risk of
postoperative complications after noncardiac surgery. 26 ACC/AHA
recommends continuing dual APT for patients with drug-eluting
stents for at least 6 months before elective noncardiac and
orthopaedic surgery, 17 and patients should be monitored for
thrombotic events for extended duration postoperatively.
Perioperative Surveillance
Many hospitals have implemented medical comanagement teams
to aid in the perioperative surveillance and management of medical
comorbidities. Particularly vulnerable groups include geriatric
patients with trauma and hip fracture as well as elderly patients
who underwent arthroplasty and spine surgery. Orthopaedic
comanagement teams including a dedicated hospitalist have been
shown to lead to a decrease in in-hospital medical complications by
30% with no increase in length of stay despite higher complexity of
medical issues. 27 Protocols are typically developed to prevent and
manage acute kidney injury, cardiopulmonary complications,
electrolyte abnormalities, nonmusculoskeletal infections, venous
thromboembolism, and cognitive issues.

Evaluation of the Patient With Orthopaedic

Trauma

Injury Severity Assessment

Being able to deliver the highest quality care as well as providing
accurate patient and family education and expectations begins in
the emergency department with postinjury severity assessment.

Glasgow Coma Scale

The Glasgow Coma Scale provides an objective method of
description of baseline level of consciousness in the patient who
has experienced trauma by the summation of points assigned to
motor, verbal, and eye responses. 28 The Glasgow Coma Scale has
been used for both field and in-hospital evaluation of patients with
trauma; however, the validity of its use in these se ings has been
questioned. It has poor interobserver reliability, its utility is based
on data with variable quality, and it is unnecessarily complex and
useful for mortality predictions only at its extremes. 29 It is,
however, a ubiquitously used and widely familiar adjunct to aid in
the assessment of the multiply injured patient and, although only
occasionally useful in isolation, this score should be taken into
consideration within the complete evaluation of the multiply
injured patient.

Injury Severity Score

The Injury Severity Score is, and has been for many years, the gold
standard in injury description and prediction. 30 It is a
multiplicative score that estimates the cumulative injury severity
and provides mortality prediction based on these scores. Point
allocation is based on the Abbreviated Injury Scale, which assigns
points to six body regions based on degree of injury severity. The
three most severely injured regions indicated by the highest scores
are identified, squared, and summed, and this calculation produces
the Injury Severity Score. 31 The scale ranges from 1 to 75 with
major trauma being considered at a score of 15 or greater and
associated with a mortality rate of 10%. 31 The New Injury Severity
Score is a modification of the Injury Severity Score, which is
calculated based on the three highest scores regardless of anatomic
region in an a empt to improve the description limitation and
be er describe the totality of injury. 31

Trauma and Injury Severity Score

The Trauma and Injury Severity Score is a standardized tool useful
for both mortality prediction as well as assessing the quality of
trauma care provided in a health care se ing. 32 It provides a
comprehensive evaluation that incorporates trauma type (blunt or
penetrating), Injury Severity Score, and the Revised Trauma Score
(respiratory rate, Glasgow Coma Scale, and systolic blood pressure
multiplied by a weighted average). 33 The Trauma and Injury
Severity Score has been compared with other scoring methods
specifically looking at accuracy of mortality prediction for the
patient with orthopaedic polytrauma with 83.6% sensitivity and
77.5% specificity. 34
Trauma Mortality Prediction Model
A more recent addition to the growing number of trauma outcome
benchmarks and predictive models, the Trauma Mortality
Prediction Model has been touted as a more robust scoring system
because it is based on regression modeling rather than calculated
ratios. 35 The Trauma Mortality Prediction Model can be calculated
based on diagnoses captured by the International Classification of
Diseases, Ninth Revision, Clinical Modification lexicon or based on
Abbreviated Injury Scale severity values. 36 In a large database
study, the Trauma Mortality Prediction Model demonstrated
superior receiver operating characteristics (0.87 for the
International Classification of Diseases, Ninth Revision model and
0.89 for the Abbreviated Injury Scale model) and was a more
accurate predictor of mortality than any other available predictive
models. 36

Emergency Room Evaluation and

Resuscitation
Advanced Trauma Life Support
Developed by the American College of Surgeons, the Advanced
Trauma Life Support program provides a standardized approach to
the patient with trauma and begins in the emergency department
or prearrival. The premise of Advanced Trauma Life Support is to
address the greatest threat to life first. The primary assessment can
be remembered with the mnemonic ABCDE: airway maintenance
with cervical spine assessment, breathing and ventilation,
circulation with breathing control, disability and neurologic
assessment, and exposure and environmental control. This primary
assessment is performed frequently and repeated any time a
change in patient status is noted, beginning with assessment of
airway patency and breathing adequacy. 37

Resuscitation and Avoiding Shock

Hemorrhagic shock is based on percentage of total blood volume
lost with increasing alteration of circulatory parameters seen with
increasing volume. Physiologic signs of impending shock include
elevated pulse pressure, tachycardia, and tachypnea with more
significant findings such as agitation and decreased urinary output
less than 30 mL/h indicative of more severe volume loss. 38
Circulatory assessment during the primary survey includes
assurance of adequate intravenous access and resuscitation
beginning with 2 L of crystalloid followed by blood products in a
1:1:1 ratio. For the orthopaedic surgeon, there are several critical
moments of influence during the primary and secondary survey to
aid in the prevention of shock and prevent limb compromise and
disability. These include general limb assessment for uncontrolled
hemorrhage, open injuries and fractures, vascular injuries, pelvic
injuries causing increased pelvic volume, and intrapelvic
hemorrhage. 38 Femur and pelvic fractures on average lose
approximately 1 L (occasionally much more dependent on severity),
whereas tibial and humeral shaft fractures average 500 mL of blood
loss. This means a patient with bilateral femur fractures averages 2
L of blood loss and may be approaching or in stage III or IV of
hemorrhagic shock. 38

Triaging Care
Timing of Transfers
Establishment of designated trauma centers has allowed for the
centralization of care of patients with trauma. Levels of care denote
the complexity of trauma and degree of acuity that facilities are able
to accommodate based on personnel availability. 39 The Emergency
Medical Treatment and Active Labor Act is a federal law that
requires the evaluation, stabilization, and treatment of all patients
presenting to the emergency room irrespective of insurance status.
It has been interpreted that centers at a higher level of care must
accept all reasonable transfers. 39 Standardization of timeliness and
appropriateness of transfers are challenging targets heavily
dependent on institutional and regional variations. Interhospital
transfer can be subdivided into three distinct phases: time to
transfer request, time from acceptance to departure from referring
facility, and the time from departure to arrival at the accepting
facility. A study of more than 1,000 patients with trauma
transferred from over 100 US facilities showed transfer times of
greater than 4 hours on average with only 40% of the total time
represented by actual patient transport, 40 indicating significant
room for improvement at all stages.

Timing of Surgical Intervention

The ideal timing of surgical fixation of orthopaedic injuries remains
a topic of debate. Early total care, or the principle of acutely
managing surgical orthopaedic injuries, has been shown to
decrease pulmonary complications by as much as 60%, reduce
ventilator days, shorten length of stay, and decrease hospital
charges. 41 Alternatively, damage control orthopaedics allows for
the temporizing of musculoskeletal injuries to allow physiologic
optimization before definitive procedures. A less aggressive
approach is preferred for patients in extremis, with traumatic head
injuries, or with significant pulmonary injury to avoid the systemic
inflammatory response seen after surgery in an already
compromised host. This has led to the concept of early appropriate
care, which modifies treatment algorithms to individual situations.
Early definitive fixation (within 36 hours) of non–life-threatening
skeletal injuries is recommended for stable patients and borderline
patients who have an appropriate response to resuscitation, have
not suffered a significant closed head injury, and have good
respiratory status at the time of treatment. All other patients who
do not meet these criteria or who are physiologically unstable
should be treated initially with damage control principles. 41

Acute Compartment Syndrome

Compartment syndrome resulting from trauma or ischemia is a
limb-threatening surgical emergency requiring immediate surgical
intervention. Manifested by a nonspecific constellation of
symptoms known as the five P’s, pain out of proportion to the
degree of injury or examination, paresthesias, pallor, and in late
stages, pulselessness and paralysis, the diagnosis of acute
compartment syndrome can be difficult. 42 Prompt identification
and surgical decompression can prevent irreversible tissue
ischemia and death. Ischemia necrosis of muscle begins as early as
3 hours, and a delay of diagnosis greater than 12 hours after the
onset of symptoms is associated with only an 8% return of function.
42
Acute compartment syndrome is a true surgical emergency that
should be surgically managed as expediently as possible to avoid
irreversible muscle death and loss of limb function.

Open Fractures
Variability in mechanism energy, fracture complexity, degree of
soft-tissue injury, and contamination burden are important
variables in the management of open fractures that affect clinical
decision making. Open fractures are complicated by a significant
infection rate as high as 25% if not treated urgently and may be
modified by time to excisional débridement and antibiotic delivery.
In Gustilo-Anderson type III open fractures, an antibiotic delay of
only 66 minutes after injury has been shown in multivariate
analyses to be an independent predictor of infection. 43 Similarly,
antibiotic delay of 3 or more hours during the treatment of open
fractures carries 1.63 times greater odds of infection than those
treated within this window. 43 Importantly, with the increased focus
on expedient antibiotic delivery, the historic 6-hour débridement
window has been challenged in recent literature. Greater soft-tissue
devitalization, large skin defects, and gross contamination continue
to carry an infection rate of almost 20% and may benefit from
earlier escalation and acute débridement and irrigation, whereas
lower energy fractures and those about the upper extremity are
much less likely to become infected. 43

Geriatric Trauma and Hip Fracture Care

Patients older than 65 years are the fastest growing demographic
group in the United States and represent a unique population
within the trauma registries because they often succumb to much
lower energy mechanisms, are treated at lower acuity facilities, and
are undertriaged as patients with trauma. 44 Ground-level falls and
head injuries in geriatric patients are frequently undertriaged and
less likely to activate a trauma assessment than in a younger cohort
despite similar injury severity. 44 Subsequently, the mortality rate
for the undertriaged geriatric patient with trauma is four times
higher than that for younger patients. 44 Poor baseline physiologic
characteristics influence resilience and recovery rates. Diminished
mobility, loss of independence, decreased strength and stamina,
waning cognition, and structural physiologic differences such as
osteopenia and osteoporosis complicate the approach to this
demographic. Restoring mobility as quickly and safely as possible
can dramatically improve mortality rates and earlier mobility
decreases rates of pulmonary compromise, skin breakdown, and
ulceration, as well as lower rates of other major medical
complications. 45
Within this demographic, hip fractures represent an extremely
common and problematic injury with disproportionately high in-
hospital and out-of-hospital mortality rates frequently reported at
approximately 30% at 1 year. 46 Survivorship after fracture is
influenced by a number of patient-specific factors, including age,
anticoagulation, degree of health, significance of comorbid
conditions, and frailty/baseline physical function. 46 Surgeon and
hospital dynamics leading to delayed surgery beyond 48 hours is
also implicated in the high rates of death in this subset of patients.
Available literature supports urgent surgical intervention in hip
fractures with a goal of less than 24 hours for those with stable
underlying medical conditions and extended to 48 hours for those
who may require optimization. 46 Surgical delay beyond this time
period, while sometimes unavoidable, has been associated with an
almost twofold increase in mortality within 1 year postoperatively.
45
Postoperative Pain Management

Multimodal Analgesia
Mitigating postoperative pain experience can yield faster
mobilization, greater participation in therapy, decreased
complications, and improved surgeon-patient relationships and
result in a faster overall recovery. 47 Multimodal analgesia has
gained traction as a preferred method of treating orthopaedic
patients with postoperative pain. This strategy includes preemptive
analgesia, psychosocial and behavioral therapy, regional pain
blocks, and nonnarcotic and narcotic medication. By using varying
medications and treatment strategies with different delivery routes
and targets of action, postoperative pain may be managed
effectively while minimizing detrimental effects of narcotic
medication alone. A 2019 survey of a endees at the annual
American Association of Hip and Knee Surgeons meeting reported
that most of the respondents implement multimodal analgesia
during the postoperative recovery period for their patients,
emphasizing the importance of alternative therapies and
widespread use of these pathways. 47

Balanced Analgesia
Balanced analgesia is the clinical application using several
mechanistically different medications working synergistically to
maximize the combined benefits of multiple analgesic medications
while minimizing the potential for adverse reactions. 48 There are
three main targets for perioperative pain control under this model
on which to focus: processing of pain, transmission of painful
stimuli, and addressing the source of pain. 48 Pain processing is
affected primarily by the use of nonnarcotic medications given at
lower doses at more frequent and regular intervals to manage the
pain response. Blocking pain transmission is accomplished through
regional anesthesia techniques including peripheral nerve blocks.
Addressing the pain source through compression, cryotherapy,
local anesthesia, and elevation can be beneficial.

Interdisciplinary Approach to Pain

Management
Often overlooked, interpreting the pain experience and identifying
sources of psychosocial exacerbation of pain can be critical to
successful recovery and optimizing surgical outcomes. Pain
catastrophizing, anxiety, depression, pos raumatic stress disorder,
and other conditions have recently become a focus as potential
variables that may interfere with a successful surgical outcome. 49
According to a 2021 randomized controlled trial, implementation of
psychosocial interventions such as cognitive behavioral therapy
may have a positive effect of immediate surgical pain reduction and
pain catastrophizing scores. 49 Although this effect may not last
beyond 3 months postoperatively, it demonstrates the clear and
intimate connection between mental and physical health.
Additional therapies that may have a positive effect on the pain
experience include those offered by physical therapists and
nonsurgical health care providers, such as the use of a
transcutaneous electrical nerve stimulation unit, cryotherapy,
compressive wrapping, iontophoresis, and other similar modalities.
50

Preemptive Analgesia
Preemptive analgesia is used before incision and demonstrates a
protective effect on central sensitization by altering nociceptive
input after a stimulus. 51 Sensitization can lead to a lowered
threshold for pain and resultant hypersensitivity, 51 and prevention
of this yields improved pain control postoperatively. Preemptive
agents have rapid onset and high antinociceptive efficacy and
include drugs such as NSAIDs and acetaminophen. 51 Regional
anesthesia and neuraxial techniques are also integrated into the
preoperative regimen and have become critical element of
preemptive multimodal analgesia.

Role of NSAIDs
NSAIDs have demonstrated efficacy in pain reduction when used
perioperatively and have been reinforced by several randomized
controlled trials. 52 NSAIDs work by preventing the production of
prostaglandins by inhibiting cyclooxygenase 1 and 2. 51 Both
selective cyclooxygenase-2 inhibitors and nonselective NSAIDs are
supported by good evidence to suggest improved pain control and
decreased opioid use. The use of NSAIDs in the se ing of spine
fusions or fracture care has been cautioned against; however, there
is no conclusive evidence to suggest impaired fracture healing or
pseudarthrosis. 50 , 53 This has led most authors to recommend the
routine use of NSAIDs as part of the multimodal analgesic
regimen. In addition, the American Academy of Orthopaedic
Surgeons clinical practice guidelines provide moderate to strong
evidence supporting the use of NSAIDs, either selective or
nonselective, to decrease perioperative pain and, subsequently,
opioid use after primary total joint arthroplasty. 54

Alpha-2 Agonists
Alpha-2 adrenergic agonists, medications such as clonidine and the
more commonly used dexmedetomidine, are neuromodulatory
medications that act on the alpha-2 adrenergic receptors found in
both the central and peripheral nervous systems. 55 , 56 These agents
act centrally in the locus coeruleus and spinal cord inhibiting
presynaptic release of norepinephrine and can reduce opioid use
and lessen postoperative nausea and vomiting. 56 Adverse effects
consist primarily of bradycardia and hypotension, and although
usually mild and transient, can affect recovery. 56 These symptoms
can be prevented by avoiding a loading dose of the medication.
N-Methyl-d-Aspartate Antagonists
N-methyl-d-aspartate receptors are a class of glutamate receptors
that are expressed both centrally and peripherally and have been
implicated in pain processing and development of chronic pain. 57
N-methyl-d-aspartate antagonists, drugs such as ketamine and
dextromethorphan, have gained popularity in this arena as
nonopioid alternatives for pain management. Ketamine,
traditionally used as an anesthetic during surgery, has recently
been used postoperatively in subanesthetic dosing for acute pain
management. 57 Dextromethorphan can also be used in
postoperative pain control regimens and reduction of postoperative
nausea and vomiting. 57

Gabapentinoids
Gabapentin and pregabalin, initially indicated as anticonvulsants,
reduce neuronal excitability and have recently been used off-label
as part of multimodal pain strategies following surgery. 53 , 57
Adverse effects of sedation, dizziness, and visual disturbances,
combined with unclear efficacy in reducing postoperative pain,
have reduced the enthusiasm for these agents, particularly in the
elderly. 57

Opioids
Previously used as a foundation of postoperative pain control,
opioids have been implicated in a number of physiologic and
psychological complications in postsurgical patients. 47 The adverse
effect profile of these medications, including cardiovascular and
respiratory sedation, nausea, vomiting, and slowing of
gastrointestinal motility, has limited enthusiasm for their use and
recently brought the utility of these medications into question. 57
Although opioid-free recovery is an enticing goal, clinical
application may be challenging.
 Prescribing practices and excessive use of opioids over the past
several decades have contributed to an unsustainable opioid
epidemic of addiction and overdose. This has resulted in medical,
social, and political scrutiny of prescribing practices and increased
pressure to restrict the use of opioids in the perioperative se ing.
Orthopaedic surgeons account for almost 8% of opioid
prescriptions in the United States 58 ; therefore, it is particularly
important to curtail controlled substance prescription, formalize
and standardize multimodal regimens, and enhance patient
education preoperatively regarding pain expectations and
alternative nonnarcotic pain interventions.
Among efforts to restrict opioid prescriptions, social and political
processes have been successful in raising awareness of the harms of
narcotics. However, as previously mentioned, these medications
continue to play a critical role in postoperative pain control and
multimodal analgesia. 58 Standardization of prescribing habits can
help contain supply and reduce access to opioids by limiting the
total number of pills given and reviewing prescription database
history to prevent duplicate orders. 58
Orthopaedic surgeons have a particularly important opportunity
to prevent inappropriate use of controlled substances accounting
for almost 9% of cases of chronic opioid dependence. 59 Long-term
use can be lessened by providing a hard limit on the number of
pills given with policies in place for refill refusal, providing
locations for the safe disposal of unused pills, focusing on patient
education, minimizing or stopping preoperative use of narcotics,
and maximizing multimodal analgesia and alternative strategies for
perioperative pain control. 60

Summary
The importance of excellent perioperative care of orthopaedic
patients is often minimized but is crucial for patient satisfaction
and successful surgical outcomes. This requires a multidisciplinary
approach to preoperative risk stratification and optimization as well
as postoperative multimodal pain management. These concepts
hold true for patients undergoing elective and outpatient
procedures as well as high-risk, complex, or urgent/emergent
management. Successful execution of these models requires
surgeons to be familiar with not only orthopaedic clinical practice
guidelines but also specialty guidelines, such as cardiology and
anesthesia, which generates appropriate referral pa erns without
overburdening an already strained health care system.

Key Study Points

Scoring criteria and risk indices provide objective data with which to make informed
decisions regarding patients’ risk of perioperative morbidity and mortality, which can
improve outcomes and safety.
Additional preoperative testing such as ECG or stress testing before orthopaedic
surgery is indicated in certain individuals in whom ACC/AHA criteria are met.
Appropriate triaging and treatment of patients with orthopaedic trauma necessitates
the ability to identify and expediently manage orthopaedic emergencies such as
acute compartment syndrome as well as treat the individual with polytrauma through
the Advanced Trauma Life Support protocol.
Familiarization with multimodal analgesic regimens allows surgeons to adequately
treat perioperative pain while responsibly limiting the number of narcotics provided to
prevent overuse and abuse.

Annotated References
1. Smilowi NR, Berger JS: Perioperative cardiovascular risk
assessment and management for noncardiac surgery: A review. J
Am Med Assoc 2020;324(3):279-290. This review article summarizes
cardiac risk assessment strategies before noncardiac surgery,
including perioperative risk assessment based on metabolic
equivalents, utility of additional preoperative testing (ECG, stress
test, echo), coronary procedures and revascularization, and
medical strategies for risk reduction. Level of evidence: V.
2. Woo SH, Marhe a GD, Cowan SW, Ackermann L: Development
and validation of a prediction model for stroke, cardiac, and
mortality risk after non-cardiac surgery. J Am Heart Assoc
 2021;10(4):e018013. The authors discuss a risk prediction model
for stroke, major cardiac events, and mortality after noncardiac
surgery, developed and validated based on more than 1 million
patients from the National Surgical Quality Improvement
Program database and creation of an online/mobile platform.
Level of evidence: III.
3. Dilaver NM, Gwilym BL, Preece R, Twine CP, Bosanquet DC:
Systematic review and narrative synthesis of surgeons’
perception of postoperative outcomes and risk. BJS Open
2020;4(1):16-26. This study made an assessment of surgeons’
ability to predict perioperative morbidity and mortality, which
showed good general morbidity prediction but poor mortality
risk and long-term outcome prediction, stressing the importance
of risk prediction tools. Level of evidence: III.
4. Sazgary L, Puelacher C, Lurati Buse G, et al: Incidence of major
adverse cardiac events following non-cardiac surgery. Eur Heart J
Acute Cardiovasc Care 2020;10(5):550-558. The authors present a
prospective observational study of 2,265 patients at high risk for
MACEs after noncardiac surgery. Results indicated that one in
five patients will experience cardiac complications within 1 year
and risk is elevated for 5 months postoperatively. Level of
evidence: II.
5. Brown KN, Cascella M: Goldman risk indices, in StatPearls
[Internet]. StatPearls Publishing, 2021. Available at:
h ps://www.ncbi.nlm.nih.gov/books/NBK546604/. The authors
review literature outlining the historic Goldman Risk Index and
more modern derivatives that are used for cardiac risk
assessment.
6. Faloye AO, Gebre MA, Bechtel AJ: Predicting cardiac risk in
noncardiac surgery: A narrative review. J Anesth 2021;35(1):122-
129. This review article provides an overview of myocardial injury
and summarizes the available clinical and laboratory findings
that put patients at increased risk of cardiac events after
noncardiac surgery. Level of evidence: V.
 7. Jankovic RJ, Dinic V, Markovic D: Pre and postoperative risk
management: The role of scores and biomarkers. Curr Opin
Anaesthesiol 2020;33(3):475-480. The authors present a summary
of preoperative cardiac risk assessment focusing on the utility of
cardiac biomarkers such as B-type natriuretic peptide,
microRNAs, high-sensitivity C-reactive protein, and others as an
alternative or adjunct to currently used risk calculators. Level of
evidence: V.
8. Namiuchi S, Sunamura S, Tanita A, et al: Higher recurrence rate
of acute coronary syndrome in patients with multiple-time
myocardial infarction. Int Heart J 2021;62(3): 493-498. A
retrospective review of 794 patients with a history of multiple
myocardial infarctions is presented to identify recurrence rate of
acute coronary syndrome in this group, which was three times
higher than those without a history of myocardial infarction
(11.9% versus 4.2%, respectively). Level of evidence: III.
9. Bash LD, White K, Patel MD, et al: Cardiovascular risk factors
and secondary events among acute and chronic stable myocardial
infarction patients: Findings from a managed care database.
Cardiol Ther 2019;8(2):329-343. In this retrospective analysis,
23,352 patients showed higher rates of recurrent acute coronary
syndrome within the first 3 months after myocardial infarction.
Patients with acute myocardial infarction had mortality rates that
remained higher for 3 years, at which point survivorship curves
paralleled those of patients with chronic myocardial infarction.
Level of evidence: III.
10. Huang D, Cheng YY, Wong YT, et al: TIMI risk score for
secondary prevention of recurrent cardiovascular events in a real-
world cohort of post-non-ST-elevation myocardial infarction
patients. Postgrad Med J 2019;95(1125):372-377. This observational
study of 891 patients validated the Thrombolysis in Myocardial
Infarction Risk Score for Secondary Prevention, a scoring system
that successfully stratified patients with post–ST-elevation
myocardial infarction in a real-world cohort. Level of evidence: II.
11. Waterman BR, Belmont PJ, Bader JO, Schoenfeld AJ: The total
joint arthroplasty cardiac risk index for predicting perioperative
myocardial infarction and cardiac arrest after primary total knee
and hip arthroplasty. J Arthroplasty 2016;31(6):1170-1174.
12. Kataria R, Iniguez R, Foy M, Sood A, Gonzalez ME: Preoperative
risk factors for postoperative cardiac arrest following primary
total hip and knee arthroplasty: A large database study. J Clin
Orthop Trauma 2021;16:244-248. This retrospective review of
National Surgical Quality Improvement Program database
identified perioperative transfusion, dyspnea at rest with
moderate exertion, and age older than 72 years are all
independently associated with cardiac arrest after total joint
arthroplasty. Level of evidence: III.
13. Panayi AC, Orkaby AR, Sakthivel D, et al: Impact of frailty on
outcomes in surgical patients: A systematic review and meta-
analysis. Am J Surg 2019;218(2):393-400. A meta-analysis of 16
studies and more than 680,000 patients across surgical specialties
identified the mFI as an important predictor of perioperative
morbidity, with higher rates of all complications and
readmissions and four times higher mortality rates than nonfrail
patients. Level of evidence: IV.
14. Traven SA, Reeves RA, Althoff AD, Slone HS, Walton ZJ: New
five-factor modified frailty index predicts morbidity and mortality
in geriatric hip fractures. J Orthop Trauma 2019;33(7):319-323. A
retrospective study of the National Surgical Quality
Improvement Program database including 58,603 patients is
presented, showing mFI-5 is a strong predictor of postoperative
morbidity and mortality in patients undergoing surgery for hip
fracture. Level of evidence: III.
15. Tracy BM, Adams MA, Schenker ML, Gelbard RB: The 5 and 11
factor modified frailty indices are equally effective at outcome
prediction using TQIP. J Surg Res 2020;255:456-462. This
retrospective study showed that the efficacy in predicting adverse
outcomes in surgical database registries is equally effective at
predicting complications and discharge dispositions in a trauma
 registry, Trauma Quality Improvement Program. Level of
evidence: III.
16. Bilimoria KY, Liu Y, Paruch JL, et al: Development and
evaluation of the universal ACS NSQIP surgical risk calculator: A
decision aid and informed consent tool for patients and
surgeons. J Am Coll Surg 2013;217(5):833-842.e1-3.
17. Fleisher LA, Fleischmann KE, Auerbach AD, et al: 2014
ACC/AHA guideline on perioperative cardiovascular evaluation
and management of patients undergoing noncardiac surgery:
Executive summary – A report of the American College of
Cardiology/American Heart Association task force on practice
guidelines. Circulation 2014;130(24):2215-2245.
18. Rubin DS, Hughey R, Gerlach RM, et al: Frequency and
outcomes of preoperative stress testing in total hip and knee
arthroplasty from 2004 to 2017. JAMA Cardiol 2021;6(1):13-20. A
cross-sectional study of over 800,000 joint replacements is
presented, evaluating trends and frequencies of cardiac stress
testing and showing a peak frequency in 2006 and a decreasing
trend to 2017 with no difference in rates of cardiac events. Level
of evidence: IV.
19. Writing Commi ee, Maddox TM, Januzzi JLJr, Allen LA, et al:
2021 update to the 2017 ACC expert consensus decision pathway
for optimization of heart failure treatment: Answers to 10 pivotal
issues about heart failure with reduced ejection fraction – A
report of the American College of Cardiology Solution Set
Oversight Commi ee. J Am Coll Cardiol 2021;77(6):772-810. The
existing American College of Cardiology guidelines are updated
regarding appropriate treatment for patients with heart failure
and reduced ejection fraction. Level of evidence: V.
20. Tharmaratnam T, Bouck Z, Sivaswamy A, et al: Association
between physicians’ appropriate use of echocardiography and
subsequent healthcare use and outcomes in patients with heart
failure. J Am Heart Assoc 2020;9(1):e013360. A retrospective review
of ordering trends for 35 Ontario-based cardiologists stratified
 into tertiles (low, moderate, and high) is presented, showing no
difference in additional tests ordered but fewer follow-ups and
less likelihood to prescribe evidence-based medication in the
high utilizer group. Level of evidence: III.
21. National Institute for Health and Care Excellence (NICE).
Routine preoperative tests for elective surgery [NICE Guideline 45].
Published April 5, 2016. h ps://www.nice.org.uk/guidance/ng45.
22. Qaseem A, Snow V, Fi erman N, et al: Risk assessment for and
strategies to reduce perioperative pulmonary complications for
patients undergoing noncardiothoracic surgery: A guideline from
the American College of Physicians. Ann Intern Med
2006;144(8):575-580.
23. Wijeysundera DN, Duncan D, Nkonde-Price C, et al:
Perioperative beta blockade in noncardiac surgery: A systematic
review for the 2014 ACC/AHA guideline on perioperative
cardiovascular evaluation and management of patients
undergoing noncardiac surgery – A report of the American
College of Cardiology/American Heart Association task force on
practice guidelines. J Am Coll Cardiol 2014;64(22):2406-2425.
24. Chacko L, Howard JP, Rajkumar C, et al: Effects of percutaneous
coronary intervention on death and myocardial infarction
stratified by stable and unstable coronary artery disease: A meta-
analysis of randomized controlled trials. Circ Cardiovasc Qual
Outcomes 2020;13(2):e006363. The authors present a meta-analysis
of randomized controlled trials assessing the success of coronary
angioplasty on mortality and myocardial infarction. This study
showed a reduction in death, cardiac death, and myocardial
infarction in patients with unstable coronary artery disease
receiving percutaneous coronary intervention but no difference
for stable disease. Level of evidence: I.
25. Kim HJ, Levin LF: The management of patients on dual
antiplatelet therapy undergoing orthopedic surgery. HSS J
2010;6(2):182-189.
26. Childers CP, Maggard-Gibbons M, Ulloa JG, et al: Perioperative
management of antiplatelet therapy in patients undergoing non-
cardiac surgery following coronary stent placement: A systematic
review. Syst Rev 2018;7(1):4.
27. Rohatgi N, Weng Y, Ki le J, Ahuja N: Merits of surgical
comanagement of patients with hip fracture by dedicated
orthopaedic hospitalists. J Am Acad Orthop Surg Glob Res Rev
2021;5(3):e20.00231. This retrospective study examined over 2,000
hip fracture admissions and found an association between
dedicated orthopaedic hospitalist involvement and fewer medical
complications. Level of evidence: III.
28. Reith FC, Van den Brande R, Synnot A, Gruen R, Maas AIR: The
reliability of the Glasgow Coma Scale: A systematic review.
Intensive Care Med 2016;42(1):3-15.
29. Hopkins E, Green SM, Kiemeney M, Haukoos JS: A two-center
validation of “patient does not follow commands” and three
other simplified measures to replace the glasgow coma scale for
field trauma triage. Ann Emerg Med 2018;72(3):259-269.
30. Lavoie A, Moore L, LeSage N, Liberman M, Sampalis JS: The
injury severity score or the new injury severity score for
predicting intensive care unit admission and hospital length of
stay? Injury 2005;36(4):477-483.
31. Javali RH, Krishnamoorthy , Patil A, et al: Comparison of injury
severity score, new injury severity score, revised trauma score
and trauma and injury severity score for mortality prediction in
elderly trauma patients. Indian J Crit Care Med 2019;23(2):73-77.
This prospective observational study compared the accuracy of
three injury severity scores. Trauma and Injury Severity Score
outperformed Injury Severity Score, New Injury Severity Score,
and Revised Trauma Score as the strongest predictor of mortality
in the elderly patient with trauma. Level of evidence: II.
32. Kimura A, Chadbunchachai W, Nakahara S: Modification of the
Trauma and Injury Severity Score (TRISS) method provides
 be er survival prediction in Asian blunt trauma victims. World J
Surg 2012;36(4):813-818.
33. Domingues CA, Coimbra R, Pogge i RS, et al: New Trauma and
Injury Severity Score (TRISS) adjustments for survival prediction.
World J Emerg Surg 2018;13:12.
34. Agarwal A, Agrawal A, Maheshwari R: Evaluation of probability
of survival using APACHE II & TRISS method in orthopaedic
polytrauma patients in a tertiary care centre. J Clin Diagn Res
2015;9(7):RC01-RC04.
35. Haider AH, Villegas CV, Saleem T, et al: Should the IDC-9
trauma mortality prediction model become the new paradigm for
benchmarking trauma outcomes? J Trauma Acute Care Surg
2012;72(6):1695-1701.
36. Cook A, Weddle J, Baker S, et al: A comparison of the injury
severity score and the trauma mortality prediction model. J
Trauma Acute Care Surg 2014;76(1):47-52.
37. Galvagno SMJr, Nahmias JT, Young DA: Advanced Trauma Life
Support® update 2019: Management and applications for adults
and special populations. Anesthesiol Clin 2019;37(1):13-32. An
overview of Advanced Trauma Life Support measures is broken
down by body regions. A description of unique considerations in
special populations such as pediatric and geriatric patients with
trauma is presented. Level of evidence: V.
38. Kowalski A, Brandis D: Shock Resuscitation. StatPearls, 2021. The
authors review the definition and physiologic parameters of
shock with a focus on hemorrhagic shock and appropriate
resuscitation measures for each.
39. O’Connell RS, Haug EC, Malasi P, et al: Appropriateness of
patients transferred with orthopedic injuries: Experience of a
level I trauma center. Eur J Orthop Surg Traumatol 2018;28(4):551-
554.
40. U er GV, Victorino GP, Wisner DH: Interhospital transfer of
acute trauma patients: How long does it take and how is the time
spent? Clin Med Insights 2008.
41. Stinner DJ, Edwards D: Surgical management of
musculoskeletal trauma. Surg Clin North Am 2017;97(5):1119-1131.
42. Guo J, Yin Y, Jin L, et al: Acute compartment syndrome: Cause,
diagnosis, and new viewpoint. Medicine (Baltimore)
2019;98(27):e16260. This review article outlines the clinical
features and diagnostic criteria of acute compartment syndrome.
The authors emphasize the importance of emergent
decompression to avoid irreversible muscle necrosis. Level of
evidence: V.
43. Rozell JC, Connolly KP, Mehta S: Timing of operative
debridement in open fractures. Orthop Clin North Am
2017;48(1):25-34.
44. Horst MA, Morgan ME, Vernon TM, et al: The geriatric trauma
patient: A neglected individual in a mature trauma system. J
Trauma Acute Care Surg 2020;89(1):192-198. A retrospective review
of more than 150,000 geriatric patients with trauma is presented.
Clusters of geriatric trauma with high Injury Severity Score and
low rates of treatment representing undertriage of this group are
discussed. Level of evidence: III.
45. Brooks SE, Pee AB: Evidence-based care of geriatric trauma
patients. Surg Clin North Am 2017;97(5):1157-1174.
46. Seong YJ, Shin WC, Moon NH, Suh KT: Timing of hip-fracture
surgery in elderly patients: Literature review and
recommendations. Hip Pelvis 2020;32(1):11-16. A literature review
of hip fracture surgery is presented, summarizing available data
regarding timing of fixation. Based primarily on observational
studies, surgery within 48 hours is superior, except in cases when
comorbid conditions can be improved; there is no increase in
mortality. Level of evidence: V.
47. Hannon CP, Keating TC, Lange JK, et al: Anesthesia and
analgesia practices in total joint arthroplasty: A survey of the
American Association of Hip and Knee Surgeons Membership. J
Arthroplasty 2019;34(12):2872-2877.e2. This study summarizes the
responses to an American Association of Hip and Knee Surgeons
 survey on multimodal anesthesia. Although there was no
consensus on optimal regimen, most of the respondents used
preemptive analgesia and some form of multimodal analgesia,
including periarticular injection or blocks in addition to opioids.
Level of evidence: IV.
48. Mariano ER, Schatman ME: A commonsense patient-centered
approach to multimodal analgesia within surgical enhanced
recovery protocols. J Pain Res 2019;12: 3461-3466. This review
article outlines appropriate individualized multimodal pain
regimen. Individual pain experience pathways and nodes within
these pathways at which to intervene to maximize enhanced
recovery pathways are reviewed. Level of evidence: V.
49. Buvanendran A, Sremac AC, Merriman PA, et al: Preoperative
cognitive-behavioral therapy for reducing pain catastrophizing
and improving pain outcomes after total knee replacement: A
randomized clinical trial. Reg Anesth Pain Med 2021;46(4):313-321.
A randomized controlled trial of 80 patients with high pain
catastrophizing scores treated with cognitive behavioral therapy
versus none is presented. Cognitive behavioral therapy showed
improved physical component summary and the Western
Ontario and McMaster Universities Osteoarthritis Index scores,
but they were not significantly different at 3 months
postoperatively. Level of evidence: I.
50. Hsu JR, Mir H, Wally MK, Seymour RB: Clinical practice
guidelines for pain management in acute musculoskeletal injury.
J Orthop Trauma 2019;33(5):e158-e182. Guidelines produced from
a panel of 15 traumatologists and pain management specialists
outline evidence-based strategies to maximize perioperative
comfort and minimize opioid use after musculoskeletal injuries.
Level of evidence: V.
51. Moucha CS, Weiser MC, Levin EJ: Current strategies in
anesthesia and analgesia for total knee arthroplasty. J Am Acad
Orthop Surg 2016;24(2):60-73.
52. Sah AP, Liang K, Sclafani JA: Optimal multimodal analgesia
treatment recommendations for total joint arthroplasty: A critical
analysis review. JBJS Rev 2018;6(6):e7.
53. Kurd MF, Krei T, Schroeder G, Vaccaro AR: The role of
multimodal analgesia in spine surgery. J Am Acad Orthop Surg
2017;25(4):260-268.
54. Fillingham YA, Hannon CP, Roberts KC, et al: Nonsteroidal
anti-inflammatory drugs in total joint arthroplasty: The clinical
practice guidelines of the American Association of Hip and Knee
Surgeons, American Society of Regional Anesthesia and Pain
Medicine, American Academy of Orthopaedic Surgeons, Hip
Society, and Knee Society. J Arthroplasty 2020;35(10):2704-2708.
Clinical practice guidelines that outline evidence-based criteria
for perioperative NSAID use, reviewed by multiple governing
bodies in orthopaedics and pain management, are presented.
Level of evidence: II.
55. Nguyen V, Tiemann D, Park E, Salehi A: Alpha-2 agonists.
Anesthesiol Clin 2017;35(2):233-245.
56. Kaye AD, Chernobylsky DJ, Thakur P, et al: Dexmedetomidine
in Enhanced Recovery After Surgery (ERAS) protocols for
postoperative pain. Curr Pain Headache Rep 2020; 24(5):21. The
authors present a clinical review of dexmedetomidine as an
adjunct to a multimodal regimen in enhanced recovery pathways.
It has been shown to decrease postoperative nausea, vomiting,
and delirium/agitation and provides anxiolysis with minimal
effect on respiratory drive. Primary adverse effects include
hypotension. Level of evidence: V.
57. Wick EC, Grant MC, Wu CL: Postoperative multimodal
analgesia pain management with nonopioid analgesics and
techniques: A review. JAMA Surg 2017;152(7):691-697.
58. Soffin EM, Waldman SA, Stack RJ, Liguori GA: An evidence-
based approach to the prescription opioid epidemic in
orthopedic surgery. Anesth Analg 2017;125(5): 1704-1713.
59. Trasolini NA, McKnight BM, Dorr LD: The opioid crisis and the
orthopedic surgeon. J Arthroplasty 2018;33(11):3379-3382. e1.
60. Pa kowski MS, Pa kowski JC: Perioperative pain management
and avoidance of long-term opioid use. Sports Med Arthrosc Rev
2019;27(3):112-118. This review article outlines opioid reduction
strategies after surgery, including preoperative counseling and
expectations, multimodal analgesia, behavioral health strategies,
and exercise-induced analgesia. Level of evidence: V.
C H AP T E R 7

Coagulation and Blood

Management
William G. Hamilton MD, FAAOS, Sean E. Slaven MD

Dr. Hamilton or an immediate family member has received royalties from DePuy, a Johnson &
Johnson Company and Total Joint Orthopedics; is a member of a speakers’ bureau or has made
paid presentations on behalf of DePuy, a Johnson & Johnson Company; serves as a paid
consultant to or is an employee of DePuy, a Johnson & Johnson Company and Total Joint
Orthopedics; and has received research or institutional support from Biomet, DePuy, a Johnson
& Johnson Company, and Inova Health Care Services. Neither Dr. Slaven nor any immediate
family member has received anything of value from or has stock or stock options held in a
commercial company or institution related directly or indirectly to the subject of this chapter.

ABSTRACT
Venous thromboembolism represents a significant and potentially
life-threatening condition, and patients undergoing major
orthopaedic surgery are at elevated risk. Mechanical and
pharmacologic prophylaxis can be implemented to mitigate the risk
of thromboembolism, but must be carefully selected and managed
to reduce the risk of bleeding and other complications. The
American Academy of Orthopaedic Surgeons and the American
College of Chest Physicians have issued clinical practice guidelines
for management of thromboprophylaxis in orthopaedic patients.
Limiting allogeneic blood transfusion is beneficial to reduce
complications, limit costs, reduce length of stay, and improve the
overall patient experience. The use of tranexamic acid has resulted
in a decreased transfusion rate with a favorable safety profile. It is
important to review preoperative, intraoperative, and postoperative
blood management protocols to further reduce the use of
allogeneic blood transfusion.
Keywords: anticoagulation; blood transfusion; tranexamic acid;
venous thromboembolism

Introduction
Knowledge of coagulation and blood management is important in
orthopaedic surgery, because orthopaedic patients can have
substantial intraoperative blood loss along with morbidity and
mortality associated with venous thromboembolism (VTE),
including deep vein thrombosis (DVT) and pulmonary embolism.
Orthopaedic surgeons must balance prophylaxis against VTE with
the risk of bleeding, postoperative hematoma, and wound drainage.
Several modalities exist to regulate the coagulation pathway and
achieve a low rate of VTE while limiting blood loss and the need for
allogeneic blood transfusion.

VTE in the Orthopaedic Patient

Patients undergoing orthopaedic surgery are at significant risk for
development of VTE, particularly those undergoing major
orthopaedic procedures such as total hip arthroplasty (THA), total
knee arthroplasty (TKA), hip fracture surgery, and surgery for
trauma. 1 - 3 Although spinal cord injury and orthopaedic oncology
conditions are less common, affected patients are also at increased
risk of VTE. 4 , 5 Orthopaedic patients are at increased risk for VTE
for several reasons, including increased age and medical
comorbidity profile, difficulty ambulating leading to immobility,
tourniquet use, and venous injury as a result of the trauma of
surgery. 6 , 7
Historically, published rates of asymptomatic VTE are as high as
30% in patients who underwent THA and TKA and who were
screened using ultrasonography; however, the rates of symptomatic
VTE are significantly lower and of greater clinical significance. 1 , 8
Rates of symptomatic VTE in patients who underwent THA and
TKA and who received VTE chemoprophylaxis are approximately
1% and have decreased substantially over the past several decades.
2 , 9
Improvements in surgical and anesthetic techniques to allow for
less tissue damage, improved pain control, and accelerated
postoperative ambulation and recovery have contributed to lower
rates of VTE. This decreasing rate of VTE and corresponding drop
in mortality from VTE has led to updates in consensus VTE
prophylaxis guidelines.

Coagulation Cascade
The goal of the coagulation cascade is to form a clot composed of
platelets, fibrin, and red blood cells to achieve hemostasis.
Coagulation begins following injury to the endothelium, which
exposes the subendothelial matrix containing collagen and von
Willebrand factor, which bind to and partially activate platelets.
Following binding, platelets release adenosine diphosphate, which
binds to P2Y1 and P2Y12, leading to platelet aggregation. P2Y12 is the
target of clopidogrel, a common antiplatelet medication. Platelets
secrete several other substances, including serotonin, fibrinogen,
platelet-derived growth factor, and thromboxane A2, which lead to
further platelet recruitment and aggregation.
The clo ing process is propagated by the initiation of the
coagulation cascade, which occurs via the extrinsic and intrinsic
pathways (Figure 1). Both pathways converge in the activation of
factor X to factor Xa, which converts prothrombin to thrombin.
Thrombin both potently activates platelets and converts soluble
fibrinogen to insoluble fibrin, enabling stable clot formation.
 Figure 1 Coagulation cascade with intrinsic and extrinsic
pathways.Pharmacologic agents are listed in red next to their targets.

Extrinsic Pathway
Endothelial injury exposes tissue factor in the subendothelial
matrix, which binds circulating factor VIIa. This TA-VIIa complex
then activates factor X to factor Xa, which binds with cofactor factor
Va to form the prothrombinase complex, which converts
prothrombin (factor II) to thrombin (factor IIa). Initial thrombin
production enhances the coagulation cascade by fully activating
platelets and providing activation of coagulation factors XI, VIII,
and V. Thrombin converts soluble fibrinogen to insoluble fibrin and
activates factor XIII to factor XIIIa, which cross-links the fibrin and
contributes to stable clot formation.

Intrinsic Pathway
Although the extrinsic pathway relies on the extrinsic exposure to
tissue factor, the intrinsic pathway is composed entirely of factors
already in circulation and initiates after exposure to a negatively
charged surface, thus termed the contact activation pathway. The
intrinsic pathway serves to propagate factor X activation, as well as
provide for alternate means of activation because of a limited
amount of tissue factor available and the presence of tissue factor
pathway inhibitor. Intrinsic pathway activation begins with the
autoactivation of factor XII upon contact with a negatively charged
substance (ie, activated platelet membrane), forming factor XIIa.
Factor XIIa activates factor XIa, which in turn activates factor IXa.
Factor IXa combines with factor VIIIa to form a complex capable of
activating factor Xa, thus converging with the extrinsic pathway and
leading to subsequent thrombin activation as outlined previously.
Clo ing can be downregulated by the activity of protein C, which
when activated binds to cofactor protein S and inhibits factor VIIIa
and factor Va.
Several of the clo ing factors in the cascade are vitamin K
dependent, including prothrombin; factors VII, IX, and X; and
anticoagulant proteins C and S. These factors undergo vitamin K–
dependent gamma-carboxylation of glutamic acid residues, which
allows for membrane binding and normal function. Vitamin K
epoxide reductase is required to reduce the now oxidized vitamin K
back to its active form. Warfarin exerts its anticoagulant effect by
inhibiting vitamin K epoxide reductase function.
The fibrin clot formed during coagulation undergoes breakdown
via fibrinolysis, a process mediated by plasmin. As the structural
integrity of the endothelium returns, endothelial cells release tissue
plasminogen activator, which converts plasminogen into active
plasmin. Plasmin then cleaves the fibrin and dissolves the clot,
releasing fibrin degradation products such as D-dimer, which can
be measured and used clinically. Tranexamic acid (TXA) decreases
blood loss by acting as an antifibrinolytic agent, binding to
plasminogen and preventing activation to plasmin, preserving the
fibrin structure of clots.

Types of VTE Prophylaxis

Mechanical
Mechanical forms of VTE prophylaxis include graduated
compression stockings and intermi ent pneumatic compression
devices, which are noninvasive, and inferior vena cava (IVC) filters.
Graduated compression stockings have no associated bleeding risk
but are more frequently associated with skin complications. 1
Intermi ent pneumatic compression devices have been shown to
reduce the risk of VTE when worn appropriately and are
recommended as a prophylactic measure according to the
American College of Chest Physicians (ACCP) guidelines. 1
Intermi ent pneumatic compression devices are often combined
with chemoprophylaxis following major orthopaedic surgery;
however, in patients at increased risk for bleeding, they can be used
in isolation. 1 , 10
IVC filter placement is an option in patients at high risk for
pulmonary embolism that limits the risk of bleeding events from
anticoagulation. The ACCP recommends against the use of IVC
filters because of the risk of harm during placement or retrieval,
low retrieval rate, unclear indications for placement, and limited
efficacy, shown in a study with 90 patients with IVC filters
predominantly receiving arthroplasty and spine surgery. 1 , 11
However, a 2021 study of patients undergoing arthroplasty and with
high risk for VTE demonstrated a reduced risk of pulmonary
embolism in those who received IVC filters (n = 119) compared with
those without filters (0.8% versus 5.5%, respectively) and a 100%
retrieval rate without complications, indicating IVC filter placement
may still be a reasonable option in high-risk individuals. 12

Pharmacologic
A list of pharmacologic agents is presented in Table 1.

Table 1
Venous Thromboembolic Prophylactic Agents
 Target or
Route of Dosage
Drug Mechanism of Antidote
Administration a
Action
Apixaban Direct factor-Xa PO 2.5 mg Andexanet alfa (400-mg
inhibitor twice bolus followed by a 480-
daily mg infusion) b
Aspirin Irreversibly inhibits PO 81 mg None
production of once or
thromboxane and twice
prostacyclin by daily, or
inhibiting COX-1 325 mg
and COX-2 once or
twice
daily
Dabigatran Direct thrombin PO 220 mg Idarucizumab
(IIa) inhibitor once
daily
Fondaparinux Indirect AT-III- SC 2.5 mg None
mediated factor- once
Xa inhibitor daily
LMWH Enhances ability SC 40 mg Protamine sulfate.
(enoxaparin) of antithrombin III once (Enoxaparin administered
to inhibit factors daily or <8 hr: 1 mg protamine
IIa, III, and Xa 30 mg sulfate per 1 mg of
twice enoxaparin; administered
daily for >8 hr: 0.5 mg
protamine sulfate per 1
mg of enoxaparin)
Rivaroxaban Direct factor-Xa PO 10 mg Andexanet alfa (400-mg
inhibitor once bolus followed by a 480-
daily mg infusion)
Warfarin Inhibits vitamin K– PO Once FFP (15-30 mL/kg),
dependent factors daily vitamin K (5-10 mg PO or
(II, VII, IX, X, and based SC), PCC (1,500-2,000
protein C and S) on INR IU)
with
goal of
2.0
AT = antithrombin, COX = cyclooxygenase, FFP = fresh-frozen plasma, INR = international
normalized ratio, IV = intravenous, LMWH = low-molecular-weight heparin, PCC =
prothrombin complex concentrate, PO = oral administration, SC = subcutaneous injection
a
Multiple other doses have been assessed. These are the most commonly prescribed
dosages.
Dosage is based on 2.5-mg twice-daily dose of apixaban.
b
Reproduced with permission from Lieberman JR, Bell JA: Venous thromboembolic
prophylaxis after total hip and knee arthroplasty. J Bone Joint Surg Am 2021;103(16):1556-
1564.

Aspirin
Aspirin acts by inhibiting platelets, specifically as a cyclooxygenase
inhibitor targeting the production of thromboxane A2 and
prostaglandin I 2, which play a role in platelet aggregation and
vasoconstriction. Aspirin is administered orally, with the typical
dose for VTE prophylaxis of 81 mg twice daily or 325 mg twice daily,
both of which have been shown to be effective. Aspirin has a half-
life of only 20 minutes, but its effect on platelets is irreversible and
lasts for the life of the platelets (approximately 10 days). 13 Platelet
function recovers at a rate of approximately 10% per day, and as
li le as 20% function may be necessary for relatively normal
hemostatic function. 13 Aspirin does not affect serum coagulation
studies, but platelet function tests can be ordered to assess platelet
function, although this is not routinely done in orthopaedic
patients.
Aspirin is an a ractive choice for VTE prophylaxis for several
reasons. It is administered orally, requires no laboratory
monitoring, is inexpensive, and has a good safety profile. Aspirin
has been shown in multiple studies to be noninferior to other
anticoagulants in preventing VTE and death after THA and TKA. 14 ,
15
A 2019 study demonstrated that using aspirin for VTE
prophylaxis may significantly reduce mortality risk, specifically
cardiac-related mortality, because of cardioprotective benefits not
offered by other anticoagulants. 16 Aspirin also has decreased rates
of hematoma formation, wound drainage, and periprosthetic joint
infection compared with other anticoagulants, which in addition to
its efficacy may explain why it is the preferred VTE prophylaxis for
88% of members of the American Association of Hip and Knee
Surgeons and has been consistently featured as an option in the
American Academy of Orthopaedic Surgeons (AAOS) clinical
practice guideline (CPG) titled Preventing Venous Thromboembolic
Disease in Patients Undergoing Elective Hip and Knee Arthroplasty
since 2007. 10 , 14 , 17 - 19 Aspirin has recently been reported to be
effective in higher risk groups, including those with cardiac and
other medical comorbidities, patients with obesity, and revision
arthroplasty. 14 , 20 , 21
A limitation to VTE chemoprophylaxis with aspirin has been the
lack of multicenter randomized controlled trials (RCTs) to compare
its efficacy with that of other anticoagulants. The Pulmonary
Embolism Prevention, or PEP, trial included 13,356 patients with
hip fracture and 4,088 patients who underwent elective arthroplasty
and found a reduction in pulmonary embolism and DVT in the hip
fracture group with aspirin compared with no treatment. 22 This
provided enough of an evidentiary basis for the American College
of Chest Physicians to include aspirin as an acceptable form of VTE
prophylaxis in its 2012 CPGs, bringing it in line with the 2011
AAOS CPGs. 1 , 10 Additional multicenter RCTs are in progress,
such as the PREVENTion of Clots in Orthopaedic Trauma
(PREVENT CLOT) trial comparing aspirin with low-molecular-
weight heparin (LMWH) in orthopaedic trauma patients and the
Pulmonary Embolism Prevention after HiP and KneE Replacement
(PEPPER) trial comparing aspirin with warfarin and rivaroxaban in
patients undergoing arthroplasty. 23 , 24 The results of these trials
will provide valuable data on the suitability of aspirin for VTE
prophylaxis in these populations.

Warfarin
Warfarin inhibits the vitamin K epoxide reductase enzyme,
reducing the levels of vitamin K and therefore vitamin K–
dependent clo ing factors (prothrombin, VII, IX, X, protein C,
protein S) as described previously. Warfarin is administered orally
daily, with dosing based on achieving and maintaining an
international normalized ratio typically between either 1.5 to 2.5 or
2.0 to 3.0. Warfarin is metabolized in the liver and has an effective
half-life of approximately 40 hours. Dose requirements can be
significantly altered by genetic variations in metabolism and by
dietary vitamin K intake. The cost of warfarin itself is low; however,
there are associated costs of laboratory monitoring that
significantly increase overall treatment costs.
Warfarin has historically been a common choice for postoperative
VTE prophylaxis, and its efficacy is well documented. However, the
need for international normalized ratio monitoring, potential for
overanticoagulation or underanticoagulation, and risk of bleeding
are significant limitations, with one study demonstrating 94% of
patients undergoing subtherapeutic anticoagulation with warfarin
at time of discharge after total joint arthroplasty. 25 In addition,
warfarin has been linked to potentially increased rates of infection,
VTE, and mortality compared with aspirin. 14 , 26

LMWH and Indirect Factor Xa Inhibitors

LMWH such as enoxaparin function by enhancement of
antithrombin III activity, thus inhibiting factors IIa (thrombin), III,
and Xa. Similarly, fondaparinux (an indirect factor Xa inhibitor)
binds to antithrombin III and enhances inhibition of factor Xa.
Both LMWH and fondaparinux are administered via subcutaneous
injection either once or twice daily, and half-lives of enoxaparin and
fondaparinux are 4.5 hours and 17 hours, respectively. LMWH and
fondaparinux, unlike heparin, do not prolong the activated partial
thromboplastin time but can be measured using an anti-factor Xa
assay, although this is infrequently done because of the predictable
linear pharmacokinetics of LMWH at prophylactic doses.
Limitations to these medications include the requirement for
injection, the risk of heparin-induced thrombocytopenia in LMWH
(but not fondaparinux), and increased postoperative wound
drainage in LMWH. 17
LMWH has proven effective at VTE prophylaxis and is the
preferred method of prophylaxis for orthopaedic patients according
to the 2012 ACCP CPGs and the standard by which many newer
direct oral anticoagulants (DOACs) are measured. 1 , 27
Fondaparinux has been shown to be potentially more effective than
LMWH in preventing VTE, but may have an increased rate of
bleeding events. 28

Direct Factor Xa Inhibitors

Direct factor Xa inhibitors include rivaroxaban and apixaban and
function by direct inhibition of factor Xa. Rivaroxaban and apixaban
are both administered orally, once and twice a day, respectively,
and are categorized (along with direct thrombin inhibitors) as
DOACs. Rivaroxaban has a half-life of 5 to 9 hours, compared with
12 hours for apixaban. Rivaroxaban and apixaban activity can be
measured with anti-factor Xa assays, but, as with LMWH, routine
laboratory monitoring is not necessary. Although there was no
widespread reversal agent when these medications were
introduced, the FDA approved andexanet alfa for reversal of
rivaroxaban and apixaban in 2018. The combined benefits of oral
administration with no laboratory monitoring make DOACs
promising candidates for VTE prophylaxis; however, they are more
expensive than the other pharmacologic options.
A 2020 large registry-based study comparing DOACs with aspirin
for VTE prophylaxis in hip and knee arthroplasty demonstrated
that VTE rates were slightly lower in the factor Xa group than in the
matched aspirin group (0.37% versus 0.59%, respectively, in THA;
0.49% versus 0.68%, respectively, in TKA), with no increase in
bleeding events, wound issues, or infection. 29 Rivaroxaban and
apixaban have also been shown in an RCT se ing to be superior to
LMWH in preventing VTE in patients who underwent hip
arthroplasty, without an increase in bleeding events. 30 , 31 Although
VTE rates after nonmajor surgery of the lower extremity are low
even when immobilized, rivaroxaban was recently shown to be
superior to LMWH in preventing VTE in this population. 32

Direct Thrombin Inhibitors

Direct thrombin inhibitors such as dabigatran function by binding
to and inactivating thrombin (factor IIa). Dabigatran is
administered orally once a day and is thus considered a DOAC, and
has a half-life of approximately 12 hours. The reversal agent for
dabigatran is a monoclonal antibody, idarucizumab, which was
FDA approved in 2015. Laboratory monitoring of dabigatran can be
performed with a dilute thrombin time; however, like the other
DOACs, routine laboratory monitoring for VTE prophylaxis is not
necessary.
Dabigatran has been shown in a pooled analysis of RCT data to
have similar efficacy and bleeding rates compared with LMWH
when used for VTE prophylaxis after hip and knee arthroplasty. 33
Recent registry data demonstrate slightly lower VTE rates using
dabigatran compared with aspirin (THA: 0.44% for dabigatran
versus 0.63% for aspirin; TKA: 0.60% for dabigatran versus 0.73%
for aspirin) and no increased bleeding events. 29

Risk Stratification
Patient risk for both VTE and bleeding is dependent on both
patient and surgical factors. From a surgical standpoint, THA, TKA,
hip fracture surgery, trauma surgery, spine surgery, and
orthopaedic oncologic surgery impart a higher risk of VTE and
bleeding, whereas the risk is lower in patients undergoing upper
extremity surgery or arthroscopic surgery, or with isolated lower leg
injuries. 1 - 3 , 5 The ACCP accordingly recommends more aggressive
chemoprophylactic regimens in patients undergoing THA, TKA,
and hip fracture surgery than patients undergoing arthroscopic
surgery or with an isolated lower leg injury.
Patients also carry their own risk profiles for VTE and bleeding,
and efforts have been made to accurately risk-stratify patients to
provide an individualized management plan that balances VTE
prevention and the prevention of bleeding events. Factors that have
been shown to increase VTE risk include previous VTE, higher body
mass index, TKA surgery, and female sex. 34 , 35 The evidence is
strongest for prior VTE being a risk factor for future VTE, which is
why the AAOS 2011 CPGs recommend assessment of this risk
factor specifically. 10 Bleeding risk was also assessed in these
guidelines, and patients with a known bleeding disorder or active
liver disease were categorized as highest risk. Mechanical
prophylaxis alone is recommended in these patients. 1 , 10
One study built upon previous a empts at practical VTE risk
stratification by developing a scoring system to risk-stratify patients
for pulmonary embolism after hip and knee arthroplasty, using
American College of Surgeons National Surgical Quality
Improvement Program data to create a model that was
subsequently validated on institutional data. 35 This study found
that factors such as age older than 70 years, female sex, higher body
mass index, and TKA surgery (versus THA) could be used to create
low-risk, medium-risk, and high-risk groups, which then had 90-day
pulmonary embolism risks of 0.44%, 1.51%, and 2.60%, respectively.
Further work is needed to bridge the gap between risk stratification
and optimal prophylactic strategy based on risk category.

Published Guidelines

AAOS 2011 Published Guidelines

The AAOS issued CPGs on Preventing Venous Thromboembolic
Disease in Patients Undergoing Elective Hip and Knee Arthroplasty
in 2011, which are summarized in Table 2. These guidelines
a empted to make VTE prophylaxis recommendations that be er
represented the risk versus benefit assessments made by
orthopaedic surgeons, notably with a focus on critical outcomes of
major bleeding, pulmonary emboli, and all-cause mortality that are
deemed patient-oriented. 10 Symptomatic DVT, any DVT, and
proximal DVT all were deemed noncritical outcomes because they
are not patient-oriented, and the guidelines strongly recommended
against routine screening for asymptomatic DVTs. In addition, the
AAOS guidelines took a more orthopaedic-specific approach to
bleeding as an outcome, as bleeding and bleeding-associated
complications in the context of joint arthroplasty that did not
qualify as a bleeding event under previous ACCP guidelines can
represent a significant risk for morbidity and repeat surgery. 36

Table 2
Summary of AAOS 2011 CPG on Preventing Venous
Thromboembolic Disease in Patients Undergoing Elective Hip
and Knee Arthroplasty

Grade of
Recommendation
Recommendation
Against routine postoperative duplex ultrasonography screening Strong
Practitioner should further assess the risk of VTE Weak
Factors other than a history of previous VTE do not have clear support Inconclusive
as risk factor for VTE
Assess for known bleeding disorders such as hemophilia and for the Consensus
presence of active liver disease Inconclusive
Factors other than the presence of a known bleeding disorder or
active liver disease do not have clear support as risk factor for
bleeding
Discontinue antiplatelet agents before undergoing elective hip or knee Moderate
arthroplasty
Use of pharmacologic agents and/or mechanical compressive Moderate
devices for prevention of VTE Inconclusive
Which prophylactic strategy is/are optimal or suboptimal Consensus
Patients and physicians should discuss the duration of prophylaxis
Patients who have also had a previous VTE, should receive Consensus
pharmacologic prophylaxis AND mechanical compressive devices
Patients who have a known bleeding disorder and/or active liver Consensus
disease, use mechanical compressive devices for preventing VTE
Early mobilization is of low cost, minimal risk to the patient, and Consensus
consistent with current practice
Use of neuraxial anesthesia to help limit blood loss, even though Moderate
evidence suggests that neuraxial anesthesia does not affect the
occurrence of VTE disease
Unable to recommend for or against inferior vena cava filter for Inconclusive
patients with contraindication for chemoprophylaxis
VTE = venous thromboembolism
Reproduced and modified with permission from The British Editorial Society of Bone & Joint
Surgery. Barrack RL: Current guidelines for total joint VTE prophylaxis: Dawn of a new day. J
Bone Joint Surg Br 2012;94-B(11 suppl A): 3-7.
ACCP 2012 Published Guidelines
The results of the 2012 ACCP CPGs, Prevention of VTE in
Orthopedic Surgery Patients, are summarized in Table 3. These
guidelines demonstrate multiple significant changes from previous
ACCP CPGs in 2008, including the addition of aspirin as an
acceptable form of VTE prophylaxis. 1 In addition, the outcome of
interest was changed to focus on “patient-important outcomes of
fatal and symptomatic pulmonary embolism and symptomatic
DVT” rather than asymptomatic DVT identified on screening
procedures. The inclusion of aspirin chemoprophylaxis and focus
on symptomatic VTE represent alignment between the AAOS and
ACCP CPGs. The ACCP also offers recommendations on
nonarthroplasty surgery, specifically isolated lower extremity
injuries and knee arthroscopy, in which thromboprophylaxis is not
recommended for those at standard risk.

Table 3
Summary of ACCP 2012 CPG on Prevention of VTE in
Orthopedic Surgery Patients

Grade Recommendation
All 1B Use of one of the following rather than no antithrombotic prophylaxis: LMWH;
a
fondaparinux; dabigatran, b apixaban, b rivaroxaban (THA or TKA but not hip
fracture surgery); low-dose unfractionated heparin; adjusted-dose vitamin K
antagonist; aspirin
1C a , c Intermittent pneumatic compression device (IPCD)
2C/2B Use of LMWH in preference to the other agents recommended as alternatives
2C In patients receiving pharmacologic prophylaxis: adding an IPCD during the
hospital stay
2B Extending thromboprophylaxis for up to 35 days
2C In patients at increased bleeding risk: an IPCD or no prophylaxis
All 1B In patients who decline injections: using apixaban b or dabigatran b
2C Suggest against using IVC filter placement for primary prevention in patients with
contraindications to both pharmacologic and mechanical thromboprophylaxis
1B Against Doppler (or duplex) ultrasonography screening before hospital discharge
2B For patients with isolated lower extremity injuries requiring leg immobilization: no
thromboprophylaxis
2B For patients undergoing knee arthroscopy without a history of VTE: no
thromboprophylaxis
IVC = inferior vena cava, LMWH = low-molecular-weight heparin, THA = total hip arthroplasty,
TKA = total knee arthroplasty, VTE = venous thromboembolism
Length of treatment minimum 10 to 14 days.
a

Not FDA approved for DVT prophylaxis prior to total joint replacement.
b

c
Recommend the use of only portable, battery-powered IPCDs capable of recording and
reporting proper wear time on a daily basis for inpatients and outpatients. Efforts should be
made to achieve 18 hours of daily compliance.
Reproduced and modified with permission from The British Editorial Society of Bone & Joint
Surgery. Barrack RL: Current guidelines for total joint VTE prophylaxis: Dawn of a new day. J
Bone Joint Surg Br 2012;94-B(11 suppl A):3-7.

Surgical Care Improvement Project

The Surgical Care Improvement Project (SCIP) was an effort
between the Centers for Medicare & Medicaid Services and the
Centers for Disease Control and Prevention to decrease the rates of
surgical site infection, VTE, cardiac adverse events, and respiratory
complications in surgical patients by 25% nationwide. SCIP tracked
four VTE quality measures: surgery patients with recommended
VTE prophylaxis ordered (SCIP VTE 1); surgery patients who
received appropriate VTE prophylaxis within 24 hours prior to
surgery to 24 hours after surgery (SCIP VTE 2); intraoperative or
postoperative pulmonary embolism diagnosed during index
hospitalization and within 30 days of surgery (SCIP VTE 3); and
intraoperative or postoperative DVT diagnosed during index
hospitalization and within 30 days of surgery (SCIP VTE 4). SCIP
guidelines defined appropriate prophylaxis as adherence to
approved guidelines and issued clarification that aspirin met these
requirements provided the rationale for its use was appropriately
documented. Limitations of these SCIP measures in orthopaedic
patients include a lack of emphasis on both clinical significance of
the VTE detected and a lack of consideration of associated bleeding
events or wound complications other than surgical site infection.
SCIP measures were retired in 2015 and have been replaced by a set
of ORYX Performance Measures through The Joint Commission.
Use of Tranexamic Acid
TXA is an antifibrinolytic agent that binds to plasminogen and
prevents activation to plasmin, preserving the fibrin structure of
clots. TXA can be administered via intravenous, oral, and topical
routes. TXA use has significantly lowered transfusion rates after
major orthopaedic surgery. TXA has reduced transfusion rates by
60% to 71% in hip and knee arthroplasty based on high-quality
network meta-analyses. 37 , 38 TXA has also been shown to decrease
transfusion rates in orthopaedic trauma patients and spine
patients. 39 , 40 TXA is relatively inexpensive, and the reduction in
transfusion rates represents an opportunity for cost reduction
perioperatively.
The American Association of Hip and Knee Surgeons, in
conjunction with the AAOS, The Hip Society, The Knee Society, and
The American Society of Regional Anesthesia and Pain Medicine,
developed CPGs for the use of TXA in primary total joint
arthroplasty in 2018. 41 The results of these guidelines are
summarized in Table 4. The guidelines indicate the benefit of TXA
in reducing blood loss and transfusion requirement, without
significantly increased risk of VTE or arterial thromboembolic
events, and regardless of administration method or dosing. The
Musculoskeletal Tumor Society and the Orthopaedic Trauma
Association have subsequently endorsed these guidelines as well.

Table 4
Summary of American Association of Hip and Knee Surgeons
2018 CPG on Tranexamic Acid in Total Joint Arthroplasty

Grade of
Recommendation
Recommendation
IV, topical, and oral TXA are all effective when compared with placebo Strong
for reducing blood loss and the need for transfusion
All methods of TXA administration (IV, topical, and oral) demonstrate Strong
equivalent efficacy at reducing blood loss and the need for transfusion
Dose amount of TXA was not found to significantly affect its reduction Strong
of blood loss or need for transfusion
 Grade of
Recommendation
Recommendation
Multiple doses of IV or oral TXA does not significantly alter the amount Strong
of blood loss or need for transfusion
Administration of IV TXA before the incision potentially reduces blood Moderate
loss and the need for transfusion compared with its administration
after incision
Administration of IV, topical, and oral TXA in patients without known Strong
history of VTE does not increase the risk of developing a VTE
compared with placebo
Administration of TXA in patients of generally higher comorbidity Moderate
burden does not suggest increased risk of adverse thromboembolic
events
Existing evidence does not suggest that TXA increases the risk of Moderate
developing an arterial thromboembolic events compared with placebo
IV = intravenous, TXA = tranexamic acid, VTE = venous thromboembolism
Despite concerns that TXA use may increase thrombotic events,
its safety profile has been favorable. In a large meta-analysis of
patients who underwent hip and knee arthroplasty, TXA was not
associated with an increased VTE risk or arterial thromboembolic
event risk. 42 In this study, TXA was also not associated with
increased VTE risk in patients with American Society of
Anesthesiologists score ≥3, which was used as a proxy for patients
at higher risk for complications because of the high rates at which
patients with a history of VTE are excluded from studies on TXA.
There have been case reports of myocardial infarction following
TXA administration as well as an increased seizure risk; however,
no increase in death or thrombotic complications was reported in a
large RCT of high-risk cardiac patients undergoing coronary artery
surgery with TXA administration. 43 In addition, TXA has
demonstrated efficacy in reducing blood loss in cardiac surgery,
and transfusion carries an independent risk of cardiac-related
complications in these patients. 43 , 44 Contraindications to TXA use
as dictated by expert consensus include preexisting active
thromboembolic disorder, disseminated intravascular coagulation
or consumptive coagulopathy, renal failure, coronary or vascular
stent placement within 1 year, and acute subarachnoid hemorrhage.
45
Allogeneic Blood Transfusion
Allogeneic blood transfusion can be necessary for the management
of postoperative anemia after major orthopaedic surgery to prevent
cardiac events. However, allogeneic blood transfusion carries
systemic transfusion-related risks as well as increases the rate of
postoperative surgical infection, likely secondary to
immunoregulatory effects. 46
To limit the complication rate and
reduce costs, efforts have been made to decrease the rates of
transfusion in orthopaedic patients in recent years. Advanced age,
higher comorbidity index, THA, and bilateral TKA are associated
risk factors for transfusion; therefore, additional counseling and
optimization may be directed toward these groups. 47
A comprehensive blood management program includes
preoperative, intraoperative, and postoperative components.
Preoperatively, laboratory testing should be performed to assess for
anemia and coagulopathy, with further referral or testing based on
the results. For surgeries with a high risk of blood loss, type and
cross-matching of blood products and communication with the
blood bank are appropriate. Patients with anemia can be optimized
for surgery with preoperative treatment including iron
supplementation and erythropoietin. Preoperative erythropoietin
administration has been shown to decrease postoperative
transfusion rates in patients undergoing orthopaedic surgery. 48
Intraoperatively, TXA is an efficacious way to reduce blood loss
and prevent transfusion, as mentioned previously. Cell salvage and
washing has also been shown to potentially decrease transfusion
rates; however, the cost-effectiveness of its use compared with other
adjuncts is less clear.
Postoperatively, hemoglobin (Hb) and hematocrit levels as well
as patient symptoms are monitored to determine the need for
allogeneic blood transfusion. Although the threshold Hb to initiate
transfusion was thought to be higher in orthopaedic patients to
improve functional recovery, an RCT of patients with hip fracture
assigned to either a liberal (Hb < 10 g/dL) or restrictive (Hb < 8
g/dL) transfusion threshold demonstrated no difference in cardiac
events, death, and other complications, which formed the basis for
the Strong recommendation from the AAOS for a transfusion
threshold no higher than 8 g/dL in asymptomatic patients with hip
fracture. 49 , 50

Summary
Surgeons should assess patient and surgical risk factors for VTE
and use appropriate prophylaxis to reduce the risk of VTE while
mitigating bleeding and wound complications. Each prophylactic
medication has strengths and limitations to consider. The AAOS
and ACCP have issued guidelines for VTE prevention, which
include a recommendation for chemoprophylaxis in patients
undergoing major orthopaedic surgery such as hip and knee
arthroplasty and hip fracture surgery. Blood management programs
focused on all phases of care can reduce the rate of allogeneic blood
transfusion and its associated risks. TXA is an effective and safe
modality to reduce blood loss and transfusion rates.

Key Study Points

Patients undergoing major orthopaedic surgery are at
elevated risk for VTE.
Aspirin, LMWH, warfarin, and DOACs all are effective at
reducing the risk of VTE; each has specific strengths and
limitations.
TXA reduces blood transfusion requirements and has a
good safety profile even in high-risk patients.
Allogeneic blood transfusion should only be used when
necessary to mitigate cost and the risk of transfusion-
related complications.
Annotated References
1. Falck-Y er Y, Francis CW, Johanson NA, et al: Prevention of
VTE in orthopedic surgery patients antithrombotic therapy and
prevention of thrombosis, ed 9. American College of Chest
Physicians evidence-based clinical practice guidelines. Chest
2012;141(2):e278S-e325S.
2. Pedersen AB, Mehnert F, Sorensen HT, Emmeluth C, Overgaard
S, Johnsen SP: The risk of venous thromboembolism, myocardial
infarction, stroke, major bleeding and death in patients
undergoing total hip and knee replacement: A 15-year
retrospective cohort study of routine clinical practice. Bone Joint J
2014;96-B(4):479-485.
3. Barrera LM, Perel P, Ker K, Cirocchi R, Farinella E, Uribe CHM:
Thromboprophylaxis for trauma patients. Cochrane Database Syst
Rev 2013;3(3):CD008303.
4. Mackiewicz-Milewska M, Jung S, Kroszczyński AC, et al: Deep
venous thrombosis in patients with chronic spinal cord injury. J
Spinal Cord Med 2015;39(4):1-5.
5. Lex JR, Evans S, Cool P, et al: Venous thromboembolism in
orthopaedic oncology: Risk factors, incidence, and prophylaxis.
Bone Joint J 2020;102-B(12):1743-1751. A systematic review of VTE
in oncology patients found a VTE rate of 10.7%, with pulmonary
embolism and lethal pulmonary embolism in 2.4% and 0.6% of
patients, respectively. Level of evidence: IV.
6. Reikerås O, Clementsen T: Time course of thrombosis and
fibrinolysis in total knee arthroplasty with tourniquet application.
Local versus systemic activations. J Thromb Thrombolys
2008;28(4):425.
7. Sharrock NE, Go G, Harpel PC, Ranawat CS, Sculco TP, Salvati
EA: The John Charnley Award. Thrombogenesis during total hip
arthroplasty. Clin Orthop Relat Res 1995;319:16-27.
8. Tsuda K, Takao M, Kim J, Abe H, Nakamura N, Sugano N:
Asymptomatic deep venous thrombosis after elective hip surgery
 could be allowed to remain in place without thromboprophylaxis
after a minimum 2-year follow-up. J Arthroplasty 2020;35(2):563-
568. The authors found that on routine ultrasound screening of
742 patients with hip arthroplasty, 33% had postoperative DVTs.
No DVTs in the calf resulted in pulmonary embolism, and 93%
later disappeared, highlighting that DVTs are common but not
always symptomatic or clinically significant. Level of evidence: II.
9. Partridge T, Jameson S, Baker P, Deehan D, Mason J, Reed MR:
Ten-year trends in medical complications following 540,623
primary total hip replacements from a national database. J Bone
Joint Surg 2018;100(5):360-367.
10. Mont MA, Jacobs JJ, Boggio LN, et al: Preventing venous
thromboembolic disease in patients undergoing elective hip and
knee arthroplasty. Am Acad Orthop Surg 2011;19(12):768-776.
11. Bass AR, Ma ern CJ, Voos JE, Peterson MGE, Trost DW: Inferior
vena cava filter placement in orthopedic surgery. Am J Orthop
2010;39(9):435-439.
12. Ahmed O, Kim YJ, Patel MV, Luu HH, Sco B, Cohen K: Efficacy
and safety of mechanical IVC filtration for preventing pulmonary
embolism in high-risk orthopedic patients undergoing total hip
or knee arthroplasty. J Arthroplasty 2021;36(7):2586-2590. IVC
filter use lowered the risk of pulmonary embolism in high-risk
patients who underwent arthroplasty, with a 100% retrieval
success rate. Level of evidence: III.
13. Awtry EH, Loscalzo J: Aspirin. Circulation 2000;101(10): 1206-
1218.
14. Huang RC, Parvizi J, Hozack WJ, Chen AF, Austin MS: Aspirin
is as effective as and safer than warfarin for patients at higher
risk of venous thromboembolism undergoing total joint
arthroplasty. J Arthroplasty 2016;31(9):83-86.
15. Matharu GS, Kunutsor SK, Judge A, Blom AW, Whitehouse MR:
Clinical effectiveness and safety of aspirin for venous
thromboembolism prophylaxis after total hip and knee
replacement. JAMA Intern Med 2020;180(3):376-384. A systematic
 review and meta-analysis of RCTs showed no significant
difference between aspirin and other anticoagulants with respect
to clinical effectiveness and safety profile in VTE prophylaxis.
Level of evidence: I.
16. Rondon AJ, Shohat N, Tan TL, Goswami K, Huang RC, Parvizi J:
The use of aspirin for prophylaxis against venous
thromboembolism decreases mortality following primary total
joint arthroplasty. J Bone Joint Surg 2019;101(6):504-513. A
retrospective review of more than 31,000 patients showed that
mortality was lower in patients who underwent arthroplasty and
who were using aspirin for VTE prophylaxis, primarily because of
a lower rate of cardiac-related death. Level of evidence: III.
17. Patel VP, Walsh M, Sehgal B, Preston C, DeWal H, Cesare PED:
Factors associated with prolonged wound drainage after primary
total hip and knee arthroplasty. J Bone Joint Surg 2007;89(1):33-38.
18. Huang R, Buckley PS, Sco B, Parvizi J, Purtill JJ:
Administration of aspirin as a prophylaxis agent against venous
thromboembolism results in lower incidence of periprosthetic
joint infection. J Arthroplasty 2015;30(9):39-41.
19. Abdel MP, Berry DJ: Current practice trends in primary hip and
knee arthroplasties among members of the American
Association of Hip and Knee Surgeons: A long-term update. J
Arthroplasty 2019;34(7):S24-S27. Summary of the poll results at
the 2018 American Association of Hip and Knee Surgeons
Annual Meeting demonstrated that 88% of respondents primarily
use aspirin for VTE chemoprophylaxis after arthroplasty. Level of
evidence: V.
20. Tang A, Sicat CS, Singh V, Rozell JC, Schwarzkopf R, Long WJ:
Aspirin use for venous thromboembolism prevention is safe and
effective in overweight and obese patients undergoing revision
total hip and knee arthroplasty. J Arthroplasty 2021;36(7):S337-
S344. Similar clinical effectiveness and complication rates were
noted in patients undergoing revision arthroplasty with obesity
 or without obesity who were on aspirin for VTE prophylaxis in a
1,578-patient retrospective study. Level of evidence: III.
21. Hovik O, Amlie EJ, Jenssen KK: No increased risk of venous
thromboembolism in high-risk patients continuing their dose of
75 mg aspirin compared to healthier patients given low-
molecular-weight heparin. J Arthroplasty 2021;36(10):3589-3592.
Aspirin 75 mg daily was shown to have similar clinical
effectiveness and complication rates compared with LMWH in
patients undergoing arthroplasty in a prospective observational
study of 6,094 patients. Level of evidence: II.
22. Pulmonary Embolism Prevention (PEP) trial Collaborative
Group: Prevention of pulmonary embolism and deep vein
thrombosis with low dose aspirin: Pulmonary Embolism
Prevention (PEP) trial. Lancet 2000;355(9212): 1295-1302.
23. O’Toole RV, Stein DM, Frey KP, et al: PREVENTion of CLots in
Orthopaedic Trauma (PREVENT CLOT): A randomised
pragmatic trial protocol comparing aspirin versus low-molecular-
weight heparin for blood clot prevention in orthopaedic trauma
patients. BMJ Open 2021;11(3):e041845. A protocol is presented
for the PREVENT CLOT trial, randomizing orthopaedic trauma
patients to aspirin or LMWH for VTE prophylaxis with all-cause
mortality as the primary outcome. Level of evidence: I.
24. Pellegrini VD, Eikelboom J, Evarts CM, et al: Selection bias,
orthopaedic style: Knowing what we don’t know about aspirin. J
Bone Joint Surg 2019;102(7):631-633. A summary of the PEPPER
trial, which aims to randomize 20,000 patients undergoing
primary or revision THA or TKA to aspirin, rivaroxaban, or
warfarin for VTE prophylaxis, is presented. Level of evidence: I.
25. Rondon AJ, Goswami K, Tan TL, Shohat N, Parvizi J: Majority of
total joint arthroplasties are subtherapeutic on warfarin at time
of discharge: Another reason to avoid warfarin as a venous
thromboembolism prophylaxis? J Arthroplasty 2018;33(9):2787-
2791.
26. Hughes LD, Lum J, Mahfoud Z, Malik RA, Anand A,
Charalambous CP: Comparison of surgical site infection risk
between warfarin, LMWH, and aspirin for venous
thromboprophylaxis in TKA or THA: A systematic review and
meta-analysis. JBJS Rev 2020;8(12):e20.00021. A systematic review
and meta-analysis including 184,037 patients showed that
warfarin VTE prophylaxis increased the risk of deep infection and
surgical site infection compared with aspirin after hip and knee
arthroplasty. Level of evidence: III.
27. Lieberman JR, Bell JA: Venous thromboembolic prophylaxis
after total hip and knee arthroplasty. J Bone Joint Surg Am
2021;103(16):1556-1564. A review of the existing guidelines and
prophylactic options for VTE prophylaxis after hip and knee
arthroplasty is presented. Level of evidence: V.
28. Kumar A, Talwar A, Farley JF, et al: Fondaparinux sodium
compared with low-molecular-weight heparins for perioperative
surgical thromboprophylaxis: A systematic review and meta-
analysis. J Am Heart Assoc 2019;8(10): e012184. A systematic
review and meta-analysis including 14,906 patients showed that
fondaparinux compared with LMWH for VTE prophylaxis had a
lower risk of VTE but increased risk of major bleeding. Level of
evidence: I.
29. Matharu GS, Garriga C, Whitehouse MR, Rangan A, Judge A: Is
aspirin as effective as the newer direct oral anticoagulants for
venous thromboembolism prophylaxis after total hip and knee
arthroplasty? An analysis from the National Joint Registry for
England, Wales, Northern Ireland, and the Isle of Man. J
Arthroplasty 2020;35(9):2631-2639.e6. This registry study of
patients undergoing hip and knee arthroplasty showed that
DOACs were associated with a reduced VTE risk compared with
aspirin, without an increase in complications. Level of evidence:
III.
30. Lassen MR, Gallus A, Raskob GE, et al: Apixaban versus
enoxaparin for thromboprophylaxis after hip replacement. N Engl
J Med 2010;363(26):2487-2498.
31. Eriksson BI, Borris LC, Friedman RJ, et al: Rivaroxaban versus
enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl
J Med 2008;358(26):2765-2775.
32. Samama CM, Laporte S, Rosencher N, et al: Rivaroxaban or
enoxaparin in nonmajor orthopedic surgery. N Engl J Med
2020;382(20):1916-1925. An RCT comparing rivaroxaban with
LMWH for VTE prophylaxis after nonmajor lower extremity
surgery showed be er effectiveness and no increased
complications for rivaroxaban. Level of evidence: I.
33. Friedman RJ, Dahl OE, Rosencher N, et al: Dabigatran versus
enoxaparin for prevention of venous thromboembolism after hip
or knee arthroplasty: A pooled analysis of three trials. Thromb Res
2010;126(3):175-182.
34. Pedersen AB, Sorensen HT, Mehnert F, Overgaard S, Johnsen
SP: Risk factors for venous thromboembolism in patients
undergoing total hip replacement and receiving routine
thromboprophylaxis. J Bone Joint Surg 2010;92(12):2156-2164.
35. Bohl DD, Maltenfort MG, Huang R, Parvizi J, Lieberman JR,
Valle CJD: Development and validation of a risk stratification
system for pulmonary embolism after elective primary total joint
arthroplasty. J Arthroplasty 2016;31(9):187-191.
36. Barrack RL: Current guidelines for total joint VTE prophylaxis:
Dawn of a new day. J Bone Joint Surg Br 2012; 94-B(11 suppl A):3-
7.
37. Fillingham YA, Ramkumar DB, Jevsevar DS, et al: The efficacy of
tranexamic acid in total hip arthroplasty: A network meta-
analysis. J Arthroplasty 2018;33(10):3083-3089.e4.
38. Fillingham YA, Ramkumar DB, Jevsevar DS, et al: The efficacy of
tranexamic acid in total knee arthroplasty: A network meta-
analysis. J Arthroplasty 2018;33(10):3090- 3098.e1.
39. Gausden EB, Qudsi R, Boone MD, O’Gara B, Ruzbarsky J, Lorich
DG: Tranexamic acid in orthopaedic trauma surgery. J Orthop
Trauma 2017;31(10):513-519.
40. Cheriyan T, Maier SP, Bianco K, et al: Efficacy of tranexamic acid
on surgical bleeding in spine surgery: A meta-analysis. Spine J
2015;15(4):752-761.
41. Fillingham YA, Ramkumar DB, Jevsevar DS, et al: Tranexamic
acid use in total joint arthroplasty: The clinical practice
guidelines endorsed by the American Association of Hip and
Knee Surgeons, American Society of Regional Anesthesia and
Pain Medicine, American Academy of Orthopaedic Surgeons, Hip
Society, and Knee Society. J Arthroplasty 2018;33(10):3065-3069.
42. Fillingham YA, Ramkumar DB, Jevsevar DS, et al: The safety of
tranexamic acid in total joint arthroplasty: A direct meta-analysis.
J Arthroplasty 2018;33(10):3070- 3082.e1.
43. Myles PS, Smith JA, Forbes A, et al: Tranexamic acid in patients
undergoing coronary-artery surgery. N Engl J Med
2017;376(2):136-148.
44. Möhnle P, Snyder-Ramos SA, Miao Y, et al: Postoperative red
blood cell transfusion and morbid outcome in uncomplicated
cardiac surgery patients. Intensive Care Med 2011;37(1):97-109.
45. Goobie SM: Tranexamic acid: Still far to go. Br J Anaesth
2017;118(3):293-295.
46. Friedman R, Homering M, Holberg G, Berkowi SD: Allogeneic
blood transfusions and postoperative infections after total hip or
knee arthroplasty. J Bone Joint Surg 2014;96(4):272-278.
47. Slover J, Lavery JA, Schwarzkopf R, Iorio R, Bosco J, Gold HT:
Incidence and risk factors for blood transfusion in total joint
arthroplasty: Analysis of a statewide database. J Arthroplasty
2017;32(9):2684-2687.e1.
48. Cho BC, Serini J, Zorrilla-Vaca A, et al: Impact of preoperative
erythropoietin on allogeneic blood transfusions in surgical
patients. Anesth Analg 2019;128(5):981-992. A systematic review
and meta-analysis that included patients undergoing orthopaedic
surgery found that preoperative erythropoietin administration
decreased the incidence of allogeneic transfusion compared with
placebo. Level of evidence: I.
49. Carson JL, Terrin ML, Noveck H, et al: Liberal or restrictive
transfusion in high-risk patients after hip surgery. N Engl J Med
2011;365(26):2453-2462.
50. Roberts KC, Brox WT, Jevsevar DS, Sevarino K: Management of
hip fractures in the elderly. J Am Acad Orthop Surg 2015;23(2):131-
137.
C H AP T E R 8

Musculoskeletal Biomechanics
and Biomaterials
Kenneth L. Urish MD, PhD, FAAOS, Gregory S. Lewis PhD,
Eni Halilaj PhD

Dr. Urish or an immediate family member serves as a paid consultant to or is an employee of

Peptilogics and Smith & Nephew; has stock or stock options held in Peptilogics; has received
research or institutional support from Peptilogics and Smith & Nephew; and serves as a board
member, owner, officer, or committee member of the American Academy of the Orthopaedic
Surgeons and ASTM. Dr. Lewis or an immediate family member has received research or
institutional support from Arthrex, Inc. and Synthes and serves as a board member, owner, officer,
or committee member of the Orthopaedic Research Society. Neither Dr. Halilaj nor any immediate
family member has received anything of value from or has stock or stock options held in a
commercial company or institution related directly or indirectly to the subject of this chapter.

ABSTRACT
Biomechanics is critical in understanding the structure and
function of the musculoskeletal system including bone, tendon,
muscle, and cartilage. Solid mechanics, material science, and
biocompatibility, including corrosion processes, are critical in
understanding the application of different principles in orthopaedic
surgery.
Keywords: biomaterials; biomechanics; corrosion

Introduction
Biomechanics is critical in understanding the structure and
function of the musculoskeletal system. The primary purpose of
bone, cartilage, and tendons is to execute movement and activity
while also supporting the subsequent loads. Different orthopaedic
diseases and pathologies alter the mechanical properties of these
tissues. The primary function of orthopaedic surgery is to provide
an intervention that helps restore mechanical function. These
procedures require a knowledge of solid mechanics, material
science, and biocompatibility.

Musculoskeletal Loads

Rigid Body Mechanics and Joint Kinetics

It is often surprising to learn that forces transmi ed through the
knee, hip, and shoulder joints often exceed three times, two times,
and one time the body weight, respectively, during activities of
daily living. Why are these forces so high, and how are they known?
What are the corresponding forces within bones, soft tissues, and
implants? These internal forces are fundamental across the
spectrum of orthopaedic care, such as deformity correction, overuse
injuries, bone remodeling, implant wear, and fixation failure.
To understand internal forces, the musculoskeletal system can
first be considered as a system of rigid links connected at the joints.
Moments arise within the joints because of external loads, such as
the ground reaction force during walking, or the force of a weight
held by the hand. A moment is a turning or twisting load and is
used somewhat interchangeably with the word torque. Joint
moments are also caused by muscle forces. Because muscles are
positioned anatomically close to joints, their pulling force must
often be substantial to control joint positions, and this is further
described in the next paragraphs. Statics analysis ignores inertial
effects associated with body movements. Conversely, more
advanced dynamics/kinetics analysis considers these inertial effects
based on masses and accelerations. Static equilibrium means that
the sum of forces and moments acting on a body segment must
equal zero (Newton’s first law). If this sum is nonzero, motion
results. For example, an initial approximation of the force in the
Achilles tendon during push-off can be estimated by considering
the foot as a free body in static equilibrium (Figure 1).

Figure 1 Illustration shows the simplified two-dimensional quasi-static analysis

of the foot during push-off, used to estimate Achilles tendon and ankle forces
(red arrows).The moment at the ankle joint due to the ground reaction force is
equal to that force (eg, 1× the body weight) multiplied by the horizontal distance
between the force and the ankle. For static equilibrium at the ankle, this moment
must be balanced by the moment from the Achilles tendon force. Because the
Achilles tendon acts at a smaller distance away from the ankle, it must exert a
force substantially larger than the ground reaction force. Subsequently summing
vertical forces on the foot, the ankle force is also much higher than the ground
reaction force.

In reality, additional lesser muscles crossing the joints are active,

some acting antagonistically, leading to additional joint
compression. The aforementioned fundamental concepts have been
greatly expanded with modern research, including computational
modeling, and in vivo patient measurements with implants
containing wireless force sensors. 1 Knowledge of joint forces, along
with typical joint motions (kinematics), is used for purposes such
as wear testing of joint replacement components.

Solid Mechanics
In addition to joint and muscle forces, it is often important to
understand how these loads are transmi ed across tissues and
implant constructs, leading to stress (local force intensity, or force
per unit area) and strain (local stretching). Failure in
musculoskeletal tissues and implants results from excessive stress
or strain where the tissues cannot adapt to these local stimuli.
There are four basic types of loading usually considered, and
during physiologic loading, all four types of loads may be present.
Tendons and ligaments resist primarily only tension (axial) loads.
For nonlong bones and portions of implants without a long axis,
bending and torsion are less applicable. Each of these loads causes
deformation and stresses in different ways, as shown Figure 2 and
outlined in Table 1.
 Figure 2 Illustration shows four fundamental loading types, for example, at the
joint of a long bone.

Table 1
Stresses and Strains Within the Diaphyseal Region of Simplified
Long Bone Arising From the Four Fundamental Loading Types

Relevant
Fundamental Resulting Stress
Cross-Sectional
Loading Load Description Distribution in a Cross
Geometric
Type Section
Property
Axial Force directed along Area (A) Evenly
the long axis, either in
tension or compression
Bending Moment in a plane that Area moment of Maximum tensile on one
includes the long axis inertia (I) side, and maximum
compressive on the
opposite side
Torsion Torque (moment) Polar moment of Maximum shear around
around the long axis inertia (J) outside
Transverse Force perpendicular to Area (A) Often negligible compared
shear the long axis with stresses from other
loading types

Area moment of inertia and polar moment of inertia properties

depend on cross-sectional geometry of the tissue or implant.
Because stresses and strains are higher at the outer surfaces in
bending and torsion, these moment of inertia properties depend
not only on how much material there is, but how far the material is
distributed away from the center. Both normal and shear stresses
(and strains) typically exist at a point in an object, and these vary in
magnitude across different locations. In simplified scenarios, such
as within the diaphyseal section of Figure 2, analytical estimates of
stresses can be made. As discussed in a 2021 study, for analysis of
more complex geometries such as metaphyseal regions of bone or
implanted constructs, a more sophisticated approach such as finite
element computational modeling is needed. 2
To experimentally measure the stiffness and strength of a long
bone, it can be tested in one of the aforementioned loading modes,
or a physiologically relevant combination of loads. In axial testing,
the force and displacement of the actuator can be recorded from
the testing machine. Analogously in torsion testing, the torque and
rotation of the actuator can be recorded. Once the force versus
displacement, or torque versus rotation, is plo ed, the slope of the
resulting linear portion of the curve indicates the axial rigidity or
torsional rigidity, respectively. These rigidities depend not only on
geometry of the object being tested (moment of inertia), but also on
the inherent material properties (elastic moduli) of the object.
Longer bones and implants will also displace overall more than
shorter ones.
Bending tests involve additional considerations because pure
bending moments are not as straightforward to apply. Instead,
forces are applied in either of the following ways, and static
equilibrium equations can be used to determine locations of
maximum bending moment:

1. In cantilever bending, one end is fixed in space, whereas force

is applied on the other end, which results in a maximum
bending moment at the fixed end.
2. In three-point bending, two fixed vertical supports are
provided to the object, while an opposing vertical loading force
is applied in the middle of the supports, which results in a
 maximum bending moment (along with shearing) at the point
of force application.
3. In four-point bending, an additional vertical loading point is
added to the three-point bending setup, resulting in a zone of
maximum bending moment instead of a single point.

Material Science

Stress-Strain Curve
The stress-strain relationship, determined from the load-
displacement relationship, is central when studying biomechanics
of materials, including native tissues and orthopaedic implants.
The stress-strain relationship is defined for a material, whereas the
load-displacement relationship is assessed for an entire structure
and thus depends on structure geometry, in addition to material. By
characterizing how a material responds to loading, the stress-strain
curve can provide insight into bone fractures or implant failures.
Stress is defined as the amount of force applied per unit of cross-
sectional area, whereas strain is defined as material lengthening
over the original length in response to this stress. The linear elastic
region, yield point, plastic region, ultimate strength, and failure are
salient features of the stress-strain curve corresponding to elastic
deformation, stress point at which the material becomes plastic,
plastic deformation, the maximum amount of stress the material
can withstand, and material failure. Although tensile loading is
typically used to characterize material properties, compression or
shear loading curves may also be generated (Figure 3).
 Figure 3 Graphs show stress-strain behavior.A, An idealized stress-strain
curve, showing the elastic and plastic regions. B, Bone exhibits different
behavior when loaded in the longitudinal and transverse directions. C, An
increasing strain rate increases stiffness.

Elastic Modulus
Young modulus, or the elastic modulus, is the slope of the elastic
region of the stress-strain curve, representing material stiffness.
Young modulus is useful for comparing and selecting materials in
orthopaedics. For example, bone-implant modulus mismatch is
often cited as one of the causes of stress shielding and implant
failure.

Yield Point and Plastic Deformation

The plastic region of the stress-strain curve is the region of
irreversible material deformation. The elastic and plastic regions
are separated by the yield point, above which the material may
sustain permanent damage. After the yield point, the material
undergoes plastic elongation or yielding with li le increase in
stress. Strain hardening, which occurs because of the material
undergoing changes in atomic and crystalline structure, is a
phenomenon where plastic deformation increases material
resistance to further deformation.

Ultimate Tensile Strength

The ultimate tensile strength is the maximum stress that the
material can withstand before failing. After the ultimate strength
point, lengthening may continue for ductile materials, but with a
reduction in stress. This is associated with necking of the material,
whereby the cross-sectional area is reduced. Because orthopaedic
implants typically fail through cyclic loading rather than acute
loading, the ultimate tensile strength is less relevant than fatigue
strength.

Fatigue Properties
In vivo physiologic loading is cyclic with every cycle of gait, arm
reach, etc. Fatigue strength, or fatigue limit, is defined as the
highest stress the material can withstand for a given number of
cycles. Incremental increases in loading cycles result in eventual
failure that is bri le in nature. When repetitive cyclic loading below
the yield strength results in failure, it is termed fatigue failure.

Viscoelastic Load Elongation Curve

Most biologic materials are viscoelastic, displaying both elastic and
viscous behavior. Elasticity is the ability of a material to return to
its original form after the stresses that induced the deformation are
removed. Viscosity is a measure of resistance to rate-dependent
deformation. A viscoelastic material returns to its original shape
after the stresses that caused deformation are removed, but it has a
viscous component to the response that determines the time it
takes to return to that original shape. Unlike elastic materials,
viscoelastic ones dissipate some of the energy from the
deformation. This dissipation, known as hysteresis, makes the
loading component of the stress-stain curve higher than the
unloading. Stress relaxation and creep are two other characteristics
associated with viscoelastic materials. Creep is defined as an
increase in the deformation of a material under a constant load. In
contrast with creep, stress relaxation refers to stress decreasing
over time under a fixed level of strain.
Experimental Testing
Benchtop tests are powerful for predicting implant performance
preclinically. Axial, bending, torsional, or combined six-degrees-of-
freedom loading is applied depending on the application (eg,
implant head versus surgical screw). Static loading assesses
material stiffness, whereas dynamic loading can determine wear
properties or fatigue strength. The most common type of test is a
load-controlled test, wherein deformation of a material is measured
in response to applied load. However, displacement-controlled
tests, wherein a given displacement is prescribed and the resulting
force is measured, are also used. 3

Ultrahigh-Molecular-Weight Polyethylene
Properties
Ultrahigh-molecular-weight polyethylene is a thermoplastic
polyethylene that is widely used as the bearing material for knee
and hip implants, dating back to the 1960s. It is associated with
higher fracture resistance and biocompatibility compared with
other polymers. Its higher crystallinity contributes to a high Young
modulus, yield strength, resistance to creep deformation, and
enhanced fatigue strength. Its high molecular mass, however,
which contributes to favorable material properties such as wear
resistance, has been shown to decrease with oxidation both ex and
in vivo. 4 Such concerns gave rise to radiation cross-linking. Highly
cross-linked ultrahigh-molecular-weight polyethylene was
introduced in the 1990s to reduce oxidative degradation. It has
become the de facto standard for hip replacements and is gaining
traction for knee implants. 5

Polymethyl Methacrylate Properties

Polymethyl methacrylate, or acrylic, is a rigid thermoplastic
material used as bone cement because of its good biocompatibility.
Although not adhesive, it acts as a space filler and relies on
mechanical interlock between the irregular bone surface and the
prosthesis to enable fixation. Bone cement is stronger in
compression than tension and has a low Young modulus. Its
properties are temperature-dependent; for example, creep increases
with temperature. All polymethyl methacrylate bone cement
exhibits creep and stress relaxation. Because the tensile stresses
decrease over time as a result of stress relaxation, the bone cement
in an implanted stem never reaches the stress levels required for
fatigue failure.

Cancellous and Cortical Bone Properties

The mechanical behavior of bone is complex because of its
heterogeneous, anisotropic, and viscoelastic nature. Cortical and
cancellous bones are continuously loaded statically and
dynamically, making fatigue loading central to their mechanical
behavior. Cortical bone is stronger and stiffer when loaded in the
longitudinal than in the transverse direction, and stronger in
compression than in tension. Strength and stiffness of cortical
bone, however, depends on loading rate, with faster loading
resulting in higher stiffness.

Biocompatibility
Orthopaedic alloys are not strictly selected based on mechanical
properties, but based on appropriate mechanical properties and
biocompatibility. There are three principal metal alloys used in
orthopaedic surgery: titanium, cobalt-chromium, and stainless
steel. Alloy-specific differences in strength, ductility, and hardness
generally determine which of these three alloys is used for a
particular application or implant component. There are other types
of alloys that have superior mechanical properties. However, it is
the high biocompatibility and corrosion resistance of all three
alloys, more than anything, that has led to their widespread use as
load-bearing implant materials.
Stainless Steel Alloys
The form of stainless steel most commonly used in orthopaedic
practice is designated 316L (American Society for Testing and
Materials F138, ASTM F138). Molybdenum is added to enhance the
corrosion resistance of the grain boundaries, whereas chromium
dissipated evenly within the microstructure allows the formation of
chromium oxide (Cr2O3) on the surface of the metal. Stainless steels
are surface treated (eg, in nitric acid) to promote the growth and
thickening of this passive oxide layer. 6 - 9

Cobalt-Chromium Alloys
Of the many cobalt-chromium alloys available, the two most
commonly used, as implant alloys, are (1) cobalt-chromium-
molybdenum (Co-Cr-Mo), which is designated ASTM F75 and F76;
and (2) cobalt-nickel-chromium-molybdenum (Co-Ni-Cr-Mo)
designated as ASTM F562. Given the stiffness and overall hardness,
the alloy is ideal for bearing surfaces.

Titanium Alloys
The stability of the oxide layer formed on titanium (Ti; and
consequently its high corrosion resistance and its relatively higher
ductility [ie, the ability to be cold worked]), compared with Ti-6Al-
4V, has led to its use in porous coatings (eg, fiber metal) of
arthroplasty components. Generally, Ti-6Al-4V (ASTM F136) is used
for joint replacement components because of its superior
mechanical properties in comparison with Ti. Titanium alloys are
particularly good implant materials because of their high corrosion
resistance compared with stainless steel and Co-Cr-Mo alloys. A
passive oxide film (primarily of TiO2) protects both Ti-6Al-4V and
commercially pure Ti. Ti-6Al-4V alloy is an example of a material
that can be approximately 15% softer than Co-Cr-Mo alloys, yet
when used in bearing applications results in significantly more
(15% greater) wear than Co-Cr-Mo, for example, total knee
arthroplasty or total hip arthroplasty femoral heads. Thus, Ti alloys
are seldom used as materials where resistance to wear is a primary
concern. 7 , 8 , 10 - 13

Ceramic Alloys
Ceramics were introduced as a bearing surface given their superior
wear resistance properties and biocompatibility. Given their
hardness, stiffness, low friction, and resistance to further oxidation
due to the ionic bonds and chemical stability (inertness), ceramics
have excellent mechanical properties and biocompatibility for
bearing surfaces. The ceramic mechanical properties are primarily
controlled by small grain size and full density. Small grain size
controls the magnitude of internal stresses from thermal
contraction during cooling. Full density is important as any voids
will increase mechanical stress. Together, these increase hardness
and decrease bri leness and rates of fracture. The primary ceramics
used in orthopaedics include alumina (Al2O3) and zirconia (ZrO2).
Alumina matrix femoral heads are composed primarily of alumina
(75%), zirconia (24%), and 1% chromium oxide. Zirconia particles
dispersed in the matrix add increased toughness, and zirconia and
chromium oxide provides increased hardness. The pink color of the
material is a result of the chromium oxide.

Zirconium and Tantalum Alloys

Zirconium (Zr) and tantalum (Ta) alloys are characterized as
refractory metals as they are extraordinarily resistant to wear
(others include molybdenum and tungsten). These refractory
metals generally possess levels of hardness and wear resistance
approximately tenfold that of Co and Ti alloys. 7 , 9 , 10 , 12 , 13 Using
oxygen enrichment, oxinium consists of a zirconium alloy that
transitions to a ceramic zirconium oxide outer surface. Porous
tantalum is also inert, restricting interaction with bone. Thermal
processing in an alkaline environment results in hydroxyapatite
formation on the surface increasing bone interdigitation. Secondary
to the high porosity, material properties are adjusted to create a
modulus of elasticity similar to cancellous bone. The coefficient of
friction is high resulting in be er initial fixation with cancellous
bone. These alloys are highly corrosion resistant as the surface has
a thick, stable passive layer, and subsequently high level of
biocompatibility.

Corrosion
Corrosion is driven by a material’s desire to go toward a lower
chemical energy state and occurs when electrons flow from the
anode (loss of electrons) to the cathode (gain of electrons). This is
an exothermic process with minimal activation energy, which allows
the reaction to occur spontaneously at either a fast or slow rate.
When a bare metal surface without a protective metal oxide film is
directly exposed to air or an aqueous solution, the reaction is
explosively exothermic. An excellent example of this is titanium.
Vacuum-processed titanium powder corrodes from a metallic state
to an oxide at such a violent rate and with such a powerful release
of energy that it has been used as solid rocket propellant. On the
opposite end of this spectrum, ASTM titanium alloys have such a
low rate of corrosion that they are an ideal material for many types
of orthopaedic implants. The difference in the rate of corrosion
between vacuum-processed titanium and ASTM titanium alloy is
that ASTM titanium alloy rapidly forms a protective oxide film (also
known as a passive layer) on its surface when it is exposed to
oxygen. This process is known as passivization. As discussed in a
2019 study, this protective oxide film nearly stops corrosion on the
surface of the metal, making a metal that can be used as a rocket
propellant safe and stable for use as an implant. 14
Corrosion occurs in three basic steps. First, metal from the
surface dissolves into the aqueous environment and cations are
removed (oxidation). Second, remaining electrons are a racted to a
differential charge at another point on the surface. A current is
generated as electrons are removed from the surface, driving the
reaction (reduction). Finally, metal oxide or metal hydroxide form
as byproducts. Metal oxides and insoluble metal hydroxides (rust)
form an insulating layer on the metal surface. 14 This precipitate
forms a film that inhibits the kinetics of the reaction and insulates
the metal from further corrosion 9 (Figure 4).
 Figure 4 Illustration of types of corrosion.A, Basic corrosion: An oxidation
reduction reaction can form either a metal hydroxide (rust) or metal oxide
(passive film). B, Pitting corrosion: The passive film prevents corrosion. A defect
in the passive film allows corrosion to occur. C, Crevice corrosion is the same
mechanism as pitting corrosion, except that it occurs in an enclosed space.
Limited diffusion can create an environment with decreased pH and low oxygen
tension, ideal conditions for corrosion. D, Mechanically assisted crevice
corrosion (MACC) has a similar mechanism as crevice corrosion, except that
there is a mechanical shear across the surface. This creates an additional
mechanical stress across the passive film causing further destruction of the
passive film, increasing the rate of corrosion.(Courtesy of Kenneth Urish, MD,
PhD, Pittsburgh, PA.)

The passive, chemically stable metal oxide layer is the key to

preventing corrosion on orthopaedic implants. The metal oxide is
more stable, less soluble, and more insulating compared with metal
hydroxide. Because the metal oxide film is nonconductive and an
insulator, it prevents the flow of ions (current) from the solution’s
aqueous layer to the metal surface and thus limits the rate of
corrosion. These films can only form with specific types of metal
alloys. Stable passive metals include Ti, Cr, Ta, Nb, and Zr. Other
metals such as Al, Cu, In, and Tn can form metal oxide layers, but
these protective layers can quickly dissolve in the presence of
chloride ions, a main constituent of physiologic solutions.
Remaining elemental metal in alloys can corrode to form a metal
hydroxide layer (ie, rust), which has a limited ability to prevent the
movement of ions and limit corrosion. A passive film is not static
and is in a constant steady state equilibrium. Its thickness and
ability to protect the alloy from corrosion is a balance between
reactions that erode and build the film 11 (Figure 4).
The basic types of corrosion that can occur on an orthopaedic
implant include pi ing, crevice, and mechanically assisted crevice
corrosion (MACC). These different types of corrosion are all part of
continuous spectrum based on a metal alloy’s ability to avoid
breakdown of the protective passivation layer. Pi ing corrosion
occurs from localized breakdown in the passive layer. Crevice
corrosion is a form of pi ing corrosion in a relatively harsher
environment with limited mass transport. Fre ing corrosion in a
crevice is a form of MACC where crevice corrosion is facilitated by
mechanical stress or mechanical motion. A total hip arthroplasty
trunnion serves as a good example to illustrate these points. 14
Pi ing corrosion: Slight inconsistencies that develop in the passive
film lead to breakdown in small areas, development of a focused
anode, and localized galvanic corrosion. For example, if one area of
the passive film has a small amount of more permeable hydroxide
(rust) than impermeable oxide, then a defect can develop over this
area of the passive surface (pi ing) creating a more permeable and
less protective film. A larger flow of metal ions can escape in this
small area creating a focused anode. A differential cathode will
develop over a large surface at a distant point in response to the
point anode that develops. This creates a large difference in
potential charge at distant points on the metal surface. 14 The
current flow between these two charges is similar to the voltage
difference across a ba ery or galvanic corrosion 15 , 16 (Figure 4).
Crevice corrosion: Pi ing corrosion that occurs with limited
diffusion of ions creates optimal conditions for corrosion. In a
crevice, there is limited diffusion of ions in and out of the local
environment producing an environment optimized for corrosion.
The total hip arthroplasty trunnion is a closed environment that
prevents ion diffusion. A water-tight seal is established at a finite
point on the neck-head taper connection, not across the entire taper
surface. This water-tight seal prevents the diffusion of ions. Oxygen
becomes depleted, limiting the ability of a passive layer to
regenerate itself (repassivation). Hydrogen and chloride ion
(hydrochloric acid) concentration increases. This creates a low pH
environment that accelerates corrosion by preventing repassivation
from the increased rate of corrosion and the low concentration of
oxygen to create metal oxide. The metal surface has a small
inconsistent passive film that is not insulated from an aqueous
solution. Essentially, crevice corrosion is pi ing corrosion in an
ideal corrosion environment 14 (Figure 4).
 Fre ing corrosion or MACC: Physical shearing forces remove the
protective passive film that serves as a barrier for the metal surface
from corrosion. The optimal environment in crevice corrosion can
be further optimized by removing even more passive film, creating
a larger surface for crevice corrosion to occur. For example, at the
trunnion interface, possible shear movement between the taper
surfaces can remove additional passive film. Increased head sizes
and femoral stem offset increase the force across the trunnion and
the potential for shear movement between the surfaces. A lack of
passive film to protect the metal surface and the optimal
environment for corrosion from the limited diffusion of crevice
corrosion set up optimal conditions for aggressive corrosion.
Fre ing corrosion or MACC are essentially identical terms 11
(Figure 4).

Summary
Understanding biomechanics and biocompatibility is a powerful
tool for the practicing orthopaedic surgeon. Application of
biomechanics, biomaterials, and biocompatibility are core
principles and concepts in the treatment and interventions in
orthopaedic surgery. It forms the foundation of innovation that
expands the orthopaedic surgeon’s ability to improve patient care.

Key Study Points

The Young modulus is useful for comparing and selecting materials in orthopaedics,
and bone-implant modulus mismatch is often cited as one of the causes of implant
failure.
Bone is stronger and stiffer when loaded in the longitudinal than in the transverse
direction, and stronger in compression than in tension.
The passive layer of the alloy serves a critical role in preventing corrosion on
orthopaedic implants.
Orthopaedic alloys have not been selected because of the best mechanical
properties (ie, strength), but because they have the best corrosion resistance.
The femoral head–neck trunnion creates an optimal environment for corrosion to
occur because of the limited fluid diffusion, acidic environment, and increased
bending moment.
Annotated References
1. Bergmann G, Graichen F, Rohlmann A, et al: Realistic loads for
testing hip implants. Bio Med Mater Eng 2010;20:65-75.
2. Lewis GS, Mischler D, Wee H, Reid JS, Varga P: Finite element
analysis of fracture fixation. Curr Osteoporos Rep 2021;19:403-416.
This is a review article focusing on the use of finite element
modeling in fracture fixation in osteoporotic fractures.
3. Schwenke T, Orozco D, Schneider E, Wimmer MA: Differences
in wear between load and displacement control tested total knee
replacements. Wear 2009;267:757-762.
4. Brach Del Prever EM, Bistolfi A, Bracco P, Costa L: UHMWPE for
arthroplasty: past or future? J Orthop Traumatol 2009;10:1-8.
5. Wang A, Yau SS, Essner A, et al: A highly crosslinked UHMWPE
for CR and PS total knee arthroplasties. J Arthroplasty 2008;
23:559-566.
6. Bundy K: Bone Prosthesis and Implant Materials. CRC Press Inc,
1989, pp 160-184.
7. Park JB: Biomaterials Science and Engineering. Plenum Press, 1984.
8. Silver FH, Christiansen DL: Biomaterials Science and
Biocompatibility. Springer, 1999.
9. Jacobs JJ, Gilbert JL, Urban RM: Corrosion of metal orthopaedic
implants. J Bone Joint Surg Am 1998;80:268-282.
10. Breme J, Biehl V: Metallic Biomaterials. 135-214. Champman and
Hall, 2001.
11. Black J: Orthopaedic Biomaterials in Research and Practice.
Churchill Livingstone, 1988.
12. Black J: Biomaterials. Marcel Dekker, Inc, 1992.
13. Black J: Prosthetic Materials. VCH Publishers, Inc, 1996.
14. Urish KL, Giori NJ, Lemons JE, Mihalko WM, Hallab N:
Trunnion corrosion in total hip arthroplasty-basic concepts.
Orthop Clin North Am 2019;50:281-288. This is a review article with
 an excellent description of the relationship between the different
types of corrosion in orthopaedic surgery, including uniform,
pi ing, crevice, and fre ing or MACC.
15. Hodgson AW, Mischler S, Von Rechenberg B, Virtanen S: An
analysis of the in vivo deterioration of Co-Cr-Mo implants
through wear and corrosion. Proc Inst Mech Eng H 2007;221:291-
303.
16. Szklarska-Smialowska Z; National Association of Corrosion
Engineers: Pi ing Corrosion of Metals. National Association of
Corrosion Engineers, 1986.
C H AP T E R 9

Musculoskeletal Imaging
Principles
John A. deVries MD, MS, Narayan Sundaram MD, MBA,
Rex Haydon MD, PhD, FAAOS

Dr. Haydon or an immediate family member serves as a board member, owner, officer, or
committee member of the American Orthopaedic Association and the OMeGA Medical Grants
Association. Neither of the following authors nor any immediate family member has received
anything of value from or has stock or stock options held in a commercial company or institution
related directly or indirectly to the subject of this chapter: Dr. deVries and Dr. Sundaram.

ABSTRACT
Imaging is indispensable for diagnosing most musculoskeletal
pathologies, including trauma, arthropathies, inflammatory
conditions, and neoplasms. Imaging is useful not only for
diagnostic but also prognostic and follow-up applications. It is
important to review indications and applications for radiography,
CT, MRI, ultrasonography, and nuclear medicine as well as recent
advances in the field.
Keywords: CT; imaging; MRI; radiography; ultrasonography

Introduction
Musculoskeletal imaging represents one of the most important
tools used by orthopaedic surgeons in patient care. The full range
of imaging techniques includes simple radiography, CT, MRI, and
ultrasonography as well as more advanced nuclear medicine tests
such as bone scans or positron emission tomography (PET) CT.
Strict indications for imaging should be followed when ordering
tests to minimize cost and risks to the patient, such as unnecessary
radiation or contrast agents. Reviewing each of these imaging
approaches will provide clinicians with a thorough understanding
of each radiographic modality to ensure accurate, safe, and cost-
effective diagnostic testing.

Conventional Radiography

Physics and Digital Format

Conventional radiography uses x-rays to generate images. X-rays
are transmi ed through the body part of interest and are
absorbed/sca ered (a enuated) to varying degrees by different
tissues to generate a two-dimensional radiographic image. The
contrast between high-a enuation bone and low-a enuation soft
tissues makes conventional radiography an excellent method for
imaging of skeletal structures. Advances in technology have
rendered traditional casse e-based film radiographs (computed
radiography) obsolete. Digital radiography uses a digital x-ray
detector to acquire images and a phosphor imaging plate to
generate a digital image. The ability to manipulate windowing
levels on digital radiography versus computed radiography does
allow for some discrimination of soft tissues, air, and fluid from
bone. 1

Technique
As a general rule, orthogonal views are obtained for most long
bones; however, certain anatomic locations may require more than
two images per site of interest. For example, three views are
routinely used for the evaluation of more distal joints, such as the
wrist/hand or ankle/foot. Oblique views are often added to standard
approaches depending on the nature of the pathology that is being
evaluated, such as Judet views of the pelvis for the evaluation of
acetabular fractures. Additionally, a wide range of specialized
radiographic techniques exists that require special positioning of
the patient and the x-ray beam to evaluate for specific conditions.
Table 1 presents a list of many of these specialized examinations.

Table 1
Special Radiographic Views, Techniques, and Pathology Being
Assessed With Each View

Name Technique Pathology Assessed

Odontoid view AP upper cervical spine, open mouth C1 or odontoid fracture,
transverse ligament
Serendipity 40° inferior from AP of upper chest Acromioclavicular
dislocation, clavicle
Grashey 45° lateral, shoulder Glenohumeral joint arthritis
or fracture
Axillary Inferior to superior toward axilla Glenohumeral dislocation,
acromion
Scapular Y 45° medial, shoulder Glenohumeral dislocation
Carpal tunnel view Wrist extended, 30° cephalad Hamate, pisiform, trapezium
fracture
Flexion/extension Lateral lumbar spine in flexion and Lumbar spine instability
lumbar spine extension
Oblique spine 45° oblique to AP Pars interarticularis defect,
Scottie dog sign
Inlet/outlet, pelvis 25° caudal (inlet), 35° cephalad Pelvic ring disruption, sacral
(outlet) fractures
Judet views, pelvis 45° lateral (iliac oblique) and medial Acetabular and pelvic
(obturator oblique) column fractures
Notch view, knee AP with knee flexed 45° Tibial plateau/eminence,
intercondylar space
Sunrise/Merchant Knee flexed 45°, beam 30° caudal Patellofemoral pathology
view, knee from AP
Mortise view, ankle 15° to 20° internal rotation from AP Malleolar fracture,
syndesmotic stability
Harris view 45° caudal from horizontal toward the Calcaneal body and middle
heel facet
Broden view Leg internally rotated 45°; 10°, 20°, Multiple views posterior talar
20°, and 40° cephalic tilt facet
Screening Techniques
Trauma Evaluation
Plain radiographs are an effective and easy modality to use. They
are very quick to obtain and of low cost. For evaluation of
musculoskeletal trauma, radiography should generally include the
joint above and below the area of interest to rule out concomitant
or occult injuries. Fractures can be readily identified, and further
imaging may not be needed to diagnose and treat many injuries.
Guidelines have been developed in less straightforward scenarios.
For example, O awa rules have been developed to help determine
when plain radiographs are indicated for the evaluation of ankle or
foot pain in the emergency department. If the patient has
tenderness directly over the midfoot or malleoli and is unable to
bear weight, radiographs are generally indicated. 2 Specific clinical
contexts will dictate when imaging is needed and where. In the
trauma bay for the multiply injured patient, plain portable
radiographs can serve as a quick screening tool (Figure 1). High-
speed trauma with a femoral fracture, for example, requires
dedicated imaging of the ipsilateral femoral neck to evaluate for a
concomitant femoral neck fracture 3 (Figure 2). Criteria such as
National Emergency X-Radiography Utilization Study Group
indicate when it is appropriate to obtain cervical spine films. 4 If
there is any suspicion for pelvic ring injury, a simple pelvis film
should be obtained in the trauma bay because these injuries can be
life-threatening and results can be obtained in minutes. For most
plain radiographs, the entire bone should be included, and
orthogonal views should be obtained when appropriate.
Figure 1 Portable AP radiograph obtained in the trauma bay showing the pelvis
of a young adult following a motor vehicle accident.Left obturator ring and sacral
fractures indicate pelvic ring disruption and high-energy mechanism. Additional
imaging and close monitoring of vital signs are necessary.
 Figure 2 AP portable radiographs of the proximal femur (A) and distal femur
(B) of a patient with trauma. Periprosthetic fracture, fracture of intramedullary
device and distal interlocking screws, distal diaphyseal and metaphyseal femoral
fracture with concomitant femoral neck fracture are shown.

Atraumatic Evaluation
In patients with atraumatic musculoskeletal pain, plain
radiographs are usually indicated before any advanced imaging is
to be ordered. Degenerative conditions, insufficiency/stress
fractures, osteomyelitis, impingement syndromes, and many
arthropathies can often be diagnosed on plain films alone. In the
spine, alongside static AP and lateral views, dynamic flexion and
extension films can help detect segment instability that may
contribute to a patient’s symptoms; however, advanced imaging is
often needed for further evaluation.
Arthritis and joint-based pathologies are readily studied with
plain radiographs. If osteoarthritis is suspected, weight-bearing
radiographs represent the gold standard for diagnosis (Figure 3).
Other inflammatory arthropathies can be diagnosed and followed
with radiographs, alongside laboratory tests and clinical
examination. 5 Plain radiographs are extremely accurate and
valuable in the evaluation of the joint space, alignment,
osteophytes, and other sequelae of joint degeneration. Other
disease processes such as gout or pseudogout, tumoral calcinosis,
myositis ossificans (Figure 4), or heterotopic ossification routinely
result in soft-tissue mineralization and can be diagnosed and
followed with plain radiographs.

Figure 3 Standing AP radiograph of bilateral knees (A) and lateral plain

radiograph of the knee (B). Significant end-stage osteoarthritic changes include
bilateral varus alignment, joint space narrowing, joint subluxation, subchondral
sclerosis, and osteophyte formation.
 Figure 4 AP radiograph of the distal femur of a 31-year-old woman
demonstrating the characteristic calcification pattern of myositis ossificans.

Neoplastic Evaluation and Considerations

The workup of benign and malignant bone and soft-tissue
pathology generally starts with plain radiographs. Especially in the
pediatric population, there are many benign bone lesions that are
characterized by radiographs and are sufficient for diagnosis and
follow-up. 6 Malignant features can also be seen, such as periosteal
reaction and bony destruction or growth. A wide zone of transition
versus well-marginated lesions may give clues as to the benign or
neoplastic nature of the pathology. Osteosarcoma as well as
chondrosarcoma may be diagnosed with radiographs. 7
Enchondromas are usually incidentally found but must be
differentiated from malignant pathology. Soft-tissue masses can
occasionally be evaluated with radiographs but, besides looking for
calcification pa erns, they are be er evaluated by advanced
imaging.

Fluoroscopy
Fluoroscopy refers to the use of radiographs in real time, where the
clinician uses the information during live manipulation of the
structure of interest. This can be used to evaluate unstable fracture
pa erns by evaluating the joint or structure of interest under stress,
such as loading the hip joint under live x-ray to assess for stability
of the joint after an acetabular fracture 8 or stressing the distal tibia-
fibula syndesmosis after fixation of an ankle fracture to test the
integrity of the syndesmotic ligament complex. However, the most
frequently used application of fluoroscopy is for intraoperative
guidance. This gives real-time feedback during spine or trauma
surgery for screw placement and fracture reduction, allowing for
be er outcomes without direct visualization, thereby making less
invasive and percutaneous surgery possible. Fluoroscopy is also
used for image-guided joint aspirations and injections.
Dual-Energy X-ray Absorptiometry
Imaging modalities to assess bone density have been developed
over the years, much of which has been adapted from x-ray-based
techniques. Dual-energy x-ray absorptiometry is currently used to
calculate bone mineral density and thereby infer risk of sustaining
an osteoporosis-related fracture such as vertebral compression
fracture, hip fracture, or distal radial fracture, 9 although more
complex and accurate modalities are being developed using
techniques that will be discussed in the next paragraphs.

Computed Tomography
CT uses a rotating x-ray beam to create cross-sectional images of
the body. The x-ray tube is placed in a circular gantry, which in turn
surrounds the CT table. The patient lies on the CT table, which
slowly moves through the gantry as the x-ray tube rotates around
the patient. The x-rays that transmit through the body part of
interest are detected by multiple detectors located opposite the x-
ray tube in the gantry. The input from all detectors surrounding the
patient is analyzed and then images are reconstructed by computer.
10

Current Advances in CT Technology

Dual-energy CT is an imaging technique that has many applications
in orthopaedic imaging. Dual-energy CT uses two different x-ray
energies to acquire images, which serves to demonstrate different
tissue contrasts. This is accomplished by using two x-ray tubes and
detectors mounted at 90º to each other (dual-source dual-energy
CT), or by using a single x-ray source that rapidly changes energy
levels and acquires data for each set during image acquisition
(rapid kilovoltage switching). Dual-energy CT has many evolving
clinical applications in orthopaedic imaging, including metal
artifact reduction, detection of monosodium urate (MSU) crystals in
gout, analysis of ligaments and tendons, detection of bone lesions,
and detection of bone marrow edema. 11
Conventional CT, despite using artifact reduction techniques, is
limited by metal artifact that degrades image quality. Dual-energy
CT can reduce artifact from metallic implants using postprocessing
techniques that combine the datasets from the two different x-ray
energies to generate an image that reduces metallic artifact from
orthopaedic prostheses. 12 This can help in identifying bone and
soft-tissue pathology adjacent to joint arthroplasties and other
metallic implants.
Dual-energy CT can be used to noninvasively diagnose gout
(Figure 5). It has been shown to accurately identify MSU crystals in
gout, taking advantage of the distinct a enuation characteristics of
calcium from bone and MSU crystals. Gout traditionally has been
diagnosed through joint fluid analysis for MSU crystals obtained
through arthrocentesis.

Figure 5 Dual-energy CT showing gout at two different kilovolts: axial (A) and
three-dimensional (B) reconstruction. Gouty tophi along the Achilles tendon,
tibialis anterior tendon, and deltoid ligament is indicated in yellow.

Dual-energy CT is an evolving technique in the detection of bone

marrow edema by removing bone from marrow and using
postprocessing techniques to generate bone marrow edema maps.
Other applications of dual-energy CT include analysis of ligaments
and tendons by taking advantage of the unique a enuation of these
collagenous structures; dual-energy CT also shows promise in
detection of bone metastases by measuring water content, bone
composition, and enhancement characteristics of bone metastases
compared with trabecular bone and benign bone lesions.
Another emerging CT technique is cone-beam CT. This uses a
cone-shaped x-ray beam and a flat-panel detector rather than a fan-
shaped beam and linear detectors used in conventional CT. In cone-
beam CT, the x-ray tube and detector rotate around the patient.
Images are then generated, which can be reconstructed in three
planes. This modality allows for weight-bearing CT images of
extremities with high spatial resolution but at a lower dose than
conventional CT. However, cone-beam CT has a limited assessment
of the soft tissues and uses a small field of view. It is used in
orthopaedics for identification of radiographically occult fractures,
weight-bearing assessment of joint osteoarthritis, and assessment
of sequestrum in chronic osteomyelitis.

Roles in Preoperative Planning and Surgical

Guidance
CT structures have had a significant effect on preoperative planning
of surgical interventions, most importantly in the areas of
evaluating and treating complex fractures, and in procedures that
incorporate various forms of surgical guidance technology. Axial CT
images can be converted into three-dimensional reconstructed
images for improved fracture reduction planning. 13 Preoperative
CT is generally required for robot-assisted surgeries. Briefly,
proprietary CT protocols are used to scan the bone or joint of
interest preoperatively (or in some cases intraoperatively). These
scans are then referenced intraoperatively relative to specific
anatomic landmarks using motion capture and additional reference
devices placed on the patient. This then allows real-time navigation
of saws, drills, or screws without the need for cu ing guides or live
fluoroscopy. This approach can be used for robot-assisted surgery
or navigated procedures performed by the surgeon. A 2021 study
has shown that this approach increases accuracy of surgical
procedures across a number of applications. 14 In addition to
dynamic real-time intraoperative guidance, preoperative CT scans
can be used to create a three-dimensional surgical plan, complete
with three-dimensional printed models of the patient’s anatomy or
three-dimensional printed cu ing guides for complicated
osteotomies or resections. Three-dimensional printed patient-
specific implants have been developed, but the cost and time
involved in manufacturing limits its use to complex and one-of-a-
kind cases. CT is also useful for evaluating implanted hardware and
is able to assess loosening, osteolysis, ingrowth, and nonunion.

Neoplasm Evaluation
For evaluation of neoplastic conditions, CT is a useful modality for
many applications. CT is the imaging modality of choice for soft-
tissue tumors in visceral organs in the chest and abdomen and is
useful for staging of most cancers. 15 MRI is generally preferred for
other soft tissues and for evaluating bone marrow; however, CT can
be used when MRI is contraindicated, as well as to detect and
characterize calcification. CT is used to evaluate bony structures
and cortical integrity and is a useful adjunct to radiography and
MRI, especially when evaluating impending fractures.

Contrast
When to Use
Generally, iodinated contrast is not indicated for most orthopaedic
applications of CT. Oral contrast has gastrointestinal indications
only. Intravenous contrast can be helpful for soft-tissue masses,
although MRI will yield significantly more information and should
be used unless contraindicated. Intravenous contrast is generally
not helpful for osseous imaging. Intra-articular contrast coupled
with CT can be helpful to assess cartilage defects as well as
meniscal and labral tears in those with contraindications to MRI.
CT myelogram is a procedure during which contrast is injected into
the thecal sac before CT. Again, this is only indicated in those with
contraindications to MRI but can be used to assess spinal cord
impingement or pathology, as described in a 2020 study. 16

Contraindications
CT contrast is not recommended in patients with an allergic
reaction to iodinated contrast. It is also important to measure the
glomerular filtration rate in patients undergoing a contrast-
enhanced CT to ensure that it does not result in renal toxicity. In
patients with a glomerular filtration rate below 30 mL/min, a careful
evaluation of the risks versus benefits of giving intravenous
contrast with CT should be considered and discussed with the
patient before proceeding with the examination.

Image-Guided Interventions
CT-guided interventions are becoming more common and are
usually performed by radiologists or interventional radiologists.
These include CT-guided needle biopsies, which are able to access
most anatomic areas and can therefore substitute for more morbid
open biopsies. CT-guided ablative techniques are becoming more
commonplace as well; CT-guided radiofrequency ablation of
osteoid osteomas is now the standard of care 17 , 18 (Figure 6). It can
also be used to ablate pain receptors in the spine or elsewhere.
Indications for microwave ablation and cryoablation procedures are
now expanding for a variety of both neoplastic and nonneoplastic
conditions. Cryoablation is a ractive as a technology because of its
visible ice ball on imaging, allowing safe targeting of lesions near
critical structures. 19
 Figure 6 CT-guided radiofrequency ablation of osteoid osteoma of the right
talus.

Bone Density Assessment, Bone Texture

Analysis, or Quantitative CT
Although dual-energy x-ray absorptiometry remains the mainstay
of osteoporosis evaluation, other adaptations of x-ray techniques
using computer-aided evaluation of radiographs, such as bone
texture analysis, have shown improved accuracy and are gaining
greater acceptance. Dual-energy x-ray absorptiometry is unable to
analyze quality or strength of bone. For bone texture analysis, a
standard two-dimensional radiograph, usually of a femoral neck or
other area of interest, is analyzed with multiple algorithms to
assess the texture and therefore strength of trabecular bone. 20
Quantitative CT uses CT technology to accomplish a similar goal,
determining bone structure and strength to a higher degree of
accuracy. 21

Magnetic Resonance Imaging

Physics of Obtaining Magnetic Resonance

Images
MRI does not use radiation to generate images but rather uses the
behavior of hydrogen protons of various body tissues in a strong
magnetic field to create an image. All body tissues contain large
numbers of hydrogen atoms, and their protons will behave like tiny
magnets themselves. The MRI scanner subjects the protons in a
tissue of interest to a magnetic field. The protons in turn will align
themselves with the magnetic field, and their magnetic fields align
themselves with the MRI magnetic field. This is termed precession.
Radiofrequency pulses are then applied to these tissues via various
coils (such as a knee coil), and if the frequency of the
radiofrequency pulse is the same as the precession frequency of the
magnetically charged protons, resonance occurs, and the protons
absorb the radiofrequency energy and their alignment is changed.
The radiofrequency pulses are then discontinued, and the protons
realign themselves again with the main magnetic field. This
realignment occurs at different rates depending on the type of
tissue being studied. Two of the key times protons in various
tissues take to realign with the MRI magnetic field are termed T1
and T2. Different tissues have different rates of T1 and T2 relaxation
times. The radiofrequency signals emi ed by protons during
relaxation are detected by radiofrequency coils on the patient, and
analyzed by a computer to generate an image. 22

What Sequences Are Used For

Imaging sequences that form the bulk of orthopaedic imaging
include T1, T2, proton density, and gradient echo. Radiofrequency
coils can use a radiofrequency pulse to block out bright fat signal in
these imaging sequences, a process termed fat suppression. Table 2
summarizes the signals seen for different tissues with each
sequence. Figure 7 shows an example of a healthy knee with a
standard set of MRI sequences.

Table 2
Signal Intensity of Various Tissues Compared With Muscle

Tissue T1 T2 STIR T1 FS + Gad

Fat ++ + − −−
Proteinaceous fluid + ++ ++ +
Simple fluid − ++ ++ −
Cortical bone −− −− −− −−
Air −− −− −− −−
Fibrous tissue/scar − − or + − or + −−
Red marrow + + + +
Normal yellow marrow ++ + −− ++
Articular cartilage + − − —
Tendon/ligament −− −− −− —
Subacute hematoma ++ ++ ++ ++
Chronic hematoma −− −− −− −−
++ = Extremely hyperintense relative to muscle, + = Hyperintense relative to muscle,− =
Hypointense relative to muscle,− − = Extremely hypointense relative to muscle.
 Figure 7 Standard series of MRI sequences of a normal knee.A, Axial proton
density-fat saturation; B, coronal T1; C, coronal T2-fat saturation; D, sagittal
proton density-fat saturation; E, sagittal T2-fat saturation.

Fluid Sequences
T2-weighted images are excellent for evaluating fluid and edema as
these appear hyperintense on T2-weighted images. As a result, T2-
weighted sequences are ideal for evaluation of pathology.

Soft-Tissue Specific Sequences

T1-weighted images are excellent for evaluating anatomy. Fat
(including marrow fat) appears bright or hyperintense on T1-
weighted imaging. Simple fluid appears dark or hypointense on T1-
weighted imaging. Postcontrast T1-weighted imaging with fat
suppression is used to assess enhancement pa erns of different
tissues.

Proton Density and Gradient Echo

Proton density is an intermediate sequence sharing some features
of both T1 and T2 sequences. Proton density is a sequence weighted
to reflect the actual density of protons (hence the name proton
density). Proton density sequences are useful in the assessment of
joints as it provides excellent contrast between fluid and cartilage.
Gradient echo sequences use gradient fields to generate images.
This alternate pathway of generating MRI versus standard T1-
weighted and T2-weighted sequences generates images that are
highly susceptible to field inhomogeneity. Degraded blood
products with hemosiderin, calcium, and metal objects will cause
dark blooming artifacts on these sequences. This, in turn, makes
gradient echo sequences useful in the identification of lesions
containing calcium or hemosiderin deposits in pigmented
villonodular synovitis.

Metallic Artifact Reduction Sequence Protocols

Metallic artifact with orthopaedic MRI is an ongoing issue that
results in poor-quality images that can obscure bone and soft-tissue
pathology adjacent to implanted metallic devices. Metallic artifacts
can also negatively affect fat suppression on MRI. There are
multiple factors that cause metallic artifacts with MRI. As an
example, magnetic field strength is directly proportional to the
amount of metallic artifact. As a result, the amount of metallic
artifact is lower with a 1.5T MRI than a 3T MRI. Traditionally,
metallic artifact reduction sequences have been performed by
altering such parameters on MRI as increasing bandwidth, thinner
slice selection, increasing echo train length, increasing image
matrix, and using short tau inversion recovery sequences for fat
suppression. Short tau inversion recovery sequences use the
varying MRI relaxation times of water and fat to generate fat-
suppressed images, and as a result provide more reliable fat
suppression in the presence of metallic devices. 23
Advances in technology have resulted in various proprietary
metal suppression techniques such as slice encoding for metal
artifact correction, multiacquisition with variable resonance image
combination, and WARP (Siemens Healthcare, Munich, Germany),
a proprietary combination of multiple technologies, which can be
used to reveal pathologic conditions previously hidden by metallic
hardware artifacts (Figure 8).

Figure 8 Coronal proton density multiacquisition with variable resonance

image combination metallic artifact reduction sequence showing pseudotumor
lesion of the left hip, following arthroplasty.

Contrast Indications/Contraindications
Gadolinium is a paramagnetic compound that is used in MRI in
analogous fashion to iodinated contrast in CT. For most
musculoskeletal imaging, contrast is not indicated; traumatic and
degenerative pathology is well visualized on MRI without contrast.
Gadolinium shows increased intensity in T1-weighted images with
increased contrast seen in fat-saturated images. It enhances in
proportion to soft-tissue vascularity and is indicated mainly for
evaluating neoplastic or infectious etiologies. It is effective in
delineating cystic (rim enhancing) versus solid masses
(heterogeneously enhancing) and can differentiate viable tumor
tissue from nonenhancing necrosis. Infectious processes such as an
abscess will have a thick enhancing wall compared with a
nonenhancing hematoma. In spine applications, contrast can help
to distinguish between enhancing early scar tissue and
nonenhancing disks. 24 Intra-articular contrast can be injected
under image guidance and can provide increased detail in large
joints, especially hip and shoulder, to investigate labral tears or
other pathology that may not be readily seen on standard MRI. 25

Magnet Strength and Resolution

MRI magnetic field strength is measured in tesla (T) units.
Advancements in technology have led to MRI being performed with
higher field strengths (ie, 3T rather than 1.5T), which, has in turn,
resulted in be er image resolution. The use of higher field strength
MRI has also resulted in shorter scan times. Open MRI is
sometimes offered for those with severe claustrophobia; however,
this results in a significant degradation in resolution, potentially
limiting its value for evaluating subtle bone and soft-tissue
pathology.

Indications
Because MRI does not use ionizing radiation, it is considered safe
during pregnancy and in pediatric patients. It is usually more
expensive and takes longer to perform compared with CT but is
associated with much be er resolution of the soft tissues. CT
remains the imaging modality of choice for issues related to
cortical/trabecular bone.
1. Trauma: suspected ligament or soft-tissue damage, stress
fixation, negative CT in spine imaging
2. Traumatic indications include suspected ligamentous or
cartilaginous injuries of any large joint, assessment of the joint
surfaces, or edema in the bone. MRI is very sensitive for stress
fractures of bone. According to a 2020 study, MRI is more
sensitive than CT, especially for detecting occult femoral neck
fractures. 26 Negative radiographs and CT of the cervical spine
may still require MRI to detect ligamentous disruption in
appropriate patients. It is also the modality of choice to
evaluate for disk disease in the spine, cord compression, and
spinal cord pathology in general.
3. Neoplasm: any suspected soft-tissue and most bone neoplasms
4. MRI is used frequently in the assessment of suspected bone
and soft-tissue neoplasms. It is part of the routine radiographic
evaluation of primary malignancies of bone, such as
osteosarcoma, chondrosarcoma, or Ewing sarcoma of bone, and
is ideal for evaluation of soft-tissue extension and to quantify
the extent of intraosseous involvement. 27 MRI is the modality
of choice for evaluating soft-tissue neoplasms. If there is
suspicion of a neoplastic process, intravenous gadolinium
contrast is usually indicated. Benign and malignant lesions can
often be distinguished from each other using the appropriate
MRI sequences and looking at pa erns of enhancement. 28
5. Joint arthritis assessment
6. For the evaluation and workup of joint degeneration, MRI is
usually not the modality of choice. Although degenerative
changes are readily seen on MRI, weight-bearing radiographs
remain the gold standard for evaluating a joint with suspected
osteoarthritis or degeneration. When MRI is performed,
cartilage thinning and damage can be seen, as well as bony
changes such as wear of the subchondral bone and
osteophytes. Ligament and tendon pathology can also be
evaluated, which can be important in specific clinical contexts,
such as assessing rotator cuff health for an anatomic versus
reverse total shoulder arthroplasty.
 p y
Ultrasonography

Physics and Techniques

Ultrasonography uses high-frequency sound waves to produce
images of soft-tissue structures. These sound waves are transmi ed
from an ultrasound probe into a soft-tissue region of interest. Some
of these sound waves are reflected back to the probe and are
processed by a computer to generate an image. Ultrasonography
uses no ionizing radiation and has the advantage of being able to
generate real-time images. Orthopaedic ultrasonography generally
uses higher frequency linear transducers, which generate higher
quality images for superficial soft-tissue structures. Lower
frequency curvilinear transducers are used for evaluation of deeper
structures.
Ultrasonography is prone to artifact. Two sources of artifact
include anisotropy and beam edge artifact. Anisotropy is an artifact
most notable with tendons, caused by the ultrasound beam being
oblique to tissue fibers resulting in artifactual loss of reflectivity. As
a result, normally bright (hyperechoic) tendon fibers can appear
dark (hypoechoic), artificially mimicking pathology. Beam edge
artifact can occur at the edge of larger tendons, where it can cause
an artificial posterior shadowing artifact, mimicking pathology.
This can, in turn, result in an incorrect diagnosis of tendon tears or
tendinosis.

Clinical Applications and Interventions

Ultrasonography has many uses in the evaluation and treatment of
musculoskeletal conditions. It can be used in clinic to guide
aspiration or injection procedures of joints that are difficult to
access. Although some joints such as the knee are easily accessible
without such guidance, ultrasonography is increasingly being used
to confirm needle placement in other joints, such as bursal or intra-
articular shoulder injections. 29 Ultrasonography is noninvasive,
efficient, radiation free, and cost effective, making it an a ractive
imaging modality for the correct indications. For example,
ultrasonography is very accurate in the evaluation of deep vein
thrombosis, superficial fluid collections or sinus tracts, and
superficial masses such as lipomas. Because of the real-time nature
of the study, the patient can be in motion, and ultrasonography is
excellent for diagnosing dynamic tendon pathology that can be
elicited by the patient during the study, such as snapping hip or
peroneal tendon instability. 30 Rotator cuff tears have been shown to
be accurately diagnosed in clinic with ultrasonography, obviating
the need for MRI 31 (Figure 9). Ultrasonography is highly user
dependent, so inexperienced technicians or clinicians may generate
less reliable results.

Figure 9 Ultrasonographic image of a full-thickness supraspinatus rotator cuff

tear and retraction from the greater tuberosity.
Nuclear Medicine

Physics Behind the Imaging and Advances in

Technology
Nuclear medicine is a functional imaging modality that requires a
radioactive material (radiopharmaceutical agent), which is usually
administered intravenously into a patient. The radiopharmaceutical
agent accumulates in the tissue of interest and emits gamma
radiation. The emi ed radiation is detected by special detectors and
images are displayed on a screen.
Nuclear medicine imaging is performed via either single photon-
emission CT or PET. Single photon-emission CT generally uses
technetium 99m as a tracer, and PET most commonly uses fluorine-
18-fluorodeoxyglucose. PET involves intravenous injection of
fluorine-18-fluorodeoxyglucose, a radionuclide-labeled glucose
analog, which accumulates in tissues with high glucose metabolic
activity. The fluorine-18 radionuclide emits positrons, which upon
contact with electrons triggers positron/electron annihilation, a
process that generates two gamma rays in opposite directions.
These gamma rays are detected by the PET scanner. Areas of
uptake are anatomically mapped by superimposing the images
from the radionuclide detector data onto simultaneously acquired
CT images.

PET Scans
PET activity is measured in Standard Uptake Value units. This can
be used to compare the results from one scan objectively with
another. PET-CT has a very high sensitivity but poor specificity.
High activity generally reflects a metabolic rate associated with a
particular tissue of interest. False-positive results are common and
include any condition that causes increases in the metabolic activity
in specific tissues, ranging from infectious or inflammatory
processes, trauma or fracture, and benign/malignant neoplasms. 32
 PET-CT is most commonly used for metastases or multicentric
neoplasms. It is an expensive study and exposes the patient to a
considerable amount of ionizing radiation because of the nature of
the test. However, its use is indispensable for picking up small sites
of metastasis that may have been missed by standard CT (Figure
10). It is also used by oncologists in determining the response to
treatment in certain entities such as lymphomas or pediatric
sarcomas. 33
 Figure 10 Positron emission tomography scan from a 15-year-old patient with
iliac wing Ewing sarcoma with widespread bony metastasis.

Bone Scan
Bone scintigraphy, or bone scan, is a whole-body imaging modality.
It is an older technology than PET-CT and uses technetium 99m
with methylene diphosphonate delivered intravenously, which
binds to osteoblasts and accumulates at sites of high bone
turnover. A three-phase bone scan consists of an initial scan
immediately after tracer administration to assess dynamic flow
(flow phase), a second scan minutes after that to assess
accumulation in tissues (blood pool phase), and a 2- to 3-hour
delayed scan to assess osseous accumulation of tracer and also soft-
tissue clearance (delayed phase). It is a relatively low-resolution
scan but is able to detect conditions that result in bone turnover
and bone formation, such as bone metastasis, stress fractures, and
inflammation or infection (osteomyelitis). 34 Like PET-CT it can
yield many false-positive results and is always active in benign
processes such as enchondroma and is therefore not indicated or
useful in making that diagnosis. It is also not reliably active in
multiple myeloma, 35 in which a bone survey radiographic series is a
more appropriate screening tool.

Radiation Safety
Because of the widespread and increasing level of fluoroscopy,
portable radiography, and intraoperative CT utilization in
orthopaedic surgery, radiation safety is of paramount importance
not only for the patient but also for the practitioner. Untoward
exposure can increase the risk of cancer and other entities such as
cataracts. The International Commission on Radiological Protection
established dosage limits for radiation exposure. The maximum
annual dose limit is 20 mSv for the body, 150 mSv for the thyroid
and eyes, and 500 mSv for the hands. 36 This belies the importance
of leaded protection in the operating room, especially for the
thyroid and hands, which are often overlooked. A 0.5-mm lead
apron can block up to 95% of radiation, and lead glasses can block
90%. The best protection, however, is distance from the radiation
source, as sca er equals 1/distance2. Therefore, four times farther
away will be one-sixteenth the exposure. Radiation exposure
associated with use of a mini C-arm is controversial. In theory, it
can be greater than normal C-arm because of the proximity to the
source despite lower levels of emi ed radiation, especially for the
hands. For this reason, a surgeon’s hands should be as far as
possible from the source during imaging. Risk to patients is
minimal; however, care should be taken when exposing pregnant
women and children to radiation. Ionizing radiation to a fetus is
generally contraindicated except in critical circumstances. Pediatric
exposure is controversial and should be avoided unless necessary.
From the standpoint of radiation exposure, MRI is safe.
Radiographs are associated with relatively low doses; however, CT
scans can be associated with much higher doses. The risk of the
development of cancer due to radiation exposure is dose-related
and generally low, but difficult to quantify. 37

Summary
Musculoskeletal imaging is a powerful diagnostic tool for the
orthopaedic surgeon. Conventional radiography is the modality of
choice for initial evaluation of most musculoskeletal conditions. CT
can provide greater detail of osseous structures and is used
routinely for preoperative and intraoperative guidance. MRI
provides superior resolution for most musculoskeletal tissues and
is particularly useful for evaluating soft-tissue injuries, spine
pathology, occult fractures, and neoplasms and infections. Contrast
enhancement is most useful in the evaluation of neoplasms and
infections. Ultrasonography is useful for real-time evaluation in the
clinic and can provide information on superficial lesions and
tendon or soft-tissue injuries, as well as guidance for needle
aspiration or injections. Nuclear medicine is an evolving field and is
used usually to evaluate tumors and infections but can also be used
for an increasingly wide range of other conditions. Care must be
taken when using these modalities to adhere to proper indications
and strict safety guidelines for the patient and the practitioner.

Key Study Points

Plain radiography remains the imaging modality of choice for osteoarthritis and
fracture as well as other conditions and should be ordered initially during workup,
especially in a trauma scenario.
CT is useful for imaging complex bony anatomy and pathology and can be used for
preoperative and intraoperative guidance. It is also used for image-guided
interventions.
MRI is best used for soft-tissue pathologies such as tendon, ligament, cartilage,
spine, or neoplastic evaluation. Contrast is useful in infectious or tumor scenarios.
Ultrasonography is inexpensive and noninvasive but prone to user error. It is used for
image-guided joint or soft-tissue aspiration/injections as well as dynamic evaluation
of muscular, tendon, or superficial soft-tissue pathology.
Care must be taken when ordering and also performing these tests because there is
some risk to the patient and the provider.

Annotated References
1. McLoughlin E, Parvin EM, James SL, Botchu R: Recent advances
in imaging and radiology in orthopedics, in Iyer KM, Khan WS,
eds: General Principals of Orthopedics and Trauma. Springer, 2019,
pp 491-525. This text covers recent developments in imaging for
orthopaedic and trauma applications. Level of evidence: V.
2. Stiell IG, McKnight RD, Greenberg GH, et al: Implementation of
the O awa ankle rules. J Am Med Assoc 1994;271(11):827-832.
3. Torne a P III, Kain MS, Creevy WR: Diagnosis of femoral neck
fractures in patients with a femoral shaft fracture. Improvement
with a standard protocol. J Bone Joint Surg Am: 2007;89(1):39-43.
4. Hoffman JR, Mower WR, Wolfson AB, Todd KH, Zucker MI:
Validity of a set of clinical criteria to rule out injury to the cervical
spine in patients with blunt trauma. National Emergency X-
 Radiography Utilization Study Group. N Engl J Med
2000;343(2):94-99. Erratum in: N Engl J Med 2001;344(6):464.
5. Jacobson JA, Girish G, Jiang Y, Resnick D: Radiographic
evaluation of arthritis: Inflammatory conditions. Radiology
2008;248(2):378-389.
6. Collier CD, Nelson GB, Conry KT, Kosmas C, Ge y PJ, Liu RW:
The natural history of benign bone tumors of the extremities in
asymptomatic children: A longitudinal radiographic study. J Bone
Joint Surg Am 2021;103(7):575-580. The authors present an analysis
of 25,000 radiographs of 262 healthy pediatric patients to assess
the natural incidence and history of benign bone tumors. Level of
evidence: IV.
7. Simon MA, Finn HA: Diagnostic strategy for bone and soft-
tissue tumors. J Bone Joint Surg Am 1993;75(4):622-631.
8. Firoozabadi R, Spitler C, Schlepp C, et al: Determining stability
in posterior wall acetabular fractures. J Orthop Trauma
2015;29(10):465-469.
9. Lorente-Ramos R, Azpeitia-Armán J, Muñoz-Hernández A,
García-Gómez JM, Díez-Martínez P, Grande-Bárez M: Dual-
energy X-ray absorptiometry in the diagnosis of osteoporosis: a
practical guide. Am J Roentgenol 2011;196(4):897-904.
10. Zbijewski WB: CT in musculoskeletal applications. in Samei E,
Pelc N, eds: Computed Tomography. Springer, 2020, pp 397-410.
This textbook chapter reviews musculoskeletal applications of
CT, in particular the recently introduced extremity cone-beam CT
with capability for weight-bearing imaging. Level of evidence: V.
11. Mallinson PI, Coupal TM, McLaughlin PD, Nicolaou S, Munk
PL, Ouelle e HA: Dual-energy CT for the musculoskeletal
system. Radiology 2016;281(3):690-707.
12. Katsura M, Sato J, Akahane M, Kunimatsu A, Abe O: Current
and novel techniques for metal artifact reduction at CT: Practical
guide for radiologists. RadioGraphics 2018;38(2):450-461.
13. Keiler A, Riechelmann F, Thöni M, Brunner A, Ulmar B: Three-
dimensional computed tomography reconstruction improves the
 reliability of tibial pilon fracture classification and preoperative
surgical planning. Arch Orthop Trauma Surg 2020;140(2):187-195.
Multiple observers reviewed conventional two-dimensional CT as
well as three-dimensional reconstructions of 35 patients and
classified fractures and formulated preoperative plan, reliability
of classifications, and plans improved with three-dimensional
reconstruction. Level of evidence: IV.
14. Kumar V, Baburaj V, Patel S, Sharma S, Vaishya R: Does the use
of intraoperative CT scan improve outcomes in orthopaedic
surgery? A systematic review and meta-analysis of 871 cases. J
Clin Orthop Trauma 2021;18:216-223. A meta-analysis of 31 studies
reviewing whether intraoperative CT scan affects implant
placement is presented. Implant placement was statistically
improved and surgical time was unaffected with intraoperative
CT scan. Level of evidence: III.
15. Rougraff BT, Kneisl JS, Simon MA: Skeletal metastases of
unknown origin. A prospective study of a diagnostic strategy. J
Bone Joint Surg Am 1993;75(9):1276-1281.
16. Patel DM, Weinberg BD, Hoch MJ: CT myelography: Clinical
indications and imaging findings. Radiographics 2020;40(2):470-
484. The authors review common and uncommon indications for
CT myelography and various pathologic conditions in which CT
myelography plays a vital role in patient treatment in the modern
era of MRI. Level of evidence: V.
17. Rosenthal DI, Hornicek FJ, Wolfe MW, Jennings LC, Gebhardt
MC, Mankin HJ: Percutaneous radiofrequency coagulation of
osteoid osteoma compared with operative treatment. J Bone Joint
Surg Am 1998;80(6):815-821.
18. Lindquester WS, Crowley J, Hawkins CM: Percutaneous thermal
ablation for treatment of osteoid osteoma: A systematic review
and analysis. Skeletal Radiol 2020;49(9):1403-1411. A meta-analysis
of 36 studies analyzing the success rate of radiofrequency
ablation and cryoablation and comparing the two techniques is
presented. An overall 92% success rate and no difference
 between radiofrequency ablation and cryoablation was reported,
with cryoablation having fewer side effects. Level of evidence: III.
19. Rose PS, Morris JM: Cryosurgery/cryoablation in
musculoskeletal neoplasms: History and state of the art. Curr Rev
Musculoskelet Med 2015;8(4):353-360.
20. Zheng K, Makrogiannis S: Bone texture characterization for
osteoporosis diagnosis using digital radiography. Annu Int Conf
IEEE Eng Med Biol Soc 2016;2016:1034-1037.
21. Makrogiannis S, Boukari F, Ferrucci L: Automated skeletal
tissue quantification in the lower leg using peripheral
quantitative computed tomography. Physiol Meas
2018;39(3):035011.
22. Pooley RA: AAPM/RSNA physics tutorial for residents:
Fundamental physics of MR imaging. RadioGraphics 2005;25:1087-
1099.
23. Talbot BS, Weinburg EP: MR imaging with metal-suppression
sequences for evaluation of total joint arthroplasty. RadioGraphics
2016;36:209-225.
24. Jinkins JR, Runge VM: The use of MR contrast agents in the
evaluation of disease of the spine. Top Magn Reson Imaging
1995;7(3):168-180.
25. Naraghi A, White LM: MRI of labral and chondral lesions of the
hip. AJR Am J Roentgenol 2015;205(3):479-490.
26. Wilson MP, Nobbee D, Murad MH, et al: Diagnostic accuracy of
limited MRI protocols for detecting radiographically occult hip
fractures: A systematic review and meta-analysis. AJR Am J
Roentgenol 2020;215(3):559-567. A systemic review and meta-
analysis of MRI use for hip fractures is presented. Mean scanning
time was 5 minutes, and a protocol of coronal T1-weighted and
short tau inversion recovery sequences is 100% sensitive. Level of
evidence: III.
27. Balach T, Stacy GS, Peabody TD: The clinical evaluation of bone
tumors. Radiol Clin North Am 2011;49(6):1079-1093.
28. Balach T, Stacy GS, Haydon RC: The clinical evaluation of soft
tissue tumors. Radiol Clin North Am 2011;49(6):1185-1196.
29. Aly AR, Rajasekaran S, Ashworth N: Ultrasound-guided
shoulder girdle injections are more accurate and more effective
than landmark-guided injections: A systematic review and meta-
analysis. Br J Sports Med 2015;49(16):1042-1049.
30. Grant TH, Kelikian AS, Jereb SE, McCarthy RJ: Ultrasound
diagnosis of peroneal tendon tears. A surgical correlation. J Bone
Joint Surg Am 2005;87(8):1788-1794.
31. Ianno i JP, Ciccone J, Buss DD, et al: Accuracy of office-based
ultrasonography of the shoulder for the diagnosis of rotator cuff
tears. J Bone Joint Surg Am 2005;87(6):1305-1311.
32. Rosenbaum SJ, Lind T, Antoch G, Bockisch A: False-positive
FDG PET uptake – the role of PET/CT. Eur Radiol 2006;16(5):1054-
1065.
33. Harrison DJ, Parisi MT, Shulkin BL: The role of 18F-FDG-PET/CT
in pediatric sarcoma. Semin Nucl Med 2017;47(3):229-241.
34. Van der Wall H, Fogelman I: Scintigraphy of benign bone
disease. Semin Musculoskelet Radiol 2007;11(4):281-300.
35. Bataille R, Chevalier J, Rossi M, Sany J: Bone scintigraphy in
plasma-cell myeloma. A prospective study of 70 patients.
Radiology 1982;145(3):801-804.
36. ICRP. 1990 Recommendations of the International Commission
on Radiological Protection. Publication 60. Ann ICRP 1991;21(1-
3):1-201.
37. Brenner DJ, Doll R, Goodhead DT, et al: Cancer risks
a ributable to low doses of ionizing radiation: Assessing what
we really know. Proc Natl Acad Sci USA 2003;100:13761-13766.
C H AP T E R 1 0

Patient Optimization
Frank Johannes Plate MD, PhD, Andrew M. Schwartz MD,
Thorsten M. Seyler MD, PhD, FAAOS

Dr. Plate or an immediate family member serves as a paid consultant to or is an employee of

Smith & Nephew and Total Joint Orthopedics; has stock or stock options held in Eventum
Orthopaedics; and has received research or institutional support from Biocomposites Inc. Dr.
Seyler or an immediate family member has received royalties from Pattern Health, Restor3d, and
Total Joint Orthopedics, Inc.; serves as a paid consultant to or is an employee of Smith &
Nephew and Total Joint Orthopedics, Inc.; has received research or institutional support from
Next Science and Zimmer; and serves as a board member, owner, officer, or committee member of
American Association of Hip and Knee Surgeons and Musculoskeletal Infection Society. Neither
Dr. Schwartz nor any immediate family member has received anything of value from or has stock
or stock options held in a commercial company or institution related directly or indirectly to the
subject of this chapter.

ABSTRACT
Patients presenting for orthopaedic procedures may have
underlying comorbidities or medical conditions that expose them
to an increased risk for intraoperative or postoperative surgical or
medical complications. Comprehensive evaluation and preoperative
optimization of patient comorbidities before any planned or
unplanned surgical procedure may alleviate perioperative risk and
subsequent resource utilization. A thorough understanding of how
medical comorbidities can influence perioperative management is
needed for an orthopaedic surgeon to provide optimal patient care
throughout the episode of care. Further evaluation and consultation
of medical specialists may be necessary when patient comorbidities
are identified properly.
Keywords: comorbidities; medical optimization; perioperative
management; preoperative clearance; risk factors

Introduction
Optimizing treatment strategies for patient comorbidities has been
shown to decrease the surgical risk for orthopaedic patients.
Specifically, for planned elective cases, appropriate perioperative
management of medical conditions that may mitigate surgical risk
needs to be implemented. In the era of value-based care, the
mitigation of surgical risk through collaboration with anesthesia
providers in a perioperative surgical home or with medicine
providers to establish surgical clearance will provide improved
patient care with the aim of decreasing postoperative resource
utilization. It is important to discuss common patient medical
conditions and comorbidities and how these influence surgical risk
and propose treatment strategies to modify these risk factors.

Modifiable Risk Factors

Modifiable risk factors are medical conditions or patient behaviors
that influence the risk of perioperative complications of an
orthopaedic procedure. Although some patient characteristics are
inherent and cannot be changed (eg, age, end-organ damage),
others are modifiable and can be changed through medical
optimization (eg, diabetes control, hypertension management) or
cessation of patient behavior (eg, smoking, alcohol). Therefore,
modifiable risk factors can positively or negatively influence the
outcomes of a surgical procedure, and their optimization needs to
be a empted to decrease perioperative risk for the patient.

Obesity

Classification
Obesity has been classified by the World Health Organization into
five body mass index (BMI) categories: less than 25 kg/m2, normal
weight; 25 to 29.9 kg/m2, preobesity; 30 to 34.9 kg/m2, obesity class I;
35 to 39.9 kg/m2, obesity class II; and greater than or equal to 40
kg/m2, obesity class III. For further risk stratification, class III
obesity can be further categorized into severe obesity BMI greater
than or equal to 35 kg/m2, morbid obesity BMI greater than or equal
to 40 kg/m2, and extreme obesity greater than or equal to 50 kg/m2.
The utilization of BMI for risk stratification for total joint
arthroplasty remains disputed, with authors proposing body fat
percentage as a more accurate predictor of perioperative
complications. 1

Pathophysiology
Obesity increases the risk of complications throughout the
perioperative episode of care. Patients with obesity have a high
prevalence of obstructive sleep apnea, decreased lung volumes with
atelectasis, and hypercapnic syndrome leading to an increased risk
of respiratory complications intraoperatively and postoperatively.
In patients with obesity, regional blocks are more difficult to place,
leading to a higher rate of block failure. 2 There is a higher risk for
postoperative deep vein thrombosis and pulmonary embolism in
these patients. Accumulation of mitochondrial oxidative stress
affecting the immune system, vascular insufficiency, and nutritional
deficiencies increase the risk for wound-healing complications such
as delayed wound healing, prolonged drainage, and superficial and
deep surgical site infection.

Metabolic Syndrome
Metabolic syndrome is closely related to obesity and affects
approximately 40% of individuals in the United States. 3 Metabolic
syndrome is characterized by increased waist circumference,
hypertension, dyslipidemia, and elevated fasting glucose levels.
Benefits of BMI Optimization
Increased BMI is associated with inferior postarthroplasty
outcomes in all domains. Furthermore, there is a sharp inflection
point for perioperative surgical and medical risk in patients whose
BMI exceeds 40 kg/m2, and this defines the point at which risk may
outweigh benefit. 4 Of similar concern, the average improvement in
joint function conferred by joint arthroplasty is stunted in patients
who have BMI greater than 40 kg/m2. Thus, although it is
understandably difficult for patients with morbid obesity to lose
weight, it is highly advisable for these patients to put forth an
exhaustive effort to lose weight, especially those with BMI in excess
of 40 kg/m2.

Diabetes

Pathophysiology
Type 1 diabetes mellitus is caused by autoimmune destruction of β
cells and resulting lack of insulin production. Type 2 diabetes
mellitus is characterized by decreased insulin secretion from β cells
in the pancreas and impaired response of insulin-sensitive tissues
in the periphery, leading to glucose dyshomeostasis. 3
Approximately 90% of individuals with diabetes mellitus have type
2; these patients present with obesity and high body fat percentage.
Decreased insulin production from β cells in combination with
peripheral insulin resistance caused by inflammatory processes in
adipose tissue leads to a disruption of the physiologic feedback
loop between insulin action and insulin secretion, resulting in
abnormally high blood glucose levels.
The stress response from surgery in conjunction with
perioperative fasting leads to increased adrenaline, noradrenaline,
cortisol, glucagon, and growth hormone release, leading to an
increase in glucose levels and insulin resistance.
 Diabetes and associated perioperative hyperglycemia lead to
impaired leukocyte function, resulting in increased risk for surgical
site infection following surgery. 5

Serologic Studies
Quantifying Disease Severity
Poor preoperative and perioperative glycemic control is associated
with increased risk of postoperative complications. 6 More than 30%
of patients undergoing total joint arthroplasty were found to have
undiagnosed diabetes mellitus. 7 Guidelines from the American
Diabetes Association recommend preoperative evaluation of
hemoglobin A1C (HbA1C) as an indirect measure of the average
patient blood glucose level over the past 3 months of the life cycle
of erythrocytes. 6 , 8 Patients with HbA1C between 5.7% and 6.4%
are classified as having prediabetes and HbA1C ≥ 6.5% is
considered diabetes. Uncontrolled diabetes is considered with
HbA1C greater than 7%. Although a threshold of HbA1C of greater
than 7.5% or 7% has been generally used as an indication for
further preoperative optimization of glycemic control, the
predictive value of HbA1C levels for postoperative complications
was found to be equivocal after total joint arthroplasty. 6
Serum fructosamine measures the level of glycated serum
proteins, mostly albumin over the prior 2 to 3 weeks based on
serum protein turnover. 6 A serum fructosamine level greater than
293 µmol/L was found to be more predictive of postoperative
infection, readmission, and revision surgery following total joint
arthroplasty than HbA1C. 9

Basis for Correction

Patients with diabetes are at greater risk for perioperative
morbidity and mortality, including surgical site infection, urinary
tract infection, myocardial infarction, blood transfusion, revision
surgery, and increased length of hospital stay after total ankle
arthroplasty or ankle fusion. 10 Patients with HbA1C level greater
than 7% had a significantly higher risk of surgical site infection
after spinal fusions. 11 Similarly, patients with elevated
fructosamine levels who underwent total knee arthroplasty had a
greater risk for prosthetic joint infection, readmission, and revision
surgery. 9 Preoperative optimization of glucose control with a goal
of HbA1C below 7% and fructosamine level below 293 µmol/L is
recommended to decrease postoperative patient morbidity and
resource utilization.

Malnutrition
Malnutrition describes the excess of nutrition as observed in
elevated BMI and metabolic syndrome as well as nutritional
deficiency. Malnutrition most commonly describes nutritional
deficiency. Several measures of malnutrition have been used,
including serologic markers, anthropometric measurements, and
nutrition scoring tools.
Serologic markers are most commonly used in orthopaedic
surgery to assess nutritional status. A total serum lymphocyte
count less than 1,500 cells/mm3 is indicative of nutritional
deficiency resulting in immunocompromise associated with an
increased risk for postoperative infection. A serum albumin
concentration less than 3.5 g/dL reveals chronic malnutrition (half-
life of approximately 3 weeks). Alternatively, prealbumin levels
indicate acute changes in protein levels with a half-life of
approximately 2 days. Serum prealbumin levels between 11 and 19
mg/dL indicate mild, 7 and 10 mg/dL moderate, and less than 7
mg/dL severe hypoproteinemia. 12 Protein depletion has been
associated with impaired wound healing and surgical site infections
following spine surgery and joint arthroplasty. 12 In addition, serum
transferrin levels less than 200 mg/dL and serum zinc levels less
than 95 µg/dL are signs of malnutrition and associated with delayed
wound healing. 13 , 14
 Anthropometric measurements of anatomic body areas assess
physical signs of decreases in body fat and skeletal muscle.
Changes in body composition are a marker of severe chronic
malnourishment, including calf circumference less than 31 cm, arm
circumference less than 22 cm, and a decreased triceps skinfold
thickness. 13 However, anthropometric changes appear late and thus
are unable to detect marginal malnutrition in a perioperative
se ing. 13
Several nutritional screening tools have been devised to identify
patient malnutrition. The Rainey-MacDonald nutritional index is a
formula based on serum albumin and transferrin level, and a low
preoperative score predicted delayed wound healing in patients
who underwent surgical fixation or hemiarthroplasty for femoral
neck and intertrochanteric hip fractures. 15 The Mini Nutritional
Assessment includes dietary questions, anthropometric measures,
and other variables for assessment in the geriatric population. 13
When compared with other tools such as the Malnutrition
Screening Tool and the Nutrition Risk Screening 2002, the Mini
Nutritional Assessment similarly predicted postoperative
morbidity and mortality following surgical fixation or arthroplasty
for geriatric hip fractures. 16 The Perioperative Nutrition Screen
specifically assesses preoperative nutritional status of ambulatory
patients and includes serum albumin, BMI, dietary intake, and
weight changes intended to improve patient nutrition before
orthopaedic surgical interventions. 17

Vitamin D Deficiency

Importance
Vitamin D deficiency is a common problem among adult and
pediatric orthopaedic patients in foot and ankle surgery, trauma,
joint arthroplasty, and spine surgery. 18 Estimates suggest a
worldwide vitamin D deficiency rate of one billion. 19 Vitamin D is
obtained from ultraviolet light exposure, diet, and dietary
supplements. The active form of vitamin D, 1,25-dihydroxy vitamin
D increases calcium absorption in the small intestine and promotes
receptor activator of nuclear factor kappa B ligand expression in
osteoblasts, leading to osteoclast activation and bone
mineralization and turnover. Vitamin D acts on skeletal muscle,
and deficiency has been shown to be a cause of muscle weakness
and increased frequency of falls. 20 Vitamin D also is an
immunomodulator that activates monocytes and macrophages and
may be implicated in a patient’s postoperative inflammatory
response. 21
Based on the recommendation by the Endocrine Society, vitamin
D insufficiency is defined as serum 1,25-dihydroxy vitamin D levels
below 30 ng/mL and deficiency below 20 ng/mL. A 2020 systematic
review of 12 studies assessing vitamin D levels in patients before
total hip arthroplasty and total knee arthroplasty reported a pooled
vitamin D insufficiency of 53.4% and pooled vitamin D deficiency
rate of 39.4%. 20
Patients with vitamin D deficiency who underwent total hip
arthroplasty were found to have decreased postoperative functional
scores at short-term follow-up. 22 Following revision total hip
arthroplasty and total knee arthroplasty, patients had a higher risk
for postoperative infection and complications within 90 days from
surgery. 23

Treatment
Sunlight exposure between 5 and 30 minutes, two to three times
weekly is recommended. There are several dietary sources of
vitamin D, such as oil-rich fish, red meat, egg yolk, cow’s milk, and
fortified foods. Vitamin D supplementation is available as vitamin
D2 (ergocalciferol) and vitamin D3 (cholecalciferol), which is more
effective as a supplement. For adult patients with vitamin D
deficiency, 1,500 to 2,000 IU daily is recommended. Because of the
high prevalence of vitamin D insufficiency and deficiency in the
orthopaedic patient population, universal screening versus
prophylactic vitamin D supplementation due to low cost and
minimal adverse effects remains debated. However, vitamin D
supplementation may be a cost-effective way to potentially decrease
readmissions and associated increase in resource utilization and
health care costs.

Smoking

Pathophysiology
Despite declining rates of cigare e smoking in the United States,
20.8% of adults reported using tobacco products (4.5% electronic
cigare es) in 2019. 24 Smoking causes atherosclerosis with
associated hypotension, chronic obstructive pulmonary disease,
and malignancies, increasing overall mortality in smokers. 25
Tobacco smoke contains reactive oxygen species, carbon monoxide,
and nicotine. Oxidative stress from smoking with release of free
radicals leads to protein and DNA damage, cell apoptosis, and
necrosis with impediment of reparative processes within cells. 25
Carbon monoxide binds to hemoglobin with 200 times greater
affinity than oxygen, causing a decreased oxygen-carrying capacity
of blood to the periphery with resulting tissue hypoxemia. 25
Nicotine causes vasoconstriction by inhibiting nitric oxide synthase
and thereby decreasing endothelium-mediated vasodilation, which
is further increased through nicotine-induced catecholamine
release. Nicotine induces thromboxane A2 generation in platelets,
causing vasoconstriction with increased vascular resistance and
platelet aggregation and increasing the risk of thrombosis.
Smoking suppresses the immune system, leading to increased risk
for postoperative infection. In combination, the effects of nicotine
lead to decreased local blood flow and tissue perfusion with a
suppressed immune response, increasing the risk for wound-
healing complications and postoperative infection. Respiratory
effects of tobacco use lead to an increased risk for pulmonary
complications and increased length of hospital stay with greater
resource utilization in the perioperative period.
The influence of nicotine on bone healing remains debated.
Although some authors have found decreased fracture healing and
osteointegration of titanium implants with decreased production of
bone morphogenetic proteins in animal models, 26 others reported a
possible dose-dependent effect of nicotine on posterior spinal
fusion mass in a rabbit model. 27

Basis for Cessation

The effects of nicotine use on complications following orthopaedic
surgical procedures have been studied extensively. A study of
78,191 patients in the American College of Surgeons National
Surgical Quality Improvement Program database who underwent
total hip and knee arthroplasties found that current smokers
(10.3%) had an increased risk of wound-healing complications. 28
Smokers were also found to have a significantly lower overall
survivorship of total hip and knee arthroplasties with an increased
risk for postoperative medical complications. 29 Following reverse
total shoulder arthroplasty, smokers were at greater risk for
revision, secondary surgeries, and postoperative complications. 30
Smoking has been shown to significantly increase the rate of
nonunion following posterior lumbar fusion from 14.2% in
nonsmokers to 26.5% in smokers. 31 In an analysis of 137,537
patients without obesity admi ed for treatment of spinal disease
including fracture, curvature, and others, smokers were found to
have increased postoperative complications, rates of intensive care
unit admission, readmission, and greater overall hospital costs. 32

Smoking Cessation Strategies

A number of interventions are available to aid patients in
overcoming nicotine addiction, including formalized counseling,
pharmacologic aids such as varenicline or bupropion, or nicotine
replacement for weaning purposes such as patches or gum. All
methods have been deemed cost effective in the joint arthroplasty
se ing and should be part of a dedicated multimodal approach to
cessation. 33

Objective Metrics of Cessation

Smoking abstinence can be tested via serum cotinine levels or
carbon monoxide breathalyzer testing. Cotinine is the main
metabolite of nicotine with a half-life of approximately 20 hours,
allowing for a quantitative assessment of nicotine use. Serum
cotinine levels >8 ng/mL indicate active nicotine use, 3 to 8 ng/mL
secondhand tobacco exposure, and levels less than 3 ng/mL are
expected in nonsmokers. However, serum cotinine levels can be
affected by nicotine replacement therapy such as nicotine gums,
transdermal patches, nasal sprays, or inhalers.
Anabasine is a minor tobacco alkaloid that is present in tobacco
products but absent in nicotine replacement therapy products.
Urine anabasine concentrations >2 ng/mL indicate active tobacco
use.
Carbon monoxide concentration in exhaled breath can be used to
assess smoking status with a breathalyzer test in the office. Carbon
monoxide is a product of cigare e smoke and eliminated through
respiration. Active smoking is indicated when greater than 6 parts
per million carbon monoxide are present in exhaled breath. Carbon
monoxide is specific to combustible tobacco products and unable to
assess other forms of tobacco use such as chewing tobacco or
electronic cigare es.

Alcohol and Drug Abuse

Pathophysiology
Chronic alcohol use, abuse, and dependence are widespread and
can negatively affect the result of orthopaedic procedures, leading
to an increased risk of postoperative complications, longer length
of hospital stay, and greater resource utilization. Alcohol use
disorder affects cognitive function leading to anxiety, inability to
follow postoperative instructions, and depression, which is
associated with suboptimal outcomes following joint arthroplasty.
34
Chronic alcohol use may cause acute hepatitis, hepatic steatosis
(fa y liver), and end-stage liver cirrhosis, which leads to decreased
production of proteins of the immune system with overall systemic
immunosuppression and the creation of a proinflammatory state.
Neurologic effects include alcoholic peripheral neuropathy,
decreased coordination from cerebellar atrophy, cerebral atrophy,
and dementia. 34
Alcohol impairs osteoblast activity, leading to bone
demineralization and osteopenia and increasing the risk of
perioperative fracture. 35 Decreased cytokine production in the liver
impairs wound healing, increasing the risk for wound-healing
problems and postoperative infection. 34 Thrombocytopenia poses
an increased risk for intraoperative bleeding. Furthermore, alcohol
withdrawal postoperatively can cause delirium tremens with the
possible need for admission to the intensive care unit, longer
length of hospital stay, and greater resource utilization.
Intravenous drug use increases the risk of postoperative infection
through blood-borne pathogens including bacterial infection,
hepatitis C, HIV, as well as inability to follow postoperative
instructions and impaired postoperative pain control leading to
relapse of drug use. Patients with active intravenous drug use who
underwent total knee arthroplasty had a higher risk of major
complications leading to transfemoral amputation. 36

Ambulatory Screening
In addition to a detailed medical history, a social history should
include quantity, frequency, and type of alcohol consumption;
history of blackouts; previous treatment strategies for alcohol use
disorder; use of other substances in conjunction with alcohol; and
family history of alcohol use. 34 Heavy alcohol use is defined by the
National Institutes of Health as more than 4 drinks on any day or
more than 14 drinks per week in men and greater than 3 drinks on
any day or more than 7 drinks per week in women.
The CAGE (cu ing down, annoyance by criticism, feeling of guilt,
need for eye-openers) and abbreviated Alcohol Use Disorders
Identification Test are validated clinical tools to identify alcohol-
related disorders preoperatively. 34
Blood serum markers indicating chronic alcohol use include
elevated gamma-glutamyl transferase greater than 35 U,
transaminitis (elevated aspartate transaminase and alanine
aminotransferase in 2:1 ratio), serum uric acid >416 mol/L,
thrombocytopenia, and leukopenia. 34

Therapies
A comprehensive treatment program for patients with alcohol use
disorder includes behavioral and group therapy and appropriate
supplementation of vitamin D and vitamin B complex (ie, B1, B2,
B12). As an adjunct to behavioral therapy, several pharmacologic
agents (eg, naltrexone, acamprosate, disulfiram, selective serotonin
reuptake inhibitors, topiramate, and ondansetron) are available. 37

Psychiatric Disease

Pathophysiology
Preoperative depression and anxiety negatively affect outcomes and
resource utilization following several orthopaedic procedures
including total joint arthroplasty, spine surgery, and sports
medicine procedures. 38 According to a 2020 study, up to 25% of
patients undergoing total joint arthroplasty have a preoperative
diagnosis of depression. 39 Patients with depression have increased
postoperative opioid consumption, postoperative complications,
significantly higher rates of 30-day and 90-day readmissions, and
lower patient-reported outcome scores. 38 , 39 Pain catastrophizing
seen in patients with depression is an exaggerated or inappropriate
response to pain, which can lead to increased postoperative pain
and opioid consumption.
Anxiety and patient’s pain-related fear of motion (kinesiophobia)
was associated with decreased active and passive knee range of
motion following total knee arthroplasty. 40

Ambulatory Screening
There are several types of depression, which can vary in features
and significance. The revised Diagnostic and Statistical Manual of
Mental Disorders, Fifth Edition (DSM-5) is used for diagnosis and
includes several criteria (eg, depressed mood, loss of interest, sleep
disturbance, impaired concentration, thoughts of death). Although
orthopaedic patients may not present with a current diagnosed
major depressive episode or previous use of antidepressant
medication, they may reveal certain features that can be evaluated
by screening questionnaires. The Short-Form 12 Health Survey is a
commonly used generic quality-of-life measure in orthopaedic
surgery. The mental component summary of Short-Form 12 Health
Survey is a validated screening tool for active and recent depressive
disorders. The Patient-Reported Outcomes Measurement
Information System includes computerized adaptive testing for
anxiety and depression assessment that can be used for screening
orthopaedic patients. The Pain Catastrophizing Scale is a 13-item
self-reported test about previous painful experiences and
associated catastrophic thinking related to pain.

Therapies
Cognitive behavioral therapy and multimodal pain therapy for
patients with pain catastrophizing has been the mainstay of
treatment with improved knee function at 6 months after total knee
arthroplasty as discussed in a 2021 study. 41 Patient education and
cognitive behavioral therapy for patients with kinesiophobia
revealed significant improvements in patient-reported outcomes,
postoperative pain, and knee function after total knee arthroplasty.
41
The effect of preoperative medical treatment of depression on
postoperative outcomes after total joint arthroplasty remains
debated. Patients with diagnosis of depression revealed similar
patient-reported outcomes following total joint arthroplasty
whether they had received medical treatment for depression or not.
39

Rheumatologic Disease Considerations

Pathophysiology
Rheumatoid arthritis is a chronic inflammatory disease of the
synovium that can lead to significant joint deterioration and
disability. Patients are also predisposed to cardiovascular disease,
interstitial lung disease, immunocompromise increasing the risk
for postoperative infection, and venous thromboembolism
associated with patients’ hypercoagulable state.

Perioperative Management of Medications

Disease-modifying antirheumatic drugs slow the progression of
rheumatoid arthritis while leading to further overall
immunocompromise. Although certain disease-modifying
antirheumatic drugs may be continued, others may need to be
stopped in the perioperative period. 42 Medications such as
methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, and
doxycycline may be continued through surgery. Biologic agents
such as tumor necrosis factor alpha inhibitors can lead to wound-
healing complications and postoperative infection and are stopped
before surgery. These drugs have dosing intervals of several weeks
and surgery is performed during the drug interval holiday 42 (Table
1).

Table 1
Recommendations for the Perioperative Management of
Disease-Modifying Antirheumatic Agents From the Joint
Statement by American College of Rheumatology and American
Association of Hip and Knee Surgeons

DMARDs: CONTINUE these medications through Dosing Continue/Withhold

surgery. Interval
Methotrexate Weekly Continue
Sulfasalazine Once or Continue
twice
daily
Hydroxychloroquine Once or Continue
twice
daily
Leflunomide (Arava) Daily Continue
Doxycycline Daily Continue
BIOLOGIC AGENTS: STOP these medications before Dosing Schedule Surgery
surgery and schedule surgery at the end of the Interval (relative to last
dosing cycle. RESUME medications at minimum 14 biologic agent
days after surgery in the absence of wound-healing dose
problems, surgical site infection, or systemic administered)
infection. during
Adalimumab (Humira) Weekly Week 2 or 3
or every
2 weeks
Etanercept (Enbrel) Weekly Week 2
or twice
weekly
Golimumab (Simponi) Every 4 Week 5
weeks Week 9
(SQ) or
every 8
weeks
(IV)
Infliximab (Remicade) Every 4, Week 5, 7, or 9
6, or 8
weeks
Abatacept (Orencia) Monthly Week 5
(IV) or Week 2
weekly
(SQ)
Certolizumab (Cimzia) Every 2 Week 3 or 5
or 4
weeks
Rituximab (Rituxan) 2 doses Month 7
2 weeks
apart
every 4-
6
months
Tocilizumab (Actemra) Every Week 2
week Week 5
(SQ) or
every 4
weeks
(IV)
Anakinra (Kineret) Daily Day 2
Secukinumab (Cosentyx) Every 4 Week 5
weeks
Ustekinumab (Stelara) Every Week 13
12
weeks
Belimumab (Benlysta) Every 4 Week 5
weeks
Tofacitinib (Xeljanz): STOP this medication 7 days before Daily or 7 days after last
surgery. twice dose
daily
SEVERE SLE-specific medications: CONTINUE these Dosing Continue/Withhold
medications in the perioperative period. Interval
Mycophenolate mofetil Twice Continue
daily
Azathioprine Daily or Continue
twice
daily
Cyclosporine Twice Continue
daily
Tacrolimus Twice Continue
daily (IV
and
PO)
NOT-SEVERE SLE: DISCONTINUE these medications Dosing Continue/Withhold
1 week before surgery. Interval
Mycophenolate mofetil Twice Withhold
daily
 Azathioprine Daily or Withhold
twice
daily
Cyclosporine Twice Withhold
daily
Tacrolimus Twice Withhold
daily (IV
and
PO)
DMARDs = disease-modifying antirheumatic drugs, IV = intravenous, PO = by mouth, SLE =
systemic lupus erythematosus, SQ = subcutaneous
From Goodman SM, Springer B, Guyatt G, et al: 2017 American College of
Rheumatology/American Association of Hip and Knee Surgeons guideline for the
perioperative management of antirheumatic medication in patients with rheumatic diseases
undergoing elective total hip or total knee arthroplasty. J Arthroplasty 2017;32(9):2628-2638,
with permission from Elsevier.

Vascular Disease

Physical Examination
Peripheral vascular disease (PVD) is a common systemic disorder
caused by arteriosclerosis with plaque formation leading to
claudication. PVD has a prevalence of 17% to 20%, and although
patients undergoing orthopaedic surgery may be asymptomatic,
there is an increased risk of wound-healing complications, vascular
injury, or venous thromboembolism. PVD can by diagnosed by
asymmetric or absent pedal pulses and by an ankle-brachial index
less than 0.9. Toe systolic pressures greater than 30 mm Hg
represent hypoperfusion with high risk of wound-healing
complications in the se ing of diabetic foot ulcers.
Chronic ischemia and associated peripheral tissue hypoperfusion
increase the risk for postoperative wound-healing complication and
deep infection following total ankle and knee arthroplasties, ankle
fracture open reduction and internal fixation, and in the se ing of
diabetic foot ulcers. 43 Although the incidence of vascular
complications following total knee arthroplasty is low (0.2%),
ischemic complications can cause compartment syndrome with an
amputation rate up 22%. 43 Ischemia may result from an arterial
occlusion from preexisting arterial plaques or more commonly
blunt pressure from retractors exacerbating chronic limb ischemia.
43

Arterial calcifications can occur in the tunica intima with the

presence of intravascular plaques or the tunica media without
restrictions in peripheral blood flow. The use of a tourniquet in
patients with intimal calcifications in the femoral artery on
radiographs remains debated: it may cause arteriosclerotic plaques
to become dislodged or the tunica intima may be stretched and
injured leading to peripheral arterial occlusion, whereas medial
calcifications may lead to tourniquet failure. 43

Treatment Algorithm
Revascularization procedures as part of limb salvage for the
treatment of diabetic foot ulcers is recommended when severe
arterial disease is present (ankle-brachial index <0.5, toe systolic
pressures <30 mm Hg).
Recommendations for revascularization before total knee
arthroplasty are sparse. Patients with moderate PVD (ankle-
brachial index 0.5 to 0.8) may undergo total knee arthroplasty with
close postoperative observation of vascular perfusion. 43 Patients
with an ankle-brachial index less than 0.5 should be evaluated for
possible revascularization procedures before total knee
arthroplasty. For patients who had previous arterial bypass and are
candidates for total knee arthroplasty, preoperative evaluation of
the graft with ultrasonography is recommended. 43 If stenosis is
present, an arterial angiogram is performed and vascular
consultation sought before total knee arthroplasty. 43

Renal Disease

Pathophysiology
Patients with chronic kidney disease (CKD) or end-stage renal
disease are at increased risk for postoperative complications,
cardiovascular accidents, worsening kidney function, and infection.
CKD is defined by a glomerular filtration rate less than 60 mL/1.73
m2 and albuminuria greater than 30 mg in 24 hours. Progression of
CKD leads to end-stage renal disease defined as a glomerular
filtration rate less than 15 mL/1.73 m2.
The kidney is a vital part of hematopoietic system and CKD can
lead to decreased erythropoietin production and resultant anemia.
44
Approximately 18% of patients with CKD stage 3 (glomerular
filtration rate 30 to 59 mL/1.73 m2) and 60% of patients with CKD 4
to 5 (<30 mL/1.73 m2) have anemia (<12.0 g/dL in women and <13.0
g/dL in men).

Effect of Hemodialysis
One study noted that there is a positive disease severity–surgical
risk relationship for patients with CKD undergoing total joint
arthroplasty. 45 The end-stage renal disease cohort on hemodialysis
represented a greater risk than patients with lower stage CKD,
most notably for infection. Additional data from a 2020 study
suggest deferring joint arthroplasty until impending renal
transplant offers a more favorable risk profile than proceeding
before transplant. 46 Patients on dialysis with no forthcoming plans
for kidney transplant should be approached with caution and
optimized extensively for all other medical conditions before
considering the patient a safe candidate for joint arthroplasty.

Consultation
Consultation with the patient’s primary nephrologist is ideal to
inquire about opportunities to optimize present renal function,
potential medications or dosages to avoid in the perioperative
period, dietary restrictions, and timing considerations in patients
who receive routine CKD therapy such as erythropoietin treatment
or hemodialysis.

Hepatitis C

Therapies
In a 2019 meta-analysis, patients with coexisting chronic hepatitis C
undergoing total joint arthroplasty were at increased risk of both
septic and aseptic causes of revision with more perioperative
medical complications. 47 Traditionally, this was viewed as a
nonmodifiable risk factor until the 2014 FDA approval of reliably
curative combination therapy with sofosbuvir and ledipasvir.

Temporal Considerations
The typical treatment duration for hepatitis C virus is
approximately 12 weeks, and given the high rates of therapeutic
success and elective nature of total joint arthroplasty, the risks of
hepatitis C on total joint arthroplasty should be mitigated by
exhausting modern therapeutic antiviral treatment before engaging
in this elective procedure.

Human Immunodeficiency Virus

Modern Treatment
Patients with HIV once had an alarmingly poor prognosis and were
rarely, if ever, considered candidates for total joint arthroplasty.
With the development and further advancement of highly active
antiretroviral therapy, enhanced screening, and increased
awareness and less stigmatization of the disease, compliant
patients lead much healthier lives. Consistent usage of directed
therapy and close monitoring by infectious disease specialists allow
these patients to maintain relatively functional immune systems.
These improvements in the care of patients with HIV also extend to
joint arthroplasty, where one study found that patients on routine
therapy with detectable viral burden and CD4 counts above 200
cells/mm3 are at no increased risk compared with uninfected
patients. 48

Basis for Treatment Compliance

Highly active antiretroviral therapy has transformed the lives of
patients living with HIV and enhanced their overall state of health
in all domains. In the focused world of elective total joint
arthroplasty, patients on highly active antiretroviral therapy have
decreased likelihood of major complications, including infection
and early readmissions after surgery according to a 2021 study. 49

Limitations of Optimization

Capacity to Optimize
There are myriad acute and chronic medical conditions that can
impart surgical risk after elective orthopaedic procedures and total
joint arthroplasty. The degree to which these comorbidities are
modifiable varies greatly from condition to condition and patient to
patient, with further complexity conferred by the potential
synergistic detriment between multiple conditions. Even when
maximal medical improvement is achieved, proceeding with
elective surgery may still be too risky in some patients.

Risk Tolerance
An interdisciplinary effort to evaluate both the number and
magnitude of conditions that deviate from ideal definitions of
preoperative optimization is necessary. It is likely that conditions
that only affect single systems are less risky than poorly managed
diseases that have multiple mechanisms of interference with
physiologic capacity to handle iatrogenic stressors such as joint
arthroplasty. Both uncontrolled diabetes and hypoalbuminemic
malnutrition have both proven especially risky, and great care
should be taken in considering such patients as candidates for joint
arthroplasty. 50

Summary
Joint arthroplasty is considered among the most successful
procedures in the world because of its capacity to reinvigorate
personal independence coupled with a relatively safe risk profile
with modern technology, surgical training, and enhanced
perioperative care. This favorable risk-benefit ratio has further been
underscored by recent efforts to ensure patients are at maximal
medical, social, and psychological function before undergoing total
joint arthroplasty. Although the degree to which comorbidities
affect the postoperative risk of joint arthroplasty varies between
diseases and patients, commitment to preoperative optimization is
of tantamount importance to both the patient and surgeon.
Orthopaedic surgeons must remain stewards of joint arthroplasty
to avoid exposing patients to personal risk that they cannot
properly appreciate without years of medical training and
experience.

Key Study Points

Preoperative optimization of all domains of health should be exercised in all patients
before total joint arthroplasty.
Optimization speaks to not only physiologic comorbidities, but also psychiatric,
social, and habitual conditions.
Failure to optimize patients not only puts the patient at inappropriate risk for
suboptimal outcome after joint arthroplasty, but also exposes the surgeon to great
risk in the era of bundled care and quality-driven reimbursements.

Annotated References
1. Ledford CK, Millikan PD, Nickel BT, et al: Percent body fat is
more predictive of function after total joint arthroplasty than
body mass index. J Bone Joint Surg Am 2016;98(10):849-857.
2. Malchow RJ, Gupta RK, Shi Y, Shotwell MS, Jaeger LM, Bowens
C: Comprehensive analysis of 13,897 consecutive regional
anesthetics at an ambulatory surgery center. Pain Med Malden
Mass 2018;19(2):368-384.
3. Golden SH, Robinson KA, Saldanha I, Anton B, Ladenson PW:
Clinical review: Prevalence and incidence of endocrine and
metabolic disorders in the United States – A comprehensive
review. J Clin Endocrinol Metab 2009;94(6):1853-1878.
4. Workgroup of the American Association of Hip and Knee
Surgeons Evidence Based Commi ee: Obesity and total joint
arthroplasty: A literature based review. J Arthroplasty
2013;28(5):714-721.
5. Akiboye F, Rayman G: Management of hyperglycemia and
diabetes in orthopedic surgery. Curr Diab Rep 2017;17(2):13.
6. Shohat N, Tarabichi M, Tischler EH, Jabbour S, Parvizi J: Serum
fructosamine: A simple and inexpensive test for assessing
preoperative glycemic control. J Bone Joint Surg Am
2017;99(22):1900-1907.
7. Capozzi JD, Lepkowsky ER, Callari MM, Jordan ET, Koenig JA,
Sirounian GH: The prevalence of diabetes mellitus and routine
hemoglobin A1c screening in elective total joint arthroplasty
patients. J Arthroplasty 2017;32(1):304-308.
8. American Diabetes Association: 2. Classification and diagnosis
of diabetes: Standards of medical care in diabetes—2021. Diabetes
Care 2021;44(suppl 1):S15-S33. The common types of diabetes are
type 1 (autoimmune beta cell destruction, absolute insulin
deficiency) and type 2 (progressive loss of beta cell insulin
secretion, insulin resistance). Diabetes can be diagnosed based
on fasting plasma glucose levels, glucose tolerance testing, or
HbA1C greater than or equal to 6.5% (48 mmol/mol).
 9. Shohat N, Tarabichi M, Tan TL, et al: 2019 John Insall Award:
Fructosamine is a be er glycaemic marker compared with
glycated haemoglobin (HbA1C) in predicting adverse outcomes
following total knee arthroplasty – A prospective multicentre
study. Bone Joint J 2019;101-B(7 suppl C):3-9. Although diabetes is
long known to be a risk factor for complications after total knee
arthroplasty, HbA1C has been criticized as slow to respond to
hypoglycemic therapy, potentially delaying surgery
unnecessarily. Fructosamine was found to be a be er risk
surrogate and assesses recent glycemic control more reliably.
Level of evidence: II.
10. Schipper ON, Jiang JJ, Chen L, Koh J, Toolan BC: Effect of
diabetes mellitus on perioperative complications and hospital
outcomes after ankle arthrodesis and total ankle arthroplasty.
Foot Ankle Int 2015;36(3):258-267.
11. Hikata T, Iwanami A, Hosogane N, et al: High preoperative
hemoglobin A1c is a risk factor for surgical site infection after
posterior thoracic and lumbar spinal instrumentation surgery. J
Orthop Sci 2014;19(2):223-228.
12. Tempel Z, Grandhi R, Maserati M, et al: Prealbumin as a serum
biomarker of impaired perioperative nutritional status and risk
for surgical site infection after spine surgery. J Neurol Surg A Cent
Eur Neurosurg 2015;76(2):139-143.
13. Cross MB, Yi PH, Thomas CF, Garcia J, Della Valle CJ:
Evaluation of malnutrition in orthopaedic surgery. J Am Acad
Orthop Surg 2014;22(3):193-199.
14. Zorrilla P, Gómez LA, Salido JA, Silva A, López-Alonso A: Low
serum zinc level as a predictive factor of delayed wound healing
in total hip replacement. Wound Repair Regen 2006;14(2):119-122.
15. Guo JJ, Yang H, Qian H, Huang L, Guo Z, Tang T: The effects of
different nutritional measurements on delayed wound healing
after hip fracture in the elderly. J Surg Res 2010;159(1):503-508.
16. Koren-Hakim T, Weiss A, Hershkovi A, et al: Comparing the
adequacy of the MNA-SF, NRS-2002 and MUST nutritional tools
 in assessing malnutrition in hip fracture operated elderly
patients. Clin Nutr 2016;35(5):1053-1058.
17. Wischmeyer PE, Carli F, Evans DC, et al: American Society for
Enhanced Recovery and Perioperative Quality Initiative joint
consensus statement on nutrition screening and therapy within a
surgical enhanced recovery pathway. Anesth Analg
2018;126(6):1883-1895.
18. Bogunovic L, Kim AD, Beamer BS, Nguyen J, Lane JM:
Hypovitaminosis D in patients scheduled to undergo orthopaedic
surgery: A single-center analysis. J Bone Joint Surg Am
2010;92:2300-2304.
19. Unnanuntana A, Saleh A, Nguyen JT, et al: Low vitamin D
status does not adversely affect short-term functional outcome
after total hip arthroplasty. J Arthroplasty 2013;28:315-322.e2.
20. Emara AK, Nageeb E, George J, Bu aro MA, Higuera C, Piuzzi
NS: Hypovitaminosis D in lower extremity joint arthroplasty: A
systematic review and meta-analysis. J Orthop 2020;21:109-116.
This systematic review looked at the association of vitamin D
deficiency and noted that both insufficiency (<30 ng/mL) and
deficiency (<20 ng/mL) are common entities and associated with
higher risk of complications and revision surgery. Level of
evidence: III.
21. Laird E, Ward M, McSorley E, Strain JJ, Wallace J: Vitamin D and
bone health; potential mechanisms. Nutrients 2010;2(7):693-724.
22. Lavernia CJ, Villa JM, Iacobelli DA, Rossi MD: Vitamin D
insufficiency in patients with THA: Prevalence and effects on
outcome. Clin Orthop Relat Res 2014;472:681-686.
23. Traven SA, Chiaramonti AM, Barfield WR, et al: Fewer
complications following revision hip and knee arthroplasty in
patients with normal vitamin D levels. J Arthroplasty 2017;32(9
suppl):S193-S196.
24. Cornelius ME, Wang TW, Jamal A, Loretan CG, Neff LJ: Tobacco
product use among adults – United States, 2019. MMWR Morb
Mortal Wkly Rep 2020;69(46):1736-1742.19.0% of US adults (47.1
 million) used any tobacco product in 2020. Cigare es were most
common (12.5%), followed by electronic cigare es (3.7%). The
overall prevalence of tobacco use in the United States declined
from 2019 to 2020.
25. Amaro EJ, Shepard N, Moss L, Karamitopoulos M, Lajam C:
Vaping and orthopaedic surgery: A review of current knowledge.
JBJS Rev 2019;7(1):e5. This is a review of the effects of electronic
cigare es in relation to their three-part detriment to the human
body: generation of oxygen free radicals, nicotine, and carbon
monoxide. Although they have become increasingly popular,
especially among a younger crowd, byproducts and vapor are as
harmful as (and even more harmful than) traditional cigare es.
Level of evidence: V.
26. Berley J, Yamano S, Sukotjo C: The effect of systemic nicotine on
osseointegration of titanium implants in the rat femur. J Oral
Implantol 2010;36(3):185-193.
27. Daffner SD, Waugh S, Norman TL, Mukherjee N, France JC:
Effect of serum nicotine level on posterior spinal fusion in an in
vivo rabbit model. Spine J 2015;15(6):1402-1408.
28. Duchman KR, Gao Y, Pugely AJ, Martin CT, Noiseux NO,
Callaghan JJ: The effect of smoking on short-term complications
following total hip and knee arthroplasty. J Bone Joint Surg Am
2015;97(13):1049-1058.
29. Møller AM, Pedersen T, Villebro N, Munksgaard A: Effect of
smoking on early complications after elective orthopaedic
surgery. J Bone Joint Surg Br 2003;85(2):178-181.
30. Samuelsen BT, Wagner ER, Houdek MT, et al: Primary reverse
shoulder arthroplasty in patients aged 65 years or younger. J
Shoulder Elbow Surg 2017;26(1):e13-e17.
31. Glassman SD, Anagnost SC, Parker A, Burke D, Johnson JR,
Dimar JR: The effect of cigare e smoking and smoking cessation
on spinal fusion. Spine 2000;25(20): 2608-2615.
32. Bisson EF, Bowers CA, Hohmann SF, Schmidt MH: Smoking is
associated with poorer quality-based outcomes in patients
 hospitalized with spinal disease. Front Surg 2015;2:20.
33. Boylan MR, Bosco JA, Slover JD: Cost-effectiveness of
preoperative smoking cessation interventions in total joint
arthroplasty. J Arthroplasty 2019;34(2):215-220. This level II study
evaluates an institutional, focused smoking cessation strategy
during the bundle period after total joint arthroplasty. Cost
savings were modest, but prosthetic joint infection risk was
decreased by a minimum of 25% at a cessation program cost of
$219. Level of evidence: II.
34. Zamorano DP, Lim PK, Haghverdian BA, Gupta R: Perioperative
management of the orthopaedic patient and alcohol use, abuse,
and withdrawal. J Am Acad Orthop Surg 2019;27(6):e249. This is a
review of the management of the relatively uncommon advanced
sequelae of alcohol abuse in the perioperative period for
orthopaedic procedures. Emphasis is placed on diagnosis via
physical examination and anticipation and prophylaxis of
potential clinical decline. Level of evidence: V.
35. Santori C, Ceccanti M, Diacinti D, et al: Skeletal turnover, bone
mineral density, and fractures in male chronic abusers of alcohol.
J Endocrinol Invest 2008;31(4):321-326.
36. Bauer DE, Hingsammer A, Ernstbrunner L, et al: Total knee
arthroplasty in patients with a history of illicit intravenous drug
abuse. Int Orthop 2018;42(1):101-107.
37. Williams SH: Medications for treating alcohol dependence. Am
Fam Physician 2005;72(9):1775-1780.
38. Kim H, Kim C-H: Association between preoperative depression
and readmission rate following primary total joint arthroplasty:
A systematic review and meta-analysis. J Arthroplasty
2021;36(11):3807-3813. This is a level III meta-analysis that
quantifies the relationship between depression and length of
hospital stay after joint arthroplasty. Depression was found to be
predictive of both readmission and longer index hospital
admission after joint arthroplasty. Level of evidence: III.
39. Halawi MJ, Gronbeck C, Savoy L, Cote MP, Lieberman JR:
Depression treatment is not associated with improved patient-
reported outcomes following total joint arthroplasty. J
Arthroplasty 2020;35(1):28-31. This is a single-institution study
that quantified the lack of modifiability in postoperative risk in
patients with depression. Patients receiving treatment for known
depression were not less likely to experience a complication.
Level of evidence: III.
40. Brown ML, Plate JF, Von Thaer S, et al: Decreased range of
motion after total knee arthroplasty is predicted by the Tampa
scale of kinesiophobia. J Arthroplasty 2016;31(4):793-797.
41. Kazarian GS, Anthony CA, Lawrie CM, Barrack RL: The impact
of psychological factors and their treatment on the results of total
knee arthroplasty. J Bone Joint Surg Am 2021;103(18):1744-1756.
This is a review of the physical manifestations of cognitive
pathology in total knee arthroplasty. It is noted that both
cognitive behavioral therapy and pharmacologic antidepressant
therapy have some support for use in modifying depressive
symptoms in patients who underwent total knee arthroplasty.
Level of evidence: V.
42. Goodman SM, Springer B, Guya G, et al: 2017 American
College of Rheumatology/American Association of Hip and Knee
Surgeons guideline for the perioperative management of
antirheumatic medication in patients with rheumatic diseases
undergoing elective total hip or total knee arthroplasty. J
Arthroplasty 2017;32(9):2628-2638.
43. Woelfle-Roos JV, Dautel L, Wernerus D, Woelfle K-D, Reichel H:
Vascular calcifications on the preoperative radiograph: Predictor
of ischemic complications in total knee arthroplasty? J
Arthroplasty 2016;31(5):1078-1082.
44. Voss B, Kurdi A, Skopec A, et al: Renal and gastrointestinal
considerations in joint replacement surgery. J Nat Sci
2015;1(2):e46.
45. Tan TL, Kheir MM, Tan DD, Filippone EJ, Tischler EH, Chen AF:
Chronic kidney disease linearly predicts outcomes after elective
total joint arthroplasty. J Arthroplasty 2016;31(9):175-179.e2.
46. Li J, Li M, Peng B-Q, Luo R, Chen Q, Huang X: Comparison of
total joint arthroplasty outcomes between renal transplant
patients and dialysis patients – A meta-analysis and systematic
review. J Orthop Surg 2020;15(1):590. This meta-analysis asks the
important question of whether, and when, to intervene on
arthritis in patients with kidney failure. Patients who undergo
successful kidney transplant have safer postoperative courses
than those who are on dialysis but have not yet undergone
transplant. Level of evidence: III.
47. Wei W, Liu T, Zhao J, Li B, Li S, Liu J: Does the hepatitis C virus
affect the outcomes of total joint arthroplasty? A meta-analysis of
ten studies. J Orthop Sci 2019;24(5):822-829. This is a meta-analysis
of patients undergoing total joint arthroplasty with chronic
hepatitis C. These patients have greater medical complication,
aseptic revision, and septic revision rates, and current medical
therapies are likely indicated before considering total joint
arthroplasty. Level of evidence: III.
48. Falakassa J, Diaz A, Schneiderbauer M: Outcomes of total joint
arthroplasty in HIV patients. Iowa Orthop J 2014;34:102-106.
49. Sax OC, Mohamed NS, Pervaiz SS, Douglas SJ, Aboulafia AJ,
Delanois RE: The effect of modern antiretroviral therapy on
complication rates after total hip arthroplasty. JB JS Open Access
2021;6(2):e20.00175. This is a level III, population-level analysis of
patients with HIV in the modern care environment. Both patients
who were and were not on antiretroviral therapy have
complication risks that are near the risk profile of the uninfected
patients undergoing total hip arthroplasty. Level of evidence: III.
50. Sta JM, Odum SM, Johnson NR, Otero JE: Failure to medically
optimize before total hip arthroplasty: Which modifiable risk
factor is the most dangerous? Arthroplasty Today 2021;10:18-23.
This article looks at independent risk factors for postoperative
infections, readmissions, complications, and death after total hip
arthroplasty and analyzed risk factors by magnitude of associated
hazards. Hypoalbuminemia, morbid obesity, active tobacco
usage, and diabetes mellitus imparted the greatest risk. Level of
evidence: IV.
C H AP T E R 11

New Technology in Orthopaedic

Surgery
Hani Haider PhD, Beau Kildow MD

Dr. Haider or an immediate family member is a member of a speakers’ bureau or has made paid
presentations on behalf of HTC Services LLC; serves as a paid consultant to or is an employee of
AMTI, Inc., HTC Services LLC, Monogram Orthopedics, Optimotion Implants, Zimmer; has stock
or stock options held in 3D Systems, HTC Services LLC, Materialise, Monogram Orthopedics,
Nuance Communications, Optimotion Implants, Pfizer, SiBone, Smith & Nephew; has received
research or institutional support from Beijing Chunlizhengda Medical Instruments, Double
Medical Technology, Exponent, Monogram Orthopedics, Optimotion Implants; and serves as a
board member, owner, officer, or committee member of ANSI/ASTM TAG to ISO/TC 150, ASTM
International, International Society for Technology in Arthroplasty. Neither Dr. Kildow nor any
immediate family member has received anything of value from or has stock or stock options held
in a commercial company or institution related directly or indirectly to the subject of this chapter.

ABSTRACT
Technology is developing exponentially in the field of orthopaedics.
In surgery, standard instrumentation and alignment jigs are being
replaced with navigation and robotics. In diagnoses from
radiographic images, artificial intelligence allows faster analysis
and provides higher accuracy than the human eye. It is important
for orthopaedic surgeons to be aware of the history and current
state of these technologies and the principles of operation of
computer navigation, robotics, augmented/mixed/virtual reality,
and machine and deep learning applications in the field of artificial
intelligence, along with the current literature on how these
technologies apply both in the surgical and clinical se ings. A basic
understanding of the current state in advanced orthopaedic
technology is needed for the ability to use, integrate, and
potentially develop these tools in practice.
Keywords: artificial intelligence; augmented reality; robotics;
surgical simulators; virtual reality

Introduction
There have been several innovations in computer-aided orthopaedic
technology spanning navigation, robotics, patient-specific
instruments (PSIs), and augmented and virtual reality systems.
Pioneering uses of artificial intelligence, machine learning, and
deep learning have been reported in the literature, and current
applications and the potential of such technologies are
commanding much a ention; therefore, the orthopaedic surgeon
should be provided with a robust framework with which to
continue self-learning in the future.

Historical Perspective in New Technology

Wins and Losses
Orthopaedic implant and instrument technologies have had a
fantastic history of wins. Hip and knee arthroplasties, in general,
have been vastly successful in reducing pain and returning patients
into much valued mobility. Sterilizing ultrahigh-molecular-weight
polyethylene (UHMWPE) bearings in an inert environment helped
reduce oxidation and fatigue to prolong implant life for knees and
hips. High cross-linking of UHMWPE improved its wear resistance
to significantly reduce the risk of wear and osteolysis. Currently,
these are clear, undisputed successes; however, some originally
were not. Hylamer was originally proposed as a superior alternative
to UHMWPE for bearings, and then proved a disaster. A large
number of metal-on-metal hip designs have since been recalled for
producing metallic particle and ionic debris that caused
unfortunate patient suffering and resulted in revision in many
patients. These were clear, substantial failures that caused damage.
Certain evidence and the ethical decisions involved should be
considered before adoption of any new technology, including
navigation and robotics.

What Evidence Criteria Should Be Met?

Although the use of navigation and robotics in orthopaedics
continues to grow, and these methods have brought much
excitement and some clinical benefits (eg, fewer outliers in hip and
knee arthroplasty implant alignment), neither mass adoption by
surgeons nor clear-cut and significant advantages have been
consistently demonstrated. A previously developed framework
(Figure 1) has condensed the judgment criteria into the following
four main factors: Would an innovation make the surgery easier,
faster, cheaper, and be er? These criteria can be thought of from
the perspectives of the main stakeholder categories in
orthopaedics: surgeons, hospitals, patients, and health care payors
(eg, insurance, government). Any one of these four major criteria
(easier, faster, cheaper, or be er) would give some advantage to a
product or service. If two or more criteria are combined, a niche in
the market can be developed. Only exceptional breakthroughs
would combine all four criteria to unequivocally sweep the market
(eg, a smartphone, or digital camera from general industry); in the
history of medicine and orthopaedics, the development of
antibiotics and radiographic imaging could clearly qualify. In the
field of arthroplasty, unlike any other product or service, it seems
that a new technology has to combine no less than all four criteria.
Therefore, the orthopaedic surgeon should consider whether any of
the technologies described herein will make overall surgery easier,
faster, cheaper, and be er.
 Figure 1 Schematic showing criteria for assessing new surgical technologies
and the stakeholders involved.

Medical Ethics Involved in the Decision to

Adopt a New Technology
New technologies in orthopaedic surgery are not always perceived
to have an explicit ethical guide as to when to use them. Surgeons
as individuals made many choices in the past; recently, hospitals
and purchasing commi ees governed the adoption of new
technologies for compliance and important economic reasons.
Usually, mere regulatory FDA clearance, which is sometimes
confused with approval, is relied on to flag whether it is ok to use a
technology. Yet, when regulators are asked, the answer is invariably
that the technology does not have approval, only clearance to sell
and use, having passed certain safety requirements as ve ed by a
bureaucratic system, and the question remains whether its efforts
can ever be good enough. However, progress in orthopaedic
technology has been most impressive, while perhaps remaining
vulnerable. Ultimately, individual surgeons’ motivations and ethics
govern how and when to adopt a new technology. 1 The ethics of
health care and government institutions can only rise to the task
once outcome registries achieve a high level of refinement and
comprehensiveness of data collection and analysis. Even then,
much debate will ensue on how to use all those data.

Robotics and Navigation in Orthopaedic

Surgery

History and the Basic Building Blocks of

Robotics and Navigation
Robotic surgery started with orthopaedics more than 35 years ago
by a veterinary surgeon at the University of California who
experienced a disabling illness that eventually prevented intricate
hand movements. A project and later a company were founded to
have a robot perform the manual bone incisions planned
beforehand. In 1985, the first experimental canine surgery with a
robot was performed with a fast-rotating burr held by a robotic arm
that was programmed to mill a proximal femur for a total hip
arthroplasty (THA) stem. The system was called Robodoc and
continued development for human joint arthroplasty from that
time to the present day. In the 1990s, navigation systems emerged
that did not involve robotics, and in the early 2000s, PSIs started for
total knee arthroplasty (TKA). All of the aforementioned navigation
systems have continued to evolve in parallel, and rely on similar
basic concepts.

Basic Constituents of Navigation and Robotic

Systems
Computer-aided surgery (CAS) robotic and navigation techniques
emerged to overcome some of the limitations of the conventional
technique by helping to provide be er alignment accuracy by
reducing outliers and supposedly complications of TKA and THA.
CAS systems are classified into the following major categories:
robotics (active and semiactive, differentiation described later),
navigation systems, PSI, and modern utilitarian smart tools, which
include augmented reality systems.
All of these systems rely on some fundamental core-enabling
technologies, functions, and steps. The systems vary by which of
those steps are done, how, and by whom. The following description
of such building blocks is hoped to provide knowledge about
semantics and principle of operation of CAS systems, providing a
solid framework for future self-learning.

Image-Guided Versus Non–image-Guided

The distinction between image-guided and non–image-guided
navigation or robotic system relates to the virtual anatomic bone
model on which, for example, a joint arthroplasty is planned and
performed. In image-guided or image-based systems, a truly
patient-specific three-dimensional (3D) model is created from CT or
MRI data of that patient. The process involves segmentation first,
and then 3D reconstruction of the data. CT, MRI, and even
radiographic data can be accessed or transferred from an imaging
machine in the DICOM (Digital Imaging and Communications in
Medicine) format. Segmentation is a technique used to
computationally extract from the full imaging data, subsets
(segments) of the data points to represent one or more bone or any
other tissue segments. Bone, for example, has high density and may
thus be represented in the CT case by all the points with
Hounsfield unit levels above a certain threshold. Other less-dense
tissues, scale to lower Hounsfield unit levels, and metallic implants,
if present in the patient, would be on the other extreme.
Reconstruction is then performed on segmented data to build
virtual 3D models of various bone segments. These models can be
volumetric form, a solid model of many tiny bricks called voxels.
More common and computationally efficient are surface models,
which are hollow, featuring the surface only and made up of
interconnected flat triangles, the vertices of which originated from
the points of the scanned image data.
Using the aforementioned image-based bone modeling, the
resulting virtual bone models have been used with general or
customized computer-aided design tools to prepare a surgical plan
for the patient. The outcome of the process can be one or more PSIs
in the form of slo ed cu ing blocks (eg, for TKA), typically built by
additive manufacturing (3D printing) so that they fit in one way to
the patient’s bone profile during surgery to facilitate bone
resections. PSI is now a mature technology offered by most
orthopaedic implant manufacturers. Its main advantage is that
tracking or robotics are not required in the operating room, and
only a few custom (disposable) alignment instruments are
necessary instead of the hundreds in a typical conventional
mechanical instrument set. However, the process has some
workflow limitations in having to involve a commercial
manufacturer in the surgical planning stage and making of the PSI
blocks.
In non–image-based systems, a bone model is displayed, but it
only mimics the patient’s bone extracted from a library (atlas) of
other people’s bones available within a database on the system and
adjusted to fit. A suitable version from the atlas is parametrized
and morphed (scaled by adjusting length, slenderness, location of
centers, bone ends, and the scaling done uniformly or
nonuniformly) to closely approximate to that of the patient.
Measurements during surgery on the patient help that morphing
process, including the location and distance between the hip center
and knee joint line, the most distal point on each condyle, the
distance between the epicondyles, and others. This process is
sometimes termed kinematic registration, in which the bone model
is approximately scaled, and tracked motions of the relative pose
(location and orientation) of different bone segments to each other
help estimate the hip, knee, and ankle joint centers, from which a
mechanical axis is determined in the virtual computer space based
on the patient’s physical one in the operating room.
Three-Dimensional Localization and Tracking
Through Navigation or Robotics
A central function by a robotic arm, and/or a navigation system, is
the ability to have the robot end effector or a navigation pointer, or
a navigated instrument, be localized in space. This includes the x-,
y-, and z-axis coordinates of the origin of the component measured,
as well as its orientation by three angles around three axes along
these dimensions. The pose that results for the patient bone and
those of other elements in the surgery field (eg, pointers, navigated
jigs, robotically held instruments, navigated implant trials) are then
all obtained at a given time (instant). The measurements are then
repeated and all elements are tracked dynamically in space from 30
to 100 times per second with current technology.
The poses of the robotic arm end effector can be measured by the
robotic arm using the onboard position and angle sensors at the
robotic arm’s articulated joints. Or, the robotic end effector can be
tracked by using an external tracking system, which also tracks the
bone and any ancillary instruments. In tracking, typically two
cameras are used, spaced apart at a small angle to each other, for
stereotactic vision resembling the configuration of human eyes. In
this way, 3D localization (including depth) is achieved with the
processing of instantaneous pairs of two-dimensional camera
images. Most cameras are filtered for infrared light only to reduce
the effects of busy optical backgrounds and noise. Magnetic
tracking can also be used, but has been much less popular because
of the inherent magnetic interference (noise) from metallic surgical
instruments in a surgical field.
In optical or infrared tracking, the cameras detect active or
passive markers, typically in a unique constellation (called a
reference frame, base, or array) composed of three or more markers
rigidly a ached to each tracked element (bone, cu ing block, etc).
Active reference frame markers are powered by ba eries and
electronics, so each marker on them is actually a small infrared LED
(light-emi ing diode) light, sometimes pulsed in a unique
identifiable sequence for that device. Passive markers are much
simpler and look like silver spheres to reflect incoming infrared
light emi ed from sources on each camera. Of course, both require
a clear line of sight from the cameras to each element tracked in the
surgical scene.

Registration
This is the process of measuring and computing to relate in 3D
space the computer system virtual bone model to the physical
anatomy of the patient. It is also required to register each of the
aforementioned tracked reference frames to the geometry of the
element to which it is a ached before the element can be tracked.
Registration can be performed in many ways: the simplest is point-
to-point, by relating preselected fiducial points one by one to their
corresponding physical anatomic landmarks, or by surface-to-
surface matching, which is performed by digitizing a physical
surface and computing where it would match with highest
correlation (least error) to an equivalent patch of surface of the
bone’s virtual model. There are various other registration
techniques beyond the scope of this chapter, and they are an area
for continued innovation and progress.

Building Blocks Integrate Into Whole Robotic

and Navigation Systems
As it became possible to build 3D virtual models of the patient’s
(actual or morphed) bone anatomy, register, and track them in the
3D physical surgical space and track relative 3D positions of
alignment jigs (eg, cu ing blocks, or bone resection instruments),
various computer-aided orthopaedic surgical systems emerged. If a
computer is programmed to move an actuator (robotic arm)
carrying a resection device to a desired accurate position to resect
bone, then that would be a surgical robot. If the robot itself was
programmed to move the resection device to desired cu ing paths,
this was called an active or semiautonomous robot (eg, Robodoc).
However, a robotic arm can be equipped with force/moment
(haptic) sensors (typically a load-cell with six degrees of freedom
near a user handle at the end effector) to detect where a surgeon
manually moves the robot’s end effector or surgical resection
instrument (eg, a milling burr or an oscillating saw blade). The
computer, through the robotic arm actuation, would then either
allow or resist the surgeon’s desired motion based on whether it
follows the presurgical plan along preapproved cu ing regions.
This variety is sometimes classified as a passive or semiactive
robotic surgery system (eg, Mako by Stryker). If the 3D tracking
software guides the user to place a cu ing block without a robot,
this has been called a navigation system. In the following sections,
additional categories of robotics and navigation systems used in
joint arthroplasty, based mainly on their basic principle of
operation, are presented.

Robots for THA and TKA (the Old and the

New)

Robodoc—The Revival
The earliest of orthopaedic surgery active robotic arms was the
aforementioned ROBODOC (by Integrated Surgical Systems/CA).
In the late 1990s until the early 2000s,
“Caspar”(OrthoMaquet/Germany) was another widely publicized
system. Both articulated robotic arms were large, clean-room
versions reconfigured from the manufacturing industry. They
accurately moved a fast-rotating cu ing burr to remove bone
following previously programmed cu ing paths much like a
computer numerical control (CNC) machining process. Termed
active (semiautonomous) robotic systems, they brought much
excitement at the time and some published studies were optimistic
if not bullish. However, multicenter studies on ROBODOC hip
replacement in the United States (136 hip joints—almost half robot
vs half conventional control systems) showed longer surgical time
and higher blood loss with the robot, which were a ributed to the
learning curve. In a series of 900 cases in Germany, the Harris Hip
Score rose from 43.7 to 91.5, and the surgical time declined quickly
from 240 minutes for the first case to 90 minutes. The system was
described as safe and effective in producing radiographically
superior implant fit and positioning while eliminating femoral
fractures. 2 The ROBODOC robot was discontinued and replaced
with a modern, updated version named the TSolution® One Robot
sold by THINK Surgical®, Inc., Fremont, CA (Figure 2).
 Figure 2 Graphical model of the TSolution One Robot—an active robot by
THINK Surgical®.(Reproduced with permission from THINK Surgical®, Inc.,
Fremont, California.)

Modern Variations of Active Robots

The aforementioned shortfalls were inevitably going to be
addressed by integrating interdisciplinary innovations. A
noncemented TKA tibial component fixation has been developed
for younger and more active patients, and also for easier revision
should the need arise later. This contemporary solution (Figure 3)
combines a radical and innovative TKA tibial component design
with additive manufacturing and robotics. A light, agile robotic arm
with a fast-rotating burr is automatically programmed during
planning to accurately mill the peripheral fixation fin channel. Here
a smaller, lighter robot is harnessed to perform a much smaller
function for insertion of an implant targeting specific clinical
advantages.
Figure 3 Graphical models of the Monogram innovative noncemented tibial
component and active robotic arm.(Reproduced with permission from
 Monogram Orthopaedics Inc., Austin, TX.)

Semiactive Surgical Robots Haptically

Guided by the Surgeon’s Hand
In this category of orthopaedic surgical robotics, the surgeon’s
hand manually maneuvers the end effector that carries a resection
instrument such as a rotating burr, or, lately, bone saws for TKA or
reamers for THA. As is standard, they are programmed with a
surgical plan, typically a CT image–based bone model rendered on
the computer screen together with a model of the burr or resection
instrument tip. Between the surgeon’s hand and the end effector is
a load cell with six degrees of freedom that senses the forces and
moments in the directions of motion the surgeon wants to move the
robotic arm end. The concept of a haptically guided, surgeon-
constraining robot was vigorously commercialized in the United
States (Mako). Mako had also eclipsed the earlier UK Acrobot
system, which had been the first (late 1990s) innovation 3 in this
category and with published clinical results. 4 Mako also started
with a rotating burr for bone resections for a unicondylar knee
arthroplasty. It has recently progressed to control a reamer in hip
arthroplasties and a burr to knees and finally holding an oscillating
power saw at the end of the robot effector for knee arthroplasties.
Again, the Mako user interface allows the surgeon to resect the
surface. The modern system’s peripheral instruments help guide
the surgeon for ligamentous tensioning and gap balancing.
A 2020 systematic review 5 that included 21 published studies on
unicompartmental knee arthroplasties performed using the Mako
system showed short-term benefits compared with the conventional
technique regarding implant alignment accuracy, soft-tissue
balance, patient function scores and satisfaction, complication
rates, and learning curve in short-term outcome. However, the
authors stated that these findings could not yet be extrapolated for
midterm and long-term outcomes. 5 A 2022 study 6 retrospectively
reviewed data from 2,392 conventional TKAs by six high-volume
surgeons matched 1:1 with robotic TKAs by another six high-
volume surgeons who used the Mako system. Outcome measures
included surgery time, hospital length of stay, total direct cost, 90-
day complications, utilization of postacute services, and 30-day
readmissions. Overall, the median length of stay was the same and
no significant difference in 90-day complication rates was found.
However, the robotic surgeries took more than 10% longer to
perform than the conventional surgeries, and the median total
direct cost per case was significantly greater at $11,615 and $8,674,
respectively (P < 0.0001). 6 These authors also speculated about the
cost justification and left it pending if it would be offset by lower
revision rates and/or improved functional results.

Surgical Robots That Position Cutting Guides

Surgical robots position cu ing guides with slots through which
oscillating saw blades are guided. One of the earliest was the
Praxim/Omni bone-mounted version (OMNIBot by Corin). It is
fixed to the side of the distal femur from inside the incision by
using two pins. The imageless configuration (Figure 4) is used for
TKA in conjunction with BalanceBot, a robotic ligament tensioning
tool. The BalanceBot has two expandable thickness paddles, one
under each knee condyle, inserted into the knee after the tibial
resection, actuated to certain force levels, and measuring medial
and lateral gaps. It aids gap balancing by quantifying the soft-tissue
envelope throughout the range of knee motion before femoral
resections. Clinical data with this system totaling more than 30,000
TKAs (10,000 with the ligament balancer) were reviewed in a 2021
study. 7 The results showed some utility in surgical planning and
modestly improved accuracy compared with conventional and even
navigation technology. Mechanical alignment improvements of
approximately 0.5° were typically achieved, with TKA survivorship
of 99.26% for one cohort over 3 years and another 766 TKA series
with 99.4% survivorship over 6 years. Gap balancing assessments
and effects on pain were also studied and showed favorable results.
8 , 9

Figure 4 A, Graphical model of the OMNIBot bone-mounted small robot (Corin,

UK). B and C, With the BalanceBot; the actuated tensor is inserted into the knee
after the tibial resection to capture joint balance as the knee is placed through a
range of motion.(Reproduced with permission from Corin, UK.)

The ROSA® Knee System (Zimmer Biomet) was introduced, and it

is much larger and non–bone-mounted (Figure 5). The robotic arm
is fixed to a large-wheeled base cabinet. A separate wheeled console
augments the system with external infrared cameras for tracking of
the end effector/cu ing block (Figure 5). This robot obviously has
more sturdy positioning of the cu ing block, but the price is the
much larger footprint. With eight orthopaedic surgeons using the
ROSA® Knee System to assist TKA surgery with three different
implant designs resulted in angle inaccuracy of less than 1° and
precision (sca er measured by standard deviation) and mean
resection plane offset and sca er of less than 1 mm, all measured
for verification by a different computer-aided system on the same
surgeries. 10
 Figure 5 Photograph shows the ROSA ® Knee System with a cutting guide
attached to a robotic arm.(Reproduced with permission from Zimmer Biomet,
Warsaw, IN.)

Surgical Robots That Constrain the Motion of

a Power Instrument
A natural progression from the aforementioned robotic systems
was to have the robotic arm constrain the motion of the power
instrument (sagi al saw) directly to move freely in a single desired
plane. The recently launched VELYS™ Robotic-Assisted Solution
(DePuy Synthes) has two-wheeled cabinets and achieves this
functionality with a relatively smaller robotic arm (Figure 6). Here,
the overall (course) positioning of the robotic arm is done manually
through adjustable/lockable hinges. The final precise positioning
that defines the final plane of saw blade motion is performed by
smaller motorized actuators closer to the robotic arm end effector.
This combination modestly reduces the size and lightens the
weight of the overall system with only a modest compromise in
rigidity. The VELYS™ Robotic-Assisted Solution is relatively new,
and reasonable-length clinical results are sparse.
 Figure 6 Graphical models of the VELYS robotic-assisted solution, Depuy (IN).
(Reproduced with permission from DePuy Synthes, Warsaw, IN.)

Accelerometer-Based Systems
These are small, smart passive devices that provide information
during a procedure (Figure 7). Compared with conventional
mechanical instrumentation, most do not require any additional
pins nor involve line-of-sight issues associated with navigation.
Some are disposable single-use, sterile handheld instruments and
some only partly so. Their operation is based on miniaturized
accelerometry such as that of smartphones. Accelerometers
measure inclination (angles) relative to the earth’s gravimetric and
magnetic fields. These systems combine an electronic compass and
sensing of the direction of gravity, in three orthogonal axes, on one
surgical instrument. Combined with the possibility of multiple
components interacting wirelessly, these smart systems can help
align fixtures and cu ing blocks for implants.
 Figure 7 Graphical models of the accelerometer-based systems.A, Lantern
(Copyright OrthAlign, Aliso Viejo, CA). B, iAssist (Copyright Zimmer Biomet,
Warsaw, IN). C, Dash (Copyright 2022 Brainlab AG, Munich, Germany).(Panel B,
Reproduced from Desseaux A, Graf P, Dubrana F, Marino R, Clavé A:
Radiographic outcomes in the coronal plane with iASSIST™ versus optical
navigation for total knee arthroplasty: A preliminary case-control study. Orthop
Traumatol Surg Res 2016;102:363-368. Elsevier Masson SAS. All rights
reserved.)

Some modest cost and potential waste are inherent in the

disposable single-use versions. Other limitations are their accuracy
and modest response rate. These are not serious as their use in
joint arthroplasty is in a quasi-steady-state fashion, with bones and
instruments moveable but assumed stationary for any given
instantaneous reading. The other, more serious limitation is the
accelerometer’s inherent inability to measure position or distance.
Only angles are navigated, and not positions. However, the same
electronic device can include miniaturized load-cell force sensors,
which can aid in flexion gap balancing and ligament tuning in TKA.
The most a ractive aspect of the accelerometer-based systems is
their essential utility compared with the large-console robotic and
navigation systems. Because of the similarity of their function
simply being a ached to mechanical cu ing blocks, they naturally
require a shorter learning curve, and have almost no extra operating
room footprint and no line-of-sight issues, therefore increasing
their appeal. Finally, the functionalities of some of these systems
can at least theoretically be integrated with bigger navigation and
robotic systems. The obvious next step is integration of two systems
in a unified user interface for easier overall surgery.
The iASSIST miniaturized (single-use) electronic pods 11 had
various clinical results published regarding accuracy and reliability.
In a short-term (6-month) prospectively matched study 12
comparing iASSIST with TKA control subjects assisted by the Ci
(DePuy Synthes/BrainLab) navigation system (38 knees in each
group), no significant differences were found in patient-reported
outcomes or alignment measurements. However, patients in the
iASSIST group had shorter surgery durations and added costs of
approximately $1,000 per surgical procedure. Efficacy of the system
to achieve alignment within a few degrees was more or less
confirmed by similar short-term to medium-term results from other
studies. 13 - 15 One system was also compared with another large
console navigation system, 13 and another compared with
conventional instrumentation. 15 No significant differences were
found in overall clinical outcomes, or patient function or
satisfaction. A 2019 systematic literature review and meta-analysis
16
pooled 558 knees, approximately one-half underwent surgery with
iASSIST and one-half with conventional instrumentation. There
were 45% fewer alignment outliers in the iASSIST group compared
with the conventional TKA techniques. However, the duration of
surgery was prolonged and without any apparent advantage in
short-term clinical functional score.
A series of clinical results using OrthAlign 17 - 21 showed more
than 96% of tibial resections were within ±2° from the desired angle
for both coronal and sagi al alignment, and more than 93.8% were
within 3° of the desired alignment for the femoral distal resection
and overall mechanical axis. A matched cohort comparison of
OrthAlign with TKAs performed with a large-console imageless
CAS system (AchieveCAS; Smith & Nephew) echoed similar results
and showed alignment on par between them. Furthermore, a
prospective randomized controlled study of 100 patients comparing
OrthAlign with conventional (extramedullary) mechanical
instruments showed that the aforementioned alignment numbers
were only achieved by less than approximately 72% with
mechanical instruments.
Therefore, the literature confirms that alignment using portable
accelerometer-based instrumentation is as accurate and precise in
TKA to achieve targets as larger navigation systems and therefore
more accurate than conventional mechanical instrumentation. It
involves additional surgical time but has a smaller footprint in the
operating room compared with large navigation systems, and is less
invasive of the intramedullary canal.

Freehand Navigated Power Tools

Another fundamentally different avenue for utility and small
footprint is to navigate orthopaedic bone resection power tools
directly while the surgeon holds them and operates them freehand
as is typical. The earliest commercialized implementation was the
Navio system (Bluebelt, now Smith & Nephew) (Figure 8),
originally for unicompartmental knee arthroplasty, and now for
TKA. The navigation system is non–image-based (relies on
kinematic registration) that tracks the handheld device and controls
the speed and fast-shields the burr tip if its position deviates from
the surgical plan. Although the CORI version is new and no clinical
results could be found, the Navio system has accumulated plenty of
clinical data, such as 99.2% survivorship in 128 patients at a mean
follow-up of 2.3 years with unicompartmental knee arthroplasty. 22
For TKA, the Navio system was recently assessed, with reported 23
accuracy in terms of mechanical axis, femoral coronal, sagi al,
rotational, tibial slope, and tibial coronal alignment. The root mean
squared error of deviation from the plan for all the burred surfaces
did not exceed 0.56°. 24 In a case-control study, 70 Navio TKAs
showed a learning curve of 11 cases to be equivalent to standard
instrumentation, with no differences in limb alignment or
component positioning. 24 For extra speed, many users burr the
distal femoral surface, place a combination cu ing jig to finish the
femur, and use the tibial jig to pin and resect, so the system can be
used in a hybrid manner. The Navio system has been improved,
and the new version is called CORI (Smith & Nephew), which has a
larger resecting and retracting burr that is five times faster and has
a swifter registration procedure. This version is so recent that
published results are not currently available.
 Figure 8 Graphical models of the CORI latest freehand navigated burr
system.The original Navio handheld burr is depicted in the top right corner.
(Reproduced with permission from Smith & Nephew, Memphis, TN.)

More typically used power tools (sagi al and reciprocal

oscillating saws and drills) have been equipped with navigation and
intelligent functionality onboard without adding too much weight
or power consumption and without complicating the freedom to
use them wirelessly, without any tethered power or signal cables. 25
- 28
The first version of these was an externally tracked tool (Figure 9,
A). Without any cu ing blocks or other mechanical instruments,
external infrared cameras track the power instrument itself so the
navigation provides surgeons with real-time 3D guidance with
graphical feedback and speed control of the power tool. The
feedback to the surgeon is provided also on the resection
instrument itself through a smartphone and optionally through
external computer monitors.
 Figure 9 Photographs show freehand navigated bone resection instruments.A,
Externally tracked tool. B, The on-tool tracking with tracking cameras and
projector onboard.(Reproduced with permission from Hani Haider, PhD.)

Another version is called on-tool tracking and does not require

the use of an external navigational 3D tracking device. Instead, the
navigation and stereotactic camera tracking components and
electronic circuits are integrated within the wireless module
mounted on top of the power instrument (Figure 9, B). Also
included is a microprojector that displays guidance or images onto
the bones to show where the surgeon should begin the cut and
orient the instrument during cu ing. In this case, the 3D tracking
cameras and electronics are all on board, and so is the graphical
feedback generated onboard and projected on the bone, thus
minimizing invasiveness in multiple ways.
The system is not commercialized yet, but the externally tracked
tool was characterized through multiple in vitro TKA experiments,
25 - 28
including two cadaver procedures. It had shorter bone
resection times than conventional instrumentation. Detailed bone
resection assessments showed adequate surface roughness and
implant fit on par with conventional instruments and superior
surface alignments. This technology is intuitive with standard
orthopaedic saws and drills, and also has the potential to improve
TKA alignment, reduce surgical time, and reduce the number of
instruments in surgery. Fewer instruments and less sterilization
could reduce costs associated with TKA.

Augmented and Virtual Reality Systems

Augmented or mixed reality is an integration of various
technologies to visualize through a display medium
(semitransparent screen or lenses) a real physical scene on which
computer output is superimposed, thus presenting virtual content
into the natural visual field of the user.
 Virtual reality provides a medium in which a user is fully
immersed in the virtual environment, so all they see is computer
output in 3D. By 3D tracking of the user’s head (and so
approximately the direction of their vision), the user feels as part of
the virtual environment as the graphics change in real time based
on the user’s perspective. Naturally, therefore, virtual reality is
applicable mainly in orthopaedic surgery training in simulators,
including those of navigation and robotics. For instance, surgical
residents can wear a headset and immediately be placed into an
artificial operating room where they can perform artificial surgery
to familiarize themselves with instruments, implants, and steps for
certain procedures prior to a real case.
The concept of augmented reality is more directly applicable to
the main navigation and robotic surgery themes of this chapter.
The early and basic challenges were how to display 3D information
on a flat computer screen, combined with the need to have the user
(head/eyes) motion automatically change the computer 3D
rendered graphical output in response to the viewer’s changing
vision perspective. Augmented reality became much easier when
combined with wearable 3D glasses (eg, HoloLens, Microsoft) with
cameras onboard 3D tracking through markers a ached to
elements on the surgical scene. The glasses move with the user
head and display in (stereovision). When 3D graphics are rendered
through two separate glass lenses (left and right), and objects are
tracked in the surgical scene, the perspective is readily determined
and matched when superimposing the virtual output onto the
physical bone.
HipInsight (Surgical Planning Associates) is an FDA-cleared
augmented reality–based 3D guidance system (Figure 10, A).
Microsoft HoloLens 2 head-mounted glasses with custom software
register and track the position of the pelvis through an image target
a ached to a mechanical frame fixed to the acetabulum. The user
views the surgical scene directly through the glasses, with virtual
overlays of the 3D patient-specific anatomy model, implants, and
instrumentation. In the hip application, handheld reaming for the
desired cup orientation is guided by lining up the physical
impactor with its virtual counterpart (Figure 10, B). The developers
claim that the system has demonstrated equivalent accuracy to
navigation and robotic systems, resulting in FDA regulatory
approval, but these results have not been published.
 Figure 10 Photographs show augmented reality platforms.A, HipInsight
(Copyright Surgical Planning Associates, Boston, MA). B and C, ARVIS
(Copyright Insight Medical Systems, Austin, TX). D, NextAR (Copyright Medacta,
Switzerland).

Another example is the Augmented Reality Visualization and

Information System, ARVIS (Insight Medical Systems) (Figure 10,
C). Its eyepiece was configured to be compatible with a typical
orthopaedic surgical helmet and the system helps in navigating
distal tibial and femoral TKA resections, and hip cup placements.
Medacta has launched the NextAR augmented reality–based
surgical platform for TKA (Figure 10, D), which allows the surgeon
to have real-time feedback with ligament balancing that is
displayed on a virtual screen. This platform has also extended its
use in shoulder arthroplasty and spine.
Naturally, such augmented reality systems feature stark contrast
to the cumbersome equipment and workflows of the traditional
surgical navigation and robotic systems. The three aforementioned
examples were so new at the time of writing this chapter; there
were no published clinical results available to be cited here.
Disadvantages to this technology are potential interference
between the surgeon’s view and the patient having to wear head-
mounted equipment. How augmented reality systems will perform
will depend on accuracy and what surgical tools or instruments are
being navigated.

Preclinical Testing and International

Standards
Orthopaedic implants and medical instruments are all tested
preclinically, and only FDA cleared when comprehensively
described through documentation, including preclinical verification
and validation tests. Most standards for implants are developed by
experts and published by the American Society for Testing and
Materials (ASTM) International, or the International Organization
for Standardization (ISO). Although the implant commi ees of
these two organizations are succinct, being the ASTM F04
commi ee on Medical and Surgical Materials and Devices and
ISO/TC150 commi ee (Implantable Devices), navigation and
robotics straddle a much wider range of commi ees, including the
very general International Electrotechnical Commission (IEC),
which deals with safety of all electrical machinery, and the
Association for the Advancement of Medical Instrumentation. One
example of such standard is IEC 80601-2-77 titled “Particular
requirements for the basic safety and essential performance of
robotically assisted surgical equipment.”
ASTM F04.38 Subcommi ee titled “Computer Assisted
Orthopaedic Surgical Systems” has developed two standards. The
first was ASTM F2554, titled “Measurement of Positional Accuracy
of Computer Assisted Surgical Systems” and the second was ASTM
F3107, “Measuring Accuracy after Mechanical Disturbances on
Reference Frames of Computer Assisted Surgery Systems.” Both
were pioneering standards and had to address the most elementary
function on which all surgical navigation and robotics rely. These
standards were a good start, but are far from adequate for
verification of a system’s overall accuracy for placing a bone
resection cu ing block, robotically guiding or constraining a burr,
or whether the resected bone surface was smooth, located, and
aligned correctly, let alone the alignment of the implant
subsequently fixed to it. Accelerated efforts by the ASTM
subcommi ee F04.38 are now underway to revise and upgrade
those two standards and to develop multiple new ones.
In a different area, an ISO standard has been developed for
creating and parameterizing virtual bone models for preoperative
surgical planning, navigation, robotic surgeries, patient-matched
instruments, and personalized total knee joint prosthesis. This
standard is ISO 19233-1 titled: “Implants for surgery—Orthopaedic
joint prosthesis—Part 1: Procedure for producing parametric 3D
bone models from CT data of the knee.” This document helps with
the conditions to scan images of bones, as well as to segment and
reconstruct 3D bone models. It can be stated that standardization
in testing is still lacking in this area because writing standards are
an international consensus activity between experts, largely from
industrial companies, regulators (eg, FDA), general scientists, and
engineers and, of course, surgeons who are the end users of such
technologies.

Artificial Intelligence and Machine Learning

What Are Artificial Intelligence, Machine

Learning, and Deep Learning?
Generally artificial intelligence refers to computer algorithms
making decisions from simple or complex, and large quantities of
data with some level of simulated cognition. Such algorithms
enable a computer to learn existing pa erns in a given data set
without complete and explicit rules for what pa ern or feature
would be associated with which outcome. There are subtle
differences that only the specialist can fully appreciate between (1)
intelligent algorithms that have been wri en in software from the
dawn of computers, (2) knowledge-based systems that started to
appear and perform much more intelligently when combined with
tabulated data sets or relational databases and programmed with
look-up procedures and rules for decision making, and (3) neural
network–based systems with far fewer rules or at least less explicit
ones. The last category rocketed in potential into modern machine
learning when the rules became fuzzy and algorithms were
programmed to look for pa erns in structured data and outcomes
or optimized decisions that a programmer could themselves not
predict unless they experiment with seemingly infinite or at least a
prohibitively large number of possibilities.
Historical (training) data have been harnessed for algorithms to
predict solutions/outcomes for hitherto unseen combinations of
input data and scenarios by the algorithm. Any new combination
can add to the data sets used by the algorithm in a continuing self-
learning process. When the data sets have even less structure (eg,
medical images such as radiographs or DICOM data from CT or
MRI being interpreted) and rules become less coherent and even
scarce, and pa erns even more complex, these are said to require
deep learning capabilities. Deep learning involves a multilayered
neural network that is structured similarly to the human brain in
which raw data input progresses through higher level abstraction.
Over the past decade, artificial intelligence has become one of the
most invested and studied concepts in essentially all sectors of
society, especially healthcare. Patients, diseases, and treatment
pathways are extremely complex processes with infinite variables,
all of which are interdependent. With the number of complex
variables, each episode of care for the same disease process can
have a wide variation in outcomes, especially when treatment
pathways have different control units (care providers). Hospital
systems and care providers, however intelligent, intuitive, and
organized, continue to struggle at optimizing diagnosis and
treatment pathways for patients in an efficient manner. The
application of artificial intelligence in all fields of medicine can
theoretically more systematically digest these variables to predict
an outcome or treatment pathway that has the highest probability
of success and continue to learn from actual patient outcomes. 29 , 30
Recent focus on collecting and analyzing big databases has not
only helped improve current efficiency and outcomes but has
fueled the field of orthopaedic surgery in using artificial
intelligence. Currently, big data are stored and analyzed in large
databases, and some are formal national registries. These databases
work by individual physicians importing data such as type of
surgery, risk factors, complications, implant type, and length of
stay. The goal is to identify certain correlations (using standard
statistical methods) that relate to good or bad outcomes, helping
physicians make be er decisions for patient care. Although this is a
powerful tool, there are many limitations, including selection bias
and many uncontrolled variables that could unintentionally
produce inaccurate correlations. Furthermore, statistical analyses
are often time intensive and nonadaptive.
The challenges with this technology include data quantity,
training of systems with past data, and extrapolation to plan safe
future performance of instances/scenarios unseen before, without
risk. In healthcare, such extrapolation to plan safe future
approaches can seem to have an inherent contradiction. However,
the increased utilization of national registries as well as platforms
that collect, store, and organize large volumes of data will continue
to improve artificial intelligence and its powerful application in
orthopaedic diagnosis and treatment pathways.
Currently, the most natural health care applications of artificial
intelligence relate to modeling and optimizing models for health
care pathways 29 , 30 with greatest success in mental health,
cardiology, 31 , 32 dermatology, 33 ophthalmology, 34 and radiology.

Specific Artificial Intelligence Applications in

Orthopaedics
There are many fields of artificial intelligence including machine
and deep learning, natural language processing, machine
perception, and automation that have application in orthopaedic
surgery. In orthopaedics, artificial intelligence has been led by and
mostly involves image recognition of fracture identification and
trauma, 35 , 36 detection and classification of osteoarthritis, 37 - 40 hip
and knee implant component identification, 41 - 44 musculoskeletal
tumors, 45 , 46 anterior cruciate ligament injuries, and spine
pathologies. 31
Leading the way again is arthroplasty, likely because of high
volumes of patients receiving similar pathways of care based on
imaging and patient factors, all of which have excellent potential for
machine learning algorithms so many applications in arthroplasty
have emerged. Even the osteoarthritis detection efforts, 37 - 40 could
not only be used to calculate the degree of osteoarthritis with
successful outcome of replacement surgery, can also help triage
patients to the appropriate surgical or nonsurgical clinic.

Implant Detection
Phenomenal advancements have been made with implant detection
from radiographic images, which is crucial for revision surgery,
especially without access to prior surgical information. 41 - 44 , 47 With
an ever-increasing number of manufacturers and designs, and no
adequate records of what implant had been used for a substantial
number of patients, recognizing what implant product is in a
patient is a challenge. It becomes a serious problem if only one
component of an implant system needs to be replaced in a revision
(eg, TKA UHMWPE bearing insert, or loose hip socket). A deep
learning implementation trained by 252 postoperative radiographic
images of three known THA implant designs automatically
identified their type on 25 new radiographs. 43 , 44 The same group
then used 402 radiographs and compared the algorithm’s results
with that of three board-certified orthopaedic surgeons, and found
the deep learning system much faster with on-par accuracy.
Another recent deep learning example 42 trained and validated by
1,766 AP radiographs of 18 different hip femoral components from
1,715 patients, and after 1,000 training cycles a deep learning
system discriminated 18 implant components from 4 different
manufacturers featured in 206 tested (untrained) AP radiographs
with accuracy greater than 99%. Similar impressive results 41
differentiated between 9 unique knee arthroplasty implants from 4
manufacturers in 74 tested radiographs with near-perfect accuracy,
with the deep learning algorithm trained by 682 radiographs across
424 patients.
When the computer can perform such identifications in seconds
or even fractions of a second, this evidence becomes compelling
that already, or very soon, artificial intelligence can identify
orthopaedic implants in patients without records faster, more
reliably, and efficiently than any human.
Clinic and Operating Room Throughput,
Efficiency, and Cost
High on the list of the discussion topics among most orthopaedic
surgeons is cost control in the medical arena. Huge efforts are
placed to reduce health care expenditure, and one main avenue to
control cost is by forming bundled payment plans, which
essentially shift the responsibility to control costs on the hospitals
and physicians. Early bundled payment plans were imperfect
because of the inevitable variability in each patient’s care without
the ability to identify factors that may result in increased cost. As
such, efforts to reduce cost resulted in a race to the bo om, often
affecting the quality of patient care and provider morale. As a
result, many hospitals and physicians opted out. These payment
models will still persist to control cost; however, efforts are being
made to be er identify and predict risk that may result in increased
cost. Therefore, machine learning algorithms were inevitable and
used preoperative patient-specific comorbidity data to calculate
risk-adjusted and patient-specific payment models for episodes of
care. 48 Being able to use artificial intelligence/machine learning for
payment models based on complex patient-specific variables will
not only help identify cost-reduction strategies but also predict
outcome expectation. As physicians and hospitals continue to
collect, record, and organize patient data, artificial intelligence will
allow for complex analysis that will not only recognize pa erns not
known to exist, but also provide highly accurate patient-specific
care in a cost-efficient and time-efficient manner.

Natural Language Processing

Natural language processing refers to the ability of computers to
recognize, interpret, and potentially analyze human language, with
the goal of constructing an adaptive simulated thought process. 49
The earliest form of language processing has been voice
recognition. Care providers more recently have been using voice
recognition technology for the translation of human language into
words in a medical record. Although this improves time efficiency
by eliminating transcription/typing, it does not analyze context or
convert the data into coherent (parametric) form or provide any
feedback in the context of individual patient interactions, so as to
fill up fields in a database for example. Natural language processing
has the capability to provide real-time feedback during a patient
visit, allowing the physician to interact with the patient and ask
questions to improve the documentation. It will also help formulate
a note that is not only accurate and tailored to a specific patient, but
compliant with coding standards.
Another feature of this technology would be to recognize
commands such as “please schedule this patient for surgery.” This
command could then schedule a surgical date as well as inform
providers of the necessary preoperative pathway from clinic to
operating room. Such “workflow” automation capability can detect
a cardiac history and automatically make a referral to the patient’s
cardiologist for preoperative clearance. This is one example among
many that may help to avoid forge ing certain prerequisites prior
to surgical intervention. One example is Dragon Ambient
eXperience (Nuance of Burlington, MA, recently taken over by
Microsoft), which is leading the way in medical natural language
processing. This recently launched artificial intelligence–powered
platform aims to improve automatic real-time documentation and
clinical intelligence.
As the technology continues to improve, it may only be years
before every clinic is equipped with an artificial intelligence–
powered platform that streamlines and improves patient care from
the very first clinic visit to a potential postsurgical outcome. Such
technology will indeed make the work of orthopaedic surgeons
easier, faster, cheaper, and be er.

Challenges of Artificial Intelligence in

Orthopaedics and Concluding Comments
Despite all the potential artificial intelligence may provide in the
field of orthopaedics, it remains in its infancy and of course with
some criticism. One main concern is the accuracy of the data, which
poses the question: Can the algorithm learn incorrectly? This has
been seen with large database studies that are dependent solely on
the quality of data that have been collected and analyzed and the
type of application. If the data lack granularity to start with, the
potential for false-negative and false-positive results increases. For,
example, imagine a TKA implant survival reported in a registry
with course data, logging overall success or failure (revision).
Suppose that TKA had an innovative and best-ever design of bone
fixation feature (fins, keel, etc) but a not-so-good sagi al and
coronal bearing conformity, compromising its constraint (knee
stability) and causing patient discomfort, and revised frequently for
that la er reason only. If the registry (which is typical) does not
report the detailed cause of failure and a ributes it to a specific
granular design feature, a false-negative result may be a ributed to
the whole system, also condemning the good fixation features.
Four critical points have been suggested for the application of
artificial intelligence in medicine: big and accurate data sets,
powerful computers, cloud computing, and open-source
algorithmic development. 50 None is far-fetched, but it is crucial to
continue to improve documentation accuracy and more granular
detailed data as this will affect the accuracy of artificial intelligence.
As the orthopaedic field continues to harness artificial
intelligence, it has the potential to become the new standard of
care, without known or sufficient checks and balances overseeing
the accuracy. Few published studies in the literature are trying to
compare the accuracy of artificial intelligence with that of current
known methodologies. However, as this technology grows, it will
far exceed the capability to compare with other areas of data
analysis, yet it can be anticipated to be relied on as the gold
standard. Additional studies analyzing the application and
accuracy of artificial intelligence are necessary not only to be
trusted but also to allow widespread adoption in healthcare.
Summary
Several important aspects of the history and principles of operation
of computer-aided orthopaedic technology such as navigation,
robotics, PSI, augmented and virtual reality, and machine and deep
learning applications of artificial intelligence are highlighted. What
are now considered classic navigation systems guide the
positioning of cu ing blocks or hip reamers. Robotics go a bit
further in that they automatically actuate the positioning of such
blocks or resection instruments. PSIs rely on the basic principles of
presurgical image-based bone modeling and surgical planning to
provide cu ing blocks without navigation or robots, but their
design and manufacture require a separate preparation process
before surgery. The future may bring additional utility with directly
navigated handheld resection instruments. All categories of
technology have weaknesses as well as clearly astonishing features.
The framework that was provided here should enable orthopaedic
surgeons to think and study further, and to be able to make links
between these technologies based on how they work. The ethics of
adopting any new technology should be considered, inviting
a ention to what must really ma er to all stakeholders whether
they are surgeons, hospitals, insurance or government payors, and
ultimately, the patients. The main question is whether a technology
would make a process easier, faster, cheaper, or be er; the
combination of all four is vital, which can be challenging.
Orthopaedics remains so exciting partly because many of its most
fundamental advances have been technology-driven, whether
imaging, implants, instruments, or the many advanced technology
topics covered here. Most likely, the best is yet to come.

Key Study Points

The ethics of adopting navigated and robotic surgery technology are complicated
with an abundance of literature. Regulatory (eg, FDA) clearance does not mean
approval. The responsibility is that of the surgeon to thoroughly review the presented
evidence and make their own judgment.
 The judgment criteria for emerging robotic technology should include whether it
would make the surgery easier, faster, cheaper, and better. In joint arthroplasty, all of
these have been found to be important and demand that innovative technologies
should transcend well beyond any initial excitement or hype.
Orthopaedics has always been influenced by big data, from local outcome studies to
national registries. Computer learning and artificial intelligence will revolutionize how
big data are harnessed. This will span from superior to human radiographic
interpretation for osteolysis and implant recognition, natural language processing
filling databases of patient records, to optimized patient-specific care, and
management of patient expectations and satisfaction.

Annotated References
1. Iserson KV, Chiasson PM: The ethics of applying new medical
technologies. Semin Laparosc Surg 2002;9:222-229.
2. Bargar WL, Bauer A, Börner M: Primary and revision total hip
replacement using the Robodoc system. Clin Orthop Relat Res
1998;354:82-91.
3. Davies BL, Harris SJ, Lin WJ, et al: Active compliance in robotic
surgery—the use of force control as a dynamic constraint. Proc
Inst Mech Eng H 1997;211:285-292.
4. Cobb J, Henckel J, Gomes P, et al: Hands-on robotic
unicompartmental knee replacement: A prospective, randomised
controlled study of the acrobot system. J Bone Joint Surg Br
2006;88:188-197.
5. Lin J, Yan S, Ye Z, Zhao X: A systematic review of MAKO-
assisted unicompartmental knee arthroplasty. Int J Med Robot
2020;16:e2124. This is a systematic review highlighting be er
implant accuracy, soft-tissue balance, and early patient function
scores using MAKO for unicompartmental knee arthroplasty.
6. Tompkins GS, Sypher K, Li H, Griffin M, Duwelius P: Robotic
versus manual total knee arthroplasty in high volume surgeons: a
comparison of cost and quality metrics. J Arthroplasty
2022;37(8S):S782-S789. This was a retrospective matched-cohort
study comparing robotic versus manual TKA. Robotic TKA
 required more operating room time, was more expensive, and did
not show any differences in length of stay or complications.
7. Shatrov J, Murphy GT, Duong J, Fritsch B: Robotic-assisted total
knee arthroplasty with the OMNIBot platform: A review of the
principles of use and outcomes. Arch Orthop Trauma Surg
2021;141:2087-2096. Robotic-assisted TKA using OMNIBot had 3-
year survivorship of 99.26% in one study and 99.48% survivorship
at 6 years.
8. Shalhoub S, Lawrence JM, Keggi JM, et al: Imageless, robotic-
assisted total knee arthroplasty combined with a robotic
tensioning system can help predict and achieve accurate
postoperative ligament balance. Arthroplast Today 2019;5:334-340.
OMNIBot with ligament balancer accurately predicts
postoperative gaps within 2 mm in more than 90% of knees
studied.
9. Wakelin EA, Shalhoub S, Lawrence JM, et al: Improved total
knee arthroplasty pain outcome when joint gap targets are
achieved throughout flexion. Knee Surg Sports Traumatol Arthrosc
2022;30:939-947. Joint gap thresholds of an equally balanced or
tighter medial compartment in extension, medial laxity ±1 mm
compared with the final insert thickness in midflexion, and a
mediolateral imbalance of less than 1.5 mm in flexion generated
subgroups that reported significantly improved Knee Injury and
Osteoarthritis Outcome Scores at 1 year. Combining any two
targets resulted in further improved outcomes, with the greatest
improvement observed when all three targets were satisfied.
Level of evidence: II.
10. Parra e S, Price AJ, Jeys LM, Jackson WF, Clarke HD: Accuracy
of a new robotically assisted technique for total knee
arthroplasty: A cadaveric study. J Arthroplasty 2019;34:2799-2803.
All six angles of bone cuts were within 1° difference with an SD
of less than ±1° of standard deviation when using Zimmer Rosa
robotic-assisted TKA platform.
11. Scuderi GR, Fallaha M, Masse V, et al: Total knee arthroplasty
with a novel navigation system within the surgical field. Orthop
Clin North Am 2014;45:167-173.
12. Goh GS, Liow MHL, Lim WS, et al: Accelerometer-based
navigation is as accurate as optical computer navigation in
restoring the joint line and mechanical axis after total knee
arthroplasty: A prospective matched study. J Arthroplasty
2016;31:92-97.
13. Desseaux A, Graf P, Dubrana F, Marino R, Clavé A:
Radiographic outcomes in the coronal plane with iASSIST™
versus optical navigation for total knee arthroplasty: A
preliminary case-control study. Orthop Traumatol Surg Res
2016;102:363-368.
14. Niehaus R, Schilter D, Fornaciari P, et al: Experience of total
knee arthroplasty using a novel navigation system within the
surgical field. Knee 2017;24:518-524.
15. Kinney MC, Cidambi KR, Severns DL, Gonzales FB: Comparison
of the iAssist handheld guidance system to conventional
instruments for mechanical axis restoration in total knee
arthroplasty. J Arthroplasty 2018;33:61-66.
16. Li J, Gao X, Li X: Comparison of iASSIST navigation system with
conventional techniques in total knee arthroplasty: A systematic
review and meta-analysis of radiographic and clinical outcomes.
Orthop Surg 2019;11:985-993. In this systematic review comparing
conventional versus iAssist navigation, iAssist significantly
improved accuracy of limb alignment but resulted in prolonged
surgical times without any apparent advantage in short-term
functional scores.
17. Nam D, Jerabek SA, Haughom B, et al: Radiographic analysis of
a hand-held surgical navigation system for tibial resection in total
knee arthroplasty. J Arthroplasty 2011;26:1527-1533.
18. Nam D, Nawabi DH, Cross MB, Heyse TJ, Mayman DJ:
Accelerometer-based computer navigation for performing the
 distal femoral resection in total knee arthroplasty. J Arthroplasty
2012;27:1717-1722.
19. Nam D, Weeks KD, Reinhardt KR, et al: Accelerometer-based,
portable navigation vs imageless, large-console computer-
assisted navigation in total knee arthroplasty: A comparison of
radiographic results. J Arthroplasty 2013;28:255-261.
20. Jones CW, Jerabek SA: Current role of computer navigation in
total knee arthroplasty. J Arthroplasty 2018;33:1989-1993.
21. Nam D, Cody EA, Nguyen JT, Figgie MP, Mayman DJ:
Extramedullary guides versus portable, accelerometer-based
navigation for tibial alignment in total knee arthroplasty: A
randomized, controlled trial—winner of the 2013 HAP PAUL
award. J Arthroplasty 2014;29:288-294.
22. Ba enberg AK, Netravali NA, Lonner JH: A novel handheld
robotic-assisted system for unicompartmental knee arthroplasty:
Surgical technique and early survivorship. J Robot Surg 2020;14:55-
60. This case series revealed 99.2% survivorship in 128 patients at
a mean 2.3-year follow-up with unicompartmental knee
arthroplasty using the Navio system.
23. Vaidya N, Jaysingani TN, Panjwani T, et al: Assessment of
accuracy of an imageless hand-held robotic-assisted system in
component positioning in total knee replacement: a prospective
study. J Robot Surg 2022;16;361-367. This case series reports
accuracy of all burred surfaces with root mean squared error of
0.56°.
24. Savov P, Tuecking LR, Windhagen H, Ehmig J, E inger M:
Imageless robotic handpiece-assisted total knee arthroplasty: a
learning curve analysis of surgical time and alignment accuracy.
Arch Orthop Trauma Surg 2021;141:2119-2128. A case-control study
of 70 Navio TKA surgeries revealed a learning curve of 11 cases to
reach time neutral compared with standard instrumentation.
There were no differences in limb alignment or component
positioning.
25. Haider H, Barrera OA, Garvin KL: Minimally invasive total knee
arthroplasty surgery through navigated freehand bone cu ing:
Winner of the 2005 “HAP” PAUL AWARD. J Arthroplasty
2007;22:535-542.
26. Barrera OA, Haider H, Garvin KL: Towards a standard in
assessment of bone cu ing for total knee replacement. Proc Inst
Mech Eng H 2008;222:63-74.
27. Garvin KL, Barrera A, Mahoney CR, Hartman CW, Haider H:
Total knee arthroplasty with a computer-navigated saw: a pilot
study. Clin Orthop Relat Res 2013;471:155-161.
28. Barrera OA, Haider H: Direct navigation of surgical
instrumentation, in Ritacco LE, Milano FE, Chao E, eds: Computer-
Assisted Musculoskeletal Surgery: Thinking and Executing in 3D.
Springer, 2016.
29. Beam AL, Kohane IS: Big data and machine learning in health
care. J Am Med Assoc 2018;319:1317-1318.
30. Bini SA: Artificial intelligence, machine learning, deep learning,
and cognitive computing: What do these terms mean and how
will they impact health care? J Arthroplasty 2018;33:2358-2361.
31. Cabi a F, Locoro A, Banfi G: Machine learning in orthopedics: a
literature review. Front Bioeng Biotechnol 2018;6:75.
32. Choy G, Khalilzadeh O, Michalski M, et al: Current applications
and future impact of machine learning in radiology. Radiology
2018;288:318-328.
33. Esteva A, Kuprel B, Novoa RA, et al: Dermatologist-level
classification of skin cancer with deep neural networks. Nature
2017;542:115-118.
34. Gulshan V, Peng L, Coram M, et al: Development and validation
of a deep learning algorithm for detection of diabetic retinopathy
in retinal fundus photographs. J Am Med Assoc 2016;316:2402-
2410.
35. Rainey C, McConnell J, Hughes C, Bond R, McFadden S:
Artificial intelligence for diagnosis of fractures on plain
 radiographs: A scoping review of current literature. Intelligence-
Based Med 2021;5:100033. All artificial intelligence models were
able to identify fractures; however, there was significant
variability in the algorithms and training methods for each
model.
36. Olczak J, Fahlberg N, Maki A, et al: Artificial intelligence for
analyzing orthopedic trauma radiographs. Acta Orthop
2017;88:581-586.
37. Joseph GB, McCulloch CE, Sohn JH, et al: AI MSK clinical
applications: cartilage and osteoarthritis. Skeletal Radiol
2022;51:331-343. Deep learning and artificial intelligence models
have been successful in detecting the severity of osteoarthritis on
radiographs as well as cartilage lesions on MRI.
38. Urish KL, Reznik AM: How Would a Computer Diagnose Arthritis
on a Radiograph? American Academy of Orthopaedic Surgeons
Now, 2018.
39. Ashinsky BG, Bouhrara M, Cole a CE, et al: Predicting early
symptomatic osteoarthritis in the human knee using machine
learning classification of magnetic resonance images from the
osteoarthritis initiative. J Orthop Res 2017;35:2243-2250.
40. Gan H, Ramlee MH, Wahab AA, Lee Y, Shimizu A: From
classical to deep learning: review on cartilage and bone
segmentation techniques in knee osteoarthritis research. Artif
Intell Rev 2021;54:2445-2494. This review discusses the role and
application of deep learning as it applies to cartilage and bone
segmentation techniques in knee osteoarthritis.
41. Karnuta JM, Luu BC, Roth AL, et al: Artificial intelligence to
identify arthroplasty implants from radiographs of the knee. J
Arthroplasty 2021;36:935-940. This study was using machine
learning and artificial intelligence for identification of femoral
implant manufacturer and model from plain radiographs. A
deep-learning system managed to accurately differentiate among
18 hip arthroplasty models from four industry leading
manufacturers.
42. Karnuta JM, Haeberle HS, Luu BC, et al: Artificial intelligence to
identify arthroplasty implants from radiographs of the hip. J
Arthroplasty 2021;36:S290-S294.e1. Using a deep-learning model,
18 different femoral components were able to be differentiated
with an accuracy of 99.6%, a sensitivity of 94.3%, and a specificity
of 99.8%.
43. Borjali A, Chen AF, Bedair HS, et al: Comparing the
performance of a deep convolutional neural network with
orthopedic surgeons on the identification of total hip prosthesis
design from plain radiographs. Med Phys 2021;48:2327-2336.
Using a trained convolutional neural network, failed total hip
implants were able to be identified with great accuracy in 0.06
seconds. This is significantly faster and more accurate than a
trained orthopaedic surgeon.
44. Borjali A, Chen AF, Muratoglu OK, Morid MA, Varadarajan KM:
Detecting total hip replacement prosthesis design on plain
radiographs using deep convolutional neural network. J Orthop
Res 2020;38:1465-1471. Convolutional neural network achieved
100% accuracy in the identification of three commonly used THA
implant designs. Such a convolutional neural network can be
used to automatically identify the design of a failed THA implant
preoperatively in just a few seconds, saving time and improving
the identification accuracy.
45. Vogrin M, Trojner T, Kelc R: Artificial intelligence in
musculoskeletal oncological radiology. Radiol Oncol 2020;55:1-6.
This review article dives into the potential for artificial
intelligence to detect bone and soft-tissue tumors.
46. Zhu Y, Green AC, Guo L, Evans HR, Mihaylova L: Machine
learning approaches for cancer bone segmentation from micro
computed tomography images, in 2020 IEEE 23rd International
Conference on Information Fusion (FUSION). IEEE, 2020, pp 1-6.
This animal-based study demonstrates the potential of
automated bone tumor segmentation using machine learning
models.
47. Makhni EC, Makhni S, Ramkumar PN: Artificial intelligence for
the orthopaedic surgeon: An overview of potential benefits,
limitations, and clinical applications. J Am Acad Orthop Surg
2021;29:235-243. This review article discusses the application of
artificial intelligence in orthopaedic surgery. This article also
identifies potential bo lenecks involved with building machine
learning algorithms.
48. Ramkumar PN, Karnuta JM, Navarro SM, et al: Preoperative
prediction of value metrics and a patient-specific payment model
for primary total hip arthroplasty: development and validation of
a deep learning model. J Arthroplasty 2019;34:2228-2234.e1. This
deep-learning model demonstrated an ability to learn in a
prediction model of value-centered outcomes. This can be
applied to patient-specific payment models based on complexity
of the case.
49. Myers TG, Ramkumar PN, Ricciardi BF, et al: Artificial
intelligence and orthopaedics: An introduction for clinicians. J
Bone Joint Surg Am 2020;102:830-840. This is another review article
discussing the application of artificial intelligence in
orthopaedics surgery. This article also identifies the challenges
and limitations of machine learning algorithms.
50. Topol EJ: Deep Medicine: How Artificial Intelligence Can Make
Healthcare Human Again. Basic Books, 2019, 400 pp. The first
book published on the topic discusses the benefits and
application of artificial intelligence in healthcare.
S E CT I ON 2

Translational Science and

Emerging Technologies
SECTION EDITOR
Francis Young-In Lee, MD, PhD, Hon MBA, FAAOS
C H AP T E R 1 2

Structure and Biology of Normal

and Diseased Bone
David Clever MD, PhD, Cecilia Pascual-Garrido MD, PhD,
Regis O’Keefe MD, PhD, FAAOS

Dr. Pascual-Garrido or an immediate family member serves as a paid consultant to or is an

employee of ARVIS and has received research or institutional support from AOSSM/Sanofi,
National Institutes of Health (NIH), OREF, and Zimmer. Dr. O’Keefe or an immediate family
member serves as a board member, owner, officer, or committee member of the American
Orthopaedic Association. Neither Dr. Clever nor any immediate family member has received
anything of value from or has stock or stock options held in a commercial company or institution
related directly or indirectly to the subject of this chapter.

ABSTRACT
The bony skeleton is the structural and biologic foundation for the
musculoskeletal system. Despite breadth of diversity in shape, size,
and function among the bones in the human skeleton, the basic
cellular building blocks and biologic processes remain consistent.
Disruption of the fundamental biologic programs that establish
and maintain bone structure, either acquired or inherited, is the
root cause of the variety of bone diseases encountered by the
orthopaedic surgeon. It is important to be knowledgeable about
pertinent elements of normal bone structure from the molecular
underpinnings to three-dimensional anatomy, along with how
perturbations of normal bone biologic processes cause the bony
changes seen in several disease states.
Keywords: bone pathology; molecular determinants of bone health;
skeletal structure
Introduction
Bone is the foundational tissue of the musculoskeletal system.
Although often thought of as only structural, bone is a dynamic
tissue with specialized properties that allow it to serve a diversity of
mechanical and metabolic functions. The myriad biologic processes
in which bones are involved include locomotion, protection of vital
structures, formation of blood and immune cells, and ion
homeostasis. Given this diversity of roles and responsibilities,
bones come in a variety of shapes and sizes unique to distinct
functional demands. The structural integrity of bone is intricately
designed and tightly orchestrated. An understanding of the basic
principles of bone structure and function, along with the
composition and function of bone and the pathologic basis of
diseases affecting bone structure, is key to recognizing and
preventing the sequelae associated with disease that disrupts
normal bone homeostasis. The composition and function of bone,
the pathologic basis of diseases affecting bone structure, and novel
therapeutic approaches that have been developed to aid in the
assessment, prevention, and management of bone disorders are
important factors.

Bone Structure in the Healthy State

The structure and composition of bone establishes the unique
properties that allow the skeleton to function in a multitude of
diverse physiologic processes. Although easy to view as an inert
tissue, bone is dynamic, constantly remodeling, and exquisitely
responsive to environmental and genetic perturbations. The
structure of bone in the healthy state comprises cellular and
acellular components, molecular regulators of skeletal elements,
and gross anatomy.

Cellular Constituents of Bone

Although there are several cell types that contribute to the overall
health and function of the skeletal system, the main cellular
components of bone are osteoblasts, osteoclasts, and osteocytes
(Figure 1). These cell types reside directly within bone and regulate
the synthesis and degradation of the acellular matrix components
of bone. 1 Bone resorption and formation are predominantly carried
out by osteoblasts and osteoclasts. Osteocytes, the most numerous
of the bone cells, are important mechanosensors that translate
mechanical stimuli to biochemical processes. A fourth cell type,
referred to as bone-lining cells, represents terminally differentiated
osteoblasts that adhere tightly to the surface of bone and play a
regulatory role in bone remodeling.
 Figure 1 Cellular constituents of bone.Histologic images and brief description
of the major cellular constituents of bone. Individual cells identified of indicated
phenotype indicated with black arrows.DKK1 = Dickkopf-1, FGF = fibroblast
growth factor, HCl = hydrogen chloride, Ihh = Indian hedgehog, M-CSF =
macrophage colony- stimulating factor, NF-κB = nuclear factor kappa B, OPG =
osteoprotegerin, Osx = osterix, PTH = parathyroid hormone, RANKL = receptor
activator of nuclear factor kappa B ligand, TGF-β = transforming growth factor
beta. (Histologic images courtesy of Deborah Veis, MD, PhD.)

Osteoblasts are the main bone-forming cells and are identified

histologically based on the expression of several components
critical to their function and regulation including alkaline
phosphatase and parathyroid hormone receptor. Osteoblasts are
efficient synthesizers of extracellular matrix (ECM). The primary
function of this cell type is secretion of osteoid (unmineralized
bone), which is predominantly composed of type 1 collagen,
osteocalcin, osteonectin, and osteopontin. On a molecular level,
osteoblasts can be identified by expression of the lineage-specifying
transcription factors Runx2. 2 Osteoblasts possess a very organized
cellular composition that allows them to sense environmental
regulators at their apical surface and secrete molecules important
for new bone formation at the basal surface. Metabolically, as
described in a 2021 study, osteoblasts use predominantly glycolytic
programs that allow for shunting of important metabolic
byproducts into biosynthesis pathways for the production of
various ECM components. 3 Osteoblasts are responsive to a variety
of hormonal stimuli. Estrogen promotes bone formation by
restricting osteoblast homeostasis, whereas chronic glucocorticoid
use can decrease bone mineral density partially through
augmentation of osteoblast and osteocyte apoptotic rate.
Osteoclasts are the main mediators of bone resorption.
Histologically, osteoclasts are identified as multinucleated giant
cells with abundant expression of the cell surface molecules
receptor activator of nuclear factor kappa B (RANK, an activator of
the osteoclast resorption program) and the integrin receptor αvβ3
(cell surface adhesion molecule critical for osteoclast adhesion to
bone surfaces). 4 The basal surface is identified by a characteristic
ruffled border, which creates a sealing zone where resorption of
mineralized bone matrix takes place. Bone resorption is stimulated
by signaling through the RANK pathway. There are several sources
of RANK ligand (RANKL) that can induce osteoclast-mediated
bone resorption, including osteoblasts, T cells, stromal fibroblasts
and adipocytes, and cancer cells. Osteoclast activity is also tightly
orchestrated by several hormonal stimuli. Estrogen has been shown
to limit c-Jun activity, thus restricting RANKL-induced osteoclast
differentiation. Histologically, osteoclasts are defined by multiple
nuclei and abundant cytoplasm containing a high density of
lysosomes and mitochondria to support their immense and diverse
energy demands. Osteoclasts have dynamic and tightly regulated
metabolic programs. Preliminary studies suggest that glycolysis is
the predominant mechanism of energy generation in osteoclasts
actively engaged in bone resorption, whereas oxidative
phosphorylation is the main bioenergetic source for osteoclast
formation. Metabolic regulation of osteoclast formation and
function remains an active area of ongoing research and potential
therapeutic intervention. 5
Osteocytes are terminally differentiated cells that originate from
osteoblasts, reside in characteristic lacunae embedded by bone
matrix, and function as the main mechanosensors in bone. 6 The
mechanisms that regulate osteoblast differentiation to mature
osteocytes remain incompletely elucidated, but involve a selective
downregulation of canonical osteoblast genes and upregulation of
selective osteocyte-associated genes: dentin matrix protein 1,
fibroblast growth factor 23 (FGF23), ECM phosphoglycoprotein, and
phosphate-regulating endopeptidase homolog X-linked. Osteocytes
are characterized by extensive dendritic cytoplasmic projections
that tunnel through mineralized bone matrix to establish the
lacunar-canalicular arrangement in bone. 6 These interconnections
coordinate intercellular communication within bone and transfer
mechanical stimuli into biochemical processes that influence bone
resorption and formation. 7 In response to mechanical signals such
as shear stress or mechanical loading, osteocytes increase RANKL
secretion (activates osteoclasts) and decrease sclerostin (an
inhibitor of osteoblast anabolism) production. 8 Collectively,
mechanical stresses on bone activate the remodeling system
mediated by osteocyte mechanotransduction of osteoblast and
osteoclast-regulating molecules.

Stem Cell Origin of Bone Cells

One of the main physiologic functions of bone is to provide a
supportive environment for bone marrow stem cell self-renewal
and differentiation. Far from simply serving as structural support,
bone cells and the proteins they secrete have important influence
on the fate commitment of various stem cell precursors. For
example, in response to mechanical stress, osteocytes coordinate
commitment of hematopoietic stem cells to the osteoclast lineage,
thus promoting skeletal remodeling in a guided manner directly in
response to mechanical stimuli.
 Resident bone marrow stem cells are localized within trabecular
spaces of the skeleton. Within these bone marrow niches reside a
variety of precursor cell types, including stem cells of mesenchymal
and hematopoietic origin that give rise to osteoblasts and
osteoclasts, respectively. Stem cells capable of forming osteoblasts
and other mesenchymal tissues were historically referred to as
mesenchymal stem cells, a term that encompasses a heterogenous
population of undifferentiated cells capable of producing cells of
osteogenic and chondrogenic origin. Recent studies have identified
a more pure skeletal stem cell characterized by distinct cell surface
markers and differentiation pa erns. 9 These cells are particularly
enriched in hypertrophic zones of the epiphyseal plate, but can also
be isolated from other regions of bone including the femoral head,
from bone morphogenetic protein 2 treated adipose cells, and from
induced pluripotent stem cells. As discussed in a 2021 study,
skeletal stem cells proliferate in the se ing of bone injury and
demonstrate age-associated phenotypic changes that predispose to
diseases such as osteoporosis. 10
Osteoclasts are a distinct bone cell in that they are derived of
hematopoietic rather than mesenchymal origin. As such, they share
many similarities to monocytes and macrophages histologically,
genetically, and functionally. Differentiation of hematopoietic stem
cells to the osteoclast lineage requires intimate interaction with
bone stromal elements. Commitment to the osteoclast lineage is
coordinated by stromal derived factors including RANKL and
colony-stimulating factor 1. RANKL activates RANK receptors on
hematopoietic stem cells, which in turn stimulates tumor necrosis
factor receptor–associated cytoplasmic factors (TRAF), including
TRAF6, to localize to the cytoplasmic portion of the RANK
receptor. TRAF6 activates signal transduction pathways that
support osteoclastogenesis by inducing expression of osteoclast-
specific genes. 11

ECM and Ion Homeostasis

Despite a multitude of specialized cell types residing within and
contributing to the many functions of bone, the physical mass of
bone tissue is predominantly composed of acellular ECM. The ECM
of bone can be largely classified into two components: organic and
mineralized. The organic ECM components are formed
predominantly by osteoblasts and are secreted in an unmineralized
form called osteoid. Osteoid is generally found over bone surfaces
and in areas of new bone formation. Mineralization of osteoid is a
hallmark in the formation of new bone. It is ultimately the
mineralized bone matrix that comprises a large majority of overall
bone mass and largely defines bone’s material properties.
The organic component of ECM is 90% type 1 collagen. Other
important organic components of ECM include osteocalcin,
fibronectin, proteoglycans, bone morphogenetic proteins, and
growth factors. In order for collagen to be secreted by osteoblasts,
it must be modified pos ranslationally. These modifications
include hydroxylation of proline groups, which mechanistically
explains why hydroxyproline can be used as a clinical marker of
collagen breakdown. Secreted collagen fibrils exist in a helical
structure and are held stable by intrinsic interactions between
helices as well as interchain covalent cross-links. This specific
collagen arrangement provides the tensile strength of bone, and
modification to the level of collagen interaction can produce bone
tissue of various tensile strengths. 12
At any given time, approximately 70% of the skeletal ECM is
mineralized. Mineralization of organic matrix refers to the
inorganic ionic components that are demoisted in close association
with collagen fibrils. The mineral crystals found in bone are a
calcium phosphate compound called hydroxyapatite. In a process
termed nucleation, calcium and phosphate ions are arranged into a
crystalline hydroxyapatite molecule, which is then deposited in
pockets of collagen fibrils under the promotion of supportive
proteins such as biglycan and bone sialoprotein. After deposition
of an initial hydroxyapatite crystal, mineralization of the organic
ECM becomes an efficient process with multidirection secondary
nucleation ensuing from the surface of the initially deposited
crystal. 1
Through mineralization and demineralization of ECM tissue,
bone plays an important role in systemic ion homeostasis,
predominantly calcium balance. As such bone is exquisitely
responsive to hormonal regulators of calcium balance. Parathyroid
hormone can activate osteoblasts to secrete RANKL, which in turn
activates osteoclasts. This leads to increased bone resorption,
demineralization of existing bone matrix, and elevation of serum
calcium levels. In the se ing of hypercalcemia, calcitonin is
produced by cells of the thyroid gland and leads to decreased
serum calcium through dual effects in activating osteoblast and
inhibiting osteoclast function. Vitamin D is a critical component of
calcium ion homeostasis as it is required for dietary calcium
absorption. Recent studies have also demonstrated a direct role for
vitamin D in stimulating the proliferation and differentiation of
human osteoblasts. 13

Three-Dimensional Anatomy of Bone

Despite significant variability in the shape and size of bones in the
human skeleton, the functional elements that support distinct
physiologic roles in bone are conserved. Mature bone structure is
characterized by its functional organization, either
trabecular/cancellous or cortical. Trabecular bone is characterized
by a loose organization of bony struts with interspersed bone
marrow and stromal elements. The bony matrix components in
trabecular bone are organized parallel to the direction of the
trabecular strut and form discrete packets of bone tissue where
bone remodeling cycles take place. Cortical bone is densely packed
compact bone arranged in an organized concentric lamellar
structure. The functional unit of cortical bone is called an osteon or
haversian system, which are concentric rings of osteocytes and
organized mineralized matrix with a central haversian canal. Each
osteon is separated from other osteons by a cement line, but
interosteon communication is facilitated by Volkmann canals,
which run approximately perpendicular to the haversian system.
All bone surfaces are covered by specialized tissues. The
outermost surface of bone is called the periosteal membrane, a
highly innervated and well-vascularized structure consisting of
fibrous connective tissue and an inner osteogenic layer of
progenitor cells that can mature in response to various cues to
stimulate the formation of new bone. Periosteal vessels supply the
outer one-third of cortical bone. The inner surface of bone is
referred to as the endosteal surface, is typically very thin, and
consists of terminally differentiated osteoblasts referred to in this
context as bone-lining cells. Vascular supply to the inner two-thirds
of cortical bone is provided by nutrient arteries that pass through
cortical foramen and travel through the haversian and Volkmann
canals. Blood supply to trabecular bone is mediated by diffusion
from adjacent bone marrow elements.

Microbial Influence on Bone Health

The effect of nutritional status on bone health and bone mineral
density is well established. Deficiencies in vitamin D lead to poor
intestinal calcium absorption and subsequent decreased bone
mineralization. As such, vitamin D and calcium supplementation
have been long-standing interventions for conditions characterized
by low bone mineral density such as osteoporosis. A rapidly
developing area of study and clinical intervention is the influence of
the gut microbiome on bone health. 14 The human microbiome
refers to the trillions of microbes that inhabit the human body and
the products they secrete. Alterations in the microbiome have been
associated with several pathologies, including osteoporosis. A
healthy intestinal microbiome maintains gut epithelial health to aid
in calcium absorption. Moreover, short chain fa y acids that are
produced from bacterial digestion of dietary fiber can limit
osteoclast differentiation and function without compromising bone
formation. 15 Recent studies demonstrate that reconstitution of
healthy gut microbiome with a specialized diet consisting of
supplemental sialylated milk oligosaccharides leads to increased
femoral trabecular bone volume and cortical thickness in
preclinical murine models and increased serum markers of
osteoblastic differentiation in malnourished children 16 , 17 (Figure
2). An understanding of the specific microbial species and their
metabolic byproducts that influence overall bone health is an
exciting area of ongoing research and represents immense clinical
opportunity for low-cost intervention for a variety of skeletal
pathologies.

Figure 2 Manipulating the microbiome to promote skeletal

development.Schematic representing the use of microbiota-directed
complementary food (MDCF) compared with standard-of-care ready-to-use
supplementary food (RUSF) for severe acute malnutrition (SAM). Augmenting
dietary regimens to support characteristic microbiome species with MDCF can
lead to increased serum levels of markers of bone and central nervous system
(CNS) development.(Figure adapted from Gehrig JL, Venkatesh S, Chang HW,
et al: Effects of microbiota-directed foods in gnotobiotic animals and
undernourished children. Science 2019;365[6449]:eaau4732.)

Skeletal Structure in Diseased States

With an understanding of the cellular constituents and gross
anatomy of bone, as well as the factors that promote and maintain
its health and structure, it is important to focus on the genetic and
environmental factors that disrupt normal bone structure and
cause common musculoskeletal pathologies.
Osteogenesis Imperfecta
Osteogenesis imperfecta, also known as bri le bone disease, is a
genetic skeletal disorder estimated to affect approximately 1 in
13,500 to 15,000 births. 18 The disease results from autosomal
dominant mutations in the genes encoding type 1 collagen
(COL1A1/2). Four types of osteogenesis imperfecta have been
described: 19 type I corresponds to the mildest form, type II to the
perinatal lethal form, type III to the most severe form compatible
with life, and type IV is an intermediate group. Over the past 10
years, the classification, which was initially phenotypically based,
has expanded to currently include more than 16 different types as
this number is constantly increasing with novel gene discovery. 18
Heterozygous mutations in the collagen genes COL1A1 and
COL1A2 are the most common cause of osteogenesis imperfecta.
The large size of these genes explains the numerous known
mutations and part of the heterogeneity of the clinical symptoms.
Two different pathophysiologies can be described: Loss-of-function
mutations such as stop mutations lead to haploinsufficiency.
Patients have a reduced amount of collagen, but this is of normal
quality. In contrast, other mutations (mostly glycine substitutions)
lead to qualitative alterations of the ECM, because the collagen
molecules and later fibrils cannot assemble properly. Because of the
reduced bone stability and the stimulated degradation, osteoblasts
produce as much osteoid as possible, but this is of lower quality.
This results in high-turnover osteoporosis. Additionally, mutations
in several other genes can result in the clinical picture of
osteogenesis imperfecta. Moreover, mutation in several genes can
result in the clinical picture of osteogenesis imperfecta without
changing the collagen sequences but rather affecting the
biosynthetic pathway and secretion of collagens. These include
P4HB, P3HI, CRTAP, PPIB, and several others.
The symptoms of the disease can be divided into skeletal and
extraskeletal findings. Skeletal symptoms are decreased bone mass
leading to reduced bone stability. This results in an increased
fracture rate of the long bones after minor trauma, as well as
deformities of vertebrae. Scoliosis is an additional problem that
develops frequently during puberty in more severely affected
patients and can lead to impairment of pulmonary function. Short
stature is present in almost all patients and extremities can be
disproportioned. As a collagen disorder, additional extraskeletal
symptoms can include hypermobility of ligaments and increased
fragility of vessels. An effect on heart valves has also been
described as well as an early loss of hearing. An obvious but not
always persistent finding is a blue-gray discoloration of the sclera in
approximately 50% of patients with osteogenesis imperfecta.
Because of the close biochemical relationship between collagen and
dentin, the teeth are affected in some patients, leading to
dentinogenesis imperfecta with amber-colored appearance and
increased bri leness. 20
Histologic changes include quantitative deficiencies in ECM
production and mineralization. In addition, the persistence of
cartilage within bone trabeculae of the diaphysis, and the absence
of lamellar bone and mature haversian systems indicate
abnormalities in the bone maturation process by which
cartilaginous precursor structures are replaced by woven bone, and
subsequently by mature lamellar bone (Figure 3, A).
Figure 3 Histologic and radiographic findings of osteogenesis imperfecta,
osteopetrosis, and Paget disease.A, Bone histologic sample from a patient with
osteogenesis imperfecta (right) demonstrating abundant unmineralized osteoid
(blue) and failure of woven bone to become lamellar bone. Standing alignment
films from a patient with osteogenesis imperfecta demonstrating characteristic
changes seen in osteogenesis imperfecta including long bone deformity, thin
cortices, and pathologic fractures (red arrow). B, Histologic features of
osteopetrosis include retained intraosseous cartilage (purple) and unorganized
woven bone (pink). Standing alignment films from a patient with osteopetrosis
with characteristic radiographic patterns including cortical sclerosis and
thickening (white arrow), pathologic femoral head collapse, osteoarthritis. C,
Histologic features seen in Paget disease include increased bone biomass in a
disorganized mosaic pattern. Thick cement lines separate lamellar bone
oriented in random pattern. Radiographic features of Paget disease include
flame-shaped or blade-of-grass appearance of remodeled cortices, long bone
bowing, and frequently end-stage osteoarthritis.(Histologic images courtesy of
Deborah Veis, MD, PhD and radiographs courtesy of Mark Miller, MD and John
C. Clohisy, MD.)
 Medical treatments with diphosphonates are currently used as
standard therapy in patients with a moderate or severe course of
the disease in childhood and adolescence. These drugs effectively
reduce bone resorption and thereby increase bone mass. In
addition, the strengthening of muscles induces an osteoanabolic
stimulus, which leads to an increase in the synthesis of ECM by
osteoblasts. Although the function of osteoblasts can be impaired
in osteogenesis imperfecta, using the muscles is still the best way to
stimulate bone formation. 21

Osteopetrosis
Osteopetrosis is a heritable disorder characterized by defective
osteoclast resorption leading to universally hard and bri le bone. 22
Three types of osteopetrosis have been described: malignant,
intermediate, and benign (Table 1). Osteopetrosis compromises the
ability of osteoclasts to remodel bone during growth; bone remains
disorganized and thick. Osteopetrosis significantly compromises
the body’s ability to acidify the Howship lacuna and to resorb bone
and calcified cartilage. This results in a generalized sclerosis.
Genetic defects in the chloride channel 7 gene (ie, CLCN7), the
proton pump, and carbonic anhydrase II result in osteopetrosis
(Figure 4). Mutations in the proton pump account for
approximately 60% of cases. Defects within the CLCN7 gene
represent the cause in approximately 12% of patients. 23

Table 1
Classification of Osteopetrosis

Radiographic
Type Inheritance Gene/Function Clinical Presentation
Features
Malignant Autosomal TCIRG1/Proton Present in infancy Increased
recessive pump Death in first decade bone density
Severe osteosclerosis Absent
Hearing/visual loss marrow cavity
Hepatosplenomegaly Abnormal
Infection metaphyses
 Radiographic
Type Inheritance Gene/Function Clinical Presentation
Features
Intermediate Autosomal CLCN7/Chloride Fractures Increased
recessive channel Cerebral calcifications bone density
CAII/Carbonic Renal acidosis Intracranial
anhydrase II Anemia (mild) calcification
Cranial nerve palsies Metaphyseal
widening
CLCN7/Chloride Frequent fractures Increased
channel Osteomyelitis of the jaw bone density
Anemia (mild) Decreased
Cranial nerve palsies marrow cavity
Abnormal
metaphyses
Benign Autosomal CLCN7/Chloride Frequent fractures Thickening of
dominant channel Coxa vara skull base and
Osteoarthritis/spondylosis vertebra end
Cranial nerve palsies plate
Endobone
appearance

Figure 4 Illustration of the molecular mechanisms of osteoclast dysfunction in

osteopetrosis.Osteopetrosis is caused by failure of acidification at the ruffled
border resulting in failure of resorption of mineralized bone matrix. Defects
known to cause osteopetrosis include mutations in the carbonic anhydrase
enzyme (CA), chloride channel CLCN7, and the H+-ATPase (left).

The histologic features of osteopetrotic bone result from the lack

of remodeling during nascent bone development. Osteoclasts never
resorb the primary spongiosa, woven bone, and calcified cartilage
present in immature bone (Figure 3, B). The lack of absorption of
the primary spongiosa during development explains the sclerotic
appearance of the disease on plain radiographs because the
spongiosa persists throughout life. Calcified cartilage and thick
trabeculae remain in the diaphysis. Because calcified cartilage has
mechanical properties inferior to those of bone, this abnormal
constitution leads to pathologic fractures. After development, bone
remains inorganic and bri le, reminiscent of ceramic, marble, or
rock. Despite a normal appearance under light microscopy, electron
microscopy reveals that the ruffled border is missing. This indicates
that osteoclasts are present but dysfunctional and thus cannot
acidify bone. The sclerosis of bone is the result of increased
thickness and disorganization, not an increase in mineralization.
The thickness of cortical bone significantly increases, causing it to
impinge on the medullary cavity. Furthermore, osteopetrotic
cancellous bone is thicker and less porous than normal bone.
Clinical presentation varies according to osteopetrosis type.
Malignant autosomal recessive osteopetrosis typically presents in
the first year of life. Only 30% of patients survive to the age of 6
years; most do not survive past the first decade. Bony overgrowth of
marrow spaces blocks hematopoiesis, leading to myelophthisic
anemia and hepatosplenomegaly. Additionally, neurologic deficits
are common and secondary to compression of cranial nerves.
Children typically present with either transverse metaphyseal and
diaphyseal fractures or epiphyseal fracture-separations. The
intermediate form of osteopetrosis shares many of the features of
the malignant form, but it is less severe and later in onset.
Fractures are common in the first decade. Intermediate forms also
display symptoms of optic, trigeminal, facial, and auditory nerve
compression. The benign autosomal dominant osteopetrosis is
most commonly seen. Most patients with the benign form first
learn of their diagnosis after a fracture. Typical features are
frequent fractures, long bone deformity, and osteoarthritis 24
(Figure 3, B). Still, almost 40% of these patients are asymptomatic.
Other manifestations include severe osteoarthritis at early age,
lumbar pain, scoliosis, and spondylolysis. Radiographic
manifestations include generalized sclerosis of the appendicular
and axial skeleton and vertebral end plate thickening.
Medical treatment includes long-term treatment with interferon
gamma, which increases bone resorption. Additionally, prednisone
ameliorates the hematologic status of patients with osteopetrosis.
Fracture fixation is challenged by difficulty inserting pins and
screws, refracture of long bones, and increased time to union.
When performing arthroplasty in these patients, the surgeon must
be aware of iatrogenic fracture during implant placement, increased
risk of osteomyelitis, and obliteration of the medullary canal by
cortical bone.

Paget Disease
Paget disease, historically known as osteitis deformans, is thought
to be an intense focal resorption of normal bone by abnormal
osteoclasts. 25 The abnormal osteoclasts make large resorption
cavities in the bone matrix. In response to the osteoclast resorption,
osteoblasts are recruited, resulting in bone formation. The
osteoblast activity is so rapid that the newly formed bone is not
organized and remains irregular and woven in nature. The newly
formed woven bone is less resistant and more elastic than typical
lamellar bone; hence, it is prone to deformity and fracture,
especially in the weight-bearing extremities. Three phases have
been described (lytic, mixed, and sclerotic). Genetically
abnormalities have been related to 5q35QTER (ubiquitin-binding
protein sequestosome) and SQSTM1 (p62/sequestosome).
Histologically, there is an increase in bone mass, but the bone is
exaggerated, disorganized, and dysfunctional. The bone appears in
a mosaic pa ern, with thick cement lines that demarcate randomly
oriented lamellar bone (Figure 3, C). The exaggerated trabeculae
and disorganized cortices result in a lack of ability to resist
deformation, and greatly increased vulnerability to fracture.
 Although the disease is regularly an incidental finding, patients
may present with bone pain, bone deformity, fracture, arthropathy,
skin temperature changes, or neurologic complications. Bone pain,
not an infrequent complaint, is characterized by a constant, poorly
localized pain that is present at rest. Patients with bone deformity
may present with a cosmetic complaint or significant functional
limitation (long bone bowing). Warmth over the affected area is
usually the result of hypervascularity of the underlying soft tissue
and bone. There is also high prevalence of neurologic
complications, including deafness and compression of other cranial
nerve palsies. Prevalence of osteoarthritis is significantly higher in
this population, and secondary sarcomas are also common to see.
Sarcomas should be suspected in a patient with history of Paget
disease and new intense pain. 26
Radiographically, typically the bone has a blade-of-grass or flame-
shaped appearance. Remodeled cortices, long bone bowing, and hip
and knee osteoarthritis are commonly seen (Figure 3, C). Serum
total alkaline phosphatase is the primary marker of bone formation
and is the most sensitive blood test for diagnosis. 27
Diphosphonates are the first-line treatment for symptomatic
Paget disease. When surgical treatment is performed in these
patients, it is important to anticipate increased intraoperative
bleeding. Preoperative treatment with calcitonin or diphosphonates
is recommended to reduce intraoperative and postoperative
bleeding. 28

Osteomalacia
Osteomalacia describes conditions in which bones and calcified
cartilage are soft because of insufficient mineralization. Generally
associated with deficiencies in vitamin D, its metabolites, or its
receptor, osteomalacia may also reflect problems with calcium or
phosphate handling. As discussed in a 2020 study, a rare form of
osteomalacia, tumor-induced osteomalacia, is a paraneoplastic
syndrome of abnormal vitamin D and phosphate metabolism
mediated by tumor secretion of FGF23. 29 Regardless of the
underlying pathology, osteomalacia is uniformly defined by
defective bone mineralization.
Classically, vitamin D deficiency can lead to poor bone
mineralization, resulting in rickets in children and osteomalacia in
adults. Vitamin D deficiency can result from several causes,
including decreased dietary intake and/or absorption, decreased
sun exposure, decreased endogenous synthesis, and increased
hepatic catabolism. Vitamin D plays a crucial role in calcium
homeostasis and bone metabolism. Vitamin D is obtained through
dietary sources, oral supplements, and exposure to sunlight (Figure
5).
 Figure 5 Illustration of the vitamin D metabolic and endocrine
pathway.Cutaneous production occurs in the skin with conversion of 7-
dehydrocholesterol to vitamin D3 by ultraviolet B (UVB) radiation. Dietary-derived
and synthesized forms of vitamin D are then hydroxylated in the liver to form 25-
hydroxyvitamin D (calcifediol). Further hydroxylation in the kidney produces the
active form of vitamin D, 1,25-dihydroxyvitamin D (calcitriol), which maintains
calcium and phosphate homeostasis through intestinal absorption and
osteoclastic mobilization of calcium and phosphate from bone. OHase =
hydroxylase, Pi = inorganic phosphate, PTH = parathyroid hormone, RANK =
receptor activator of nuclear factor kappa B, RANKL = receptor activator of
nuclear factor kappa B ligand

In adults, osteomalacia can present as isolated or symmetric

bone pain, often with proximal muscle group weakness.
Radiographically, osteomalacia can appear as thinned cortices,
indistinct trabeculae, or a radiolucent Looser line on the concave
portion of long bones. 30 As discussed in a 2019 study, large
amounts of accumulated osteoid is the key histologic feature of
osteomalacia. 31 In addition, researchers have identified a range of
histologic features suggestive of osteomalacia, including defective
mineralization adjacent to cement lines, areas of incomplete
mineralization, resorptive borders, bearded/halo osteocyte lacunae,
and enlarged osteocyte lacunae.
 As the phenotypic consequences of osteomalacia are commonly
secondary to vitamin D deficiency, nutritional supplementation
remains a mainstay of treatment. Medical treatment for patients
with insufficient vitamin D levels of between 25 and 30 ng/mL, a
daily oral dose of 2,000 to 4,000 IU of vitamin D3 is often effective.
For patients with levels less than 25 ng/mL, 50,000 IU of vitamin D2
administered weekly for 8 to 12 weeks is preferred. In addition,
1,000 mg of daily calcium supplementation for adults younger than
50 years and 1,200 mg of daily calcium for adults older than 50 years
has been recommended. In all patients, vitamin D levels should be
rechecked at 3-month intervals after initiation of treatment. For
causes of vitamin D deficiency other than decreased nutritional
intake or cutaneous synthesis, patients may not respond to typical
supplementation. Tumor-induced osteomalacia is frequently cured
with surgical resection of the tumor. If unresectable, novel agents
targeting FGF23 have recently been approved. 29

Osteoporosis
Osteoporosis is a disease characterized by low bone mass,
microarchitectural deterioration of bone tissue leading to bone
fragility, and a consequent increase in fracture risk. The World
Health Organization defined osteoporosis as a bone mineral
density T-score less than −2.5 as measured by dual-emission x-ray
absorptiometry. In adults, remodeling, or removing and replacing
packets of bone, is the primary mechanism whereby bone is
renewed and adapts to changes in load bearing. There are two
categories of remodeling: targeted remodeling to repair
microdamage and preserve the mechanical integrity of the skeleton,
and stochastic remodeling that supports plasma calcium
homeostasis. Stochastic remodeling can affect overall bone strength
if excessive and may weaken through loss of bone mass that occurs
because of trabecular penetration. Furthermore, an excess of bone
structural units, during excessive activation of resorption and
reversal phases, causes an excess of weakened loci in trabeculae
and an increase in microdamage that outpaces the ability to repair.
32
Thus, microdamage can accumulate and result in structural
failure.
Histologically, osteoporosis is associated with a decrease in the
number and size of trabeculae. The trabeculae became thinner and
rodlike in shape, replacing the stronger platelike morphology that
is seen in nonosteoporotic bone. The excessive remodeling seen in
most patients with osteoporosis is likely to be the primary cause of
these changes in microarchitecture.
Genetics plays a significant role in bone strength; the genetic
contribution to osteoporosis risk is multifactorial and involves
interaction between multiple genes. Elements such as bone size,
bone shape, and bone density have strong associations. The genetic
predisposition combined with environmental factors contributes to
an individual’s fracture risk. The collagen type 1a1 (COL1A1) has
been shown to be related to both bone mineral density and fracture
risk in the general population.
Treatment of osteoporosis focuses on two strategies:
antiresorptive and anabolic (Table 2). The options include not only
estrogen and calcitonin, but also a selective estrogen receptor
modulator, diphosphonates (alendronate, risedronate, ibandronate,
and zoledronic acid), a human monoclonal antibody to RANKL
(denosumab), and the parathyroid hormone analog teriparatide. 33 ,
34

Table 2
Treatment of Osteoporosis

Antiresorptive Anabolic
Diphosphonates PTH
Selective estrogen receptor modulators (SERM) Antisclerostin antibody (in development)
Denosumab (RANKL inhibitors) Anti-DKK-1 inhibitor (in development)
Estrogen
Calcitonin
Cathepsin K inhibitors (in development)
 Additionally, several agents are currently under investigation as
potential treatment option for osteoporosis. Cathepsin K is a
lysosomal enzyme responsible for the degradation of bone collagen
by osteoclasts. Conceptually, selective inhibition of cathepsin K in
osteoclasts reduces their resorptive activity but leaves them alive,
allowing paracrine signaling to the osteoblasts. This selective
inhibition was thought to result in intact osteoblast function, unlike
other antiresorptive drugs that concurrently reduce osteoclast and
osteoblast activity. The WNT signaling pathway is involved in bone
formation through the LRP5 pathway, and both sclerostin and
Dickkopf-1 (DKK-1) are known inhibitor of this pathway. Antibody
to sclerostin and DKK-1 has been developed as potential
intermi ent-dose anabolic agents. 35

Bone Structure and Diphosphonate Use:

Atypical Femur Fractures
With an overall aging population, the incidence of osteoporosis and
related fragility fractures are an increasing and significant source of
patient morbidity and healthcare expenditures. The most
commonly used antiresorptive agents are diphosphonates, which
can reduce overall fracture risk in postmenopausal women by up to
50%. 36 These agents function by inhibiting osteoclast-mediated
bone resorption. By inducing osteoclast apoptosis, diphosphonates
decrease the activation frequency of bone remodeling units (an
osteoclast-driven process). This causes retention of trabecular
connectivity, prolonging the duration of secondary mineral
deposition, and increases the percentage of bone structural units
that are fully mineralized. Consequently, this leads to an increase in
overall bone density and reduces fragility fracture risk. 37
Despite the efficacy of diphosphonate use in reducing fragility
fractures, in the past decade a class of atypical femoral shaft
fractures associated with chronic diphosphonate use has become
increasingly common. 38 Consistent with bony structural pathology
as a predisposing factor in atypical femoral shaft fractures,
mechanisms of injury are commonly low-energy trauma. These
fractures, commonly seen in the se ing of extended- duration
diphosphonate use, are often preceded with complaints of
preexisting vague thigh or hip pain. Radiographically, atypical
femoral shaft fractures are characterized by localization within the
subtrochanteric region just distal to the lesser trochanter, a
transverse, minimally comminuted pa ern with a medial
unicortical beak, and thickening of the lateral cortex at the fracture
site (Figure 6). According to a 2019 study, the risk of atypical
femoral shaft fracture and the fracture location seem to be
influenced by the degree of femoral bowing resulting in focused
tensile stress on the anterolateral femur. 39 Tissue from women
treated with a diphosphonate for atypical femoral shaft fracture was
harder and more mineralized and had lower crack-initiation
toughness and less crack deflection at osteonal boundaries. 40
Collectively, these histologic and biomechanical changes with long-
term diphosphonate use cause a reduction in intrinsic and extrinsic
toughening mechanisms.
 Figure 6 A and B, Radiographs showing an atypical femur fracture occurring
in a patient with long-term diphosphonate use. Radiographic features of atypical
femur fractures include lateral cortex thickening, cortical beaking (arrow),
transverse fracture morphology, and subtrochanteric localization at a region of
high tensile stress.

Although atypical fractures of the subtrochanteric region of the

femoral shaft in postmenopausal women are frequently associated
with diphosphonate use, the absolute risk is very low, ranging from
3.2 to 50 cases per 100,000 person-years. This risk increases in a
dose-dependent manner in the se ing of chronic use. Therefore,
atypical femoral shaft fractures represent only a small fraction of
fragility fractures seen in the patient population with osteoporosis.
The significant reduction in more typical fragility fractures seen
with diphosphonate use far outweighs the increased risk of atypical
femur fractures, thus supporting their continued use to limit
skeletally related events in patient populations with osteoporosis. 41

Skeletal Changes in Malignancy

Cancers of various histologies have significant direct and indirect
effects on the skeletal system that compromise bone structure and
predispose to deleterious events such as pain, electrolyte
derangement (hypercalcemia), and pathologic fracture. Moreover,
the development of pathologic fractures is often a poor prognostic
factor in cancer survival. Much has been discovered and published
about the mechanisms supporting skeletal tropism and survival of
metastatic tumor cells within the bony microenvironment. 42 There
are skeletal structural changes that occur in the se ing of cancer
that predispose to functional consequences, such as pathologic
fracture.

Systemic Effect of Cancer on Bone Structure

Although tumors typically originate from a single cell
histologically, cancer is a systemic disease affecting many organ
systems. Many treatments for cancer often have widespread
systemic toxicities. Therefore, the metabolic consequences
associated with cancer and its treatment can induce secondary
osteoporosis and compromise bone integrity. 43 Inactivity secondary
to toxicities associated with conventional antineoplastic therapies
reduces mechanical anabolic signals for healthy bone remodeling.
Radiation, either in the form of routine imaging or as an
antineoplastic agent, can have a detrimental effect on the health of
skeletal stem cells. Additionally, hormonal dysregulation, either by
cancer-mediated alterations to the systemic hormonal environment,
or intentionally through the use of aromatase inhibiting therapies,
can lead to decreased bone mineral density. Collectively, according
to a 2021 study the systemic changes seen in malignancy cause an
overall decrease in skeletal bone marrow density, trabecular bone
volume, and subsequent increase in pathologic fracture risk. 44
Multiple therapeutic strategies have been proposed to limit the
loss of bone density associated with malignancy. Conventional
therapies include antiresorptive agents such as diphosphonates
and anti-RANKL monoclonal antibodies. 45 However, novel
therapies are in development and show early promise. As discussed
in a 2021 study, these include anabolic agents such as teriparatide
and mechanical interventions including formal exercise programs
and low-intensity vibrational mechanical stimulation. 46

Structural Changes in Skeletal Metastases

In addition to the systemic changes seen within a host in the se ing
of malignancy that can predispose to pathologic structural
alterations in the skeleton, normal bone structure can also be
affected by direct metastatic infiltration. Bone is one of the most
common areas for cancers of various histologies to spread. The
vicious cycle of skeletal metastases proposes an intimate
interaction exists between tumor cells and bone resorbing cells. As
discussed in a 2020 study, factors released by or in response to
colonizing tumor cells stimulate osteoclastogenesis, whereas
osteoclast-driven bone destruction releases factors that support
tumor survival in the skeletal microenvironment. 47

Geographic Localization of Skeletal

Metastases
In the most basic sense, metastatic lesions affecting the skeletal
system compromise skeletal integrity by replacing normal bony
cellular constituents and ECM architecture with pockets of cancer
cells. Metastatic lesions can be encountered in bones of all shapes
and sizes; short, long, flat, and irregular. The risk of catastrophic
failure is most relevant and apparent when skeletal metastases are
localized to load-bearing areas, such as in long bones in the upper
and lower extremity or the vertebrae, especially at junctional
locations. Within long bones, metastatic lesions tend to have
metaphyseal predilection. The metaphyseal tropism of circulating
tumor cells, while incompletely elucidated, is likely driven by the
metaphysis being an area of high bone turnover and marrow
cellularity. 48 Moreover, the sinusoidal vascular architecture in the
metaphysis results in slowed blood flow, making an ideal
environment for movement of cells between bone and circulation.
Recently, unique properties of immature hydroxyapatite
nanocrystals in the premetastatic niche have been identified as
another factor supporting skeletal metastasis localization to
metaphyseal regions. 49 The structural consequence of replacement
of metaphyseal bone density with foci of cancerous lesions
predisposes these regions to pathologic fracture often necessitating
prophylactic stabilization or replacement of the affected
metaphyseal and epiphyseal regions (Figure 7).

Figure 7 Pathologic fracture in skeletal metastasis.Bone scintigraphy (A) and

plain radiographs ( (B and C)) from a patient with breast cancer. Skeletal
metastases are localized to the metaphyseal region of the proximal femur. This
lesion progressed to a pathologic fracture (B) requiring hip replacement (C).

Structural Alterations in Skeletal Metastases:

Blastic and Lytic Lesions
Skeletal metastases are broadly classified based on their structural
architecture as either osteoblastic or osteolytic. Osteoblastic lesions
are characterized by deposition of new bone, whereas osteolytic
lesions are defined by destruction of normal bone. Both types of
metastatic lesions can cause changes to underlying bone structure,
resulting in symptoms such as pain and predisposition to
pathologic fracture.
Prostate cancer skeletal lesions are the prototypical osteoblastic
metastatic lesion. Although osteoblastic lesions are characterized
by new bone deposition and a sclerotic appearance
radiographically, the bone resorptive and formative processes are
dysregulated in these lesions. Histologically, osteoblastic lesions
are surrounded by a dense accumulation of osteoblasts. The bone
deposited within an osteoblastic lesion is a woven, disorganized
pa ern and is disruptive to the underlying lamellar structure of
host bone. Osteoblast activity facilitates bony deposition in such
lesions. Upon colonization of the skeletal microenvironment,
infiltrating metastatic tumor cells develop a distinct bonelike
phenotype and can produce several molecular activators of
osteoblast activity such as endothelin-1, parathyroid hormone–
related peptide, several bone morphogenetic proteins and
insulinlike growth factors, and fibroblast growth factors (FGFs).
Lytic lesions can be seen in the se ing of skeletal metastases
from cancers of various histologies, most commonly breast and
lung, and multiple myeloma. Osteoclast activation is a requisite for
the formation of osteolytic lesions. Structurally, osteoclast
activation leads to destruction of both cortical and cancellous bone,
potentially rendering affected areas at high risk for pathologic
fracture under physiologic loads. As discussed in a 2020 study,
several soluble mediators produced by tumor cells or surrounding
stromal cells can directly activate preexisting osteoclasts or promote
the proliferation and differentiation of hematopoietic precursor
cells into mature osteoclasts. 50 The most well characterized of these
mediators include RANKL and the inflammatory cytokine tumor
necrosis factor alpha. Several other inflammatory cytokines
including interleukin 6 and interleukin 1b produced directly by
tumor cells or immune cells in the tumor microenvironment have
osteoclast-activating effects (Figure 8). Although monoclonal
antibodies targeting inflammatory cytokines have a demonstrated
clinical benefit in diminishing osteoclast activity and improving
overall bone mineral density in various rheumatologic conditions,
their clinical utility in restricting functional consequences of
skeletal metastases has not been established but remains an active
area of research.
Figure 8 Illustration of the mechanisms and mediators of osteoblast and
osteoclast activation in skeletal metastases.Impaired balance of osteoblast and
osteoclast activity is frequently seen in both osteoblastic and osteolytic lesions.
Osteoblastic lesions are characterized by osteoblast-mediated production of
immature, woven bone. Preferential osteoclast activation leads to osteolytic
lesions. As normal bone is replaced with metastatic lesions, factors in the
extracellular matrix including growth factors (insulinlike growth factors), Ca2+,
and transforming growth factor beta are released and can directly support tumor
growth, a process termed the tumor-bone vicious cycle. BMP = bone
morphogenetic protein, Ca = calcium, DKK = Dickkopf, ET-1 = endothelin-1,
FGF = fibroblast growth factor, IGF = insulin-like growth factor, IL = interleukin,
OPG = osteoprotegerin, PTHrP = parathyroid hormone-related protein, RANK =
receptor activator of nuclear factor kappa B, RANKL = receptor activator of
nuclear factor kappa B ligand, TGF-β = transforming growth factor beta, TNF-α
= tumor necrosis factor alpha, VEGF = vascular endothelial growth factor.(From
 Wang M, Xia F, Wei Y, Wei X: Molecular mechanisms and clinical management
of cancer bone metastasis. Bone Res 2020;8[1]:30.)

Summary
The skeleton provides the structural foundation of the
musculoskeletal system. The macroscopic structure of bone is
highly organized and specific to meet several physiologic needs
including locomotion, vital organ protection, hematopoiesis, and
ion balance. Rather than a static structure, bone is a highly dynamic
tissue responsive to its mechanical and physiologic environment.
The skeleton is in a constant state of remodeling, a process
organized at the molecular level and coordinated through the
actions of diverse cellular components. Alterations in normal
skeletal dynamics, be it genetically or in response to external insult,
can lead to structural changes that influence bone form and
function. The understanding of the many processes that support
bone structure, the pathologies that affect it, and the novel
therapies that aim to restore bone health continue to evolve and
advance.

Key Study Points

Cellular constituents of bone are derived from precursors of mesenchymal and
hematopoietic origin. Their proliferation, differentiation, and function are tightly
orchestrated by environmental and genetic factors.
Genetic, nutritional, and environmental disturbances to the functional elements of
healthy bone manifest as a variety of pathologic conditions—both inherited and
acquired—that affect overall skeletal structure.
Novel therapies supporting bone health are an active area of research and clinical
development.

Annotated References
1. Schlesinger PH, Blair HC, Beer Stolz D, et al: Cellular and
extracellular matrix of bone, with principles of synthesis and
 dependency of mineral deposition on cell membrane transport.
Am J Physiol Cell Physiol 2020;318(1):C111-C124. This review
article provides an in-depth discussion on the cellular and matrix
components of bone.
2. O o F, Thornell AP, Crompton T, et al: Cbfa1, a candidate gene
for cleidocranial dysplasia syndrome, is essential for osteoblast
differentiation and bone development. Cell 1997;89(5):765-771.
3. van Gastel N, Carmeliet G: Metabolic regulation of skeletal cell
fate and function in physiology and disease. Nat Metab
2021;3(1):11-20. This review article provides an overview of the
metabolic phenotypes adopted by various bone cells and the way
metabolic programs support each cell type’s unique functional
demands.
4. Teitelbaum SL: Osteoclasts: What do they do and how do they
do it? Am J Pathol 2007;170(2):427-435.
5. Arne TR, Orriss IR: Metabolic properties of the osteoclast. Bone
2018;115:25-30.
6. Moharrer Y, Boerckel JD: Tunnels in the rock: Dynamics of
osteocyte morphogenesis. Bone 2021;153:116104. The authors
provide a review of osteocyte ontogeny, differentiation, and
function.
7. Robling AG, Castillo AB, Turner CH: Biomechanical and
molecular regulation of bone remodeling. Annu Rev Biomed Eng
2006;8:455-498.
8. Dallas SL, Prideaux M, Bonewald LF: The osteocyte: An
endocrine cell ... and more. Endocr Rev 2013;34(5): 658-690.
9. Chan CKF, Gulati GS, Sinha R, et al: Identification of the human
skeletal stem cell. Cell 2018;175(1):43-56.e21.
10. Ambrosi TH, Marecic O, McArdle A, et al: Aged skeletal stem
cells generate an inflammatory degenerative niche. Nature
2021;597(7875):256-262. This preclinical study identifies unique
a ributes of skeletal stem cells isolated from older individuals.
These stem cells are involved with creating inflammatory
 microenvironment predisposing to imbalance of bone
remodeling characteristic of osteoporosis.
11. Boyle WJ, Simonet WS, Lacey DL: Osteoclast differentiation and
activation. Nature 2003;423:337-342.
12. Young MF: Bone matrix proteins: Their function, regulation, and
relationship to osteoporosis. Osteoporos Int 2003;14(suppl 3):S35-
S42.
13. Atkins GJ, Anderson PH, Findlay DM, et al: Metabolism of
vitamin D3 in human osteoblasts: Evidence for autocrine and
paracrine activities of 1 alpha,25-dihydroxyvitamin D3. Bone
2007;40(6):1517-1528.
14. Hernandez CJ, Guss JD, Luna M, Goldring SR: Links between
the microbiome and bone. J Bone Miner Res 2016;31(9):1638-1646.
15. Lucas S, Omata Y, Hofmann J, et al: Short-chain fa y acids
regulate systemic bone mass and protect from pathological bone
loss. Nat Commun 2018;9(1):55.
16. Cowardin CA, Ahern PP, Kung VL, et al: Mechanisms by which
sialylated milk oligosaccharides impact bone biology in a
gnotobiotic mouse model of infant undernutrition. Proc Natl Acad
Sci USA 2019;116(24):11988-11996. This preclinical study evaluates
mechanistically the microbiome-mediated changes in bone cell
function. This study suggests that dietary modifications that
support a healthy microbiome could be a novel therapy to
promote bone biogenesis.
17. Gehrig JL, Venkatesh S, Chang HW, et al: Effects of microbiota-
directed foods in gnotobiotic animals and undernourished
children. Science 2019;365(6449):eaau4732. This randomized
clinical trial of a supplemental microbiome supportive diet in
children with severe acute malnutrition demonstrated that
modulating the human microbiome through dietary agents can
affect bone and neural development. Level of evidence: I.
18. Mortier GR, Cohn DH, Cormier-Daire V, et al: Nosology and
classification of genetic skeletal disorders: 2019 revision. Am J
Med Genet 2019;179(12):2393-2419. Updated classification on the
 genetic origins of various musculoskeletal pathologies is
presented.
19. Sillence DO, Senn A, Danks DM: Genetic heterogeneity in
osteogenesis imperfecta. J Med Genet 1979;16(2): 101-116.
20. Etich J, Leßmeier L, Rehberg M, et al: Osteogenesis imperfecta-
pathophysiology and therapeutic options. Mol Cell Pediatr
2020;7(1):9. This is an up-to-date review on the current standard
of care diagnostic and treatment options for osteogenesis
imperfecta with a discussion on the pathophysiology of the
disorder. Level of evidence: I.
21. Mueller B, Engelbert R, Bara a-Ziska F, et al: Consensus
statement on physical rehabilitation in children and adolescents
with osteogenesis imperfecta. Orphanet J Rare Dis 2018;13(1):158.
22. Tolar J, Teitelbaum SL, Orchard PJ: Osteopetrosis. N Engl J Med
2004;351:2839-2849.
23. Fra ini A, Orchard PJ, Sobacchi C, et al: Defects in TCIRG1
subunit of the vacuolar proton pump are responsible for a subset
of human autosomal recessive osteopetrosis. Nat Genet
2000;25(3):343-346.
24. Gupta R, Gupta N: Femoral fractures in osteopetrosis: Case
reports. J Trauma 2001;51(5):997-999.
25. Demulder A, Takahashi S, Singer FR, Hosking DJ, Roodman
GD: Abnormalities in osteoclast precursors and marrow
accessory cells in Paget’s disease. Endocrinology 1993;133(5):1978-
1982.
26. Parvizi J, Klein GR, Sim FH: Surgical management of Paget’s
disease of bone. J Bone Miner Res 2006;21(suppl 2):P75-P82.
27. Alvarez L, Guañabens N, Peris P, et al: Discriminative value of
biochemical markers of bone turnover in assessing the activity of
Paget’s disease. J Bone Miner Res 1995;10(3):458-465.
28. Parvizi J, Schall DM, Lewallen DG, Sim FH: Outcome of
uncemented hip arthroplasty components in patients with
Paget’s disease. Clin Orthop Relat Res 2002;403:127-134.
29. Dahir K, Zanche a MB, Stanciu I, et al: Diagnosis and
management of tumor-induced osteomalacia: Perspectives from
clinical experience. J Endocr Soc 2021;5(9):bvab099. This study
discusses the pathophysiology and treatment strategies for a rare
disease. Level of evidence: I.
30. Pa on CM, Powell AP, Patel AA: Vitamin D in orthopaedics. J
Am Acad Orthop Surg 2012;20(3):123-129.
31. Charoenngam N, Shirvani A, Holick MF: Vitamin D for skeletal
and non-skeletal health: What we should know. J Clin Orthop
Trauma 2019;10(6):1082-1093. This is an updated review on the
mechanism of action of vitamin D in supporting skeletal health
and how it is used clinically to promote improved bone mineral
density. Level of evidence: I.
32. Akhter MP, Lappe JM, Davies KM, Recker RR: Transmenopausal
changes in the trabecular bone structure. Bone 2007;41(1):111-116.
33. Kearns AE, Khosla S, Kostenuik PJ: Receptor activator of nuclear
factor kappaB ligand and osteoprotegerin regulation of bone
remodeling in health and disease. Endocr Rev 2008;29(2):155-192.
34. Neer RM, Arnaud CD, Zanche a JR, et al: Effect of parathyroid
hormone (1-34) on fractures and bone mineral density in
postmenopausal women with osteoporosis. N Engl J Med
2001;344(19):1434-1441.
35. Khosla S, Ho auer LC: Osteoporosis treatment: recent
developments and ongoing challenges. Lancet Diabetes Endocrinol
2017;5(11):898-907.
36. Eastell R, Walsh JS, Wa s NB, Siris E: Bisphosphonates for
postmenopausal osteoporosis. Bone 2011;49(1):82-88.
37. Boivin GY, Chavassieux PM, Santora AC, Yates J, Meunier PJ:
Alendronate increases bone strength by increasing the mean
degree of mineralization of bone tissue in osteoporotic women.
Bone 2000;27(5):687-694.
38. Black DM, Kelly MP, Genant HK, et al: Bisphosphonates and
fractures of the subtrochanteric or diaphyseal femur. N Engl J
Med 2010;362(19):1761-1771.
39. Park YC, Yoon SP, Yang KH: Localization of atypical femoral
fracture on straight and bowed femurs. J Bone Metab
2019;26(2):123-131. Radiographic characterization of the location
of atypical femur fractures based on femoral morphology is
presented. Level of evidence: IV.
40. Lloyd AA, Gludova B, Gludova C, et al: Atypical fracture with
long-term bisphosphonate therapy is associated with altered
cortical composition and reduced fracture resistance. Proc Natl
Acad Sci USA 2017;114(33):8722-8727.
41. Black DM, Geiger EJ, Eastell R, et al: Atypical femur fracture risk
versus fragility fracture prevention with bisphosphonates. N Engl
J Med 2020;383(8):743-753. Updated recommendations on the use
of diphosphonates as first-line therapy for osteoporosis to
prevent fragility fracture are presented. Risk reduction in
prevention of pathologic fracture far outweighs the increased risk
of atypical femur fracture with chronic diphosphonate use. Level
of evidence: II.
42. Ho auer LC, Bozec A, Rauner M, Jakob F, Perner S, Pantel K:
Novel approaches to target the microenvironment of bone
metastasis. Nat Rev Clin Oncol 2021;18(8):488-505. This review
discusses established and experimental treatments to minimize
the bone loss associated with skeletal metastases. Level of
evidence: V.
43. Drake MT: Osteoporosis and cancer. Curr Osteoporos Rep
2013;11:163-170.
44. Gnant M, Fi al F, Rinnerthaler G, et al: Duration of adjuvant
aromatase-inhibitor therapy in postmenopausal breast cancer. N
Engl J Med 2021;385(5):395-405. Updated recommendations on the
use of aromatase inhibitors in breast cancer are presented.
Current recommendations suggest 5 years as an adequate time to
prevent breast cancer recurrence but also limit the consequential
loss of bone mineral density with the use of these agents. Level of
evidence: I.
45. Waqas K, Lima Ferreira J, Tsourdi E, Body JJ, Hadji P, Zillik MC:
Updated guidance on the management of cancer treatment-
induced bone loss (CTIBL) in pre- and postmenopausal women
with early-stage breast cancer. J Bone Oncol 2021;28:100355. Up-to-
date recommendations on established and experimental
therapies to limit or reverse bone loss associated with breast
cancer treatment and skeletal metastases are presented. Level of
evidence: I.
46. Pagno i GM, Thompson WR, Guise TA, Rubin CT: Suppression
of cancer-associated bone loss through dynamic mechanical
loading. Bone 2021;150:115998. This review discusses the use of
formal exercise programs and novel dynamic mechanical loading
therapies to increase bone mineral density in cancer. Level of
evidence: V.
47. Coleman RE, Croucher PI, Padhani AR, et al: Bone metastases.
Nat Rev Dis Primers 2020;6(1):83. This is an up-to-date review on
the epidemiology, mechanisms, clinical consequences, and
management of bone metastases. Level of evidence: I.
48. Muscarella AM, Aguirre S, Hao X, Waldvogel SM, Zhang XH:
Exploiting bone niches: Progression of disseminated tumor cells
to metastasis. J Clin Invest 2021;131(6):e143764. This up-to-date
review discusses the niches within the skeleton that support
localization of cancer metastases.
49. He F, Chiou AE, Loh HC, et al: Multiscale characterization of the
mineral phase at skeletal sites of breast cancer metastasis. Proc
Natl Acad Sci USA 2017;114(40):10542-10547.
50. Wang M, Xia F, Wei Y, Wei X: Molecular mechanisms and
clinical management of cancer bone metastasis. Bone Res
2020;8(1):30. This is an up-to-date review on the unique
mechanisms of osteoblastic and osteolytic metastatic lesions, as
well as management strategies for skeletal metastases. Level of
evidence: I.
C H AP T E R 1 3

Biomaterials and Implants

Samuel J. Laurencin MD, PhD, Wayne Cohen-Levy MD, MS

Neither of the following authors nor any immediate family member has received anything of value
from or has stock or stock options held in a commercial company or institution related directly or
indirectly to the subject of this chapter: Dr. Laurencin and Dr. Cohen-Levy.

ABSTRACT
Injury to musculoskeletal tissues often requires medical or surgical
intervention to aid in recovery through repair or replacement.
Natural and synthetic polymers without targeted tissue-specific
biologic adjuncts to aid in repair are limited in their ability to fully
restore native tissue biomechanical properties. Furthermore,
readily available grafts for tissue repair or replacement are often
lacking because of limited supply or donor-host geometric
mismatch, among other challenges. The in vitro generation of
native tissue that can then be used as replacements for
compromised tissue has been explored as a means to overcome the
limitations of contemporary treatment methods. Regenerative
engineering has emerged as a field with broad applications,
including the management of orthopaedic injuries. Through the
deep convergence of materials science, stem cell technology, and
developmental biology, it is anticipated that novel composite
materials can be developed with scalable properties from the
submicron level to bulk material macrostructure features. The
production of a translational, patient-specific tissue, organ system,
or limb would be the realization of the current potential of this
field. It is important to explore current limitations of traditional
materials and implant fabrication techniques, provide context for
the general goals of regenerative engineering in replicating native
tissues, and review the benefits and drawbacks of various scaffold
preparation techniques including electrospinning and three-
dimensional printing.
Keywords: biomaterials; electrospinning; regenerative engineering;
three-dimensional printing

Introduction
Host and tissue-specific factors can affect the body’s self-repair
capabilities, with adult articular cartilage being a prime example of
a tissue with limited self-repair capabilities to any significant
clinical and functional level. Management of musculoskeletal
injuries often uses techniques focused on direct repair or
replacement, which can be full or partial. Repaired tissues using
traditional orthopaedic synthetic materials typically fail to regain
their preinjury biomechanical functionality despite acceptable
clinical outcomes that are often a ainable. Polymers, ceramics, and
metals are the primary classes of materials that have been used to
support tissue healing 1 (Table 1). When cells or cellular products
are added to these materials, they act as scaffolds to support native
tissue production and improved host tissue integration. Autografts
and allografts have been cornerstones for tissue replacement when
the outcome of direct repair would be unfavorable or not possible.
Autografts are host-derived tissues and are ideal because of a lack
of host immune response but are plagued by donor site morbidity.
Allografts are tissues sourced externally from the intended
recipient and circumvent the donor site morbidity of autografts.
However, allografts place the patient at risk for immune system
graft rejection and infection transmission, in addition to limitations
on a readily available supply of size and geometry-matched graft
options. Advances in scaffold fabrication techniques and the ability
to direct in vitro and in vivo cellular behavior for targeted tissue
repair or replacement have led to novel therapies that can overcome
the current limitations of both autografts and allografts with great
translational potential.

Table 1
Benefits and Limitations of Common Material Classes Used in
Regenerative Engineering for Orthopaedic Applications

Comparison of scaffold materials

Manufacturing
Benefits Potential Limitations
Material
Hydrogels
High water content/growth Mechanical properties limit
media inclusion allows for use in load-bearing
cell encapsulation and constructs
growth Optimizing printing
Mechanical properties can conditions for individual
be modified through cross- hydrogels can be time
linking consuming
Controlled drug/growth factor Physical manipulation of
release possible constructs can be difficult
Ease of patterning via three- Loading evenly with cells can
dimensional printing to mimic be challenging
tissue microarchitectures

Polymers
Natural polymers can be Natural and synthetic
derived from extracellular polymers generally lack
matrix, ensuring high mechanical properties for
biocompatibility and low load bearing
toxicity Pathologic impurities such
Biodegradable as endotoxin may be present
Often contain biofunctional in natural polymers
molecules on their surface Synthetic polymers are often
Synthetic polymers offer hydrophobic and lack cell
improved control over recognition sites
physical properties
 Comparison of scaffold materials
Manufacturing
Benefits Potential Limitations
Material
Ceramics
Osteoconductive and Hard and brittle when used
osteoinductive properties alone
allow strong integration with May display inappropriate
host tissue degradation/resorption rates,
Similar composition to host with decline in mechanical
bone mineral content properties as a result
Can be delivered as granules
or paste or in an injectable
format

Bioactive
glasses Osteoconductive, Inherent brittleness
osteoinductive properties Difficult to tune resorption
Adapted into clinical rate
prosthesis already Manipulation of constructs
into three-dimensional
shapes to treat specific
defects challenging

Metals
Biocompatible Potential for release of toxic
Superior strength metal ions
Superior mechanical Superior modulus can lead to
properties can be stress-shielding
advantageous in situations Poor biodegradability may
where slow bone growth is result in further
likely surgery/impairment of tissue
ingrowth
Secondary release of metal
ions may cause local and
distal toxicity

Adapted with permission from Turnbull G, Clarke J, Picard F, et al: 3D bioactive composite
scaffolds for bone tissue engineering. Bioact Mater 2018;3(3):278-324.

Regenerative Engineering
The human body has tremendous self-repair capabilities through
resident stem cells, but it can be severely limited in certain clinical
se ings or injury conditions. The physical distance between injured
tissues in the se ing of segmental long bone fractures compounded
by the disruption of blood flow to the injury site is an example of a
condition where self-repair potential is limited. 2 Regenerative
engineering exists as a deep convergence between materials
science, stem cells, developmental biology, physical science, and
clinical translation. 3 , 4 This field emerged in part through a need to
address the limitations of contemporary approaches to
management of musculoskeletal tissue injury, such as those
evident with the use of autografts or allografts. 5 Research in this
field occurs from a top-down approach, gaining thorough
understanding of the pathophysiology of clinical challenges and
identifying points where engineering principles can be harnessed
to halt and ultimately provide a new path for tissue regeneration
and clinical functional improvement. Research can also occur in a
bo om-up approach through a deep understanding of stem cells
and cell signaling and how spatial and temporal factors through
biomaterials and controlled exposure to growth factors,
respectively, can yield the regeneration of native tissues. 6
Ultimately, this field and the work being done within it aims to
regenerate and not simply repair complex tissues and organ
systems. For success and translation from the bench top to the
bedside, a clear understanding of the clinical challenges for
material integration and utilization must always be appreciated
from the start. Gains are being made regularly with broad clinical
applications, and the field of orthopaedics stands to gain much
through continued investigation of regenerative engineering
principles.
Native tissues maintain a complex hierarchical structure, where
the characteristics of the cell-tissue interaction on the nanoscale
influence the microstructure tissue features, which in turn lead to
the macrostructure material properties. 7 Cellular vitality is
supported through the transport of nutrients and oxygen and
removal of waste through diffusion and integrated vascularity.
Biomechanical integrity must be maintained for the tissues to
provide functional support of organ systems. The cell-cell and cell-
matrix interactions allow for maintenance of extracellular matrix
using cell-specific signaling cascades and the influence of growth
factors, matrix surface, and bulk features. 6 Although great
advances in biomaterials for orthopaedics have occurred, the ability
for regenerative engineered structures to be incorporated into the
human body while functioning in tandem with native tissues to
generate a specific biomechanical group function remains difficult. 8
To circumvent the limitations of single-tissue substitution, such as
the potential for poor osteointegration in bone tissue engineering,
the ability to replace complex tissue groups, joints, or complete
limbs remains the overarching goal of regenerative engineering. 9

Scaffold Design Considerations

The scaffold is the foundation for regenerative engineering
applications as the replication of native extracellular matrix can aid
in cellular differentiation and proliferation while also providing
mechanical integrity for functional benefit. 10 Collagen and
proteoglycans, among other components in the extracellular matrix
of musculoskeletal tissues, provide porosity and topography and
the transport of growth factors to influence cellular behavior. 11
High porosity allows for cell migration, nutrient transport, growth
factor delivery, and waste removal. 12 , 13 Of great importance in
mesenchymal stem cell differentiation is the cell-matrix
relationship, which can participate in cell-fate decisions. 14 Because
of the interrelationship with matrix components and water,
mechanical integrity is inherent to the matrix, and
mechanotransduction also has been found to influence cell
function. 15 More recently, the viscosity of the matrix, in particular,
demonstrated importance in mechanotransduction through
activation of YAP/TAZ mechanosensitive transcriptional activators,
as discussed in a 2020 study. 16 This highlights the complex and
interactive nature of the native cellular environment and must be
considered when developing biomaterials to direct cellular
behavior in vitro and in vivo.
 Regenerative engineering of bone is best supported by scaffolds
displaying properties to promote osteoblast migration and
proliferation (osteoconductive), progenitor cell differentiation
(osteoinductive), and permi ing well integration into the host local
tissue environment (osteointegrative). Additional design criteria
for regenerative engineering applications include (1)
biocompatibility, (2) mechanical integrity based on the tissue’s
native function, and (3) biodegradable products that do not cause
local adverse tissue response and can be easily metabolized. The
complex hierarchical nature of native bone requires a fabrication
technique that can provide control on various scales of the scaffold,
including submicron topography and macrostructure bulk material
properties. 17 , 18 A myriad of synthetic and natural biomaterials
have been explored for regenerative medicine applications. 19
Development of engineered tissues has been a empted via (1) cell-
only substrates; 20 (2) scaffold-only substrates with in vivo
regeneration capability; 21 , 22 or (3) a combination approach relying
on the in vitro interaction between the cells and substrates. 23 For
example, ligament and tendon repair or regeneration has been
explored using biodegradable polymers with and without inclusion
of pluripotent stem cells with in vitro, in vivo, and some
translational success. 24 To permit cellular infiltration of scaffolds,
various techniques have been explored to introduce porosity into
the scaffolds. To date, scaffold manufacturing techniques such as
freeze-drying, solvent casting with particle leaching, and gas
foaming are examples of fabrication techniques to create porous
biocompatible scaffolds for orthopaedic applications. 25 , 26 Figure 1
highlights common scaffold synthesis techniques used in
regenerative engineering. 27 Postsynthesis processing and
functionalization or incorporation of growth factors can make
scaffolds biomimetic and aid in in vitro and in vivo cellular
response for improved scaffold functionality. 6 , 28
 Figure 1 Schematic illustration depicts common scaffold fabrication
techniques.A, Solvent casting-particle leaching process. B, Gas foaming. C,
Freeze-drying. D, Phase separation. E, Electrospinning. F, Rapid-prototyping.
(Adapted with permission from Shi C, Yuan Z, Han F, Zhu C, Li B: Polymeric
biomaterials for bone regeneration. Ann Joint 2016;1[9].)

A study explored large defect bone regeneration in a rabbit

animal model using alendronate-loaded degradable chitosan
microspheres in a polylactic acid–based scaffold, showing the
benefit of a degradable scaffold phase for local delivery of agents to
support native tissue regeneration 29 (Figure 2). These more
traditional scaffold fabrication techniques are often limited by
challenges in rapid prototyping and scalability. 30 Furthermore, the
fabrication method of materials greatly influences the physical and
mechanical properties a ainable. Considering these facts,
researchers have explored novel material fabrication techniques for
regenerative engineering in orthopaedic applications.
 Figure 2 A, Radiographs show comparison of polylactic acid (PLA) scaffolds
with chitosan microspheres loaded with alendronate (CM-ALs [10%]) and those
without alendronate (CM-ALs [0%]). The CM-AL (10%) scaffolds showed earlier
and superior bone regeneration in the rabbit radius in vivo model. B, The
scanning electron micrograph shows PLA scaffold (black arrow) and integrated
microspheres (white arrow).(Adapted with permission from Wu H, Lei P, Liu G,
et al: Reconstruction of large-scale defects with a novel hybrid scaffold made
from poly (L-lactic acid)/nanohydroxyapatite/alendronate-loaded chitosan
microsphere: in vitro and in vivo studies. Sci Rep 2017;7[1]:359.)

Electrospinning has been established as a scalable method with

flexibility regarding materials available for use, including
composites, and it can be performed in a controlled, reproducible
manner. 13 Three-dimensional (3D) printing continues to show great
promise as a process with variability in materials that can be used
while providing great control at various scales for precision of
tissue internal structure in a rapid production manner. 31
Bioprinting using compatible bioinks for bone and soft-tissue
engineering continues to be an area of research within rapid
prototyping of scaffolds of significant interest and promise. 23

Electrospinning Scaffold Fabrication

Numerous studies have explored the potential for electrostatic
spinning of polymeric fibers for the controlled fabrication of
scaffolds for orthopaedic applications. 32 - 34 Electrospinning uses
polymer solutions exposed to a high-power electric field serving as
an electrode. The polymer droplet is delivered through a
millimeter-scale nozzle, which then deforms into a Taylor cone
subsequent to the electrical field application. When the force across
the polymer droplet exceeds the surface tension of the polymer,
this results in a charged jet stream directed toward the
complementary electrode. When the polymer is initially dissolved
with an appropriate solvent, the process is subclassified as solution
electrospinning and yields in a fiber once the collected sample’s
solvent evaporates in the air gap between the source and collector.
A newer technique uses a solventless melted polymer subclassified
as melt electrospinning and produces fibers once the collected
sample cools. This produces continuous fibers for subsequent
processing and optimization. 35 Through preprogrammed geometry
and the relative motion of the polymer source and collector, a
group of fibers can be oriented. The produced nonwoven
nanofibrous mats mimic the extracellular matrix and provide
advantageous high surface area to volume ratio and controllable
porosity. With further investigation, the use of the fibers is
influenced by multiple material and processing parameters,
including applied voltage, solution flow rate, solvent properties,
polymer properties, material collector distance, and solution
rheologic behavior, providing additional opportunities to direct
ideal bulk scaffold functional qualities.
An excess of 200 types of polymers, both natural and synthetic,
have been explored for electrospinning fabrication for a variety of
applications. These polymers can be created as blends with other
polymers to form composites or with the inclusion of bioactive
factors. Systems with open interconnected or closed pores or well-
aligned or pseudorandom fiber arrangement are possible with the
same electrospinning fabrication technique. Control of bulk
material properties is in part a function of the control provided in
directing fiber orientation and density. After the collection of
individual fibers and the creation of fiber mats, the complex,
anisotropic hierarchical structure of native musculoskeletal tissues
can be re-created through layer-by-layer stacking, 3D weaving, or
template deposition. Multiaxial fiber structures can be aligned to
create the interlacing internal fiber network often as organized
uniaxially aligned, radially aligned, or wavy arrangement based on
the needs of the scaffold application. 36 The authors of one study
developed a combination silk and poly(lactic-co-glycolic) acid–
based scaffold produced via electrospinning. 37 A scaffold hierarchy
was created by using mechanically robust microfibrous silk
scaffold, whereas an extracellular matrix–like topography was
provided by a nanofibrous PLGA scaffold. The scaffold was further
optimized for ligament or tendon regeneration by incorporating
basic fibroblast growth factor into the PLGA fibers for controlled
release, promoting tenogenic differentiation of seeded
mesenchymal progenitor cells (Figure 3).
 Figure 3 Images showing electrospun silk–poly(lactide-co-glycolide) scaffold
with basic fibroblast growth factor (bFGF) for ligament or tendon regeneration.A
and B, Scanning electron microscopy (SEM) at different magnifications
highlighting the bFGF denoted by the black arrows. C, SEM shows both
nanofibers (eF) and microfibers (μF). D and E, Photographs show the
composite scaffold before and after twisting, respectively.(Adapted from Sahoo
S, Toh SL, Goh JC: A bFGF-releasing silk/PLGA-based biohybrid scaffold for
ligament/tendon tissue engineering using mesenchymal progenitor cells.
Biomaterials 2010;31[11]:2990-2998, with permission from Elsevier.)

It has been demonstrated that there is control afforded to fiber

orientation in the development of a biodegradable, biomimetic
polyphosphazene-polyester–based nanofiber matrix with fiber
diameter of 50 to 500 nm, which is on scale with native collagen. 38
The fibers were used for bone regeneration and thus oriented in a
concentric manner with an open central cavity to re-create outer
lamellar bone and the central marrow cavity. The biomimetic
nature of the scaffold allowed osteoblasts to be added in vitro with
subsequent cellular adhesion and proliferation throughout the
structure. The blended nature also promoted an elevated
osteoblastic phenotype compared with polyester nanofibers. The
osteoblastic infiltration and extracellular matrix production yielded
a native bone–like architecture with comparable cell-matrix
organization. In addition, the mechanical properties were on par
with native bone with a compressive modulus in the midrange of
values for trabecular bone. It was important to demonstrate that the
rate of extracellular matrix production could match or exceed the
rate of scaffold degradation to maintain the scaffold’s mechanical
properties as a load-bearing construct. Work has recently expanded
to show that polyphosphazene-based fibers can form miscible
blends with poly(lactide-co-glycolide). The incorporation of
poly(lactide-co-glycolide) with polyphosphazene can act in a
synergistic manner by providing improved control over the blend’s
degradation properties in addition to adding the buffering capacity
of the degradation products to prevent adverse local cellular
response, while continuing to allow for control over bulk
mechanical properties. 39
In addition to electrospun fibers serving an osteoconductive and
osteogenic role, research has been conducted demonstrating their
osteoinductive capabilities. The influence of mechanotransduction
on immature cell differentiation and phenotype expression
maintenance has been used on scaffolds developed through
electrospinning. Poly(ether sulfone) and polycaprolactone blends
have been used with the materials arranged to form a core and
shell, respectively. 40 By forming a blend, the modulus was
increased by a factor of four over electrospun polycaprolactone
alone. The scaffolds were fabricated to have identical
microstructures and surface chemistries, thus allowing for the
effect of moduli on cellular response in vitro to be assessed. The
lower modulus polycaprolactone created a local environment that
promoted chondrogenesis, with cartilage-specific extracellular
matrix component generation and upregulation of markers for
chondrocyte phenotypic expression including Sox9 messenger
RNA, type II collagen messenger RNA, and aggrecan protein
staining. The core-shell organized blend with higher moduli
created a pro-osteoblastic environment with increased presence of
osteogenic markers including Runx2, alkaline phosphatase, and
osteocalcin gene expression. For regenerative engineering
purposes, the ability for electrospinning blends with tunable
mechanical properties to direct specific cellular lineages further
highlights the breadth of control possible over directing bulk
material properties and the great potential for specific tissue-type
regeneration.

Postfabrication Modification in
Electrospinning
The surfaces of electrospun fibers can be pos reated after
collection through various methods to aid in desired functionality
such as improving bioactivity through surface modification. 41 Poly-
(L)-lactide acid–based nanofibers have been shown to permit
functionalization with type I collagen and influenced by the
incorporation of bone morphogenetic protein (BMP). 42 The
functionalization with collagen resulted in increased mesenchymal
stem cell adhesion, increased cell density, and cellular proliferation.
The presence of BMP led to production of scaffolds with smaller
pore size and smaller fiber size while also promoting osteoblast
differentiation evident through increased expression of alkaline
phosphatase and osteocalcin. Surface modification can also be used
to directly cross-link electrospun fibers, thus dramatically
modifying the mechanical properties. Electrospun hydroxyapatite-
containing, chitosan-based nanofibers were cross-linked using
genipin, a fruit-derived water-soluble bifunctional cross-linking
reagent. 43 The cross-linking increased the modulus by a factor of
five and showed potential in non–weight-bearing bone tissue
regeneration. Similar to the addition of polymers to nanofiber
functionalization or to provide a nidus for cross-linking,
electrospun fibers can be coated to direct cellular response.
Calcium phosphate has been explored as a coating on the block
copolymer poly(ethylene oxide terephthalate)-polybutylene
terephthalate. After the addition of mesenchymal stem cells in
44

vitro, cellular proliferation was evident on both scaffold types.

However, in vivo it was shown that subcutaneous implantation of
the scaffolds in nude mice only resulted in new bone formation in
the surface-coated scaffolds. There is great versatility provided in
electrospinning for postfabrication processing to further control
and direct the tissue-specific regeneration goals.

Current Limitations and Future Directions of

Electrospinning
Full control of fiber orientation is limited by inherent process
instabilities: axisymmetric Rayleigh instability, electric field–
induced axisymmetric instability, and whipping/bending
instability. The instability predominant type and extent of impact
45

are influenced by the synthesis parameters used, such as surface

charge density and radius of the produced jet. For example, by
increasing the electric field strength, the electric instability is
enhanced but the Rayleigh instability is decreased. This causes a
greater extent of chaotic whipping of the fibers and compromises
the ability to direct fiber spatial orientation. Optimized techniques,
including near-field electrospinning and melt electrowriting, have
been investigated as modifications of traditional solution or melt
electrospinning to reduce the extent of chaotic fiber deposition. 35 It
is likely that continued investigation in electrospinning will yield
applications for which this fabrication technique can be used as a
specific aspect of a composite or multiphasic scaffold where control
over submicron scale topography and functionality is needed.

3D Printing Scaffold Fabrication

When considering product manufacturing, two broad categories
exist: subtractive and additive. Subtractive manufacturing involves
cu ing, milling, or otherwise shaping raw materials to obtain the
final structure, which results in wasting of raw materials. 46 In
contrast, additive manufacturing involves constructing successive
layers until a final product is achieved. 3D printing is an additive
manufacturing technology for scaffold fabrication that has
numerous orthopaedic applications. 47 The process involves
creating a computer-aided design model based on information
gathered from advanced imaging modalities such as CT and MRI
and creating a volumetric model from the raw imaging data. The
model is then used to fabricate the product layer by layer and then
completing any post-processing surface modifications. Within the
3D additive manufacturing process, two broad classifications can be
created based on the materials and manufacturing: nonbiologic and
biologic.. 47 In the case of nonbiologic printing, materials must be
heat-stable at extreme temperatures while being completely
biocompatible. In contrast, biologic structures must be porous to
allow nutrient and waste movement, support cellular fastening
growth and differentiation, and be mechanically stable to tolerate
the load of the body. Numerous applications have been researched
for 3D printing applications. Traditional orthopaedic materials such
as metals, ceramics, and polymers have been 3D bioprinted with
expanding utility through continued scientific investigation. The
versatility of this technology, customizability of the printed
products, and the increasing cost-effectiveness as the 3D printers
decrease in price make this a very a ractive area of research and
innovation in all fields including orthopaedics.

Traditional and Novel 3D Printing

Applications
3D printing has been used in various capacities in orthopaedics
including preoperative surgical planning, patient and resident
education, and custom jigs for intraoperative osteotomies, as a
small number of examples. The lower cost of the technology now
possible and expansion of material selection have led medical
device companies to use additive manufacturing principles to
produce patient-specific and non–patient-specific implants. For
example, aseptic loosening is still among the leading reasons for
failure of hip arthroplasty. By increasing the coefficient of friction
and adding a highly porous structure as described in a 2021
retrieval study, 3D printing presents an emerging technology that
can help to solve this problem. 48 Because this represents newer
technology, long-term follow-up and retrieval studies are limited;
however, the 2021 retrieval study did find that 3D printed
acetabular components achieved greater bone ingrowth, suggesting
be er osteointegration. 48
More research is being performed for 3D printing in regenerative
engineering of orthopaedic tissues. Bone is a commonly
transplanted tissue in the management of musculoskeletal injuries.
49
Donor site morbidity and transmission of infectious diseases are
disadvantages when considering the bone autograft and allograft,
respectively. Bone tissue engineering using 3D printing has
emerged as an important area of research to innovate and meet the
demands of newer surgical procedures. A critical function of any
scaffold design for bone tissue engineering is the capability of
stimulating bone regeneration. Silicate bioactive ceramics have
excellent osteogenic and angiogenic bioactivity in vitro and in vivo
and have therefore been the subject of significant research.
However, just as bone is composed of different elements such as
collagen, lipids, and other proteins, the ideal scaffold may be a
composite material to allow for elements of increased bioactivity
and stability. Bone tissue scaffolds are intended to be replaced with
host bone with time; therefore, porosity to allow for cell
a achment, proliferation, and differentiation is critical.

Combined Electrospinning and 3D Printed

Scaffolds
Given the unique and promising aspects of both electrospinning
and 3D printing, it is a natural progression of material science
investigation that combined systems would be explored. A 3D
printed biphasic polycaprolactone–hyaluronic acid hydrogel with
bone morphogenetic protein 2 (BMP-2) incorporated for bone
regeneration was studied. 50 The periphery of the scaffold consisted
of a cortical bone–like shell based on the hydrogel to provide
optimal mechanical strength. A second phase consisted of porous,
cancellous bone–like, melt electrospun microfibrous mesh. The
mesh phase allowed for osteogenesis and angiogenesis and
supported hydrogel phase load bearing. There was upregulation of
osteogenic bone markers including osteopontin, osteocalcin, and
type I collagen up to day 14 in the presence of BMP-2 and sustained
high cell viability for over 21 days. Using a rabbit model,
incorporation of the scaffolds in vivo led to new bone formation.
Chondrocytes were added to composite 3D printed-electrospun
scaffolds based on polycaprolactone. 51 Using a two-stage process,
electrospun nanofibers were glued to 3D printed single-layer grids
using a polycaprolactone solution in chloroform and ethanol as the
adhesive. Using an adhesive to combine multiple layers gave more
control on maximum scaffold thickness. Chondrocytes in this
environment demonstrated excellent cell infiltration, viability, and
proliferation, but it was also shown that partial chondrocyte
dedifferentiation occurred. This highlights the challenges that exist
working with certain cell lines in vitro and that opportunities for
further investigation exist to identify what scaffold properties are
needed to be optimized to maintain a specific cellular phenotype
for tissue regeneration.
Methods to introduce cells into the scaffolds can vary. Further
exploration of combining electrospinning and 3D printing was
performed in the se ing of myoblast cell-printing for skeletal
muscle tissue regeneration. 23 The hierarchy afforded by the
polycaprolactone-based struts providing structural shape with
electrospun aligned nanofibers provided topological cues for
myoblast proliferation and alignment and promoted the production
of myotubes. The novel introduction of the myoblasts from cell-
laden struts printed onto the scaffold gave greater control of initial
cellular arrangement and density within the structure. Observed
increased expression of myogenic genes was greatly influenced by
fiber alignment. Continued investigation more recently has
included human umbilical vein endothelial cells into the same
scaffold co-cultured with printed myoblasts to aid in angiogenesis
in addition to myogenesis. 52 The co-cultured scaffolds had greater
myogenic gene expression and a high degree of myosin heavy chain
with striated pa erns.
A 2020 study investigated the utility of 3D printing stem cells
directly without a scaffold support for cartilage regeneration. 53
Adipose tissue–derived mesenchymal stem cells were collected into
a 3D form adequate for manipulation and implantation once a
sufficient cell density was obtained. The bio-3D printed structure
was implanted into a trochlear groove of a rabbit 4.8-mm diameter
full-thickness cartilage defect. Tissue regeneration was evaluated 3
months after implantation. There was superior cartilage tissue
regeneration with graft incorporation compared with the control
specimens with full-thickness defects alone (Figure 4). The direct
fabrication of biologic grafts without scaffold support further
highlights the versatility of rapid prototyping for regenerative
engineering applications.
 Figure 4 Images showing bio-3D printed adipose-derived mesenchymal stem
cell graft for cartilage regeneration.A and B, Photographs of the top view and
side view, respectively, of the printed construct immediately following stacking in
a needle array. C and D, Photographs of the top and side views, respectively,
following 6 days of cell culture. E and F, Photographs of the rabbit cartilage
defect with the cultured bio-3D printed graft in place at initial implantation and
after 3 months in vivo. G and H, Histology images showing features of the defect
following 3 months of graft implantation and the control defect without graft
implantation, respectively.(Adapted from Murata D, Kunitomi Y, Harada K,
Tokunaga S, Takao S, Nakayama K: Osteochondral regeneration using scaffold-
free constructs of adipose tissue-derived mesenchymal stem cells made by a
bio three-dimensional printer with a needle-array in rabbits. Regen Ther
2020;15:77-89, with permission from Elsevier.)

Current Limitations and Future Directions of

3D Printing
A newer advancement within the additive manufacturing process is
four-dimensional (4D) printing, which uses the same principles as
3D printing but allows for select materials to be printed and
accommodate their shape in response to specific environmental
cues. 54 A limitation of the three axes (X, Y, and Z axes) in 3D
printing is poor scaffold matching of complex curved structures
encountered in the macroscale geometries of most orthopaedic
tissues. 4D printing was proposed as a solution because such
implants can reshape based on exposure to a variety of stimuli
including temperature, pH, and magnetic field. This represents a
potential advancement as these products can be easily molded to
accommodate specific defects encountered intraoperatively.
Furthermore, smart materials that are environmentally responsive
have great potential for regeneration of tissues in which mechanical
properties vary dramatically with patient activity level, such as
muscle. Although both 3D and 4D printing have shown significant
potential in addressing current needs in orthopaedics and serving
as a cornerstone in future regenerative engineering efforts of
orthopaedic tissues, the next evolution of additive manufacturing to
five-dimensional (5D) printing may represent the most direct step
toward in vitro fabrication of biomechanically optimized, smart
material scaffolds to fulfill to goals of complex tissue, joint and
ultimately limb regeneration. 5D printing uses five axes of printing
where the printer head moves across five separate axes in addition
to the movement of the printer bed, overcoming the three axes
limitation in 3D printing. Current 5D printing machines use both
additive and subtraction manufacturing principles to keep material
waste and production costs low. The direct fabrication of curved
structures afforded by the two additional axes allows for inherently
stronger and complex geometries to be created, which overcomes
the limitation of 3D printed flat, layered structures. 3D, 4D, and 5D
printing technologies are still in their infancy with respect to
orthopaedic and regenerative engineering applications, but all
display great potential to advance the ability for creation of rapid
prototyped, complex, large-scale tissue regeneration.

Summary
Advances in materials science, an understanding of factors
influencing stem cell differentiation and proliferation, and
improved accessibility of technology for complex scaffold
fabrication and characterization have led to exponential growth in
research dedicated to regenerative engineering for orthopaedic
applications. The field is currently benefiting from advances in 3D
printing technology and pluripotent cell utilization. Future work to
fulfill the potential of electrospinning fabrication, 4D printing with
smart biomaterials, and 5D complex, strength-optimized scaffold
fabrication will help steer the field of regenerative engineering to
the future of providing translatable medical devices for
musculoskeletal tissue, joint, and limb replacement.

Key Study Points

Scaffold principles for regenerative engineering applications include biocompatibility
with tissue-specific optimized mechanical strength and porosity to permit cellular
migration and proliferation.
Scaffold features including pore density and compressive modulus can direct
pluripotent stem cells to pro-chondrogenesis cell line or pro-osteoblastic cell line
when placed in low-modulus and high-modulus environments, respectively.
Electrospinning can create nanoscale fiber scaffolds through a charged polymer
solution requiring solvent evaporation for fiber generation or a heated polymer melt
requiring polymer cooling for fiber generation. Both processes can create highly
organized fiber arrangements but is limited by various process instabilities.
3D printed scaffolds use additive manufacturing principles with multiple polymer
layers used to form complex structures. 4D printing makes use of select polymers
that respond to environmental cues. 5D printing has the potential to form stronger
complex structures through the relative motion of the polymer source and printer
collecting bed, often using both additive and subtractive manufacturing principles.

Annotated References
1. Turnbull G, Clarke J, Picard F, et al: 3D bioactive composite
scaffolds for bone tissue engineering. Bioact Mater 2018;3(3):278-
324.
2. Cushnie EK, Ulery BD, Nelson SJ, et al: Simple signaling
molecules for inductive bone regenerative engineering. PLoS One
2014;9(7):e101627.
3. Laurencin CT, Nair LS: Regenerative engineering approaches to
limb regeneration and other grand challenges. Regen Eng Transl
Med 2015;1(1):1-3.
4. Laurencin CT, Khan Y: Regenerative engineering. Sci Transl Med
2012;4(160):160ed9.
 5. Baldwin P, Li DJ, Auston DA, Mir HS, Yoon RS, Koval KJ:
Autograft, allograft, and bone graft substitutes: Clinical evidence
and indications for use in the se ing of orthopaedic trauma
surgery. J Orthop Trauma 2019;33(4):203-213. Several bone graft
options exist to aid surgeons in treating patients with traumatic
injuries. These include autograft, allograft, and synthetic bone
graft substitutes. Most of the evidence evaluating bone grafts and
substitutes consists of low-level studies. Surgeons must be aware
of the advantages and disadvantages of each option so that the
best option can be selected for the given clinical scenario. An
overview of graft options in orthopaedics is presented.
6. Murphy MB, Moncivais K, Caplan AI: Mesenchymal stem cells:
Environmentally responsive therapeutics for regenerative
medicine. Exp Mol Med 2013;45(11):e54.
7. Ogueri KS, Jafari T, Escobar Ivirico JL, Laurencin CT: Polymeric
biomaterials for scaffold-based bone regenerative engineering.
Regen Eng Transl Med 2019;5(2):128-154. The authors present an
overview of material options for bone regeneration.
8. Cooper JAJr, Sahota JS, Gorum WJ II, Carter J, Doty SB,
Laurencin CT: Biomimetic tissue-engineered anterior cruciate
ligament replacement. Proc Natl Acad Sci USA 2007;104(9):3049-
3054.
9. Gardiner DM, Bryant S, Muneoka K: Engineering limb
regeneration: Lessons from animals that can regenerate, in
Laurencin CT, Khan Y, eds: Regenerative Engineering. CRC Press,
Taylor & Francis, 2013, p 28.
10. Karamanos NK, Theocharis AD, Piperigkou Z, et al: A guide to
the composition and functions of the extracellular matrix. FEBS J
2021;288(24):6850-6912. An overview of native matrix features is
presented. The extracellular matrix has an important role in
structural support and cell signaling. Understanding the specific
extracellular matrix constituents and their functions is important
to advancing understanding of disease progression and can help
guide the development of new therapeutic agents.
11. Chen D, Smith LR, Khandekar G, et al: Distinct effects of
different matrix proteoglycans on collagen fibrillogenesis and
cell-mediated collagen reorganization. Sci Rep 2020;10(1):19065.
Biomimetic features of scaffolds to influence collagen generation
are presented. Proteoglycans in the extracellular matrix have
distinct effects on collagen behavior despite structural similarity.
Understanding the functions of these proteoglycans can help
advance understanding of certain diseases.
12. Spiller KL, Laurencin SJ, Lowman AM: Characterization of the
behavior of porous hydrogels in model osmotically-
conditioned articular cartilage systems. J Biomed Mater Res B Appl
Biomater 2009;90(2):752-759.
13. Deng M, James R, Laurencin CT, Kumbar SG: Nanostructured
polymeric scaffolds for orthopaedic regenerative engineering.
IEEE Trans Nano Bioscience 2012;11(1):3-14.
14. Muncie JM, Weaver VM: The physical and biochemical
properties of the extracellular matrix regulate cell fate. Curr Top
Dev Biol 2018;130:1-37.
15. Steward AJ, Kelly DJ: Mechanical regulation of mesenchymal
stem cell differentiation. J Anat 2015;227(6):717-731.
16. Cantini M, Donnelly H, Dalby MJ, Salmeron-Sanchez M: The
plot thickens: The emerging role of matrix viscosity in cell
mechanotransduction. Adv Healthc Mater 2020;9(8):2192-2264.
Advances in studying cell mechanotransduction through the
development of newer materials have furthered understanding of
how cells respond to changes in the extracellular matrix. The
authors explore the molecular clutch model, which is central to
adhesion-based mechanostransduction.
17. Weiner S, Wagner HD: The material bone: Structure-
mechanical function relations. Annu Rev Mater Sci 1998;
28(1):271-298.
18. Rho J-Y, Kuhn-Spearing L, Zioupos P: Mechanical properties
and the hierarchical structure of bone. Med Eng Phys
1998;20(2):92-102.
19. Koons GL, Diba M, Mikos AG: Materials design for bone-tissue
engineering. Nat Rev Mater 2020;5:584-603. An overview of
material design considerations for tissue engineering is
presented.
20. Sobajima S, Vadala G, Shimer A, Kim JS, Gilbertson LG, Kang
JD: Feasibility of a stem cell therapy for intervertebral disc
degeneration. Spine J 2008;8(6):888-896.
21. Aamodt JM, Grainger DW: Extracellular matrix-based
biomaterial scaffolds and the host response. Biomaterials
2016;86:68-82.
22. Nie X, Wang DA: Decellularized orthopaedic tissue-
engineered grafts: Biomaterial scaffolds synthesised by
therapeutic cells. Biomater Sci 2018;6(11):2798-2811.
23. Yeo M, Lee H, Kim GH: Combining a micro/nano- hierarchical
scaffold with cell-printing of myoblasts induces cell alignment
and differentiation favorable to skeletal muscle tissue
regeneration. Biofabrication 2016;8(3):035021.
24. Mengsteab PY, Nair LS, Laurencin CT: The past, present and
future of ligament regenerative engineering. Regen Med
2016;11(8):871-881.
25. Spiller KL, Laurencin SJ, Charlton D, Maher SA, Lowman AM:
Superporous hydrogels for cartilage repair: Evaluation of the
morphological and mechanical properties. Acta Biomater
2008;4(1):17-25.
26. Sola A, Bertacchini J, D’Avella D, et al: Development of solvent-
casting particulate leaching (SCPL) polymer scaffolds as
improved three-dimensional supports to mimic the bone marrow
niche. Mater Sci Eng C Mater Biol Appl 2019;96:153-165. The
authors study the solvent-casting particulate leaching technique,
which fabricates 3D porous structures to mimic the bone marrow
niche in vitro. Preliminary tests indicate that stromal cells grown
associated with the supports keep their well-known protective
and prosurvival effect on cancer cells, making this a useful
 technique to mimic the bone marrow environment and therefore
to assess the efficacy of novel therapies in preclinical studies.
27. Shi C, Yuan Z, Han F, Zhu C, Li B: Polymeric biomaterials for
bone regeneration. Ann Joint 2016;1(9).
28. Park JY, Park SH, Kim MG, Park SH, Yoo TH, Kim MS:
Biomimetic scaffolds for bone tissue engineering. Adv Exp Med
Biol 2018;1064:109-121.
29. Wu H, Lei P, Liu G, et al: Reconstruction of large-scale defects
with a novel Hybrid scaffold made from poly(L- lactic
acid)/nanohydroxyapatite/alendronate-loaded chitosan
microsphere: In vitro and in vivo studies. Sci Rep 2017;7(359).
30. Koyyada A, Prabhakar O: Recent advancements and associated
challenges of scaffold fabrication techniques in tissue
engineering applications. Reg Eng Trans Med 2020;7:147-159. An
overview of fabrication options for tissue engineering is
presented.
31. Zhang L, Yang G, Johnson BN, Jia X: Three-dimensional (3D)
printed scaffold and material selection for bone repair. Acta
Biomater 2019;15(84):16-33. The authors present an overview of
material options for 3D printing.
32. Li WJ, Laurencin CT, Caterson EJ, Tuan RS, Ko F: Electrospun
nanofibrous structure: A novel scaffold for tissue engineering. J
Biomed Mater Res 2002;60(4):613-621.
33. Bhardwaj N, Kundu SC: Electrospinning: A fascinating fiber
fabrication technique. Biotechnol Adv 2010;28(3):325-347.
34. Nair LS, Bha acharyya S, Laurencin CT: Development of novel
tissue engineering scaffolds via electrospinning. Expert Opin Biol
Ther 2004;4(5):659-668.
35. King WEIII, Bowlin GL: Near-field electrospinning and melt
electrowriting of biomedical polymers-progress and limitations.
Polymers 2021;13(7):1097. The authors discuss novel techniques
for electrospinning including the benefits of solventless
production.
36. Johnson R, Ding Y, Nagiah N, Monnet E, Tan W: Coaxially-
structured fibres with tailored material properties for vascular
graft implant. Mater Sci Eng C Mater Biol Appl 2019;97:1-11. The
authors discuss control of fiber orientation for vascular tissue
regeneration. They present their experience constructing vascular
grafts composed of coaxially structured polycaprolactone/gelatin
nanofibers. The structure provides mechanical stability and kink
resistance while maintaining flexibility and antithrombogenicity.
37. Sahoo S, Toh SL, Goh JC: A bFGF-releasing silk/PLGA- based
biohybrid scaffold for ligament/tendon tissue engineering using
mesenchymal progenitor cells. Biomaterials 2010;31(11):2990-2998.
38. Deng M, Kumbar SG, Nair LS, Weikel AL, Allcock HR,
Laurencin CT: Biomimetic structures: Biological implications of
dipeptide-substituted polyphosphazene–polyester blend
nanofiber matrices for load-bearing bone regeneration. Adv Funct
Mater 2011;21(14):2641-2651.
39. Ogueri KS, Escobar Ivirico JL, Nair LS, Allcock HR, Laurencin
CT: Biodegradable polyphosphazene-based blends for
regenerative engineering. Regen Eng Transl Med 2017;3(1):15-31.
40. Nam J, Johnson J, Lannu i JJ, Agarwal S: Modulation of
embryonic mesenchymal progenitor cell differentiation via
control over pure mechanical modulus in electrospun nanofibers.
Acta Biomater 2011;7:1516-1524.
41. Narayanan N, Jiang C, Uzunalli G, Ko appally S, Laurencin CT,
Deng M: Polymeric electrospinning for musculoskeletal
regenerative engineering. Regen Eng Transl Med 2016;2(2):69-84.
42. Schofer MD, Veltum A, Theisen C: Functionalisation of PLLA
nanofiber scaffolds using a possible cooperative effect between
collagen type I and BMP-2: Impact on growth and osteogenic
differentiation of human mesenchymal stem cells. J Mater Sci
Mater Med 2011;22(7):1753-1762.
43. Frohhbergh ME, Katsman A, Bo a GP: Electrospun
hydroxyapatite-containing chitosan nanofibers crosslinked with
 genipin for bone tissue engineering. Biomaterials
2012;33(36):9167-9178.
44. Anandkumar N, Liang Y, Habibovic P, Bli erswijk C: Calcium
phosphate coated electrospun fiber matrices as scaffolds for bone
tissue engineering. Langmuir 2010;26(10):7380-7387.
45. Hohman M: Electrospinning and electrically forced jets: I.
Stability theory. Phys Fluids 2001;13(8):2201.
46. Wixted CM, Peterson JR, Kadakia RJ, Adams SB: Three-
dimensional printing in orthopaedic surgery: Current
applications and future developments. J Am Acad Orthop Surg
Glob Res Rev 2021;5(4):e20.00230-11. The authors review 3D
printing advances. 3D printing has revolutionized patient care
across all subspecialties through the development of custom and
noncustom implants, patient-specific instrumentation, anatomic
models, and prosthetics. Bioprinting cartilage and bone
represents the next frontier in managing a range of clinical
conditions from cartilage injury to bone defects and tumors.
47. Lal H, Patralekh MK: 3D printing and its applications in
orthopaedic trauma: A technological marvel. J Clin Orthop
Trauma 2018;9(3):260-268.
48. Dall’Ava L, Hothi H, Henckel J, et al: Osseointegration of
retrieved 3D-printed, off-the-shelf acetabular implants. Bone Joint
Res 2021;10(7):388-400. Novel 3D printed implants for
arthroplasty applications are discussed. The authors compared
bone integration between 3D printed and conventional
acetabular implants to evaluate the effect of 3D printing on
osteointegration. Histologic analysis demonstrated superior bone
ingrowth and greater bone a achment in 3D printed acetabular
implants compared with conventional implants.
49. Okolie O, Stachurek I, Kandasubramanian B, Njuguna J: 3D
printing for hip implant applications: A review. Polymers
2020;12(11):2682. In this review article, the authors discuss
various aspects of 3D printing for hip surgery including
fabrication techniques and surface modifications. The challenges,
 ethics, and trends in the 3D printing are also discussed. Three-
dimensional printing has immense promise and potential to
improve the implants used for hip arthroplasty.
50. Kumar S, Hashimi S, Saifzadeh S, Vaque e C: Additively
manufactured biphasic construct loaded with BMP-2 for vertical
bone regeneration: A pilot study in rabbit. Mater Sci Eng C Mater
Biol Appl 2018;92:554-564.
51. Rampichová M, Košt’áková Kuželová E, Filová E, et al:
Composite 3D printed scaffold with structured electrospun
nanofibers promotes chondrocyte adhesion and infiltration. Cell
Adh Migr 2018;12(3):271-285.
52. Yeo M, Kim G: Micro/nano-hierarchical scaffold fabricated using
a cell electrospinning/3D printing process for co-culturing
myoblasts and HUVECs to induce myoblast alignment and
differentiation. Acta Biomater 2020;15(107):102-114. The authors
demonstrate scaffold topography on cell proliferation. They
present a method for co-culturing human umbilical vein
endothelial cells and myoblasts using cell electrospinning and 3D
bioprinting. This method produced high cell viability, allowing
for meaningful mechanical stability and homogeneous cell
distribution.
53. Murata D, Kunitomi Y, Harada K, Tokunaga S, Takao S,
Nakayama K: Osteochondral regeneration using scaffold- free
constructs of adipose tissue-derived mesenchymal stem cells
made by a bio three-dimensional printer with a needle- array in
rabbits. Regen Ther 2020;15:77-89. This is an in vivo analysis of 3D
printed structure using consolidated mesenchymal stem cells to
form a defect-filling, scaffold-free articular cartilage graft. The
authors demonstrate direct rapid prototyping and cellular
printing and make tissue substitutes with regenerative
capabilities.
54. Reddy PR, Devi PA: Review on the advancements of additive
manufacturing-4D and 5D printing. Int J Mech Prod Eng Res Dev
2018;8(4):397-402.
C H AP T E R 1 4

Musculoskeletal Mechanics and

Kinesiology
Christian Klemt PhD, Young-Min Kwon MD, PhD, FAAOS

Dr. Kwon or an immediate family member has received research or institutional support from
Biomet, Corentec, DePuy, a Johnson & Johnson Company, Smith & Nephew, Stryker, and Zimmer.
Neither Dr. Klemt nor any immediate family member has received anything of value from or has
stock or stock options held in a commercial company or institution related directly or indirectly to
the subject of this chapter.

ABSTRACT
Musculoskeletal mechanics involves the application of basic
mechanical principles to the musculoskeletal system. It analyzes
the behavior of the musculoskeletal system during functional
activities and under physiologic loading conditions. Forces can be
applied to the human musculoskeletal system either through
internal contraction of muscles or through external sources.
Kinesiology is the scientific study of human body movement. The
forces act on the musculoskeletal system to accelerate body
segments around joints, thereby facilitating locomotion. A
numerical analysis of locomotion is provided by Newton’s law of
motion, which involves the calculation of muscle forces and joint
torques required to perform functional activities. Applications of
musculoskeletal mechanics and technologies include motion
capture analysis, dual fluoroscopy imaging systems, and wearable
devices, which enable the orthopaedic surgeon to evaluate the
dynamic performance of human lower and upper limb joints and
joint replacements.
Keywords: fluoroscopy; in vivo kinematics; motion capture;
musculoskeletal mechanics; wearable technology

Introduction
The application of forces to the musculoskeletal system generates
moments around joints, thereby facilitating locomotion. It is
important for the orthopaedic surgeon to have an understanding of
the various applications of musculoskeletal biomechanics and
related concepts including implant design considerations, wear
mechanisms, and rigid body mechanics.

Force, Moment, and Free-Body Diagrams

A force is defined as a quantity that changes the velocity and/or
direction of an object of the musculoskeletal system. Its magnitude
is given by the product of the mass of the object and its
acceleration. The unit of the force is given in Newtons (N = kg·m/s2).
When a force acts on the musculoskeletal system over a distance
from the joint center, the force creates a torque around the joint. A
moment is defined as a quantity that changes the angular velocity
of an object of the musculoskeletal system. The magnitude of the
moment is defined by the product of its moment of inertia and its
angular acceleration. The unit is the Newton-meter (N·m).
When an external force acts on a segment of the musculoskeletal
system, for example, when a weight is being held with an
outstretched arm, the moment created around the shoulder joint is
equal to the product of the force acting on the body segment as well
as the perpendicular distance between the line of action of the force
and the joint center of rotation (defined as moment arm).
Therefore, the moment acting on the shoulder joint as shown in
Figure 1 is 80 N m. To resist the external load and keep the
outstretched arm in an equilibrium position, internal muscle forces
must be generated through the contraction of shoulder muscles
including the deltoid to counteract the moment created by the
external load.

Figure 1 An illustration of a person holding a weight (10 kg) that creates a

moment (80 N m) around the shoulder joint.

The static equilibrium refers to the state of the musculoskeletal

system, in which there is no acceleration of body segments. This
means that the body segments are either at rest or moving with a
constant velocity.

The concept of static equilibrium can be used to calculate the

force required by the biceps muscle to keep the arm, as shown in
Figure 2, in an equilibrium position. Without any acceleration of
body segments, the sum of the forces and moments around the
elbow joint must be zero. If the weight in the hand and the biceps
force are considered the only two forces generating a moment
around the elbow joint, then the extension moment caused by the
weight must be offset by the flexion moment created through the
contraction of the biceps. As the moment arm of the biceps muscle
around the elbow is an order of magnitude smaller than the
 g
moment arm of the weight (4 cm versus 30 cm), the biceps must
generate a 7.5 times greater force to create the same magnitude
moment around the elbow joint as was generated by the weight.

Figure 2 An illustration of a person holding a weight of 5 N in the hand that

creates a moment of 1.5 N m around the elbow joint.

Free-body diagrams are used to identify all forces and moments

acting on a segment of the musculoskeletal system to correctly
apply the equilibrium equations. For that purpose, the
musculoskeletal system is isolated from its surroundings and
forces as well as moments are used to replace the effect of the
surrounding environment. Figure 3 shows a forearm holding a
weight. Point O describes the fixed axis of rotation for the elbow.
Point A quantifies the biceps muscle a achment with the radius,
point B describes the forearm center of gravity, and point C
describes the center of gravity of the weight. W O is the mass of the
object and W F is the total weight of the forearm. F B connotates the
biceps force exerted on the radius, whereas R F connotates the
elbow joint reaction force. The line of action for the muscle forces
as well as the gravitational forces is assumed to be vertical.
 Figure 3 Free-body diagram showing the forces acting on the forearm while
holding a weight.

The elbow joint reaction force (R F) as well as the muscle force (F

B) can be computed through consideration of the equilibrium
conditions at the forearm. Analyzing the rotational equilibrium
conditions of the forearm around the elbow joint will lead to:
 Analyzing the translation forearm equilibrium along the y-
direction leads to:

These rotational and translational equilibrium equations can be

solved for R F and F B for any given set of parameters. For example,
if a = 4 cm, b = 15 cm, c = 35 cm, WO = 80 N, and WF = 20 N, this
would yield a force of 775 N for F B and a force of 675 N for R F.
Free-body diagrams can also be used to calculate external
intersegmental forces and moments at different joints during
locomotion. In Figure 4, A, the subscripts f, s, and t denote foot,
shank, and thigh, respectively. I denotes the moment of inertia,
whereas α stands for the angular acceleration. The gravitational
acceleration is denoted by g, whereas m and a stand for the
segmental mass and linear acceleration, respectively. In Figure 4, B,
the subscripts g, k, a, and h denote the ground, knee, ankle, and
hip. The force is denoted by F, whereas T denotes the resultant
torque. Following the creation of the free-body diagrams,
equilibrium equations serve to calculate the unknown proximal
forces. The calculations start from the distal end and proceed to the
proximal end of the body segment, starting with the foot. Both the
torque as well as the force at the distal part of the shank are equal
and opposite to the torque and force of the ankle. With the
knowledge of distal force and torque of the shank, the proximal
force and torque of the shank can then be calculated.
 Figure 4 Free-body diagrams of the lower limb.A, Inertial properties. B,
Intersegmental forces and moments.

Musculoskeletal Tissue Mechanics

Bone represents the most abundant of the tissues in the
musculoskeletal system. Bones contain 40% inorganic material
(hydroxyapatite), 35% organic matrix (type I collagen), and 25%
water. 1 When loaded, the inorganic material contributes to the
compressive behavior and the type I collagen plays a significant
role in the tensile properties of bones. At the micrometer level,
bone is composed of mineralized collagen fibrils that are
embedded within the organic extracellular matrix. The fibrils are
arranged into lamellae with a thickness of 7 to 10 µm.
Circumferential structures of numerous lamellae with a central
haversian canal form osteon, a structure that is approximately 200
µm in diameter. Lamellae as well as osteons form cortical and
cancellous bone structures at the highest level of scale (greater than
1 mm). The cortical bone is made up of longitudinally oriented
lamellae and osteons, whereas cancellous bone (cortical bone) is
characterized by an open cellular structure with a variable
microstructure of trabeculae and struts.
Based on the hierarchical structure of bones, its material
properties are anisotropic (vary in different directions) and
viscoelastic (dependent on loading rate). Cortical bone loaded
longitudinally is more resistant compared with loads applied in the
transverse direction. 1 The cortical bone is loaded the greatest
extent in the longitudinal direction during functional daily
activities including walking and running. Additionally, cortical
bone is stronger in compression, when compared with tension.
Stiffness and strength of cortical bone are dependent on the
loading rate, with a stiffer behavior and a decreased failure strain
when loaded more quickly 2 (Figure 5). With regard to cancellous
bone, its material properties are more challenging to generalize. Its
material properties are dependent on the apparent density,
quantified through linear or exponential relationships. 3 Cancellous
bone, similar to cortical bone, is stronger in compression compared
with tension.
 Figure 5 Graph shows the stress-strain curve of bone.

Tendon and Ligament Mechanics

The mechanical behavior of tendons and ligaments is similar,
despite their different functions in the musculoskeletal system.
Ligaments connect bone to bone to provide joint stability, whereas
tendons connect muscle to bone to transfer muscle-generated force
to the skeleton to facilitate motion. The tissue matrices of both
tendons and ligaments are composed of type I collagen (75% to 80%
dry weight) and proteoglycans (1% to 3% dry weight). 4 They are
both highly hydrated, with one major difference. Ligaments contain
a greater percentage of elastin (10% to 15% dry weight) compared
with tendons (less than 3% dry weight). With regard to tendons, the
collagen fibers are aligned uniformly along the loading direction of
the tendon. In contrast, the collagen fibril orientation in ligaments
is less structural, reflecting the greater range of loading conditions
experienced by ligaments.
The mechanical properties of tendons and ligaments are
characterized by anisotropic behavior. The tensile stiffness of
tendons and ligaments is smaller in comparison with bone but
greater than that of cartilage. The nonlinear behavior of tendons
and ligaments under tensile loading conditions is characterized by
an initial toe region, where low loads lead to high deformations as
fiber realignment occurs. The toe region is followed by a linear
region where the aligned fibers bear the load and elongate until
yield and failure occur.

Hip and Knee Joint Implant Mechanics

The knee and hip joints are diarthrodial joints, which facilitate the
relative movement of the articulating bones in the synovial cavity.
The joint motions are commonly defined in three mutually
perpendicular anatomic planes: coronal (frontal), sagi al
(longitudinal), and transverse (horizontal). Rotations of the lower
limb in the coronal plane are defined as abduction (leg is raised
away from the center of the body) and adduction (leg moves back
toward the center of the body). Rotations in the sagi al plane are
defined as flexion (hip rotates forward) and extension (hip rotates
back toward straightened position). With regard to the transverse
plane, rotations are defined as internal rotation (rotate around its
longitudinal axis toward the center of the body) and external
rotation (rotate around its longitudinal axis outward). The hip joint
allows all three of these rotations, thus it has three degrees of
freedom for rotation, in addition to the three degrees of freedom
for translation, making the hip joint an articulation with six degrees
of freedom. The knee joint allows the translation of the articulating
surfaces in the three anatomic directions, in addition to the three
rotations, thus the knee joint has six degrees of freedom. With
regard to hip and knee total joint arthroplasties, current implant
designs preserve these degrees of freedom to restore joint
functionality.
The rotational motion of the hip joint has been quantified during
numerous functional activities including gait, sit-to-stand, and stair
climbing. Hip joint rotations during walking are shown in Figure 6
based on findings from a 2019 study. 5 The stance phase (leg in
contact with the ground) encompasses approximately 60% of the
gait cycle and starts with heel strike and finishes with toe-off. The
swing phase (leg in no contact with the ground) makes up
approximately 40% of the gait cycle and starts with toe-off and ends
with another heel strike. Figure 6 illustrates that the hip joint
extends in the sagi al plane by almost 35° during the stance phase,
before flexing back during the swing phase. Abduction/adduction
angles as well as internal/external rotation angles both cover a
range of 10° during the gait cycle. The first half of the stance phase
is characterized by hip abduction and internal rotation, whereas the
second half of the stance phase is characterized by a hip adduction
and external rotation in order to return to its equilibrium position.
Because the hip joint is a ball-and-socket joint, the hip rotations
require a relative sliding motion of the femoral head with regard to
the acetabulum. Relative sliding motion occurs during functional
daily activities, with the largest sliding motion required for
flexion/extension rotations.
Figure 6 Graphs show hip rotations during gait.
 The complex motions of the knee joint during functionally
strenuous activities have been studied in the literature.
Representative data for flexion/extension, internal/external rotation,
and anterior/posterior translation during gait are presented in a
study 6 and are shown in Figure 7. These data are derived from
average patient data and used to program knee simulators for the
assessment of wear pa erns of knee arthroplasties. With regard to
the gait cycle as shown in Figure 7, the knee is almost fully
extended at heel strike, with the tibia being slightly rotated with
regard to the femur. During the first 50% of the stance phase, knee
flexion angles of up to 20° can be observed, whereas the tibia
demonstrates internal rotation and anterior translation relative to
the femur. During the last 50% of the stance phase, the knee
demonstrates almost full extension, with the tibia rotating
externally and displacing posteriorly relative to the femur. With
regard to the swing phase, a large amount of knee flexion occurs
(almost 60°) before the knee returns to full extension in time for the
next gait cycle. The largest loads and contact stresses occur during
the stance phase, in which the leg is in contact with the ground.
 Figure 7 Graphs show kinematics of the knee during the gait cycle.

Because of the complex interplay of knee rotations and knee

translations during functional daily activities, the knee joint
demonstrates a combination of rolling and sliding motions. As a
result, the location of contact between tibial and femoral
components of the joint replacement moves during functional daily
activity. The precise motion of the contact location is highly
dependent on the design of the articulating surfaces. One example
of a potential motion pa ern for a total knee arthroplasty design is
shown in Figure 8. The medial condylar contact pathway and the
lateral condylar contact pathway both typically follow a narrow “8”
shape. There are differences with regard to the pathway between
the medial and lateral condyle as shown in Figure 8, which
facilitates the internal/external rotation of the femoral component
relative to the tibial component.
 Figure 8 Illustration shows contact path motion of the medial and lateral
condyle of the femoral component during gait.The contact path motions are
described relative to the tibial component with polyethylene liner of the total knee
arthroplasty.

Clinical Applications of Musculoskeletal

Mechanics and Technologies
The numerical outputs of musculoskeletal models require
substantial validation and verification to provide clinical utility. For
that purpose, experimental methods including instrumented
implants and the telemetric transmission of load, strain, or
pressure data have been successfully developed. With regard to the
hip joint, most experimental studies used strain gauges a ached to
the neck of the femoral component of the hip arthroplasty 6 , 7
(Figure 9). The output of the strain gauge is transmi ed to a
receiver where data analysis for forces acting on the femoral head
can be performed. In terms of the knee joint, a limited number of
prior experimental studies tested instrumented knee implants
(distal portion of the femur) with a telemetric transmission of
measured data. 8 A different approach has been used, whereby the
tibial knee prosthesis was instrumented for the measurement of
knee loads during functional tasks. 9 The most complete database
for multiple joint replacements (hip, knee, shoulder, spine) and
numerous functional tasks is provided by OrthoLoad
(h ps://orthoload.com/).

Figure 9 Graph shows hip joint contact force during gait.

With regard to in vivo loads of the musculoskeletal system

during functional daily activities, recent studies showed in vivo
shoulder loads of up to one to two times the body weight. 9 , 10 In
vivo joint forces in the lower extremities are higher and often reach
multiple times the body weight during routine daily activities. In
vivo joint loads of up to two to eight times the body weight have
been recorded for the hip and knee joint during strenuous
activities, including running and jumping, 10 - 15 as shown in Table 1.
Table 1
Peak Hip Joint Contact Forces During Functional Daily Activities

Functional Activity Maximum Hip Force (Body Weight) Reference

Level walking (slow) 4.8 Paul (1976) 14
Level walking (slow) 2.4 Bergmann et al (2001) 6
Level walking (normal) 2.3 Bergmann et al (2001) 6
Level walking (normal) 3.0-3.3 Prendergast et al (2005) 15
Level walking (fast) 7.5 Paul (1976) 14
Level walking (fast) 2.5 Bergmann et al (2001) 6
Downhill walking 5.1 Paul (1976) 14
Uphill walking 5.9 Paul (1976) 14
Descending stairs 7.2 Paul (1976) 14
Descending stairs 2.6 Bergmann et al (2001) 6
Ascending stairs 2.4 Bergmann et al (2001) 6
Ascending stairs 2.8-3.2 Prendergast et al (2005) 15

Motion Capture Technology and

Musculoskeletal Modeling
The use of motion capture technology in combination with
computational musculoskeletal models of the upper and lower limb
has demonstrated great potential to assist in the clinical decision-
making process for patients with musculoskeletal disorders. 11 The
application of these technologies can provide information on
variables of the musculoskeletal system such as muscle forces and
joint contact forces, parameters that are clinically highly relevant
but are challenging to measure in vivo without invasive surgical
procedures, including the placement of sensors in tendons or the
implantation of instrumented joint replacements. 12 Therefore, the
use of motion capture technology and musculoskeletal modeling
has seen an increased use in clinical practice over recent years, for
example, to assess orthoses, to assist in surgical decision-making, to
aid the development of new rehabilitation protocols, to design new
surgical interventions, and to aid the development of new joint
replacements. 13
 Motion capture technology involves the tracking of body
segments during locomotion through the means of either optical
sensors or nonoptical sensors (inertial sensors, magnetic sensors,
stretch sensors, acoustic sensors). For most research and clinical
and industrial applications, optical sensors (markers coated with
retroreflective material) are used because they are inexpensive,
highly reliable, and user friendly. The retroreflective optical
markers are tracked by infrared cameras, captured with a rate that
is at least two times the frequency rate of the desired motion to
avoid inaccuracies. The motion capture system commonly consists
of 5 to 10 infrared cameras to obtain a 360° view of the markered
subject (Figure 10). At least three different cameras need to be able
to capture the motion of each retroreflective optical marker to
accurately track the motion of body segments. 16 The retroreflective
markers are placed in specific anatomic locations (bony landmarks)
that serve to construct coordinate frames for each body segment,
which in turn are required to compute the positions of the body
segments relative to each other. With regard to the coordinate
frames, the International Society of Biomechanics has established
these anatomic landmarks, which were proven to be highly reliable
and accurate for motion tracking. 17
 Figure 10 Illustration shows optical motion capture experimental setup
including infrared cameras.

Musculoskeletal models of upper and lower limb joints represent

computational tools that estimate the loading of the
musculoskeletal system during locomotion. These musculoskeletal
models use motion capture data as input to calculate the required
muscle forces to complete the recorded motion as well as the
resultant joint contact forces associated with the recorded motion.
The musculoskeletal models are represented by a skeletal system
consisting of all bony body segments and all muscular a achments
of the human body (Figure 11). The bony anatomy and muscle
morphology are commonly obtained from the dissection and
digitization of a cadaver specimen to parametrize the
musculoskeletal model. The muscles of the musculoskeletal model
are represented by taut strings that wrap around geometric objects
that resemble the articulating joints. 18 To adapt the anatomy of a
generic musculoskeletal model to an individual subject from the
motion capture experiment, the generic skeletal geometry of the
computational musculoskeletal model is scaled to an individual
subject using body height and body weight. Recent studies have
used medical imaging and statistical modeling approaches for
model scaling to facilitate the customization of musculoskeletal
modeling with the overall purpose of enhancing its clinical
applicability. 19

Figure 11 Illustration depicts a musculoskeletal shoulder model including

muscle lines of action.

Most of the musculoskeletal models use an inverse dynamic

approach to calculate muscle and joint contact forces during
locomotion. Inverse dynamics use the equations by Newton to
calculate intersegmental forces and moment for each time frame of
the recorded motion data. 18 Load-sharing optimization is
consequently performed to ensure that the computed muscle forces
and resultant joint contact forces are in equilibrium with the
calculations from inverse dynamics. Load-sharing optimization
commonly minimizes the sum of squared muscle stresses to ensure
activation of all muscles spanning the joint, with an overall goal of
minimizing energy consumption. 20 Musculoskeletal models of the
upper and lower limb have been validated against instrumented
implant measurements and electromyography measurements as
well as the measurement of muscle moment arms from cadaver
specimens. 21 , 22
Musculoskeletal models have been used in a variety of clinical
se ings including assessment of nonsurgical treatment, orthoses,
surgical intervention, and the effectiveness of exercise and
rehabilitation programs. 13 In terms of nonsurgical treatment,
studies have investigated the effect of botulinum toxin on the force
of the rectus femoris muscle and the effect of an androgen
deprivation therapy on the use of muscles involved in vertical
stability during gait in patients with hemiparetic conditions. 23 , 24
With regard to orthotic devices, studies have looked at the use of
joint contact force to assess the effect of insoles, lateral foot wedges,
and knee braces on the treatment of knee osteoarthritis. 25 , 26 In
terms of surgical intervention, previous studies have focused on the
outcomes of patients after anterior cruciate ligament surgery and
the potential for the development of osteoarthritis resulting from
altered joint loading. 27 , 28 Studies on rehabilitation have assessed
the outcomes of exercise and rehabilitation strategies with regard
to improved joint contact forces and muscle loading. 9 , 29

Dual Fluoroscopy
Fluoroscopy provides an opportunity for real-time, interactive x-ray
projection imaging. Fluoroscopic procedures are commonly
performed with an image intensifier to detect x-ray pa erns
following the removal of sca ered radiation through an antisca er
grid. The x-rays are captured using a cesium iodide (CsI) scintillator
and converted to light photons, which are subsequently guided
toward the photocathode layered on the back of the scintillator. 30 A
proportional number of electrons are generated and accelerated as
a result of a large voltage (>20,000 V) between the photocathode
and the anode, which is located on the other side of the tube. The
focus of electron trajectories is maintained by electromagnetic
focusing coils, which additionally reduce the large area electron
distribution to the area of the photocathode. As the electrons make
contact with the output photocathode, the resultant light image is
amplified (>5,000) by a factor in the image intensifier. 31 The light
pa erns are detected by a television camera and displayed on a
monitor. Fluoroscopy allows the use of continuous currents in the
x-ray tube as well as the use of discontinuous currents, which
generate a series of x-ray projection images (typically 30 frames per
second) with an overall reduction in radiation exposure.
Dual fluoroscopic imaging systems (DFIS) were recently
developed to accurately quantify in vivo total joint arthroplasty
kinematics (Figure 12). This is achieved through the use of two
orthogonal fluoroscopic imagers in combination with two-
dimensional/three-dimensional (2D/3D) registration techniques. In
the first step, a CT scan of the patient’s joint serves to create a 3D
subject-specific model of the osseous anatomy. Similarly, a 3D
model of the joint replacement is generated to obtain a customized
3D reconstruction of the patient’s bony anatomy including the joint
arthroplasty. 32 Both osseous anatomy and joint replacement are
assigned anatomic coordinate frames in concordance with the
International Society of Biomechanics. 17 A 3D mirroring technique
is used to assign anatomic coordinate systems to the surgically
treated joint, which allow the minimization of residual surface-to-
surface registration errors between the remaining bone on the
surgical side and mirrored nonsurgical side 33 (Figure 13). The joint
rotations are consequently computed based on the assigned local
coordinate frames using Cardan angle sequences, which represent
joint rotation angles applied in a specific sequence.
 Figure 12 Illustration shows the fluoroscopy imaging system.

Figure 13 Three-dimensional knee model of unilateral total knee arthroplasty

reconstructed from CT images.

After the CT scan is obtained, patients perform functional tasks

of daily living under DFIS surveillance with the two fluoroscopic
imagers positioned orthogonally to one another. Both fluoroscopes
record images synchronously, commonly at 30 Hz, thereby
producing a tandem view of the targeted joint from orthogonal
positions. 34 The fluoroscopic images are consequently processed
together with the 3D models of the osseous anatomy and joint
arthroplasty to virtually align the 3D models to match the
silhoue e of the patient’s anatomy observed on the orthogonal
fluoroscopic images (Figure 14). All fluoroscopic images are
analyzed in this way to generate a series of 3D images that depict
the patient’s motion during this activity. This provides clinically
useful information on in vivo joint motion in all six degrees of
freedom during functional activities, with prior studies
investigating numerous tasks including treadmill gait, sit-to-stand,
stair climbing, single-leg deep lunge, squats. 35 , 36 The accuracy of
DFIS is comparable with that of gold-standard radiostereometric
analysis with errors of less than 0.9 mm for translations and 0.6° for
rotations. 33 Although DFIS technologies inherently expose patients
to an increased amount of radiation compared with
radiostereometric methods, current DFIS technologies keep the
radiation exposure low (5 to 6 mSv).

Figure 14 Illustration of a dual fluoroscopic imaging system (DFIS) setup.A,

DFIS during dynamic activity. B, Image registration.

DFIS technology has been used in a variety of se ings to assist in

clinical decision-making. In vivo joint kinematics were investigated
for different arthroplasty designs, demonstrating that despite the
potential to restore healthy knee kinematics in vivo, contemporary
hip and knee joint arthroplasties do not fully restore healthy joint
kinematics during functionally strenuous activities. 35 , 37 , 38
Additionally, DFIS technology was used to assess the effect of
surgical approaches on in vivo joint kinematics. The study findings
illustrate that robotic-assisted hip replacement surgery leads to
higher implant positioning accuracy, when compared with freehand
total hip arthroplasty; however, this did not translate into
significantly improved in vivo kinematics. 39 , 40 Similarly, a previous
study investigated the effect of anterior, lateral, and posterior
surgical approach for total hip arthroplasty, reporting that
differences exist with regard to in vivo kinematics for different
surgical approaches. 41 In addition to arthroplasty designs and
surgical approaches, prior studies commonly used DFIS technology
to investigate the effect of pathology on in vivo joint kinematics.
These prior studies evaluated in vivo kinematics for patients with
cam femoroacetabular impingement syndrome, labral injuries,
cruciate ligament reconstruction, and muscle atrophy. 42 - 44

Wearable Devices
The term wearable technology refers to all devices that can be worn
on the human body. Since the introduction of the wristwatch
several decades ago, the concept of wearable technology has
a racted strong human interest. This technology becomes
increasingly prevalent, especially in technology-driven countries.
These wearable devices collect data that are then transmi ed to the
user through a monitoring interface. Following the great success of
wearable technology for fitness tracking, there is growing interest
from orthopaedic surgeons to use wearable devices because of their
potential to streamline communication between physicians and
patients, optimizing patient care and potentially reducing the rising
health- care costs.
With the advancement of technology, wearable devices present
great opportunities for integration into orthopaedics. The generic
data that most wrist devices track (heart rate, activity levels,
sleeping pa erns, nutritional information) provide valuable
information to orthopaedic surgeons in terms of assessing the
baseline of each patient. This facilitates the development of a
patient-specific treatment plan, in addition to the opportunity for
patients to objectively report their outcomes. Furthermore, these
wrist trackers provide an opportunity to monitor any alteration in
the postoperative recovery period and to guide personalized
physical therapy protocols. Prior research studies have reported
that wearable technology can be used to improve patient adherence
to treatment plans, rehabilitation protocols, and self-management
of different medical conditions. 45 - 47
Wearable technology that provides insight into more
orthopaedic-related measures including range of motion, stride
length, and pelvic rotation has the potential to quantify disease
severity, monitor clinical patient outcomes, and track the recovery
process. 48 One application of these wearable devices includes the
quantification of mobility in patients with spinal stenosis to detect
worsening of walking tolerance. Additionally, these wearable
devices were applied to monitor the postoperative recovery process
in patients who have experienced a stroke to optimize patient
outcomes. 49 The remote monitoring of a patient’s health may assist
orthopaedic surgeons by providing a more complete preoperative
picture of the disease and the possibility to track acute
postoperative disease progression. These devices may also be used
in future applications to monitor range of motion for patients
following anterior cruciate ligament reconstructions to ensure that
patients abide by mobility restrictions as part of their rehabilitation
protocols. This remote monitoring of patient data has great clinical
potential because it allows the transmission of data wirelessly to
physicians, which may implement preventative intervention in real
time to optimize patient outcomes and reduce healthcare costs. 50
Despite the great potential of wearable technology in orthopaedic
se ings, numerous limitations have to be overcome for widespread
adoption of this technology. First, age dynamics represent a hurdle
for the incorporation of wearable technology as a regular tool in
orthopaedic environments. Although elderly patients have
demonstrated an increasing interest in the use of wearable
technology to improve mental and physical health, prior research
has demonstrated a limited overall use among elderly patients. 51
Second, wearable technology can be costly for the patients, with
some of these devices costing several hundred dollars, which may
inherently lead to a stratification of patient care. Recent research
supports this notion, reporting that despite an overall high patient
satisfaction for wearable fitness trackers, the high costs were the
main concern for dissatisfaction. 52 Third, security concerns
associated with the utilization of wearable technologies exist.
Consumer-marketed devices often lack standardized provisions for
security and user authentication. 53 Therefore, the protection of
confidential patient information remains a significant challenge
associated with the use of wearable technology in clinical se ings.
Finally, a fundamental concern for the utility of wearable
technology is based on the validity of the measured parameters.
One study compared numerous wearable devices for the
measurement of physical activity, reporting considerable variations
in accuracy (as high as 25%). 54

Summary
It is essential to have an understanding of the basic principles of
biomechanics and kinesiology including the analysis of forces
acting on the musculoskeletal system, bone, tendon and ligament
mechanics, and the biomechanics of the hip and knee joint.
Applications of musculoskeletal biomechanics include motion
capture technologies, dual fluoroscopy imaging systems, and
wearable technology, which enable the orthopaedic surgeon to
evaluate the performance of human lower and upper limb joints
and joint replacements.

Key Study Points

Free-body diagrams are used to identify all forces and moments acting on a
segment of the musculoskeletal system.
Telemetry provides an effective tool to measure in vivo loading of joints through the
use of instrumented implants.
Motion capture technology and musculoskeletal modeling provide insight into the
loading of muscles and joint through computational analysis of motion.
Dual fluoroscopy allows for the accurate assessment of in vivo joint replacement
kinematics through optimal matching of hip and knee computer-aided design model
projections with the dynamic fluoroscopic images.
Wearable devices are worn on the human body for the study of external parameters
of the musculoskeletal system such as range of motion.
Annotated References
1. Reilly DT, Burstein AH: The elastic and ultimate properties of
compact bone tissue. J Biomech 1975;8(6):393-405.
2. McElhaney JH, Fogle JL, Melvin JW, Haynes RR, Roberts VL,
Alem NM: Mechanical properties on cranial bone. J Biomech
1970;3(5):495-511.
3. Rice JC, Cowin SC, Bowman JA: On the dependence of the
elasticity and strength of cancellous bone on apparent density. J
Biomech 1988;21(2):155-168.
4. Silver FH, Freeman JW, Bradica G: Structure and function of
ligaments, tendons, and joint capsule. in Walsh WR, ed: Repair
and Regeneration of Ligaments, Tendons, and Joint Capsule. Humana
Press, 2006, pp 15-47.
5. Peng Y, Arauz P, Desai P, Byers A, Klemt C, Kwon Y-M: In vivo
kinematic analysis of patients with robotic-assisted total hip
arthroplasty during gait at 1-year follow-up. Int J Med Robot
2019;15(5):e2021. This study uses dual fluoroscopy to study in
vivo total hip arthroplasty kinematics. The study findings show
that improved accuracy in restoring native hip geometry achieved
by the robotic arm–assisted total hip arthroplasty procedure did
not fully translate into improved gait symmetry. Level of
evidence: III.
6. Bergmann G, Deure bacher G, Heller M, et al: Hip contact
forces and gait pa erns from routine activities. J Biomech
2001;34(7):859-871.
7. Rydell NW: Forces acting on the femoral head-prosthesis. A
study on strain gauge supplied prostheses in living persons. Acta
Orthop Scand 1966;37(suppl 88):1-132.
8. Taylor SJ, Walker PS: Forces and moments telemetered from two
distal femoral replacements during various activities. J Biomech
2001;34(7):839-848.
9. Klemt C, Prinold JA, Morgans S, et al: Analysis of shoulder
compressive and shear forces during functional activities of daily
 life. Clin Biomech (Bristol, Avon) 2018;54:34-41.
10. Bergmann G, Graichen F, Bender A, Kaab M, Rohlmann A,
Westerhoff P: In vivo glenohumeral contact forces –
Measurements in the first patient 7 months postoperatively. J
Biomech 2007;40(10):2139-2149.
11. Prinold JA, Masjedi M, Johnson GR, Bull AM: Musculoskeletal
shoulder models: A technical review and proposals for research
foci. Proc Inst Mech Eng H 2013;227(10):1041-1057.
12. Bull AMJ, Reilly P, Wallace AL, Amis AA, Emery RJH: A novel
technique to measure active tendon forces: Application to the
subscapularis tendon. Knee Surg Sports Traumatol Arthrosc
2005;13(2):145-150.
13. Smith SHL, Coppack RJ, van den Bogert AJ, Benne AN, Bull
AMJ: Review of musculoskeletal modelling in a clinical se ing:
current use in rehabilitation design, surgical decision making
and healthcare interventions. Clin Biomech 2021;83:105292. This
study represents a systematic review of the use of
musculoskeletal modeling in clinical environments for
rehabilitation design, surgical decision-making, and healthcare
interventions. A clinically useful overview of the potential
applications of musculoskeletal models in clinical se ings is
provided. Level of evidence: IV.
14. Paul JP, Ford SH, Swanson SAV, Tyrrell DAJ: Approaches to
design - force actions transmi ed by joints in the human body.
Proc R Soc Lond B Biol Sci 1976;192(1107):163-172.
15. Prendergast PJ, van der Helm F, Duda GN: Analysis of muscle
and joint loads. Basic Orthop Biomech Mechano-Biology 2005;8:29-
89.
16. Menolo o M, Komaris D-S, Tedesco S, O’Flynn B, Walsh M:
Motion capture technology in industrial applications: A
systematic review. Sensors 2020;20(19):5687. This study provides
an overview of motion capture technology as well as summary of
motion capture applications in industrial environments. It details
its strengths and limitations to elaborate on the application in
 industrial se ings. Future industrial applications of motion
capture technology are discussed. Level of evidence: IV.
17. Wu G, van der Helm FCT, Veeger HEJD, et al: ISB
recommendation on definitions of joint coordinate systems of
various joints for the reporting of human joint motion – part II:
Shoulder, elbow, wrist and hand. J Biomech 2005;38(5) :981-992.
18. Charlton IW, Johnson GR: A model for the prediction of the
forces at the glenohumeral joint. Proc Inst Mech Eng H
2006;220(8):801-812.
19. Klemt C, Nolte D, Ding Z, et al: Anthropometric scaling of
anatomical datasets for subject-specific musculoskeletal
modelling of the shoulder. Ann Biomed Eng 2019;47(4):924-936.
This study validates subject-specific musculoskeletal models of
the shoulder. The study highlights that subject-specific shoulder
models yield significant improvements in model reliability, when
compared with always using a single generic model. This has
strong potential to apply these models clinically to support
clinical decision-making. Level of evidence: III.
20. Cleather DJ, Bull AMJ: Lower-extremity musculoskeletal
geometry affects the calculation of patellofemoral forces in
vertical jumping and weightlifting. Proc Inst Mech Eng H
2010;224(9):1073-1083.
21. Westerhoff P, Graichen F, Bender A, et al: In vivo measurement
of shoulder joint loads during walking with crutches. Clin
Biomech (Bristol, Avon) 2012;27(7):711-718.
22. Pandis P, Prinold JAI, Bull AMJ: Shoulder muscle forces during
driving: sudden steering can load the rotator cuff beyond its
repair limit. Clin Biomech 2015;30(8):839-846.
23. Lampire N, Roche N, Carne P, Cheze L, Pradon D: Effect of
botulinum toxin injection on length and lengthening velocity of
rectus femoris during gait in hemiparetic patients. Clin Biomech
(Bristol, Avon) 2013;28(2):164-170.
24. Cheung AS, Gray H, Schache AG, et al: Androgen deprivation
causes selective deficits in the biomechanical leg muscle function
 of men during walking: A prospective case-control study. J
Cachexia Sarcopenia Muscle 2017;8(1):102-112.
25. Brandon SCE, Brown MJ, Clouthier AL, Campbell A, Richards
JD, Deluzio KJ: Contributions of muscles and external forces to
medial knee load reduction due to osteoarthritis braces. Knee
2019;26(3):564-577. Knee braces reduced medial tibiofemoral
loads primarily by applying a direct, and substantial, abduction
moment to each subject’s knee. To further enhance brace
effectiveness, future brace designs should seek to enhance the
magnitude of this unloader moment, and possibly exploit
additional kinematic or neuromuscular gait modifications. Level
of evidence: III.
26. Clouthier AL, Hassan EA, Brandon SCE, Campbell A, Rainbow
MJ, Deluzio KJ: Identification of good candidates for valgus
bracing as a treatment for medial knee osteoarthritis. J Orthop Res
2018;36(1):351-356.
27. Capin JJ, Khandha A, Zarzycki R, Manal K, Buchanan TS,
Snyder-Mackler L: Gait mechanics after ACL reconstruction differ
according to medial meniscal treatment. J Bone Joint Surg Am
2018;100(14):1209-1216.
28. Khandha A, Manal K, Capin J, et al: High muscle co-contraction
does not result in high joint forces during gait in anterior cruciate
ligament deficient knees. J Orthop Res 2019;37(1):104-112. The
results of this study indicate that high muscle co-contraction
does not always result in high knee joint loading, which is
thought to be associated with knee osteoarthritis. Long-term
follow-up is required to evaluate how gait alterations progress in
nonosteoarthritic versus osteoarthritic subjects. Level of
evidence: III.
29. Song Z, Nie C, Li S, Dario P, Dai JS: A muscle-specific
rehabilitation training method based on muscle activation and
the optimal load orientation concept. Appl Bionics Biomech
2018;2018:2365983.
30. Stahl CM, Meisinger QC, Andre MP, Kinney TB, Newton IG:
Radiation risk to the fluoroscopy operator and staff. AJR Am J
Roentgenol 2016;207(4):737-744.
31. Pasha K, Khan HR, Sumon AA: Staying safe from radiation
exposure in cath lab: a review. Mymensingh Med J 2018;27(2):437-
439.
32. Arauz P, Klemt C, Limmahakhun S, An S, Kwon Y-M: Stair
climbing and high knee flexion activities in bi-cruciate retaining
total knee arthroplasty: in vivo kinematics and articular contact
analysis. J Arthroplasty 2019;34(3):570-576. The contemporary
bicruciate-retaining total knee arthroplasty design demonstrated
asymmetric femoral rollback, medial translation, as well as lateral
pivoting in about half of the patient cohort, suggesting that in
vivo tibiofemoral kinematic parameters were not fully restored
during strenuous flexion activities in patients who underwent
bicruciate-retaining total knee arthroplasty. Level of evidence: III.
33. Tsai T-Y, Li J-S, Wang S, et al: A novel dual fluoroscopic imaging
method for determination of THA kinematics: in-vitro and in-
vivo study. J Biomech 2013;46(7):1300-1304.
34. Grieco TF, Sharma A, Dessinger GM, Cates HE, Komistek RD:
In vivo kinematic comparison of a bicruciate stabilized total knee
arthroplasty and the normal knee using fluoroscopy. J
Arthroplasty 2018;33(2):565-571.
35. Klemt C, Drago J, Tirumala V, Kwon Y-M: Asymmetrical tibial
polyethylene geometry-cruciate retaining total knee arthroplasty
does not fully restore in-vivo articular contact kinematics during
strenuous activities. Knee Surg Sports Traumatol Arthrosc
2022;30(2):652-660. Although lateral femoral rollback and lateral
pivoting pa erns were observed during strenuous functional
daily activities, asymmetric contact kinematics still persisted in
patients who underwent unilateral cruciate-retaining total knee
arthroplasty. This suggests the specific investigated
contemporary cruciate-retaining total knee arthroplasty design
 evaluated in this study does not fully replicate healthy knee
contact kinematics. Level of evidence: III.
36. Hennessy D, Arauz P, Klemt C, An S, Kwon Y-M: Gender
influences gait asymmetry following bicruciate-retaining total
knee arthroplasty. J Knee Surg 2020;33(6):582-588. Results
demonstrated that there are 3D motion asymmetries of the knee
during gait in both male and female patients who underwent
unilateral bicruciate-retaining total knee arthroplasty, with
anterior-posterior interlimb asymmetries significantly greater in
female than in male participants. This suggests that gender may
influence the in vivo knee kinematics in patients who underwent
bicruciate-retaining total knee arthroplasty. Level of evidence: III.
37. Grieco TF, Sharma A, Komistek RD, Cates HE: Single versus
multiple-radii cruciate-retaining total knee arthroplasty: An in
vivo mobile fluoroscopy study. J Arthroplasty 2016;31(3):694-701.
38. Tsai T-Y, Liow MHL, Li G, et al: Bi-cruciate retaining total knee
arthroplasty does not restore native tibiofemoral articular contact
kinematics during gait. J Orthop Res 2019;37(9):1929-1937.
Bicruciate-retaining total knee arthroplasty (BCR TKA)
demonstrated no significant differences in anterior-posterior
translation and varus rotation, when compared with normal
healthy knees. However, sagi al plane motion and tibiofemoral
articular contact characteristics were not fully restored during
gait in patients who received BCR TKA, suggesting that BCR TKA
does not restore native tibiofemoral articular contact kinematics.
Level of evidence: III.
39. Peng Y, Arauz P, Desai P, Byers A, Klemt C, Kwon YM: In vivo
kinematic analysis of patients with robotic-assisted total hip
arthroplasty during gait at 1-year follow-up. Int J Med Robot
Comput Assist Surg 2019;15(5):1-8. This study aimed to determine
whether robotic arm–assisted total hip arthroplasty (THA) be er
restores gait symmetry than freehand THA. This study used
biplanar dual fluoroscopy to demonstrate improved accuracy in
restoring native hip geometry through robotic arm–assisted THA
 procedures, which however did not fully translate into improved
gait symmetry. Level of evidence: III.
40. Watanabe T, Abbasi AZ, Condi MA, et al: In vivo kinematics of
a robot-assisted uni- and multi-compartmental knee arthroplasty
J Orthop Sci. 2014;19(4):552-557.
41. Petis S, Howard J, Lanting B, Jones I, Birmingham T, Vasarhelyi
E: Comparing the anterior, posterior and lateral approach: gait
analysis in total hip arthroplasty. Can J Surg 2018;61(1):50-57.
42. Atkins PR, Fiorentino NM, Hartle JA, et al: In vivo pelvic and
hip joint kinematics in patients with cam femoroacetabular
impingement syndrome: a dual fluoroscopy study. J Orthop Res
2020;38(4):823-833. The purpose of this study was to use dual
fluoroscopy to quantify in vivo kinematics of patients with cam
impingement relative to asymptomatic, morphologically normal
control participants during various activities. The results show
that even during submaximal range of motion activities, patients
may alter pelvic motion. Level of evidence: IV.
43. Kono K, Inui H, Tomita T, et al: In vivo kinematics and cruciate
ligament forces in bicruciate-retaining total knee arthroplasty. Sci
Rep 2021;11(1):5645. The study shows that preoperatively, anterior
cruciate ligament forces correlated with anteroposterior
translation of the femoral condyles. Postoperatively, posterior
cruciate ligament forces correlated with anteroposterior
translation of the lateral femoral condyle. Bicruciate-retaining
total knee arthroplasty altered knee kinematics during high
flexion activity, which correlated significantly with changes in
cruciate ligament forces. Level of evidence: III.
44. Navacchia A, Kefala V, Shelburne KB: Dependence of muscle
moment arms on in vivo three-dimensional kinematics of the
knee. Ann Biomed Eng 2017;45(3):789-798.
45. Belsi A, Papi E, McGregor AH: Impact of wearable technology
on psychosocial factors of osteoarthritis management: A
qualitative study. BMJ Open 2016;6(2):e010064.
46. Louis AA, Turner T, Gre on M, Baksh A, Cleland JGF: A
systematic review of telemonitoring for the management of heart
failure. Eur J Heart Fail 2003;5(5):583-590.
47. Subih MA, Arifin N, Al-Fakih E: 16 - portable electronic
pressure control device for below-knee prosthetic socket: A
loading static assessment during preliminary, in Hoque ME,
Sharif A, Jawaid M, eds: Green Biocomposites for Biomedical
Engineering. Woodhead Publishing, 2021, pp 353-362.
48. Burnham JP, Lu C, Yaeger LH, Bailey TC, Kollef MH: Using
wearable technology to predict health outcomes: A literature
review. J Am Med Inf Assoc 2018;25(9):1221-1227.
49. Slade Shan JA, Veille e CJH: The application of wearable
technology in surgery: Ensuring the positive impact of the
wearable revolution on surgical patients. Front Surg 2014;1:39.
50. Park S, Chung K, Jayaraman S: Chapter 1.1 - wearables:
Fundamentals, advancements, and a roadmap for the future, in
Sazonov E, Neuman MR, eds: Wearable Sensors. Academic Press,
2014, pp 1-23.
51. Kekade S, Hseieh C-H, Islam MM, et al: The usefulness and
actual use of wearable devices among the elderly population.
Comput Methods Progr Biomed 2018;153:137-159.
52. Jia Y, Wang W, Wen D, Liang L, Gao L, Lei J: Perceived user
preferences and usability evaluation of mainstream wearable
devices for health monitoring. PeerJ 2018;6:e5350.
53. Tahir H, Tahir R, McDonald-Maier K: On the security of
consumer wearable devices in the internet of things. PLoS One
2018;13(4):e0195487.
54. Lee J-M, Kim Y, Welk GJ: Validity of consumer-based physical
activity monitors. Med Sci Sports Exerc 2014;46(9):1840-1848.
C H AP T E R 1 5

Normal and Abnormal Fracture

Healing
Francis Y. Lee MD, PhD, Hon MBA, FAAOS, Hicham Drissi
PhD

Dr. Lee or an immediate family member serves as a paid consultant to or is an employee of L&J
Bio and has received research or institutional support from Musculoskeletal Transplant
Foundation, National Institutes of Health (NIAMS & NICHD), and OREF. Dr. Drissi or an
immediate family member serves as a paid consultant to or is an employee of Merck and has
received research or institutional support from Merck.

ABSTRACT
Normal fracture healing means restoration of bone continuity with
respect to structural, mechanical, and biochemical integrity.
Fracture healing process is a cascade of well-orchestrated cellular
events consisting of acute injury (inflammatory) phase, recruitment
of reparative progenitor cells for callus formation, tissue transition
from callus to mature bone, and remodeling. Each fracture healing
stage is affected by host factors such as aging, diabetes,
endocrinopathies, infection, drugs, smoking, and mechanical
stability during fracture healing. Rigorous modern scientific
research has identified specific causes for impaired fracture
healing.
Keywords: delayed union; fracture healing; nonunion; pathologic
fractures

Introduction
Fracture healing is not always unfailing. Impaired fracture healing
remains a serious clinical dilemma. A significant percentage of
surgically and nonsurgically managed fractures are associated with
delayed union and nonunions. A tremendous effort was geared
toward understanding the mechanisms of successful and failed
fracture healing using preclinical models. The use of rodents
enabled the scientific community to get at the mechanistic aspects
of fracture healing and at such patient factors as metabolic
diseases, aging, infection, genetics, pain, and behavior as well as
functional outcome measures and mechanics. Learning from
normal fracture healing, orthopaedic surgeons are now in a
position to rescue impaired fracture healing by rectifying
dysregulated cellular events secondary to pathologic conditions. It
is important to discuss fundamentals of bone repair using long
bone fractures and in the context of several risk factors of impaired
healing.

Normal Fracture Healing

Bone has a remarkable capacity for regeneration, and in most cases,
bone heals without complications. 1 Fracture healing is a complex
process that involves inputs from many different tissues and cell
populations. The nature of the fracture and clinical management
will determine how a fracture will heal. Normal fracture healing can
progress through (1) primary intramembranous (direct) or (2)
secondary healing, which involves both intramembranous and
endochondral (indirect) processes. Primary bone repair requires
accurate anatomic reduction and rigid fixation, typically with plate
and screws. Secondary fracture healing is a common mechanism
through which most bones heal clinically after stabilization with
casting or intramedullary fixation.

Biology of Primary Bone Healing

Primary healing progresses through intramembranous ossification,
which occurs through contact healing or gap healing. During this
process, new bone is directly deposited at the fracture site and does
not require a cartilaginous intermediate. These mechanisms are
discussed in the next paragraphs.

Contact Healing
When anatomic reduction and rigid fixation are achieved, contact
healing can take place.
The distance between the two ends of the fracture site should be
less than 0.01 mm and the interfragmentary strain less than 2%. 2
Cu ing cones, a tunnel lined by leading osteoclasts and following
osteoblasts, are formed at the end of osteons. At the tip of the
osteons, osteoclasts cross the fracture line and generate
longitudinal cavities at a rate of 50 to 100 µm/d. 1 Osteoblasts then
form bone to fill these cavities and bony union is achieved. The
restoration of the haversian system and the generation of bony
union happen simultaneously, which is a characteristic of contact
primary bone healing process. 1 , 3 Ultimately, the bridging osteons
mature into lamellar bone and bone healing is achieved without the
formation of a periosteal callus.

Gap Healing
For this type of fracture healing to occur, rigid fixation must be
achieved and the gap between the two bony fragments should be
less than 1 mm. 3 The gap between the fractured ends is filled with
lamellar bone that is oriented perpendicular to the long axis and a
secondary osteonal reconstruction is necessary. 1 The lamellar bone
being perpendicular to the long axis is mechanically weak.
Remodeling of this bone through a similar process observed during
contact healing takes place after 3 to 8 weeks. This will fully restore
the anatomic and biomechanical properties of the bone. 2

Biology of Secondary Fracture Healing

Secondary fracture healing progresses through a series of
sequential yet overlapping events (Figure 1). These events or stages
have been broadly grouped into a four-phase or three-phase model
of secondary bone repair. In the four-phase model, an initial
hematoma will form that will be replaced by a soft cartilaginous
callus. This soft callus undergoes ossification to form a hard bony
callus that is remodeled in a final phase to restitute the initial
geometry of the broken bone before fracture. 1 The three-phase
model is defined as having a reactive, repair, and remodeling phase.
The reactive phase occurs immediately following trauma and is
driven by the local disruption of blood vessels and surrounding soft
tissue. This localized tissue injury promotes the formation of a
hematoma that eventually coagulates to serve as the template for
callus formation. Simultaneously, this initiates an acute
inflammatory response that recruits immune cells to the fracture
site. These cells invade the hematoma where they facilitate the
removal of dead cells and debris as well as secrete cytokines and
chemokines. These factors are responsible for recruiting
immunosuppressive mesenchymal progenitor cells from the
periosteum, bone marrow, and systemic circulation that ultimately
leads to resolution of inflammation and initiation of the repair
phase. During the repair phase, mesenchymal stem cells undergo
differentiation into chondrocytes, which lead to the formation of
the soft cartilaginous callus. This avascular callus undergoes
vascularization that facilitates the transition of the soft callus into
hard bony callus. The remodeling phase requires the activities of
osteoclasts to resorb the hard bony callus consisting of woven bone
and osteoblasts to deposit lamellar bone. At the conclusion of this
phase, the original geometry (shape and architecture) of the bone is
restored with no outward signs that a fracture has occurred (ie, no
scarring).
 Figure 1 Schematic representation of fracture repair.On fracture induction
(middiaphyseal break under Frax), hematoma formation and inflammation occur
shortly after (in red; first 3 weeks in human adults) and within days (week 4 in
humans and first week in C57/bl6 mice); a soft cartilaginous callus will initiate
bridging. The soft callus will be invaded with vessels and cartilage is
progressively replaced by bone to form a more mechanically stable bony callus
(up to 12 months following fracture in humans and 2 to 3 weeks in C57/bl6
mice). The last phase of healing involved callus remodeling to recover the initial
geometry of the long bone (remodeling phase around 6 months in humans and 2
to 3 weeks in C57/bl6 mice).

The Reactive Phase

Immediately following trauma there is rupture of blood vessels
inside and around the fracture site, creating a local hematoma. The
hematoma will serve as a scaffold for different inflammatory cells,
cytokines, and chemokines (eg, interleukin [IL]-1, IL-6, CCL2, and
others) to initiate the inflammatory cascade. 4 Various immune cells
including peripheral blood mononuclear cells, monocytes, and
macrophages infiltrate the fracture site. Macrophages are polarized
to the M1 phenotype. Peripheral blood mononuclear cells and
macrophages clear the area of dead cells and debris and the process
shifts to the resolution of inflammation. In this phase,
inflammation and the synthesis of proinflammatory mediators are
both reduced. For the resolution of acute inflammation,
macrophages are polarized to the M2 phenotype and begin to
secrete anti-inflammatory cytokines (eg, IL-4, IL-10, and IL-13).
Mesenchymal stem cells primarily from the bone marrow and
periosteum are also a racted to the fracture site by cytokines such
as tumor necrosis factor alpha 5 and stromal cell–derived factor 1. 6

The Repair Phase

After the formation of the primary hematoma, a fibrin-rich
granulation tissue forms. 1 This tissue serves as the initial template
for the callus that will undergo endochondral bone formation at the
fracture site. Intramembranous ossification also occurs during this
phase; however, this new process primarily occurs proximal and
distal to the fracture site. During endochondral ossification, the
mesenchymal stem cells from the bone marrow and periosteum
differentiate into chondrocytes, which will facilitate the formation
of the soft cartilaginous callus. The degree of micromotion at the
fracture site will strongly influence the size of the soft callus. The
soft callus is avascular initially and undergoes vascular invasion as
the chondrocytes undergo hypertrophy. 7 This permits the
transition of the soft callus into a hard callus as cartilaginous callus
is resorbed and is replaced by bone by osteoblasts or possibly by
transdifferentiating hypertrophic chondrocytes. The fracture
becomes semirigid with the bridging of this central hard callus. 4
Further mineralization of the cartilaginous callus will increase the
mechanical stability of the callus and ultimately the formation of
hard callus. 4

The Remodeling Phase

After the formation of a hard callus, a resorptive phase is initiated,
which will replace the hard callus with a lamellar bone structure
with a central medullary cavity. 4 The remodeling is achieved by the
simultaneous resorptive activity of osteoclasts and deposition of
bone by osteoblasts. 1 The external callus is replaced by lamellar
bone and the internal callus reestablishes the medullary canal in
the case of diaphyseal bone fracture. 1 The fracture is considered
healed when the central medullary canal is reestablished and
cortical bridging has been achieved.
Abnormal Fracture Healing
Although in most cases fracture healing progresses without
complications, certain individuals experience delays or
impairments in the fracture healing process. Suboptimal or
superphysiologic fracture healing environments can result in
nonunions, malunions, or delayed unions. Several factors have
been identified as influencing the rate of fracture healing, including
biomechanical factors related to types of stabilization methods, and
other patient-specific factors such as diabetes, smoking, nutritional
status, aging, inflammation, and infection.

Mechanical Factors
Excessive shear stress, rotational instability, gap between fracture
ends, and distraction force are known to change callus tissue
differentiation and impair fracture healing. 8 , 9 Intermi ent cyclic
axial compression and pneumatic compression are known to
enhance fracture healing in experimental studies. 10 , 11 Controlled
distraction osteogenesis results in sequential bone formation at the
elongating gap with combined intramembranous and
endochondral ossification when distraction is applied at 1 mm/d
divided three to four times. 12

Biologic Factors That Negatively Influence

Fracture Healing
Diabetes
Both type 1 and type 2 diabetes affect bone quality and the fracture
healing process. Type 1 diabetes is associated with decreased bone
mass, osteoporosis, and increased risk for fractures. In type 2
diabetes, bone may have apparently increased bone mass but its
biomechanical property is suboptimal with increased risks for
fractures. 13 Fracture healing is impaired because of inflammation,
decreased stem cell function, advanced glycation end-products,
abnormal insulin signaling, and hyperglycemia 14 (Figure 2). There
are reports suggesting low parathyroid hormone (PTH) levels in
patients with type 2 diabetes. According to a 2020 study,
intermi ent PTH rescued impaired fracture healing in a murine
type 2 diabetes fracture healing model. 15

Figure 2 Coronal reformatted microCT images show impaired femoral

fracture healing in various murine models representing human type 2 diabetes
mellitus.Fracture healing is mostly impaired in Tallyho strain, resembling diverse
impaired fracture healing in human patients with type 2 diabetes mellitus with
heterogeneous causes.

Smoking
Cigare es contain thousands of chemical compounds, including
nicotine. Effects of cigare e smoking was more pronounced in
129X1/SvJ mice compared with C57BL/6J and BALB/cJ mice,
suggesting that effects of cigare e smoking on fracture healing
depend on host factors. 16 Skeletal stem cells and soft callus
formation were reduced by chronic cigare e smoking for 3 to 6
months. Inflammatory cells and cytokines increased at the fracture
site. Vascular endothelial growth factor expression (a proangiogenic
factor) and angiogenesis were reduced after cigare e smoking
exposure in the fracture callus in a rat fracture healing model. 17
Moreover, rats exposed to cigare e smoke inhalation showed
decreased callus formation, delayed cartilaginous to bony callus
transition, decreased stiffness, and maximal load to failure at the
fracture site. 17 , 18

Nutritional Status
Nutrition has long been recognized as a critical patient-specific
factor that influences fracture healing. Certain nutritional
deficiencies can prolong the healing process and even result in
nonunions. Perhaps the most common nutrient deficiency
encountered clinically in patients with fractures is vitamin D
deficiency. For example, it is estimated that 40% to 70% of elderly
patients with fractures are vitamin D deficient. Epidemiologic
studies have also demonstrated that the odds of development of a
nonunion are significantly higher in individuals with vitamin D
deficiency. Supplementation with 1,25-dihydroxyvitamin D3 has
been reported to promote fracture healing by improving
histomorphometric parameters, mechanical strength, and tendency
to increase transformation of woven bone into lamellar bone in an
ovariectomized rat model. 19
Abnormal calcium and phosphate metabolism can change bone
quality and lead to impaired fracture healing. Primary and
secondary hyperparathyroidism increase calcium immobilization
from bone, and inhibition of vitamin D3 production.

Parathyroid Hormone
PTH has multiple effects on bone and fracture healing. Although
systemic subcutaneous injection of PTH1-34 daily, a well-known
bone-anabolic regimen for osteoporosis, promotes overall fracture
healing, 20 hyperparathyroidism simulated by continuous infusion
of PTH delays maturation of endochondral callus, whereas
apparent callus volume seems to be larger than in control patients
in a murine fracture healing study. 21

Genetic Bone Diseases

Neurofibromatosis type 1 (NF1) is associated with the most-
difficult-to-heal congenital psuedarthrosis. A genetic loss of
function of NF1 in osteoprogenitor in a mouse fracture healing
model showed delayed fracture healing, failed osteoblastic
differentiation, increased fibroblastic differentiation even in the
presence of rhBMP2, increased epidermal growth factor receptor
signaling, increased Ras/MEK1/pERK1/2 signaling, and increased β-
catenin signaling. 22 - 24 Pharmacologic inhibitor of β-catenin
signaling, (RS)-5-methyl-1-phenyl-1,3,4,6-tetrahydro-2,5-
benzoxazocine (nefopam, a centrally acting, nonnarcotic analgesic
agent), or trametinib, a MEK1 inhibitor, improved bone repair in
fractures of Nf1−/− fracture calluses.
Osteogenesis imperfecta, a heterogeneous bone collagen defect
syndrome, is known to have type I collagen defects and propensity
for fractures. Although fracture healing provides a new opportunity
to build a new bone crossing the fracture site, the newly formed
fracture callus fails to build a normal bone because of collagen
defects. Delayed union, hyperplastic callus, hypoplastic callus, and
refractures are common.

Infection
Infected nonunion and delayed unions are common consequences
of grade III open fractures and surgical site infections. A 2021
murine fracture-healing study using an open osteotomy model and
methicillin-resistant Staphylococcus aureus showed nonunions,
increased inflammatory cytokines, impaired ossification of
endochondral fracture callus, and involucrum away from the
fracture sites 25 (Figure 3). In the same study, local application of
hydrogel preloaded with rifampin, a cell membrane-penetrating
antibiotic, significantly improved fracture healing. 25 A similar
study showed elevation of cytokines and increased
osteoclastogenesis in infected calluses. Infection is one cause of
26

bone resorption around the implant and may lead to impaired

fracture repair secondary to loss of stable internal fixation at the
fracture site.

Figure 3 Lateral radiographs and microCT images show impaired fracture

healing in methicillin-resistant Staphylococcus aureus (MRSA)-infected murine
tibial femoral fractures at 4 weeks.Purulence, impaired endochondral
ossification, presence of bacteria in sequestrum, and positive MRSA culture
colonies are in MRSA-infected fractures.

Aging
Patients with advanced age show slower and less robust healing
than children and young adults. Advanced age is associated with a
lower number of skeletal repair cells, function of reparative
capacity of skeletal repair cells, increased inflammatory status
(inflamm-aging), and decreased immune function. 27 , 28 When
proinflammatory nuclear factor kappa B activation was reversed
with a pharmacologic inhibitor, regenerative capacity of skeletal
repair cells increased. 28

Drugs
Atypical fractures are defined as iatrogenic insufficiency fractures,
which have been strongly associated with long-term diphosphonate
treatments. Exact mechanisms remain to be determined. In a 2020
study, a rabbit fracture healing model showed decreased bone
turnover at the fracture site, increased bone volume, and relatively
decreased bone anabolism when rabbits were pretreated with
pamidronate. 29 Biopsies of fracture sites from seven human
patients with 10 years of diphosphonate therapy showed fracture
lines with persistent gaps with amorphous materials, suggesting
failures of microcracks. 30 A radiographic study of the lower
extremity alignments in 14 human patients with diphosphonate-
associated femoral fractures showed varus lower limb alignment,
predisposing tensile stress in the femur. 31
The effects of NSAIDs on fracture healing have been assumed to
impair fracture healing. Inhibitory effects of NSAIDs seem to be
dependent on the severity and duration of the inhibition of the
COX-2 pathway. COX-2(−/−) mice showed impaired
osteoblastogenesis and fracture healing compared with COX-1(−/−)
and wild-type mice. 32 Pharmacologic inhibition alone in COX-2(+/−)
rats did not show impaired fracture healing. Randomized clinical
trials of Colles fractures and pediatric long bone fractures did not
demonstrate impaired fracture healing. 33 , 34 Follow-up studies with
different doses and durations may yield different effects.

Skeletal Metastases
With the introduction of molecular cancer therapies increasing
lifespan of patients with advanced cancer, the incidence of
pathologic fractures secondary to osteolytic metastatic breast, lung,
kidney, thyroid cancers is increasing. Prostate cancers result in less
frequent pathologic fractures because of apparently increased bone
formation in an irregular manner. Certain types of metastatic
cancers to bone produce proteins such as cytokines and sclerostin
that cause sustained inflammation and inhibition of osteogenesis,
resulting in impaired fracture healing.
Summary
It is clear that fracture healing is a complex process, which involves
the cooperative involvement of a variety of cellular and molecular
events, the sequence of which is tightly controlled.

Key Study Points

Although fracture healing recapitulates some of the developmental events that occur
during skeletal organogenesis, there are differences between skeletal development
and repair.
Understanding of the basic biology of fracture healing has significantly improved with
the use of preclinical models.
Correlations between controlled fracture experiments in the laboratory and naturally
occurring fractures in orthopaedic trauma are increasingly possible.
It is important to continue mimicking patient factors when studying the basic
fundamentals of fracture healing in the laboratory.

Annotated References
1. Marsell R, Einhorn TA: The biology of fracture healing. Injury
2011;42(6):551-555.
2. Shapiro F: Cortical bone repair. The relationship of the lacunar-
canalicular system and intercellular gap junctions to the repair
process. J Bone Joint Surg Am 1988;70(7):1067-1081.
3. Kaderly RE: Primary bone healing. Semin Vet Med Surg Small
Anim 1991;6(1):21-25.
4. Gerstenfeld LC, Cullinane DM, Barnes GL, Graves DT, Einhorn
TA: Fracture healing as a post-natal developmental process:
Molecular, spatial, and temporal aspects of its regulation. J Cell
Biochem 2003;88(5):873-884.
5. Kon T, Cho TJ, Aizawa T, et al: Expression of osteoprotegerin,
receptor activator of NF-kappaB ligand (osteoprotegerin ligand)
and related proinflammatory cytokines during fracture healing. J
Bone Miner Res 2001;16(6):1004-1014.
 6. Kitaori T, Ito H, Schwarz EM, et al: Stromal cell-derived factor
1/CXCR4 signaling is critical for the recruitment of mesenchymal
stem cells to the fracture site during skeletal repair in a mouse
model. Arthritis Rheum 2009;60(3):813-823.
7. Keramaris NC, Calori GM, Nikolaou VS, Schemitsch EH,
Giannoudis PV: Fracture vascularity and bone healing: A
systematic review of the role of VEGF. Injury 2008;39(suppl
2):S45-S57.
8. Augat P, Burger J, Schorlemmer S, Henke T, Peraus M, Claes L:
Shear movement at the fracture site delays healing in a
diaphyseal fracture model. J Orthop Res 2003;21(6):1011-1017.
9. Aro HT, Chao EY: Bone-healing pa erns affected by loading,
fracture fragment stability, fracture type, and fracture site
compression. Clin Orthop Relat Res 1993;293:8-17.
10. Hente R, Fuchtmeier B, Schlegel U, Ernstberger A, Perren SM:
The influence of cyclic compression and distraction on the
healing of experimental tibial fractures. J Orthop Res
2004;22(4):709-715.
11. Gardner MJ, van der Meulen MC, Demetrakopoulos D, Wright
TM, Myers ER, Bostrom MP: In vivo cyclic axial compression
affects bone healing in the mouse tibia. J Orthop Res
2006;24(8):1679-1686.
12. Ai-Aql ZS, Alagl AS, Graves DT, Gerstenfeld LC, Einhorn TA:
Molecular mechanisms controlling bone formation during
fracture healing and distraction osteogenesis. J Dent Res
2008;87(2):107-118.
13. Henderson S, Ibe I, Cahill S, Chung YH, Lee FY: Bone quality
and fracture-healing in type-1 and type-2 diabetes mellitus. J Bone
Joint Surg Am 2019;101(15):1399-1410. This article described
suboptimal bone quality and fracture healing secondary to
diabetes mellitus. Level of evidence: V.
14. Jiao H, Xiao E, Graves DT: Diabetes and its effect on bone and
fracture healing. Curr Osteoporos Rep 2015;13(5):327-335.
15. Alder KD, White AH, Chung YH, et al: Systemic parathyroid
hormone enhances fracture healing in multiple murine models of
type 2 diabetes mellitus. JBMR Plus 2020;4(5):e10359. Type 2
diabetes slows down endochondral fracture healing depending
on genetic backgrounds in murine femoral fracture healing
models. Intermi ent PTH regimen rescued impaired fracture
healing.
16. Hao Z, Li J, Li B, et al: Smoking alters inflammation and skeletal
stem and progenitor cell activity during fracture healing in
different murine strains. J Bone Miner Res 2021;36(1):186-198.
There have been controversies on the effects of smoking on
fracture healing. Many previous studies have used nicotine
perfusion to simulate human cigare e smoking. The authors
conducted more rigorous experiments using cigare e smoke
inhalation for 3 to 6 months and showed systemic inflammation
and suboptimal healing depending on genetic background. These
findings are consistent with observations on diverse effects of
cigare e smoking on fracture healing in human patients.
Individual susceptibility to chronic smoking in human patients
varies.
17. Chang CJ, Jou IM, Wu TT, Su FC, Tai TW: Cigare e smoke
inhalation impairs angiogenesis in early bone healing processes
and delays fracture union. Bone Joint Res 2020;9(3):99-107.
Cigare e smoke inhalation was associated with decreased
expression of angiogenic markers in the early bone healing phase
and with impaired bone healing.
18. El-Zawawy HB, Gill CS, Wright RW, Sandell LJ: Smoking delays
chondrogenesis in a mouse model of closed tibial fracture
healing. J Orthop Res 2006;24(12):2150-2158.
19. Fu L, Tang T, Miao Y, Hao Y, Dai K: Effect of 1,25-dihydroxy
vitamin D3 on fracture healing and bone remodeling in
ovariectomized rat femora. Bone 2009;44(5):893-898.
20. Yamashita J, McCauley LK: Effects of intermi ent
administration of parathyroid hormone and parathyroid
 hormone-related protein on fracture healing: A narrative review
of animal and human studies. JBMR Plus 2019;3(12):e10250.
Intermi ent PTH therapy promotes fracture healing and revealed
the strong therapeutic potential of PTH in various animal models.
Human subject studies were fewer and not as consistent as the
animal studies yet provide insight into the potential of
intermi ent PTH administration on fracture healing. Level of
evidence: V.
21. Yukata K, Kanchiku T, Egawa H, et al: Continuous infusion of
PTH1-34 delayed fracture healing in mice. Sci Rep 2018;8(1):13175.
22. El-Hoss J, Sullivan K, Cheng T, et al: A murine model of
neurofibromatosis type 1 tibial pseudarthrosis featuring
proliferative fibrous tissue and osteoclast-like cells. J Bone Miner
Res 2012;27(1):68-78.
23. Baht GS, Nadesan P, Silkstone D, Alman BA: Pharmacologically
targeting beta-catenin for NF1 associated deficiencies in fracture
repair. Bone 2017;98:31-36.
24. Tahaei SE, Couasnay G, Ma Y, et al: The reduced osteogenic
potential of Nf1-deficient osteoprogenitors is EGFR-independent.
Bone 2018;106:103-111.
25. Cahill SV, Kwon HK, Back J, et al: Locally delivered adjuvant
biofilm-penetrating antibiotics rescue impaired endochondral
fracture healing caused by MRSA infection. J Orthop Res
2021;39(2):402-414. Infected fracture callus showed delayed
endochondral ossification and sustained elevation of cytokines in
the fracture callus compartment in a murine femoral fracture
healing model.
26. Wagner JM, Jaurich H, Wallner C, et al: Diminished bone
regeneration after debridement of pos raumatic osteomyelitis is
accompanied by altered cytokine levels, elevated B cell activity,
and increased osteoclast activity. J Orthop Res 2017;35(11):2425-
2434.
27. Clark D, Nakamura M, Miclau T, Marcucio R: Effects of aging on
fracture healing. Curr Osteoporos Rep 2017;15(6):601-608.
28. Josephson AM, Bradaschia-Correa V, Lee S, et al: Age-related
inflammation triggers skeletal stem/progenitor cell dysfunction.
Proc Natl Acad Sci USA 2019;116(14):6995-7004. Aging is
associated with inflammation that leads to slow fracture repair.
Inflammation rather than biologic aging is more determinant in
suppressing skeletal stem cell activities during fracture repair.
29. Morse A, McDonald MM, Mikulec K, Schindeler A, Munns CF,
Li le DG: Pretreatment with pamidronate decreases bone
formation but increases callus bone volume in a rat closed
fracture model. Calcif Tissue Int 2020;106(2):172-179. This study
showed that high-dose diphosphonates lead to increase in bone
volume, mineral content, and density while decreasing bone
turnover during fracture repair. However, overall soft callus
remodeling was not affected.
30. Schilcher J, Sandberg O, Isaksson H, Aspenberg P: Histology of
8 atypical femoral fractures: Remodeling but no healing. Acta
Orthop 2014;85(3):280-286.
31. Saita Y, Ishijima M, Mogami A, et al: The fracture sites of
atypical femoral fractures are associated with the weight-bearing
lower limb alignment. Bone 2014;66:105-110.
32. Zhang X, Schwarz EM, Young DA, Puzas JE, Rosier RN, O’Keefe
RJ: Cyclooxygenase-2 regulates mesenchymal cell differentiation
into the osteoblast lineage and is critically involved in bone
repair. J Clin Invest 2002;109(11):1405-1415.
33. Aliuskevicius M, Ostgaard SE, Hauge EM, Vestergaard P,
Rasmussen S: Influence of ibuprofen on bone healing after
Colles’ fracture: A randomized controlled clinical trial. J Orthop
Res 2020;38(3):545-554. This human clinical study showed no
inhibitory effects of ibuprofen on healing of Colles fracture. This
result is different from COX-2−/− fracture healing data in a murine
fracture healing model. Dose and duration of COX-2 inhibition
seems to be a factor. Level of evidence: I.
34. Nuelle JAV, Coe KM, Oliver HA, Cook JL, Hoernschemeyer DG,
Gupta SK: Effect of NSAID use on bone healing in pediatric
fractures: A preliminary, prospective, randomized, blinded study.
J Pediatr Orthop 2020;40(8):e683-e689. Ibuprofen is an effective
medication for fracture pain in children and its use does not
impair clinical or radiographic long bone fracture healing in
skeletally immature patients. Level of evidence: I.
C H AP T E R 1 6

Articular Cartilage Biology,

Osteoarthritis, Biologics, and
Stem Cell Therapy
Karin A. Payne PhD, Lacey Favazzo PhD, Michael Zuscik
PhD

Dr. Payne or an immediate family member serves as a board member, owner, officer, or committee
member of the Orthopaedic Research Society. Dr. Zuscik or an immediate family member serves
as an unpaid consultant to Solarea BIO. Neither Dr. Favazzo nor any immediate family member
has received anything of value from or has stock or stock options held in a commercial company
or institution related directly or indirectly to the subject of this chapter.

ABSTRACT
The current understanding of osteoarthritis is viewed from the
perspective that articular cartilage is lost in disease, the whole joint
degenerative process is associated with cartilage loss, and clinically
accessible treatment strategies have potential to support symptom
mitigation and structural effects. Thus, to form a broad view of
osteoarthritis disease as a clinical challenge, it is important to first
review the basic concepts of articular cartilage biology related to
the cartilage and joint degenerative process. Various factors
including age, injury, genetics, and obesity that cause, perpetuate,
or accelerate disease are critical to understand and establish the
concept that osteoarthritis is a syndrome with multiple etiologies
that will likely require personalized medicine approaches that
target the process uniquely in each etiologic context. The field has
not clinically progressed to support any disease-modifying
therapeutic agents, let alone a personalized medicine approach.
However, there are several clinical interventions with documented
efficacy in reducing symptoms and providing cartilage structural
repair for generalized osteoarthritis, including orthobiologics
involving platelet-rich plasma and stem cells, as well as tissue
engineering approaches that repair cartilage defects and can restore
joint function.
Keywords: articular cartilage; chondrocyte; orthobiologics;
osteoarthritis; stem cell

Introduction
Osteoarthritis is a multifaceted, degenerative disease of the whole
joint that causes loss of articular cartilage, subchondral bone
sclerosis, synovitis, and myriad other symptoms and presentations,
ultimately resulting in joint failure. It causes a substantial decrease
in quality of life and poses an enormous financial burden. 1 With as
much as 10% of the US population experiencing various forms of
osteoarthritis, there is a clear and urgent need to develop treatment
methods that lessen symptoms and improve disease outcomes.
Osteoarthritis can affect any weight-bearing or non–weight-bearing
joint in the body. The origins of disease are complex and include
genetics/epigenetics, sex-related/hormonal differences,
obesity/inflammation, gut microbiome changes, injury,
aging/senescence, and other factors. Orthobiologics include
platelet-rich plasma, hyaluronic acid, and stem cell–based
therapies, as well as tissue engineering approaches. However, lack
of standardization in methods, outcomes, study design, and the
placebo effect make drawing conclusions about the efficacy of a
given therapy difficult. It is important to review the fundamentals
of joint biology, the complex etiologies of osteoarthritis, and
various orthobiologics currently in use.

Articular Cartilage Biology

Articular cartilage is formed during embryogenesis through a
sequential series of steps that include pa erning of cell types and
tissue structure at the sites of developing joints. 2 Chondrocytes
residing in articular cartilage are mainly formed from interzone
cells. Unlike chondrocytes in the epiphyseal plates, which undergo
orchestrated differentiation leading to longitudinal bone growth
and culminating in apoptosis, articular chondrocytes achieve a
nonterminally hypertrophic state that supports their main cellular
function: maintenance of extracellular matrix. Structurally, articular
cartilage is maintained as four distinct cellular zones from the
surface to the underlying bone: superficial, intermediate, radial,
and calcified cartilage (Figure 1). The superficial zone consists of
one to two cell layers of fla ened chondrocytes expressing
proteoglycan 4 (Prg4) (also known as superficial zone protein or
lubricin), Sox9, Col2a1(IIb), Agc1, Tnc, and low levels of cartilage
intermediate layer protein (Cilp). 2 Chondrocytes of the
intermediate zone are round and express many of the same
molecules as the superficial zone except for Prg4, although they
have higher levels of Cilp. Radial and calcified cartilage zone
chondrocytes express markers of chondrocyte differentiation and
hypertrophy, including Col10a1 (1).
 Figure 1 Schematic illustration showing healthy articular cartilage
structure.Tissue zones are demarcated with brackets, and the major matrix
components are enumerated for each. The location of key structural transitions
(articular surface, tide mark, calcified cartilage) are noted on the left of the
image.Created with BioRender.com.

The understanding of the behavior of articular chondrocytes has

its foundations in broad literature studying these cells in vitro and
in vivo. Articular chondrocytes removed from their matrix tend to
dedifferentiate into type 1 collagen-expressing fibroblasts and lose
their ability to express Col2a1 and other matrix components
including proteoglycans. 3 When cultured in suspension or in a
three-dimensional (3D) matrix made of collagen, agar, or alginate,
the cells will more accurately maintain their chondrocytic
phenotype, 3 emphasizing the importance of cell-matrix interactions
in controlling gene expression. The predominant matrix protein in
cartilage is type II collagen, which is composed of three individual
Col2a1 chains forming a triple helix. 2 Like type I collagen, it is
secreted as triple helical proprotein, which is cleaved extracellularly
by proteinases. 2 The other major organic component of the matrix
is proteoglycan, which includes a hyaluronic acid chain tethered to
several proteins that are covalently bound to glycosaminoglycan
side chains. 2 The major proteoglycan is aggrecan, which consists of
a protein core associated with chondroitin sulfate and keratan
sulfate side chains. These negatively charged polysaccharides serve
to a ract positively charged electrolytes to the proteoglycan
superstructure, which serve to create the Donnan osmotic pressure
that provides hydration and structural integrity of articular
cartilage. 4 In addition to type II collagen and aggrecan, articular
chondrocytes produce a series of minor collagens that also
contribute to tissue structure, including type VI, IX, X, and XI
collagens. Type VI collagen is a pericellular matrix protein, whereas
type IX is a collagen molecule with a proteoglycan moiety. Type IX
collagen molecules coat the outer surface of type II collagen fibrils
supporting interactions with matrix proteoglycans, an important
basis for interconnections between the collagen and proteoglycan
matrix.
Because cartilage degeneration leading to its loss is a seminal
feature of the osteoarthritis disease process, study of cartilage
structure and articular chondrocyte function in this context has
been a major focus of the work in the field. In general, chondrocyte
maintenance of the matrix is a homeostatic process that persists
through adulthood unless stress-related injury, inflammation (local
or systemic), senescence, or genetic defects lead to loss of the
signals required to maintain or inhibit inappropriate differentiation
of chondrocytes (Figure 2). When pathways that decelerate or
prevent chondrocyte hypertrophy are disrupted or impaired,
progressive loss of mechanically appropriate articular cartilage
matrix leads to degenerative disease. 3 It is now understood that the
inappropriate articular chondrocyte differentiation process of
chondrocytes leading to cartilage loss needs to be viewed from a
whole joint perspective (Figure 3, A), with subchondral bone,
synovium, ligaments, tendons, and menisci (specifically in the knee
joint) having a role to play in the loss of high-integrity cartilage.
This holistic view of the joint sets the stage for the enumeration of
the underpinnings of osteoarthritis disease initiation and
progression and approaches for therapeutic intervention (Figure 3,
B).

Figure 2 Schematic illustration shows the etiologies of osteoarthritis.The

major etiologic factors and comorbid factors that drive osteoarthritis disease
include genetics, aging, sex, obesity, and injury.Created with BioRender.com.
 Figure 3 Schematic illustration showing that osteoarthritis is a whole-organ
disease.A, Using the knee joint as the example, all tissues within the joint,
including cartilage, bone, synovium, and connective tissue (ligaments and
tendons), play a role and intercommunicate in the initiation and progression of
degeneration. B, Common clinically used orthobiologic interventions for
osteoarthritis. Key interventions include hyaluronic acid injections, blood-derived
products (eg, platelet-rich plasma), and stem cell/tissue engineering approaches
aimed at tissue regeneration.Created with BioRender.com.

Joint Degeneration in Osteoarthritis

Cartilage
Osteoarthritis is the most common form of arthritis that is
characterized by dysfunction of articular chondrocytes,
degeneration of articular cartilage (and meniscus if the focus is the
knee), periarticular bone formation (osteophytes), synovitis, and
enhanced bone density below the articular cartilage surface
(subchondral sclerosis) 3 (Figure 3, A). Although the etiology of
osteoarthritis is not fully understood, it is generally held that
biochemical, metabolic, genetic, and trauma-related factors
participate in the progression of overall joint degeneration.
Although osteoarthritis is a disease of the whole joint, articular
cartilage degeneration is a defining feature. In healthy tissue,
cartilage is composed of a relatively small number of chondrocytes
living in abundant extracellular matrix composed of collagen and
proteoglycans. As described previously, in this environment,
chondrocytes maintain homeostasis of the matrix, which in turn
preserves the structure of cartilage. In osteoarthritis, the cartilage
aspect of the disease involves degradation of this extracellular
matrix. Although synovial cells initially induce a short-term
increase in matrix synthesis (Agc1, Col2a1) and articular
chondrocyte proliferation via catabolic cytokine production, this
a empt at repair occurs only in early stages of the disease. 5 As
osteoarthritis progresses, enhanced production of collagenases,
such as matrix metalloproteinases 1, 8, 9, and 13, and the
aggrecanases ADAMTS4 (human) and ADAMTS5 (mouse) are
induced by tumor necrosis factor alpha, interleukin (IL)-17, IL-18,
IL-1, and prostaglandin E2, 6 , 7 resulting in cartilage degradation
and disease progression.

Bone
Articular and calcified cartilage form just part of the osteochondral
unit; subchondral cortical and trabecular bone are also key
components stratified anatomically by their mechanical, biologic,
and architectural function. 8 Beneath the protective layer of calcified
cartilage that separates articular cartilage from the subchondral
bone is a cortical bone plate that melds with a system of relatively
more metabolically active and porous trabecular bone. 8 To adapt to
the many changing physiologic needs and conditions of the joint,
the subchondral bone undergoes constant remodeling via
osteoclast-associated bone resorption proceeded by osteoblast-
mediated bone formation. 8 Osteocytes are located throughout the
trabecular and cortical bone matrix and serve as mechanosensors. 9
In early osteoarthritis, increased bone remodeling and cortical bone
porosity occur, followed by an increase in cortical plate thickness
and decrease in subchondral bone mass accompanied by
architectural changes. 8 As disease progresses into late-stage
osteoarthritis, osteophyte formation driven by transforming growth
factor beta and bone morphogenetic protein 2, bone cysts,
apoptotic osteocytes, and a disruption of the osteocyte
mechanosensing network are observed. 8

Synovium
A third major component of the joint that contributes to both
osteoarthritis initiation and progression is the synovium. Normal
nonarthritic synovium is a unique connective tissue that is
composed of an outer, subintimal layer and an inner, intimal layer.
10
The healthy subintimal layer can be 5 mm thick and is made of
various connective tissue, including both fibrous and adipose
tissue. Although this layer is comparatively acellular, it features
lymphatic vessels and nerve fibers. The normal intimal layer is one
to four synoviocytes thick and directly abuts the joint cavity. In the
absence of osteoarthritis, most of the synoviocytes are fibroblastic,
with a heterogenous population of monocyte and macrophage
lineage cells as well as varying populations of immune system
players including B and T cells. 6 The synovium serves a crucial
function by acting as a major source of nutrition for the cartilage,
providing joint lubrication, and preserving articular joint mobility.
11
Because synovitis is a clinical and diagnostic feature of
osteoarthritis in more than 50% of patients, 12 understanding its
role in initiating or driving disease is critically important. In the
disease state, the synovium becomes hyperplastic, with the intima
becoming orders of magnitude thicker in cell depth. 10 This
becomes critical as synovium thickness is correlated with
inflammatory cell infiltration, including populations of CD68+
macrophages, T cells, B cells, and mast cells. 13 Immune cell
migration to and inflammation of the synovium is mediated by a
variety of cytokines, including interleukin 1-beta, tumor necrosis
factor alpha, IL-6, IL-15, IL-17, and IL-18. 14 Cytokines produced by
the synovial membrane and released into the synovial fluid can lead
to inappropriate chondrocyte hypertrophy and apoptosis and cyclic
production of proteolytic enzymes, which in turn contribute to
cartilage degradation and enhanced inflammation of the synovium
by matrix degradation products. 14

Ligaments, Meniscus, and Tendons

It is important to consider the effect of ligaments and the meniscus
in the context of osteoarthritis as a whole-organ disease. Unlike
tendons, which connect bone to muscle, ligaments mechanically
connect bones or fibrocartilaginous structures with other bones or
fibrocartilaginous structures, including menisci in the knee. They
are critical to proprioception and rich in mechanosensors, which
may contribute to joint dysfunction if impeded. 15 Recent studies
have estimated that the rate of knee osteoarthritis development in
individuals with a history of knee injury may fall between 286% and
495% greater than in individuals without injury history, 16 and in as
many as one-third of patients who sustain an anterior cruciate
ligament injury, osteoarthritis develops within a decade of injury. 17
The four meniscotibial ligaments in the joint cavity are exposed to
the inflammatory synovial fluid milieu in osteoarthritis. 18 Because
these ligaments mediate fixation of the meniscal horns, they are a
common point of joint instability and osteoarthritis development. 18
Ligament entheses and signaling pathways are critically
understudied and may provide insight into the role of ligaments in
osteoarthritis development.

The Etiologies of Osteoarthritis

In much the same way that osteoarthritis is a whole-organ disease
that involves interplay between various elements of the joint and
whole body, there is no single etiologic mechanism of
osteoarthritis. The osteoarthritis syndrome, which is characterized
by the tissue phenotypes described earlier, is driven by numerous
factors, including aging and cellular senescence; obesity and
systemic inflammation; gut microbiome, genetic, and epigenetic
factors; and sex hormones. Although the end point of the disease
looks similar despite etiology, understanding etiology in a
personalized medicine perspective will be critical in the
development of targeted therapeutic approaches.

Aging and Senescence

The most prominent risk factor for development of osteoarthritis is
age. Although some studies have indicated that osteoarthritis of
the hand peaks between 60 and 64 years of age, there is additional
evidence that osteoarthritis of the hip and knee continue to
increase with age. 19 There are many facets of aging that contribute
to osteoarthritis in aging populations, including age-related chronic
inflammation, mitochondrial dysfunction, dysregulated nutrient
sensing, altered epigenetics, changes in intercellular
communication, and cellular senescence. Although many of these
19

factors contribute to osteoarthritis on their own, natural aging

serves as a perfect storm of increased fat mass, decreased muscle
mass, and increased levels of adipokine and cytokine levels that
contribute to systemic inflammation. 20 , 21 As the population ages,
osteoarthritis increases, and age-related risk factors and biologic
changes accumulate in the context of this senescence-associated
secretory phenotype. 21
Cellular senescence is a general state of cessation of cellular
division, which can be because of any number of factors, but
naturally increases during aging and during osteoarthritis
progression. 21 In the case of osteoarthritis, cellular stresses likely
contribute to senescence and senescence-associated secretory
phenotype. 21 Because the sole source of cells in cartilage is
inherently nonmitotic chondrocytes, they may be particularly
susceptible to senescence signals such as DNA damage 21 that
accumulate with aging. It is important to note that although aging
cartilage and osteoarthritis cartilage share many features, such as
diminished extracellular matrix in the joint, bone alterations, and
loading changes, they differ in terms of nonenzymatic crosslinking,
cartilage loss, synovial inflammation, and others. 21

Sex
Sex differences also play a role in the etiology of osteoarthritis. In
general, osteoarthritis of the knee, hand, and foot is more likely to
develop in women, whereas men have higher rates of shoulder and
cervical spine osteoarthritis, but the overall incidence of
osteoarthritis is similar between the sexes until middle age. 22 - 24
After age 50 years, osteoarthritis is more likely to develop in
women. 24 These sex differences are likely a complex series of
contributing events including social, economic, sex hormone, and
age-related changes. 22 , 25 It is noteworthy that the age at which
osteoarthritis develops in more women than men coincides with
the average age that menopausal transition occurs, 24 and
menopause itself is associated with an increase in osteoarthritis. 23

Obesity and Gut Microbiome

Increased body mass and the concomitant development of type 2
diabetes has long been associated with osteoarthritis, and although
weight and joint loading certainly remain critical components,
there is an increasing interest in the role obesity plays in
osteoarthritis at a systemic level. Globally, knee osteoarthritis
accounts for 85% of the osteoarthritis burden 26 and is also the most
closely associated with obesity-related variables, compared with
osteoarthritis of the hand or hip. 25 However, the fact that obesity
significantly increases osteoarthritis development in non–weight-
bearing joints, such as the hand, 27 indicates the presence of a
systemic change caused by obesity that contributes to
osteoarthritis. Obesity leads to a metabolic state of chronic,
systemic inflammation including increased presence of
peptidoglycans, inflammatory cytokines, lipopolysaccharide, free
fa y acids, pa ern recognition receptors, Toll-like receptors, and
matrix metalloproteinases. 28 The mechanisms by which these
changes may drive osteoarthritis remain active areas of study and
may involve disrupted intestinal barrier, adipokine production,
immune cell changes, and immunometabolic disorders. It has been
repeatedly established that obesity creates a state of chronic, low-
level inflammation, 29 and this inflammation contributes to
osteoarthritis development and progression. 30 , 31
When osteoarthritis is considered as both a whole-organ and a
systemic disease, the role of the gut microbiome must also be
considered. The number of microorganisms in the alimentary tract
is at least equal to the total number of human cells in the body, and
their genomic content is orders of magnitude greater than is
present in humans. 32 This vast network of microorganisms
provides the host with immense amounts of metagenomic content,
which in turn contributes to metabolic products that can influence
host health. The effect of a dysbiotic gut microbiome on
osteoarthritis, particularly in the context of obesity and
consumption of a Western diet, has been established. 30 , 33 In fact,
specific taxa have been implicated in the presence of joint pain in
humans, 34 and molecules produced by microbiota have been
implicated in human disease at a systemic level. 35

Genetics and Epigenetics

Thus, with a singular focus on the chondrocyte, the genetic basis of
disease progression may be related to defects that are specific to
signaling pathways involved with controlling articular chondrocyte
maturation. For example, one early study established that increased
beta-catenin signaling, caused by an inactivating polymorphism of
the Wnt decoy receptor FrzB, is associated with increased incidence
of hip osteoarthritis in women. 36 This study has prompted the
growth of the field’s focus on the genetic basis of osteoarthritis,
with work over the past 15 years identifying other osteoarthritis-
associated single nucleotide polymorphisms (SNPs), with a pool of
more than 50 disease-associated SNPs identified. 37 Included are
various insulin like growth factor signaling modifiers; vascular
endothelial growth factors; IL-6, IL-8, IL-16, and IL-17; insulin
receptor; transforming growth factor beta 1 and associated Smad-
signaling molecules; and COX2. Some of these mutations have been
validated in studies using mouse genetics, and development of
cartilage-targeted therapeutic strategies may hinge directly on the
understanding of these signaling networks in the context of
disease.
Epigenetic changes associated with disease that could lead to
altered gene profiles in chondrocytes or other cells/tissues in the
joint have garnered significant a ention recently. Epigenetic
changes to the DNA occur without altering the DNA sequence, but
instead lead to modifications of nucleotides that lead to altered
expression of genes at loci where DNA structure is changed as a
result of these modifications. This can occur via methylation of
nucleotides and/or histone protein modifications, with layers of
epigenetic control also involving noncoding RNAs. 38 At least 18
genetic loci have been identified that involve methylation-related
structural change that correlates with genotype at osteoarthritis-
associated SNPs. 38 One example is an osteoarthritis risk locus
located on chromosome 6p21.1 marking a domain containing two
genes: SUPT3H and RUNX2. 39 The chromosomal alteration at this
locus leads to increased expression of RUNX2, a transcription factor
involved in skeletal mineralization that is also involved in
chondrocyte hypertrophy in the epiphyseal plate and during the
osteoarthritis process. In general, work studying epigenetic
mediators of osteoarthritis disease therefore represents an
important link between osteoarthritis genetic risk factors and the
initiation and progression of osteoarthritis disease.
The osteoarthritis syndrome, which is driven etiologically by the
various primary and comorbid factors described previously,
remains elusive to effectively treat. Osteoarthritis disease modifiers
must be able to support mitigation of pain and provide structural
effects consistent with deceleration of structural degeneration or
evidence of regeneration, cartilage regeneration particularly. To
date, despite dozens of clinical trials to test various treatments with
potential to support disease modification in humans with
osteoarthritis, no treatments have advanced that support a clinical
effect. 40 Thus, development of mitigative management of
osteoarthritis, even in the context of a single etiology of disease, is a
critical unmet clinical need. Currently, the only interventions
available to the orthopaedic surgeon are palliative (ie, symptom
modifying) with only questionable potential as disease modifiers;
the most relevant clinical interventions that fall into this category
are discussed in the next paragraphs.

Biologic and Stem Cell Therapies Targeting

Osteoarthritis
Although the disease burden of osteoarthritis remains high,
management options remain limited. Patients with chronic pain
and disability have become increasingly interested in biologics and
stem cell therapy as a potential means to alleviate the pain and
regenerate the lost cartilage. These orthobiologics can include
hyaluronic acid, platelet-rich plasma (PRP), or cell-based therapies
(Figure 3, B) and can be administered either on their own or as an
adjunct to surgery. Because there is substantial patient demand for
these biologics, there has been an increase in direct-to-consumer
marketing. 41 The concern over misinformation provided through
these marketing strategies has led to several professional
organizations, including the American Academy of Orthopaedic
Surgeons (AAOS), to establish a consensus framework to
standardize use and reporting of outcomes with orthobiologics. 41 ,
42
This includes clear nomenclature for cellular therapies and
biologics, standardized reporting of clinical outcomes, and the
establishment of registries and clinical trial networks to rigorously
assess these new therapies.

Hyaluronic Acid
The polysaccharide backbone of the proteoglycan superstructure,
hyaluronic acid, is found in articular cartilage and synovial fluid
and plays an important role in lubrication of the knee joint. The
concentration of hyaluronic acid in synovial fluid decreases with
increasing osteoarthritis severity, leading to the notion that intra-
articular injection of hyaluronic acid into the knee joint could
improve osteoarthritis symptoms through its lubricating
properties. Despite its widespread use, the efficacy of hyaluronic
acid remains controversial. 43 A meta-analysis that included 12,667
patients found that hyaluronic acid injections did not lead to a
clinically beneficial improvement, suggesting that its use be
discouraged. 44 However, several studies have reported that
hyaluronic acid injections are effective in reducing functional
impairment and relieving pain early pos reatment. 45 It should be
noted that this benefit can vary depending on the formulation of
hyaluronic acid, particularly its molecular weight. 46 Overall, there is
no evidence demonstrating a reversal or halting of osteoarthritis
progression with hyaluronic acid injections, but it does seem to
provide limited short-term improvement in pain, which led to
hyaluronic acid being conditionally recommended by the
Osteoarthritis Research Society International guidelines for the
nonsurgical management of knee osteoarthritis. 40

Platelet-Rich Plasma
One of the most widely studied orthobiologic treatments for
osteoarthritis is PRP. It is an autologous blood-derived product that
is minimally manipulated to concentrate the platelets. It has been
shown to contain various cytokines, growth factors, and
inflammatory mediators that can help suppress inflammation and
potentially promote matrix synthesis. 47 A variety of commercial
systems and manual processing methods are used to generate
different formulations of PRP, such as leukocyte-poor PRP or
leukocyte-rich PRP. This leads to variations in platelet
concentration, as well as growth factor and cytokine composition,
and it remains unclear what the optimal quantity of each
component should be for it to have a beneficial effect in
osteoarthritis. The composition of PRP also can vary widely
between individuals, and variation can exist even when PRP is
obtained from the same individual at different times or processed
using different systems. 48 In addition, few studies describe the
preparation protocol or report on the composition of the final PRP
product that is injected. 49 This lack of standardization makes
comparisons between studies difficult.
The inherent variability of PRP may explain the conflicting data
surrounding its efficacy. Several studies have shown that PRP can
lead to decreased levels of pain up to 12 months postinjection. 50 - 52
A 2021 meta-analysis of randomized controlled trials concluded
that PRP led to clinically meaningful improvements in function and
pain-related outcomes when compared with placebo for the
management of symptomatic knee osteoarthritis at a minimum of
6-month follow-up. 53 In a 2019 randomized, double-blind, triple-
parallel, placebo-controlled clinical trial comparing PRP, hyaluronic
acid, and normal saline injections in patients with mild to moderate
osteoarthritis, all three groups showed statistically significant
improvements in outcome measures after 1 month, but PRP was the
only group to maintain the improvement for 1 year. 54 However,
several other studies have not shown a beneficial effect. A 2021
randomized, double-blind, placebo-controlled study was performed
on 62 participants with knee osteoarthritis divided into three
groups that received two injections of either PRP, plasma, or saline
with a 2-week interval. Participants were followed for 6, 12, and 24
weeks, with all three groups reporting improvement in overall pain
and functional parameters, and no statistical difference between
the groups. 55 Similarly, an intra-articular injection of saline for hip
osteoarthritis pain performed as well as other injectables, including
PRP. 56 In 2021, the RESTORE randomized clinical trial provided
strong evidence that PRP is not an effective symptom-mitigating or
disease-modifying intervention. One aggregate, the RESTORE trial,
demonstrated that PRP did not significantly improve knee pain,
alter cartilage structure, or slow disease progression. 57 This trial
involved 288 adults age 50 years or older with mild to moderate
knee osteoarthritis. The participants received three intra-articular
injections at weekly intervals of either leukocyte-poor PRP or saline.
Knee pain scores and medial tibial cartilage volume were assessed
at 12-month follow-up with neither assessment being significantly
different between the PRP and saline placebo groups. Although
results from this study may not be generalizable to all PRP
formulations, given the heterogeneity of PRP products that are
used, they do highlight that (1) a placebo effect should not be
overlooked in studies evaluating the efficacy of PRP for
osteoarthritis, and (2) long-term follow-up is needed. 58 Overall,
although outcome data on PRP are quite variable and conflicting,
there is some evidence that it may lead to pain improvement.
Although PRP should not be advertised as promoting cartilage
regeneration, it may warrant further investigation in pain
management, particularly on the best formulation to use, the
amount to inject, and number of injections. Standardization will be
of utmost importance to compare studies and advance the field.

Stem Cell–Based Therapies

Another facet of orthobiologics for the management of
osteoarthritis involves stem cell–based therapies. Stem cells are
defined as a cell that can self-renew by dividing and making a copy
of itself and can also undergo differentiation to become a more
specialized cell. Many tissues such as blood, bone marrow, adipose
tissue, or amniotic tissue contain stem cells. However, it should be
noted that these stem cells make up a small percentage of the cells
within these tissues, often requiring enzymatic digestion,
significant processing, and culture expansion to obtain sufficient
stem cells for therapeutic purposes. Products currently available to
patients in the United States for musculoskeletal conditions involve
adult cells obtained through minimal manipulation, such as bone
marrow aspirate (BMA) and bone marrow aspirate concentrate
(BMAC).
 BMA and BMAC are obtained from the bone marrow and contain
approximately 0.001% to 0.01% mesenchymal stem cells (MSCs), as
well as hematopoietic stem cells, endothelial progenitor cells, and
cytokines that can play a role in immunomodulation, have anti-
inflammatory effects, and could also promote chondrogenesis. 59
Even though MSCs make up a small percentage of the total cells,
these injectables are often advertised as a stem cell therapy, leading
patients to think that they will restore their degenerated cartilage. 41
The use of BMA and BMAC for knee osteoarthritis has been
investigated in several studies; as seen with other biologics, they
have shown some improvement in pain, but there are also mixed
results. A 2020 retrospective case study of 10 patients with severe
knee osteoarthritis injected with BMA demonstrated significant
pain relief up to 64 ± 26 weeks postinjection. 60 However, a 2019
randomized, blinded, placebo-controlled study of 25 patients with
mild to moderate bilateral knee osteoarthritis receiving a BMAC
injection into one knee and saline into the other demonstrated that
both injections resulted in significant pain decrease with BMAC not
showing superiority to saline. 61 Quality of life was increased in
both groups at 12-month follow-up, but quantitative MRI mapping
did not show significant structural cartilage change because of
saline or BMAC injection. A 2021 systematic review of the literature
on BMAC for knee osteoarthritis confirmed that BMAC led to
improvements in pain level 62 ; however, several comparative
studies did not show clinical superiority of BMAC. 63 A randomized
controlled trial performed between 2000 and 2005 in 120 knees of 60
patients recently reported its 15-year follow-up, where they
compared injection of BMA in the subchondral bone to that into
the synovial fluid. 64 Injection of cells, regardless of location, led to
improvement in pain scores, but injection of BMA in the
subchondral bone led to a larger proportion of injected knees that
had delayed arthroplasty.
A 2021 study evaluated the combined approach of subchondral
and intra-articular injections of BMAC for knee osteoarthritis and
also showed that BMAC has emerged as a safe injectable to
significantly improve pain. 65 Because the percentage of MSCs
remains very low, even after concentration, it is thought that any
beneficial effects seen with BMA and BMAC may be a result of the
growth factors and anti-inflammatory cytokines found in these
minimally manipulated products. Although the therapy is viewed
as safe and may offer some improvement in pain management, a
more thorough evaluation of BMA and BMAC injectables should
continue to be pursued to determine its true efficacy long term.
Although BMAC a empts to concentrate MSCs, it never reaches
a high level of stem cells for delivery to the joint. To do so, it is
necessary to expand MSCs through cell culture. MSCs can be found
in several tissues, such as the bone marrow, adipose tissue, muscle,
and amniotic fluid. Because of their ability to undergo
chondrogenic differentiation, MSCs have traditionally held promise
for tissue regeneration. Although this regenerative potential has
been shown in preclinical animal models, it remains to be clearly
seen in human trials. 66 Rather, it is the paracrine effects of MSCs
that have been emphasized in recent years, with these cells offering
immunomodulatory and immunogenic properties. 67 A 2020
randomized, controlled, double-blind clinical trial was performed
on 47 patients with radiographic and symptomatic osteoarthritis.
The patients were randomized into one of three groups: intra-
articular injections of autologous bone marrow–derived culture-
expanded MSCs, MSCs with PRP, or corticosteroids. 68 The intra-
articular injection of MSCs, regardless of the addition of PRP, led to
significant improvements in functional assessments after 12
months, whereas the corticosteroid injections had a shorter
beneficial effect. In another study, allogeneic bone marrow–derived
MSCs were tested in 15 patients with grade II-IV osteoarthritis and
compared with 15 similar patients receiving a hyaluronic acid
injection. 69 Pain was significantly reduced by 6 and 12 months after
MSC injection, whereas the patients injected with hyaluronic acid
showed more limited improvements that did not reach significance.
Both of these studies support that culture-expanded MSCs can be
beneficial in knee osteoarthritis to reduce pain.
 Adipose-derived mesenchymal stromal cells (AD-MSCs) have
also been tested as an orthobiologic for osteoarthritis. They have
become increasingly popular because of the accessibility to adipose
tissue and the higher number of MSCs per volume than that found
in bone marrow. 70 A prospective, randomized, double-blind,
placebo-controlled trial in patients with osteoarthritis compared a
single injection of autologous AD-MSCs with saline. 71 MSC
injection led to a significant improvement in pain and physical
function at 6 months pos reatment, and no serious adverse events
were reported; however, there were no changes in radiologic
outcomes. A 2019 study compared the clinical outcomes of culture-
expanded AD-MSCs with that of stromal vascular fraction, which
does not require any culture expansion. Both intra-articular
injections led to improvements in pain, but culture-expanded AD-
MSCs led to an earlier reduction in symptoms, suggesting that a
treatment modality that contains predominantly stem cells could
be beneficial for osteoarthritis. 72 Although these favorable
outcomes with stem cell–based therapies are promising, studies
often lack standardized expansion protocols, differential stem cell
characterization, and heterogeneity in culture conditions,
particularly whether fetal bovine serum is added or lack of
a ention to batch variation. 66 To uncover the promise of stem cells
for osteoarthritis, it will be important to have phase III studies in
which trials are blinded, randomized, placebo-controlled, and
multicentered to include a larger number of patients. 66

Cartilage Tissue Engineering

Although current orthobiologics have been demonstrated as safe
and somewhat effective in reducing pain associated with
osteoarthritis, there remains a need to develop regenerative
medicine approaches that could restore damaged or degenerated
cartilage to prevent or delay the need for arthroplasty. More than 30
years ago, the first cell-based approach to repair articular cartilage
was introduced when healthy autologous chondrocytes were
isolated from the patient, expanded in culture, and injected back
into the lesion under a periosteal patch. 73 This autologous
chondrocyte implantation (ACI) method has seen several
iterations, including the addition of a matrix to be er hold the cells
in what is now known as matrix-induced or matrix-assisted ACI.
Overall, ACI has shown positive outcomes in long-term results, but
the need for two procedures and a limited source of healthy
autologous chondrocytes has led to investigating alternative
approaches to repair articular cartilage. 74
Cartilage tissue engineering relies on three main components:
scaffolds, cells, and signaling factors. Several biomaterials have
been tested as scaffolds for cartilage tissue engineering, including
natural and synthetic polymers, and extracellular matrix-based
materials. Hydrogels are of particular interest because they can be
injected in a minimally invasive procedure and polymerized in situ
by physical or chemical crosslinking. 75 The incorporation of cells
such as chondrocytes or MSCs from various tissue sources or even
pluripotent stem cells has been shown to improve cartilage
formation in vitro and in small animal models. 76 The chondrogenic
differentiation of these cells within scaffolds has been facilitated by
the incorporation of signaling molecules such as transforming
growth factor beta 3, insulin-like growth factor 1, and fibroblast
growth factor.
One of the major barriers to effective cartilage repair is the
integration of the new repair tissue with the surrounding native
cartilage tissue, often because of the inferior mechanical properties
of the implanted repair tissue/scaffolding. 77 This may be overcome
with 3D bioprinting technology, as it can produce complex
structures that be er mimic the native cartilage composition and
mechanical properties. A 2021 study demonstrated the ability to
resurface an osteochondral lesion in a canine hip osteoarthritis
model using a resorbable tissue-engineered implant containing 3D
woven textile, a 3D printed base, and bone marrow–derived MSCs.
78
After 6 months, the dogs receiving the implant displayed normal
functional outcomes and good integration of the implant with
mechanical properties approaching that of normal cartilage. Given
the inflammatory environment present during osteoarthritis, it is
also important to target the immune system as a therapeutic
approach. Self-regulating synthetic gene circuits where the cells are
engineered to produce IL-1Ra when they sense IL-1 in the
environment are currently being developed and can be
incorporated into implants to potentially provide a tissue
engineering–based therapeutic. 79

Summary
It is now established that osteoarthritis is a disease of the whole
joint, characterized by dysfunction of chondrocytes, degeneration
of articular cartilage, formation of osteophytes, synovitis, and
increased bone density below the articular surface. Although the
etiology is not fully understood, osteoarthritis can be driven by
several factors such as aging and cellular senescence, obesity and
systemic inflammation, gut microbiome, genetic and epigenetic
factors, and sex hormones. Understanding etiology in a
personalized medicine perspective will be critical for the
development of targeted therapeutic approaches. To date, various
treatments with disease-modifying potential in humans with
osteoarthritis have been tested in clinical trials, but none is
currently approved. Despite this, several orthobiologics are being
used clinically to provide pain relief, including hyaluronic acid,
PRP, BMA, BMAC, and culture-expanded MSCs. Despite some
variable and conflicting outcomes and uncertain mechanisms of
action of orthobiologics, current data suggest that in some contexts
they may reduce pain, likely because of their immunomodulatory
properties. Additional high-level, standardized investigations are
needed, with (1) long-term follow-up, (2) a ention to the
molecular/cellular make-up of the formulation, (3) study designs
that circumvent the placebo effect that is common when using
patient-reported outcomes to study osteoarthritis, and (4) a focus
on elucidating the biologic effects that could be associated with
therapeutic potential in a given context. A ention to these aspects
in future clinical trials will be needed to fully understand the
benefit and mechanism of action of orthobiologics. Cartilage tissue
engineering approaches are an exciting avenue to repair and
regenerate cartilage tissue and continue to be a major area of
research focus in the musculoskeletal field. Understanding how to
best modulate inflammation so that repair and regeneration can
occur will help maximize the potential of regenerative therapies
and lead to be er treatment modalities for osteoarthritis.

Key Study Points

Cartilage degeneration is a seminal feature of osteoarthritis disease, making the
study of cartilage structure and articular chondrocyte function in healthy and
diseased cartilage important to better understand disease progression.
Osteoarthritis is a whole-organ disease that involves interplay between various
tissue elements of the joint, including cartilage, bone, synovium, ligaments, tendons,
and other musculoskeletal soft tissues (eg, meniscus in the knee).
Osteoarthritis is driven by numerous factors, including aging and cellular
senescence; obesity and systemic inflammation; gut microbiome, genetic, and
epigenetic factors; and sex hormones, which must be understood to develop
targeted therapeutic approaches in a personalized medicine perspective.
Orthobiologics such as hyaluronic acid, PRP, or cell-based therapies have been
shown to be safe with some evidence that they may alleviate pain; however, the
most up-to-date studies suggest they are no better than placebo at supporting
symptom mitigation or disease modification. Conflicting data are likely because of
the heterogeneity of the products administered and lack of standardization in study
design, as well as a reported placebo effect, a common challenge in osteoarthritis
clinical trials.
Understanding how to best modulate inflammation and balance repair/regeneration,
as well as continuing to study cartilage tissue engineering approaches, will help
maximize the potential of regenerative therapies and lead to better treatment
modalities for osteoarthritis.

Annotated References
1. Zhao X, Shah D, Gandhi K, et al: Clinical, humanistic, and
economic burden of osteoarthritis among noninstitutionalized
adults in the United States. Osteoarthritis Cartilage
2019;27(11):1618-1626. The authors present an observational study
using the 2015 Medical Expenditure Panel Survey to estimate the
burden of osteoarthritis in noninstitutionalized US adults.
 Osteoarthritis affects 10.5% of noninstitutionalized US adults,
resulting in increased annual total healthcare costs and lost
wages among adults with osteoarthritis. Level of evidence: IV.
2. Las Heras F, Gahunia HK, Pri ker KP: Articular cartilage
development: A molecular perspective. Orthop Clin North Am
2012;43(2):155-171, v.
3. Schulze-Tanzil G: Activation and dedifferentiation of
chondrocytes: Implications in cartilage injury and repair. Ann
Anat 2009;191(4):325-338.
4. Zimmerman BK, Nims RJ, Chen A, Hung CT, Ateshian GA:
Direct osmotic pressure measurements in articular cartilage
demonstrate nonideal and concentration-dependent phenomena.
J Biomech Eng 2021;143(4):041007. This study examines cartilage
swelling magnitude in situ in the context of ideal Donnan law
and salt. Findings indicate both nonideal and concentration-
dependent behavior, and importantly that cartilage exhibits
Donnan osmotic and Poisson-Bol mann electrostatic
interactions.
5. Lorenzo P, Bayliss MT, Heinegård D: Altered pa erns and
synthesis of extracellular matrix macromolecules in early
osteoarthritis. Matrix Biol 2004;23(6):381-391.
6. Goldring MB: Osteoarthritis and cartilage: The role of cytokines.
Curr Rheumatol Rep 2000;2(6):459-465.
7. Nagase H, Kashiwagi M: Aggrecanases and cartilage matrix
degradation. Arthritis Res Ther 2003;5(2):94-103.
8. Goldring SR, Goldring MB: Changes in the osteochondral unit
during osteoarthritis: Structure, function and cartilage-bone
crosstalk. Nat Rev Rheumatol 2016;12(11): 632-644.
9. Xiong J, Onal M, Jilka RL, Weinstein RS, Manolagas SC, O’Brien
CA: Matrix-embedded cells control osteoclast formation. Nat Med
2011;17(10):1235-1241.
10. Mathiessen A, Conaghan PG: Synovitis in osteoarthritis:
Current understanding with therapeutic implications. Arthritis
Res Ther 2017;19(1):18.
11. Hügle T, Geurts J: What drives osteoarthritis?-synovial versus
subchondral bone pathology. Rheumatology (Oxford, England)
2017;56(9):1461-1471.
12. Sarmanova A, Hall M, Moses J, Doherty M, Zhang W: Synovial
changes detected by ultrasound in people with knee
osteoarthritis – A meta-analysis of observational studies.
Osteoarthritis Cartilage 2016;24(8):1376-1383.
13. Ghouri A, Conaghan PG: Update on novel pharmacological
therapies for osteoarthritis. Ther Adv Musculoskelet Dis
2019;11:1759720X19864492. This review is an update on
pharmacologic treatments for osteoarthritis. Although disease-
modifying anti-rheumatic drugs have been used in the
management of rheumatoid arthritis, they are not effective in
treating patients with osteoarthritis. Level of evidence: V.
14. Wojdasiewicz P, Poniatowski ŁA, Szukiewicz D: The role of
inflammatory and anti-inflammatory cytokines in the
pathogenesis of osteoarthritis. Mediat Inflamm 2014;2014:561459.
15. Nagelli CV, Cook JL, Kuroki K, Bozynski C, Ma R, Hewe TE:
Does anterior cruciate ligament innervation ma er for joint
function and development of osteoarthritis? J Knee Surg
2017;30(4):364-371.
16. Harkey MS, Luc BA, Golightly YM, et al: Osteoarthritis-related
biomarkers following anterior cruciate ligament injury and
reconstruction: A systematic review. Osteoarthritis Cartilage
2015;23(1):1-12.
17. Luc B, Gribble PA, Pietrosimone BG: Osteoarthritis prevalence
following anterior cruciate ligament reconstruction: A systematic
review and numbers-needed-to-treat analysis. J Athl Train
2014;49(6):806-819.
18. Schulze-Tanzil G: Intraarticular ligament degeneration is
interrelated with cartilage and bone destruction in osteoarthritis.
Cells 2019;8(9):990. There is a fundamental relationship between
ligament and cartilage degeneration with synovitis and
subchondral bone remodeling. Level of evidence: V.
19. Loeser RF, Collins JA, Diekman BO: Ageing and the
pathogenesis of osteoarthritis. Nat Rev Rheumatol 2016;12(7):412-
420.
20. Morrise e-Thomas V, Cohen AA, Fülöp T, et al: Inflamm-aging
does not simply reflect increases in pro-inflammatory markers.
Mech Ageing Dev 2014;139:49-57.
21. Zhang XX, He SH, Liang X, Li W, Li TF, Li DF: Aging, cell
senescence, the pathogenesis and targeted therapies of
osteoarthritis. Front Pharmacol 2021;12:728100. This study
establishes the concept that inhibition of cellular senescence may
aid in the development of disease-modifying osteoarthritis drugs.
Level of evidence: V.
22. Williams VF, Clark LL, Oh GT: Update: Osteoarthritis and
spondylosis, active component, U.S. Armed Forces, 2010-2015.
MSMR 2016;23(9):14-22.
23. Jin X, Wang BH, Wang X, et al: Associations between
endogenous sex hormones and MRI structural changes in
patients with symptomatic knee osteoarthritis. Osteoarthritis
Cartilage 2017;25(7):1100-1106.
24. Hussain SM, Cicu ini FM, Alyousef B, Wang Y: Female
hormonal factors and osteoarthritis of the knee, hip and hand: A
narrative review. Climacteric 2018;21(2):132-139.
25. Vina ER, Kwoh CK: Epidemiology of osteoarthritis: Literature
update. Curr Opin Rheumatol 2018;30(2):160-167.
26. Martín-Millán M, Castañeda S: Estrogens, osteoarthritis and
inflammation. Joint Bone Spine 2013;80(4):368-373.
27. Visser AW, Ioan-Facsinay A, de Mutsert R, et al: Adiposity and
hand osteoarthritis: The Netherlands Epidemiology of Obesity
study. Arthritis Res Ther 2014;16(1):R19.
28. Liu Y, Ding W, Wang HL, et al: Gut microbiota and obesity-
associated osteoarthritis. Osteoarthritis Cartilage 2019;27(9):1257-
1265. This study provides evidence that a gut dysbiosis may
contribute to initiation and propagation of osteoarthritis. Level of
evidence: V.
29. Saltiel AR, Olefsky JM: Inflammatory mechanisms linking
obesity and metabolic disease. J Clin Invest 2017;127(1):1-4.
30. Scho EM, Farnsworth CW, Grier A, et al: Targeting the gut
microbiome to treat the osteoarthritis of obesity. JCI Insight
2018;3(8):e95997.
31. Sun AR, Panchal SK, Friis T, et al: Obesity-associated metabolic
syndrome spontaneously induces infiltration of pro-inflammatory
macrophage in synovium and promotes osteoarthritis. PLoS One
2017;12(8):e0183693.
32. Gill SR, Pop M, Deboy RT, et al: Metagenomic analysis of the
human distal gut microbiome. Science 2006;312(5778):1355-1359.
33. Favazzo LJ, Hendesi H, Villani DA, et al: The gut microbiome-
joint connection: Implications in osteoarthritis. Curr Opin
Rheumatol 2020;32(1):92-101. This review summarizes the basis
for the existence of a fundamental relationship between the gut
and its microbiome and osteoarthritis. Level of evidence: V.
34. Boer CG, Radjabzadeh D, Medina-Gomez C, et al: Intestinal
microbiome composition and its relation to joint pain and
inflammation. Nat Commun 2019;10(1):4881. This investigation
looks at the gut-joint access in the context of the Ro erdam
cohort and pain indices. Some Streptococcus spp. are associated
with increased osteoarthritic pain, which is driven by knee
osteoarthritis inflammation.
35. Blacher E, Bashiardes S, Shapiro H, et al: Potential roles of gut
microbiome and metabolites in modulating ALS in mice. Nature
2019;572(7770):474-480. Preclinical study investigating the effect
of the gut microbiome and metabolites in modulating
amyotrophic lateral sclerosis (ALS) in mice. The study suggests a
potential modulatory involvement of the gut microbiome in ALS
that may help to be er understand aspects of its
pathophysiology, and provides an opportunity to identify
modifiable environmental and microbial therapeutic targets. This
study also includes a small pilot study of patients with ALS
compared to household controls and suggests that there may be
 a role of the gut microbiome in ALS and warrants further
investigation.
36. Loughlin J, Dowling B, Chapman K, et al: Functional variants
within the secreted frizzled-related protein 3 gene are associated
with hip osteoarthritis in females. Proc Natl Acad Sci USA
2004;101(26):9757-9762.
37. Wang T, Liang Y, Li H, et al: Single nucleotide polymorphisms
and osteoarthritis: An overview and a meta-analysis. Medicine
(Baltimore) 2016;95(7):e2811.
38. Rice SJ, Beier F, Young DA, Loughlin J: Interplay between
genetics and epigenetics in osteoarthritis. Nat Rev Rheumatol
2020;16(5):268-281. This review article describes how many
osteoarthritis genetic risk signals, or risk loci, interact with or
correlate with epigenetic mediators. This suggests that the effect
of epigenetic mechanisms on gene expression could help
osteoarthritis genetic risk polymorphisms exert their functional
effect. This interplay can provide mechanistic insight into
osteoarthritis susceptibility and could lead to novel therapeutic
targets.
39. Rice SJ, Aubourg G, Sorial AK, et al: Identification of a novel,
methylation-dependent, RUNX2 regulatory region associated
with osteoarthritis risk. Hum Mol Genet 2018;27(19):3464-3474.
40. Bannuru RR, Osani MC, Vaysbrot EE, et al: OARSI guidelines
for the non-surgical management of knee, hip, and polyarticular
osteoarthritis. Osteoarthritis Cartilage 2019;27(11):1578-1589.
Evidence for 60 osteoarthritis interventions was evaluated with a
systematic database search. A variety of metrics, including
RevMan, GRADE, and GRADEpro were used to evaluate these
interventions; education, exercise, weight management, NSAIDs,
COX-2 inhibitors with proton pump inhibitors were
recommended, whereas intra-articular corticosteroids, hyaluronic
acid injections, and aquatic exercise were sometimes
recommended. Acetaminophen and opioids were not
 recommended to treat patients with osteoarthritis. Level of
evidence: V.
41. Chu CR, Rodeo S, Bhutani N, et al: Optimizing clinical use of
biologics in orthopaedic surgery: Consensus recommendations
from the 2018 AAOS/NIH U-13 conference. J Am Acad Orthop
Surg 2019;27(2):e50-e63. A report from a collaborative symposium
to establish a consensus framework for the use of biologic
therapies for musculoskeletal diseases is presented. The first
recommendation was that minimally manipulated cell products
be referred to as cell therapy and the uncharacterized nature of
these treatments be clearly communicated within the profession,
to patients and the public. Also, minimum reporting standards
for product characterization in clinical studies should be
followed, and high-quality patient registries should be
established. Osteoarthritis was designated as a serious medical
condition and a framework for clinical trial design was proposed.
Level of evidence: V.
42. Frank RM, Sherman SL, Chahla J, et al: Biologic association
annual summit: 2020 report. Orthop J Sports Med
2021;9(6):23259671211015667. A summary of the first annual
meeting of the Biologic Association, comprised of several
scientific societies to lead coordinated efforts on the responsible
use of biologics in the musculoskeletal field, is presented. Level
of evidence: V.
43. Gilat R, Haunschild ED, Knapik DM, Evuarherhe AJr, Parvaresh
KC, Cole BJ: Hyaluronic acid and platelet-rich plasma for the
management of knee osteoarthritis. Int Orthop 2021;45(2):345-354.
The study authors present a literature review on the use of
hyaluronic acid, PRP, and hyaluronic acid-PRP conjugates for the
management of symptomatic knee osteoarthritis. Hyaluronic acid
and PRP provide short-term improvement in pain and function.
Limited data suggest that hyaluronic acid-PRP may provide a
synergistic effect but needs further investigation. Level of
evidence: V.
44. Rutjes AW, Jüni P, da Costa BR, Trelle S, Nüesch E,
Reichenbach S: Viscosupplementation for osteoarthritis of the
knee: A systematic review and meta-analysis. Ann Intern Med
2012;157(3):180-191.
45. Phillips M, Vannabouathong C, Devji T, et al: Differentiating
factors of intra-articular injectables have a meaningful impact on
knee osteoarthritis outcomes: A network meta-analysis. Knee Surg
Sports Traumatol Arthrosc 2020;28(9):3031-3039. A network meta-
analysis design was used to evaluate the efficacy and safety of
intra-articular treatments of primary knee osteoarthritis at 3
months follow-up. Sixty-four articles (9,710 patients) met
inclusion criteria. High-molecular-weight hyaluronic acid was the
only treatment to show improvements in pain and function when
compared with saline. The effect of PRP remained unclear
because of wide confidence intervals. Level of evidence: I.
46. Altman RD, Bedi A, Karlsson J, Sancheti P, Schemitsch E:
Product differences in intra-articular hyaluronic acids for
osteoarthritis of the knee. Am J Sports Med 2016;44(8):2158-2165.
47. Andia I, Maffulli N: Platelet-rich plasma for muscle injury and
tendinopathy. Sports Med Arthrosc Rev 2013;21(4):191-198.
48. Xiong G, Lingampalli N, Koltsov JCB, et al: Men and women
differ in the biochemical composition of platelet-rich plasma. Am
J Sports Med 2018;46(2):409-419.
49. Chahla J, Cinque ME, Piuzzi NS, et al: A call for standardization
in platelet-rich plasma preparation protocols and composition
reporting: A systematic review of the clinical orthopaedic
literature. J Bone Joint Surg Am 2017;99(20):1769-1779.
50. Campbell KA, Sal man BM, Mascarenhas R, et al: Does intra-
articular platelet-rich plasma injection provide clinically superior
outcomes compared with other therapies in the treatment of
knee osteoarthritis? A systematic review of overlapping meta-
analyses. Arthroscopy 2015;31(11):2213-2221.
51. Patel S, Dhillon MS, Aggarwal S, Marwaha N, Jain A: Treatment
with platelet-rich plasma is more effective than placebo for knee
 osteoarthritis: A prospective, double-blind, randomized trial. Am
J Sports Med 2013;41(2):356-364.
52. Chen P, Huang L, Ma Y, et al: Intra-articular platelet-rich plasma
injection for knee osteoarthritis: A summary of meta-analyses. J
Orthop Surg Res 2019;14(1):385. Four meta-analyses were
summarized in this study, with three of them indicating that PRP
led to pain relief and functional improvement compared with a
control group, whereas one analysis showed no difference for
short-term follow-up (≤1 year). No difference in the risk of an
adverse event was observed between groups. Level of evidence: I.
53. Singh H, Knapik DM, Polce EM, et al: Relative efficacy of intra-
articular injections in the treatment of knee osteoarthritis: A
systematic review and network meta-analysis. Am J Sports Med
2021; 3635465211029659 [Epub ahead of print]. A systematic
review and network meta-analysis of randomized controlled trials
was performed to assess and compare the efficacy of hyaluronic
acid, corticosteroids, PRP, and plasma rich in growth factors, with
a minimum 6-month follow-up. All treatments, except
corticosteroids, led to a significant improvement in outcomes
compared with placebo. PRP was found to have the highest
probability of efficacy, followed by plasma rich in growth factors,
hyaluronic acid, corticosteroids, and placebo. Level of evidence: I.
54. Lin KY, Yang CC, Hsu CJ, Yeh ML, Renn JH: Intra-articular
injection of platelet-rich plasma is superior to hyaluronic acid or
saline solution in the treatment of mild to moderate knee
osteoarthritis: A randomized, double-blind, triple-parallel,
placebo-controlled clinical trial. Arthroscopy 2019;35(1):106-117. A
randomized, dose-controlled, placebo-controlled, double blind,
triple-parallel clinical trial was performed involving 87
osteoarthritis knees (53 patients) that received 3 weekly
injections of either leukocyte-poor PRP, hyaluronic acid, or saline.
All treatments led to function and pain improvement after 1
month, with PRP showing a sustained improvement out to 1 year.
Level of evidence: I.
55. Dório M, Pereira RMR, Luz AGB, Deveza LA, de Oliveira RM,
Fuller R: Efficacy of platelet-rich plasma and plasma for
symptomatic treatment of knee osteoarthritis: A double-blinded
placebo-controlled randomized clinical trial. BMC Musculoskelet
Disord 2021;22(1):822. A randomized, double-blind, placebo-
controlled trial was performed involving 62 patients receiving two
injections of either PRP, plasma, or saline with a 2-week interval.
PRP and plasma were not superior to placebo for pain and
function improvement up to 24 weeks postinjection. Level of
evidence: I.
56. Gazendam A, Ekhtiari S, Bozzo A, Phillips M, Bhandari M:
Intra-articular saline injection is as effective as corticosteroids,
platelet-rich plasma and hyaluronic acid for hip osteoarthritis
pain: A systematic review and network meta-analysis of
randomised controlled trials. Br J Sports Med 2021;55(5):256-261. A
network meta-analysis was performed to compare the efficacy of
corticosteroids, hyaluronic acid, and PRP for management of hip
osteoarthritis at up to 6 months of follow-up. Eleven trials
comprising 1,353 patients were included. No intervention
outperformed placebo for pain and functional outcomes. Level of
evidence: I.
57. Bennell KL, Paterson KL, Metcalf BR, et al: Effect of intra-
articular platelet-rich plasma vs placebo injection on pain and
medial tibial cartilage volume in patients with knee
osteoarthritis: The RESTORE randomized clinical trial. J Am Med
Assoc 2021;326(20):2021-2030. A randomized, placebo-controlled,
blind clinical trial included 288 patients with mild to moderate
radiographic knee osteoarthritis who were treated with 3 weekly
intra-articular injections of either leukocyte-poor PRP or saline.
The mean change in knee pain scores at 12 months was not
significantly different between the two groups, nor was the mean
change in medial tibial cartilage volume assessed by MRI. The
findings do not support the use of PRP for the management of
knee osteoarthritis. Level of evidence: I.
58. Previtali D, Merli G, Di Laura Fra ura G, Candrian C, Zaffagnini
S, Filardo G: The long-lasting effects of “Placebo Injections” in
knee osteoarthritis: A meta-analysis. Cartilage 2021;13(1
suppl):185s-196s. A meta-analysis of randomized controlled
trials, including 50 articles on 4,076 patients, was performed to
quantify the placebo effect of intra-articular injections for knee
osteoarthritis in terms of pain, function, and objective outcomes.
Placebo effect was found to be significant up to the 6-month
follow-up for pain and functional improvements. The results of
the placebo effect should not be overlooked in future trials. Level
of evidence: II.
59. Hernigou P, Poignard A, Beaujean F, Rouard H: Percutaneous
autologous bone-marrow grafting for nonunions. Influence of the
number and concentration of progenitor cells. J Bone Joint Surg
Am 2005;87(7):1430-1437.
60. Colberg RE, Jurado Vélez JA, Walsh KP, Fleisig G: Short-term
outcomes after pure bone marrow aspirate injection for severe
knee osteoarthritis: A case series. Regen Med 2020;15(7):1851-1859.
A retrospective case study of 10 patients (13 knees) with severe
knee osteoarthritis who were treated with BMA injection is
discussed. Statistically significant improvements in pain scores
were reported at 2 and 12 weeks postinjection. At 64 ± 26 weeks
postprocedure, average knee pain remained significantly less
than preprocedure. Level of evidence: IV.
61. Shapiro SA, Arthurs JR, Heckman MG, et al: Quantitative T2
MRI mapping and 12-month follow-up in a randomized, blinded,
placebo controlled trial of bone marrow aspiration and
concentration for osteoarthritis of the knees. Cartilage
2019;10(4):432-443. Twenty-five patients with mild-to-moderate
bilateral osteoarthritic knee pain were randomized to receive
BMAC into one knee and saline into the other. Overall knee pain
remained significantly decreased from baseline at 12-month
follow-up for both treatments, with no apparent difference
between BMAC-treated and saline-treated knees. T2 MRI
 cartilage mapping showed no significant difference because of
treatment. Level of evidence: II.
62. Keeling LE, Belk JW, Kraeutler MJ, et al: Bone marrow aspirate
concentrate for the treatment of knee osteoarthritis: A systematic
review. Am J Sports Med 2021;50(8):2315-2323. A systematic review
of the literature to evaluate the efficacy of isolated BMAC
injection in the management of knee osteoarthritis is presented.
Eight studies totaling 299 knees with a mean follow-up of 12.9
months were included. BMAC was shown to be effective in
improving pain and patient-reported outcomes at short-term to
midterm follow-up. However, it did not demonstrate clinical
superiority compared with PRP and microfragmented adipose
tissue, or in relation to placebo. Level of evidence: IV.
63. Dai W, Leng X, Wang J, et al: Intra-articular mesenchymal
stromal cell injections are no different from placebo in the
treatment of knee osteoarthritis: A systematic review and meta-
analysis of randomized controlled trials. Arthroscopy
2021;37(1):340-358. The study authors present a meta-analysis of
13 randomized controlled trials to evaluate the efficacy and safety
of intra-articular injections of MSCs for knee osteoarthritis
treatment. MSC injection was not found to be superior to placebo
in pain relief and functional improvement. Level of evidence: I.
64. Hernigou P, Bouthors C, Bastard C, Flouzat Lachanie e CH,
Rouard H, Dubory A: Subchondral bone or intra-articular
injection of bone marrow concentrate mesenchymal stem cells in
bilateral knee osteoarthritis: What be er postpone knee
arthroplasty at fifteen years? A randomized study. Int Orthop
2021;45(2):391-399. A prospective randomized controlled clinical
trial with 120 knees of 60 patients with painful bilateral knee
osteoarthritis with a similar osteoarthritis grade is presented. A
40-mL bone marrow concentrate was divided into two equal
parts, with one part injected into the subchondral bone of femur
and tibia of one knee (subchondral group) and the other part
injected into the joint for the contralateral knee (intra-articular
group). At 2-year follow-up, clinical and imaging improvement
 was higher in subchondral bone group. At 15 years, implantation
of MSCs in the subchondral bone was more effective to postpone
total knee arthroplasty. Level of evidence: I.
65. Kon E, Boffa A, Andriolo L, et al: Subchondral and intra-
articular injections of bone marrow concentrate are a safe and
effective treatment for knee osteoarthritis: A prospective,
multi-center pilot study. Knee Surg Sports Traumatol Arthrosc
2021;29(12):4232-4240. Thirty patients with symptomatic knee
osteoarthritis were treated with a combination of an intra-
articular and two subchondral BMAC injections (femoral condyle
and tibial plateau). Positive outcomes were reported for
functional and pain scores up to 12 months of follow-up. Level of
evidence: II.
66. Barry F: MSC therapy for osteoarthritis: An unfinished story. J
Orthop Res 2019;37(6):1229-1235. This review article describes the
origins and biology of MSCs, how they are being used, their
mechanism of action, and challenges that have surrounded their
use in the treatment of osteoarthritis. Although progress has
been made, additional clinical studies with a ention to design
and long-term follow-up are needed, as well as the development
of appropriate manufacturing standards and release criteria for
defining MSCs. Level of evidence: V.
67. Phinney DG, Pi enger MF: Concise review: MSC-derived
exosomes for cell-free therapy. Stem Cell 2017;35(4):851-858.
68. Bastos R, Mathias M, Andrade R, et al: Intra-articular injection
of culture-expanded mesenchymal stem cells with or without
addition of platelet-rich plasma is effective in decreasing pain
and symptoms in knee osteoarthritis: A controlled, double-blind
clinical trial. Knee Surg Sports Traumatol Arthrosc 2020;28(6):1989-
1999. Forty-seven patients with radiographic and symptomatic
knee osteoarthritis were randomized into three groups and
received intra-articular injections of autologous bone marrow-
derived culture-expanded MSCs, autologous bone marrow-
derived culture-expanded MSCs + PRP or corticosteroid. Bone
marrow-derived culture-expanded MSCs with or without PRP
 improved function and decreased pain at 12-month follow-up.
Level of evidence: II.
69. Vega A, Martín-Ferrero MA, Del Canto F, et al: Treatment of
knee osteoarthritis with allogeneic bone marrow mesenchymal
stem cells: A randomized controlled trial. Transplantation
2015;99(8):1681-1690.
70. Murphy MB, Moncivais K, Caplan AI: Mesenchymal stem cells:
Environmentally responsive therapeutics for regenerative
medicine. Exp Mol Med 2013;45(11):e54.
71. Lee WS, Kim HJ, Kim KI, Kim GB, Jin W: Intra-articular
injection of autologous adipose tissue-derived mesenchymal
stem cells for the treatment of knee osteoarthritis: A phase IIb,
randomized, placebo-controlled clinical trial. Stem Cells Transl
Med 2019;8(6):504-511. The study authors present a prospective
double-blinded, randomized controlled trial of 24 patients who
were administered an intra-articular injection of either AD-MSCs
or saline and evaluated for 6 months. An intra-articular injection
of autologous AD-MSCs provided functional improvement and
pain relief, without causing adverse events at 6 months’ follow-
up. No significant change in MRI was observed. Larger sample
size and long-term follow-up are warranted. Level of evidence: II.
72. Yokota N, Ha ori M, Ohtsuru T, et al: Comparative clinical
outcomes after intra-articular injection with adipose-derived
cultured stem cells or noncultured stromal vascular fraction for
the treatment of knee osteoarthritis. Am J Sports Med
2019;47(11):2577-2583. In a retrospective study of patients with
knee osteoarthritis, including 42 patients (59 knees) receiving
intra-articular injection with AD-MSCs and 38 patients (69 knees)
receiving a stromal vascular fraction, both groups reported
clinical improvements at 6-month pos reatment. AD-MSCs led
to be er outcomes than stromal vascular fraction at earlier time
points. Level of evidence: III.
73. Bri berg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O,
Peterson L: Treatment of deep cartilage defects in the knee with
 autologous chondrocyte transplantation. N Engl J Med
1994;331(14):889-895.
74. Ebert JR, Fallon M, Wood DJ, Janes GC: Long-term prospective
clinical and magnetic resonance imaging-based evaluation of
matrix-induced autologous chondrocyte implantation. Am J Sports
Med 2021;49(3):579-587. In a prospective study, 87 patients
underwent matrix-induced autologous chondrocyte implantation
and were followed for a minimum of 10 years. Overall, matrix-
induced autologous chondrocyte implantation provided
sustained clinical outcomes and high levels of patient
satisfaction, as well as adequate graft survivorship assessed by
MRI. Level of evidence: IV.
75. Wu J, Chen Q, Deng C, et al: Exquisite design of injectable
hydrogels in cartilage repair. Theranostics 2020;10(21):9843-9864.
The study authors present a comprehensive review of injectable
hydrogels for cartilage repair, including their advantages,
characteristics, and application. Level of evidence: V.
76. Deng Z, Jin J, Wang S, et al: Narrative review of the choices of
stem cell sources and hydrogels for cartilage tissue engineering.
Ann Transl Med 2020;8(23):1598. This article presents a review of
hydrogels and cell sources used for cartilage tissue engineering.
Preclinical and clinical studies that use hydrogels and cells for
cartilage regeneration are summarized.
77. Trengove A, Di Bella C, O’Connor AJ: The challenge of cartilage
integration: Understanding a major barrier to chondral repair.
Tissue Eng Part B Rev 2021;28(1): 114-128. This review article
describes the challenges surrounding the integration of cartilage
repair tissue with native cartilage. The intrinsic limitations of
chondrocytes to remodel injured cartilage and the significant
challenges posed by a compromised biomechanical environment
are discussed. Current scaffold and cell-based therapies and
methods to assess mechanical integrity also are described. Level
of evidence: V.
78. Estes BT, Enomoto M, Moutos FT, et al: Biological resurfacing in
a canine model of hip osteoarthritis. Sci Adv 2021;7(38):eabi5918.
This is a preclinical study to evaluate the ability of an
anatomically shaped tissue-engineered implant to replace the
load-bearing cartilage surface of the femoral head in a canine
model. The implant consisted of autologous bone marrow–
derived MSCs on a 3D woven scaffold and was compared with an
untreated defect for up to 6 months. Dogs receiving the implant
returned to normal preoperative values of pain and function.
Anatomic structure and functional biomechanical properties
were also restored. This did not occur in the untreated dogs.
79. Choi YR, Collins KH, Springer LE, et al: A genome-engineered
bioartificial implant for autoregulated anticytokine drug delivery.
Sci Adv 2021;7(36):eabj1414. This is a laboratory study that uses
CRISPR-Cas9 genome editing of induced pluripotent stem cells
to create a self-regulating synthetic gene circuit that senses levels
of endogenous inflammatory cytokines such as IL-1 to trigger a
proportional therapeutic response by releasing IL-1Ra. Cells were
tested in vitro and in vivo and could provide a potential new
system for long-term drug delivery.
C H AP T E R 1 7

Muscle and Nerve Disorders

Qingnian Goh PhD, Roger Cornwall MD, FAAOS

Dr. Cornwall or an immediate family member serves as a board member, owner, officer, or
committee member of American Society for Surgery of the Hand and Orthopaedic Research
Society. Neither Dr. Goh nor any immediate family member has received anything of value from
or has stock or stock options held in a commercial company or institution related directly or
indirectly to the subject of this chapter.

ABSTRACT
The pathogenesis of various myopathies and nerve disorders
remains unclear, limiting the search for effective therapies or cures.
Recent advances in genetics and pharmacology offer novel insights
for deciphering causative mechanisms and designing curative
therapies. It is important to highlight the molecular findings from
contemporary work pertaining to common muscle, neuromuscular,
and neurodegenerative disorders, with an emphasis on disease
pathogenesis and/or potential treatment strategies.
Keywords: denervation; muscle; muscular dystrophy; myopathy;
nerve

Introduction
Advances in molecular genetics, particularly the development of
genomic tools and transgenic mouse models, have greatly
enhanced the understanding of clinical diseases. These advances
have identified potential mechanisms responsible for myriad
muscle and nerve disorders and allowed for specific targeting of
causative molecules, genes, and pathways. The orthopaedic surgeon
should be aware of the recent molecular and genetic findings
pertaining to the underlying pathogenesis and/or therapeutic
interventions in various well-established muscle diseases and
neuromuscular disorders, including acute flaccid myelitis (AFM),
which is a recently identified neurologic disorder.

Muscle Disorders

Muscular Dystrophies—Duchenne Muscular

Dystrophy
Duchenne muscular dystrophy (DMD) is an X-linked recessive
neuromuscular disorder and among the most frequent lethal
inherited disease in males, affecting 1 in 3,500 to 5,000 live births.
Mutations in the dystrophin gene lead to the loss of functional
dystrophin in muscle cells, which destabilizes the dystrophin
glycoprotein complex and causes myofiber membrane fragility.
DMD is thus characterized by chronic muscle
degeneration/regeneration and weakness that progress to
wheelchair dependence and premature death. Although
pharmacologic corticosteroid therapy mitigates inflammation and
slows disease progression, there are currently no curative treatment
strategies for DMD.
A hallmark of DMD is the ongoing fusion of muscle stem
cells/satellite cells during repeated cycles of muscle regeneration.
In a mouse model of DMD (mdx), satellite cell deletion of the
fusogenic protein myomaker severely exacerbated existing
pathology, whereas myofiber deletion of myomaker improved
muscle function and myofiber integrity, indicating a deleterious
effect of myofiber expression of myomaker on overall membrane
integrity. 1 These findings show that although myocyte fusion is
required for effective muscle regeneration in DMD, chronic
myomaker activation in dystrophic myofibers due to ongoing fusion
contributes to DMD pathology. Single-nucleus transcriptomics in a
separate mouse model of DMD lacking dystrophin exon 51 further
revealed transcriptional heterogeneity of myonuclei (satellite cell
progeny) within normal and dystrophic myofibers and led to the
discovery of a distinct regenerative myonuclear population in DMD
muscle. 2 Hence, the collective findings from these recent studies
extend critical mechanistic insights into DMD pathogenesis and
identify potential molecular targets for novel
pharmacologic/genetic therapies.
Gene editing represents the latest advancement in the search for
the elusive cure for DMD. In particular, CRISPR/Cas9 editing
provides a novel approach to correct DMD by eliminating
mutations at the genomic levels and restoring dystrophin
expression in myofibers. Despite initial preclinical successes in
DMD, the safety of the CRISPR system needs to be thoroughly
validated before clinical translation because of the prevalence of off-
target editing and immunogenicity. In addition, the delivery of
CRISPR components needs to be further optimized to ensure
efficient delivery to skeletal muscles.

Myasthenia Gravis
Myasthenia gravis is an autoimmune disorder of the neuromuscular
junction, caused by antibodies against the acetylcholine receptor
(AChR), and it is characterized by skeletal muscle weakness and
fatigue. As such, serum testing for autoantibodies to AChR has
made diagnosis of myasthenia gravis relatively straightforward in
patients with typical symptoms and also identifies the disease
subtypes. Detection of anti-AChR antibodies can be performed
through several types of assays. 3 The most widely used and most
specific test is the radioimmunoprecipitation assay (RIPA), which
involves the binding of antibodies in the serum to radiolabeled
antigens. To avoid radioactivity, an alternative test involves the
enzyme-linked immunosorbent assay, although it is considered less
specific and sensitive than RIPA. A cell-based assay is another
option, although it is difficult to administer in clinical se ings and
is also less sensitive than RIPA. Besides AChR, autoantibodies to
muscle-specific kinase cause a separate myasthenia gravis disease
subtype. Muscle-specific kinase autoantibodies and myasthenia
gravis account for 6% to 8% of all myasthenia gravis cases and are
detected primarily through RIPA. 3 In addition to AChR and
muscle-specific kinase, recent studies have identified that a small
subset of myasthenia gravis is caused by antibodies against low-
density lipoprotein receptor–related protein 4. 3 Future work will
likely continue to elucidate its utility in the clinical diagnosis of
myasthenia gravis.
The Myasthenia Gravis Foundation of America assembled a Task
Force of international experts in 2013 to develop recommendations
for several treatment topics based on the RAND/UCLA
appropriateness method. This advisory panel subsequently
reconvened in 2019 to update existing recommendations and
develop new guidelines for the use of rituximab, eculizumab, and
methotrexate as supported by the evidence in a 2021 study. 4
Rituximab improved clinical outcomes in 68% of patients with
AChR-Ab+ myasthenia gravis, with 36% achieving remission. 5
Eculizumab was effective in reducing myasthenia gravis
exacerbation rate by 75% 1 year after treatment, with 56% of
patients with refractory generalized AChR-Ab and myasthenia
gravis achieving remission. 6 In addition, functional improvements
with eculizumab were maintained through 3 years. With regard to
methotrexate, although data supporting its use are limited and
unconvincing, the Myasthenia Gravis Foundation of America Task
Force recommends its consideration as a corticosteroid-sparing
agent in patients with generalized myasthenia gravis in whom other
types of steroid-sparing agents are contraindicated. 4

Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is an autosomal recessive motor
neuron disorder caused by homozygous deletions and point
mutations in the survival of motor neuron 1 gene (SMN1). A
splicing defect of the neighboring SMN2 gene leads to exon 7
skipping and produces a truncated and unstable protein (SMNΔ7).
Clinically, SMA is classified into four subtypes (1 through 4)—in
descending order of clinical severity and ascending order of
achieved motor function and age of onset. A large-scale correlation
analysis has verified that clinical severity in SMA is inversely
related to the copy numbers of the SMN2 gene. 7
To leverage this association to SMA severity, current gene
therapies include pharmaceutical agents that alter the splicing of
SMN2. The most promising candidate is nusinersen, an antisense
oligonucleotide that binds to intron 7 of SMN2 and suppresses the
binding of other splice factors. Nusinersen thereby increases exon 7
incorporation into SMN2 messenger RNA transcripts, which
promotes the translation of functional full-length SMN proteins.
The efficacy of nusinersen in the management of SMA was recently
validated in three separate phase III studies (Table 1). In the
ENDEAR study, repeated intrathecal injections of nusinersen
delayed mortality, reduced the need for ventilator support, and
improved motor milestones achievement (Hammersmith Infant
Neurological Examination Section 2) in infants (younger than 7
months) with SMA type 1 compared with a sham control group. 8 In
the CHERISH study of children approximately 4 years old with
SMA type 2 and onset of symptoms after 6 months of age,
nusinersen treatment improved motor functions over baseline
levels compared with sham intervention (+4.0 from baseline versus
−1.9 from baseline, respectively) based on the Hammersmith
Functional Motor Scale Expanded scale. 9 In infants (younger than 6
weeks) with presymptomatic SMA and carrying two or three copies
of the SMN2 gene (NURTURE study), nusinersen facilitated
independent si ing and independent walking in 100% and 88% of
patients, respectively. 10 Nusinersen has since been approved as the
first prescription medicine for SMA by the FDA and the European
Medicines Agency and is commercially available as Spinraza.

Table 1
Summary of the Results of Clinical Trials of Nusinersen
(Spinraza) in Spinal Muscular Atrophy (SMA)

Age
Trial Disease Severity Treatment Results With Nusinersen
Group
NURTURE <6 wk Presymptomatic Improved independent sitting and walking
SMA; 2-3 copies of
SMN2 gene
ENDEAR <7 mo SMA type 1 Delayed mortality, reduced ventilator
support, improved motor milestones versus
sham control
CHERISH 4 yr SMA type 2 onset of Improved motor functions versus sham
symptoms after 6 control
months

In addition to altering SMN2 splicing, an alternative gene

therapy entails replacement of the SMN1 gene. A single
intravenous high dose of onasemnogene abeparvovec (Zolgensma),
which carries an adeno-associated viral vector containing DNA that
codes for wild-type SMN, improved survival, motor function, and
achievement of motor milestones in SMA type 1 infants with 2
SMN2 copies (younger than 8 months) compared with historical
cohorts (START study). 11 Ongoing work in the STRONG study is
currently exploring the effects of onasemnogene abeparvovec
(Zolgensma) in children with SMA type 2 (younger than 6 years).

Congenital Myopathy—Nemaline Myopathy

Nemaline myopathies are one of the most common congenital
myopathies and are caused by mutations in the genes encoding
thin filaments of the sarcomere. As mutations in as many as 12
different genes are associated with nemaline myopathies, they are a
genetically and clinically heterogenous group of myopathies. In this
regard, nemaline myopathy can be autosomal dominant or
recessive and present in different subtypes based on severity. The
most severe subtype gives rise to weakness of respiratory muscles,
hypotonia, and respiratory failure and eventually leads to early
mortality, whereas the milder subtypes are nonprogressive and do
not affect life expectancy. To address this heterogeneity and
optimize clinical care, a 2021 cross-sectional study a empted to
establish the natural history of nemaline myopathy disease. 12 In
this study, the most common clinical presentation was typically
congenital (54%), which is classified as one of the milder subtypes
of nemaline myopathy. Despite this, most of the study cohort
required mechanical support (58%), with more than one-fourth of
this subgroup (26%) requiring wheelchair, ventilator, and feeding
tube assistance. 12 Interestingly, disease progression in patients
with unresolved genotypes was worse than in those with identified
mutations, indicating that unknown gene mutations regulate the
more severe subtypes of nemaline myopathy.
Although there is currently no specific treatment modality for
nemaline myopathy, the fast skeletal muscle troponin activator,
tirasemtiv, offers a promising pharmacologic therapy for
overcoming the associated muscle weakness. Tirasemtiv amplifies
the binding between troponin and calcium to expose myosin-
binding sites in fast skeletal muscle fibers, thereby enhancing thin
filament function and increasing muscle force generation. 13 In a
2021 study, tirasemtiv successfully improved muscle function and
force output in a nemaline myopathy mouse model with an alpha-
actin 1 (ACTA1) mutation, a gene commonly modified in patients
with nemaline myopathy. 14
A rarer but more deadly muscle disorder is sporadic late-onset
nemaline myopathy (SLONM). It is characterized by proximal
muscle weakness and atrophy, as well as the presence of nemaline
rods in skeletal muscle fibers, and is commonly associated with
coexisting conditions such as HIV. A subset of SLONM is
associated with the presence of a monoclonal protein, which
presents a more aggressive and often lethal disease progression
with severe muscle weakness and early respiratory failure. 15 It is
currently unclear whether SLONM + monoclonal protein represents
a malignant or dysimmune condition. Hence, although
chemotherapy has recently been shown to improve survival,
neurologic function, and hematologic remission in patients with
SLONM + monoclonal protein, 15 there is much debate surrounding
whether a chemotherapy-based intervention represents the best
treatment modality for this disease. Additional work is needed to
further establish the safety and efficacy of this approach.

Inflammatory Myopathy
Idiopathic inflammatory myopathies are a heterogeneous group of
rare autoimmune diseases characterized by muscle inflammation
(myositis). Apart from muscles, they can manifest in multiple
organs and systems, including the skin, lungs, and joints, often
leading to diminished quality of life. Although there is currently no
consensus for the classification systems of idiopathic inflammatory
myopathies, the five most recognized subtypes of inflammatory
myopathies are dermatomyositis, inclusion body myositis,
immune-mediated necrotizing myopathy, overlap myositis, and
polymyositis.
A 2019 systematic review of physical rehabilitation programs in
adult patients with idiopathic inflammatory myopathies concluded
physical therapy to be safe during the stable stage of disease and an
effective intervention for improving various physiologic and
functional outcomes. It consequently recommended rehabilitative
programs to include aerobic training three times a week. 16 In 2021,
a 24-week supervised training program combining activities of daily
living with resistance and stability exercises prevented progressive
deterioration and significantly improved muscle strength,
endurance, stability, and global disability in patients with
idiopathic inflammatory myopathies. 17 These findings emphasize
the critical roles of nonpharmacologic interventions, specifically
physical exercise and training, in the care and management of adult
idiopathic inflammatory myopathies.
The recent coronavirus disease (COVID-19) pandemic has
introduced new challenges for patients with idiopathic
inflammatory myopathies. Based on case reports, COVID-19
infections exacerbate the disease phenotypes in dermatomyositis
and immune-mediated necrotizing myopathy, although the precise
pathogenesis of COVID-19–induced myositis is currently unclear.
Proposed mechanisms include direct entry of the SARS-CoV-2 virus
into muscle tissue via angiotensin-converting enzyme 2 receptors, 18
SARS-CoV-2–induced binding and activation of Toll-like receptor 4
to increase angiotensin-converting enzyme 2 expression, which
triggers a hyperinflammatory response in inflamed tissues, 19 or in
the case of patients with dermatomyositis, SARS-CoV-2–induced
overactivation of CD8 T cells, which triggers the adaptive innate
response. 20 Furthermore, because of the need for continual follow-
up care in patients with idiopathic inflammatory myopathies,
limited in-person interaction during the COVID-19 pandemic has
led to detrimental effects in one-third of surveyed respondents,
with medication-related issues reported as the most common
complication. 21 With a slow recovery in global healthcare
underway, remote monitoring and patient self-reported outcomes
should be considered to control disease progression in
inflammatory myopathies. In particular, self-directed physical
assessments such as walking distance test, sit to stand test, and arm
raise test are recommended outcome measures for remote
monitoring. 22

Volumetric Muscle Loss

Volumetric muscle loss is the drastic wasting of skeletal muscle
tissue, which arises from surgical ablation and orthopaedic trauma
involving extremity injuries. Because of the extensive loss of muscle
mass with this pathologic condition, skeletal muscle regenerative
capacity is severely compromised, ultimately resulting in significant
long-term functional deficits and chronic disability. In response to
its increasing prevalence in civilian se ings and disproportionate
frequencies in military sectors, volumetric muscle loss is an
emerging area of study in orthopaedic surgery and regenerative
medicine. Despite ongoing efforts, current treatment strategies are
limited in restoring muscle mass and function because of
incomplete understanding of mechanisms that drive the impaired
regenerative response associated with volumetric muscle loss.
The etiology of volumetric muscle loss differs from progressive
muscle atrophy associated with aging or disease. 23 Furthermore,
endogenous mechanisms of muscle repair/remodeling fail to fully
restore function typically observed in other models of acute trauma.
24
Specifically, the sustained inability of ablated muscle fibers to
regenerate drives functional deficits following volumetric muscle
loss. 25 This lack of endogenous muscle fiber regeneration can be
a ributed to the substantial loss of satellite cells and extracellular
matrix that formerly reside in the space from which original muscle
fibers were ablated. Moreover, volumetric muscle loss alters the
immune response through prolonged upregulation of
proinflammatory genes, leading to fibrosis throughout the
traumatized muscle compartment. 26
As surgical intervention and physical therapy fail to improve
muscle regeneration, reconstructive therapy such as tissue
engineering has emerged as a promising option for building new
muscular tissue. Various biologic extracellular matrix and acellular
biomaterials have been explored, and occasionally in combination
with stem/progenitor cells and assorted growth factors. Recent
network meta-analyses determined that the combination of
acellular biomaterial with stem/progenitor cells resulted in the
greatest improvement in functional deficits. 24 Ongoing work in this
area is needed to guide the clinical translation of regenerative
therapeutics for volumetric muscle loss.

Nerve Disorders

Acute Flaccid Myelitis

AFM is a polio-like inflammation of the spinal cord that primarily
affects children. It is characterized by acute onset of flaccid
weakness of one or more limbs, with lesions targeting the anterior
horn cells of the spinal cord and motor nuclei of the brain stem. 27
An emerging disorder, AFM is now recognized as a global disease
less than a decade since the first reported cases in the United States
in 2012. Its clinical presentation mimics other acute neurologic
illnesses, and diagnosis is further confounded by the lack of a
single specific test for AFM. Despite its infrequency, the acute stage
of AFM can result in severe disability with long-term rehabilitation
needs. Key insights into this relatively new disease will help guide
its assessment, care, and treatment.
AFM in the United States occurs in geographical clusters and
follows a seasonal, biennial pa ern, as evident by increased cases in
2014, 2016, and 2018. The main driver of these outbreaks is
suspected to be enterovirus D68, although the precise mechanism
or mechanisms by which this virus strain leads to AFM are
currently unknown and need to be fully interrogated. Mild
respiratory symptoms and fever are observed in more than 90% of
patients with AFM, consistent with the role of enterovirus D68 in
respiratory disease. These prodromal illnesses usually precede the
onset of neurologic symptoms by 1 to 10 days. 28 The presentation
of flaccid weakness is typically asymmetric and can manifest in
multiple limbs, which subsequently become hyporeflexic or
areflexic. 27 , 28 This acute weakness preferentially targets the upper
limbs and more profoundly affects proximal muscle groups in the
C5 to C6 distribution than distal muscle groups in the C8 to T1
distribution. 28 In addition to weakness in the limbs, weakness in
the neck, trunk, diaphragm, respiratory muscles, bulbar and facial
muscles, and extraocular muscles has also been reported with AFM.
The degree of weakness severity is highly variable among patients
with AFM, ranging from mild/moderate unilateral limb weakness
to complete paralysis of all limbs, and axial and bulbar muscles. 27
Assessment of AFM can be complicated by the overlapping of
clinical features with other causes of acute flaccid paralysis
including Guillain-Barré syndrome, spinal cord stroke,
demyelinating myelitis, poliomyelitis, and other infectious
myelitides. 27 A distinctive clinical feature that distinguishes AFM
from these acute neurologic disorders is the aforementioned
asymmetry in muscle weakness. This asymmetry can present as
severe weakness in upper limbs with normal strength in lower
limbs, or a difference of more than 2 points on the Medical
Research Council scale between right and left limbs. 29
The most useful diagnostic tests for AFM include MRI of the
spinal cord and assessment of cerebrospinal fluid pleocytosis
levels. In patients with AFM, T2 hyperintensity is prominent in the
gray ma er of the spinal cord (Figure 1), whereas white blood cell
count is slightly elevated during the acute phase (<100/µL) and is
restored to normal levels in the subsequent weeks. 27 , 28 In addition
to these tests, reverse transcription polymerase chain reaction,
although not singularly diagnostic, can further distinguish AFM
from other neurologic disorders through viral identification of
enterovirus D68. Similarly, although nerve conduction testing does
not directly diagnose AFM, the detection of electrophysiologic
changes can be valuable in differentiating AFM from other acute
neurologic disorders. Because compound motor action potential is
reduced or lost several days from the onset of neurologic
symptoms, electromyography is particularly useful during the early
stages of AFM investigation. 27
 Figure 1 Magnetic resonance imaging of the spine and brain in an 8-year-old
child with acute flaccid myelitis 24 hours after onset of neurologic symptoms.A,
Sagittal T2 image shows extensive central/anterior spinal cord lesion. B, Axial
T2 image from C5 to C6 shows hyperintensity of the entire gray matter. C, Axial
T2 image from T7 shows greater hyperintensity in the right gray matter,
indicating asymmetry. D, Axial T2 image from T10 shows hyperintensity of the
entire gray matter. E, Axial FLAIR image at the level of the middle cerebellar
peduncle. Arrow indicates the dorsal pons, which shows hyperintensity.
(Reprinted from Murphy OC, Messacar K, Benson L, et al: Acute flaccid myelitis:
Cause, diagnosis, and management. Lancet 2021;397[10271]:334-346, with
permission from Elsevier.)

Recovery from AFM is highly variable and is most rapid in the

first few months after onset of symptoms. Although motor strength
is improved in most patients during this period, fewer than 10% of
patients achieve full recovery from neurologic deficits. 27 In
particular, limb recovery is weakest in muscle groups scored 0 on
the Medical Research Council Scale for Muscle Strength at clinical
nadir. 29 Early recovery in the limb also appears to occur mainly
from a distal to proximal pa ern. 30 Therefore, limb recovery in
patients with AFM can be highly asymmetrical. 29
The efficacy of pharmacologic interventions for AFM is impeded
by a limited understanding of its pathogenesis, which prevents
specific targeting of the underlying molecular mechanism or
mechanisms. Current therapeutic strategies include administration
of intravenous immunoglobulin, such as neutralizing antibodies,
which provides putative antiviral and immunomodulatory effects
against the different enterovirus D68 strains. 31 Other potential
therapies for AFM include small-molecule antiviral agents and
monoclonal antibodies against nonpolio enteroviruses. 32
In addition to pharmacologic therapies, nerve transfers are also
suggested for patients with AFM with poor recovery in an affected
muscle group lasting 3 months or more from disease onset. 27
However, upper extremity nerve transfers are associated with
variable results, with improved outcomes for restoration of elbow
function, but less favorable outcomes for restoration of shoulder
function. 33 , 34 There is currently li le evidence of successful
outcomes involving lower extremity nerve transfers and phrenic
nerve transfers. These discrepancies suggest heterogeneity in AFM
pathogenesis, potentially involving both aberrant muscle and
abnormal nerve/spinal cord. Future work is therefore needed to
further understanding of this disease and establish effective
treatment strategies for improving clinical outcomes.

Acute Nerve Injury

Acute injury to the peripheral nerves can present in 3% to 5% of
trauma patients, with combined motor vehicle and motorcycle
crashes accounting for more than 50% of peripheral nerve injuries.
These traumatic peripheral nerve injuries are broadly classified into
three grades according to ascending order of severity: neurapraxia,
axonotmesis, and neurotmesis. Despite advances in reconstructive
surgery with allografts, autografts, nerve conduits, and nerve
transfers, peripheral nerve injuries are associated with highly
variable functional recoveries and lifelong disabilities. In addition,
although not immediately life threatening, complications arising
from unresolved peripheral nerve injuries have a major effect on
employment and result in considerable health care costs.
 Because of postsynaptic changes at the neuromuscular junction
with peripheral nerve injuries, the ensuing motor end plate (MEP)
degeneration is irreversible and could potentially limit functional
recovery. Although prior rodent studies revealed critical roles for
signaling molecules such as agrin and enzymes such as matrix
metalloproteinase 3 in the maintenance of normal MEP
architecture, morphologic and molecular differences between
rodent and human MEP confound the therapeutic potential of these
molecular targets. 35 In addition, a 2020 clinical investigation of
biopsies from denervated muscles of patients with peripheral nerve
injuries found that MEPs remain innervated and structurally intact
beyond the recommended 6-month window for surgical
intervention. 36 More research is therefore needed to establish the
optimal timing of surgical and other potential therapeutic
interventions targeting the molecular machinery involved in MEP
degradation. Further discussion of the indications, timing, and type
of nerve reconstruction is beyond the scope of this chapter.

Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative
disorder characterized by degeneration of both upper and lower
motor neurons in the brain and spinal cord. As the most prevalent
type of motor neuron disease, ALS rapidly progresses from muscle
weakness and wasting to death from ventilatory failure/respiratory
paralysis. Despite extensive research, the pathogenesis of ALS
development remains elusive, which limits treatment options for
improving clinical outcomes. Although most ALS cases are
idiopathic or sporadic, 10% of patients have familial forms of ALS
and harbor gene mutations. Ongoing research on these genes has
been invaluable in the overall understanding of ALS pathogenesis.
The most extensively characterized genes in familial ALS are
chromosome 9 open reading frame 72 (C9ORF72), fused in sarcoma
(FUS), copper-zinc superoxide dismutase (SOD1), and transactive
response DNA-binding protein 43 (TDP-43) encoded by the
TARDBP gene; variations and mutations in these genes lead to
disease. In particular, the most common genetic cause of familial
ALS is G4C2 hexanucleotide repeat expansions within the C9ORF72
gene, which leads to an accumulation of sense G4C2 and antisense
G2C4 repeat-containing RNA and causes decreased C9ORF72
messenger RNA and protein expression. 37 C9ORF72 mutations
elevate the vulnerability of motor neurons to glutamate-mediated
excitotoxicity through increased expression of GluA1 AMPA
receptor (AMPAR) subunit, thereby increasing calcium-permeable
AMPAR expression and leading to motor neuron degeneration. 38
Repeat expansions also cause haploinsufficiency for C9ORF72
activity in ALS, which disrupts lysosomal biogenesis in motor
neurons, increases the accumulation of glutamate receptors leading
to excitotoxicity, and impairs the clearance of neurotoxic dipeptide
repeat proteins derived from the repeat expansion. 39 This
cooperative pathogenesis between gain and loss of function
mechanisms triggers the ensuing neurodegeneration in patients
with ALS. 39
The first gene associated with familial ALS was SOD1, of which
more than 185 disease-associated variants have been identified.
Most of these variants arise from missense mutations, with the
D90A variant the most common. More recently, misfolded wild-
type SOD1 was observed in the spinal and cortical motor neurons
of patients with ALS with the aforementioned hexanucleotide
repeat expansions in C9ORF72, as well as patients with mutations
of FUS, Kinesin heavy chain isoform 5 A (KIF5A), NIMA-related
kinase 1 (NEK1), ALSIN (ALS2), and vesicle-associated membrane
protein-associated protein B/C (VAPB). 40 Because inclusions
containing misfolded wild-type SOD1 are found in mutations in six
ALS-linked genes other than SOD1, misfolding of wild-type SOD1
may be part of a common downstream event in ALS pathogenesis.
40

TDP-43 is a highly conserved and ubiquitously expressed nuclear

ribonucleoprotein implicated in myriad molecular processes.
Accumulation of mutant TDP-43 and its aggregated forms, along
with loss of wild-type TDP-43, has been suggested as the potential
cause of neurodegeneration. Despite this, its underlying biologic
function in ALS progression is not clear. Recent morphologic and
functional analyses in mouse primary cortical neurons, fibroblasts
derived from patients with ALS, and induced pluripotent stem cell–
derived neurons revealed that aggregated and disease-linked TDP-
43 triggers the sequestration and/or mislocalization of nucleoporins
and transport factors. 41 In addition, pathologic TDP-43 expression
disrupts nuclear membrane and nuclear pore complexes, leading to
reductions in nuclear protein import and mRNA export. 41 Genome-
wide assessment of RNA synthesis and stability in fibroblasts
derived from patients with ALS and induced pluripotent stem cells
further showed that TDP-43 accumulation destabilizes ribosomal
and mitochondrial transcripts, thereby disrupting mitochondrial
and protein synthesis pathways. 42 RNA sequence analysis
identified STMN2, which encodes a protein necessary for motor
neuron axonal outgrowth and repair, as a potential RNA substrate
in TDP-43–linked neurodegeneration. 43 STMN2 expression is
reduced in human motor neurons following TDP-43 knockdown
and mislocalization and is also decreased in ALS-affected spinal
cords of cadavers, indicating a likely clinical relevance for STMN2
depletion from loss of TDP-43 activity. 43
Apart from these commonly researched genes, genome-wide
association studies and next-generation sequencing have further
identified several additional genes associated with ALS in the past
decade, including but not limited to ANXA11, ATXN1, CCNF,
CHCHD10, C21ORF2, DNAJC7, GLT8D1, KIF5A, LGALSL, MATR3,
NEK1, SS18L1, TBK1, and TUBA4A. Future genetic studies to
identify additional genes and establish mechanistic insights into
their causative roles are paramount for deciphering the molecular
mechanisms underlying ALS and identifying potential therapeutic
targets.

Brachial Plexus Birth Injury

Brachial plexus birth injury (BPBI) is the most common birth injury
and the leading cause of pediatric upper limb paralysis. The initial
nerve injury leads to permanent neurologic deficits and formation
of secondary muscle contractures in 20% to 40% of affected
children. These disabling and incurable contractures severely
impede joint range of motion and limit functional use and are the
primary drivers of dysfunction and deformity in the upper limbs.
Rodent models and clinical studies in infants and children all have
corroborated that contractures arise from impaired longitudinal
growth of the denervated muscle, which is characterized by fewer
but overstretched sarcomeres in series, thereby corresponding to a
functionally shorter muscle. 44
Deciphering the causative mechanisms of impaired longitudinal
muscle growth is therefore paramount for designing therapies to
prevent contractures and, ultimately, manage BPBI. The biology of
normal longitudinal muscle growth and molecular regulation of
muscle length are surprisingly not well elucidated. In light of this,
there is strong interest in the role of satellite cell fusion to growing
multinucleated myofibers (myonuclear accretion) because of its
therapeutic potential. Although recent mouse models of hindlimb
immobilization led to depletion of satellite cells in denervated
muscles, 45 , 46 these specimens were obtained and analyzed after
contractures have formed. In contrast, when a mouse model of
BPBI was used to manipulate satellite cell function during the
neonatal time period of contracture development, neither satellite
cell number nor myonuclear accretion was impaired in denervated
muscles. 44 Instead, deficits in longitudinal muscle growth after
BPBI were found to be caused by elevated levels of muscle protein
degradation mediated through increased catalytic activity of the 20
S proteasome. 44 These results posit a critical mechanistic role for
proteasome-mediated dysregulation of muscle proteostasis in
driving the impairment of longitudinal muscle growth that
ultimately causes contractures. As proof of concept, inhibition of
protein degradation with bortezomib, an FDA-approved
proteasome inhibitor, restored longitudinal growth and reduced
contracture formation in denervated muscles after BPBI. 44
However, a bortezomib treatment regimen is required throughout
postnatal development to prevent contractures at skeletal maturity,
even though its efficacy is diminished beyond the neonatal period.
47
Prolonged administration of proteasome inhibitors results in
potential cumulative toxicity as these drugs nonspecifically block
degradation and cause tissue damage to many organs, such as the
brain, and even impede musculoskeletal development. 47 To
overcome these limitations, future studies should explore novel
mechanisms to truncate the necessary period of proteasome
inhibition. Alternatively, future studies could explore safer
strategies to prevent denervation-induced contractures by targeting
skeletal muscle–specific regulators of proteostasis to restore the
balance between protein synthesis and degradation.

Cerebral Palsy
Cerebral palsy is among the most prevalent, severe, and costly
pediatric neurodevelopmental disorders. Recent advances in
genetics have improved overall understanding of the pathogenesis
of cerebral palsy, although caution must be exercised to avoid
misinterpreting data arising from genetic mimics of cerebral palsy,
noncompliance with guidelines defining cerebral palsy, and lack of
appropriate control patients. 48 In addition, although findings from
prior studies found satellite cell depletion in long-standing
contractures from cerebral palsy, 49 - 51 the causative role or roles of
altered satellite cell behavior in cerebral palsy–derived contractures
is still unclear as characterization of contractures in these studies
occurred after they have formed.
Two separate whole-exome sequencing studies in 2020 and 2021
in patients with cerebral palsy revealed an enrichment of loss of
function and missense de novo mutations 48 and determined that
the prevalence of pathogenic variants was approximately 33% in a
pediatric cohort and approximately 10% in an adult cohort. 52 A
corresponding gene overrepresentation analysis further identified
an enrichment of Rho guanosine triphosphatase, extracellular
matrix, focal adhesion, and cytoskeleton pathways associated with
cerebral palsy. 48 Critically, both studies separately identified two
common genes that harbored multiple de novo mutations—
TUBA1A and CTNNB1. 48 , 52 The detection of these gene mutations
in at least two patients and replication of findings across different
cohorts indicate prominent roles for both these genes in the
pathogenesis of cerebral palsy. In addition to cerebral palsy,
heterozygous mutations in TUBA1A have been associated with
autosomal dominant brain malformations, microcephaly,
intellectual disability, and epilepsy, 53 whereas CTNNB1 autosomal
dominant germline mutations have been linked to intellectual
disability, spasticity, microcephaly, and visual defects. 54 Whole-
exome sequencing additionally identified two novel monogenic
variants in two genes, RHOB and FBXO31, that had not been
implicated in cerebral palsy. 48 In particular, FBXO31 encodes a
widely expressed tumor suppressor, and FBXO31 mutation leads to
degradation of cyclin D. 48 The recurrent FBXO31 de novo missense
variant has since been reported in a third individual, 55 thereby
strengthening the link between variant FBXO31 and cerebral palsy.
In addition to genomic variance in neuritogenesis genes, cerebral
palsy is also associated with an altered inflammatory profile. Flow
cytometry revealed higher numbers and frequencies of invariant
natural killer T and Vδ2 T cells in children with cerebral palsy
compared with healthy children, whereas mucosal-associated
invariant T and Vδ1 T cells were depleted from children with
cerebral palsy. 56 Furthermore, the cytokine environment is altered
in children with cerebral palsy, who exhibit elevated baseline serum
levels of erythropoietin and diminished secretion of interleukin
(IL)-1α, IL-1β, IL-2, and IL-6 in response to ex vivo
lipopolysaccharide exposure. 57 Hence, these combined
perturbations in innate and adaptive immune cell number and
function may potentially contribute to the pervasive
neuroinflammation in cerebral palsy.
Compression Neuropathies (Nerve
Compression Syndrome)
Compressive/entrapment neuropathies or nerve compression
syndromes caused by the compression and/or irritation of
peripheral nerves are the most common peripheral neuropathies.
The resulting neuropathic pain and concomitant sensory loss and
muscle weakness can lead to functional disability. The most
common types of compression neuropathies are carpal tunnel
syndrome, followed by ulnar nerve entrapment at the elbow
(cubital tunnel syndrome). Although sciatica is also common, there
is some discrepancy in its reported prevalence because of varying
definitions of this condition.
The etiology of compression neuropathies is currently unclear
although they share several environmental risk factors, including
increased body mass index and preexisting metabolic disorders
such as diabetes or hypothyroidism. In particular, a recent
longitudinal, population-based study in Sweden demonstrated a
strong association between diabetes mellitus with both carpal
tunnel syndrome and cubital tunnel syndrome, 58 further
confirming diabetes as a risk factor for compression neuropathies.
Despite this, hyperglycemia was associated with an increased risk
only for carpal tunnel syndrome and not cubital tunnel syndrome,
which suggests that it differentially affects the median and ulnar
nerves. 58 Likewise, quantitative sensory testing of sensory nerve
function was comparable between patients with cervical
radiculopathy and carpal tunnel syndrome, but patients with
cervical radiculopathy reported more intense and frequent pain
a acks. 59 These collective findings indicate distinct underlying
pathomechanisms in the different types of compression
neuropathies despite their similar anatomic features.
Genetic studies have focused on deciphering the pathogenesis of
compression neuropathies, especially carpal tunnel syndrome. A
2019 genome-wide association study found 16 susceptibility loci for
carpal tunnel syndrome and identified variants within carpal tunnel
syndrome–linked genes implicated in skeletal growth and
extracellular matrix architecture. 60 RNA sequencing additionally
revealed expression of these potentially implicated genes—
ADAMTS10, ADAMTS17, and EFEMP1—in surgically resected
tenosynovium of patients with carpal tunnel syndrome. 60 Genetic
linkage analysis of two large families in China with hereditary
bilateral carpal tunnel syndrome further identified two associated
mutations in the cartilage oligomeric matrix protein gene that
segregate carpal tunnel syndrome into two subtypes—with or
without multiple epiphyseal dysplasia. 61 These genetic studies
highlight the critical roles of extracellular matrix proteins in the
pathogenesis of carpal tunnel syndrome.
In addition to disease onset and progression, genetic factors also
influence postoperative recovery following carpal tunnel release.
Transcriptional profiling of the skin revealed ADCYAP1, which
encodes the pituitary adenylate cyclase–activating peptide, as the
most differentially expressed gene during substantial cutaneous
reinnervation. 62 Given that pituitary adenylate cyclase–activating
peptide signals through G-protein–coupled receptors and functions
as a neurotrophic factor, neuromodulator, and neurotransmi er,
this molecular pathway serves as a promising therapeutic target for
nerve regeneration.

Multiple Sclerosis
Multiple sclerosis is the most prevalent chronic inflammatory,
autoimmune demyelinating, and neurodegenerative disease of the
central nervous system worldwide, affecting approximately 350 in
100,000 persons and representing almost one million cases in the
United States alone. As the leading cause of nontraumatic
neurologic disability in young adults (diagnosis typically made
between 20 and 30 years of age), multiple sclerosis impairs physical
and cognitive functions, activities of daily living, and overall quality
of life. The pathogenesis of multiple sclerosis is multifactorial and
influenced by both genetic and environmental factors including low
serum levels of vitamin D, cigare e smoking, childhood obesity,
ambient ultraviolet radiation, and Epstein-Barr virus infection. 63
Despite this, most of the genetic risk for multiple sclerosis is
unknown.
Two studies by the International MS Genetics Consortium have
advanced the understanding of multiple sclerosis genetic risk
factors, implicating a prominent role for innate immune
dysregulation in multiple sclerosis susceptibility. 64 , 65 In a 2019
study, a total of 233 novel autosomal variants associated with
multiple sclerosis susceptibility were identified, including the first
multiple sclerosis locus identified on a single sex chromosome (X).
64
Given that multiple sclerosis affects women disproportionately at
a ratio of 2.5:1, this identification of the first X chromosome variant
could represent a breakthrough in deciphering the genetic
component of sex dimorphisms in multiple sclerosis. Gene
expression profile analysis revealed an enrichment of multiple
sclerosis–linked genes in both microglia and peripheral innate and
adaptive immune cells, 64 indicating putative roles for these genes
in multicellular immune processes. Through meta-analysis of
rare/low frequency variants within gene coding regions, one study
further identified four novel genes associated with multiple
sclerosis susceptibility that were independent of common-variant
signals and involved in adaptive and innate immunity. 65 Future
investigations into mechanisms by which all these novel variants
affect multiple sclerosis risk are essential for developing effective
preventive strategies.
Current interventions for multiple sclerosis include
pharmacologic disease-modifying therapies (DMTs) to reduce
disease activity and progression. The proposed mechanism for all
DMTs is an a enuation of neuroinflammation and, to a lesser
extent, neurodegenerative processes such as brain atrophy. As of
July 2020, there are nine classes of DMTs (interferons, glatiramer
acetate, teriflunomide, sphingosine-1-phosphate receptor
modulators, fumarates, cladribine, natalizumab, ocrelizumab, and
alemtuzumab) approved for the management of relapsing-
remi ing multiple sclerosis and active secondary progressive
multiple sclerosis, which have greater inflammatory disease
activity. 63 Ocrelizumab is the only DMT approved for treatment of
primary progressive multiple sclerosis, which has less
neuroinflammation and more neurodegeneration. Ocrelizumab
reduces B cell–mediated inflammation leading to
neurodegeneration, thereby serving as a B cell–depleting strategy
for managing disease progression. 63
Beyond DMT, recent preclinical studies have demonstrated the
potential for cell-based therapies such as hematopoietic stem cell
transplantation for prolonging time to disease progression in
relapsing-remi ing multiple sclerosis. 66 Recent clinical trials have
also tested the potential of remyelination therapies with different
compounds to slow or reverse disability. Although a phase I trial of
mesenchymal stem cells improved functional outcomes in
secondary progressive multiple sclerosis and ambulatory patients
with minimal adverse effect, 67 phase II trials of biotin in primary
and secondary progressive multiple sclerosis and opicinumab in
relapse-remi ing multiple sclerosis and secondary progressive
multiple sclerosis with relapses were ineffective in improving
disability and instead were associated with adverse reactions. 68 , 69
Additional work is required to validate the safety and efficacy of
alternate therapies for improving multiple sclerosis disease and
disability.

Summary
Scientific advances in genetics and pharmacology will continue to
drive the understanding of muscle and nerve disorders and guide
the translation of effective therapies. Although recent findings
across the different diseases and disorders have been promising,
caution must be exercised to avoid overinterpretation of their
clinical relevance. Future work is required to rigorously validate
these preliminary findings in clinical se ings and optimize
corresponding treatment strategies.
Key Study Points
Advances in the understanding of the molecular genetics of spinal muscular atrophy
have led to the FDA approval of the gene therapy agent, nusinersen (Spinraza).
AFM is a recently identified, currently incurable, paralytic disorder with unclear
postinfectious etiology associated with enterovirus D68.
Investigations into the molecular mechanisms in many neuromuscular disorders are
identifying potential pharmacologic targets for conditions currently only treatable with
rehabilitation and surgery.

Annotated References
1. Petrany MJ, Song T, Sadayappan S, Millay DP: Myocyte-derived
myomaker expression is required for regenerative fusion but
exacerbates membrane instability in dystrophic myofibers. JCI
Insight 2020;5(9):e136095. In a dystrophin-deficient mouse model
(mdx) of DMD, targeted deletion of myomaker (a fusogenic
protein essential for muscle stem cell fusion and muscle
formation) in dystrophic myofibers improved muscle function
and reduced muscle damage. These findings thus indicate that
chronic myomaker expression in dystropic myofibers may further
compromise membrane stability and muscle integrity in DMD.
2. Chemello F, Wang Z, Li H, et al: Degenerative and regenerative
pathways underlying Duchenne muscular dystrophy revealed by
single-nucleus RNA sequencing. Proc Natl Acad Sci USA
2020;117(47):29691-29701. In a mouse model of DMD lacking
dystrophin exon 51 (a common site of mutation in humans),
single-nucleus RNA sequencing identified distinct populations of
myonuclei (muscle stem cell progeny) between myofibers of wild-
type versus dystrophic mice, thereby providing novel insights on
transcriptional pathways underlying DMD.
3. Lazaridis K, Tzartos SJ: Autoantibody specificities in myasthenia
gravis; implications for improved diagnostics and therapeutics.
Front Immunol 2020;11:212. Advances in the detection of
autoantibodies against the AChR, muscle-specific kinase, and
 low-density lipoprotein receptor–related protein 4 have led to
improvements in the diagnosis of myasthenia gravis. Level of
evidence: V.
4. Narayanaswami P, Sanders DB, Wolfe G, et al: International
consensus guidance for management of myasthenia gravis: 2020
update. Neurology 2021;96(3):114-122. Updated consensus
guidance and recommendations for managing myasthenia gravis
by a task force appointed by the Myasthenia Gravis Foundation of
America are presented. Level of evidence: V.
5. Di Stefano V, Lupica A, Rispoli MG, Di Muzio A, Brighina F,
Rodolico C: Rituximab in AChR subtype of myasthenia gravis:
Systematic review. J Neurol Neurosurg Psychiatry 2020;91(4):392-
395. This systematic review of studies investigating rituximab (a
monoclonal antibody directed against CD20 antigen on B cells)
treatment in myasthenia gravis found improvements and
prolonged time to relapse in many patients with AChR-Ab+
myasthenia gravis. Level of evidence: II.
6. Muppidi S, Utsugisawa K, Benatar M, et al: Long-term safety and
efficacy of eculizumab in generalized myasthenia gravis. Muscle
Nerve 2019;60(1):14-24. In the ongoing REGAIN study, interim
analysis of eculizumab (a monoclonal antibody that binds with
high affinity to complement protein C5) supports its long-term
clinical effectiveness and safety in patients with refractory
generalized AChR-Ab+ myasthenia gravis. Level of evidence: II.
7. Calucho M, Bernal S, Alias L, et al: Correlation between SMA
type and SMN2 copy number revisited: An analysis of 625
unrelated Spanish patients and a compilation of 2834 reported
cases. Neuromuscul Disord 2018;28(3): 208-215.
8. Finkel RS, Mercuri E, Darras BT, et al: Nusinersen versus sham
control in infantile-onset spinal muscular atrophy. N Engl J Med
2017;377(18):1723-1732.
9. Mercuri E, Darras BT, Chiriboga CA, et al: Nusinersen versus
sham control in later-onset spinal muscular atrophy. N Engl J
Med 2018;378(7):625-635.
10. De Vivo DC, Bertini E, Swoboda KJ, et al: Nusinersen initiated
in infants during the presymptomatic stage of spinal muscular
atrophy: Interim efficacy and safety results from the phase 2
NURTURE study. Neuromuscul Disord 2019;29(11):842-856. In the
ongoing NURTURE study, interim analysis reported that
treatment with nusinersen during the presymptomatic stage in
infants genetically diagnosed with spinal muscular atrophy
dramatically improved independent si ing and walking, thereby
establishing the importance of early and proactive treatment.
Level of evidence: II.
11. Mendell JR, Al-Zaidy S, Shell R, et al: Single-dose gene-
replacement therapy for spinal muscular atrophy. N Engl J Med
2017;377(18):1713-1722.
12. Amburgey K, Acker M, Saeed S, et al: A cross-sectional study of
nemaline myopathy. Neurology 2021;96(10):e1425-e1436. This
cross-sectional study evaluated disease features and quantitative
measures in a cohort of 57 patients with nemaline myopathy and
was complemented by longitudinal assessment in a subset of
cases. Findings here established a comprehensive natural history
of nemaline myopathy. Level of evidence: II.
13. Russell AJ, Hartman JJ, Hinken AC, et al: Activation of fast
skeletal muscle troponin as a potential therapeutic approach for
treating neuromuscular diseases. Nat Med 2012;18(3):452-455.
14. de Winter JM, Gineste C, Minardi E, et al: Acute and chronic
tirasemtiv treatment improves in vivo and in vitro muscle
performance in actin-based nemaline myopathy mice. Hum Mol
Genet 2021;30(14):1305-1320. In a nemaline myopathy mouse
model with a mutation in alpha-actin 1 (Acta1 H40Y ), acute and
chronic treatment with tirasemtiv (a fast skeletal troponin
activator that targets the thin filament) increased force
generation in various hindlimb muscles and improved
diaphragm contractility. These findings suggest a therapeutic
role for fast skeletal troponin activators in alleviating muscle
weakness in nemaline myopathy.
15. Kotchetkov R, Susman D, Bhutani D, Broch K, Dispenzieri A,
Buadi FK: Chemotherapy-based approach is the preferred
treatment for sporadic late-onset nemaline myopathy with a
monoclonal protein. Int J Cancer 2021;148(11):2807-2814. A
comparison of outcomes between chemotherapy-based and
nonchemotherapy-based modalities in a cohort of 53 patients
with SLONM with a monoclonal protein found higher survival
and be er neurologic outcomes with chemotherapy and also a
correlation between neurologic improvements and hematologic
remission. Level of evidence: II.
16. Van Thillo A, Vulsteke JB, Van Assche D, Verschueren P, De
Langhe E: Physical therapy in adult inflammatory myopathy
patients: A systematic review. Clin Rheumatol 2019;38(8):2039-
2051. This systematic review of physical therapy in patients with
idiopathic inflammatory myopathies across five randomized
controlled and seven open-label nonrandomized noncontrolled
trials concluded that physical therapy is a safe and effective
intervention for improving functional outcomes and further
recommended the inclusion of endurance training in the physical
therapy program. Level of evidence: I.
17. Spiritovic M, Hermankova B, Oreska S, et al: The effect of a 24-
week training focused on activities of daily living, muscle
strengthening, and stability in idiopathic inflammatory
myopathies: A monocentric controlled study with follow-up.
Arthritis Res Ther 2021;23(1):173. In a cohort of 57 patients with
idiopathic inflammatory myopathies, a 24-week supervised
resistance training program focusing on activities of daily living
and stability led to clinically meaningful improvements (>20%) in
muscle strength and endurance, global disability, and stability
compared with home-based exercise (regular outpatient care).
Level of evidence: II.
18. Ferrandi PJ, Alway SE, Mohamed JS: The interaction between
SARS-CoV-2 and ACE2 may have consequences for skeletal
muscle viral susceptibility and myopathies. J Appl Physiol
2020;129(4):864-867. This commentary posited that skeletal
 muscle is susceptible to direct viral infection from SARS-CoV-2
because of its robust expression of angiotensin-converting
enzyme 2, which serves as a putative entry receptor for the S1
spike domain of the virus. This speculation is supported by
clinical evidence of skeletal muscle pain, weakness, fatigue, and
injury as common symptoms of COVID-19 infection. Level of
evidence: V.
19. Aboudounya MM, Heads RJ: COVID-19 and toll-like receptor 4
(TLR4): SARS-CoV-2 may bind and activate TLR4 to increase
ACE2 expression, facilitating entry and causing
hyperinflammation. Mediators Inflamm 2021;2021:8874339. This
review proposed a role for Toll-like receptor 4, a transmembrane
receptor expressed on immune and tissue-resident cells that
recognizes pathogen-associated molecular pa erns from bacteria,
viruses, and other pathogens, in mediating SARS-CoV-2 viral
entry. In this model, the spike glycoprotein of SARS-CoV-2 binds
to Toll-like receptor 4, which activates Toll-like receptor 4
signaling to increase cell-surface expression of angiotensin-
converting enzyme 2, thereby facilitating viral entry into host
tissues. Level of evidence: V.
20. Megremis S, Walker TDJ, He X, et al: Antibodies against
immunogenic epitopes with high sequence identity to SARS-
CoV-2 in patients with autoimmune dermatomyositis. Ann Rheum
Dis 2020;79(10):1383-1386. Through next-generation sequencing
and epitope mapping, this study identified sequence similarity in
immunogenic epitopes from SARS-CoV-2 and patients with
dermatomyositis. These epitopes are further speculated to
activate CD8 T cells. Level of evidence: III.
21. Gupta L, Lilleker JB, Agarwal V, Chinoy H, Aggarwal R: COVID-
19 and myositis – Unique challenges for patients. Rheumatology
(Oxford) 2021;60(2):907-910. Through a large-scale anonymized
survey, this study found that the COVID-19 pandemic has
disrupted the continuity of medical care for many patients with
idiopathic inflammatory myopathy. Level of evidence: IV.
22. Saud A, Naveen R, Aggarwal R, Gupta L: COVID-19 and
myositis: What we know so far. Curr Rheumatol Rep 2021;23(8):63.
This comprehensive review of COVID-19–induced myositis
recommended self-directed physical assessments for remote
monitoring of patients. Level of evidence: V.
23. Corona BT, Wenke JC, Ward CL: Pathophysiology of volumetric
muscle loss injury. Cells Tissues Organs 2016;202(3-4):180-188.
24. Greising SM, Corona BT, McGann C, Frankum JK, Warren GL:
Therapeutic approaches for volumetric muscle loss injury: A
systematic review and meta-analysis. Tissue Eng B Rev
2019;25(6):510-525. This systematic review and meta-analysis of
the efficacy of regenerative therapies in restoring skeletal muscle
function after volumetric muscle loss found that combining
acellular material with stem and/or progenitor cells yielded the
greatest treatment effectiveness. Level of evidence: I.
25. Corona BT, Flanagan KE, Brininger CM, Goldman SM, Call JA,
Greising SM: Impact of volumetric muscle loss injury on
persistent motoneuron axotomy. Muscle Nerve 2018;57(5):799-807.
26. Aguilar CA, Greising SM, Wa s A, et al: Multiscale analysis of a
regenerative therapy for treatment of volumetric muscle loss
injury. Cell Death Discov 2018;4:33.
27. Murphy OC, Messacar K, Benson L, et al: Acute flaccid myelitis:
Cause, diagnosis, and management. Lancet 2021;397(10271):334-
346. This comprehensive review of AFM described its
epidemiology, clinical features, natural history, and outcomes
and discussed current diagnosis, management, and rehabilitation
strategies. Level of evidence: V.
28. Messacar K, Schreiner TL, Van Haren K, et al: Acute flaccid
myelitis: A clinical review of US cases 2012-2015. Ann Neurol
2016;80(3):326-338.
29. Gordon-Lipkin E, Munoz LS, Klein JL, Dean J, Izbudak I, Pardo
CA: Comparative quantitative clinical, neuroimaging, and
functional profiles in children with acute flaccid myelitis at acute
and convalescent stages of disease. Dev Med Child Neurol
 2019;61(3):366-375. In this retrospective case study of 16 children
with AFM who were evaluated at a single-institution, follow-up
assessment of functional outcomes (median 4 months) revealed
limited overall motor recovery and persistence of disabilities
despite intensive rehabilitation programs. In addition, limb
recovery occurred asymmetrically, with be er recovery in distal
than proximal muscle groups. Level of evidence: IV.
30. Melicosta ME, Dean J, Hagen K, et al: Acute flaccid myelitis:
Rehabilitation challenges and outcomes in a pediatric cohort. J
Pediatr Rehabil Med 2019;12(3):245-253. This is a retrospective
review of the functional outcomes in a cohort of 31 children with
AFM who underwent activity-based restorative therapy at a
single institution. Clinical muscle testing revealed that motor
function recovery occurred in a distal to proximal pa ern, with
lower limb recovery manifesting before recovery of upper limb
and core/cervical musculature. Despite improved lower limb
function, most children continued to require ambulatory
assistance devices. Level of evidence: IV.
31. Zhang Y, Moore DD, Nix WA, Oberste MS, Weldon WC:
Neutralization of enterovirus D68 isolated from the 2014 US
outbreak by commercial intravenous immune globulin products.
J Clin Virol 2015;69:172-175.
32. Vogt MR, Fu J, Kose N, et al: Human antibodies neutralize
enterovirus D68 and protect against infection and paralytic
disease. Sci Immunol 2020;5(49):eaba4902. To develop an antibody
therapy for AFM, this study screened B cells from participants
previously infected with enterovirus D68 (EV-D68; a human
respiratory virus associated with AFM) and isolated a series of
human monoclonal antibodies. EV68-228, a highly cross-reactive
antibody, bound a conformational epitope on the viral capsid and
protected immunodeficient mice from EV-D68–induced
respiratory and neurologic disease when given either before or
after infection.
33. Pino PA, Intravia J, Kozin SH, Zlotolow DA: Early results of
nerve transfers for restoring function in severe cases of acute
 flaccid myelitis. Ann Neurol 2019;86(4):607-615. In this
retrospective case study of 16 patients with AFM who underwent
nerve transfers from 2007 to 2018, follow-up assessments
(minimum 6 months postsurgery) revealed higher recovery rates
in elbow flexion (87%) and extension (67%) than in shoulder
external rotation (50%) and abduction (20%). Level of evidence:
IV.
34. Doi K, Sem SH, Ha ori Y, Sakamoto S, Hayashi K, De la Red-
Gallego MA: Surgical reconstruction for upper-extremity
paralysis following acute flaccid myelitis. JB JS Open Access
2019;4(4):e0030. In this cohort of eight patients with AFM who
underwent reconstructive surgery, follow-up assessments
(median 39 months) revealed shoulder abduction of ≤70° and
≥90° in equal halves of the cohort. In contrast, all patients who
received free muscle transfer or nerve transfer obtained elbow
flexion of ≥140°. Level of evidence: IV.
35. Jones RA, Harrison C, Eaton SL, et al: Cellular and molecular
anatomy of the human neuromuscular junction. Cell Rep
2017;21(9):2348-2356.
36. Gupta R, Chan JP, Uong J, et al: Human motor endplate
remodeling after traumatic nerve injury. J Neurosurg
2020;135(1):220-227. A cohort analysis of biopsies taken from
denervated muscles of 18 patients with traumatic brachial plexus
and axillary nerve injuries found that MEPs from multiple
patients persisted and retained their structures ≥6 months after
injury, and even beyond 3 years in 2 patients. Level of evidence:
IV.
37. Gendron TF, Petrucelli L: Disease mechanisms of C9ORF72
repeat expansions. Cold Spring Harb Perspect Med
2018;8(4):a024224.
38. Selvaraj BT, Livesey MR, Zhao C, et al: C9ORF72 repeat
expansion causes vulnerability of motor neurons to Ca(2+)-
permeable AMPA receptor-mediated excitotoxicity. Nat Commun
2018;9(1):347.
39. Shi Y, Lin S, Staats KA, et al: Haploinsufficiency leads to
neurodegeneration in C9ORF72 ALS/FTD human induced motor
neurons. Nat Med 2018;24(3):313-325.
40. Forsberg K, Graffmo K, Pakkenberg B, et al: Misfolded SOD1
inclusions in patients with mutations in C9orf72 and other
ALS/FTD-associated genes. J Neurol Neurosurg Psychiatry
2019;90(8):861-869. Through a panel of antibodies specifically
lacking reactivity to natively folded SOD1, this study detected
misfolded wild-type SOD1 in the spinal and cortical motor
neurons of a cohort of 29 patients with mutations in an
assortment of ALS-linked genes. Level of evidence: IV.
41. Chou CC, Zhang Y, Umoh ME, et al: TDP-43 pathology disrupts
nuclear pore complexes and nucleocytoplasmic transport in
ALS/FTD. Nat Neurosci 2018;21(2): 228-239.
42. Tank EM, Figueroa-Romero C, Hinder LM, et al: Abnormal RNA
stability in amyotrophic lateral sclerosis. Nat Commun
2018;9(1):2845.
43. Klim JR, Williams LA, Limone F, et al: ALS-implicated protein
TDP-43 sustains levels of STMN2, a mediator of motor neuron
growth and repair. Nat Neurosci 2019;22(2):167-179. To elucidate
TDP-43 function in ALS pathogenesis, this study performed
siRNA knockdown of TDP-43 in motor neurons derived from
human pluripotent stem cells. RNA-sequencing of this cell line
detected a substantial decline in STMN2 (which encodes a
microtubule regulator) transcript abundance. The role of STMN2
in ALS was further substantiated by reduced STMN2 levels in iPS
cell–derived motor neurons generated from patients with TDP-43
mutations and in spinal cords of ALS-affected cadavers.
44. Nikolaou S, Cramer AA, Hu L, Goh Q, Millay DP, Cornwall R:
Proteasome inhibition preserves longitudinal growth of
denervated muscle and prevents neonatal neuromuscular
contractures. JCI Insight 2019;4(23):e128454. This study used a
surgical mouse model of BPBI to establish critical insights on
growth impairments in pediatric muscle contractures. Targeted
 deletion of the fusogenic protein myomaker in muscle
progenitors failed to alter longitudinal growth of denervated
muscles, whereas pharmacologic treatment with a proteasome
inhibitor preserved functional length and prevented contractures
in denervated muscles 4 weeks post–brachial plexus injury. These
collective findings presented a paradigm whereby the muscle
growth impairments that cause contractures arise from
dysregulation of muscle proteostasis rather than dysregulation of
muscle stem cells.
45. Dayanidhi S, Kinney MC, Dykstra PB, Lieber RL: Does a reduced
number of muscle stem cells impair the addition of sarcomeres
and recovery from a skeletal muscle contracture? A transgenic
mouse model. Clin Orthop Relat Res 2020;478(4):886-899. This
study performed hindlimb immobilization in a transgenic mouse
model of muscle stem cell deletion, and reported a reduced
number of muscle stem cells and serial sarcomeres in
immobilized muscles.
46. Kinney MC, Dayanidhi S, Dykstra PB, McCarthy JJ, Peterson CA,
Lieber RL: Reduced skeletal muscle satellite cell number alters
muscle morphology after chronic stretch but allows limited serial
sarcomere addition. Muscle Nerve 2017;55(3):384-392.
47. Goh Q, Nikolaou S, Shay-Winkler K, Emmert ME, Cornwall R:
Timing of proteasome inhibition as a pharmacologic strategy for
prevention of muscle contractures in neonatal brachial plexus
injury. FASEB J 2021;35(2):e21214. By testing varying durations of
the proteasome inhibitor, bortezomib, in a surgical mouse model
of BPBI, this study found that proteasome inhibition is required
throughout skeletal growth to preserve muscle length and
prevent contractures long term. Therefore, neonatal denervation
causes a permanent longitudinal growth deficiency that must be
continuously ameliorated during skeletal growth.
48. Jin SC, Lewis SA, Bakhtiari S, et al: Mutations disrupting
neuritogenesis genes confer risk for cerebral palsy. Nat Genet
2020;52(10):1046-1056. In this cross-sectional study of two
independent cohorts, whole-exome sequencing of 250 parent-
 offspring trios revealed an enrichment of damaging de novo
mutations in cases of cerebral palsy. Out of eight identified genes
with multiple damaging de novo mutations, TUBA1A and
CTNNB1 met genome-wide significance. The study further
identified two novel monogenic etiologies, FBXO31 and RHOB,
which were not previously implicated in cerebral palsy. Last, the
authors estimated the excess de novo or recessive variants
identified here can explain 14% of cerebral palsy cases. Level of
evidence: II.
49. Dayanidhi S, Dykstra PB, Lyubasyuk V, McKay BR, Chambers
HG, Lieber RL: Reduced satellite cell number in situ in muscular
contractures from children with cerebral palsy. J Orthop Res
2015;33(7):1039-1045.
50. Mathewson MA, Lieber RL: Pathophysiology of muscle
contractures in cerebral palsy. Phys Med Rehabil Clin N Am
2015;26(1):57-67.
51. Smith LR, Chambers HG, Lieber RL: Reduced satellite cell
population may lead to contractures in children with cerebral
palsy. Dev Med Child Neurol 2013;55(3):264-270.
52. Moreno-De-Luca A, Millan F, Pesacreta DR, et al: Molecular
diagnostic yield of exome sequencing in patients with cerebral
palsy. J Am Med Assoc 2021;325(5):467-475. In this cross-sectional
study of two independent cohorts comprising 1,526 patients with
cerebral palsy, exome sequencing revealed the prevalence of
pathogenic and likely pathogenic variants was 32.7% and 10.5% in
children and adults, respectively. In addition, this study detected
several genes that were mutated in two or more unrelated
patients with cerebral palsy, including CTNNB1, KIF1A, GNAO1,
and TUBA1A. Level of evidence: II.
53. Hebebrand M, Huffmeier U, Trollmann R, et al: The mutational
and phenotypic spectrum of TUBA1A-associated tubulinopathy.
Orphanet J Rare Dis 2019;14(1):38. In a review of 107 cases from
prior studies, the most commonly reported clinical features of
TUBA1A variants were global developmental delay (98.1%),
 microcephaly (76.0%), epilepsy (71.2%), and spasticity (62.5%).
Common neuroradiologic features include abnormalities of the
corpus callosum (96.2%), abnormal cortical gyration (99.0%), and
lissencephaly (70.0%). Note that reporting was incomplete in the
different studies. Level of evidence: II.
54. Kharbanda M, Pilz DT, Tomkins S, et al: Clinical features
associated with CTNNB1 de novo loss of function mutations in
ten individuals. Eur J Med Genet 2017;60(2): 130-135.
55. Dzinovic I, Skorvanek M, Pavelekova P, et al: Variant recurrence
confirms the existence of a FBXO31-related spastic-dystonic
cerebral palsy syndrome. Ann Clin Transl Neurol 2021;8(4):951-
955. This case report identified a third child with a recurrent
missense variant (c.1000G > A, p. Asp334Asn) in FBXO31, which
was first reported in two unrelated children. All three patients
shared consistent features of motor and speech delay, muscle
spasticity leading to cerebral palsy diagnosis, as well as dystonia.
Level of evidence: IV.
56. Taher NAB, Kelly LA, Al-Harbi AI, et al: Altered distributions
and functions of natural killer T cells and γδ T cells in neonates
with neonatal encephalopathy, in school-age children at follow-
up, and in children with cerebral palsy. J Neuroimmunol
2021;356:577597. Flow cytometry of blood samples from 47
neonates and 43 school-aged children revealed that both innate
and conventional lymphocytes are numerically elevated in
neonates with neonatal encephalopathy, and this altered
inflammatory profile may persist into school age. Level of
evidence: II.
57. Zareen Z, Strickland T, Fallah L, et al: Cytokine dysregulation in
children with cerebral palsy. Dev Med Child Neurol 2021;63(4):407-
412. Assessment of serum cytokines in 24 school-aged children
revealed elevated baseline levels of erythropoietin in children
with cerebral palsy. In response to lipopolysaccharide, however,
children with cerebral palsy secreted reduced levels of multiple
key cytokines (IL-1α, IL-1β, IL-2, and IL-6), suggesting a
compromised inflammatory response. Level of evidence: II.
58. Rydberg M, Zimmerman M, Go sater A, Nilsson PM, Melander
O, Dahlin LB: Diabetes mellitus as a risk factor for compression
neuropathy: A longitudinal cohort study from southern Sweden.
BMJ Open Diabetes Res Care 2020;8(1):e001298. In a follow-up
assessment (median 21 years) to a population-based study in
Sweden, multivariate Cox regression analyses revealed that
baseline diabetes mellitus is independently associated with
incident carpal tunnel syndrome (hazard ratio 2.10) and ulnar
nerve entrapment (hazard ratio 2.20). Logistic regression analyses
further showed that higher hemoglobin A1C (odds ratio 1.029)
and plasma glucose levels (odds ratio 1.154) are associated only
with the development of carpal tunnel syndrome. Level of
evidence: IV.
59. Tampin B, Vollert J, Schmid AB: Sensory profiles are
comparable in patients with distal and proximal entrapment
neuropathies, while the pain experience differs. Curr Med Res
Opin 2018;34(11):1899-1906.
60. Wiberg A, Ng M, Schmid AB, et al: A genome-wide association
analysis identifies 16 novel susceptibility loci for carpal tunnel
syndrome. Nat Commun 2019;10(1):1030. A genome-wide
association was performed across 547,011 single-nucleotide
polymorphisms in a cohort of 12,312 participants of white British
ancestry with carpal tunnel syndrome to identify causal genes in
carpal tunnel syndrome pathogenesis. Expression of these genes
was subsequently confirmed by RNA sequencing in surgically
resected tenosynovium of patients with carpal tunnel syndrome.
Level of evidence: II.
61. Li C, Wang N, Schaffer AA, et al: Mutations in COMP cause
familial carpal tunnel syndrome. Nat Commun 2020;11(1):3642.
Genetic linkage analysis of one family in China with an
inheritance pa ern of severe carpal tunnel syndrome symptoms
identified a heterozygous missense mutation, c.197 T > A, in exon
3 of the COMP gene, which encodes cartilage oligomeric matrix
protein. In a second family with both carpal tunnel syndrome
and multiple epiphyseal dysplasia, whole-exome sequencing
 identified a different heterozygous missense mutation, c.2152 C >
T, in COMP. Level of evidence: II.
62. Baskozos G, Sandy-Hindmarch O, Clark AJ, et al: Molecular and
cellular correlates of human nerve regeneration:
ADCYAP1/PACAP enhance nerve outgrowth. Brain
2020;143(7):2009-2026. In a cohort study of carpal tunnel
syndrome, RNA sequencing of skin samples taken presurgical
and postsurgical release from 47 patients identified substantial
upregulation of the ADCYAP1 gene, which encodes a key protein
(PACAP) that facilitates neuronal survival after injury and
neurite outgrowth. Level of evidence: II.
63. McGinley MP, Goldschmidt CH, Rae-Grant AD: Diagnosis and
treatment of multiple sclerosis: A review. J Am Med Assoc
2021;325(8):765-779. This comprehensive review described current
findings on the epidemiology, pathophysiology, clinical
presentation, diagnosis, natural history, and disease outcomes of
multiple sclerosis and discussed contemporary treatment
strategies including different classes of DMTs, lifestyle
modifications to reduce comorbidities, and symptomatic
treatment. Level of evidence: V.
64. International Multiple Sclerosis Genetics Consortium: Multiple
sclerosis genomic map implicates peripheral immune cells and
microglia in susceptibility. Science 2019;365(6460):eaav7188.
Through genome-wide association studies in 47,429 multiple
sclerosis cases, the International Multiple Sclerosis Genetics
Consortium identified 233 risk loci in multiple sclerosis. Gene
expression studies further detected the enrichment of multiple
sclerosis susceptibility genes and risk variants in major immune
cell types, especially the microglia. The genetic and genomic
findings in this study explain up to 48% of the estimated
heritability for multiple sclerosis. Level of evidence: II.
65. International Multiple Sclerosis Genetics Consortium: Low-
frequency and rare-coding variation contributes to multiple
sclerosis risk. Cell 2018;175(6):1679-1687.e7.
66. Burt RK, Balabanov R, Burman J, et al: Effect of
nonmyeloablative hematopoietic stem cell transplantation versus
continued disease-modifying therapy on disease progression in
patients with relapsing-remi ing multiple sclerosis: A
randomized clinical trial. J Am Med Assoc 2019;321(2):165-174. In
this randomized clinical trial of 110 patients with relapsing-
remi ing multiple sclerosis, treatment with nonmyeloablative
hematopoietic stem cell transplantation significantly prolonged
time to disease progression compared with DMT (hazard ratio
0.07; median follow-up was 24 months). Level of evidence: I.
67. Harris VK, Stark J, Vyshkina T, et al: Phase I trial of intrathecal
mesenchymal stem cell-derived neural progenitors in progressive
multiple sclerosis. E Bio Medicine 2018;29:23-30.
68. Cadavid D, Mellion M, Hupperts R, et al: Safety and efficacy of
opicinumab in patients with relapsing multiple sclerosis
(SYNERGY): A randomised, placebo-controlled, phase 2 trial.
Lancet Neurol 2019;18(9):845-856. In this randomized, double-
blind, placebo-controlled clinical trial of 419 patients with
relapsing-remi ing multiple sclerosis and secondary progressive
multiple sclerosis with relapses, treatment with four different
doses of opicinumab (a human monoclonal antibody against
LINGO-1, an inhibitor of oligodendrocyte differentiation and
axonal regeneration) did not lead to a significant dose-linear
improvement in disability over 72 weeks compared with placebo.
Level of evidence: I.
69. Cree BAC, Cu er G, Wolinsky JS, et al: Safety and efficacy of
MD1003 (high-dose biotin) in patients with progressive multiple
sclerosis (SPI2): A randomised, double-blind, placebo-controlled,
phase 3 trial. Lancet Neurol 2020;19(12):988-997. In this
randomized, double-blind, placebo-controlled clinical trial of 642
patients with primary or secondary progressive multiple
sclerosis, treatment with biotin (a cofactor for four essential
carboxylases that might enhance neuronal and oligodendrocyte
energetics) did not improve disability or walking speed compared
with placebo. Level of evidence: I.
C H AP T E R 1 8

Orthopaedic Infections and

Microbiology
James E. Cassat MD, PhD

Neither Dr. Cassat nor any immediate family member has received anything of value from or has
stock or stock options held in a commercial company or institution related directly or indirectly to
the subject of this chapter.

ABSTRACT
Infection is one of the most feared and medically significant
complications of musculoskeletal trauma and orthopaedic
procedures. The treatment of orthopaedic infection is difficult,
typically requiring prolonged antimicrobial therapy in conjunction
with surgical débridement and implant removal. Such treatments
can trigger high morbidity, and a subset of patients will progress to
chronic infection despite appropriate therapeutic interventions.
Although the fundamental treatment approach for orthopaedic
infections, antibiotics and débridement, has remained relatively
unchanged for many decades, new developments stemming from
translational research offer hope for novel treatment strategies. It is
important for orthopaedic surgeons to review the pathophysiology,
microbiology, and evidence-based treatment approaches for
infection of bone, muscle, and joint tissues. There have been recent
developments from translational research focusing on orthopaedic
infection, resulting in avenues for future research and novel
therapeutics.
Keywords: microbiology; osteomyelitis; prosthetic joint infection;
pyomyositis; septic arthritis

Introduction
In an increasingly complex medical population, orthopaedic
procedures are a necessary and increasing facet of healthcare.
Despite advances in perioperative care, these procedures carry a
calculable risk of infection, and infection risk increases dramatically
with increasing severity of injury and in the presence of medical
comorbidities. For example, the rate of infection following fracture
ranges from approximately 1% to 2% for minor injuries to up to
30% for open fractures with extensive soft-tissue damage and
environmental contamination. 1 Infection also occurs in 1% to 2% of
patients who undergo total joint arthroplasty. 2 Outside of patient-
level variables, the prevalence of orthopaedic infection is strongly
influenced by the virulence mechanisms of prototypical
musculoskeletal pathogens, which have evolved to adhere to
skeletal tissues and orthopaedic implants, to subvert immune
responses, and to resist antimicrobial therapy. Accordingly,
management of orthopaedic infection requires prolonged
antimicrobial therapy. Yet, the antibiotic armamentarium is
increasingly limited in the current era of widespread antimicrobial
resistance. Although antimicrobial therapy alone is efficacious in
managing some presentations of musculoskeletal infection,
patients frequently require one or more surgical débridements or
orthopaedic implant removal for cure. Collectively, these
observations establish orthopaedic infection as a significant public
health burden with high patient morbidity. It is important to
summarize the pathologic mechanisms, microbiology, and
evidence-based treatment of orthopaedic infection, including
osteomyelitis, periprosthetic joint infection (PJI), and pyomyositis,
and to review recent translational discoveries, emerging research
paradigms, and opportunities for future investigation.
Osteomyelitis

Pathophysiology, Classification, and Disease

Manifestations
Although strictly defined as any inflammatory process in bone,
osteomyelitis is most commonly caused by infection. Osteomyelitis
is paradigmatic of treatment-refractory invasive infectious disease,
in that cure is notoriously difficult and requires prolonged
antibiotic therapy in conjunction with surgical débridement. Even
with such extreme treatment measures, many patients experiencing
osteomyelitis eventually experience chronic infection or sustain
highly morbid complications. Treatment failure or recurrence of
infection occurs in an estimated 13% to 30% of cases. 3 , 4 Thus, the
development of new strategies to manage osteomyelitis and
mitigate associated disease morbidity is a high priority.
Osteomyelitis occurs following one of three general pathologic
mechanisms: (1) secondary to a contiguous focus of infection; (2)
secondary to vascular insufficiency or neuropathy; or (3) secondary
to hematogenous seeding of bone. 5 Osteomyelitis that occurs
secondary to a contiguous focus of infection is the most common
mechanism in adults and encompasses an array of pathology such
as surgical site infection, orthopaedic implant–associated
osteomyelitis, and infection following penetrating trauma (eg,
contaminated open fractures). Hematogenous osteomyelitis is
predominantly a disease of the pediatric population, with two
important exceptions. First, hematogenous seeding is the presumed
inciting event for native vertebral osteomyelitis, which is the most
common form of hematogenous osteomyelitis in patients older
than 50 years. 6 Second, persons who inject drugs are at risk for
hematogenous seeding of bones and joints and resultant
osteomyelitis and septic arthritis. Osteomyelitis that occurs
secondary to vascular insufficiency or neuropathy characteristically
follows skin and soft-tissue ulceration that results from repetitive
trauma, leading to bone exposure and subsequent microbial
contamination. This mechanism of osteomyelitis is most common
in patients with diabetes; foot ulcers that involve bone develop in a
large percentage of these patients.
In addition to classifying osteomyelitis based on the inciting
pathologic mechanism, additional schemes have been proposed
that codify osteomyelitis based on factors such as location of
disease, patient comorbidities, radiographic features, and histologic
findings. 7 , 8 The Cierny-Mader classification scheme characterizes
osteomyelitis based on four anatomic types and three host
physiologic classes to comprise 12 clinical stages. 9 Anatomic types
are (I) medullary, in which the disease is endosteal; (II) superficial,
in which a contiguous focus of infection causes disease on the
superficial surface of the bone; (III) localized, in which disease is
full thickness with cortical sequestration and/or cavitation,
combining elements of both medullary and superficial disease; and
(IV) diffuse, in which disease is permeative, circumferential, and
associated with skeletal instability. 9 Patient classification in the
Cierny-Mader system includes normal hosts (A), compromised
hosts (B), and hosts in which the treatment is more injurious than
the bone disease itself (C). Class B hosts are further classified based
on the presence of local (BL, eg, lymphedema, venous stasis,
scarring), systemic (BS , eg, malnutrition, immunodeficiency,
diabetes), or local and systemic (BLS ) comorbidities. 9 The 12
resulting clinical classifications are then used to infer prognosis
and drive treatment algorithms, including surgical débridement,
dead space management, and antibiotic therapy. 9
A precise classification of osteomyelitis as acute versus chronic
has been more elusive and controversial. 7 Suggested definitions of
chronic osteomyelitis based solely on disease duration have been
variable, ranging from 2 weeks to 6 months. 7 , 8 Acute versus
chronic osteomyelitis is also segregated based on radiographic
findings and histologic evaluation. Classic radiographic features of
chronic osteomyelitis include the presence of necrotic fragments of
bone known as sequestra, areas of surrounding reactive bone
formation known as involucrum, and sinus tract formation. 5 The
classic histopathologic finding of acute osteomyelitis is a
neutrophilic infiltrate, whereas features associated with chronic
osteomyelitis include lymphocytic inflammation and marrow
fibrosis. However, histologic features of both acute and chronic
osteomyelitis can be observed in the same lesion and may not
perfectly correlate with the disease duration. 7 Accordingly, many
experts recommend avoiding classifications of disease that are
solely based on time since symptom onset. 2

Microbiology
The inciting pathologic mechanisms leading to osteomyelitis (eg,
hematogenous versus secondary to a contiguous infection) strongly
influence the resulting microbial pathogens present in infected
bone. Across all pathologic mechanisms, the gram-positive
bacterium Staphylococcus aureus is the most common etiologic agent
of bone infection. Accordingly, much of the current knowledge
regarding bacterial virulence mechanisms that contribute to the
pathogenesis of osteomyelitis come from studies of S. aureus. Table
1 lists the most commonly isolated microorganisms from
musculoskeletal infections, as classified based on inciting disease
mechanism. Importantly, current knowledge of infectious
etiologies of osteomyelitis is largely based on traditional
microbiologic culture methods, whereas newer analyses leveraging
molecular diagnostics, 16s ribosomal RNA (rRNA) sequencing, or
metagenomics suggest that such traditional methods may
underestimate the microbial diversity encountered in osteomyelitis.
One study compared conventional culture methods with 16s rRNA
sequencing for the diagnosis of diabetic foot osteomyelitis and
found that culture failed to identify a pathogen in 23.5% of cases,
yet Staphylococcus species were detected by 16s rRNA sequencing in
75% of the culture-negative bone samples. 13 The most commonly
detected microbial genera in this study were Staphylococcus,
Corynebacterium, Streptococcus, and Cutibacterium (formerly
Propionibacterium). In addition, significantly more anaerobic
bacteria were detected by 16s rRNA sequencing (86.9% of samples)
than by traditional culture methods (23.1% of samples). 13 One
study also used 16s rRNA sequencing to characterize the
microbiota of open fractures. 17 A diverse microbiota was observed
in the wound center and adjacent skin, including six genera
(Staphylococcus, Corynebacterium, Streptococcus, Acinetobacter,
Anaerococcus, and Pseudomonas) present at greater than 1% of the
median relative abundance. 17 Notably, bacterial community
structure differed significantly in complicated versus
uncomplicated cases, suggesting that 16s rRNA-based molecular
diagnostics might have prognostic value. 17 These studies highlight
that osteomyelitis stemming from a contiguous source or vascular
disease is frequently polymicrobial, and although conventional
culture techniques can identify dominant pathogens, such methods
typically underestimate the diversity of infecting microbes. In
contrast, hematogenous and vertebral osteomyelitis are typically
monomicrobial diseases.

Table 1
Microbiology of Musculoskeletal Infection

Infection Organisms g Notes

Acute Staphylococcus aureus, 1
Nontyphoidal Salmonella serovars
hematogenous Streptococcus pneumoniae, are important causes of
osteomyelitis a Streptococcus pyogenes, osteomyelitis in patients with sickle
Salmonella enterica 1, endemic cell anemia
mycoses (Histoplasma capsulatum,
Blastomyces dermatitidis,
Coccidioides spp.), Candida spp.
Native S aureus, Streptococcus spp., 1
P aeruginosa, Candida spp., and
vertebral Escherichia coli, Pseudomonas S aureus are commonly isolated
osteomyelitis b
aeruginosa 1 , Candida spp. 1 , from persons who inject drugs
Brucella spp. 2 , Mycobacterium 2
In endemic regions
tuberculosis, 2 and nontuberculous 3
More common in
mycobacteria3 immunocompromised patients
 Infection Organisms g Notes
Implant- S aureus, coagulase-negative 1
E coli, Klebsiella spp.,
associated Staphylococcus, enteric gram- Enterobacter spp.
osteomyelitis c
negative bacilli1, P aeruginosa, 2
Increased incidence in soldiers
Acinetobacter baumannii 2, who experience extremity trauma
Streptococcus spp., Enterococcus while deployed
spp., anaerobic organisms
Diabetic foot S aureus, coagulase-negative 1
Infections are typically
osteomyelitis d
Staphylococcus, Streptococcus polymicrobial, and traditional
spp., E coli, Klebsiella pneumoniae, cultures may underestimate
P aeruginosa, Proteus spp., microbiologic diversity
Enterobacter spp., anaerobic
organisms 1
Periprosthetic S aureus, coagulase-negative 1
Cutibacterium acnes, formerly
joint infection e Staphylococcus, Enterococcus known as Propionibacterium
spp., beta-hemolytic Streptococcus acnes, is a fastidious and low-
spp., E coli, P aeruginosa, Klebsiella virulence anaerobe that is an
spp., Enterobacter spp., Proteus important cause of periprosthetic
spp., anaerobic organisms 1 joint infection, especially involving
the shoulder.
Pyomyositis f
S aureus, group A Streptococcus 1 1
Rare causes include anaerobic
organisms (eg, Fusobacterium
necrophorum), other
Streptococcus spp., Enterococcus
spp., and Enterobacteriaceae
a
Data compiled from references 10 and 11.
b
Data compiled from references 6 and 10.
c
Data compiled from references 10, 11, and 12.
d
Data compiled from references 13 and 14.
e
Data compiled from references 2, 10, and 15.
Data compiled from references 10 and 16.
f

g
Superscript numbers 1 to 3 refer to corresponding Notes in the right-hand column.

Atypical etiologies of osteomyelitis, including rare bacterial

pathogens as well as mycobacterial and fungal infection, are often
suggested by a careful exposure history. Approximately 1% to 5% of
Mycobacterium tuberculosis infections involve the skeleton. 10 M
tuberculosis osteomyelitis presents subacutely and frequently
involves vertebrae or periarticular surfaces. Patients may have a
prior history of positive skin testing, travel to endemic areas,
known contact exposure, or prior latent tuberculosis. Disease can
occur as a function of primary disseminated infection or through
reactivation of an osteoarticular nidus that was hematogenously
seeded during a primary infection. 18 More than 50% of tuberculous
osteomyelitis cases involve the spine, although in contrast with
other infectious etiologies of vertebral osteomyelitis, systemic
symptoms are typically absent. 10 , 18 Importantly, the absence of
abnormal findings on chest radiograph does not exclude the
diagnosis of tuberculous osteomyelitis. 19 Nontuberculous
mycobacteria are also important causes of musculoskeletal
infection. Like tuberculous osteoarticular infection, nontuberculous
mycobacteria musculoskeletal infection can occur via
hematogenous seeding in compromised patients, but infection also
occurs in healthy patients following traumatic inoculation of
contaminated water or soil, where nontuberculous mycobacteria are
ubiquitously found. 19 Dimorphic fungi are important causes of
osteoarticular infection in endemic regions of the United States.
Coccidioides species are dimorphic fungi endemic to the
Southwestern United States that typically cause respiratory
infection, although musculoskeletal tissues are a frequent site of
extrapulmonary disease. 10 Bone involvement most frequently
follows a primary septic arthritis, but hematogenous seeding of
long bones and vertebrae are also reported. 10 Histoplasma
capsulatum and Blastomyces dermatitidis are dimorphic fungi that are
most highly endemic to the Ohio and Mississippi River valleys. Like
Coccidioides species, both fungi typically cause pulmonary infection
but can cause disseminated disease, with bone and joint tissues
frequently involved. 10 , 20 B dermatitidis in particular has a high
tropism for skin and bone during disseminated disease, and
concomitant cutaneous and skeletal disease is common. 10 Risk
factors for both histoplasmosis and blastomycosis include exposure
to recent soil excavation or construction. Histoplasmosis is also
strongly linked to exposure to bird and bat guano, and therefore
entry into chicken coops and caves, respectively. 10 Other important
causes of fungal osteomyelitis include Candida and Aspergillus
species. Candidal osteomyelitis is typically the result of prior
hematogenous seeding, and bone disease can manifest years after
 g g y
the initial infection. Aspergillus musculoskeletal infection is most
20

common in immunocompromised adults and can occur via spread

from a contiguous focus or as the result of hematogenous seeding.
20
Atypical bacterial pathogens should also be considered in the
context of particular exposures and medical comorbidities.
Osteoarticular involvement is observed in approximately one-half
of patients with Brucellosis, which is caused by the gram-negative
pathogens Brucella melitensis, Brucella suis, and Brucella abortus. 10
Infection occurs following ingestion of contaminated goat or sheep
milk, or via direct inoculation of skin, lungs, or conjunctivae
following contact with infected animals. Musculoskeletal
involvement comprises a spectrum of clinical findings including
vertebral osteomyelitis, sacroiliitis, diskitis, and septic arthritis. 10
Nontyphoidal serovars of Salmonella enterica are important causes
of long bone osteomyelitis in patients with sickle cell anemia,
although S aureus remains a frequent pathogen in this population.
10

Bacterial Virulence Mechanisms—Lessons

Learned From S aureus
Given that S aureus is the predominant pathogen causing
osteomyelitis in both children and adults, it is not surprising that
most of the current knowledge of the virulence mechanisms, host
immune responses, and pathophysiology of osteomyelitis comes
from basic and translational studies that focus on this pathogen.
Animal studies of osteomyelitis have been particularly useful in
dissecting the microbial factors that contribute to the
establishment of osteomyelitis, bacterial survival in bone, bone
loss, and treatment recalcitrance. 21 S aureus has a broad
armamentarium of virulence factors to facilitate invasive infection,
and molecular dissection of these factors defines strategies that can
be generalized to other successful pathogens causing
musculoskeletal infection. Staphylococcal virulence factors
promoting osteomyelitis can be broadly divided into those that (1)
facilitate adherence to skeletal tissues or orthopaedic implants, (2)
promote biofilm formation, (3) evade host immune responses, and
(4) resist antimicrobial therapy. To facilitate binding to host tissues,
S aureus possesses a group of adhesins known as microbial surface
components recognizing adhesive matrix molecules. Microbial
surface components recognizing adhesive matrix molecules enable
adhesion to components of the extracellular matrix in skeletal
tissues, including fibrinogen, fibronectin, collagen, elastin, and
bone sialoprotein. 21 , 22 These proteins also facilitate the formation
of biofilms, which are defined as structured microbial communities
that are encased within an extracellular matrix. 23 Biofilm formation
is widely accepted as a critical mechanism underlying the treatment
recalcitrance of musculoskeletal infection. Biofilm growth is a
highly regulated process in S aureus, with bacteria cycling through
successive phases of adhesion to host and abiotic surfaces,
proliferation and extracellular matrix production, and biofilm
structuring and detachment. 23 The composition of the
staphylococcal biofilm matrix, or extracellular polymeric substance,
is strain dependent and consists mostly of polysaccharide, protein,
and extracellular DNA. 23 The most well-characterized
polysaccharide component of the staphylococcal biofilm matrix is
poly-β(1-6)-N-acetylglucosamine, which is produced by the
intracellular adhesin (ica) operon. 23 However, many clinical isolates
of S aureus produce a largely proteinaceous matrix, and the role of
poly-β(1-6)-N-acetylglucosamine is less pronounced. 23 , 24 The final
stage of the biofilm cycle, detachment, is facilitated by the
regulated expression of a variety of bacterial proteases as well as
two nucleases that degrade proteins and extracellular DNA in the
matrix, respectively. 23
In addition to factors that promote adhesion and biofilm
formation, S aureus produces a large repertoire of virulence factors
that facilitate evasion of immune responses. These immunoevasive
factors include cytolytic toxins that destroy or incapacitate immune
cells, surface and secreted proteins that misdirect immune
responses, and adhesins and enzymes that facilitate physical
sequestration of bacteria from immune effectors and antimicrobial
compounds. 25 , 26 S aureus exotoxins constitute a major fraction of
the total bacterial secretome and induce cellular cytotoxicity by
both receptor-dependent and receptor-independent methods. 25
Notable receptor-dependent cytotoxins include alpha-hemolysin
(Hla) and the bicomponent leukotoxins (eg, Panton-Valentine
leukocidin). Hla has been shown to contribute to osteomyelitis
pathogenesis. 27 However, the precise contribution of other
leukotoxins to osteomyelitis pathogenesis has been more difficult
to determine given that some leukotoxins show high species
specificity and therefore cannot be fully evaluated in rodent
models. 21 , 25 The phenol-soluble modulins are small amphipathic
peptides that are expressed under the control of the S aureus
accessory gene regulator (Agr) system and trigger host cell lysis in
a receptor-independent manner. 21 , 25 Both Agr and the alpha-type
phenol-soluble modulins have been shown to trigger bone cell
death and contribute to pathologic bone destruction in vivo in
murine models. 28 Conversely, inactivation of the agr locus leads to
increased biofilm formation in vitro, and clinical isolates of S aureus
taken from patients with chronic osteomyelitis have been
documented to have inactivating mutations in agr. 21 Thus, the role
of the Agr system in osteomyelitis may be specific to the phase of
infection. In addition to toxins, S aureus produces a number of
virulence factors that prevent innate immune activation or subvert
immune effector mechanisms. This includes proteins that inhibit
complement activation, neutrophil chemotaxis and activation,
opsonization and phagocytosis, and bacterial killing. 26 Although a
detailed discussion of these factors is outside of the scope of this
chapter, at least two immunoevasive proteins, staphylococcal
protein A (Spa) and major histocompatibility complex class II
analog protein (Map), have been linked to the pathogenesis of
osteomyelitis. 21 Spa inhibits humoral effector mechanisms through
its ability to bind the Fc portion of antibodies and serve as a B-cell
superantigen. 26 Of importance to bone infection, Spa can bind to
osteoblasts and trigger enhanced receptor activator of nuclear
factor kappa B ligand (RANKL) production and apoptosis. 29 Spa
 pp g p p p p
also can enhance osteoclastogenesis by binding to receptors on
osteoclast precursor cells. 30 Map was found to contribute to septic
arthritis and periarticular osteomyelitis incidence and severity in a
murine model of hematogenous S aureus infection. 31 A third class
of S aureus immunoevasive virulence factors includes those that
facilitate the formation of protected intracellular or extracellular
reservoirs in the host. S aureus is capable of surviving intracellularly
in a variety of host cells, including osteoblasts and osteoclasts. 32 - 34
Interestingly, treatment of monocyte lineage cells with RANKL
leads to enhanced intracellular burdens of S aureus, suggesting that
osteoclasts might be an important niche during osteomyelitis. 33
Once it is intracellular, S aureus can adopt a more metabolically
quiescent state known as a small colony variant. Small colony
variants are tolerant to multiple classes of antibiotics and are
thought to contribute to chronic and recalcitrant infections,
including osteomyelitis. 35 In addition to intracellular growth, S.
aureus also leverages virulence factors to physically sequester itself
from host defenses during extracellular growth. The characteristic
inflammatory lesion encountered during invasive S aureus infection
is the abscess. Abscesses consist of a three-dimensional community
of bacteria surrounded by viable and necrotic neutrophils and
additional immune cells such as macrophages, 32 along with a
pseudocapsule that creates a physical barrier preventing neutrophil
access to the bacteria. Production of the pseudocapsule is
dependent on S aureus virulence factors with coagulase activity,
including staphylocoagulase (Coa) and von Willebrand factor
binding protein (vWbp), which activate prothrombin to cleave
fibrinogen into fibrin. 32 , 36 In this way, S aureus usurps the host
clo ing system to physically sequester bacterial cells from immune
cells.

Antimicrobial Therapy for Osteomyelitis

Detailed recommendations on treatment of osteomyelitis are
presented in the Infectious Diseases Society of America (IDSA)
Clinical Practice Guidelines for methicillin-resistant S aureus
(MRSA) infection (including osteomyelitis and implant-associated
osteomyelitis), 37 native vertebral osteomyelitis, 6 and diabetic foot
infections. 14 In general, the mainstays of osteomyelitis treatment
are targeted antimicrobial therapy, surgical débridement when
necessary, and removal of orthopaedic hardware when feasible. The
ability to administer targeted antimicrobial therapy is, in turn,
dependent on the ability to obtain a microbiologic diagnosis.
Accordingly, sampling of the involved tissues prior to antibiotic
administration is ideal. After provision of microbiologic specimens,
empiric therapy is initiated to target the most likely microbial
etiologies, while factoring in the presence of comorbid medical
conditions, the local prevalence of antimicrobial-resistant isolates,
and the presence of any drug allergies. Given the frequency of S
aureus infection across all classifications of osteomyelitis, empiric
regimens will typically include antistaphylococcal agents. However,
in the era of community-acquired MRSA, antimicrobial choices are
more limited. Suggested parenteral antibiotics for MRSA
osteomyelitis and septic arthritis in the IDSA Clinical Practice
Guidelines include vancomycin and daptomycin (B-II level of
evidence). 37 Additional suggested agents with parenteral or oral
administration routes include clindamycin, linezolid, or
trimethoprim-sulfamethoxazole. Many experts would recommend
an intravenous bactericidal agent for empiric therapy of suspected
MRSA musculoskeletal infection in patients who are critically ill,
have hemodynamic instability, or in whom concomitant bacteremia
is likely. For patients who are not acutely ill, it is reasonable to
administer oral antibiotics as empiric therapy. In areas where the
prevalence of clindamycin-resistant MRSA is low, clindamycin
monotherapy could be considered for empiric MRSA coverage.
However, many medical centers have rates of clindamycin
resistance that exceed 15% to 20%, and therefore empiric
clindamycin might lead to an unacceptable rate of treatment
failure.
Osteomyelitis that results from contiguous infection or vascular
insufficiency is typically polymicrobial, and therefore empiric
antibiotic regimens should target not only gram-positive bacteria
such as S aureus, but also gram-negative and anaerobic organisms.
The IDSA Clinical Practice Guidelines for severe diabetic foot
infection recommend vancomycin or daptomycin plus one of the
following drugs: ceftazidime, cefepime, piperacillin-tazobactam,
aztreonam, or a carbapenem. 14 Similarly, for implant-associated
and vertebral osteomyelitis, gram-negative bacilli are important
etiologic considerations, and therefore empiric regimens typically
include coverage for these organisms in addition to MRSA and
other gram-positive agents. 10 , 11 In patients in whom postsurgical
wound infections involving bone develop, multidrug-resistant
hospital-acquired organisms also need to be considered in the
provision of empiric antibiotic therapy. Institutional antibiograms
can be particularly helpful in this regard. Finally, an important
distinction should be drawn between empiric antibiotic treatment
and preemptive (prophylactic) antibiotic treatment. Whereas
empiric therapy is given after the onset of signs and symptoms
suggestive of musculoskeletal infection, preemptive antibiotics may
be given when the injury mechanism makes subsequent infection
highly likely. The most common scenario for the administration of
preemptive antibiotics to prevent osteomyelitis is in patients with
grade III open fractures. 21 A Cochrane review concluded that
antibiotics reduce the incidence of early infection following open
fracture. 38 Although the precise antibiotic regimens used for
preemptive therapy of open fractures vary across institutions, most
experts recommend a short duration of 1 to 3 days. 10 , 39
The optimal duration of targeted antibiotic therapy for
osteomyelitis is unknown, because there are few prospective
clinical trials on length of therapy. 10 Most experts recommend 4 to
6 weeks of targeted antibiotic therapy for acute hematogenous
osteomyelitis in adults. 10 , 11 For implant-associated osteomyelitis,
the duration of therapy is highly dependent on the retention versus
removal of infected hardware. The Fracture-Related Infection
Consensus Group published recommendations for antibiotic
therapy of fracture-related infection in 2020. 12 Six weeks of
antibiotic therapy is recommended following immediate implant
removal, whereas 12 weeks of therapy is recommended for one-
stage or two-stage implant exchange. For those patients in whom
implant removal is not immediately feasible, antibiotic treatment is
continued indefinitely until implant removal, with an additional 1
to 2 weeks of therapy thereafter. 12 For vertebral osteomyelitis, the
IDSA recommends 6 weeks of therapy, with the exception of
osteomyelitis due to Brucella species. 6 Importantly, the safety and
efficacy of an early switch from parenteral to oral therapy is now
well established. The results of a multicenter, open-label,
randomized controlled noninferiority trial comparing oral versus
intravenous antibiotics for the first 6 weeks of treatment for
musculoskeletal infection (extra-axial and vertebral osteomyelitis,
septic arthritis, PJI, and implant-associated infection) were
published in 2019. 3 No difference was observed in treatment failure
rates between oral and intravenous therapy groups.

Periprosthetic Joint Infection

Medical Effect, Clinical Presentation, and

Diagnosis
PJI is associated with a profound medical burden, accounting for
up to one-fourth of all revision surgeries for total knee or hip
arthroplasty 34 , 40 and resulting in an estimated economic burden of
greater than $1.1 billion for inpatient care alone in 2020. 41 Risk
factors for PJI include obesity (moderate strength evidence) and a
number of additional medical comorbidities such as cardiovascular
disease, prior joint infection, immunocompromise, diabetes,
malnutrition, and tobacco and alcohol use (limited strength
evidence). 42 Clinical signs and symptoms of early PJI (commonly
defined as less than 3 months after surgery) are redness, swelling,
pain, and discharge, with or without systemic symptoms such as
fever or chills. In delayed (3 months to 12 to 24 months after
surgery) or late-onset infection (>12 to 24 months after surgery),
patients may present with chronic pain or the presence of a sinus
tract. 15 However, PJI may also develop months to years after the
arthroplasty as a result of hematogenous seeding of the implant. In
this scenario, patients may have a more acute onset of pain and
systemic symptoms. Evidence-based diagnostic guidelines for PJI
were published by the AAOS in 2020. 42 Diagnosis of PJI is
supported by preoperative blood tests (erythrocyte sedimentation
rate, C-reactive protein, serum interleukin 6), synovial fluid analysis
and culture (aerobic and anaerobic), periprosthetic tissue and
implant sonication cultures, and histopathology. 42 A minimum of
three cultures are recommended. 2 Routine acid-fast bacilli and
fungal cultures are not recommended but should be considered in
patients with risk factors for atypical infection. 2 Importantly,
intraoperative Gram stain is not recommended as a sole diagnostic
maneuver to rule out PJI, and when possible, antibiotics should be
withheld prior to obtaining cultures if the offending pathogen has
not been identified. 2 , 42 In terms of risk mitigation during
arthroplasty, irrigation with dilute betadine solution is
recommended by the World Health Organization and the Centers
for Disease Control and Prevention, whereas there is no evidence
for the routine use of topical vancomycin powder for prevention of
PJI. 2

Microbiology and Treatment

The most common etiologic agents of PJI include S aureus,
coagulase-negative staphylococci, enterococci, beta-hemolytic
streptococci, and gram-negative bacilli (Escherichia coli, Pseudomonas
aeruginosa, Klebsiella spp., Proteus spp., and Enterobacter spp.). 2 , 10 , 15
Anaerobic organisms, most prominently Cutibacterium acnes
(formerly Propionibacterium acnes), are also important causes of PJI.
Polymicrobial infection occurs in approximately 6% to 36% of PJIs
and is associated with lower treatment success rates. 2 , 15 More rare
causes of PJI include Corynebacterium spp, Pasteurella spp.,
tuberculous and nontuberculous mycobacteria, and fungi (Candida
and Aspergillus spp.). 15 PJI is culture negative in 5% to 15% of cases.
15

Treatment of PJI requires targeted antimicrobial therapy and one

of the following surgical interventions: débridement with
antibiotics and implant retention (DAIR), prosthesis removal
without reimplantation, one-stage exchange (complete implant
removal, débridement, and immediate replacement of new
prosthesis), two-stage exchange (complete implant removal,
débridement, and delayed replacement of a new prosthesis
following antibiotic therapy), or amputation. 15 , 42 DAIR is reserved
for patients who (1) are within 30 days of implantation or have
experienced symptoms for less than 3 weeks; (2) have a well-fixed
prosthesis; and (3) have no sinus tract. 43 Two-stage exchanges are
common in the United States and typically include the provision of
local antibiotic therapy in cement or spacers during the implant-
free period. 15 , 43 Detailed recommendations for antimicrobial
therapy of PJI are provided by the IDSA Clinical Practice
Guidelines. For staphylococcal PJI managed with DAIR or one-
stage exchange, 2 to 6 weeks of intravenous therapy (nafcillin,
cefazolin, or ceftriaxone for oxacillin-susceptible isolates;
vancomycin for oxacillin-resistant isolates) in combination with oral
rifampin are recommended. 43 Following intravenous therapy, this
treatment can be stepped down to oral therapy (eg, a
fluoroquinolone plus rifampin) to complete 3 to 6 months of
therapy. However, it should be noted that not all experts agree with
the duration of antibiotics recommended by the IDSA for PJI. 2
Some practitioners recommend indefinite chronic antibiotic
suppression following initial treatment. 15 , 43 For patients treated
with two-stage exchange, 4 to 6 weeks of intravenous or highly
bioavailable oral antibiotic therapy are recommended. 43 An open-
label, randomized controlled noninferiority clinical trial published
in 2021 compared 6 with 12 weeks of antibiotic therapy for
microbiologically confirmed PJI managed with DAIR or one-stage
or two-stage revision. 44 The primary outcome was persistent or
recurrent infection present at 2 years following completion of
antibiotic therapy. The median duration of intravenous therapy in
both groups was 9 days, and the most common oral agents were
fluoroquinolones and rifampin. In patients treated with 6 weeks of
therapy, 18.1% had persistent infection at 2 years, compared with
9.4% in the 12-week group. Thus, 6 weeks cannot be considered
noninferior to 12 weeks of therapy. 44

Pyomyositis
Pyomyositis is defined as an intramuscular infection that is not the
result of contiguous infection of soft tissues or bone. 10 , 16 This
infection has also been termed tropical pyomyositis given that
many cases have been reported in tropical regions. 16 The presumed
mechanism of disease initiation is transient bacteremia with direct
seeding of the musculature in the se ing of local, nonpenetrating
injury. 10 Pyomyositis can also occur in the se ing of a disseminated
bacteremic infection, such as endocarditis. The most common
etiologic agent is S aureus, followed by group A streptococci. 16 Rare
causes of pyomyositis include other Streptococcus spp., anaerobic
bacteria, Enterobacteriaceae, and Enterococcus faecalis. 10 , 16
Fusobacterium necrophorum is an important cause of anaerobic
bacterial pyomyositis in the se ing of Lemierre syndrome, wherein
disseminated infection develops in patients following septic
thrombophlebitis of the internal jugular vein. 16 Patients with
isolated pyomyositis typically present with fever, local swelling, and
tenderness. Suppuration may progress over a 10- to 21-day period. 16
The most frequently affected muscles are the quadriceps, iliopsoas,
and gluteus group. 10 Diagnosis hinges on imaging and
percutaneous drainage for aerobic and anaerobic culture. Blood
cultures should also be obtained in the event that the pyomyositis
reflects a distant primary focus of infection. Empiric therapy should
target S aureus, including MRSA, and therefore vancomycin,
daptomycin, clindamycin, or linezolid can be considered. In
immunocompromised or critically ill patients, most experts would
recommend the addition of a second broad-spectrum agent to cover
gram-negative and anaerobic organisms. 10 , 16
Translational Research in Orthopaedic
Infection: Recent Developments and
Emerging Opportunities
The prevention, diagnosis, and management of musculoskeletal
infection remain a considerable clinical challenge. Antimicrobial
resistance is an ever-increasing threat to global health, and
therefore the development of new therapeutic agents for
orthopaedic infection is a high priority. At the same time, studies
that aim to refine existing therapeutic regimens or ameliorate
infection-induced tissue damage will help to preserve the efficacy of
current standard-of-care treatments. In this regard, translational
research leveraging preclinical models of musculoskeletal infection
is an integral facet of orthopaedic surgery. Recent discoveries are
driving new paradigms for translational research related to
orthopaedic infection.

Serologic Analyses to Diagnose Infection and

Predict Outcomes
Despite appropriate tissue sampling, orthopaedic infection is
culture-negative in a significant number of cases. 10 , 11 , 21 This
complicates treatment in that it can be difficult to narrow empiric
therapy, and patients then receive broad-spectrum regimens for the
duration of treatment. Therefore, culture-independent diagnostics
can be of high value in select patients. One culture-independent
approach to the diagnosis and prognosis of orthopaedic infection is
the measurement of serologic responses to pathogens. For example,
a 2020 study evaluated serologic responses to three S aureus biofilm-
upregulated antigens as potential diagnostic assays for chronic
osteomyelitis. 45 The authors found that one target, a bacterial
manganese transporter, showed high specificity in a lateral flow
assay when testing sera from S aureus-infected rabbits and synovial
fluid from humans with orthopaedic implant infection. 45 As
described in another 2021 study, a multiplex assay was developed to
query the immunoproteome during S aureus musculoskeletal
infection. 46 Interestingly, antibody responses to some antigens
correlated with positive outcomes, whereas responses to other
antigens (eg, the iron-regulated surface determinant B) were
associated with adverse outcomes. Validation of this multiplex
panel using a 194-patient registry confirmed the prognostic
potential of serologic responses. 46 Taken together, these studies
emphasize the utility of serologic assays for both diagnosis and
prognosis of orthopaedic infection and suggest that future studies
on humoral responses to musculoskeletal pathogens are an
important focus for translational research.

Characterizing Bacterial Niches That

Contribute to Infection Chronicity
During invasive infection, bacterial pathogens can persist in host
niches that are protected from both immune effector mechanisms
and antibiotic therapy. With respect to orthopaedic infection, the
propensity of bacteria to form biofilm and to invade and persist
within both phagocytic and nonphagocytic cells has been
hypothesized to strongly contribute to treatment recalcitrance and
progression to chronic infection. Therefore, an important area for
ongoing translational research is to characterize how bacteria
establish protected niches in musculoskeletal tissues, and then to
leverage this information to create improved treatments. S aureus
was recently found to invade and proliferate within the osteocyte
lacunar-canalicular network in both murine models and in human
tissues. 32 , 47 Invasion of the osteocyte lacunar-canalicular network
contributes to antibiotic recalcitrance and is facilitated, in part, by
the S aureus transpeptidase Pbp4. 48 As noted previously, S aureus
also can invade and persist within osteoclasts. 33 This observation,
together with the observation that bone infection induces
osteoclastogenesis and bone loss, raises the possibility that
therapeutic blockade of RANKL could improve outcomes of
musculoskeletal infection. A 2022 study tested the effects of anti-
RANKL antibody therapy in comparison with the diphosphonate
zoledronic acid in a murine model of acute S aureus osteomyelitis. 49
Both treatments were effective in reducing infection-associated
osteolysis. However, zoledronic acid delayed the clearance of
bacterial burdens over time as measured by in vivo
bioluminescence. 49 Future studies are needed to determine how
therapeutic blockade of RANKL alters host immune responses and
bacterial killing during orthopaedic infection. Immunomodulatory
therapies also can be combined with antimicrobial agents that
target intracellular bacterial reservoirs to improve outcomes of
orthopaedic infection. A 2021 study determined that locally
delivered cell-penetrating antibiotics, in combination with
therapeutic blockade of the NLRP3 inflammasome, protected
articular cartilage and enhanced bacterial eradication in a murine
model of S aureus septic arthritis. 50 Taken together, these
observations suggest that characterization of antibiotic-protected
and immune-protected host niches can lead to the development of
new antimicrobial and immunomodulatory targets to improve the
treatment of orthopaedic infection.

Humanized Mice to Model Host-Pathogen

Interactions
Animal models of orthopaedic infection have been invaluable for
defining fundamental mechanisms of microbial pathogenesis,
testing novel treatments, and elucidating osteoimmunologic
crosstalk during orthopaedic infection. Yet, animal models cannot
fully recapitulate human disease, especially for microbial
pathogens that have evolved to predominantly infect humans. This
is particularly important for S aureus, which possesses a number of
toxins that are highly species-specific, including toxins with potent
biologic activity toward human cells but li le activity toward rodent
cells. 25 These observations have led investigators to create new
model systems for orthopaedic infection that incorporate human
cells or tissues. A 2021 study evaluated humanized mice in a model
of implant-associated osteomyelitis. 51 The development of
humanized mice typically occurs by engrafting human
hematopoietic stem cells onto mice that lack B and T lymphocytes
and other components of the murine immune system (eg, NOD-scid
IL2Rgammanull or NSG mice). Using this approach, humanized mice
were found to have increased susceptibility to implant-associated
osteomyelitis, with exacerbated weight loss, osteolysis, abscess
formation, and bacterial burdens relative to wild-type mice. 51
Accordingly, humanized mice will be valuable to basic and
translational scientists who seek to understand the pathobiology of
human orthopaedic infection. Moreover, these in vivo models are a
tractable solution to explore the contribution of human genetics to
orthopaedic infection risk, as mice can be engrafted with cells from
patients with known or suspected genotypic features that enhance
susceptibility to musculoskeletal disease.

Summary
Bone and joint infections remain a common and highly morbid
complication of trauma and orthopaedic surgery. The microbiology
of orthopaedic infection is heavily influenced by the inciting
disease mechanism, the presence of patient comorbidities, and the
virulence potential of infecting microorganisms. Effective and
tailored antimicrobial therapy depends on identification of the
infectious etiology and is further guided by evidence-based clinical
practice guidelines. Yet, a significant proportion of patients who
receive appropriate medical and surgical therapy for
musculoskeletal infection go on to develop chronic disease or life-
altering complications of infection. Therefore, ongoing translational
research leveraging preclinical models, patient cohorts, and human
biospecimens is a critical endeavor to identify new therapeutic
approaches for orthopaedic infection.

Key Study Points

 The microbiology of orthopaedic infection is heavily influenced by the mechanism of
disease initiation.
S aureus is the most common etiology of bone and joint infection across all disease
mechanisms.
Virulence features of successful musculoskeletal pathogens include the presence of
microbial adhesins that bind components of the skeletal extracellular matrix, biofilm
formation, the ability to evade or destroy immune effectors, and the propensity to
establish antibiotic-protected niches within host tissues.

Annotated References
1. Metsemakers W-J, Morgenstern M, Senneville E, et al: General
treatment principles for fracture-related infection:
Recommendations from an international expert group. Arch
Orthop Trauma Surg 2020;140:1013-1027. This article from the
Fracture-Related Infection Consensus Group summarizes general
treatment principles (diagnosis, classification, host optimization,
surgical principles, antimicrobial therapy, and follow-up) of
fracture-related infection. Level of evidence: V.
2. Schwarz EM, Parvizi J, Gehrke T, et al: 2018 International
Consensus Meeting on Musculoskeletal Infection: Research
priorities from the general assembly questions. J Orthop Res
2019;37:997-1006. This article outlines recommendations from the
2nd International Consensus Meeting on Musculoskeletal
Infection held in 2018. Delphi methodology was used to define a
subset of the 164 General Assembly questions that are of high
priority for future research. Level of evidence: V.
3. Li HK, Rombach I, Zambellas R, et al: Oral versus intravenous
antibiotics for bone and joint infection. N Engl J Med
2019;380:425-436. This study presents the results of a multicenter,
open-label, parallel-group, randomized, controlled, noninferiority
trial comparing oral versus intravenous antibiotics for the first 6
weeks of management of bone and joint infection. Level of
evidence: II.
4. Garcia Del Pozo E, Collazos J, Carton JA, Camporro D, Asensi V:
Factors predictive of relapse in adult bacterial osteomyelitis of
 long bones. BMC Infect Dis 2018; 18:635.
5. Lew DP, Waldvogel FA: Osteomyelitis. Lancet 2004;364: 369-379.
6. Berbari EF, Kanj SS, Kowalski TJ, et al: 2015 Infectious Diseases
Society of America (IDSA) Clinical Practice Guidelines for the
Diagnosis and Treatment of Native Vertebral Osteomyelitis in
Adults. Clin Infect Dis 2015;61:e26-e46.
7. Masters EA, Trombe a RP, de Mesy Bentley KL, et al: Evolving
concepts in bone infection: Redefining “biofilm”, “acute vs.
chronic osteomyelitis”, “the immune proteome” and “local
antibiotic therapy”. Bone Res 2019;7:20. This review article
summarizes current concepts in musculoskeletal infection, with a
focus on mechanisms of treatment recalcitrance, immune
responses, and novel treatment strategies.
8. Hotchen AJ, McNally MA, Sendi P: The classification of long
bone osteomyelitis: A systemic review of the literature. J Bone
Joint Infect 2017;2:167-174.
9. Cierny GIII, Mader JT, Penninck JJ: A clinical staging system for
adult osteomyelitis. Clin Orthop Relat Res 2003;414:7-24.
10. Benne JE, Dolin R, Blaser MJ: Mandell, Douglas, and Benne ’s
Principles and Practice of Infectious Diseases, ed 9. Elsevier, 2019.
This textbook is a comprehensive infectious diseases resource
with specific chapters focused on musculoskeletal infection and
the most common infecting pathogens.
11. Zimmerli W: 1 Online Resource. Wiley Blackwell, 2015.
12. Depypere M, Kuehl R, Metsemakers W-J, et al:
Recommendations for systemic antimicrobial therapy in fracture-
related infection: A consensus from an international expert
group. J Orthop Trauma 2020;34:30-41. This article summarizes
recommendations for systemic antimicrobial therapy from the
Fracture-Related Infection Consensus Group. Level of evidence:
V.
13. van Asten SAV, La Fontaine J, Peters EJG, Bhavan K, Kim PJ,
Lavery LA: The microbiome of diabetic foot osteomyelitis. Eur J
Clin Microbiol Infect Dis 2016;35:293-298.
14. Lipsky BA, Berendt AR, Cornia PB, et al: 2012 Infectious
Diseases Society of America Clinical Practice Guideline for the
Diagnosis and Treatment of Diabetic Foot Infections. Clin Infect
Dis 2012;54:e132-173.
15. Tande AJ, Patel R: Prosthetic joint infection. Clin Microbiol Rev
2014;27:302-345.
16. Crum-Cianflone NF: Bacterial, fungal, parasitic, and viral
myositis. Clin Microbiol Rev 2008;21:473-494.
17. Hannigan GD, Hodkinson BP, McGinnis K, et al: Culture-
independent pilot study of microbiota colonizing open fractures
and association with severity, mechanism, location, and
complication from presentation to early outpatient follow-up. J
Orthop Res 2014;32:597-605.
18. Agashe VM, Johari AN, Shah M, et al: Diagnosis of
osteoarticular tuberculosis: Perceptions, protocols, practices, and
priorities in the endemic and non-endemic areas of the World-A
WAIOT view. Microorganisms 2020;8:1312. This review manuscript
highlights the challenges in diagnosis of osteoarticular infections
caused by tuberculosis.
19. Hogan JI, Hurtado RM, Nelson SB: Mycobacterial
musculoskeletal infections. Infect Dis Clin 2017;31:369-382.
20. Bariteau JT, Waryasz GR, McDonnell M, et al: Fungal
osteomyelitis and septic arthritis. J Am Acad Orthop Surg
2014;22:390-401.
21. Urish KL, Cassat JE: Staphylococcus aureus osteomyelitis: Bone,
bugs, and surgery. Infect Immun 2020;88:e00932-19. This
manuscript reviews the epidemiology, treatment, and
pathophysiology of S aureus osteomyelitis.
22. Foster TJ: The MSCRAMM family of cell-wall-anchored surface
proteins of gram-positive cocci. Trends Microbiol 2019;27:927-941.
This review article discusses the microbial surface components
recognizing adhesive matrix molecule family of adhesins,
including proteins that have been reported to bind to
 components of the bone extracellular matrix and contribute to
biofilm formation.
23. Schilcher K, Horswill AR: Staphylococcal biofilm development:
Structure, regulation, and treatment strategies. Microbiol Mol Biol
Rev 2020;84:e00026-19. This review comprehensively covers the
development and physiology of staphylococcal biofilms.
24. Fi patrick F, Humphreys H, O’Gara JP: Evidence for icaADBC-
independent biofilm development mechanism in methicillin-
resistant Staphylococcus aureus clinical isolates. J Clin Microbiol
2005;43:1973-1976.
25. Tam K, Torres VJ: Staphylococcus aureus secreted toxins and
extracellular enzymes. Microbiol Spectr 2019;7(2). This review
article highlights the diverse array of secreted toxins produced by
S aureus.
26. de Jong NWM, van Kessel KPM, van Strijp JAG: Immune
evasion by Staphylococcus aureus. Microbiol Spectr 2019;7(2). This
review article summarizes mechanisms of immune evasion used
by S aureus.
27. Wang Y, Cheng LI, Helfer DR, et al: Mouse model of
hematogenous implant-related Staphylococcus aureus biofilm
infection reveals therapeutic targets. Proc Natl Acad Sci USA
2017;114:E5094-E5102.
28. Cassat JE, Hammer ND, Campbell JP, et al: A secreted bacterial
protease tailors the Staphylococcus aureus virulence repertoire to
modulate bone remodeling during osteomyelitis. Cell Host
Microbe 2013;13:759-772.
29. Claro T, Widaa A, O’Seaghdha M, et al: Staphylococcus aureus
protein A binds to osteoblasts and triggers signals that weaken
bone in osteomyelitis. PLoS One 2011;6:e18748.
30. Mendoza Bertelli A, Delpino MV, La ar S, et al: Staphylococcus
aureus protein A enhances osteoclastogenesis via TNFR1 and
EGFR signaling. Biochim Biophys Acta 2016;1862:1975-1983.
31. Lee LY, Miyamoto YJ, McIntyre BW, et al: The Staphylococcus
aureus Map protein is an immunomodulator that interferes with
 T cell-mediated responses. J Clin Invest 2002;110:1461-1471.
32. Gimza BD, Cassat JE: Mechanisms of antibiotic failure during
Staphylococcus aureus osteomyelitis. Front Immunol 2021;12:638085.
This review article discusses potential mechanisms of antibiotic
failure during musculoskeletal infection.
33. Krauss JL, Roper PM, Ballard A, et al: Staphylococcus aureus
infects osteoclasts and replicates intracellularly. mBio
2019;10:e02447-19. This study demonstrates that S aureus can
invade and replicate within osteoclasts both in vitro and in vivo.
34. Alder KD, Lee I, Munger AM, et al: Intracellular Staphylococcus
aureus in bone and joint infections: A mechanism of disease
recurrence, inflammation, and bone and cartilage destruction.
Bone 2020;141:115568. This review article focuses on how
intracellular bacteria contribute to the pathogenesis of
musculoskeletal infection.
35. Kahl BC, Becker K, Loffler B: Clinical significance and
pathogenesis of staphylococcal small colony variants in persistent
infections. Clin Microbiol Rev 2016;29:401-427.
36. Cheng AG, McAdow M, Kim HK, Bae T, Missiakas DM,
Schneewind O: Contribution of coagulases towards Staphylococcus
aureus disease and protective immunity. PLoS Pathog
2010;6:e1001036.
37. Liu C, Bayer A, Cosgrove SE, et al: Clinical practice guidelines
by the Infectious Diseases Society of America for the treatment
of methicillin-resistant Staphylococcus aureus infections in adults
and children. Clin Infect Dis 2011;52:e18-e55.
38. Gosselin RA, Roberts I, Gillespie WJ: Antibiotics for preventing
infection in open limb fractures. Cochrane Database Syst Rev
2004;2004(1):CD003764.
39. Chang Y, Bhandari M, Zhu KL, et al: Antibiotic prophylaxis in
the management of open fractures: A systematic survey of
current practice and recommendations. JBJS Rev 2019;7:e1. This
systematic survey of the literature reviews the spectrum of
 current clinical practices and recommendations for antibiotic
prophylaxis of open fractures. Level of evidence: V.
40. Parvizi J, Pawasarat IM, Azzam KA, Joshi A, Hansen EN, Bozic
KJ: Periprosthetic joint infection: The economic impact of
methicillin-resistant infections. J Arthroplasty 2010;25:103-107.
41. Premkumar A, Kolin DA, Farley KX, et al: Projected economic
burden of periprosthetic joint infection of the hip and knee in the
United States. J Arthroplasty 2021;36:1484-1489.e3. This study
reports the recent and projected hospital costs of PJI of the hip
and knee using data from the Nationwide Inpatient Sample
database. Level of evidence: V.
42. Tubb CC, Polkowksi GG, Krause B: Diagnosis and prevention of
periprosthetic joint infections. J Am Acad Orthop Surg
2020;28:e340-e348. This article presents the American Academy of
Orthopaedic Surgeons Clinical Practice Guideline for Diagnosis
and Prevention of Periprosthetic Joint Infections. Level of
evidence: V.
43. Osmon DR, Berbari EF, Berendt AR, et al: Diagnosis and
management of prosthetic joint infection: Clinical practice
guidelines by the Infectious Diseases Society of America. Clin
Infect Dis 2013;56:e1-e25.
44. Bernard L, Arvieux C, Brunschweiler B, et al: Antibiotic therapy
for 6 or 12 weeks for prosthetic joint infection. N Engl J Med
2021;384:1991-2001. This study presents the results of an open-
label, randomized, controlled, noninferiority trial comparing 6
versus 12 weeks of antibiotic therapy in patients with
microbiologically confirmed prosthetic joint infection. Level of
evidence: II.
45. Harro JM, Shirtliff ME, Arnold W, et al: Development of a novel
and rapid antibody-based diagnostic for chronic Staphylococcus
aureus infections based on biofilm antigens. J Clin Microbiol
2020;58:e01414-19. This study evaluated the diagnostic utility of
antibody-based assays for S aureus biofilm antigens for the
 diagnosis of osteomyelitis in animal models and orthopaedic
implant-associated infection in human synovial fluid samples.
46. Muthukrishnan G, Beck CA, Owen JR, Xie C, Kates SL, Daiss JL:
Serum antibodies against Staphylococcus aureus can prognose
treatment success in patients with bone infections. J Orthop Res
2021;39:2169-2176. This study reports the development of a
multiplex assay to assess humoral immune responses during S
aureus musculoskeletal infection. The assay showed prognostic
value when applied to samples from the AO Trauma Clinical
Priority Program Bone Infection Registry.
47. de Mesy Bentley KL, Trombe a R, Nishitani K, et al: Evidence of
Staphylococcus aureus deformation, proliferation, and migration in
canaliculi of live cortical bone in murine models of osteomyelitis.
J Bone Miner Res 2017;32:985-990.
48. Masters EA, de Mesy Bentley KL, Gill AL, et al: Identification of
Penicillin Binding Protein 4 (PBP4) as a critical factor for
Staphylococcus aureus bone invasion during osteomyelitis in mice.
PLoS Pathog 2020;16:e1008988. This study reports the
identification of penicillin binding protein 4 as an important
contributor to S aureus bone invasion and antibiotic recalcitrance
in a murine model of implant-associated osteomyelitis.
49. Kobayashi H, Fujita R, Hiratsuka S, et al: Differential effects of
anti-RANKL monoclonal antibody and zoledronic acid on
necrotic bone in a murine model of Staphylococcus aureus-induced
osteomyelitis. J Orthop Res 2022;40(3):614-623. This preclinical
study reports the effect of zoledronic acid or anti-RANKL
antibody therapy on bacterial clearance and osteolysis in a
murine model of acute S aureus osteomyelitis.
50. Kwon H-K, Lee I, Yu KE, et al: Dual therapeutic targeting of
intra-articular inflammation and intracellular bacteria enhances
chondroprotection in septic arthritis. Sci Adv 2021;7:eabf2665.
This study reports a new therapeutic strategy consisting of locally
delivered, cell-penetrating antibiotics combined with blockade of
the NLRP3 inflammasome to treat S aureus septic arthritis.
51. Muthukrishnan G, Wallimann A, Rangel-Moreno J, et al:
Humanized mice exhibit exacerbated abscess formation and
osteolysis during the establishment of implant-associated
Staphylococcus aureus osteomyelitis. Front Immunol 2021;12:651515.
This study reports enhanced pathogenesis of S aureus implant-
associated osteomyelitis in humanized mice.
C H AP T E R 1 9

Applications of Three-
Dimensional Technologies in
Orthopaedic Surgery
Daniel H. Wiznia MD, FAAOS, Lisa Lattanza MD, FAAOS

Dr. Wiznia or an immediate family member has stock or stock options held in Intellijoint. Dr.
Lattanza or an immediate family member is a member of a speakers’ bureau or has made paid
presentations on behalf of Acumed, LLC; serves as a paid consultant to or is an employee of
Acumed, LLC and Materialise; has stock or stock options held in Mylad; and serves as a board
member, owner, officer, or committee member of the American Orthopaedic Association, the
American Society for Surgery of the Hand, and The Perry Initiative.

ABSTRACT
Three-dimensional technology is transforming patient care by
providing personalized tools for surgeons to customize treatments
for their patients. It is important to discuss some cu ing-edge,
emerging three-dimensional technologies. Orthopaedic surgery is
currently experiencing a three-dimensional technology revolution
in four major uses: anatomic models, patient-specific tools, custom
implants, and robotics.
Keywords: 3D printing; 3D surgical planning; custom implants;
custom instruments; personalized surgery

Introduction
There is currently a three-dimensional (3D) technologic revolution
in orthopaedic surgery. Underlying technologies are maturing (eg,
computer processing, 3D imaging, image-processing capabilities,
artificial intelligence, mechatronics, materials science, and 3D
printing), enabling the development of personalized medical
devices and surgical techniques. In addition, as FDA regulation has
matured, there has been an emerging effort to develop point-of-care
manufacturing centers. It is important to review new developments
within four major uses of 3D technology: anatomic models, patient-
specific tools, custom implants, and robotics (Table 1).

Table 1
Three-Dimensional Applications in Orthopaedic Surgery

Application Description
Model creation Using high-resolution CT and MRI to create virtual models
3D The ability to interact with 3D anatomic models to plan surgeries
preoperative
planning
Patient-specific Building custom instrumentation as a result of 3D surgical planning
instrumentation
Robotics and The ability to accurately position implants and instrumentation
computer intraoperatively with the assistance of image model-based robotics
navigation platforms
Custom 3D Custom implantable medical devices that are manufactured specifically
implants for a specific patient’s anatomy and pathology
Intraoperative The ability to collect high-resolution imaging intraoperatively, process the
3D imaging imaging to create 3D models, and allow the surgeon to interact with these
models and make surgical decisions intraoperatively
3D printing Modalities allow for the creation of 3D printed instrumentation, implants,
and tissue

Model Creation
As discussed in a 2020 study, the cornerstone of 3D technology in
orthopaedic surgery is the ability to create patient-specific 3D
models from high-resolution medical imaging. 1 The development
of accessible software tools to process 3D imaging (CT scans or
MRI) to create 3D models (steps include identifying anatomic
structures using special image segmentation software that uses
both automated and manual components) 2 and subsequent custom
interventions (ie, anatomic models, surgical plans, 3D printed
instruments, and implants) has provided surgeons the ability to
provide patient-specific treatments at hospital centers across the
country. 3 The predominant image-processing tools in current use
include software packages such as Simpleware ScanIP (Synopsis),
Osirix, 3D Slicer (open access), and MIMICS (Materialise Inc).

3D Preoperative Planning

3D Anatomic Models
3D anatomic models allow the surgeon and engineer to manipulate
a 3D representation of the anatomy. 3 These models can be used for
virtual preoperative planning, in which the effects of osteotomies
and the fit of implant selection can be simulated either on a two-
dimensional display or in a virtual reality environment 1 , 2 (Figure
1). 3D surgical planning of deformity cases has demonstrated that
two orthogonal radiographs do not capture a rotational component
of the deformity, which is commonly recognized during the 3D
modeling process by comparing the surgical side with the
contralateral healthy side. 4 , 5 Surgeons have supported the utility
of these preoperative modeling techniques, with the literature
demonstrating improved operating metrics (eg, length of time in
the operating room, functional outcomes, reduced complications,
decreased blood loss, and rates of transfusion). 6 , 7
 Figure 1 Steps involved in virtual preoperative planning using a three-
dimensional anatomic model.A, Imaging is performed. B, Head and cervical CT
(sagittal, coronal, and axial views). C, 3D Printing for Anatomic Disease model.
D, 3D printed model of the osteoarthritic knee with a subluxated patella to assist
the arthroplasty surgeon with preoperative surgical planning to assess patellar
tracking.(Reproduced with permission from the Yale School of Medicine.)

The 3D models can come to life as 3D prints, to be physically

examined by the surgical team 8 , 9 and the patient, 6 , 10 can be
sterilized and manipulated during a surgical case, and are regularly
used for simulating surgery 7 and prebending/contouring of
hardware (commonly for acetabular fractures). 3 , 11 Surgeons have
found that these models facilitate understanding of the anatomy
and improve their surgical technique. 8 , 12 As 3D printed materials
have improved to allow for more machining and instrumentation,
they have become widely used to train medical students, residents,
and fellows. 10 In addition, these models are becoming more widely
available, with the advent of FDA-approved point-of-care 3D
printing pathways. 9

Patient-Specific Instruments
Patient-specific instruments, such as drill guides and cu ing
guides, fit to the unique bone shape with cortical read, providing a
personalized navigation template 7 for correction of deformity.
These instruments are 3D printed and sterilized preoperatively,
and then used during surgery to assist with drill trajectory,
osteotomies, and component positioning and orientation (Figure 2).
These instruments have a proven track record and efficacy with
total knee arthroplasty 13 and have been gradually gaining
acceptance in spine, upper extremity, 4 , 14 deformity correction, and
trauma applications. 11 Regarding spine surgery, 3D printed drill
guides provide guidance in terms of screw trajectory, depth, and
size, limiting the risk of injury to neurovascular structures. 6 , 10 , 15 A
2021 study has shown that 3D printed drill guides demonstrated
improvements in accuracy of pedicle screw placement, decreased
blood loss, reduced surgical times, and reduced fluoroscopic times.
16
Studies have shown that these benefits of reducing blood loss,
fluoroscopy time, and surgical time have also been demonstrated in
pediatric orthopaedic surgery, 1 , 7 , 17 , 18 total joint arthroplasty, and
trauma surgery. 5 , 8 , 11 , 19 - 21
 Figure 2 Steps involved in patient-specific instrumentation for surgical
treatment of deformity.A, AP radiograph of the knee. B, Axial MRI of the knee. C,
Images showing tibial osteoarthritic deformity, planned resection, three-
dimensional (3D) virtual placement of the tibial baseplate implant, and patient-
specific instruments used to position varus/valgus, slope, and rotation of the
tibial baseplate for total knee arthroplasty. D, 3D-guided surgical resection, total
knee arthoplasty. E, Postoperative radiograph of the knee implant in place.
(Reproduced with permission from the Yale School of Medicine.)

Robotics and Computer Navigation

Robotic arm–assisted total joint arthroplasty requires the creation
of a 3D model from a high-resolution CT scan. 22 After a 3D surgical
plan has been prepared, the bony anatomy is registered to the 3D
model, and a robot assists in executing the plan. Studies have
demonstrated that the robotic system provides accurate and
reliable cuts consistent with the 3D plan, and more accurate
positioning of components when compared with manual
techniques. 22 Recent studies have demonstrated improved
functional scores and implant longevity. 23 - 25
3D Custom Implants
3D custom implants are finding a broad array of applications. A
variety of materials are used for 3D printed implants, including
titanium and polyether ether ketone. 7 For example, in Europe and
China, custom spine implants have been 3D printed in porous
titanium to treat bone defects caused by tumor resections. 6 , 26 - 28 In
the United States, based on a patient’s unique anatomy, Conformis
produces custom and personalized hip (titanium) and knee (cobalt-
chromium, titanium, and polyethylene) replacements. 2 To treat
patients with severe acetabular defects and abnormal femoral
anatomy, Zimmer Biomet custom manufactures a personalized
acetabular component, which is machined from titanium stock
using computer numerical control. 3D customized printed revision
components are not currently approved in the United States. 2 , 29
Zimmer Biomet also produces a limited number of machined
custom hip stems for total hip arthroplasty and custom glenoid
implants for reverse total shoulder arthroplasty (Figure 3).
 Figure 3 Steps involved in creating three-dimensional (3D) custom implants.A,
CT scan of the thigh. B, 3D model of the femur. C, Computer-aided designs of
implants. D, The meshed model retaining bone density data. E, Finite element
analysis for implant selection. The proximal femur fracture is modeled with
fixation using a blade plate in an osteoporotic model.(Reproduced with
permission from the Yale School of Medicine.)

Intraoperative 3D Imaging
New high-resolution intraoperative CT imaging technologies (such
as O-Arm [Medtronic], Iso-C 3D [Siemens], Airo [Brainlab]) assist
surgeons intraoperatively to navigate complex anatomy and
conduct minimally invasive surgery. 30 This technology has
demonstrated marked improvement in the accuracy of implant
positioning, but a 2021 study has shown it to result in longer
surgical times. 30 Modern 3D intraoperative scanners have improved
resolution, increased the field of view, and improved image-
processing software, which is able to reduce distortion from metal
artifact. Intraoperative 3D imaging has demonstrated its utility in
foot and ankle, trauma, spine, and tumor surgery.
Emerging Technologies

Biologic Materials
3D printing of biologic musculoskeletal tissues (ie, cartilage, bone,
tendons) is actively being investigated. 31 , 32 According to a 2020
study, 3D printing technology with increased resolution has
improved the ability to produce complex composite tissues with
varying material properties. 33 Musculoskeletal research is focused
on reproducing articular cartilage, bone, meniscus, and
intervertebral disks. The integration of the use of live human-
derived pluripotent cells in the development of cartilage 3D
printing holds promise. 3 , 33 Custom printing of anatomically
complex bone graft substitute is also being developed 3 with the
promise of loading drugs, biologic agents, and proteins as carriers
within the 3D printed material 2 (known as four-dimensional
printing). 5 , 6 Current fields of research are focusing on developing
four-dimensional printed implants such as custom bone graft with
mapped vascular progenitor cells and signaling molecules, or
implants that can grow and adapt with pediatric patients by
changing the properties of biomaterials. 34

Augmented Reality
The development of intraoperative use of 3D augmented reality
systems is being pursued in oral surgery, hip and knee surgery, and
spine surgery. 35 These systems are in their infancy and will require
the technologic refinement of 3D visualization algorithms, accurate
model registration methodology, and reliable methods to establish
common reference points and arrays. 35 These systems will likely
become more widespread as the technology (eg, headsets,
algorithms) matures.

Summary
The use of 3D technology in orthopaedic surgery is advancing at a
steady pace. Over the next few years, growth can be expected in
point-of-care printing centers within hospital systems, the
advancement of FDA regulatory approval of custom implant
systems, and the acceptance and standardization of robotic surgery.
The promise of improved outcomes and function will continue to
support the investment in personalized surgical techniques,
instruments, implants, and robotics.

Key Study Points

3D technology allows for custom surgery for patients with the goal to improve patient
outcomes.
The FDA is developing a point-of-care 3D printing pathway for hospital systems; this
will eventually allow the onsite custom fabrication of implantable devices.
Robotics improves accuracy and customization and facilitates complex cases with
demonstrated improvements in patient outcomes.
Bioprinting is an emerging technology with the promise to manufacture custom
tissue.

Annotated References
1. Baraza N, Chapman C, Zakani S, Mulpuri K: 3D – Printed patient
specific instrumentation in corrective osteotomy of the femur and
pelvis: A review of the literature. 3D Print Med 2020;6:34. The
authors present a systematic review of the literature examining
the use of patient-specific instrumentation to treat pediatric
deformity. Level of evidence: IV.
2. Wong KC: 3D-printed patient-specific applications in
orthopedics. Orthop Res Rev 2016;8:57.
3. Bagaria V, Bhansali R, Pawar P: 3D printing- creating a blueprint
for the future of orthopedics: Current concept review and the
road ahead! J Clin Orthop Trauma 2018;9:207-212.
4. de Muinck Keizer RJO, Lechner KM, Mulders MAM, Goslings
JC, Schep NWL, Eygendaal D: Three-dimensional virtual
planning of corrective osteotomies of distal radius malunions: A
 systematic review and meta-analysis. Strategies Trauma Limb
Reconstr 2017;12:77-89.
5. Lal H, Patralekh MK: 3D printing and its applications in
orthopaedic trauma: A technological marvel. J Clin Orthop
Trauma 2018;9:260-268.
6. Cai H, Liu Z, Wei F, Yu M, Xu N, Li Z: 3D printing in spine
surgery, in Zheng G, Tian W, Zhuang X, eds: Intelligent
Orthopaedics: Artificial Intelligence and Smart Image-Guided
Technology for Orthopaedics. Springer, 2018, vol 1093, pp 345-
359.
7. Tack P, Annemans L, Victor J, Gemmel P: 3D-printing
techniques in a medical se ing: A systematic literature review.
Biomed Eng Online 2016;15:115.
8. Mishra A, Verma T, Vaish A, Vaish R, Maini L, Vaishya R: Virtual
preoperative planning and 3D printing are valuable for the
management of complex orthopaedic trauma. Chin J Traumatol
2019;22:350-355. An observational study of 91 trauma cases
managed with virtual preoperative planning and 3D printing is
presented. Level of evidence: IV.
9. Schulze M, Gosheger G, Bockholt S, et al: Complex bone tumors
of the trunk-the role of 3d printing and navigation in tumor
orthopedics: A case series and review of the literature. J Pers Med
2021;11:517. The authors present a case series of five patients with
complex bone tumors of the trunk who were treated with 3D
printing and navigation. A review of the literature is included.
Level of evidence: IV.
10. Lopez CD, Boddapati V, Lee NJ, et al: Three-dimensional
printing for preoperative planning and pedicle screw placement
in adult spinal deformity: A systematic review. Global Spine J
2020;11(6):936-949. A systematic review, using the PRISMA
guidelines, of the use of 3D printing to assist with the
management of adult spinal deformity is presented. Level of
evidence: IV.
11. Marinescu R, Popescu D, Laptoiu D: A review on 3D-printed
templates for precontouring fixation plates in orthopedic surgery.
J Clin Med 2020;9:1-17. A systematic review of the literature using
PRISMA guidelines on 3D-printed anatomic models to be used
for precontouring plates for orthopaedic surgery is presented.
Level of evidence: IV.
12. Xie L, Chen C, Zheng W, Chen H, Cai L, Zhang Y: Three-
dimensional printing assisted ORIF versus conventional ORIF for
tibial plateau fractures: A systematic review and meta-analysis.
Int J Surg 2018;57:35-44.
13. Vaishya R, Vijay V, Agarwal AK, Vaish A: Computed
tomography based 3D printed patient specific blocks for total
knee replacement. J Clin Orthop Trauma 2018;9:254-259.
14. Chen C, Cai L, Zhang C, Wang J, Guo X, Zhou Y: Treatment of
die-punch fractures with 3D printing technology. J Invest Surg
2018;31:385-392.
15. Wen Z-J, Gao Z-C, Lu T, Wang Y-B, Liang H, He X-J: Comparison
of the effect of navigation template assisted spinal pedicle
fixation and traditional pedicle screw fixation: A meta-analysis.
Article in Chinese. Zhongguo Gu Shang 2018;31:1069-1076.
16. Azimi P, Yazdanian T, Benzel EC, Azimi A, Montazeri A: 3D-
printed navigation template in cervical spine fusion: A systematic
review and meta-analysis. Eur Spine J 2021;30:389-401. The authors
present a systematic review and meta-analysis examining the
effectiveness of 3D printed navigation templates to assist with
cervical spine fusion, compared with conventional surgery. Level
of evidence: III.
17. Bauer AS, Storelli DAR, Sibbel SE, McCarroll HR, La anza LL:
Preoperative computer simulation and patient-specific guides are
safe and effective to correct forearm deformity in children. J
Pediatr Orthop 2017;37:504-510.
18. Raza M, Murphy D, Gelfer Y: The effect of three-dimensional
(3D) printing on quantitative and qualitative outcomes in
paediatric orthopaedic osteotomies: A systematic review. EFORT
 Open Rev 2021;6:130-138. A systematic review, with the use of
PRISMA guidelines, of the use of 3D printing for pediatric
orthopaedics is presented. Level of evidence: IV.
19. Gonzalez-Alonso M, Hermida-Sanchez M, Martinez-Seijas P,
Ruano-Ravina A: Application of 3D printing in the treatment of
appendicular skeleton fractures: Systematic review and meta-
analysis. J Orthop Res 2021;39(10):2083-2092. A systematic review
and meta-analysis of the application of 3D printing in the
surgical management of complex fractures of the appendicular
skeleton is presented. Level of evidence: III.
20. Levesque JN, Shah A, Ekhtiari S, Yan JR, Thornley P, Williams
DS: Three-dimensional printing in orthopaedic surgery: A
scoping review. EFORT Open Rev 2020;5:430-441. A review on 3D
printing within orthopaedic surgery is presented, examining the
current uses and geographic trends. Level of evidence: III.
21. Wang J, Wang X, Wang B, et al: Comparison of the feasibility of
3D printing technology in the treatment of pelvic fractures: A
systematic review and meta-analysis of randomized controlled
trials and prospective comparative studies. Eur J Trauma Emerg
Surg 2021;47(6):1699-1712. A systematic review and meta-analysis
of randomized controlled trials and prospective comparative
studies comparing the feasibility of 3D printing technology in the
management of pelvic fractures is presented. Level of evidence:
IV.
22. Hampp EL, Chughtai M, Scholl LY, et al: Robotic-arm assisted
total knee arthroplasty demonstrated greater accuracy and
precision to plan compared with manual techniques. J Knee Surg
2019;32(3):239-250.
23. Iturriaga C, Salem HS, Ehiorobo JO, Sodhi N, Mont MA:
Robotic-assisted versus manual unicompartmental knee
arthroplasty: A systematic review. Surg Technol Int 2020;37:275-
279. A review to compare the outcomes of manual versus robotic-
assisted unicompartmental knee arthroplasty is presented. Level
of evidence: IV.
24. Dretakis K, Igoumenou VG: Outcomes of robotic-arm-assisted
medial unicompartmental knee arthroplasty: Minimum 3-year
follow-up. Eur J Orthop Surg Traumatol 2019;29:1305-1311. A
cohort study is presented in which 51 patients were followed for 3
years after robotic-assisted unicompartmental knee arthroplasty.
Level of evidence: IV.
25. Lonner JH, Klement MR: Robotic-assisted medial
unicompartmental knee arthroplasty: Options and outcomes. J
Am Acad Orthop Surg 2019;27:e207-e214. The authors present a
review article on robotic-assisted medial unicompartmental knee
arthroplasty. Level of evidence: IV.
26. Xu N, Wei F, Liu X, et al: Reconstruction of the upper cervical
spine using a personalized 3D-printed vertebral body in an
adolescent with Ewing sarcoma. Spine (Phila Pa 1976) 2016;41:E50-
E54.
27. Kim D, Lim JY, Shim KW, et al: Sacral reconstruction with a 3D-
printed implant after hemisacrectomy in a patient with sacral
osteosarcoma: 1-year follow-up result. Yonsei Med J 2017;58:453-
457.
28. Wei R, Guo W, Ji T, Zhang Y, Liang H: One-step reconstruction
with a 3D-printed, custom-made prosthesis after total en bloc
sacrectomy: A technical note. Eur Spine J 2017;26:1902-1909.
29. Baauw M, van Hellemondt GG, van Hooff ML, Spruit M: The
accuracy of positioning of a custom-made implant within a large
acetabular defect at revision arthroplasty of the hip. Bone Joint J
2015;97-B:780-785.
30. Kumar V, Baburaj V, Patel S, Sharma S, Vaishya R: Does the use
of intraoperative CT scan improve outcomes in orthopaedic
surgery? A systematic review and meta-analysis of 871 cases. J
Clin Orthop Trauma 2021;18:216-223. The authors present a
systematic review and meta-analysis of patients undergoing
orthopaedic surgery with the use of intraoperative 3D imaging.
Level of evidence: IV.
31. Trauner KB: The emerging role of 3D printing in arthroplasty
and orthopedics. J Arthroplasty 2018;33:2352-2354.
32. Zheng X, Huang J, Lin J, et al: 3D bioprinting in orthopedics
translational research. J Biomater Sci Polym Ed 2019;30:1172-1187.
A review of the state of 3D bioprinting in orthopaedics
translational research is presented. Level of evidence: V.
33. Larsen CG, Stapleton EJ, Sgaglione J, et al: Three-dimensional
bioprinting in orthopaedics. JBJS Rev 2020;8(4):e0204. An expert
review of 3D bioprinting in orthopaedics is presented. Level of
evidence: V.
34. Javaid M, Haleem A: Significant advancements of 4D printing in
the field of orthopaedics. J Clin Orthop Trauma 2020;11:S485-S490.
An expert review of 4D printing techniques in orthopaedics is
presented. Level of evidence: V.
35. Ma L, Fan Z, Ning G, Zhang X, Liao H: 3D visualization and
augmented reality for orthopedics. Adv Exp Med Biol
2018;1093:193-205.
C H AP T E R 2 0

Inflammation and Immunology

Benjamin F. Ricciardi MD, FAAOS, Edward M. Schwarz PhD

Dr. Ricciardi or an immediate family member serves as a paid consultant to or is an employee of

DePuy, a Johnson & Johnson Company and has received research or institutional support from
Johnson & Johnson. Dr. Schwarz or an immediate family member is a member of a speakers’ bureau
or has made paid presentations on behalf of Asahi KASEI Pharma Corporation; serves as a paid
consultant to or is an employee of Asahi KASEI Pharma Corporation, DePuy, a Johnson & Johnson
Company, Integrated Biotechnology, MedImmune, Musculoskeletal Transplant Foundation, and
Regeneron; has stock or stock options held in Parvizi Surgical Innovations, LLC, and Telephus
Biosciences; has received research or institutional support from DePuy, a Johnson & Johnson
Company, Eli Lilly, and Telephus; and has received nonincome support (such as equipment or
services), commercially derived honoraria, or other non–research-related funding (such as paid
travel) from Telephus Biosciences.

ABSTRACT
Host responses to trauma, infection, and diseases are central to all
orthopaedic injury repairs, and thus a fundamental understanding of
the immediate, acute, chronic, and lifelong molecular and cellular
mechanisms that govern inflammation and immunology is critical for
an understanding of musculoskeletal disease. It is important to be
knowledgeable about basic immunology, including innate immune
responses driven by proinflammatory cytokines and chemokines from
myeloid cells that initiate host defense and tissue repair, and its
transition to antigen-specific acquired immunity and lifelong
protection against pathogens by lymphocytes. As sustained
production of proinflammatory cytokines (tumor necrosis factor,
interleukins 1 and 6) leads to chronic inflammation that inhibits tissue
repair and promotes immune-mediated inflammatory disorders (such
as inflammatory arthritis), new small-molecule drugs and biologics
have emerged as standards of care. Additionally, there have been
transformative advances in cancer immune checkpoint regulator
therapy (programmed cell death protein 1 and programmed cell death
ligand 1 inhibitors). As all areas of medicine have been dramatically
affected by the COVID-19 pandemic, the cytokine storm, described as
a mechanism of severe acute respiratory syndrome, and the
fundamentals of active vaccinations (traditional protein antigen,
replication-defective DNA viral vectors, and messenger RNA
nanoparticles) versus passive immunization (convalescent sera and
monoclonal antibodies) are important topics as well as the limitations
of immunization approaches, including nonneutralizing antibodies,
transient immunity, and breakthrough strains. Inflammation and
immunology are two essential translational science disciplines that
need to be considered in understanding pathophysiology and
mechanisms of many emerging disease-modifying drugs for
orthopaedic disorders.
Keywords: active vaccination; biologics; checkpoint inhibition;
cytokines; inflammation; innate immunity; passive immunization

Introduction
Trauma and environmental insults to the human body trigger an
immediate innate immune response to endogenous and exogenous
factors that result in local inflammation proportionate to the noxious
stimulus. For effective tissue repair, the acute insult needs to be
resolved by phagocytic cells (neutrophils and macrophages) that are
recruited into the tissue from the blood. Phagocytic cells are
responsible for clearing debris, invading pathogens, and dead
(necrotic) and dying (apoptotic) cells. Additionally, these
inflammatory cells can further amplify this innate immune response
by producing cytokines and chemokines that lead to edema and
further tissue catabolism, which is the etiology of chronic
musculoskeletal diseases such as rheumatoid arthritis. In the cases of
pathogenic challenge and neoplasia, the phagocytic cells present
antigens to helper T cells that orchestrate acquired cellular and
humoral immune responses. It is important to discuss the
fundamentals of these innate and adaptive immune responses and the
molecular and cellular pathways that control them, many of which can
be targeted by specific drugs and biologic antagonists. Immunizations
work but there are limitations to their effectiveness.

Innate Immunity and Inflammation

All eukaryotic cells are susceptible to infection by viruses and
bacteria, and thus have evolved intracellular triggers and responses to
defend themselves against pathogens. These intracellular defense
mechanisms include the interferon (IFN)-induced double-stranded
RNA-dependent protein kinase that shuts down protein synthesis in
virus-infected cells, 1 xenophagy that mediates degradation of
pathogens in membrane-bound compartments, and IFN-regulated
guanosine triphosphatases that promote rupture of pathogen-
containing vacuoles and microbial degradation. 2 Multicellular
organisms have the additional burden of protecting their uninfected
cells from infected and traumatized cells within a tissue. Hence, they
have evolved intercellular mechanisms that rely on soluble proteins
(cytokines and chemokines) released from the damaged cells that
signal the healthy cells to protect themselves by inducing intracellular
immune mechanisms, and recruit activated phagocytes to clear the
necrotic and apoptotic cells and invaders. Collectively, these molecular
and cellular immediate-response systems are known as innate
immunity, which is highly conserved from fruit flies to humans. 3
There are two central signaling pathways that are used in innate
immunity. The first is the Toll-like receptor (TLR) signaling pathway,
in which transmembrane receptors recognize foreign molecules or
pathogen-associated molecular pa erns (PAMPs), 4 which cannot be
synthesized by eukaryotic cells (Figure 1). These include flagella and
bacterial cell wall components. There also are biochemicals that are
released from necrotic host cells that act as TLR ligands. These include
DNA and RNA and are referred to as damage-associated molecular
pa erns (DAMPs). Once TLRs are activated by PAMPs or DAMPs, 4 , 5
they initiate signal transduction through the nuclear factor kappa B
pathway, which results in proinflammatory cytokine synthesis within
minutes. 6 These proinflammatory cytokines, which include IFNs,
tumor necrosis factor (TNF), and interleukins (ILs), constitute the
second central signaling event during innate immune responses
(Figure 2). TNF receptor signaling activates the nuclear factor kappa B
cascade, similar to TLR signaling, 7 but it also activates apoptosis
through its death domain. 8 Thus, TNF signaling initiates and
amplifies inflammation by inducing the synthesis of other
proinflammatory molecules such as IL-1, IL-6, and prostaglandins, and
commences the end of inflammation by initiating programmed cell
death in all of the inflammatory cells recruited into the tissue. Once all
the PAMPs and DAMPs are cleared from the tissue by the
inflammatory macrophages (referred to as M1 macrophages), these
cells undergo apoptosis and are cleared by scavenger macrophages
(referred to as M2 macrophages), and the tissue returns to
homeostasis. 9
Figure 1 Illustration of Toll-like receptor (TLR) signaling.Inflammation is initiated by
TLR signaling in response to molecules from microbes that cannot be synthesized
by eukaryotic cells (pathogen-associated molecular patterns) and intracellular
biochemicals (damage-associated molecular patterns) that are released from
necrotic host cells. Of note is that other endogenous ligands (eg, uric acid crystals)
can also activate TLRs and can lead to inflammatory joint disease (gout). TLR
signaling is initiated at the plasma membrane and at intracellular compartments.
After stimulation by TLR ligands directly or in combination with accessory molecules
such as CD14, MD2, and CD36, TLRs dimerize, and signal transduction occurs via
adaptor molecules such as myeloid differentiation factor 88 (MYD88), Toll/IL-1R
domain-containing adaptor-inducing interferon beta (TRIF), Toll/interleukin-1 receptor
domain-containing adaptor protein (TIRAP), and TRIF-related adaptor molecule
(TRAM). This leads to activation of transcription factors in the nucleus, including
nuclear factor kappa B (NFκB) and interferon regulatory factors (IRFs), and results
in proinflammatory cytokine and chemokine synthesis, which initiate inflammation in
the tissue.(Redrawn with permission from Nature, Rakoff-Nahoum S, Medzhitov R:
Toll-like receptors and cancer. Nat Rev Cancer 2009;9[1]:57-63.)
Figure 2 Illustration of proinflammatory cytokine signaling and biologic therapies for
selective inhibition.Following Toll-like receptor signaling, proinflammatory cytokines
are produced and amplify innate immunity by inducing more proinflammatory
cytokines and chemokines, which results in edema, inflammatory cell infiltration,
angiogenesis, and tissue catabolism. Tumor necrosis factor (TNF) is at the apex of
this proinflammatory cascade and signals through TNF receptor–associated factors
(TRAFs) that activate the nuclear factor kappa B (NFκB) transcription factor to
synthesize downstream gene expression. TNF also initiates the apoptosis program
through TNF receptor–associated death domain (TRADD) proteins. The role of TNF
overexpression in the pathogenesis of chronic proinflammatory diseases such as
inflammatory arthritis, psoriasis, and Crohn disease has been proven by the
establishment of anti-TNF biologics as a standard-of-care treatment. Interferons and
interleukins signal through Janus kinases (JAKs) and signal transducer and activator
of transcription (STAT) proteins. These pathways are also upregulated in rheumatoid
arthritis, psoriatic arthritis, and ankylosing spondylitis. Monoclonal antibodies against
the cytokines (eg, ustekinumab) and oral small-molecule JAK inhibitors (eg,
tofacitinib) are now commonly used as second-line therapies in patients who have
inadequate responses to anti-TNF therapy.(Reproduced from Pedersen J, Coskun
M, Soendergaard C, Salem M, Nielsen OH: Inflammatory pathways of importance for
management of inflammatory bowel disease. World J Gastroenterol 2014;20[1]:64-
77.)
Orthopaedic Disease From Chronic
Inflammation
In addition to its critical role in host defense, innate immunity also
initiates tissue repair responses, including angiogenesis, recruitment
of mesenchymal stem cells, and the induction of growth and
differentiation factors (eg, bone morphogenetic proteins). 10 However,
if proinflammatory cytokine expression persists, so does tissue
catabolism, which can lead to musculoskeletal disease (Table 1).
Certain chronic inflammatory diseases can be caused by perpetual
exposure to PAMPs and DAMPs, such as deep bacterial infections or
implant wear debris–induced osteolysis. 11 In these cases, cure often
requires surgical elimination of the proinflammatory stimulator. There
also are genetic mutations that lead to exaggerated innate immune
responses, including chronic recurrent multifocal osteomyelitis, which
results in tissue damage from sterile inflammation, which can be
effectively treated with anti-TNF therapy. 12 Unfortunately, there are
also immune-mediated inflammatory disorders in which the etiology
of the chronic inflammation is unknown (eg, rheumatoid arthritis,
multiple sclerosis). 13 Although biologic therapies have had a major
effect on immune-mediated inflammatory disorder severity and
progression, there is no cure, and clinical management of
breakthrough flares remains a major challenge.

Table 1
Examples of Orthopaedic Inflammatory and Immunologic Disorders

Inflammatory
or Patient Common Anatomic Known
Immunologic Demographics Locations Pathogenesis
Disorders
Inflammatory
or Patient Common Anatomic Known
Immunologic Demographics Locations Pathogenesis
Disorders
Rheumatoid
arthritis Most common Small joints (hands, Autoimmune
form of feet) most common; disorder with
inflammatory large joints and synovial
arthritis cervical spine also inflammation
Female > Male affected B cells, T cells,
Age 30 to 50 yr Systemic macrophages all
most common manifestations can play a role
but any age include vasculitis,
possible pericarditis,
rheumatoid nodules,
splenomegaly and
leukopenia (Felty
syndrome), fever/
rash/splenomegaly
(Still disease)

Ankylosing
spondylitis Male > Female Sacroiliac joint and Autoimmune
Age 20 to 40 yr, spine disorder with
any age possible Systemic enthesis
More common in manifestations inflammation
HLA-B27 carriers include uveitis and Origin unknown
iritis, gastrointestinal —combination
inflammation, of genetics
pulmonary fibrosis, (HLA-B27 +),
renal amyloidosis, environmental
aortitis factors
(microbial
exposure),
endocrine
effects
Inflammatory
or Patient Common Anatomic Known
Immunologic Demographics Locations Pathogenesis
Disorders
Systemic
lupus Female >> Male Systemic disorder Autoimmune
erythematosus Age 15 to 44 yr affecting many organ disorder: loss of
most common systems self-tolerance
Skin manifestations leading to
(rash), mucosal activation of
surfaces (ulcers), autoreactive B
serositis (pericarditis and T cells with
or pleuritic), renal autoantibody
disorders, neurologic production
disorders, and Diagnostic
hematologic criteria and
disorders all a part of pathogenesis
diagnostic criteria include
Joint involvement autoantibody
displays synovitis, production (eg,
but less erosive antinuclear
disease than antibody, anti-
rheumatoid arthritis double-stranded
Osteonecrosis is a DNA, anti-Smith,
common cause of antiphospholipid)
joint pain Diagnosis also
includes a range
of clinical criteria

Juvenile
idiopathic Diagnosis of Different categories Autoimmune
arthritis exclusion (systemic—multiple disorder: genetic
Age younger joints plus systemic predisposition,
than 16 yr, at manifestations; humoral
least 6 wk of polyarthritis—five or immunity,
symptoms, more joints involved; autoantibody
unknown etiology oligoarthritis—less production in
Some categories than five joints conjunction with
more common in involved, etc) environmental
females factors may all
(oligoarthritis), play role
others more
common in
males
(enthesitis-
related)
Inflammatory
or Patient Common Anatomic Known
Immunologic Demographics Locations Pathogenesis
Disorders
Psoriatic
arthritis 20% to 30% of Enthesitis—distal Autoimmune
patients with interphalangeal joint disorder:
psoriasis may involvement interaction of
have psoriatic common, large joints genetic
arthritis and spine also predisposition
Male = Female affected (most and
Age 30 to 40 yr commonly environmental
most common oligoarticular—less factors
than five joints) CD8+ T cells
Skin disease usually appear to play
precedes joint an important role
disease but not
always
Arthritis mutilans—
severe destructive
joint deformity most
common in hands
and feet

Myositis
Different types of Common findings Interaction
myositis (eg, may include fatigue, between genetic
dermatomyositis, muscle weakness, or predisposition,
polymyositis, pain innate immunity,
inclusion body Systemic findings adaptive
myositis) including skin rash or immunity, and
Age and sex other organ system environmental
differences involvement factors
depend on depending on
underlying subtype
diagnosis Some types affect
more proximal
muscle groups
(polymyositis) versus
others with more
distal involvement
(inclusion body
myositis)
Inflammatory
or Patient Common Anatomic Known
Immunologic Demographics Locations Pathogenesis
Disorders
Gout and
pseudogout Male > Female Can have acute and Gout—
Age 30 to 60 yr chronic hyperuricemia,
most common; manifestations monosodium
women typically Gout—lower > upper urate crystals in
postmenopausal extremities. First synovial fluid or
Pseudogout metatarsophalangeal soft tissue
typically older joint common, also Pseudogout—
metatarsal joints, calcium
ankle, knee, wrist, pyrophosphate
metacarpophalangeal dihydrate
joints in hand crystals at
Pseudogout cartilage surface
Monosodium
urate and
calcium
pyrophosphate
dihydrate
crystals trigger
local release of
inflammatory
cytokines from
mononuclear
phagocytes and
neutrophils,
which can lead
to cartilage
damage and
bone erosion
Inflammatory
or Patient Common Anatomic Known
Immunologic Demographics Locations Pathogenesis
Disorders
Biomaterial
foreign body No age or sex Periarticular most Any commonly
reactions predisposition common at site of used
joint replacement biomaterials can
lead to foreign
body reaction
(most
commonly
polyethylene,
metallic
corrosion
products,
cement
particles)
Wear particles
stimulate
phagocytic cells
to release
inflammatory
cytokines
resulting in
osteolysis, less
commonly
periarticular soft-
tissue
inflammation

Biologic Therapies in Orthopaedics

Biologic therapies are defined as treatments that are produced in
living organisms, in contrast to herbal extracts and chemically
synthesized small molecules. Another distinction is that biologics are
primarily protein in nature and must be injected or infused into
patients to bypass the digestive system. 14 Mechanistically, biologics
either act as ligands to a host cell surface receptor (eg, teriparatide,
bone morphogenetic protein 2) or block a host receptor by
sequestering its ligand (eg, etanercept, denosumab) or binding to the
receptor directly (eg, anakinra, tocilizumab) (Figure 3). Another virtue
of biologics is that they are very specific against one target, and their
mechanism of action is completely understood. Thus, biologics are
critical tools for gain and loss of function research, and much of what
is known about human immunology comes from clinical trials with
biologic therapies. Because rheumatoid arthritis is the most prevalent
immune-mediated inflammatory disorder (0.5% to 1% of adults, 4.5%
of the population older than 55 years, with 5 to 50 per 100,000 new
cases annually 15 ), and there is no cure, this disease was the primary
indication of many FDA-approved biologics. Moreover, rheumatoid
arthritis displays both chronic inflammatory and autoimmune
features. Thus, biologics targeting a broad array of soluble factors,
receptors, and cell types have been developed (Figure 3). However,
there are major shortcomings of biologic therapy for rheumatoid
arthritis that remain significant. The first is the very low bar of efficacy
upon which drugs are FDA approved for rheumatoid arthritis,
specifically a 20% improvement in the American College of
Rheumatology’s criteria (ACR20). 16 The other is that all of these
biologics are inherently immunosuppressive, such that they cannot be
used in combination because of the known risks of opportunistic
infections. 17 In addition, there are recommendations for a biologic
therapy holiday prior to elective surgeries (eg, stopping anti-TNF
therapy 2 to 4 weeks before total joint replacement 18 ).
 Figure 3 Illustration of biologic therapies for rheumatoid arthritis.This schematic
illustrates the huge array of FDA-approved biologic agents for rheumatic diseases
and the cytokines, receptors, and specific cell types that they target. The most
broadly used biologics are the anti–tumor necrosis factor (TNF) inhibitors. Other
biologics that target innate immunity include anakinra and tocilizumab that block the
IL-1 and IL-6 receptors, respectively. Biologics that target autoantibodies (eg,
anticitrullinated peptide antibody [ACPA], rheumatoid factor [RF]) and upstream B
cell pathways and antigen-presenting cells (APCs) are shown (proliferation-inducing
ligand [APRIL], B cell activating factor [BAFF], and its receptor [BAFF-R]). There are
also biologics that specifically target T cell subsets (Th1 and Th17 cell) and receptor
activator of nuclear factor kappa B ligand (RANKL), which is required for osteoclast
differentiation and survival.(Redrawn from Her M, Kavanaugh A: Alterations in
immune function with biologic therapies for autoimmune disease. J Allergy Clin
Immunol 2016;137[1]:19-27, with permission from Elsevier.)

Adaptive Immunity in Orthopaedics

In addition to primitive innate immunity, organisms with longevity
evolved very complex adaptive immune responses to specific foreign
molecules (antigens). These mechanisms involved the interaction of a
large array of soluble factors and cells over a prolonged time period
(weeks to months) and are collectively referred to as adaptive
immunity. The COVID-19 pandemic has shown that all healthcare
workers need to have a fundamental understanding of how protective
immunity develops against lethal pathogens, and the risks and
benefits of vaccination.
There are two parallel arms of adaptive immunity: cellular
immunity, with the goal of developing antigen-specific cytotoxic T
lymphocytes (CTLs) that kill host cells that express this antigen, and
humoral immunity, with the goal of developing antigen-specific
neutralizing antibodies that inactivate dangerous molecules (such as
soluble toxins and spike protein) and facilitate their clearance via
opsonophagocytosis. Development of adaptive immunity commences
with the generation of peptide antigens by dendritic cells. 19 The
antigen peptides are either produced from de novo synthesized
protein by the antigen-presenting cell (APC) and displayed on the
plasma membrane within the major histocompatibility complex class I
(MHC I), or digested from internalized proteins and presented in
MHC II by the APC (Figure 4). The next step is the generation of
antigen-specific helper T (Th) cells, which recognize the peptide
antigen presented by the MHC II molecule via its T-cell receptor
(TCR). This TCR activation leads to proliferation and differentiation
into Th cells that support cellular immunity (Th1) or humoral
immunity (Th2) based on the cytokine milieu that is present.
Prototypic Th1 cytokines include interferon gamma, TNF, and IL-2;
and prototypic Th2 cytokines include IL-4, IL-5, and IL-13. Th1 cells
promote proliferation and activation of CTL, which must also receive
TCR stimulation from peptide antigen within MHC I on the APC. Th2
cells promote proliferation and activation of B cells, which must also
receive activation signals through the B-cell receptor (BCR) that
recognizes full-length and peptide antigens that are free or cell bound.
This process also stimulates B-cell differentiation into plasma cells in
which immunoglobulin heavy chain gene recombination converts the
plasma membrane–bound antigen-specific BCR (immunoglobulin
[Ig]M) into a soluble antibody molecule (IgG) that is secreted into
blood by these cells. In a protective adaptive immune response, Th1,
Th2, CTL, and B cells that recognize the same antigen collaborate at
the infection site to eradicate the pathogen, and then die from
apoptosis when there is no more antigen stimulation to sustain them.
Immunologic memory also can be achieved when some of the Th1,
Th2, CTL, and B cell precursors, which were not involved at the site of
the infection, home to the bone marrow where they persist as lifelong
memory cells that can be released to fight a recurrent infection.
 Figure 4 Illustration of endogenous versus exogenous antigen presentation to
cytotoxic versus helper T cells.Cytotoxic T cells respond to peptide antigens
presented in the major histocompatibility complex class I (MHC I) molecule that is
expressed on virtually all human cells. As illustrated on the left-hand side, these
endogenous antigens originate from host cell protein synthesis; the full-length
proteins are digested into peptides by proteasomes and are transported to the
endoplasmic reticulum, where they are further clipped by aminopeptidases and
loaded onto the MHC I molecule. The right-hand side illustrates MHC II peptide
antigen presentation to helper T cells (Th). This process commences by exogenous
protein antigen uptake by professional antigen-presenting cells. The peptide antigens
are generated via proteolytic cleavage in lysosomes and are loaded into newly
synthesized MHC II molecules from the endoplasmic reticulum, and then transported
to the plasma membrane.(From Neerincx A, Castro W, Guarda G, Kufer TA: NLRC5,
at the heart of antigen presentation. Front Immunol 2013;4:397.)

Immune Checkpoint Inhibitors, Autoimmunity,

and Cancer Immunotherapy
Shortly after the passive transfer of antibody from mother to fetus and
neonate was demonstrated in 1892, a series of experiments was
completed that demonstrated hemolytic antibodies that result when
animals are injected with xenogeneic and allogenic blood. From this
the original autoimmunity hypothesis, termed horror autotoxicus, was
postulated. 20 Indeed, autoantibodies and CTL against host proteins
are the primary cause of serious human diseases (such as Graves
hyperthyroidism and type 1 diabetes, respectively), and an array of
autoimmune connective tissue disease also exists 21 (Table 1). To
prevent these catastrophic consequences from regular occurrence, the
mammalian immune system has evolved several mechanisms of
central tolerance, including B cell clonal deletion in the bone marrow
and negative selection of T cells in the thymus, which eliminate
autoreactive lymphocytes during their hematopoietic development.
However, central tolerance is not foolproof, and it is estimated that
approximately 10% of B cells and T cells escape and must be held in
check by mechanisms of peripheral tolerance. The most fundamental
of these is the requirement of co-stimulation by APC during activation
through antigen-specific BCR and TCR signaling. This two-signal
hypothesis posits that B cells and T cells can only respond to antigen if
an additional signal is present. 22 In the absence of this second signal,
lymphocytes stimulated through their BCR and TCR undergo
apoptosis or a prolonged state of nonresponsiveness called anergy.
Although several second signals exist, CD40-ligand (CD40L)
stimulation of CD40 on B cells and B7 ligand (CD80 or CD86)
stimulation of CD28 on T cells are used in most adaptive immune
responses. Additionally, these signals can be antagonized such as the
binding of cytotoxic T lymphocyte–associated protein 4 (CTLA-4) to B7
ligand on APCs, which will block the co-stimulatory signal of CD28 on
T cells. The importance of these co-stimulatory pathways has been
demonstrated by human mutations, as patients with X-linked
agammaglobulinemia/hyper IgM syndrome are genetically deficient in
CD40L, and genetic polymorphisms in the CTLA-4 gene are associated
with risk of solid organ transplant rejection.
Although most healthcare workers are aware of patients with
terminal cancer who have markedly outlived their prognosis following
immunotherapy, few are aware of the early treatment of these patients
with a bacterial extract (Coley toxin) that led to several remarkable
cures of end-stage bone and soft-tissue sarcomas. 18 , 23 However, in the
absence of a scientific rationale for this crude treatment that could not
achieve highly reproducible outcomes, treatment with this bacterial
extract was discredited until the discovery of checkpoint inhibitors.
Most notably, two checkpoints have been successfully manipulated by
biologic therapies (Figure 5): CTLA-4 and the programmed cell death
protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1). 24 , 25 It
should be noted that orthopaedic oncologists have reported patients
with terminal metastatic cancer with chronic osteomyelitis who have
survived well beyond their prognosis on suppressive antibiotic
therapy. 26 Taken together, the mechanism of Coley toxins appears to
be PAMP-TLR signaling that downregulates CTLA-4, PD-1, and/or PD-
L1, which is now achieved by FDA-approved immunotherapies.
 Figure 5 Illustration of checkpoint inhibitors and biologic antagonists for cancer
immunotherapy.Cancer cells can be killed by activating T cells and preventing T cell
death. The T cell checkpoint inhibitor cytotoxic T lymphocyte–associated protein 4
(CTLA-4) functions by binding to B7 (CD80 and CD86) on antigen-presenting cell
(APC) and prevents stimulation of CD28, which is the critical co-stimulatory signal
required to activate T cells following T-cell receptor (TCR) stimulation by specific
antigen presented by the major histocompatibility complex (MHC). Ipilimumab binds
to CTLA-4 and allows continuous co-stimulation and activation via CD28/B7
interaction. Cancer cells escape host immune surveillance by downregulating
immune cells that attack cancer cells. Cancer cells make proteins called PD-L1
(programmed cell death ligand 1) that binds to programmed cell death receptor (PD-
1) to kill T cells. PD-L1 is also expressed on APC and other host cells.
Pembrolizumab and nivolumab both bind to PD-1, whereas atezolizumab blocks
PD-L1. The result of these biologic therapies is inactivation of the negative PD-1/PD-
L1 signal, which allows all T cells receiving TCR and CD28 stimulation to become
activated and proliferate. This includes tumor infiltrating lymphocytes (TIL), cytotoxic
T cells (CTLs) that recognize unique tumor antigens, and autoreactive T cells that
mediate autoimmunity and horror autotoxicus. Thus, given the serious risks
associated with these biologics, immune checkpoint inhibitor therapy should only be
used in patients with metastatic cancers for which no other treatments exist.
(Reproduced from Erinjeri JP, Sze DT: Immunotherapy and checkpoint inhibitors: A
primer for the interventional radiologist. Endovascular Today 2019;18[10]:99-103.)

There is also a cellular cancer immunotherapy that involves the

generation of chimeric antigen receptor T cells. 27 Currently, this
experimental treatment is only available for cancers that express cell
type–specific surface receptors (eg, B-cell leukemias, lymphomas,
multiple myelomas) and involves reprogramming the patient’s T cells
to target and kill all cells that express that receptor. The science
behind chimeric antigen receptor T cell therapy takes advantage of
recombinant DNA technology, which combines antibody genes that
recognize the tumor antigen (known as a single-chain variable
fragment), with the transmembrane domain of the CTL protein CD8,
and the cytoplasmic domain of CD3 that transmits signals from
activated TCRs. Figure 6 illustrates tisagenlecleucel chimeric antigen
receptor T cell therapy for relapsed or refractory B cell precursor acute
lymphoblastic leukemia and diffuse large B cell lymphoma as an
example. 27
Figure 6 Illustrations of chimeric antigen receptor (CAR)-T cell therapy.(A) The
structure of tisagenlecleucel CAR, which specifically recognizes CD19-expressing B
cells (normal and cancerous), is shown to illustrate the three distinct functional
domains of the CAR, which is transfected into the patient’s T cells. The extracellular
domain (FMC63) is a single-chain variable fragment derived from a monoclonal
antibody that binds tightly to CD19, which is fused to the transmembrane domain of
CD8 (exclusively expressed by cytotoxic T cells), which is fused to the cytoplasmic
tail of the T-cell receptor that delivers signal 1 (CD3 zeta) and the co-stimulatory
domain of the 4-1BB receptor (CD137) that delivers signal 2. (B) The process of
CAR-T cell therapy has several steps. The patient’s leukocytes are harvested (1),
and sent to a manufacturing facility where they are activated and transfected with the
CAR gene (2). The CAR-expressing T cells are then expanded (3) and sent back to
the hospital where the patient receives lymphodepleting chemotherapy (4), and is
ready to receive an infusion of the CAR-T cells (5). One advantage of CAR-T cell
therapy over radiation, chemotherapy, and biologics is that a single administration is
designed to be lifelong, as the memory CAR-T cells are known to home and persist
in the bone marrow, and can respond to a relapse on their own. However, the
serious adverse events associated with lymphodepletion and autoimmunity should
not be understated.(Reproduced from Tyagarajan S, Spencer T, Smith J: Optimizing
CAR-T cell manufacturing processes during pivotal clinical trials. Mol Ther Methods
Clin Dev. 2020;16:136-144.)
Active Versus Passive Immunization and
Lessons From the COVID-19 Pandemic
Vaccines have been hailed as one of the greatest inventions of the 20th
century, and their cost-effectiveness for prevention, and in some cases
eradication, of serious infectious disease is unparalleled in medicine.
Surgical site infections remain a major complication of orthopaedic
surgery, and current treatments for implant-associated osteomyelitis
continue to have poor outcomes that have remained largely
unchanged over the past 50 years. An additional challenge includes
the emergence of antibiotic-resistant, highly virulent bacterial strains
that threaten current treatment paradigms. Further advances in
antimicrobial therapy are needed to address these complex issues, and
improving the efficacy of vaccines is currently among the greatest
priorities in musculoskeletal research. 28 Additionally, the COVID-19
pandemic provides contemporary proof of human susceptibility to
microbial pathogenesis, and the enormous knowledge gap in the
understanding of protective versus nonprotective antibody-mediated
immunity (Figure 7), and how to achieve it. 29
Figure 7 Illustration of neutralizing versus nonneutralizing antibodies and antigenic
drift during the COVID-19 pandemic.Schematic illustration of protective versus
nonprotective antibody-mediated immunity from viral infection. The left side depicts
protective immunity in which specific neutralizing antibodies contribute to the
elimination of the virus via: (1) inhibition of viral attachment to host cells (eg, in the
case of COVID-19 the spike protein cannot bind to the angiotensin-converting
enzyme 2 [ACE2]), and (2) opsonophagocytosis in which the antibodies bind to the
virus and mediate its internalization through CD32 (FсγRII receptor that targets all
endocytosed molecules for immediate destruction in lysosomes). In contrast, the
right side depicts immunopathology via antibody-dependent infection enhancement
(ADE). This occurs when viral antigens mutate, and host antibodies generated
against the antigen from prior exposure or vaccination form imperfect complexes
with the virus. When these unstable antibody–virus complex bind to the FсγRII
receptor of immune cells, the virus can escape the endosome prior to fusion with
lysosomes and begins its virulent replicative cycle. Severe acute respiratory
syndrome (SARS) can occur in the setting of extensive viral replication, which
produces large quantities of pathogen-associated molecular patterns (PAMPs) from
the virus and damage-associated molecular patterns (DAMPs) from necrotic-
infected cells. This triggers massive simultaneous activation of both the innate and
adaptive immune system resulting in a cytokine storm that can be manifested as
SARS, septic shock, or sudden death of the patient. Thus, although it may seem
counterintuitive, patients with serious viral infections are given immunosuppressive
therapy (eg, corticosteroids) to prevent cytokine storm.(Reproduced from Zaichuk
 TA, Nechipurenko YD, Adzhubey AA, et al: The challenges of vaccine development
against betacoronaviruses: Antibody dependent enhancement and Sendai virus as a
possible vaccine vector. Mol Biol 2020;54[6]:922-938.)

There are three forms of immunization: natural immunity that

comes following host recovery from a pathogenic challenge; active
immunization that follows vaccination of the host with antigen(s) from
a pathogen or toxin; and passive immunization in which neutralizing
antibodies are transferred to the host from milk or drug infusion.
Knowledge of natural immunity is the weakest because of the great
variation in adaptive immune responses between people to the same
pathogenic challenge. Although there are several explanations for this
diversity, a dominant factor is that MHC genes are highly polymorphic
by evolutionary design, such that all members of a species present
different antigens during natural infection to the same pathogen,
which increases the probability that some will achieve protective
immunity and avoid extinction. Another enigma of natural immunity
is the theory of herd immunity, which posits that a species becomes
protected from a specific pathogen once a threshold immunity within
the population is achieved. As is now known from the COVID-19
pandemic, the type (quality and quantity of cellular and humoral
immunity) and threshold (60% to 90% of the population) required for
herd immunity are unclear, if they exist at all.
The first scientific a empt to control an infectious disease by
deliberate active vaccination was reported in 1796. 30 There are two
critical components to active vaccines: the adjuvant (eg, PAMPs and
DAMPs that stimulate TLRs) that upregulates antigen presentation
and second signals on APCs while downregulating checkpoint
inhibitors; and the antigen(s). Currently, there are six different types
of vectors that can be used for active immunization (Figure 8). In the
case of COVID-19, messenger RNA nanoparticle vaccines against the
spike protein (BioNTech/Pfizer BNT162bi and Moderna messenger
RNA-1273) have emerged as the most effective, largely for unknown
reasons. 31 However, the limited efficacy of the replication-defective
recombinant adenoviral vectors that deliver the gene encoding the
spike protein (Ad26.COV2.8 Janssen Johnson & Johnson, AZD1222
AstraZenecca/Oxford) may in part be due to the host’s immune
response to the vector, which is known to limit boosters. 32 Overall, the
major strengths of active immunization is the ability to focus cellular
and humoral adaptive responses at a particular antigen, potentially
proven to be protective in preclinical studies, and low cost (COVID-19
vaccines cost approximately $20 per dose). However, the major
limitations are that efficacy is completely dependent on the individual
patient’s immune response to the vaccine, which ranges from lifelong
protection to undetectable, and that active vaccines cannot be used for
treatment.

Figure 8 Illustration of different types of vectors for active immunization.Six

different types of vectors have been used to make human vaccines. Each has its
advantages and limitations. Based on its efficacy in the COVID-19 pandemic and
manufacturing efficiencies, it is likely that the new mRNA nanoparticle vaccines will
become the new clinical standard for active immunization.(Reproduced from
Grigoryan L, Pulendran B: The immunology of SARS-CoV-2 infections and vaccines.
Semin Immunol 2020;50:101422.)

Because immunocompromised people cannot be actively vaccinated

efficiently, passive immunizations consisting of convalescent sera or
monoclonal antibodies have been developed. Because these antibodies
work immediately but have a limited half-life on the order of 3 to 4
months, passive immunizations are primarily used as a therapy. As an
example, the REGEN-COV passive immunization for COVID-19 is a
cocktail of two recombinant human monoclonal antibodies
(casirivimab and imdevimab) against the spike protein of SARS-CoV-
2. Although this drug is mostly used in patients with serious infection,
it is also FDA approved for the unvaccinated or people with weak
immune systems at high risk of severe disease because of COVID-19
exposure.

Summary
Inflammation is central to all orthopaedic conditions and surgeries,
and the extent and duration of the inflammatory insult determines
tissue healing potential and pathology. It is now known that chronic
expression of proinflammatory cytokines from autoimmunity,
genetics, and orthopaedic biomaterials contribute to a diverse group
of musculoskeletal diseases from inflammatory arthropathies such as
rheumatoid arthritis, inflammatory conditions such as chronic
recurrent multifocal osteomyelitis, and periprosthetic osteolysis,
respectively. Based on this science, there are FDA-approved drugs (eg,
JAK inhibitors) and biologics (eg, anti-TNF agents) that are now
standard-of-care treatments for rheumatoid arthritis, psoriatic
arthritis, ankylosing spondylitis, and other musculoskeletal
conditions. In the presence of neoantigens, inflammation from innate
immunity is translated to adaptive immunity by T cells and B cells.
Critical to this process is the downregulation of checkpoint inhibitor
signaling, which is recapitulated by PD-L1 and PD-1 antagonists
during cancer immunotherapy. The activation of antigen-specific
lymphocytes is also central to active vaccination, whose efficacy is
dependent on the host’s ability to generate lifelong immunity against
a pathogen (eg, CTLs and neutralizing antibodies against COVID-19
spike protein). However, for an active infection, passive immunization
with convalescent sera or neutralizing monoclonal antibodies can also
be effective.

Key Study Points

Inflammation is initiated by specific microbial products that cannot be synthesized by
eukaryotic cells (PAMPs), and intracellular biochemicals (DAMPs) released from
 necrotic host cells, which bind to TLRs that signal for proinflammatory cytokine and
chemokine synthesis.
Chronic expression of proinflammatory cytokines (TNF, IL-1, IL-6) from congenital
disease, autoimmunity, infection, and implant wear debris can lead to orthopaedic
disorders including inflammatory-erosive arthritis and osteolysis.
Small-molecule drugs (JAK inhibitors) and biologics (TNF inhibitor) that specifically
target proinflammatory signaling are standard-of-care treatments for inflammatory
orthopaedic conditions. Because these drugs are immunosuppressive, they cannot be
given in combination, which leads to opportunistic infections.
Lifelong acquired immunity against pathogens and cancer cells requires downregulation
of immune checkpoint inhibitors (PD-L1 and PD-1) that prevent T cell activation and
proliferation. Biologic antagonists of these checkpoint inhibitors have proven to be
effective immunotherapies for untreatable cancers, but can also lead to immune-related
adverse events (such as type 1 diabetes).
The efficacy of active vaccines is dependent on the host’s ability to generate antigen-
specific T cells and neutralizing antibodies, whereas passive immunization provides
infected patients neutralizing antibodies in convalescent sera or monoclonal antibody
cocktails.

Annotated References
1. Garcia MA, Meurs EF, Esteban M: The dsRNA protein kinase PKR:
Virus and cell control. Biochimie 2007;89(6-7):799-811.
2. Mitchell G, Isberg RR: Innate immunity to intracellular pathogens:
Balancing microbial elimination and inflammation. Cell Host Microbe
2017;22(2):166-175.
3. Medzhitov R, Janeway CJr: Innate immunity. N Engl J Med
2000;343(5):338-344.
4. Rakoff-Nahoum S, Medzhitov R: Toll-like receptors and cancer. Nat
Rev Cancer 2009;9(1):57-63.
5. Liu-Bryan R, Sco P, Sydlaske A, Rose DM, Terkeltaub R: Innate
immunity conferred by Toll-like receptors 2 and 4 and myeloid
differentiation factor 88 expression is pivotal to monosodium urate
monohydrate crystal-induced inflammation. Arthritis Rheum
2005;52(9):2936-2946.
6. Verma IM, Stevenson JK, Schwarz EM, Van Antwerp D, Miyamoto
S: Rel/NF-kappa B/I kappa B family: Intimate tales of association
and dissociation. Genes Dev 1995;9(22):2723-2735.
 7. Pedersen J, Coskun M, Soendergaard C, Salem M, Nielsen OH:
Inflammatory pathways of importance for management of
inflammatory bowel disease. World J Gastroenterol 2014;20(1):64-77.
8. Fas SC, Fri sching B, Suri-Payer E, Krammer PH: Death receptor
signaling and its function in the immune system. Curr Dir
Autoimmun 2006;9:1-17.
9. Martinez FO, Gordon S: The M1 and M2 paradigm of macrophage
activation: Time for reassessment. F1000Prime Rep 2014;6:13.
10. Gallo J, Raska M, Kriegova E, Goodman SB: Inflammation and its
resolution and the musculoskeletal system. J Orthop Translat
2017;10:52-67.
11. Pajarinen J, Jamsen E, Kon inen YT, Goodman SB: Innate immune
reactions in septic and aseptic osteolysis around hip implants. J Long
Term Eff Med Implants 2014;24(4):283-296.
12. Ferguson PJ, Sandu M: Current understanding of the pathogenesis
and management of chronic recurrent multifocal osteomyelitis. Curr
Rheumatol Rep 2012;14(2):130-141.
13. Kuek A, Hazleman BL, Ostor AJ: Immune-mediated inflammatory
diseases (IMIDs) and biologic therapy: A medical revolution.
Postgrad Med J 2007;83(978):251-260.
14. Her M, Kavanaugh A: Alterations in immune function with
biologic therapies for autoimmune disease. J Allergy Clin Immunol
2016;137(1):19-27.
15. Sco DL, Wolfe F, Huizinga TW: Rheumatoid arthritis. Lancet
2010;376(9746):1094-1108.
16. Felson DT, Anderson JJ, Boers M, et al: American College of
Rheumatology. Preliminary definition of improvement in
rheumatoid arthritis. Arthritis Rheum 1995;38(6):727-735.
17. Genovese MC, Cohen S, Moreland L, et al: Combination therapy
with etanercept and anakinra in the treatment of patients with
rheumatoid arthritis who have been treated unsuccessfully with
methotrexate. Arthritis Rheum 2004;50(5):1412-1419.
18. Rezaieyazdi Z, Sahebari M, Khodashahi M: Preoperative evaluation
and management of patients receiving biologic therapies. Arch Bone
Jt Surg 2019;7(3):220-228. This article reviews the current available
 guidelines regarding the use and preoperative management of
biologic agents in the se ing of surgery. Level of evidence: V.
19. Neerincx A, Castro W, Guarda G, Kufer TA: NLRC5, at the heart of
antigen presentation. Front Immunol 2013;4:397.
20. Silverstein AM: Autoimmunity versus horror autotoxicus: The
struggle for recognition. Nat Immunol 2001;2(4):279-281.
21. Wang Q, Shangguan J, Zhang Y, Pan Y, Yuan Y, Que W: The
prevalence of thyroid autoantibodies in autoimmune connective
tissue diseases: A systematic review and meta-analysis. Expert Rev
Clin Immunol 2020;16(9):923-930. This article is a review of case-
control studies examining the prevalence of thyroid autoantibodies
in patients with autoimmune connective tissue disease versus
control patients. The authors found an association between
antithyroid antibodies in patients with autoimmune connective
tissue diseases. Level of evidence: III.
22. Bretscher PA: The history of the two-signal model of lymphocyte
activation: a personal perspective. Scand J Immunol 2019;89(6):e12762.
This article explains the process of discovering the Two-Signal
Model of lymphocyte activation. Level of evidence: V.
23. Coley WB: The treatment of inoperable sarcoma by bacterial toxins
(the mixed toxins of the Streptococcus erysipelas and the Bacillus
prodigiosus). Proc R Soc Med 1910;3(Surg Sect):1-48.
24. Robert C: A decade of immune-checkpoint inhibitors in cancer
therapy. Nat Commun 2020;11(1):3801. This is a review article on the
development and use of checkpoint inhibitors for cancer therapy.
Level of evidence: V.
25. Erinjeri JP, Sze DT: Immunotherapy and checkpoint inhibitors: A
primer for the interventional radiologist. Endovascular Today
2019;18(10):99-103. This article reviews the background on
immunotherapy and checkpoint inhibitors for oncological
diagnoses. Level of evidence: V.
26. Paul D, Lander S, Cooper AR, Tyler WK: Long-term survival of
large cell neuroendocrine lung carcinoma with bony metastases: A
case of immunoprotectivity? J Orthop Oncol 2016;2(2):110.
27. Tyagarajan S, Spencer T, Smith J: Optimizing CAR-T cell
manufacturing processes during pivotal clinical trials. Mol Ther
Methods Clin Dev 2020;16:136-144. This is a review article on the
development of CD19-specific chimeric antigen receptor (CAR)-T
cell therapy for leukemia and lymphoma. Level of evidence: V.
28. Schwarz EM, Parvizi J, Gehrke T, et al: 2018 International
Consensus Meeting on Musculoskeletal Infection: Research
priorities from the general assembly questions. J Orthop Res
2019;37(5):997-1006. This article describes the expert consensus
opinion on further research priorities from the International
Consensus Meeting on Musculoskeletal Infection in 2018. Level of
evidence: V.
29. Zaichuk TA, Nechipurenko YD, Adzhubey AA, et al: The
challenges of vaccine development against betacoronaviruses:
Antibody dependent enhancement and Sendai virus as a possible
vaccine vector. Mol Biol 2020;54(6): 922-938. This review article
discusses the challenges of developing a vaccine against
betacoronaviruses using nonpathogenic viral vectors. Level of
evidence: V.
30. Riedel S: Edward Jenner and the history of smallpox and
vaccination. SAVE Proc 2005;18(1):21-25.
31. Grigoryan L, Pulendran B: The immunology of SARS-CoV-2
infections and vaccines. Semin Immunol 2020;50:101422. This review
article discusses human immune response to SARS-CoV-2 infection
and their implications for vaccine design. Level of evidence: V.
32. Dai Y, Schwarz EM, Gu D, Zhang WW, Sarvetnick N, Verma IM:
Cellular and humoral immune responses to adenoviral vectors
containing factor IX gene: Tolerization of factor IX and vector
antigens allows for long-term expression. Proc Natl Acad Sci USA
1995;92(5): 1401-1405.
S E CT I ON 3

Trauma
SECTION EDITOR
Jonah Hebert-Davies, MD, FRCSC, FAAOS
C H AP T E R 2 1

Polytrauma Care
Milton T. M. Little MD, FAAOS, FAOA, Geoffrey S. Marecek
MD, FAAOS, FAOA

Dr. Little or an immediate family member serves as a paid consultant to or is an employee of

DePuy, a Johnson & Johnson Company and Globus Medical. Dr. Marecek or an immediate
family member has received royalties from Globus Medical; serves as a paid consultant to or is
an employee of BoneSupport AB, Globus Medical, NuVasive, restor3d, Smith & Nephew, Stryker,
Synthes, and Zimmer; has stock or stock options held in restor3d; and serves as a board member,
owner, officer, or committee member of the Orthopaedic Trauma Association and the Western
Orthopaedic Association.

ABSTRACT
Patients with polytrauma are uniquely challenging and require
orthopaedic surgeons to interact with general surgeons,
neurosurgeons, and other specialists to provide timely and effective
treatment. Surgeons play an important role in the evaluation,
resuscitation, and early treatment of these patients. It is necessary
to understand the pathophysiology of trauma and how different
injuries affect the timing and extent of interventions. The concepts
of damage-control orthopaedics and early appropriate care have
evolved to provide a framework for delivering timely and
potentially lifesaving care to these patients.
Keywords: damage control; femur fracture; pelvic fracture;
polytrauma; resuscitation

Introduction
All orthopaedic surgeons should be familiar with treatment of
patients with polytrauma. This is the rare opportunity where direct
action (or inaction) can affect a patient’s survival. Understanding
Advanced Trauma Life Support principles is an essential first step
in evaluating patients and managing the early stages of care.
Surgeons must understand patient resuscitation and the specific
interventions that aid in resuscitation. Familiarity with the
management of nonorthopaedic injuries and their effect on the
timing of orthopaedic care is important because it will help the
surgeon determine when to employ early appropriate care or
damage-control orthopaedics (DCO). These concepts have
expanded how physicians think about care of the polytrauma
patient and expedited care for patients with pelvic, acetabular,
spine, and femoral fractures.

Initial Assessment and Management

The initial management of the patient with polytrauma uses a
team-based approach and the Advanced Trauma Life Support
manual’s principles of a primary, secondary, and tertiary survey for
a systematic assessment of the patient. 1 - 4 The primary survey
identifies immediate life-threatening injuries that require life-
sustaining interventions. The secondary survey identifies additional
injuries that may cause disability, blood loss, or affect
hemodynamic stability. 3 The tertiary survey is critical to finding
additional injuries once the patient’s mental status has improved
and distracting injuries have been stabilized. 5 This systematic
approach is essential to avoid missing potentially significant
injuries at every step of the survey.

Primary Survey
The primary survey uses the ABCDEs (airway, breathing,
circulation, disability, exposure), a stepwise algorithm to
systematically assess the patient to prevent a fatal outcome. This
assessment occurs simultaneously with resuscitation described in
the next paragraphs.

Airway
Confirmation of a patent airway is critical to appropriate patient
oxygenation. Patients must be immediately assessed for airway
obstruction or inability to maintain their airway (ie, intoxication,
head injury, waning consciousness, facial trauma) in the field and
upon arrival to the trauma bay. 3 , 4 If concerns arise regarding
airway protection, the patient should be intubated immediately,
and mechanical ventilation should be initiated. Cervical
precautions should be maintained, and a team approach to
intubation should be performed. 3 , 6 The Glasgow Coma Scale
(GCS) provides a compressive assessment of patient consciousness
7
(Table 1). Patients with a GCS score of 8 or lower should be
intubated immediately.

Table 1
Glasgow Coma Scale

Eyes Verbal Motor Score

— — Follows commands 6
— Oriented Localizes pain 5
Open spontaneously Confused Withdrawal from pain 4
Open to commands Inappropriate words Flexes to pain 3
Open to pain Incomprehensible sounds Extension to pain 2
Do not open No motor response No motor response 1
GCS Score
Mild: 13-15 Moderate: 9-12 Severe 3-8
Modified from Teasdale G, Jennett B: Assessment of coma and impaired consciousness.
Lancet 1974;81:84. with permission.

Breathing
The trauma team must confirm appropriate lung oxygenation by
assessing bilateral breath sounds with or without intubation. All
patients should receive supplemental oxygen and pulse oximetry to
monitor oxygen saturation. 4 Chest injuries (ie, tension
pneumothorax, simple/open pneumothorax, and pulmonary
contusions) may prevent appropriate ventilation. 8 During the
primary survey, an AP chest radiograph can identify these injuries,
whereas occult injuries may be identified later with CT of the chest,
abdomen, and pelvis in stable patients.

Circulation
Blood pressure and heart rate are criteria used to assess shock in
patients with polytrauma 9 (Table 2). Systolic blood pressures
should be maintained above 90 mm Hg, and inability to do so is
commonly due to decreased blood volume or hypovolemic shock 2 -
4 , 6
(Table 3). Two critical steps are necessary to maintain
appropriate circulation: identification of and stopping the cause of
the hypotension and rapid volume replacement. When necessary,
blood products should be used for resuscitation at a 1:1:1 ratio for
red blood cells, fresh-frozen plasma, and platelets to prevent
dilutional hypocoagulability. 2 , 10 Fluid should be warmed or
administered in a warming device to prevent hypothermia because
core hypothermia <35°C is an independent predictor of mortality. 2

Table 2
Borderline Patient Criteria for Borderline Trauma

Patient Criteria
ISS > 20 and additional thoracic trauma (AIS > 2)

Hemodynamic shock (initial systolic blood pressure <90 mm Hg)

Abdominal/pelvic trauma
Liver hematoma: subcapsular, >50% surface area, ruptured subcapsular or
parenchymal hematoma, intraparenchymal hematoma ≥10 cm or expanding
Liver laceration: >3 cm parenchymal depth

ISS > 40 in the absence of additional thoracic injury

Radiographic findings of bilateral lung contusion
Initial mean pulmonary arterial pressure 24 mm Hg
 Patient Criteria
Pulmonary artery pressure increases during intramedullary nailing by 6 mm Hg
AIS = Abbreviated Injury Score, ISS = Injury Severity Score
Data from Nicola R: Early total care versus damage control: Current concepts in the
orthopedic care of polytrauma patients. ISRN Orthop 2013;2013:329452 and Hildebrand F,
Giannoudis P, Kretteck C, et al: Damage control: Extremities. Injury 2004;35:678-689.

Table 3
Hemorrhagic Shock Classification

Class 1 Class 2 Class 3 Class 4

15% loss of blood Loss of 15%-30% of Loss of 30%-40% >40% blood loss
volume (<750 blood volume (750-1,500 blood loss (1,500- (>2,000 mL)
mL) mL) 2,000 mL)
Minimal clinical Tachycardia Significant tachycardia Severe
symptoms tachycardia
— Tachypnea Tachypnea Tachypnea
— Decreased pulse Decreased systolic Severely
pressure blood pressure decreased pulse
pressure
— Mild mental status Mental status changes Obtunded
changes
Data from Brautigam RTSr, Robinson KJ, Jacobs LM: Evaluation and treatment of the
multiple-trauma patients, in Browner J, Leveine AM, Tafton PG, Krettek C, eds: Skeletal
Trauma. Saunders Elsevier, 2003, pp 177-195.

Circulatory compromise can occur as a result of decreased blood

volume or inadequate cardiac output. 4 Five potential sources of
major bleeding are large skin lesions, chest injuries, abdominal
injuries, pelvic fractures, and additional lower extremity fractures. 2
Chest injuries and blunt abdominal trauma are common sources of
exsanguination and mortality. 8 , 11 , 12 A plain AP radiograph of the
pelvis can identify severe vertical shear or volume-expanding
anteroposterior compression injuries (68% sensitive for all
fractures). 2 , 4 , 13 Stabilization of these injuries can be accomplished
with internal rotation of the lower extremities, circumferential
sheeting, or pelvic binder application during the primary survey. 3 ,
13 - 16
Femoral fractures, multiple open fractures, or mangled
extremities are sources of significant bleeding, and unrecognized
blood loss may lead to underestimates in the patient’s resuscitation
needs. 2 , 17
Simultaneous performance of a Focused Assessment with
Sonography for Trauma, or FAST, examination can identify free
abdominal fluid and/or organ injury and as li le as 20 mL of fluid in
the chest cavity. 4 , 8 , 11 Hemodynamically unstable patients with a
positive FAST examination should undergo emergent surgical
exploration. 3 , 4

Disability
Neurologic status is assessed with the GCS, which classifies a
patient’s eye, motor, and verbal responsiveness and determines the
patient’s level of dysfunction 4 , 7 , 9 (Table 1). Patients with severe
dysfunction or a GCS score of 3 to 8 should be intubated
immediately because they are unable to protect their airway. 3 , 4
Severe head injury is a major determinant of mortality in
polytrauma patients and can increase mortality twofold to
threefold. 18 Neurologic injuries leading to neurogenic shock
present as hypotension and bradycardia unresponsive to fluid
resuscitation and may require vasopressors to maintain systolic
blood pressure >90 mm Hg and cerebral perfusion. 6

Exposure
The patient should be disrobed and examined from head to toe
upon arrival to identify areas of trauma and possible sources of
bleeding. Following thorough evaluation of all areas including the
patient’s spine using logroll precautions, the patient should be
covered with warm blankets immediately. Hypothermia can
exacerbate coagulopathy by inactivating certain coagulation
proteins. 1 , 2 , 19 Avoiding the lethal triad of hypothermia,
coagulopathy, and acidosis is essential to avoid devastating effects
to the patient. Infusion of cold fluids/blood products, increased
exposure, and surgical interventions can increase lactate production
and cause metabolic acidosis. 1 , 2 , 4 , 20

Secondary Survey
After the primary survey has been completed and the patient’s
hemodynamic instability has begun to stabilize, the secondary
survey should be performed. This includes the patient’s history and
physical examination and a more thorough head-to-toe assessment
of all body parts. 4 Assessment of the spine with an accompanying
motor/sensory and rectal examination for open injuries and tone
should be performed. In hemodynamically stable patients, CT will
provide additional information because it is more sensitive for
assessment of intra-abdominal, chest, head, and spinal injuries. 6 , 8 ,
11

Tertiary Survey
The tertiary survey is performed 24 to 48 hours after the patient is
stabilized and may identify missed injuries (present in
approximately 10% of patients). 5 Major risk factors for missed
injuries are lower GCS, intensive care unit (ICU) admissions, and
high Injury Severity Scores. Approximately 63% of missed injuries
are discovered during admission after the first tertiary examination,
but up to 15% are found after hospital discharge. 5 Multiple tertiary
surveys should be performed by the orthopaedic team because
extremity injuries are the injuries most often missed. 5 , 21

Resuscitation
The act of resuscitation is critically important in the early stages of
polytrauma care. Many of these patients arrive in hypovolemic
shock; it is necessary to both restore the patient’s oxygen delivery
capacity and to stop ongoing bleeding from various sites.
Employing alternative techniques (such as tranexamic acid [TXA],
circumferential pelvic wrapping, interventional angiography, and
use of the retrograde endovascular balloon occlusion of the aorta
[REBOA]) can all help stop ongoing bleeding.
Historically, large-volume crystalloid resuscitation was the
standard for patients in hemorrhagic shock, but it can cause acute
traumatic coagulopathy and resuscitation-associated coagulopathy.
1
More recently, reducing the volume of fluid administered in favor
of blood products using a 1:1:1 ratio of plasma, platelets, and red
blood cells has improved survival and reduced complication rates. 10
, 22

Thromboelastography is a measure of the efficacy of coagulation.

According to a 2020 study, thromboelastography-guided
resuscitation has been shown to reduce mortality, the quantity of
blood products given, and interventions for hemorrhage control. 23
Prompt and effective resuscitation is important in avoiding acute
respiratory distress syndrome (ARDS). 24 Serum lactate has been
proposed as a marker of the adequacy of resuscitation, particularly
as it applies to the timing of surgical intervention. 1 , 24
Ongoing hemorrhage lessens the effect of volume repletion and
transfusion. The lysine receptor on plasminogen is competitively
inhibited by TXA, and it is used both topically and intravenously.
According to a 2021 study, prehospital administration of TXA is
associated with lower rates of massive transfusion protocol and
lower early in-hospital mortality. 25 It is also effective in the hospital
se ing within 3 hours of arrival. 26 Until recently, intracranial
hemorrhage was a contraindication, though one study suggests it is
not. 26
Circumferential pelvic wrapping can be performed with a
commercially available binder or a hospital sheet 13 , 14 , 27 to reduce
the pelvic volume and allow tamponade of venous bleeding. The
wrap should be centered over the greater trochanter to provide
maximum effect and may be combined with skeletal traction to
reduce a pelvic ring injury (Figure 1).
 Figure 1 Radiographs showing severe vertical shear pelvic fracture with
significant cranial displacement of the left hemipelvis and unstable pubic
symphysis.A, AP pelvis radiograph at presentation in the trauma bay. B, AP
pelvis radiograph following pelvic angiography, suprapubic catheter placement,
application of distal femoral traction, and pelvic sheeting.

The use of REBOA is a relatively new option for hemorrhage

control in trauma patients. Endovascular access is typically
established in the femoral artery, and a balloon is passed into the
aorta and subsequently inflated to diminish blood flow to the
extremities. Although recent meta-analyses have demonstrated
decreased mortality, 28 the specific indications in pelvic and
orthopaedic trauma, as well as the understanding of potential
complications, continue to evolve. 29
Angiography with embolization is often performed when either
contrast extravasation is seen on CT angiography, or the patient
remains hemodynamically unstable despite continued aggressive
resuscitation. Selective embolization involves only embolizing
those terminal branches from which bleeding is identified, whereas
nonselective embolization involves embolizing further upstream.
Whenever possible, nonselective bilateral iliac artery embolization
should be avoided in patients who require pelvic and/or acetabular
surgery because it results in higher complication rates. 30
Nonselective angioembolization may also increase thromboembolic
complications. 31 , 32
 Another option for hemorrhage control is preperitoneal pelvic
packing (PPP). PPP should be combined with external fixation
and/or antishock iliosacral screws to provide venous tamponade.
Lap sponges are inserted into the preperitoneal and or
retroperitoneal space though a Pfannenstiel or vertical midline
incision. 33 A 2020 meta-analysis assessing the effectiveness of PPP
found that PPP was noninferior to angioembolization, but superior
to resuscitation alone. 23 Recent literature has a empted to compare
PPP to REBOA, with mixed results. 34 , 35 A 2019 study found no
increased risk of infection when PPP was used for pelvic ring
injuries but raised concerns when it was used for acetabular
fractures. 36

Management of Nonorthopaedic Injuries

Nonorthopaedic injuries are the most common causes of mortality
in patients with polytrauma. Simultaneous evaluation and
management of these injuries by the surgical teams is critical to
patient survival. Communication and coordination are paramount
to allow for utilization of hybrid surgical suites, radiolucent tables,
and multiple skilled surgical teams to promptly provide a
multifaceted approach to these patients. Three of the most common
nonorthopaedic injuries are chest/thoracic trauma, abdominal
trauma, and head trauma.

Chest/Thoracic Trauma
Twenty-five percent of deaths in patients with severe trauma are
due to chest trauma, and 50% of unrestrained drivers will present
with a chest or thorax injury. 8 The most common presenting
injuries are rib fractures (86%), pneumothorax (59%), pulmonary
contusions (50%), and hemothorax (21.8%). 37 Ninety percent of
patients with thoracic trauma can be treated without surgery, but
more than 50% will require thoracostomy tube placement for
pneumothorax, hemothorax, or tension pneumothorax. Immediate
thoracostomy tube placement should be performed in patients with
absent breath sounds and difficulty ventilating. Conservative
management is reserved for stable patients with a pneumothorax
smaller than 2 cm. 37 Tension pneumothorax should undergo
immediate release through needle decompression at the second
intercostal. 8 Pulmonary contusions are common and often
overlooked initially but can lead to significant pulmonary sequela. 37
Fifty percent of patients with contusions will have a normal chest
radiograph at presentation, and 92% of patients will have a chest
radiograph positive for pulmonary sequela 24 hours after injury. 8
Management of pulmonary contusions is primarily supportive and
guided by the patient’s ventilation and oxygen requirements.

Abdominal Trauma
According to a 2020 study, abdominal trauma is the third most
commonly affected (30%) site of injury with an associated mortality
of 10% to 36%. 38 The most frequently injured organs are the spleen
(40% to 55%), liver (35% to 45%), and small bowel (5% to 10%). 4
Physical examination signs of abdominal trauma include the seat
belt sign (bruising in the chest region), which may suggest bowel
injury or blood at the urethral meatus, vagina, or rectum,
suggesting pelvic fractures. Hemodynamically unstable patients
should undergo simultaneous FAST examination during the
primary survey to identify free fluid or organ injury (found in up to
72% of patients). 11 Exploratory surgical intervention should be
performed in hemodynamically unstable patients with free
abdominal fluid on FAST examination following the primary
survey. 4 , 38 , 39 Hemodynamically stable patients can defer the FAST
examination and undergo CT of the abdomen for further
assessment because it is more sensitive at identifying subtle
injuries. 11 , 39

Head Trauma
Almost 90% of prehospital trauma-related deaths and 44.9% of
fatalities in patients who reach the hospital involve central nervous
system (CNS) trauma. 4 , 40 Even with continued improvement in the
care of patients with polytrauma, CNS trauma continues to be the
leading cause of death in 21% to 71% of patients. 40 Concomitant
head injuries can increase the mortality of severe bodily injury from
7.3% to 22.4% and increase the risk of organ failure from 22.5% to
53.3%. 18 The GCS score should be calculated for all patients 7 (Table
1). CNS trauma occurs in two phases: primary injury and secondary
injury.
Primary brain injury may result from four categories of injury: 9

1. A direct contusion of the brain at the site of trauma (coup) or

opposite the site of trauma with the skull (contrecoup)
2. Diffuse axonal injury caused by high-velocity impact or
deceleration injuries that disturb the normal gray/white ma er
border
3. Foreign object or penetrating trauma
4. Skull fractures leading to resultant parenchymal injury

Secondary brain injury can occur because of cerebral hypoxemia,

cerebral hypertension or hypotension, increased intracranial
pressure, hypothermia or hypothermia, and metabolic
abnormalities. 4 , 9 To prevent secondary brain injuries, efforts
should be directed at early evacuation of expanding intracranial
masses, and maintaining normal intravascular volume and mean
arterial pressures while limiting blood loss. The normal intracranial
pressure is 10 mm Hg, and sustained pressures greater than 22 mm
Hg are associated with poor outcomes. 4

Early Total Care Versus Damage Control

Versus Early Appropriate Care
Appropriate timing for definitive management of orthopaedic
injuries has been debated extensively, and there are three eras of
orthopaedic management.
Early Total Care
The primary approach to management of long bone fractures in
polytrauma patients in the 1980s and 1990s was early total care and
early intramedullary nailing. 41 - 43 Early total care was made
possible with growing improvements in surgical techniques and
instrumentation as well as improved ability to ventilate patients. 20
It has been shown that early definitive fixation of femoral fractures
allowed for early mobility, decreased risk of pulmonary embolism
and pulmonary complications, and decreased length of
hospital/ICU length of stay. 43 Although this treatment was
successful in many patients, in a subset of patients, unexpectedly
high rates of pulmonary complications developed (ARDS) along
with multiple organ dysfunction. 20 , 44

Second-Hit Phenomenon
The immediate injury, or first hit, results in significant systemic
changes to the patient’s immune system. It initiates a local
inflammatory response that increases proinflammatory cytokines,
including interleukin 6, complement factors, coagulation proteins,
and neutrophils, and leads to microvascular damage. 1 , 45 The
second hit refers to early prolonged definitive surgical intervention
that causes blood loss and ischemia and activates the primed
immune systems to a heightened response resulting in significant
tissue permeability, pulmonary edema, ARDS, multiorgan
dysfunction, and mortality. 46 This systemic inflammatory response
syndrome is life threatening, and DCO was developed to prevent it
from occurring. 42 , 47

Damage Control
The damage control concept was used by general surgeons in the
management of abdominal trauma in the hemodynamically
unstable patient. The three-stage protocol consists of rapid
resuscitation and early surgical intervention to limit the lethal triad.
42
 Stage 1: immediate surgery and abdominal packing to control
hemorrhage and contamination
Stage 2: ICU resuscitation
Stage 3: definitive surgery once the patient is medically and
hemodynamically stabilized 42 , 48

DCO involves rapid stabilization of orthopaedic injuries to limit

prolonged surgery, limit blood loss, expedite resuscitation, and
prevent the second hit from causing systemic inflammatory
response syndrome. 1 , 13 , 16 , 42 DCO can be separated into four
phases: 14 , 16 , 20 phase 1: lifesaving procedures; phase 2: temporary
stabilization of major skeletal fractures; phase 3: ICU monitoring
and resuscitation; stage 4: definitive fixation once medically
optimized.
Broad application of DCO resulted in healthier patients having
prolonged hospital stays, delays to mobilization, and minimal
improvement in long-term outcomes. 45 , 46 , 48 Trauma patients have
since been classified into the following four categories to help
direct treatment: stable, borderline, unstable, and in extremis. 20 , 45
DCO is now limited to patients who are classified as unstable or in
extremis. The management of patients classified as borderline has
become more nuanced, and the characteristics of these patients are
listed in Table 3. 20 , 45 Careful evaluation of patient resuscitation is
necessary to determine when to proceed with definitive
intervention and when to proceed with DCO, and this has been
studied extensively. 20 , 24

Early Appropriate Care

The concept of early appropriate care (EAC) has grown from the
lower rate of DCO practiced in American trauma centers (12%)
compared with 36% to 37% of patients in European centers (36% to
37%). 24 This aggressive resuscitative strategy for patients classified
as borderline emphasized correcting patient lactate levels to ≤2.5
mmol/L to allow for definitive fixation of femoral shaft fractures
within 24 hours of admission. 24 Definitive intramedullary nailing
was performed as early as 8 hours in 48% of patients, the overall
ARDS rate was 1.5%, and the death rate was 2.0%. 24
One study retrospectively evaluated aggressive resuscitative
strategy, patient parameters, and outcomes. 41 With early
hemorrhage control and aggressive resuscitation, metabolic
acidosis was minimized. Patients who were corrected to a lactate
level less than 4.0 mmol/L, pH greater than 7.25, or base excess
greater than 5.5 mmol/L had decreased risks of pulmonary
complications in definitive management of those injuries. 41
In another study, the implementation of the protocol was
prospectively evaluated for definitive management of femoral,
pelvic, acetabular, and lumbar spinal fractures if resuscitation had
achieved those values. Eighty-two percent of patients were treated
within 36 hours of admission and had a decreased complication
rate (16.3%) compared with those treated after 36 hours (33.3%). 49 ,
50
Sixty-seven percent of the delays were due to surgeon-mediated
delay. 50 Delayed surgery was associated with longer hospital/ICU
stays and higher rates of sepsis and acute renal failure.
Although there are limitations to these studies, they do support
the concept of EAC. If patients classified as unstable or borderline
can be appropriately resuscitated to an isolated lactate level less
than 2.5 mmol/L or a lactate level less than 4.0 mmol/L with a
downward trend, pH greater than 7.25, and base excess less than 5.5
mmol/L, early definitive management can be considered.
Additional patient characteristics including pulmonary/chest
injury, brain injury, and abdominal injury must be evaluated before
definitive management. EAC can decrease hospital stay or ICU stay
without significantly increasing ARDS, multiple organ dysfunction
syndrome, and death.

Management of Orthopaedic Injuries

Management of orthopaedic injuries may be broadly viewed as
those interventions done to promote survival or facilitate staged
treatment as well as those done for definitive treatment. Early
management consists of fracture splinting and prompt reduction of
any dislocations. Skeletal traction can provide stability for
diaphyseal femoral fractures and help reduce pelvic and acetabular
fractures.
Open fractures should be débrided as soon as the patient is
considered stable or headed to the operating room. It is important
to anticipate that patients may not be considered stable to return to
the operating room for several days, so a thorough and systematic
débridement and provisional stabilization should be performed.
Management of pelvic ring injuries is inextricably linked to the
resuscitation of patients with polytrauma. Strategies including
external fixation, circumferential sheeting or wrapping, and pelvic
packing have been mentioned. Skeletal traction will assist in
reducing a pelvic ring injury with cranial and posterior
displacement of the hemipelvis or prevent displacement of
minimally displaced pelvic ring injury; however, it should be
avoided if the hemipelvis is caudal and anteriorly displaced.
Occasionally, an antishock iliosacral screw will be necessary and/or
beneficial to provide temporary stability. 16 For acetabular fractures,
skeletal traction can help maintain reduction of the femoral head
beneath the acetabular dome and prevent ongoing chondral injury
from the fracture edges. The timing of fixation for pelvic and
acetabular fractures follows the principle of EAC. If percutaneous
fixation is anticipated, doing so early before patients can generate
an ileus is helpful for visualization.
Femoral fractures are perhaps the most studied injury in the
polytrauma se ing. Skeletal traction may be a viable alternative to
external fixation when DCO is necessary. 51 The timing of femoral
fracture fixation should follow the principles of DCO and EAC.
When DCO is employed, conversion to definitive fixation should be
performed as soon as the patient is appropriately stable, though
infection rates are low after conversion. 52 , 53 Extra caution must be
taken when patients have bilateral femoral fractures, which are
associated with increased mortality, though significant
improvements have been made in recent years. 54 , 55 Surgeons
should be prepared to rapidly change tactics and use damage
control when pursuing EAC. Patients can be treated with EAC, 55
though it is difficult to predict which patients may have
complications, apart from those with lung injury. 55 A 2021 study
compared single-stage versus two-stage medullary nailing for
bilateral femoral fractures and found a higher rate of ARDS in the
two-stage group. 17
Chest wall and shoulder girdle injuries often occur in
combination in the se ing of polytrauma and have gained a ention
in recent years. 56 Specifically, analgesia or stabilization of these
injuries may improve outcomes for polytraumatized patients.
Recent studies have shown that regional anesthesia for patients
with multiple rib fractures can reduce in-hospital mortality and
pneumonia 57 and delirium in elderly patients. 58 Flail chest
(segmental fractures of three or more adjacent rib segments) alters
the mechanics of ventilation. Surgical stabilization of flail chest has
been shown to reduces mortality 59 and may have other benefits
including shorter length of hospital stay, fewer days on a ventilator,
and lower incidence of pneumonia. 60 , 61 Stabilization of multiple
simple rib fractures is more controversial (Figure 2). However,
recent literature has demonstrated similar reductions in terms of
length of stay and pneumonia. 62 , 63 A 2020 randomized controlled
trial showed reduced pain and fewer lung space complications with
rib fixation. 64
 Figure 2 Images from a patient who sustained significant chest and lung
injuries, including fracture of ribs 3 to 11.A, A three-dimensional CT
reconstruction demonstrates the rib fractures and presence of a chest tube. B,
An AP chest radiograph demonstrates plating of most of the fractured ribs.

Controversies and Evidence-Based Care

Many of the emerging techniques and controversies in polytrauma
care focus on resuscitation. Use of thromboelastography and
immune response to guide resuscitation are areas in which new
evidence is constantly emerging. 1 Neutrophil-guided resuscitation
uses neutrophil epitope expression to determine the patient’s
immune status. Recent studies have shown several different
expression phenotypes based on injury severity, which may aid in
outcome prediction. 1 , 65
Specific interventions for hemorrhage control also remain
controversial. The function and utility of pelvic packing and REBOA
were described previously. The specific patients who may benefit
from these techniques and when they are to be employed remains
an ongoing source of debate. Higher quality evidence is necessary
to define the role that these interventions should play in
polytrauma care.
Summary
Management of the patient with polytrauma requires coordinated
care between multiple specialists to identify and control sources of
hemorrhage and appropriately resuscitate the patient. The ABCDEs
provide a systematic guide to primary assessment of the patient.
DCO is reserved for unstable or in extremis patients to prevent a
second hit and development of systemic inflammatory response
syndrome, ARDS, multiorgan dysfunction, and mortality. EAC is
reserved for stable and appropriately resuscitated patients (isolated
lactate <2.5 mmol/L or down trending lactate <4 mmol/L, pH > 7.25,
base excess <5.5 mmol/L). Appropriate resuscitation with a 1:1:1
ratio of red blood cells, fresh-frozen plasma, and platelets has been
shown to improve resuscitation and decrease complications. In
addition to standard stabilization techniques such as pelvic binder
placement, pelvic sheeting, and external fixation, the growing use
and investigation of REBOA, pelvic packing, rib stabilization, TXA
administration, and thromboelastography have continued to
expand options for resuscitation and patient stabilization.
Coordinated care of nonorthopaedic injuries can be lifesaving and
should be approached aggressively. A team approach to
management of these patients can continue to decrease morbidity
and mortality in polytrauma patients.

Key Study Points

Thorough evaluation using Advanced Trauma Life Support guidelines is an essential
first step in the treatment of the patient with polytrauma.
The orthopaedic surgeon must be involved in resuscitation by providing skeletal
stability and stopping hemorrhage. Aggressive and adequate resuscitation is
necessary to facilitate orthopaedic care.
The timing of orthopaedic intervention is dependent on the patient’s physiologic
status. Fully resuscitated patients will benefit from early fixation of long bone injuries,
whereas borderline patients may benefit from damage control. EAC is a guiding
concept for these decisions.
Management of orthopaedic injuries begins by providing early skeletal stability.
Special attention should be paid to pelvic ring injuries, open fractures, bilateral
femoral fractures, and rib fractures.
Annotated References
1. Pape HC, Leenen L: Polytrauma management – What is new and
what is true in 2020? J Clin Orthop Trauma 2021;12:88-95. This
review article examines the evolution and changes in treatment of
patients with polytrauma. The article describes biologic
predilections to systemic inflammatory response syndrome,
ETC/DCO/EAC, and the evolution of resuscitation strategies.
2. Guerado E, Medina A, Mata MI, et al: Protocols for massive
blood transfusion: When and why, and potential complications.
Eur J Trauma Emerg Surg 2016;42:283-295.
3. Pryor JP, Reilly PM: Initial care of the patient with blunt
polytrauma. Clin Orthop Relat Res 2004:30-36.
4. Advanced Trauma Life Support Manual. American College of
Surgeons, 2018.
5. Ferree S, Houwert RM, van Laarhoven JJ, et al: Tertiary survey in
polytrauma patients should be an ongoing process. Injury
2016;47:792-796.
6. Harris MB, Sethi RK: The initial assessment and management of
the multiple-trauma patient with an associated spine injury. Spine
(Phila Pa 1976) 2006;31:S9-S15.
7. Mehta R, Trainee GP, Chinthapalli K, et al: Glasgow coma scale
explained. Br Med J 2019;365:l1296. This is a review of the Glasgow
coma scale.
8. Bernardin B, Troquet JM: Initial management and resuscitation
of severe chest trauma. Emerg Med Clin North Am 2012;30:377-400,
viii-ix.
9. Brautigam RT, Sheppard R, Robinson KJ, Jacobs LM: Evaluation
and treatment of the multiple-trauma patients, in Browner J,
Leveine , Tafton , Kre ek , eds: Skeletal Trauma. Saunders
Elsevier, 2003, pp 177-195.
10. Holcomb JB, Tilley BC, Baraniuk S, et al: Transfusion of plasma,
platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and
 mortality in patients with severe trauma: The PROPPR
randomized clinical trial. J Am Med Assoc 2015;313:471-482.
11. Heyn J, Ladurner R, Ozimek A, et al: Diagnosis and pre-
operative management of multiple injured patients with
explorative laparotomy because of blunt abdominal trauma. Eur J
Med Res 2008;13:517-524.
12. Jakob DA, Benjamin ER, Cho J, et al: Combined head and
abdominal blunt trauma in the hemodynamically unstable
patient: What takes priority? J Trauma Acute Care Surg
2021;90:170-176. This study used the National Trauma Data Bank
to determine whether there are admission characteristics that
predict the need for craniotomy in patients presenting with
abdominal and head trauma. Only 1.5% of patients required
craniotomy and laparotomy within 24 hours of admission. GCS
score of 7 to 8 was an independent predictor for craniotomy in
hypotensive patients requiring laparotomy, whereas GCS score
higher than 8 was associated with later evaluation and
intervention. Level of evidence: IV.
13. Rou MLJr, Falicov A, Woodhouse E, et al: Circumferential
pelvic antishock sheeting: A temporary resuscitation aid. J Orthop
Trauma 2002;16:45-48.
14. Rou MLJr, Falicov A, Woodhouse E, et al: Circumferential
pelvic antishock sheeting: A temporary resuscitation aid. J Orthop
Trauma 2006;20:S3-S6.
15. Gardner MJ, Parada S, Chip Rou MLJr: Internal rotation and
taping of the lower extremities for closed pelvic reduction. J
Orthop Trauma 2009;23:361-364.
16. Gardner MJ, Chip Rou MLJr: The antishock iliosacral screw. J
Orthop Trauma 2010;24:e86-e89.
17. Flagstad IR, Tatman LM, Heare A, et al: Single-stage versus 2-
stage bilateral intramedullary nail fixation in patients with
bilateral femur fractures: A multicenter retrospective review. J
Orthop Trauma 2021;35:499-504. This is a multicenter retrospective
evaluation of single-stage and two-stage intramedullary nailing of
 bilateral femoral shaft fractures. Seventy percent of the patients
in the single-stage cohort underwent definitive fixation within 24
hours of admission. Single-stage fixation was associated with a
significantly lower rate of ARDS, rhabdomyolysis, and inpatient
dialysis. The single-stage cohort had a higher in-hospital
mortality rate (2.7% versus zero), but this was not statistically
significant. Level of evidence: III.
18. Lefering R, Paffrath T, Linker R, et al: Head injury and outcome
– What influence do concomitant injuries have? J Trauma
2008;65:1036-1043.
19. Guerado E, Bertrand ML, Cano JR, et al: Damage control
orthopaedics: State of the art. World J Orthop 2019;10:1-13. This
review article reports the evolution of DCO, the second hit effect,
and implications of DCO strategies.
20. Nicola R: Early total care versus damage control: Current
concepts in the orthopedic care of polytrauma patients. ISRN
Orthop 2013;2013:329452.
21. Giannakopoulos GF, Sal herr TP, Beenen LF, et al: Missed
injuries during the initial assessment in a cohort of 1124 level-1
trauma patients. Injury 2012;43:1517-1521.
22. Black JA, Pierce VS, Juneja K, et al: Complications of
hemorrhagic shock and massive transfusion-a comparison before
and after the damage control resuscitation era. Shock 2021;56:42-
51. This is a review of the evolution of resuscitation strategies for
patients with polytrauma. The article examines the implications
of the previous strategies of large-volume resuscitation and the
development of the current strategy of the 1:1:1 ratio of packed
red blood cells, fresh-frozen plasma, and platelets.
23. Bugaev N, Ra an R, Goodman M, et al: Preperitoneal packing
for pelvic fracture-associated hemorrhage: A systematic review,
meta-analysis, and practice management guideline from the
Eastern Association for the Surgery of Trauma. Am J Surg
2020;220:873-888. This meta-analysis assessed the role of PPP
combined with angioembolization, external fixation, and
 resuscitation in patients with hypotension and with polytrauma.
PPP was shown to be an effective strategy limiting mortality and
infection in isolation or combined with embolization or external
fixation. Level of evidence: III.
24. O’Toole RV, O’Brien M, Scalea TM, et al: Resuscitation before
stabilization of femoral fractures limits acute respiratory distress
syndrome in patients with multiple traumatic injuries despite
low use of damage control orthopedics. J Trauma 2009;67:1013-
1021.
25. Imach S, Wafaisade A, Lefering R, et al: The impact of
prehospital tranexamic acid on mortality and transfusion
requirements: Match-pair analysis from the nationwide German
TraumaRegister DGU®. Crit Care 2021;25:277. The International
TraumaRegister DGU in Germany was retrospectively evaluated
for patients treated with prehospital TXA and compared with a
cohort of patients who did not receive TXA prior to arriving to
the hospital. The prehospital patients treated with TXA had a
lower rate of massive transfusion and early in-hospital mortality
with no significant increase in thromboembolic events. Level of
evidence: III.
26. Roberts I, Shakur H, Coats T, et al: The CRASH-2 trial: A
randomised controlled trial and economic evaluation of the
effects of tranexamic acid on death, vascular occlusive events and
transfusion requirement in bleeding trauma patients. Health
Technol Assess 2013;17:1-79.
27. Copp J, Eastman JG: Novel resuscitation strategies in patients
with a pelvic fracture. Injury 2021;52:2697-2701. This review article
describes current advances in treatment of hemodynamically
unstable patients with pelvic ring injuries. The article stresses the
importance of developing a protocol-based resuscitation strategy
to improve patient outcomes.
28. Castellini G, Gianola S, Biffi A, et al: Resuscitative endovascular
balloon occlusion of the aorta (REBOA) in patients with major
trauma and uncontrolled haemorrhagic shock: A systematic
 review with meta-analysis. World J Emerg Surg 2021;16:41. This is a
systematic review of the use of REBOA compared with
resuscitative thoracotomy with/without REBOA or no REBOA for
treatment of patients with noncompressible torso injuries and
hypotension. REBOA demonstrated a positive effect when
compared with resuscitative thoracotomy, but given the
variability in indications for use, further investigation was
warranted. Level of evidence: III.
29. Marchand LS, Sepehri A, Hannan ZD, et al: Resuscitative
endovascular balloon occlusion of the aorta in hemodynamically
unstable patients with pelvic ring injuries. J Orthop Trauma
2021;36(2):74. This is a retrospective case series examining the use
of REBOA as an adjuvant treatment to trauma resuscitation in
patients with pelvic ring injuries. REBOA was used at the
discretion of the trauma surgeons in the critically ill patients. The
mortality rate in this cohort was 48%, 28% of patients required
fasciotomy, and 20% required amputation. Given the high rate of
complications, universal use of REBOA in these patients should
be further investigated. Level of evidence: IV.
30. Lindvall E, Davis J, Martirosian A, et al: Bilateral internal iliac
artery embolization results in an unacceptably high rate of
complications in patients requiring pelvic/acetabular surgery. J
Orthop Trauma 2018;32:445-451.
31. Hymel A, Asturias S, Zhao F, et al: Selective versus nonselective
embolization versus no embolization in pelvic trauma: A
multicenter retrospective cohort study. J Trauma Acute Care Surg
2017;83:361-367.
32. Hundersmarck D, Hietbrink F, Leenen LPH, et al: Pelvic packing
and angio-embolization after blunt pelvic trauma: A
retrospective 18-year analysis. Injury 2021;52:946-955. This is a
retrospective examination of embolization in hemodynamically
stable patients and PPP with temporary external fixation and
embolization for hemodynamically unstable pelvic ring fractures.
In-hospital mortality was 44% in the PPP cohort compared with
4% in the embolization cohort. This difference is likely due to the
 severity of presenting injury and hemodynamic instability in the
PPP cohort. Level of evidence: IV.
33. Langford JR, Burgess AR, Liporace FA, et al: Pelvic fractures:
Part 1. Evaluation, classification, and resuscitation. J Am Acad
Orthop Surg 2013;21:448-457.
34. Mikdad S, van Erp IAM, Moheb ME, et al: Pre-peritoneal pelvic
packing (PPP) for early hemorrhage control reduces mortality
compared to resuscitative endovascular balloon occlusion of the
aorta (REBOA) in severe blunt pelvic trauma patients: A
nationwide analysis. Injury 2020;51:1834-1839. This retrospective
analysis of the Trauma Quality Improvement Program (TQIP)
compared the outcomes of PPP and REBOA use in
hemodynamically unstable patients. Despite patients having
similar Injury Severity Score and hemodynamics at presentation,
REBOA was associated with higher 24-hour mortality and in-
hospital mortality. Level of evidence: III.
35. Asmar S, Bible L, Chehab M, et al: Resuscitative endovascular
balloon occlusion of the aorta vs pre-peritoneal packing in
patients with pelvic fracture. J Am Coll Surg 2021;232:17-26.e12.
This is a retrospective comparison of REBOA, preperitoneal
packing (PP), and REBOA with PP for the treatment of
hemodynamically unstable patients. Using the ACS Trauma
Quality Improvement Database, the REBOA was shown to have
improved outcomes when compared with REBOA + PP and PP.
REBOA + PP was associated with higher rates of 24-hour
mortality, in-hospital mortality, and 4-hour packed red blood cell
units compared with the REBOA and PP groups. Additional
investigation is warranted in the use of the less invasive REBOA.
Level of evidence: III.
36. Stahel PF, Moore EE, Burlew CC, et al: Preperitoneal pelvic
packing is not associated with an increased risk of surgical site
infections after internal anterior pelvic ring fixation. J Orthop
Trauma 2019;33:601-607. This is a retrospective observational
cohort study comparing single-stage primary internal fixation
with staged internal fixation after PPP and external fixation for
 management of unstable pelvic ring injuries. There was no
significant difference in the infection rate between the two
cohorts despite the PPP cohort undergoing multiple surgical
procedures. Level of evidence: III.
37. Chrysou K, Halat G, Hoksch B, et al: Lessons from a large
trauma center: Impact of blunt chest trauma in polytrauma
patients-still a relevant problem? Scand J Trauma Resusc Emerg
Med 2017;25:42.
38. Gönültaş F, Kutlutürk K, Gok AFK, et al: Analysis of risk factors
of mortality in abdominal trauma. Ulus Travma Acil Cerrahi Derg
2020;26:43-49. This was a retrospective evaluation of patients
presenting to a single emergency room following blunt and
penetrating abdominal trauma to assess the risk factors for
mortality. The presence of elevated liver enzymes, (alanine
transaminase), retroperitoneal bleeds, extra-abdominal injuries,
and lower mean arterial pressures were associated with high
rates of mortality. Level of evidence: IV.
39. Brenner M, Hicks C: Major abdominal trauma: Critical decisions
and new frontiers in management. Emerg Med Clin North Am
2018;36:149-160.
40. Pfeifer R, Tarkin IS, Rocos B, et al: Pa erns of mortality and
causes of death in polytrauma patients – Has anything changed?
Injury 2009;40:907-911.
41. Vallier HA, Wang X, Moore TA, et al: Timing of orthopaedic
surgery in multiple trauma patients: Development of a protocol
for early appropriate care. J Orthop Trauma 2013;27:543-551.
42. Giannoudis PV, Giannoudi M, Stavlas P: Damage control
orthopaedics: Lessons learned. Injury 2009;40(suppl 4):S47-S52.
43. Bone LB, Johnson KD, Weigelt J, et al: Early versus delayed
stabilization of femoral fractures. A prospective randomized
study. J Bone Joint Surg Am 1989;71:336-340.
44. Ecke H, Faupel L, Quoika P: Considerations on the time of
surgery of femoral fractures [German]. Unfallchirurgie 1985;11:89-
93.
45. Hildebrand F, Giannoudis P, Kre eck C, et al: Damage control:
Extremities. Injury 2004;35:678-689.
46. Pape HC, Giannoudis P, Kre ek C: The timing of fracture
treatment in polytrauma patients: Relevance of damage control
orthopedic surgery. Am J Surg 2002;183:622-629.
47. Pape HC, Halvachizadeh S, Leenen L, et al: Timing of major
fracture care in polytrauma patients – An update on principles,
parameters and strategies for 2020. Injury 2019;50:1656-1670. This
systematic review was performed to evaluate changes in
resuscitation strategies, diagnostic options, and surgical
treatment for patients presenting with polytrauma. The article
details the changes and current treatment modalities for these
complex patients. Level of evidence: III.
48. Moore TA, Simske NM, Vallier HA: Fracture fixation in the
polytrauma patient: Markers that ma er. Injury 2020;51(suppl
2):S10-S14. This article discussed the transition of orthopaedic
management of patients with polytrauma from ETC to DCO to
EAC. The article describes goals of resuscitation (lactate < 4
mmol/L, pH ≥ 7.25, base excess ≥ −5.5 mmol/L) to improve the
safety of definitive management of femur, pelvis, acetabulum,
and lumbar fractures within 36 hours of admission.
49. Vallier HA, Moore TA, Como JJ, et al: Complications are
reduced with a protocol to standardize timing of fixation based
on response to resuscitation. J Orthop Surg Res 2015;10:155.
50. Vallier HA, Moore TA, Como JJ, et al: Teamwork in trauma:
System adjustment to a protocol for the management of multiply
injured patients. J Orthop Trauma 2015;29:e446-e450.
51. Scannell BP, Waldrop NE, Sasser HC, et al: Skeletal traction
versus external fixation in the initial temporization of femoral
shaft fractures in severely injured patients. J Trauma 2010;68:633-
640.
52. Nowotarski PJ, Turen CH, Brumback RJ, et al: Conversion of
external fixation to intramedullary nailing for fractures of the
 shaft of the femur in multiply injured patients. J Bone Joint Surg
Am 2000;82:781-788.
53. Della Rocca GJ, Crist BD: External fixation versus conversion to
intramedullary nailing for definitive management of closed
fractures of the femoral and tibial shaft. J Am Acad Orthop Surg
2006;14:S131-S135.
54. O’Toole RV, Lindbloom BJ, Hui E, et al: Are bilateral femoral
fractures no longer a marker for death? J Orthop Trauma
2014;28:77-81.
55. Lane MK, Nahm NJ, Vallier HA: Morbidity and mortality of
bilateral femur fractures. Orthopedics 2015;38:e588-592.
56. Sweet AAR, Beks RB, FFA IJ, et al: Epidemiology of combined
clavicle and rib fractures: A systematic review. Eur J Trauma
Emerg Surg 2021; June 1 [Epub ahead of print]. This systematic
review evaluated the incidence of combined clavicle and rib
fractures and the relationship between these injuries in
polytrauma patients. Combined clavicle and rib fractures
occurred in 18.6% of patients in one of the included studies and
the high correlation of these injuries may have implications on
outcomes and treatment modalities. Level of evidence: IV.
57. Uhlich R, Kerby JD, Bosarge P, et al: Use of continuous
intercostal nerve blockade is associated with improved outcomes
in patients with multiple rib fractures. Trauma Surg Acute Care
Open 2021;6:e000600. This retrospective comparison of
continuous regional anesthesia with the standard of care for
management of multiple rib fractures demonstrated decreased
rates of pneumonia, in-hospital mortality, and need for
tracheostomy. There were no differences in ICU-free or
ventilator-free days between the cohorts. Level of evidence: III.
58. O’Connell KM, Patel KV, Powelson E, et al: Use of regional
analgesia and risk of delirium in older adults with multiple rib
fractures: An Eastern Association for the Surgery of Trauma
multicenter study. J Trauma Acute Care Surg 2021;91:265-271. This
retrospective multicenter cohort study compared the effect of
 regional anesthesia to oral/intravenous pain management on the
incidence of delirium in older adult patients sustaining multiple
rib fractures. The multivariate analysis demonstrated a 35%
reduction in delirium in the regional anesthesia cohort. Level of
evidence: III.
59. Taghavi S, Ali A, Green E, et al: Surgical stabilization of rib
fractures is associated with improved survival but increased acute
respiratory distress syndrome. Surgery 2021;169:1525-1531. This is
a retrospective analysis of the National Trauma Data Bank
comparing surgical with nonsurgical management of rib
fractures. Patients with flail chest were more likely to undergo rib
fracture fixation compared with patients with a single rib fracture
or multiple rib fractures. Surgical stabilization of rib fractures in
patients with flail chest was associated with improved mortality
but varying effects on ARDS. Fixation of three or more rib
fractures was associated with a higher incidence of ARDS.
Further investigation is indicated. Level of evidence: III.
60. Long R, Tian J, Wu S, et al: Clinical efficacy of surgical versus
conservative treatment for multiple rib fractures: A meta-analysis
of randomized controlled trials. Int J Surg 2020;83:79-88. This
meta-analysis of RCTs comparing surgical with nonsurgical
management of multiple rib fractures showed that surgical
fixation is associated with shorter length of stay, decreased ICU
stay, and decreased duration of mechanical ventilation.
Additionally, surgical treatment resulted in less chest wall
deformity and pneumonia. Level of evidence: I.
61. Ingoe HM, Coleman E, Eardley W, et al: Systematic review of
systematic reviews for effectiveness of internal fixation for flail
chest and rib fractures in adults. BMJ Open 2019;9:e023444. This
review of systematic reviews compares surgical with nonsurgical
management of multiple rib fractures in patients with
polytrauma. Surgical management demonstrated some
improvements in hospital length of stay, duration of intubation,
and length of ICU stay when compared with nonsurgical
treatment.
62. Wijffels MME, Prins JTH, Perpetua Alvino EJ, et al: Operative
versus nonoperative treatment of multiple simple rib fractures: A
systematic review and meta-analysis. Injury 2020;51:2368-2378.
This review investigated the effect of fixation of multiple simple
rib fractures on patient outcomes. Fixation of multiple simple rib
fractures was not associated with changes in duration of
mechanical ventilation or ICU length of stay but did decrease the
risk of pneumonia, mortality, and hospital length of stay. These
benefits must be balanced with a risk of infection that ranged
from zero to 9.4%.
63. Gerakopoulos E, Walker L, Melling D, et al: Surgical
management of multiple rib fractures reduces the hospital length
of stay and the mortality rate in major trauma patients: A
comparative study in a UK major trauma center. J Orthop Trauma
2019;33:9-14. This study investigated the use of a new guideline to
categorize rib fractures to compare surgical with nonsurgical
management of multiple rib fractures. Rib fracture fixation was
associated with significantly decreased ICU admissions,
decreased hospital length of stay, and decreased mortality. Level
of evidence: III.
64. Pieracci FM, Leasia K, Bauman Z, et al: A multicenter,
prospective, controlled clinical trial of surgical stabilization of rib
fractures in patients with severe, nonflail fracture pa erns (Chest
Wall Injury Society NONFLAIL). J Trauma Acute Care Surg
2020;88:249-257. This multicenter prospective study compared
surgical with nonsurgical management of multiple rib fractures
in patients without flail chests. There was no difference in
hospital or ICU length of stay. There were improvements in
pleural space complications and quality of life at 2-week follow-
up after surgical fixation. Additional studies are warranted in
patients best treated with surgical fixation in the absence of flail
chest. Level of evidence: III.
65. Spijkerman R, Hesselink L, Bongers S, et al: Point-of-care
analysis of neutrophil phenotypes: A first step toward immuno-
based precision medicine in the trauma ICU. Crit Care Explor
2020;2:e0158. This point-of-care study was performed to assess
the feasibility of using flow cytometry of blood drawn from
patients with polytrauma to determine neutrophil marker
expression and correlate phenotypes with the Injury Severity
Score and infectious complications. The neutrophil profile
CD16dim /CD62Lbright was correlated with patient Injury Severity
Score and infectious complications. Level of evidence: IV.
C H AP T E R 2 2

Management of Open Fractures

Kevin J. Perry MD, DPT, Matthew R. Garner MD, FAAOS

Dr. Garner or an immediate family member serves as a paid consultant to or is an employee of

DePuy, a Johnson & Johnson Company and Globus Medical; has stock or stock options held in
ROM3 Rehab; has received research or institutional support from DePuy, a Johnson & Johnson
Company and Orthopaedic Trauma Association; and serves as a board member, owner, officer, or
committee member of the Orthopaedic Trauma Association. Neither Dr. Perry nor any immediate
family member has received anything of value from or has stock or stock options held in a
commercial company or institution related directly or indirectly to the subject of this chapter.

ABSTRACT
Appropriate management of open fractures is dependent on
fracture pa ern, anatomic location, and severity of soft-tissue
injury. Although these injuries are common, they remain both a
topic of debate and ongoing study. Antibiotic management,
including systemic prophylaxis and local delivery, is evolving.
Modern surgical techniques are allowing for earlier definitive
management. It is important to be up to date on the treatment
options and outcomes of open fractures.
Keywords: antibiotic prophylaxis; open fracture; soft-tissue
management

Introduction
Open fractures occur across a spectrum of patient ages and through
a variety of mechanisms. Despite their frequent occurrence and
abundant research supporting their care, open fractures remain a
clinical challenge with many unresolved questions. These injuries
occur at a rate of 3.4 per 100,000 and at a mean age of 45.5 years
with a male predominance. Seventy-five percent of open fractures
are a ributable to finger, distal radial, and lower extremity injuries,
particularly tibial and ankle fractures. Motor vehicle collisions
account for 34.1% of open fractures. 1 However, a single-center
epidemiologic study showed a decline in motor vehicle–related
open fractures between 1988 and 2010, which can be a ributed to
improved safety features of vehicles as well as alcohol and speeding
restrictions. 2

Classification
Open fractures are classified in an a empt to guide treatment,
improve communication, predict outcomes, and allow for
comparative analysis. Classification is performed at the time of
surgical débridement. The Gustilo-Anderson classification is the
most commonly used system based on their pivotal research in
1976. 3 The original classification has been modified, but in its
contemporary form the Gustilo-Anderson classification stratifies
open fractures by the size of the open wound, fracture pa ern, the
amount of periosteal stripping, contamination, and need for free-
tissue transfer or vascular repair. 3 , 4 The Orthopaedic Trauma
Association published an open fracture classification (OTA-OFC) in
2010 based on expert consensus. The OTA-OFC stratifies injuries
based on severity of injury to skin, muscle, and arteries as well as
level of contamination and amount of bone loss. 5
Although classification systems enhance communication about
open fractures, they do not always provide enough information to
make specific treatment decisions. A comparative study found
similar moderate rates of interobserver reliability between the
Gustilo-Anderson classification and the OTA-OFC but note that the
OTA-OFC provides more information about the injury. 6
Photographs of injuries before and after débridement have become
invaluable as data-sharing technology has improved. A 2019 study
in the United Kingdom found that use of a smartphone-based app
improved government-compliant information transfer of open
fracture images to patient medical records. 7 Clinical photographs
often provide information to providers that description or
classification cannot and may prove a useful tool in
interdisciplinary communication regarding care of open fractures
(Figure 1).

Figure 1 Clinical photograph (A) and radiograph (B) of an open calcaneal

fracture. Although the wound is relatively small with no visible contamination,
there is significant periosteal stripping and bone loss due to the high-energy
mechanism of injury. The radiograph, combined with the clinical image, provides
a more complete understanding of the injury.

Ideally, classification would predict outcomes. A multicenter

retrospective review shows subcategories of the OTA-OFC to be
predictive of outcomes. Specifically, the OTA-OFC skin subcategory
correlated strongly with type of definitive closure, the OTA-OFC
muscle subcategory was predictive of nonunion, and the
subcategories muscle and arterial were predictive of amputation. 8
A 2021 retrospective review of upper extremity open fractures
shows that the OTA-OFC correlates with definitive type of closure.
This same study shows that the OTA-OFC muscle subcategory
correlates with 90-day wound complications. 9

Initial Management
The mechanism of injury of open fractures can vary widely. Initial
management includes a general trauma assessment based on
Advanced Trauma Life Support guidelines. Open fractures can be a
dramatic source of distracting injury, and a systematic evaluation is
essential to avoid missing other injuries. Although open fractures
in isolation are the focus of discussion, the overall condition of the
patient is an essential component of decision making. In the most
severe cases, life over limb is a valuable treatment-guiding mantra.
Related to open fracture management, early administration of
parenteral antibiotics is essential to infection prevention. The
importance of systemic antibiotics in open fractures was first
demonstrated in 1974. 10 A subsequent study showed that timing of
antibiotics is also important in identifying a significant difference
in infection rates if antibiotics were administered within 3 hours of
injury. 11 This finding has been corroborated in multiple studies
and trauma guidelines, including Eastern Association for the
Surgery of Trauma (EAST), Surgical Infection Society, and British
Orthopaedic Association Standard for Trauma, that recommend
antibiotic administration as soon as possible to prevent infection in
open fractures. 12 - 15 In the emergency department, open fractures
should be cleared of gross contamination, covered in a saline-
soaked gauze dressing, and splinted to avoid further soft-tissue
injury. Neurovascular examination and compartment syndrome
assessment are critical. 13

Antibiotic Management
Antibiotic selection and duration for prophylaxis in open fractures
is an evolving issue. Traditionally, antibiotic treatment has been
guided by the Gustilo-Anderson classification and the presence of
gross contamination. Seasonal and geographic variations in
antibiograms make a single best-practice protocol challenging to
define. 16
The EAST guidelines recommend gram-positive coverage alone
for type I and II open fractures. For type III fractures, coverage is
expanded to provide coverage against gram-negative species.
Penicillin may be added for suspected soil or fecal contamination. 12
The British Orthopaedic Association Standard for Trauma
guidelines recommend antibiotic administration ideally within 1
hour of injury but make no antibiotic recommendations. 13 Based on
available literature, the Surgical Infection Society recommends
gram-positive prophylaxis with cephalosporin monotherapy as soon
as possible but is unable to recommend gram-negative or
clostridial coverage. 15
The addition of gram-negative coverage in type III open fractures
has been questioned. A single-center retrospective series of type III
open fractures showed no change in the incidence of infection with
the addition of aminoglycoside but an increased incidence of acute
kidney injury from 4% to 10%. 17 Polytraumatized patients have
multiple risk factors for acute kidney injury, and the addition of a
nephrotoxic antibiotic may not be benign. Risk factors for acute
kidney injury in the se ing of open fracture and administration of
gentamicin include female sex, obesity, intensive care unit
admission, CT contrast administration, and age older than 60 years.
18
One study evaluated combat-related open fractures and the
addition of extended gram-negative coverage. There was a noted
benefit for prevention of skin and soft-tissue infections, but no
difference in the rate of osteomyelitis. The patients who had
received extended gram-negative coverage and in whom
osteomyelitis developed were more likely to have an antibiotic-
resistant organism. It was concluded that, for combat-related open
fractures, cefazolin or clindamycin monotherapy is recommended.
19
According to a 2020 review on gram-negative coverage and type
III open fractures, a strong case was made for cefazolin
monotherapy as the antibiotic choice for all open fractures. 20
A 2021 multicenter study of more than 1,200 patients reviewed
antibiotic selection for open fractures and found moderate
adherence to the EAST guidelines in type I and II open fractures
and low adherence in type III fractures. In this series, only 17.2% of
type III open fractures received cefazolin and aminoglycoside
therapies as suggested per the EAST guidelines. A total of 31.0% of
type I and II open fractures inappropriately received gram-negative
coverage in this series. 21
The addition of high-dose penicillin for fecal and soil
contamination has also been called into question. Penicillin was
originally recommended for clostridial gangrene and group A beta-
hemolytic Streptococcus coverage. A 2011 guideline endorsed by the
Infectious Diseases Society of America and the Surgical Infection
Society recommends against the use of penicillin in postinjury
antimicrobial coverage for combat-related injuries. 22 That was
echoed in a prospective study in which aminoglycosides,
vancomycin, and penicillin were removed from the treatment
protocol for open fracture antibiotic prophylaxis, with no significant
difference in rate of infection or rate of resistant organism
infection. 23
Antibiotic duration is as controversial as antibiotic selection. It is
unclear whether there is any benefit to extending antibiotic
coverage beyond 24 hours. A meta-analysis showed no benefit for
prolonged antibiotics defined as 72 hours; subgroup analysis
showed shorter antibiotic durations of 24 to 48 hours were
equivalent to a 72-hour treatment duration. 24 A 2020 secondary
analysis from the Fluid Lavage of Open Wounds, or FLOW trial,
a empted to shed light on the ambiguity of extended antibiotic
duration, which they defined as more than 72 hours. This
multicenter prospective study found a differential effect of
extended antibiotic duration depending on the level of
contamination. In open fractures with mild contamination,
extended antibiotic duration showed a tendency toward increased
infection rate. However, extended antibiotic duration was strongly
protective of surgical site infection in highly contaminated open
fractures. 25
The indications for application of local antibiotics to open
fractures, in isolation or in addition to systemic antibiotics,
continue to evolve. Although antibiotic beads and pouches have
been used for years for local control of or prophylaxis against
infection, consensus regarding indications, duration, dosing, and
carrier medium has not been reached. A systematic review with
pooled meta-analysis including 2,738 patients with open fractures
showed a significantly lower infection rate when local antibiotics
were applied, with a risk reduction of 11.9%. This review included
eight studies, six of which compared antibiotic-loaded polymethyl
methacrylate (PMMA) beads with systemic antibiotics with
systemic antibiotics alone and two studies that evaluated the
addition of antibiotic powder without a carrier medium to standard
care. 26 An animal study compared irrigation and débridement
alone with the addition of vancomycin powder or PMMA beads
containing vancomycin and tobramycin. The addition of local
antibiotics significantly decreased bacterial colonization 14 days
after inoculation. There was no significant difference between
bacterial counts when comparing powder with PMMA beads. 27 In a
2020 animal study, early application of a gentamicin-loaded
hydrogel without the use of systemic antibiotics was more effective
than systemic antibiotics at eliminating bacterial contamination 7
days after injury. 28
A 2020 review describes the benefits and drawbacks to multiple
modes of local antibiotic delivery including PMMA beads,
antibiotic powder, hydrogels, collagen sponges, and calcium sulfate
or phosphate beads. 29 Dense carriers such as PMMA provide
structural stability, fill dead space, and can promote formation of
an induced membrane in the se ing of bone defects, but have
relatively poor elution compared with other carriers and often
require surgical removal. Antibiotic powders and hydrogels have
rapid high-concentration elution potential and can diffuse into
small spaces but may not last as long and may be washed away
from their intended target by hematoma or drain suction. Calcium
sulfate beads and collagen sponges fall somewhere in between. The
most efficient carrier has not been identified, and indications for
use continue to evolve.
Initial Surgical Management
Goals of treatment at the initial débridement include a thorough
and systematic assessment of the traumatic wounds, exploration of
the zone of injury, and débridement of all foreign debris and
nonviable tissues, as well as obtaining hemostasis and sterile
coverage in the form of primary closure or temporization with a
sterile dressing. Each of these steps is essential for prevention of
infection with emphasis on surgical débridement. Questions
remain regarding optimal timing of débridement, extent of
débridement, quantity of irrigation, and whether primary closure or
dressing is necessary.
Optimal timing of débridement of open fractures continues to be
a controversial issue. The historic basis for the 6-hour rule, which
was once a pervasive teaching in orthopaedic training, was
reviewed. 30 Based on animal studies without the use of antibiotics,
it was once recommended that all open fractures be débrided
within 6 hours. This theory has since been refuted in multiple
studies with no clear temporal relationship between time to
débridement and surgical site infections. 30 Consistent with
multiple recent small observational and retrospective series, a 2020
retrospective review of 215 open tibial fractures showed no
statistically significant relationship between time to débridement
and infection. Risk factors for infection in that study included
smoking, diabetes, surgical time, and higher Gustilo-Anderson
classification. 31 Similar results were observed in a retrospective
review of 45 open fractures managed with a two-stage orthoplastic
algorithm. No relationship was observed between deep infection
and time to débridement or time to definitive soft-tissue coverage.
32

A 2021 review with a meta-analysis of 18,239 patients found a

time-dependent association between time to débridement and
surgical site infections. Débridements performed beyond 12 hours
had an odds ratio of 1.51 and beyond 24 hours had an odds ratio of
2.17. This finding was most evident for severe open fractures with a
different temporal relationship for less severe fractures. 33 A 2021
commentary published in response to this meta-analysis aptly
encourages surgeons to débride open fractures in a timely manner.
All open fractures should ideally be débrided within the first 24
hours if there is no gross contamination and antibiotics are
administered early. However, the pendulum may be swinging back
toward earlier débridement for severe open fractures, ideally within
the first 12 hours. 34 Surgical timing is often dictated by factors
other than severity of the open fracture; the entirety of the patient’s
care needs to be considered. Quality of débridement should not be
sacrificed for early surgical intervention.
Surgical débridement of open fractures should involve a
systematic evaluation of skin, subcutaneous tissues, fascia, muscle,
and bone throughout the zone of injury (Figure 2). Sharp
débridement should be used to remove all foreign debris and
nonviable tissues. Exposure of all bony surfaces including
evaluation of the intramedullary canal may be required in high-
energy injuries. Defining tissue viability may prove difficult, with
li le evidence to support a specific treatment algorithm. The classic
teaching of the four C’s—color, consistency, circulation, and
contractility—has not been shown to correlate with histologic
evaluation. 35 The tug test, a colloquialism commonly taught,
defines that any tissue that can be removed with a light tug should
be removed during initial débridement. The current best-practice
dogma for infection prevention is for aggressive débridement of
open fractures, although this has recently been challenged. In a
2019 single-center cohort study, devitalized large bone fragments
were retained if their removal would cause an iatrogenic bone
defect. In this series of IIIB open tibias with early soft-tissue
coverage, infection rates were not significantly different if a
devitalized bone fragment was retained at time of initial
débridement. 36
 Figure 2 A and B, Clinical photographs of a severe open tibial fracture before
and after surgical débridement. The zone of injury was much larger than the
open wound because of an internal degloving injury.

Subsequent or serial débridement is performed to assist with

evacuation of surgically débrided tissue. Irrigation alone should not
be used as a surrogate for adequate débridement. The volume of
irrigation is often a topic of debate with no current human clinical
studies to guide decision making. The use of 3 L of irrigation per
increasing type of Gustilo-Anderson classification is often taught
but is not evidence-based. Ideal irrigation volume should be at the
surgeon’s discretion, with the volume proportionate to the size of
the wound and level of contamination.
 A 2020 review details prior controversies regarding ideal
irrigation solution including the use of surfactants and/or
antibiotics. Prior studies have revealed that irrigation with normal
saline without the use of surfactants or antibiotics has the lowest
complication rate. The pressure of irrigation solution does not
appear to affect the rate of surgical site infections, despite higher
rebound bacterial cell counts with the use of high-pressure
techniques. 37 A series of 109 open lower-limb fractures compared
isotonic saline with distilled water for irrigation. Despite a high rate
of wound infections in both groups (34% distilled water, 44%
isotonic saline), there was not a statistically significant difference in
infection rates between groups. Given the increased availability and
decreased cost of distilled water compared with isotonic saline,
particularly in austere environments, this may serve as a useful
alternative. 38
After a thorough débridement and irrigation is performed, the
traumatic wound must be temporized with dressings or closed.
Deciding which traumatic wounds can be immediately closed is
controversial and should be made at the surgeon’s discretion. A
2020 retrospective review compared wound care practices (primary
versus delayed closure) relative to open fractures at two level 1
trauma centers. Site 1 had a primary closure rate of 78% compared
with 36% at site 2. There were no significant differences in rates of
complications, nonunions, or amputations. The average number of
surgical procedures to achieve definitive closure was 1.5 at site 1
compared with 3.4 at site 2. 39 Similarly, a single-center study of 84
matched pairs of open fractures showed fewer deep infections and
fewer nonunions when primary closure was performed. 40 Ninety-
six pediatric Gustilo-Anderson type II and IIIA open fractures were
reviewed and showed similar rates of complications between
primary closure and delayed closure. 41 Acute closure of traumatic
wounds appears safe, provided an atraumatic closure can be
achieved with minimal soft-tissue tension.
When wounds are unable to be closed during the initial
procedure, temporizing with dressings or negative-pressure wound
therapy (NPWT) is preferred. Despite its abundant application,
recent studies show no clear benefit to the use of NPWT. A 2018
Cochrane systematic review with pooled meta-analysis showed no
difference in infection rate, no difference in patient-reported
outcomes, and no cost benefit to the use of NPWT compared with
dressings alone. 42 Similarly, a 2020 study from the United Kingdom
Major Trauma Network across 24 hospitals that included 1,548
patients with major lower extremity trauma showed no difference
in rate of infection at 30 or 90 days, no difference in patient-
reported outcomes, and no difference in scar appearance with
NPWT. 43

Definitive Management of Fracture

Temporizing fixation is often advisable in the se ing of severe open
fractures with or without contamination. This may be due to the
need for multiple débridements or the inability of a patient to
handle definitive procedures. Static external fixation is often used
initially because it can be applied quickly with limited surgical
insult and allows for fracture stabilization as well as soft-tissue rest.
Definitive treatment is patient-dependent and fracture-dependent,
typically using intramedullary or plate fixation. Circular ring
fixation has been used for both fracture stabilization and to permit
delayed primary wound closure by introducing an intentional
shortening or angular deformity. 44 , 45 For definitive internal
fixation, timing is again related to a patient’s overall condition,
fracture pa ern, the ability to obtain a clean wound bed, and timing
of the planned soft-tissue coverage.
Definitive soft-tissue management should follow the established
reconstructive ladder and be both patient-dependent and provider-
dependent. One study has suggested that definitive soft-tissue
coverage within 7 days had lower complication rates. 46 This is
supported by a series of 140 consecutive IIIB tibias from a single
center; there was a statistically insignificant 36% increase in risk of
osteomyelitis if flap coverage was performed after 7 days.
Interestingly in this series, the risk of nonunion was lower with
delayed flap coverage. It was concluded in this 2019 study that
outcomes are similar with coverage before and after 7 days, and
delays to soft-tissue coverage should not encourage amputation. 47
The Bioburden study is a Major Extremity Trauma Research
Consortium multicenter trial of type III open tibial fractures
investigating contamination at the time of definitive soft-tissue
coverage or closure and its correlation with deep infection. The
results of the study have yet to be released. 48

Outcomes
Institutions should make efforts to expedite care of open fractures.
Institutional guidelines can eliminate interdisciplinary confusion
and streamline care of open fractures. Antibiotic protocols,
education for emergency providers, dedicated orthopaedic trauma
operating rooms, orthoplastic surgery teams, and institutional
clinical pathways can all improve the care of patients with open
fractures. 36 , 49 - 51 After implementation of an open fracture clinical
pathway at a single center, significant differences were observed,
including a 37.5% decrease in length of stay. For type III fractures,
length of stay decreased 46.7%, and the number of surgical
procedures decreased by 50%. 51 Infection following open fracture is
not uncommon. In the prospective FLOW cohort of 2,445 patients
with open fractures, superficial surgical site infections developed in
168 patients. Eighty-three percent (n = 139) were treated with
antibiotics alone, with a 70% success rate. 52 Deep infections require
surgical treatment and can be detrimental to a patient’s quality of
life while imposing a significant economic burden. In a prospective
study out of the United Kingdom, deep surgical-site infection after
open fracture was associated with a significant difference in quality-
adjusted life years and a mean increase in healthcare costs of 1,950
pounds ($2,703 US dollars). 53

Summary
Open fractures are and will remain common and challenging
clinical problems. As new evidence guides management, it is
important that those who treat patients with these injuries are up
to date on current treatment options and recommendations.
Although debate continues on several topics, early administration
of systemic antibiotics and a thorough surgical débridement
remain the mainstay of infection prevention. Definitive
management of fracture and soft tissues remains injury-dependent
and provider-dependent.

Key Study Points

Early administration of intravenous antibiotics in the setting of an open fracture
decreases the risk of late infection.
Surgical débridement of open fractures should be performed as soon as possible,
taking into account fracture and wound severity, as well as the overall condition of
the patient.
Definitive fracture and soft-tissue management requires a coordinated effort
between involved providers and defined clinical pathways may improve patient
outcomes.

Annotated References
1. Court-Brown CM, Bugler KE, Clement ND, Duckworth AD,
McQueen MM: The epidemiology of open fractures in adults. A
15-year review. Injury 2012;43(6):891-897.
2. Winkler D, Goudie ST, Court-Brown CM: The changing
epidemiology of open fractures in vehicle occupants, pedestrians,
motorcyclists and cyclists. Injury 2018;49(2): 208-212.
3. Yim GH, Hardwicke JT: The evolution and interpretation of the
Gustilo and Anderson classification. J Bone Joint Surg Am
2018;100(24):e152.
4. Kim PH, Leopold SS: In brief: Gustilo-Anderson classification.
[corrected]. Clin Orthop Relat Res 2012;470(11):3270-3274.
5. Orthopaedic Trauma Association: Open Fracture Study Group:
A new classification scheme for open fractures. J Orthop Trauma
 2010;24(8):457-464.
6. Ghoshal A, Enninghorst N, Sisak K, Balogh ZJ: An interobserver
reliability comparison between the Orthopaedic Trauma
Association’s open fracture classification and the Gustilo and
Anderson classification. Bone Joint J 2018;100-B(2):242-246.
7. Li MK, Howard DP, King R: “A picture tells a thousand words”
smartphone-based secure clinical image transfer improves
compliance in open fracture management. Injury 2019;50(7):1284-
1287. Information on governance-compliant clinical photography
of open fracture wounds is compared before and after the
introduction of departmental smartphones with a clinical
photography application. The implementation of departmental
smartphones can improve compliance rates while improving
documentation, communication, and patient care. Level of
evidence: IV.
8. Garner MR, Warner SJ, Heiner JA, Kim YT, Agel J: Evaluation of
the orthopaedic trauma association open fracture classification
(OTA-OFC) as an outcome prediction tool in open tibial shaft
fractures. Arch Orthop Trauma Surg 2021; May 16 [Epub ahead of
print]. Retrospective reviews of 501 open tibial fractures at two
trauma centers are presented. The OTA-OFC correlated with type
of definitive soft-tissue coverage, the development of a 90-day
wound complication, and nonunion. OTA-OFC muscle was
predictive of nonunion, whereas OTA-OFC muscle and arterial
were predictive of amputation. Level of evidence: IV.
9. Putnam SM, Dunahoe J, Agel J, Garner MR: Clinical correlation
of the orthopaedic trauma association open fracture classification
with wound closure and soft-tissue complications in open upper
extremity fractures. J Orthop Trauma 2021;35(6):e184-e188. The
authors present a retrospective review of 280 open upper
extremity fractures at a single trauma center. All OTA-OFC
classifications correlated with type of definitive wound
management. OTA-OFC muscle correlated with and was
predictive of 90-day wound complications. Level of evidence: III.
10. Pa akis MJ, Harvey JP, Ivler D: The role of antibiotics in the
management of open fractures. J Bone Joint Surg Am
1974;56(3):532-541.
11. Pa akis MJ, Wilkins J: Factors influencing infection rate in open
fracture wounds. Clin Orthop Relat Res 1989;243:36-40.
12. Hoff WS, Bonadies JA, Cachecho R, Dorlac WC: East practice
management guidelines work group: Update to practice
management guidelines for prophylactic antibiotic use in open
fractures. J Trauma 2011;70(3):751-754.
13. British Orthopaedic Association Trauma Commi ee: British
Orthopaedic Association Standard for Trauma (BOAST): Open
fracture management. Injury 2020;51(2):174-177. Evidence-based
management guidelines to be applied to all patients with open
fractures (excluding hand, wrist, forefoot, or digits) within the
United Kingdom are discussed. Level of evidence: V.
14. Garner MR, Sethuraman SA, Schade MA, Boateng H: Antibiotic
prophylaxis in open fractures: Evidence, evolving issues, and
recommendations. J Am Acad Orthop Surg 2020;28(8):309-315. A
review of recent published data on prophylactic antibiotic choice
and duration in the se ing of open fractures is presented. The
authors also provide their institution’s current policy. Level of
evidence: V.
15. Hauser CJ, Adams CA, Eachempati SR; Council of the Surgical
Infection Society: Surgical Infection Society guideline:
Prophylactic antibiotic use in open fractures – An evidence-based
guideline. Surg Infect 2006;7(4):379-405.
16. Sagi HC, Donohue D, Cooper S, et al: Institutional and seasonal
variations in the incidence and causative organisms for
pos raumatic infection following open fractures. J Orthop Trauma
2017;31(2):78-84.
17. Bankhead-Kendall B, Gutierrez T, Murry J, et al: Antibiotics and
open fractures of the lower extremity: Less is more. Eur J Trauma
Emerg Surg 2019;45(1):125-129. The authors present a
retrospective review of 126 GustiloAnderson type III open lower
 extremity fractures at a single center. The addition of an
aminoglycoside for prophylaxis was associated with an increase
in acute kidney injury but showed no benefit with regard to
infection rates. Level of evidence: III.
18. Folse J, Hill CE, Graves ML, et al: Risk factors for kidney
dysfunction with the use of gentamicin in open fracture
antibiotic treatment. J Orthop Trauma 2018;32(11):573-578.
19. Lloyd BA, Murray CK, Shaikh F, et al: Early infectious outcomes
after addition of fluoroquinolone or aminoglycoside to
pos rauma antibiotic prophylaxis in combat-related open
fracture injuries. J Trauma Acute Care Surg 2017;83(5):854-861.
20. Hand TL, Hand EO, Welborn A, Zelle BA: Gram-negative
antibiotic coverage in Gustilo-Anderson type-III open fractures. J
Bone Joint Surg Am 2020;102(16):1468-1474. Review and
recommendations regarding the use of prophylactic antibiotics in
Gustilo-Anderson type III open fractures are presented. Level of
evidence: V.
21. Lin CA, O’Hara NN, Sprague S, et al: Low adherence to
recommended guidelines for open fracture antibiotic
prophylaxis. J Bone Joint Surg Am 2021;103(7):609-617. A
prospective analysis of adherence to EAST’s prophylactic
antibiotic recommendations within 24 trauma centers is
presented. For Gustilo-Anderson type I and type II fractures,
there was 61% compliance with cefazolin monotherapy. For type
III fractures, there was 17.2% compliance with recommended
cefazolin and aminoglycoside therapy. Level of evidence: IV.
22. Hospenthal DR, Murray CK, Andersen RC, et al: Executive
summary: Guidelines for the prevention of infections associated
with combat-related injuries 2011 update. Endorsed by the
Infectious Diseases Society of America and the Surgical Infection
Society. J Trauma 2011;71(2 suppl 2):S202-S209.
23. Rodriguez L, Jung HS, Goulet JA, Cicalo A, MachadoAranda
DA, Napolitano LM: Evidence-based protocol for prophylactic
antibiotics in open fractures: Improved antibiotic stewardship
 with no increase in infection rates. J Trauma Acute Care Surg
2014;77(3):400-407.
24. Messner J, Papakostidis C, Giannoudis PV, Kanakaris NK:
Duration of administration of antibiotic agents for open
fractures: Meta-analysis of the existing evidence. Surg Infect
2017;18(8):854-867.
25. Stenne CA, O’Hara NN, Sprague S, et al: Effect of extended
prophylactic antibiotic duration in the treatment of open fracture
wounds differs by level of contamination. J Orthop Trauma
2020;34(3):113-120. In a retrospective review of 2,400 patients with
open fractures the authors discuss whether duration of
prophylactic antibiotics (>72 hours) after wound closure is
associated with deep surgical site infection. Extended antibiotics
were protective against infection in severely contaminated
wounds but may increase infections in mildly contaminated
wounds. Level of evidence: III.
26. Morgenstern M, Vallejo A, McNally MA, et al: The effect of local
antibiotic prophylaxis when treating open limb fractures: A
systematic review and meta-analysis. Bone Joint Res 2018;7(7):447-
456.
27. Caroom C, Moore D, Mudaliar N, et al: Intrawound vancomycin
powder reduces bacterial load in contaminated open fracture
model. J Orthop Trauma 2018;32(10):538-541.
28. Vallejo Diaz A, Deimling C, Morgenstern M, et al: Local
application of a gentamicin-loaded hydrogel early after injury is
superior to perioperative systemic prophylaxis in a rabbit open
fracture model. J Orthop Trauma 2020;34(5):231-237. The local
application of a gentamicin-loaded hydrogel was found to be
superior to conventional systemic antibiotics in the reduction of
staphylococcal bacterial burden using an open, contaminated
rabbit fracture model.
29. Metsemakers WJ, Fragomen AT, Moriarty TF, et al: Evidence-
based recommendations for local antimicrobial strategies and
dead space management in fracture-related infection. J Orthop
 Trauma 2020;34(1):18-29. The authors present a review of available
literature and recommendations regarding the use of local
antimicrobial agents and for dead space management in the
se ing of fracture-related infections. Level of evidence: V.
30. Rozell JC, Connolly KP, Mehta S: Timing of operative
debridement in open fractures. Orthop Clin North Am
2017;48(1):25-34.
31. Li J, Wang Q, Lu Y, et al: Relationship between time to surgical
debridement and the incidence of infection in patients with open
tibial fractures. Orthop Surg 2020;12(2):524-532. A retrospective
analysis of 215 patients with open tibial fractures at a single
center is presented. Although infection rates increased with
severity of open fracture based on Gustilo-Anderson
classification and patient comorbidities, no association was
identified between time from injury to initial débridement. Level
of evidence: V.
32. Al-Hourani K, Fowler T, Whitehouse MR, Khan U, Kelly M: Two-
stage combined ortho-plastic management of type IIIB open
diaphyseal tibial fractures requiring flap coverage: Is the timing
of debridement and coverage associated with outcomes? J Orthop
Trauma 2019;33(12):591-597. In a retrospective review of 45
patients treated with twostage orthoplastic reconstruction for
severe open tibial fractures, time to initial débridement and time
to definitive reconstruction was not found to be associated with
infection, flap failure, or nonunion. Level of evidence: III.
33. Foote CJ, Torne a P, Reito A, et al: A reevaluation of the risk of
infection based on time to debridement in open fractures:
Results of the GOLIATH meta-analysis of observational studies
and limited trial data. J Bone Joint Surg Am 2021;103(3):265-273. A
meta-analysis of observational studies and randomized
controlled trials (84 studies, 18,239 patients) was performed to
assess the effect of delay to débridement on infection risk in open
fractures. For severe open fractures (Gustilo-Anderson type III),
a 1.5-fold increase in infection was found with initial
débridement being performed after more than 12 hours and a
 twofold increase in infection was found with débridement being
performed after more than 24 hours. Level of evidence: IV.
34. Scho el PC: The Pendulum Swings On: Earlier Open Fracture
Debridement May Be Best. Commentary on an article by Clary J
Foote, MD, MSc, et al: “A reevaluation of the risk of infection
based on time to debridement in open fractures. Results of the
GOLIATH meta-analysis of observational studies and limited
trial data.” J Bone Joint Surg Am 2021;103(3):e12. A commentary is
presented on the strengths and weaknesses of the GOLIATH
Meta-Analysis assessing effect of surgical timing on infection risk
in open fractures. Level of evidence: V.
35. Sassoon A, Riehl J, Rich A, et al: Muscle viability revisited: Are
we removing normal muscle? A critical evaluation of dogmatic
debridement. J Orthop Trauma 2016;30(1):17-21.
36. Al-Hourani K, Stoddart M, Khan U, Riddick A, Kelly M:
Orthoplastic reconstruction of type IIIB open tibial fractures
retaining debrided devitalized cortical segments: The Bristol
experience 2014 to 2018. Bone Joint J 2019;101-B(8):1002-1008. The
authors present a consecutive series of 113 severe open tibial
fractures (Gustilo-Anderson type IIIB). Complication and success
rates with orthoplastic reconstruction and retention of
devitalized but mechanically relevant bone fragments are
discussed. Level of evidence: III.
37. Heckmann N, Simcox T, Kelley D, Marecek GS: Wound
irrigation for open fractures. JBJS Rev 2020;8(1):e0061. A review of
available literature surrounding wound irrigant for open
fractures is presented. The authors comment specifically on
irrigant agent, volume, delivery pressure, and timing. Level of
evidence: V.
38. Olufemi OT, Adeyeye AI: Irrigation solutions in open fractures
of the lower extremities: Evaluation of isotonic saline and
distilled water. SICOT J 2017;3:7.
39. Garner MR, Warner SJ, Heiner JA, Kim YT, Agel J: Soft tissue
management in open tibial shaft fractures: A comparison of
 institutional preferences and resultant early clinical outcomes.
Bone Jt Open 2020;1(8):481-487. A retrospective comparison of
soft-tissue management practices for open tibial shaft fractures
at two US trauma centers is presented. No differences were noted
in 90-day wound complications, nonunion rates, or need for
amputation for a empted primary closure versus delayed
closure/coverage. Level of evidence: III.
40. Scharfenberger AV, Alabassi K, Smith S, et al: Primary wound
closure after open fracture: A prospective cohort study examining
nonunion and deep infection. J Orthop Trauma 2017;31(3):121-126.
41. Wang KK, Rademacher ES, Miller PE, et al: Management of
Gustilo-Anderson type II and IIIA open long bone fractures in
children: Which wounds require a second washout? J Pediatr
Orthop 2020;40(6):288-293. The authors compared early versus
delayed primary wound closure in 96 children with Gustilo-
Anderson type II or IIIA open long bone fractures. No difference
was identified in complication rates after controlling for
mechanism of injury, age, and Gustilo-Anderson classification.
Level of evidence: III.
42. Iheozor-Ejiofor Z, Newton K, Dumville JC, Costa ML, Norman
G, Bruce J: Negative pressure wound therapy for open traumatic
wounds. Cochrane Database Syst Rev 2018;7:CD012522.
43. Costa ML, Achten J, Knight R, et al: Negative-pressure wound
therapy compared with standard dressings following surgical
treatment of major trauma to the lower limb: The WHiST RCT.
Health Technol Assess 2020;24(38):1-86. This multicenter
randomized controlled trial assessed the utility of incisional
NPWT compared with standard dressings in lower limb trauma.
No differences were found in rate of deep infections. Level of
evidence: I.
44. Hernández-Irizarry R, Quinnan SM, Reid JS, et al: Intentional
temporary limb deformation for closure of sof issue defects in
open tibial fractures. J Orthop Trauma 2021;35(6):e189-e194. A
case series of 19 patients treated at three centers with hexapod
 external fixation and intentional bony deformity to facilitate
primary soft-tissue closure in Gustilo-Anderson type IIIB or IIIC
open tibial fractures is presented. After soft-tissue healing,
gradual deformity correction was performed. Level of evidence:
IV.
45. Jones CM, Roberts JM, Sirlin EA, et al: Acute limb shortening or
creation of an intentional deformity to aid in soft tissue closure
for IIIB/IIIC open tibia fractures. J Plast Reconstr Aesthet Surg
2021;74(11):2933-2940. A series of 18 severe open tibial fractures
managed with ring fixator shortening or intentional deformity for
(1) skeletal indications with traditional free soft-tissue transfer;
(2) skeletal and soft-tissue indications to augment reconstructive
measures; (3) skeletal and soft-tissue indications to avoid
microsurgery are discussed. Level of evidence: IV.
46. D’Alleyrand JC, Manson TT, Dancy L, et al: Is time to flap
coverage of open tibial fractures an independent predictor of
flaprelated complications? J Orthop Trauma 2014;28(5):288-293.
47. Clegg DJ, Rosenbaum PF, Harley BJ: The effects of timing of soft
tissue coverage on outcomes after reconstruction of type IIIB
open tibia fractures. Orthopedics 2019;42(5):260-266. A
retrospective series of 140 consecutive Gustilo-Anderson type
IIIB open tibial fractures is presented. Although there was a
trend toward the development of adverse outcomes with delayed
soft-tissue coverage, salvage can still be obtained with coverage
occurring up to 6 weeks from the time of injury. Level of
evidence: IV.
48. Bosse MJ, Murray CK, Carlini AR, et al: Assessment of severe
extremity wound bioburden at the time of definitive wound
closure or coverage: Correlation with subsequent postclosure
deep wound infection (bioburden study). J Orthop Trauma
2017;31(suppl 1):S3-S9.
49. Steeby SF, Harvin WH, Worley JR, et al: Use of the dedicated
orthopaedic trauma room for open tibia and femur fractures:
Does it make a difference? J Orthop Trauma 2018;32(8):377-380.
50. Collinge CA, McWilliam-Ross K, Kelly KC, Dombroski D:
Substantial improvement in prophylactic antibiotic
administration for open fracture patients: Results of a
performance improvement program. J Orthop Trauma
2014;28(11): 620-625.
51. Tan WJ, Kwek EBK: Outcomes after implementation of an open
fracture clinical pathway. Arch Orthop Trauma Surg
2020;140(10):1373-1379. A retrospective comparison was made of
open tibial and femoral fractures before and after
implementation of a clinical management pathway. The pathway
reduced the number of external fixation surgeries, length of stay,
and number of procedures without an increase in complications.
Level of evidence: III.
52. Prada C, Tanner SL, Marcano-Fernández FA, et al: How
successful is antibiotic treatment for superficial surgical site
infections after open fracture? A fluid lavage of open wounds
(FLOW) cohort secondary analysis. Clin Orthop Relat Res
2020;478(12):2846-2855. A secondary analysis of FLOW trial data
set is presented, demonstrating that antibiotics alone for
superficial surgical site infection after open fracture treatment
was 70% successful in infection eradication. Level of evidence: III.
53. Parker B, Petrou S, Masters JPM, Achana F, Costa ML: Economic
outcomes associated with deep surgical site infection in patients
with an open fracture of the lower limb. Bone Joint J 2018;100-
B(11):1506-1510.
C H AP T E R 2 3

Upper Extremity Trauma

Mara Schenker MD, FAAOS, Michael McDonald DO,
Thomas Moore Jr MD

Dr. Schenker or an immediate family member serves as a paid consultant to or is an employee of

Johnson & Johnson and serves as a board member, owner, officer, or committee member of the
AO North America and Orthopaedic Trauma Association. Neither of the following authors nor
any immediate family member has received anything of value from or has stock or stock options
held in a commercial company or institution related directly or indirectly to the subject of this
chapter: Dr. McDonald and Dr. Moore.

ABSTRACT
The upper extremity is unique in that it is not weight bearing and
with a few exceptions most areas have good vascular supply with
reliable healing potential. Certain areas of the upper extremity such
as the clavicle, scapula, humerus, distal radius, and fingers are able
to tolerate deformity because of the large range of motion of
adjacent joints. This creates controversy in the management of
these injuries, especially in lower demand populations. Although
most proximal humeral fractures can be managed nonsurgically,
reverse total shoulder arthroplasty is gaining popularity for
severely displaced fractures in the geriatric population. A large
number of humeral shaft fractures initially managed nonsurgically
eventually require surgical intervention for various reasons. Despite
limited evidence on the benefits of surgery, many distal radius
fractures are managed surgically in patients older than 60 years.
There is certainly room to grow in terms of be er defining who will
benefit from surgical intervention for some of these controversial
upper extremity fractures rather than strictly age-based cutoffs.
Conversely, many injuries clearly benefit from surgery such as
forearm fractures and intra-articular injuries about the elbow. In
these fractures, debate often exists regarding the best methods of
fixation rather than surgery versus nonsurgical management. A
shared decision-making process with each patient based on injury
characteristics, activity level, overall health, and preference is
critical.
Keywords: clavicle fracture; distal radius fractures; humeral shaft
fracture; proximal humerus fracture; terrible triad fracture

Introduction
It is important to provide an overview of evidence-based practice
for the management of upper extremity fractures to guide
practitioners in their clinical decision-making. With recent well-
conducted studies having brought into question some traditional
treatment options for certain fractures of the upper extremity, every
practitioner should critically evaluate the literature to apply
evidence-based medicine into their practice.

Acromioclavicular Joint Injuries

Management of acromioclavicular joint injuries remains
controversial; however, nonsurgical management is appropriate for
most of these injuries. Rockwood type I and type II injuries reliably
do well with nonsurgical management. Type III and type V
acromioclavicular joint injury management is controversial, with
much of the literature supporting initial nonsurgical management.
Type III injuries can be divided into stable (IIIA) and unstable
(IIIB), with unstable injuries being those that cause persistent pain,
weakness, decreased flexion and abduction, and scapular
dyskinesis; early surgical intervention for the unstable group may
be beneficial. Although considerably rare, types IV and VI
acromioclavicular joint injuries are generally considered for
surgical management.
 A 2019 Cochrane database review of five randomized controlled
trials (RCTs) with 357 patients was performed comparing surgical
versus nonsurgical management of acromioclavicular joint
dislocations in adults. 1 It was concluded that surgical management
is not beneficial in terms of return to activity, quality of life, overall
function, pain at 1-year follow-up, secondary surgery, and cosmetic
patient satisfaction. A meta-analysis of 10 trials was performed
comparing nonsurgical and surgical management of type III
injuries, and it was concluded that there was no difference in pain,
weakness, tenderness, pos raumatic arthritis, restriction of
strength, unsatisfactory function, or functional outcome scores. 2
The type of surgical fixation is also controversial, with more than
60 described techniques in the literature. In 2020, a meta-analysis of
TightRope (Arthrex) versus hook-plate fixation for types III-V
injuries was performed and demonstrated an advantage for
TightRope fixation in terms of postoperative pain. 3 A 2019 meta-
analysis of 1,704 patients compared the outcomes of different
surgical techniques and found that there was no significant
difference in reduction loss, complications, or revisions between
open and arthroscopic techniques. 4

Clavicular Fractures
Optimal treatment for displaced midshaft clavicular fractures has
been debated for multiple decades, with the pendulum swinging
between nonsurgical and surgical management. Most studies have
shown a higher nonunion rate with nonsurgical management;
however, the clinical significance has been questioned.
A 2020 meta-analysis 5 evaluated 22 RCTs and found that union
rates were lower in the nonsurgical groups (88.9%) compared with
the surgical groups (96.7%), with a number needed to treat of 10.
This study also found that the surgical group did show
improvement in Disabilities of the Arm, Shoulder and Hand
(DASH) and Constant scores although these differences did not
meet the defined minimal clinically important difference (MCID).
Another 2019 meta-analysis evaluated nine well-designed RCTs and
showed that surgical management had be er union rates (98.7%
versus 86.6%), appearance dissatisfaction rates, and shoulder
appearance defect rates. 6 A different meta-analysis in 2019 looked
at 1,469 patients to compare surgical and nonsurgical management
and concluded that surgery does not improve functional outcomes
or affect pain and that nonsurgical management may decrease the
risk of unplanned secondary surgery. 7 Symptomatic malunion was
more common in the nonsurgical group (11.3% versus 1.2%);
however, there was no significant difference in adverse outcomes
between the two groups.
Anteroinferior versus superior plate position is a topic of debate.
A meta-analysis of 1,484 patients was performed to compare the
two plate positions (390 anteroinferior and 1,104 superior). 8 No
difference was found in terms of outcomes except that the superior
plating group had a significantly higher rate of symptomatic
hardware and subsequent removal. Another study looked at four
RCTs and eight observational studies comparing the two plate
positions and found that anteroinferior plating had decreased
surgical time, blood loss, and time to union. 9 Dual plating has
become a popular technique for treating clavicular fractures.
Although several biomechanical studies demonstrate similar or
improved stability with dual plating, there is as of yet no high-level
evidence to support this treatment. In 2020, a meta-analysis
comparing plate fixation with intramedullary nailing (IMN) for
displaced clavicle fractures found that the IMN group had
improved Constant and DASH scores (that did not meet MCID),
lower infection rates, and shorter duration of surgery and hospital
stay, but higher implant removal rate. 10

Scapular Fractures
Scapular fractures are relatively uncommon injuries that typically
occur as a result of high-energy mechanisms and are often
accompanied by other injuries. High-quality evidence is limited,
with most of the literature composed of small case series and
retrospective reviews. Most of these fractures are minimally
displaced and can be managed nonsurgically with good success.
Fractures involving the glenoid are often categorized as isolated
glenoid rim fractures as a result of instability events and glenoid
fossa fractures extending into the neck or body as a result of high-
energy mechanisms.
Surgical indications for displaced scapular fractures are
controversial. Several have been proposed: more than 2 cm of
scapular body lateralization, at least 45° of angulation on a scapular
Y view, combined ≥30° of angulation with at least 15 mm of
scapular body lateralization, glenopolar angle less than 22°, at least
1 cm displaced double disruption of the superior shoulder
suspensory complex, and >4 mm intra-articular step-off. However,
intra-articular displacement of scapular fractures involving the
glenoid is controversial with acceptable displacement ranging from
2 to 10 mm. A 2020 systematic review evaluated extra-articular
scapula fractures from 42 studies with 669 patients in total; 464
patients were treated surgically and 205 nonsurgically. 11 A total of
316 patients in the surgical group were treated using the
aforementioned indications, whereas 148 patients were treated with
additional study-specific indications. A union rate of 99.4%, mean
Constant score of 84.4, and forward flexion of 158° were found in
the surgical group compared with a union rate of 85.1%, mean
Constant score of 79.0, and forward flexion of 153° in the
nonsurgical group. Of note, only one of the studies in the review
was an RCT and one was a prospective cohort, the rest were
retrospective reviews, case series, or case reports.

Humeral Fractures

Proximal Humeral Fractures

Proximal humeral fractures are very common injuries, and despite
numerous high-quality studies, there is a lack of consensus on the
ideal treatment. It is well accepted that minimally displaced
fractures do well if managed without surgery. Displaced fractures
are typically classified into parts based on the Neer classification. In
general, nonsurgical management for three-part and four-part
fractures has led to poor functional scores and range of motion
(ROM) limitations. Surgical treatment options include open
reduction and internal fixation (ORIF) with locking plates, reverse
total shoulder arthroplasty (rTSA), hemiarthroplasty, and IMN,
among others.
An RCT published in 2019 compared nonsurgical management
with ORIF of displaced (>1 cm or >45°) two-part proximal humeral
fractures. 12 There were no statistical differences in multiple
outcome scores between the two groups at 2 years postoperatively,
and there were more complications in the surgical group. In a 2019
retrospective review of 368 patients with severely displaced
proximal humeral fractures and fracture-dislocations that were
managed with ORIF, 13 the authors found that the revision surgery
rate at 10 years postoperatively was 26%; however, when revision
surgeries for stiffness were excluded, the rate dropped to 10%. The
patients were surveyed at an average of 10 years postoperatively
and reported good to excellent function, pain, and satisfaction
rates. IMN for proximal humeral fractures has been gaining
popularity. An RCT in 2019 comparing locking blade IMN with
ORIF in 68 patients found improved DASH scores at 1 year
postoperatively and decreased reduction loss and screw cutout in
the IMN group. 14
rTSA has been gaining popularity and has largely replaced
hemiarthroplasty as a treatment option for proximal humeral
fractures in the elderly. A meta-analysis of eight RCTs compared
nonsurgical treatment, ORIF, rTSA, and hemiarthroplasty for three-
part and four-part proximal humeral fractures. 15 It was concluded
that rTSA resulted in fewer adverse events and be er clinical
outcome scores than hemiarthroplasty. However, it was also
reported that nonsurgical treatment was associated with lower rates
of unplanned surgery and adverse events compared with ORIF and
similar clinical scores, adverse events, and unplanned surgeries
compared with hemiarthroplasty and rTSA. The DELPHI trial is a
well-designed RCT that compared rTSA with ORIF in displaced
proximal humeral fractures in the elderly population (older than 65
years). 16 A total of 124 patients were evaluated and significantly
be er Constant scores were found in the rTSA group. Another
recent study using Nordic registry data evaluated the 5-year
survival rate of rTSA for 1,523 proximal humeral fractures and
found that survivorship was 97%. 17 However, another study using
the same registry evaluated 3,245 patients who underwent delayed
rTSA for proximal humeral fractures and found 1-, 5-, and 10-year
survival rates of 94%, 89%, and 85%, respectively. 18 This indicates
that delayed rTSA may have more complications than acute rTSA
for proximal humeral fractures.

Humeral Shaft Fractures

Most humeral shaft fractures, even if displaced, do well with
nonsurgical management and this remains the mainstay of
treatment. There are few high-level studies comparing nonsurgical
and surgical management. Absolute surgical indications include
fractures with an associated brachial plexus injury, vascular injury
requiring repair, floating elbow, and severe soft-tissue injury or
bone loss. Radial nerve palsy with a humeral shaft fracture occurs
approximately 20% of the time, but most cases (90%) recover
spontaneously.
A 2020 RCT performed in Finland compared outcomes of
nonsurgical management with those of ORIF in 78 closed displaced
humeral shaft fractures. 19 The study authors found no statistically
significant difference in DASH scores at 12 months but a nonunion
rate of 25% in the nonsurgical group with a 30% crossover rate into
the surgical group. 20 It was concluded that patients should be
informed that nonsurgical management typically yields successful
outcomes, and up to one-third of patients will convert to surgical
management and may have decreased functional results if surgery
is delayed. An RCT in 2019 21 compared nonsurgical management
with ORIF in 60 patients and found a shorter time to union in the
ORIF group with no difference in DASH scores at 12 months.

Distal Humeral Fractures

Distal humeral fractures range from high-energy injuries in the
young patient to low-energy injuries in the geriatric population. In
patients with adequate bone quality and a fracture that is
reconstructable, ORIF provides the best opportunity to achieve a
functional elbow. Total elbow arthroplasty (TEA) for elderly
patients with poor bone quality and/or fractures that are not
reconstructable has become increasingly more common.
A meta-analysis of 362 patients from 5 well-designed studies
compared those who underwent ulnar nerve transposition with
those who had in situ release of the ulnar nerve at the time of
fixation. 22 This study found that there was a higher rate of ulnar
neuropathy in the transposition group (23.5% versus 15.3%) and
recommended against regularly transposing the nerve at the time
of fixation. A 2019 follow-up study from a prior RCT reported the
results of 15 patients treated with ORIF and 25 treated with TEA
with a mean follow-up of 12.5 years for patients still alive and 7.7
years for deceased patients. 23 Four of 15 in the ORIF group and 3 of
25 in the TEA group underwent revision surgery, with 1 revision
TEA, 1 heterotopic ossification excision, and 1 elbow contracture
release. A total of 7 patients treated with TEA were living with their
original implant and 15 had died with functioning implants in
place.

Fracture-Dislocations of the Elbow

The most frequently discussed fracture-dislocations about the
elbow are terrible triad and Monteggia fractures. Terrible triad
injuries are characterized by elbow dislocation, radial head/neck
fracture, and a coronoid fracture. Monteggia fractures are fractures
of the proximal ulna associated with a radial head dislocation and
are distinguished from transolecranon fracture-dislocation in that
the proximal radioulnar joint is disrupted (Figure 1). There is
limited high-quality literature regarding these complex injuries that
are difficult to manage and are often accompanied by
complications.
 Figure 1 A, AP and B, lateral radiographs demonstrating a transolecranon
fracture-dislocation with an intact proximal radioulnar joint. C, AP and D, lateral
radiographs demonstrating a Monteggia fracture-dislocation with disruption of
the proximal radioulnar joint.

Terrible Triad Injuries

A 2019 meta-analysis evaluated 115 patients with terrible triad
injuries from four studies and found that patients who underwent
radial head arthroplasty (n = 64) rather than ORIF (n = 51) had
be er DASH scores, Mayo Elbow Performance scores (MEPS),
be er ROM, and fewer postsurgical complications. 24 The largest
cohort study to date that was recently published retrospectively
reviewed 62 terrible triad injuries with more than 1-year follow-up.
The study authors found a 45% revision surgery rate due to
stiffness (21%), symptomatic hardware (18%), ulnar neuropathy
(16%), instability (6%), incisional neuroma (2%), and wound
problems (2%). 25 In contrast to the aforementioned meta-analysis
the only factor correlated with revision surgery was radial head
treatment in favor of ORIF. However, these findings are limited in
that only 4 of the patients underwent ORIF, whereas 55 had radial
head replacements, and 3 had radial head excisions.

Monteggia Fractures
A retrospective multicenter study was performed in 2018 to
evaluate midterm results of 46 patients after ORIF of Monteggia
fractures with or without radial head replacement or fixation. 26
Using the Mayo Modified Wrist Score and the MEPS, results were
excellent (63% and 68%, respectively). A 2019 study evaluated 78
patients with Monteggia fractures and found that those with
associated coronoid fractures and Mason III radial head fractures
requiring arthroplasty were associated with significantly worse
outcomes. 27 A similar retrospective study conducted in 2020
evaluated Monteggia-like injuries that had associated radial head
fractures requiring replacement among 27 patients. 28 A
complication rate of 41% was reported, leading to 15 revision
surgeries in 9 patients (33%).

Olecranon Fractures
Olecranon fractures are fairly common injuries around the elbow
and can be caused by a direct blow, typically leading to a
comminuted fracture, or an indirect mechanism, leading to a
simpler fracture pa ern. Although surgical fixation (plate, tension
band) has traditionally been the standard, there has been growing
evidence of acceptable results with nonsurgical management in
medically unwell patients even with displaced olecranon fractures.
A meta-analysis conducted in 2019 evaluated plate fixation (n =
369) and tension band wiring (n = 270) among 24 different RCTs and
observational studies. 29 The plate fixation group had significantly
lower complication rates (relative risk 0.48) and hardware removal
(12% versus 33%) than the tension band group. In contrast, a meta-
analysis of RCTs published in 2021 evaluated different fixation
options for olecranon fractures among four studies and found no
differences between tension band wiring and plate fixation in terms
of patient-rated or clinical outcomes. 30 A 2021 retrospective
analysis evaluated nonsurgical management of displaced olecranon
fractures in 28 medically unwell patients and found that despite a
nonunion rate of 82%, generally good results can be obtained. 31

Radial Head Fractures

In general, radial head fractures occur in isolation from a fall on an
outstretched arm or are part of a complex elbow injury as a result of
a high-energy mechanism. Minimally displaced (<5 mm) isolated
radial head fractures without a mechanical block to motion can be
managed nonsurgically. Radial head fractures with displacement,
with or without mechanical block to motion, are managed
surgically with either ORIF, excision, or radial head arthroplasty.
A 2021 systematic review analyzed 319 patients with type II
fractures from 11 different studies to compare nonsurgical
management with ORIF. 32 The ORIF group (n = 218) did not have
significantly be er functional outcomes in terms of the MEPS or the
Broberg and Morrey score. The study authors found that 7.1% of the
ORIF group required secondary surgery and that the rates of
arthritis were comparable at long-term follow-up. A 2021 meta-
analysis evaluated 526 patients with comminuted radial head
fractures from 12 comparative studies and 1 RCT comparing ORIF,
RHA, and excision. 33 The RHA group had significantly higher
MEPS and ORIF group had the highest complication rates. These
meta-analyses are limited in that the studies included in the
analysis are not of high quality and are mostly retrospective in
nature.

Forearm Fractures
ORIF with plate and screw fixation remains the gold standard
treatment for adult forearm fractures and is associated with
excellent union rates and outcomes; thus, there have not been any
groundbreaking changes in treatment standards since the advent of
dynamic compression plates. Forearm fracture nonunion is a rare
problem that is typically caused by severe soft-tissue compromise
and/or bone loss, infection, or technical factors.
A recent well-designed retrospective study evaluated 73 high-
energy open forearm fractures among military combatants in 2019.
34
All patients underwent an initial and a second irrigation and
débridement. Union rates were achieved primarily in 85% with final
union achieved in 96% of the patients. Interestingly, 45% of the
patients in this cohort were smokers and 88% required soft-tissue
coverage; however, healing may have been influenced positively by
young age and otherwise good overall health. Synostosis developed
in 19% of patients and was associated with significantly lower ROM;
none of the 14 patients was able to achieve a flexion arc more than
100°. Risk factors for nonunion included bone loss at the fracture
site and infection.
Galeazzi fracture-dislocations are defined as radial shaft
fractures, typically distal third, associated with distal radioulnar
joint (DRUJ) dislocation. Controversy exists on the definition and
management of the unstable DRUJ in the se ing of Galeazzi
injuries, but it is mostly based on anecdotal opinions rather than
high-quality evidence. A 2021 study of 14 patients who sustained a
Galeazzi fracture-dislocation looked at the long-term radiographic
and functional outcomes specific to the DRUJ. 35 All 14 patients
initially treated with ORIF of the radius and closed reduction of the
DRUJ were evaluated for ROM, strength, ballo ement test, pain on
axial loading, visual analog scale scores, and DASH scores at a
minimum 6-year follow-up. Radiographs and dynamic CT scans
were used to assess DRUJ instability/arthritis. A total of 43% of
patients had a positive ballo ement test; however, none of those
patients had associated pain with axial loading. There were no
differences in ROM and mean grip strength was 77% of the
contralateral side. The dynamic CT scans did not show subluxation
or arthritis in any of the patients. This study demonstrates a good
prognosis for patients with DRUJ injuries treated with closed
reduction after ORIF of the radius.

Distal Radial Fractures

Distal radial fractures are the most common fractures of the upper
extremity and occur in a bimodal distribution. In general, young
patients with more than 3 mm of shortening, more than 2 mm
intra-articular step-off, and more than 10° of dorsal tilt will benefit
from surgical intervention. However, there is strong evidence that
patients older than 65 years have no long-term benefit from surgical
intervention.
A meta-analysis published in 2021 of 4,789 patients from 70 RCTs
compared volar locking plating, bridging and nonbridging external
fixation, dynamic external fixation, percutaneous pinning,
intramedullary fixation, dorsal plating, fragment-specific plating,
and nonsurgical management. 36 At 1-year follow-up, the volar
locking plate (VLP) group ranked the best in terms of DASH scores,
but this did not meet the MCID. Based on a subgroup analysis, this
study concluded that VLP may have a lower complication rate,
especially with intra-articular fractures, but in patients older than
60 years there is no clear evidence of an advantage compared with
nonsurgical management.
The Wrist and Radius Injury Surgical Trial, or WRIST, is a
multicenter RCT of 304 patients that sought to compare different
treatment options for distal radial fracture in patients older than 60
years. 37 A total of 117 patients elected to receive nonsurgical
treatment, whereas the remaining 187 patients were randomized
into internal or external fixation and percutaneous pinning. At 1
year postinjury there was no difference in Michigan Hand
Outcomes Questionnaire scores between the groups, despite
malunion occurring in 48% of the nonsurgical group. However, at 6
weeks postoperatively the internal fixation group had significantly
improved Michigan Hand Outcomes Questionnaire scores
compared with all other groups. A secondary analysis of the WRIST
study performed in 2020 38 found that increased final radiographic
displacement correlated with decreased grip strength in 166
patients older than 70 years. However, these radiographic outcomes
were not associated with Michigan Hand Outcomes Questionnaire
total or function scores, thus showing that accurate restoration of
wrist anatomy is not necessarily associated with be er outcomes at
1 year. Another secondary analysis from the WRIST study
published in 2020 found that a delay in surgery greater than 1 week
and increased pain in the preoperative period correlated with
chronic pain, whereas patients treated with VLP had decreased risk
of chronic pain. 39

Wrist and Hand Fractures

Scaphoid Fractures
The scaphoid is the most commonly fractured carpal bone that is
notorious for slow healing because of its tenuous blood supply. In
general, nondisplaced fractures about the scaphoid waist can be
managed nonsurgically. Displaced fractures and those presenting
as nonunions are best managed with surgical intervention.
The Scaphoid Magnetic Resonance Imaging in Trauma RCT
conducted in London in 2019 40 evaluated clinical and cost
implications of using MRI for the acute diagnosis of scaphoid
fractures with negative radiographs. This study randomized
patients to undergo an MRI or not in the emergency department.
This study found that the patients who underwent MRI in the
emergency department had less overall cost at 3 months. Surgery
versus cast immobilization for adults with a bicortical fracture of
the scaphoid waist (SWIFFT) is another well-designed RCT out of
England and Wales published in 2020 that evaluated 408 patients
randomized to surgical and nonsurgical treatment. 41 No difference
was found in mean patient-rated wrist evaluation at 52 weeks
postinjury.

Perilunate Injuries
Perilunate injuries are extremely rare; thus, high-level evidence on
the management of these injuries is limited. A 2021 retrospective
review of 27 perilunate injuries after ORIF was performed to assess
midterm clinical and radiographic outcomes. 42 Mean visual analog
scale score was 2.3 at rest and 3.3 with activity, mean grip strength
and ROM (flexion-extension and radial/ulnar deviation) reached
approximately 60% to 75% of the contralateral side, and mean Mayo
and DASH scores were 63.3 and 24.1, respectively. Mean
scapholunate angle was 61.6° (range: 40° to 83°), 1 wrist had
scapholunate widening, 11 had dorsal intercalated segmental
instability, and mean carpal height was within normal range.

Metacarpal Fractures
Metacarpal fractures are the most common fractures in the hand.
The first and second metacarpals tolerate less deformity than the
more mobile fourth and fifth metacarpals. Relative indications for
surgery include multiple fractures, rotational deformity, and intra-
articular displacement. Open fracture management is controversial,
with a theoretically low risk of infection due to the vast blood
supply.
A prospective comparative study published in 2019 compared
intramedullary pin fixation with low-profile locking plates of 75
second through fifth metacarpal fractures. 43 There was no
difference between the two groups in terms of union, final
angulation, and visual analog scale scores. However, at 2 years
postoperatively the intramedullary pin group had be er DASH
scores, grip strength, less extension lag, and lower rates of
secondary surgery. A 2019 meta-analysis looking at 169 metacarpal
fractures from nine studies managed with intramedullary screws
found that 100% of fractures achieved union, mean grip strength
was 96% compared with the contralateral side, and no serious
complications were reported. 44 Although average follow-up was 11
months, some of the studies reported as li le as 2 weeks of follow-
up, which is inadequate to determine complication rates.
A prospective RCT published in 2020 evaluated 72 fifth
metacarpal neck fractures with less than 70° of angulation to
compare closed reduction and casting with buddy taping at 9
weeks. 45 The buddy taping group had less time off work and
displayed be er ROM and DASH scores, but the difference did not
meet MCID. There were more complications in the closed reduction
and cast group. Similar radiographic outcomes were found between
the two groups. Another multicenter RCT published in 2019
evaluated single versus double Kirschner wire fixation of 290 fifth
metacarpal neck fractures. 46 Mean DASH scores as well as
radiographic outcomes at 6 months were similar between the two
groups, although there was a trend toward greater shortening and
rotational malalignment in the single-wire group. The argument for
single-wire fixation is that it is less technically demanding to insert
a single thick Kirschner wire than two thinner wires. A limitation of
this study is that the 6-month follow-up rate was only 52%.

Phalangeal Fractures
Phalangeal fractures are common injuries most of which can be
managed without surgery. A 2019 RCT evaluated 61 patients with
proximal phalangeal fractures to compare transarticular fixation
through the metacarpophalangeal joint and extra-articular cross
pinning. 47 No differences were found between the two groups in
terms of ROM, return to activities and work, and complications.
Final ROM increased significantly from 3 to 6 months
postoperatively and was inversely related to patient age. Another
2019 RCT of 40 patients with unstable transverse, long oblique, or
spiral diaphyseal fractures of the proximal and middle phalanx
evaluated low-profile titanium plating compared with pin fixation. 48
Improved mean total active motion at 6 months and fewer
complications were found in the plating group with no difference in
functional outcomes.

Summary
Some of the rarer injuries of the upper extremity require
multicenter high-level evidence on best practice. However, many of
the recent high-level studies of the more common upper extremity
fractures highlight the role of nonsurgical management.
Nonsurgical management in many of these injuries should be
discussed with the patient in a shared decision-making se ing.
Future studies and those currently underway on rTSA longevity and
outcomes for proximal humeral fractures, humeral shaft fracture
management, and TEA for distal humeral fractures may provide
further insight on how to optimize risks and benefits for such
injuries. Additionally, studies on conjoint analysis to elicit patient
preferences for the management of distal radial fractures are
starting to emerge and may provide a tool to guide decision making
for these injuries in the future. Cost analysis of different treatment
options is also important to consider.

Key Study Points

Displaced midshaft clavicular fractures have a higher nonunion rate with nonsurgical
treatment, but similar functional outcomes at 1 year postinjury. Additionally, many
patients with a nonunion are still able to function without the need for nonunion repair.
rTSA may provide superior functional outcomes for displaced three-part and four-
part proximal humeral fractures in the elderly, but long-term implant survivorship is
still under question.
Approximately one-third of patients who initially undergo nonsurgical treatment for a
humeral shaft fracture end up having surgery for their fracture for various reasons,
and those who are treated in a delayed fashion may have worse clinical outcomes.
 Monteggia fractures with associated coronoid and/or radial head fractures are
associated with worse outcomes and may represent more of a terrible triad variant.
Currently, there is no evidence of long-term (1 year) functional differences in patients
older than 60 years with distal radial fractures treated with ORIF compared with
nonsurgical management, although VLP may provide superior functional results
early on.

Annotated References
1. Tamaoki MJ, Lenza M, Matsunaga FT, Belloti JC, Matsumoto MH,
Faloppa F: Surgical versus conservative interventions for treating
acromioclavicular dislocation of the shoulder in adults. Cochrane
Database Syst Rev 2019;10:CD007429. This review of five RCTs with
357 patients compared surgical versus nonsurgical management
of acromioclavicular joint dislocations in adults. The study
authors did not find any significant benefit to surgical
management. Level of evidence: I.
2. Tang G, Zhang Y, Liu Y, Qin X, Hu J, Li X: Comparison of
surgical and conservative treatment of Rockwood type-III
acromioclavicular dislocation: A meta-analysis. Medicine
(Baltimore) 2018;97(4):e9690.
3. Pan X, Lv RY, Lv MG, Zhang DG: TightRope vs clavicular hook
plate for Rockwood III-V acromioclavicular dislocations: A meta-
analysis. Orthop Surg 2020;12(4):1045-1052. This meta-analysis
compared suspensory fixation with hook-plate fixation of type III-
V acromioclavicular joint injuries among 179 patients from four
different studies. The study authors found that suspensory
fixation may have be er postoperative pain, but no difference in
functional outcomes or complications. Level of evidence: I.
4. Gowd AK, Liu JN, Cabarcas BC, et al: Current concepts in the
operative management of acromioclavicular dislocations: A
systematic review and meta-analysis of operative techniques. Am
J Sports Med 2019;47(11):2745-2758. This meta-analysis evaluated
1,704 patients from 54 different studies to compare open versus
arthroscopic management of acromioclavicular joint injuries. The
 study authors found no significant difference in outcomes or
complication rates. Level of evidence: I.
5. Axelrod DE, Ekhtiari S, Bozzo A, Bhandari M, Johal H: What is
the best evidence for management of displaced midshaft clavicle
fractures? A systematic review and network meta-analysis of 22
randomized controlled trials. Clin Orthop Relat Res
2020;478(2):392-402. This systematic review of 22 RCTs compared
nonsurgical management with surgical management of displaced
midshaft clavicular fractures. The study authors found a higher
nonunion rate in the nonsurgical group, similar revision surgery
rates, and improvements in functional outcomes in the surgical
group. However, other than the anterosuperior plating group, the
functional outcome differences did not meet the MCID. Level of
evidence: I.
6. Qin M, Zhao S, Guo W, et al: Open reduction and plate fixation
compared with non-surgical treatment for displaced midshaft
clavicle fracture: A meta-analysis of randomized clinical trials.
Medicine (Baltimore) 2019;98(20):e15638. This meta-analysis of
nine RCTs compared surgical and nonsurgical management of
displaced midshaft clavicular fractures. The study authors found
higher union rates in the surgical group as well as improved
appearance dissatisfaction rates and shoulder appearance defect
rates. They also found lower complications in the nonsurgical
group. Level of evidence: I.
7. Lenza M, Buchbinder R, Johnston RV, Ferrari BA, Faloppa F:
Surgical versus conservative interventions for treating fractures
of the middle third of the clavicle. Cochrane Database Syst Rev
2019;1:CD009363. This systematic review compared surgical
management with nonsurgical management for displaced
midshaft clavicular fractures among 1,469 patients from eight
RCTs. The study authors found no difference in functional
outcomes or pain, but there was increased risk of unplanned
secondary surgery in the surgical group. Level of evidence: I.
8. Nourian A, Dhaliwal S, Vangala S, Vezeridis PS: Midshaft
fractures of the clavicle: A meta-analysis comparing surgical
 fixation using anteroinferior plating versus superior plating. J
Orthop Trauma 2017;31(9):461-467.
9. Ai J, Kan SL, Li HL, et al: Anterior inferior plating versus
superior plating for clavicle fracture: A meta-analysis. BMC
Musculoskelet Disord 2017;18(1):159.
10. Li L, Yang X, Xing F, Jiang J, Tang X: Plate fixation versus
intramedullary nail or Knowles pin fixation for displaced
midshaft clavicle fractures: A meta-analysis of randomized
controlled trials. Medicine (Baltimore) 2020;99(39):e22284. This
meta-analysis compared intramedullary fixation with plate
fixation of displaced midshaft clavicular fractures among 839
patients from 12 RCTs. The study authors found improved
functional scores, lower infection rates, and shorter duration of
surgery and hospital stay in the intramedullary group. However,
increased implant removal rates were found in the
intramedullary group. Level of evidence: I.
11. Bi AS, Kane LT, Butler BA, Stover MD: Outcomes following
extra-articular fractures of the scapula: A systematic review.
Injury 2020;51(3):602-610. This systematic review evaluated 662
patients with extra-articular scapular fractures from 42 different
studies to compare surgical and nonsurgical outcomes. Slightly
higher union rates, improved Constant scores, and increased
forward flexion were noted in the surgical group. Level of
evidence: III.
12. Launonen AP, Sumrein BO, Reito A, et al: Operative versus non-
operative treatment for 2-part proximal humerus fracture: A
multicenter randomized controlled trial. PLoS Med
2019;16(7):e1002855. This RCT compared nonsurgical
management with ORIF of displaced two-part proximal humerus
fractures. There was no difference in outcomes scores at 2 years
but more complications in the surgical group. Level of evidence:
I.
13. Robinson CM, Stirling PHC, Goudie EB, MacDonald DJ,
Strelzow JA: Complications and long-term outcomes of open
 reduction and plate fixation of proximal humeral fractures. J Bone
Joint Surg Am 2019;101(23):2129-2139. This retrospective review
evaluated 368 patients with severely displaced proximal humeral
fractures treated with ORIF at 10 years postoperatively. Most of
the revision surgeries were due to stiffness, and most patients
reported good to excellent function, pain, and satisfaction. Level
of evidence: III.
14. Plath JE, Kerschbaum C, Seebauer T, et al: Locking nail versus
locking plate for proximal humeral fracture fixation in an elderly
population: A prospective randomised controlled trial. BMC
Musculoskelet Disord 2019;20(1):20. This RCT of 68 patients
compared locking blade intramedullary fixation with ORIF with a
plate for proximal humeral fractures. Improved DASH scores at 1
year postoperatively and decreased reduction loss and screw
cutout in the intramedullary group were reported. Level of
evidence: I.
15. Orman S, Mohamadi A, Serino J, et al: Comparison of surgical
and non-surgical treatments for 3- and 4-part proximal humerus
fractures: A network meta-analysis. Shoulder Elbow 2020;12(2):99-
108. This meta-analysis of eight RCTs compared nonsurgical
treatment, ORIF, rTSA, and hemiarthroplasty for three-part and
four-part proximal humeral fractures. The study authors found
fewer adverse events and be er clinical outcomes in the rTSA
compared with the hemiarthroplasty group and noted decreased
rates of unplanned surgery in the nonsurgical group. Level of
evidence: I.
16. Fraser AN, Bjordal J, Wagle TM, et al: Reverse shoulder
arthroplasty is superior to plate fixation at 2 years for displaced
proximal humeral fractures in the elderly: A multicenter
randomized controlled trial. J Bone Joint Surg Am 2020;102(6):477-
485. This multicenter RCT compared rTSA with ORIF for
displaced proximal humeral fractures among 124 patients older
than 65 years. Significantly be er Constant scores were seen in
the arthroplasty group, especially in the subgroup of type C2
fractures. Level of evidence: I.
17. Lehtimaki K, Rasmussen JV, Kukkonen J, et al: Low risk of
revision after reverse shoulder arthroplasty for acute proximal
humeral fractures. JSES Int 2020;4(1):151-155. This study
evaluated the 5-year survival rate of reverse total shoulder
arthroplasty for 1,523 proximal humeral fractures from Nordic
registry data. A 97% survivorship at 5 years postoperatively was
noted.
18. Unbehaun D, Rasmussen S, Hole R, et al: Low arthroplasty
survival after treatment for proximal humerus fracture sequelae:
3,245 shoulder replacements from the Nordic Arthroplasty
Register Association. Acta Orthop 2020; July 17 [Epub ahead of
print]. This study evaluate 3,245 patients from a Nordic registry
who had subacute reverse total shoulder arthroplasty for a
proximal humeral fracture. The study authors noted survival
rates of 94%, 89%, and 85% at 1, 5, and 10 years, respectively.
19. Ramo L, Sumrein BO, Lepola V, et al: Effect of surgery vs
functional bracing on functional outcome among patients with
closed displaced humeral shaft fractures: The FISH randomized
clinical trial. J Am Med Assoc 2020;323(18):1792-1801. This RCT out
of Finland compared nonsurgical management with ORIF for
displaced humeral shaft fractures among 78 patients. No
difference in functional outcomes was found, but a 25% rate of
nonunion was found in the nonsurgical group and 30% of
patients converted from nonsurgical to surgical management.
Level of evidence: I.
20. Ramo L, Paavola M, Sumrein BO, et al: Outcomes with surgery
vs functional bracing for patients with closed, displaced humeral
shaft fractures and the need for secondary surgery: A
prespecified secondary analysis of the FISH randomized clinical
trial. JAMA Surg 2021; April 14 [Epub ahead of print]. This
secondary analysis of an RCT compared patients who
successfully underwent nonsurgical management, those who
underwent initial nonsurgical management but converted to
surgical management, and those who underwent initial surgical
management for humeral shaft fractures. Functional outcomes
 were significantly worse in the conversion group. Level of
evidence: I.
21. Hosseini Khameneh SM, Abbasian M, Abrishamkarzadeh H, et
al: Humeral shaft fracture: A randomized controlled trial of
nonoperative versus operative management (plate fixation).
Orthop Res Rev 2019;11:141-147. This RCT compared surgical
management with nonsurgical management for humeral shaft
fractures. There was a decreased time to union in the surgical
group (13.9 weeks) compared with the nonsurgical group (18.7
weeks), but similar functional outcomes were achieved at 1 year
postoperatively. Level of evidence: I.
22. Shearin JW, Chapman TR, Miller A, Ilyas AM: Ulnar nerve
management with distal humerus fracture fixation: A meta-
analysis. Hand Clin 2018;34(1):97-103.
23. Dehghan N, Furey M, Schemitsch L, et al: Long-term outcomes
of total elbow arthroplasty for distal humeral fracture: Results
from a prior randomized clinical trial. J Shoulder Elbow Surg
2019;28(11):2198-2204. A long-term follow-up study on an RCT
comparing open reduction internal fixation with total elbow
arthroplasty for distal humeral fractures is presented. There were
no significant differences, but there were relatively low numbers.
Level of evidence: II.
24. Chen H, Shao Y, Li S: Replacement or repair of terrible triad of
the elbow: A systematic review and meta-analysis. Medicine
(Baltimore) 2019;98(6):e13054. This meta-analysis of 115 terrible
triad injuries compared radial head arthroplasty with radial head
fixation. The arthroplasty group had be er functional outcomes,
improved range of motion, and fewer complications. Level of
evidence: II.
25. Ostergaard PJ, Tarabochia MA, Hall MJ, et al: What factors are
associated with reoperation after operative treatment of terrible
triad injuries? Clin Orthop Relat Res 2021;479(1):119-125. A
retrospective review of 62 terrible triad injuries with longer than
1 year follow-up is presented. The study authors report a 45%
 revision surgery rate with nearly half of these (21%) being due to
stiffness. Level of evidence: IV.
26. Jungbluth P, Tanner S, Schneppendahl J, et al: The challenge of
Monteggia-like lesions of the elbow: Mid-term results of 46 cases.
Bone Joint J 2018;100-B(2):212-218.
27. Klug A, Konrad F, Gramlich Y, Hoffmann R, Schmidt-Horlohe K:
Surgical treatment of the radial head is critical to the outcome of
Monteggia-like lesions. Bone Joint J 2019;101-B(12):1512-1519. This
retrospective case series reviewed 78 Monteggia fractures with
more than 2 years of follow-up. Those who had associated
coronoid fractures and radial head fractures requiring
arthroplasty reported significantly worse outcomes. Level of
evidence: IV.
28. Jung M, Groe ner-Schmidt C, Porschke F, Gru ner PA,
Guehring T, Schne ke M: Monteggia-like lesions in adults
treated with radial head arthroplasty-mid-term follow-up of 27
cases. J Orthop Surg Res 2020;15(1):5. This retrospective analysis
evaluated 27 patients with Monteggia-like injuries with
associated radial head fractures requiring arthroplasty. A 41%
complication rate and a 33% secondary surgery rate were noted.
Level of evidence: IV.
29. Koziarz A, Woolnough T, Oitment C, Nath S, Johal H: Surgical
management for olecranon fractures in adults: A systematic
review and meta-analysis. Orthopedics 2019;42(2):75-82. This meta-
analysis of RCTs and observational studies compared plate
fixation with tension band fixation for olecranon fractures. A
lower complication rate and hardware removal rate were found in
the plate group. Level of evidence: I.
30. Rantalaiho IK, Miikkulainen AE, Laaksonen IE, Aarimaa VO,
Laimi KA: Treatment of displaced olecranon fractures: A
systematic review. Scand J Surg 2021;110(1):13-21. This meta-
analysis of four RCTs evaluated various fixation methods for
olecranon fractures. No significant clinical differences were noted
 between plate fixation and tension band wiring. Level of
evidence: I.
31. Aibinder WR, Sims LA, Athwal GS, King GJW, Faber KJ:
Outcomes of nonoperative management of displaced olecranon
fractures in medically unwell patients. JSES Int 2021;5(2):291-295.
This retrospective analysis evaluated nonsurgical management
for displaced olecranon fractures in medically unwell patients.
Despite an 82% nonunion rate, generally good clinical results can
be obtained. Level of evidence: IV.
32. Lanzerath F, Hackl M, Wegmann K, Muller LP, Leschinger T:
The treatment of isolated Mason type II radial head fractures: A
systematic review. J Shoulder Elbow Surg 2021;30(3):487-494. This
systematic review of 319 patients with type II radial head
fractures from 11 different studies compared nonsurgical
management with ORIF. Comparable rates of arthritis at more
than 3 years’ follow-up and comparable functional outcomes
were found, but a higher secondary surgery rate in the surgical
group. Level of evidence: III.
33. Chaijenkij K, Arirachakaran A, Kongtharvonskul J: Clinical
outcomes after internal fixation, arthroplasty and resection for
treatment of comminuted radial head fractures: A systematic
review and network meta-analysis. Musculoskelet Surg
2021;105(1):17-29. This meta-analysis compared 526 radial head
fractures managed with ORIF, arthroplasty, and excision from 12
comparative studies and 1 randomized controlled trial. Be er
functional outcomes were found in the arthroplasty group and
higher complication rates were found in the fixation group. Level
of evidence: II.
34. Nappo KE, Hoyt BW, Balazs GC, et al: Union rates and reported
range of motion are acceptable after open forearm fractures in
military combatants. Clin Orthop Relat Res 2019;477(4):813-820. A
retrospective analysis of 73 high-energy open both-bone fractures
among military combatants is presented. Primary union rates
were achieved in 85% of patients and eventual union was
achieved in 96% of patients. Synostosis developed in 19% and was
 associated with significantly lower range of motion. Risk factors
for nonunion were bone loss at the fracture site and infection.
Level of evidence: III.
35. Donndorff AG, Petrucelli EM, Gallucci GL, et al: Galeazzi
fracture-dislocations: Long-term prognosis of the distal
radioulnar joint. Hand Surg Rehabil 2021;40(5):572-578. This case
series of 14 patients with previous Galeazzi fracture-dislocations
treated with plate fixation of the radius and closed reduction of
the distal radioulnar joint looked at radiographic and functional
outcomes more than 6 years postoperatively. Forty-three percent
of patients had a positive ballo ement test, but none of those
patients had associated pain with axial load. Level of evidence:
IV.
36. Woolnough T, Axelrod D, Bozzo A, et al: What is the relative
effectiveness of the various surgical treatment options for distal
radius fractures? A systematic review and network meta-analysis
of randomized controlled trials. Clin Orthop Relat Res
2021;479(2):348-362. This meta-analysis evaluated 4,789 patients
from 70 RCTs to compare various treatment options for distal
radial fractures. Volar locking plates had the best functional
outcomes, but the difference did not meet MCID. Volar locking
plates and intramedullary fixation had a lower risk of
complications when compared with nonsurgical management for
intra-articular fractures. Level of evidence: I.
37. Chung KC, Kim HM, Malay S, Shauver MJ: Wrist, radius injury
surgical trial G. The wrist and radius injury surgical trial: 12-
month outcomes from a multicenter international randomized
clinical trial. Plast Reconstr Surg 2020;145(6):1054e-1066e. This
multicenter RCT evaluated various treatment options for distal
radial fractures among 304 patients. Despite a 48% malunion rate
in the nonsurgical group, there were no differences in functional
outcome scores. The internal fixation group did have significantly
be er outcomes at 6 weeks postoperatively compared with all
other groups. Level of evidence: I.
38. Chung KC, Cho HE, Kim Y, Kim HM, Shauver MJ, Group W:
Assessment of anatomic restoration of distal radius fractures
among older adults: A secondary analysis of a randomized
clinical trial. JAMA Netw Open 2020;3(1):e1919433. A secondary
analysis of a multicenter RCT compared radiographic parameters
with patient outcomes in 166 patients older than 60 years with
distal radial fractures. For patients older than 70 years every
millimeter increase toward neutral variance was associated with a
10.4-point improvement in Michigan Hand Outcomes
Questionnaire, and every degree increase in radial inclination
away from normal resulted in decreased grip strength by 1.1 kg.
These results did not reach clinical significance at 1 year
postoperatively. Level of evidence: I.
39. Yoon AP, Wang C, Speth KA, Wang L, Chung KC, WRIST
Group: Modifiable factors associated with chronic pain 1 year
after operative management of distal radius fractures: A
secondary analysis of a randomized clinical trial. JAMA Netw
Open 2020;3(12):e2028929. A secondary analysis of a multicenter
RCT evaluated factors associated with chronic pain at 1 year
postoperatively for distal radial fractures. Eighty-seven of 146
patients experienced chronic pain at 1 year. A delay in surgery of
more than 1 week was found to lead to a threefold increased risk
for chronic pain. Level of evidence: I.
40. Rua T, Malhotra B, Vijayanathan S, et al: Clinical and cost
implications of using immediate MRI in the management of
patients with a suspected scaphoid fracture and negative
radiographs results from the SMaRT trial. Bone Joint J 2019;101-
B(8):984-994. This RCT evaluated clinical and cost implications for
using MRI for the acute diagnosis of scaphoid fractures with
negative radiographs. In their healthcare model in this study, the
overall cost was decreased for those who underwent advanced
imaging in the emergency department. Level of evidence: I.
41. Dias JJ, Brealey SD, Fairhurst C, et al: Surgery versus cast
immobilisation for adults with a bicortical fracture of the
scaphoid waist (SWIFFT): A pragmatic, multicentre, open-label,
 randomised superiority trial. Lancet 2020;396(10248):390-401. This
RCT compared surgical with nonsurgical treatment of 408
patients with scaphoid waist fractures. No significant differences
were found at 52 weeks postinjury. Fourteen percent of the
surgical group experienced a potentially serious adverse event
and 18% of the nonsurgical group had a cast-related
complication. Level of evidence: I.
42. Colak I, Bulut G, Bekler HI, Cecen GS, Gulabi D: Mid-term
clinical and radiographic outcomes of perilunate injuries treated
with open reduction and internal fixation. Acta Orthop Traumatol
Turc 2021;55(1):57-61. This retrospective review of perilunate
injuries evaluated midterm clinical and radiographic outcomes
after ORIF. At an average follow-up of 45 months, this study
showed satisfactory clinical and radiographic outcomes for these
injuries. Level of evidence: IV.
43. Cha SM, Shin HD, Kim YK: Comparison of low-profile locking
plate fixation versus antegrade intramedullary nailing for
unstable metacarpal shaft fractures – A prospective comparative
study. Injury 2019;50(12): 2252-2258. This prospective study
evaluated 75 metacarpal fractures, excluding the first metacarpal,
to compare intramedullary pin fixation with low-profile locking
plates. At 2 years postoperatively the intramedullary group had
improved DASH scores, improved grip strength, and less
extension lag. Level of evidence: II.
44. Beck CM, Horesh E, Taub PJ: Intramedullary screw fixation of
metacarpal fractures results in excellent functional outcomes: A
literature review. Plast Reconstr Surg 2019;143(4):1111-1118. This
meta-analysis reviewed 169 metacarpal fractures managed with
intramedullary screws from nine different retrospective studies.
At an average follow-up of 11 months, the study authors noted a
100% union rate, excellent grip strength and motion, no serious
complications, and nine minor complications. Level of evidence:
III.
45. Martinez-Catalan N, Pajares S, Llanos L, Mahillo I, Calvo E: A
prospective randomized trial comparing the functional results of
 buddy taping versus closed reduction and cast immobilization in
patients with fifth metacarpal neck fractures. J Hand Surg Am
2020;45(12):1134-1140. This RCT compared closed reduction and
casting with buddy taping for 72 fifth metacarpal neck fractures
with less than 70° of angulation. The buddy taping group had
decreased time back to work, improved clinical outcomes, and
fewer complications. Level of evidence: I.
46. Eisenschenk A, Spi muller R, Guthoff C, et al: Single versus
dual Kirschner wires for closed reduction and intramedullary
nailing of displaced fractures of the fifth metacarpal neck (1-2
KiWi): A randomized controlled trial. Bone Joint J 2019;101-
B(10):1263-1271. This RCT compared single and double Kirschner
wire fixation for 290 fifth metacarpal neck fractures. No
significant differences between the two groups were found. A
substantial limitation of the study was 52% follow-up at 6
months. Level of evidence: II.
47. Saied AR, Sabet Jahromi M: Treatment of proximal phalanx
fractures: Transarticular pinning the metacarpophalangeal joint
or cross pinning from the base of the proximal phalanx-a
prospective study. Eur J Trauma Emerg Surg 2019;45(4):737-743.
This RCT compared transarticular fixation with extra-articular
cross pinning for 61 proximal phalangeal fractures. No significant
differences between the two groups were found at 3 and 6
months postoperatively. Level of evidence: I.
48. El-Saeed M, Sallam A, Radwan M, Metwally A: Kirschner wires
versus titanium plates and screws in management of unstable
phalangeal fractures: A randomized, controlled clinical trial. J
Hand Surg Am 2019;44(12): 1091.e1-1091.e9. This RCT evaluated
40 patients with unstable transverse, long oblique, or spiral
diaphyseal fractures of the proximal and middle phalanges to
compare low-profile titanium plating with pin fixation. The study
authors noted improved motion and fewer complications in the
plating group. Level of evidence: II.
C H AP T E R 2 4

Lower Extremity Trauma

Augustine M. Saiz Jr MD, Ryan Mayer MD, Timothy Achor
MD, FAAOS

Dr. Achor or an immediate family member serves as a paid consultant to or is an employee of

Globus Medical, Stryker, and Synthes and has stock or stock options held in Imagen
Technologies. Neither of the following authors nor any immediate family member has received
anything of value from or has stock or stock options held in a commercial company or institution
related directly or indirectly to the subject of this chapter: Dr. Saiz and Dr. Mayer.

ABSTRACT
Lower limb musculoskeletal trauma continues to be highly
prevalent, with significant consequences for patients’ life and
quality. Given the ongoing challenges in the management of lower
limb musculoskeletal trauma, the body of evidence for treatment
recommendations continues to expand.
Keywords: external fixation; fracture; injury; internal fixation; lower
extremity

Introduction
Trauma remains a leading cause of morbidity and mortality
worldwide. Lower extremity trauma can result in devastating
consequences regarding patients’ physical function, mental health,
economic welfare, and ability to function independently. Long-term
sequelae, such as pos raumatic osteoarthritis due to articular
injuries, nonunion/malunion, limb-length discrepancy, or limb
deformity, occur if proper treatment principles of fracture
reduction and stabilization are not followed. Nonetheless, even
with proper nonsurgical or surgical management, complications
can still arise. Open fractures are quite common in lower extremity
trauma with expected worse outcomes and increased complications.
It is important to review the most recent evidence-based treatment
recommendations regarding different anatomic locations of injury.

Femoral Head
Femoral head fractures are rare injuries most often associated with
11% of high-energy hip dislocations. 1 Often these fractures require
fixation to restore hip stability, whether or not an associated
posterior wall fracture is present. Surgical fixation consists of
headless screws or countersunk screws to prevent articular
incongruity. The two surgical approaches are the Smith-
Petersen/modified Heuter approach and surgical hip dislocation. In
a 2020 study comparing the two approaches in patients with Pipkin
I and II femoral head fractures treated with open reduction and
internal fixation (ORIF), surgical time, blood loss, and pain scores
were lower in the modified Heuter group; however, there were no
differences in day-of-discharge pain scores, length of hospital stay,
union, osteonecrosis, or functional outcomes as measured by
modified Merle d’Aubigné and Oxford hip scores. 2
A 2020 study investigated the long-term outcomes of femoral
head fractures. 1 Twenty-eight femoral head fractures with at least
10-year follow-up were examined. All patients were treated with
one or a combination of the following: nonsurgical management,
ORIF, fragment excision, or total hip arthroplasty (THA), and
functional outcomes were measured by the Oxford hip score. The
average follow-up was 14 years, and patients’ average age at the
time of injury was 39.2 years with 86% of patients having surgery.
Overall, seven patients had late conversion to THA, with three of
those patients requiring a later THA revision. The average Oxford
hip scores in all 28 patients was 37 in the native femoral head
retained group, 41 in the primary THA group, and 31.4 in the group
requiring a secondary THA. 1 Overall, the study shows that ORIF of
the femoral head may have satisfactory long-term outcomes, but
currently outcomes remain unpredictable.

Femoral Neck
Femoral neck fractures are typically categorized as either low-
energy fractures in geriatric patients with poor bone quality or
high-energy fractures in young patients. This differentiation is
important for displaced fractures because it affects treatment
algorithms: younger patients undergo surgical reduction and
fixation, whereas geriatric patients are treated with arthroplasty.
Definitive treatment options are based on physiologic age, bone
density, and fracture pa ern.
In physiologically young patients with displaced femoral neck
fractures, the goal of care remains anatomic reduction and stable
fixation to achieve union and preserve hip biomechanics. Although
open reduction is considered the gold standard, recent literature
has reexamined whether this is always necessary. A 2020
multicenter retrospective study evaluated the factors associated
with performing an open reduction and the association of revision
surgery with open versus closed reduction. 3 Open reduction was
associated with study center, younger age, transcervical fracture
location, posterior fracture comminution, no history of
osteoporosis, and surgery within 12 hours. 3 For open reduction,
71% had acceptable reduction and 33% underwent revision surgery
compared with 69% acceptable reduction and a 28% revision
surgery rate in fractures treated with closed reduction, with the
revision surgery rate being statistically significant, representing a
2.4-fold greater propensity-adjusted hazard of revision surgery. 3
However, the study could neither determine causality nor eliminate
injury severity as potential bias.
Fixation constructs for femoral neck fractures continue to evolve.
Historically, these fractures have been stabilized with cannulated
screws or sliding hip screws. Newer technology and techniques,
including fibular strut grafts and novel fixed-angle locking plates
with controlled dynamic compression, aim to increase stability of
fracture fixation 4 (Figure 1).

Figure 1 A, AP radiograph from a 32-year-old woman involved in a high-speed

motor vehicle collision, revealing a widely displaced vertical femoral neck
fracture. B, Radiograph obtained immediately after open reduction and internal
fixation using a novel fixed-angle femoral neck plate.

As the geriatric population continues to grow, so does the

incidence of geriatric hip fractures and multicenter randomized
controlled trial (RCT) investigation outcomes. The HIP fracture
Accelerated surgical TreaTment And Care tracK (HIP ATTACK)
international RCT examined whether patients with earlier surgical
treatment had be er outcomes than patients who received standard
of care. Patients older than 45 years with a hip fracture were
randomized to receive accelerated surgical care (within 6 hours of
diagnosis) or standard of care (within 48 hours). There were 2,970
patients randomized: 1,487 to the accelerated surgical procedure
group and 1,483 to standard treatment group. 5 The median time
from hip fracture diagnosis to the surgical procedure was 6 hours in
the accelerated surgical procedure group and 24 hours in the
standard-care group. 5 Mortality and major complications were
similar between the groups. The study showed that with standard
care, an accelerated surgical procedure did not lower the risk of
mortality or major complications.
A subset analysis of the Fixation using Alternative Implants for
the Treatment of Hip fractures (FAITH) study, an RCT comparing
cannulated screws with sliding hip screws, assessed posterior tilt
and need for arthroplasty in patients with Garden I and II femoral
neck fractures. Patients with posterior tilt greater than 20° on
preoperative imaging had a 2.2-fold increased risk of subsequent
arthroplasty after initial fixation. 6 In addition, patients older than
80 years were also at increased risk. Given these results, primary
arthroplasty instead of internal fixation may be warranted in older
patients with femoral neck fractures, especially those presenting
with greater than 20° of posterior tilt.
For patients undergoing arthroplasty, typically THA has been
favored over hemiarthroplasty for active, high-functioning geriatric
patients. The Hip Fracture Evaluation with Alternatives of Total Hip
Arthroplasty versus Hemi-Arthroplasty (HEALTH) study is an
international, multicenter RCT that compared THA with
hemiarthroplasty. 7 A total of 1,495 patients with hip fracture who
were age 50 years or older were randomized to THA or
hemiarthroplasty and followed for 24 months. Differences were
noted in terms of the primary outcome of secondary surgical
procedure nor mortality. Patients who received a THA had a
twofold increased risk of dislocation compared with those who had
hemiarthroplasty in addition to slightly increased risk of serious
adverse events. Functional outcomes using the Western Ontario
and McMaster Universities Osteoarthritis Index were slightly be er
with THA compared with hemiarthroplasty but did not meet
clinically important difference, and there were no differences in the
Timed Up and Go tests. A similar RCT of 120 octogenarians with
displaced femoral neck fractures found no difference between the
THA and hemiarthroplasty groups regarding hip function, quality
of life, complications, or pain. 8 Although the potential advantages
of THA for hip fractures may not be as strong as previously
thought, data beyond 2 years remain limited.
For patients being treated with hemiarthroplasty, recent studies
have evaluated optimal surgical techniques. A meta-analysis of 21
studies with 61,487 patients with hip fractures treated with
hemiarthroplasty compared surgical approaches (anterior, lateral,
posterior). 9 The posterior approach was associated with the
greatest risk of dislocation compared with lateral or anterior
approaches. In addition, the posterior approach was also associated
with increased risk of revision surgery compared with the other
approaches. An RCT of 400 patients with hip fractures treated with
hemiarthroplasty compared cemented with cementless techniques
at 1-year follow-up. 10 Mortality was higher in the cementless group,
and mobility improved in the cemented group. Revision surgery
rates were similar. In agreement with the American Academy of
Orthopaedic Surgeons Clinical Practice Guideline on Management
of Hip Fractures in the Elderly, cemented femoral stems for
patients with femoral neck fractures are recommended.
Femoral neck fractures remain common in the geriatric
population and can also be seen in young patients with high-energy
trauma. In physiologically young patients, ORIF remains the
standard of care to optimize reduction and outcomes. For geriatric
patients, arthroplasty may be a more reliable treatment method
than fixation, although this remains dependent on patient factors,
fracture morphology, and implant construct.

Intertrochanteric Femur
The primary treatment of intertrochanteric femoral fractures is
reduction and fixation regardless of age. Understanding these
fracture pa erns have taken on increased importance in
understanding reduction and fixation strategies. A study compared
CT with plain radiographs in evaluating intertrochanteric femoral
fracture pa erns. 11 The study found poor correlation between the
two imaging modalities and that CT could be er predict fixation
failure because coronal pa erns and lateral wall integrity were
be er assessed. Understanding the fracture pa ern is important, as
recent studies demonstrated that reduction is critical to successful
union and to prevent femoral neck shortening, which has been
associated with inferior clinical results. 12 , 13
Fixation of intertrochanteric femoral fractures with short or long
cephalomedullary nail constructs has long been debated. A meta-
analysis examined the growing literature examining this question in
AO 31-A1 and 31-A2 fractures. 14 Six high-quality studies were
included after screening 2,741 articles, and outcomes of interest
were revision surgery rate, surgical time, length of hospital stay, 1-
year mortality. No differences were found between the groups,
except short nails had decreased surgical time compared with long
nails. In addition, using the Danish Multidisciplinary Hip Fracture
Registry, 2,245 pertrochanteric fractures were identified; 1,867 were
treated with a short intramedullary nail, and 378 were treated with
a long intramedullary nail. 15 This study confirmed that for
subtrochanteric fractures, a long intramedullary nail has a lower
rate of major revision surgeries compared with a short
intramedullary nail. In contrast, a short intramedullary nail has a
lower rate of major revision surgeries compared with a long
intramedullary nail for pertrochanteric fractures.
The theoretical concerns regarding short nails (periprosthetic
fractures, instability, implant failures) have not borne out in the
literature. Short nails may be broadly applied to intertrochanteric
femoral fractures except for those fracture pa erns with
subtrochanteric extension.

Subtrochanteric Femur
Subtrochanteric femoral fractures are now routinely treated with
intramedullary fixation, but issues with mechanical alignment and
nonunion are continual challenges. A study investigated the
nonunion risk factors associated in subtrochanteric femoral
fractures treated with intramedullary fixation. 16 A retrospective
review of 74 patients with subtrochanteric femoral fractures treated
with intramedullary fixation over a 6-year period found a nonunion
rate of 23% (17 of 74). The risk factors associated with nonunion
were postoperative varus malalignment, postoperative lack of
medial cortical support, and autodynamization of the nail within
the first 12 weeks after surgery. Accuracy of each of these three
parameters to predict nonunion was greater than 0.70. Furthermore,
the nonunion rate significantly increased with the number of risk
factors (no risk factor: 2.9%, one risk factor: 23.8%, two risk factors:
52.9%, and three risk factors: 100%). This was further strengthened
by a similar study looking at risk factors for nonunion/delayed
healing in subtrochanteric femoral fractures. 17 Sixty-one patients
with subtrochanteric femoral fractures were retrospectively
analyzed. Quality of the reduction, caput-collum-diaphyseal angle,
tip-apex distance, leg-length shortening, and fracture healing
according to the Radiographic Union Score for Hip were assessed.
Patients with be er reductions and caput-collum-diaphyseal angles
had higher rates of union. As these studies demonstrate, quality of
reduction remains the most important factor in fracture healing.

Femoral Shaft
The optimal treatment for adult femoral shaft fractures remains a
reamed, statically locked intramedullary nail. With any high-energy
shaft fracture, though, an ipsilateral femoral neck fracture must be
ruled out. Historically this was done with thin-cut CT; however,
subtle fractures can still be missed. A new study investigated the
role of a modified, quick coronal MRI protocol. 18 In a series of 39
high-energy shaft fractures that received both thin-cut CT and
novel MRI protocol to evaluate for ipsilateral femoral neck fracture,
four patients had a femoral neck fracture identified on MRI that
was missed by CT (Figure 2). For geriatric low-energy femoral shaft
fractures, intramedullary nails that have fixation into the femoral
neck should be used. In a study from Sweden, patients older than
55 years with femoral shaft fractures had a higher rate of peri-
implant fractures, especially hip fractures, in the group without
femoral neck protection compared with the group with femoral
neck protection. 19 In the patient with polytrauma, early appropriate
care, including early intramedullary fixation of femoral shaft
fractures, is associated with improved outcomes systemically. 20
Figure 2 A and B, AP and lateral radiographs from a 32-year-old man after a
motor vehicle collision. The patient sustained a midshaft femoral fracture. C,
While the CT scan was negative for a femoral neck fracture, coronal magnetic
resonance images (D and E) reveal signal enhancement about the femoral
neck, consistent with a likely femoral neck fracture. F and G, AP and lateral
radiographs after percutaneous cannulated screw placement to protect femoral
neck, followed by retrograde intramedullary nailing of the femoral fracture.
Distal Femur
For native distal femoral fractures with intra-articular extension,
ORIF remains the mainstay of treatment. The implants used for
these fractures have been under evolution. A 2019 study examined
fixation of these fractures with the traditional lateral locked plate in
addition to a medial plate or intramedullary nailing. 21 In this
biomechanical study examining AO 33-C distal femoral fractures,
the lateral plate-intramedullary nail and lateral plate-medial plate
constructs had the strongest baseline stiffness, greatest
survivability, and tolerated the most cycles to failure compared with
lateral plating alone.
Distal femoral periprosthetic fractures above total knee
arthroplasty implants have become increasingly frequent (Figure 3).
A 2020 systematic review looked at fixation of these fractures
comparing plating with intramedullary nailing. 22 Plating had an
overall decreased rate of complications or revision surgery.
However, intramedullary nailing was associated with earlier weight
bearing and more patients returning to preinjury level of function.
For some fractures, distal femoral replacement (DFR) has been
considered a treatment option. A meta-analysis compared the
outcomes between DFR and ORIF for periprosthetic femoral
fractures and found similar rates of complications but be er
motion in the ORIF group. 23 Internal fixation techniques, including
retrograde intramedullary nailing and locked plating, are favored in
most fractures when bone stock in the distal fragment allows for
appropriate fixation and stability. In the se ing of deficient distal
femoral bone stock or femoral component loosening, revision
arthroplasty with DFR is the favored technique.
 Figure 3 A and B, AP and lateral radiographs from a 74-year-old woman after
a fall, revealing a comminuted periprosthetic distal femoral fracture above a
previously well-functioning total knee arthroplasty. Immediate postoperative AP
radiograph (C) and lateral radiograph (D) after surgical stabilization. Notice the
retrograde intramedullary nail with supplemental lateral locking plate fixation.
Sufficient fixation and stability should be achieved to allow for immediate full
weight-bearing activities. If inadequate bone stock or bone quality exists,
consideration should be given to revision arthroplasty options including distal
femoral replacement.

Patella
Various fixation constructs exist for patellar fractures, each with
their own unique advantages and disadvantages (Figure 4). A 2021
biomechanical study compared anterior plating with cannulated
screw tension band technique in transverse patellar fractures. 24 The
two constructs performed equally in ultimate load-to-failure
strength and fatigue endurance under cyclical loading, although the
tension band group had increased overall failures compared with
the plating group. For inferior pole patellar fractures, often these
have been treated with partial patellectomy and patellar tendon
advancement. Although this generally restores the extensor
mechanism, this procedure has been complicated by failure of
bone-tendon healing, stiffness due to restrictive rehabilitation
protocols, or patella baja. A 2021 study investigated managing
these inferior pole fractures with suture anchors. 25 Of 21 patients
treated with suture anchors, all patients had healing by 4 months
and restoration of the knee extensor mechanism, and knee arc
range of motion restored to an average of 135°. Overall, the goals of
contemporary fixation strategies for the patella remain restoration
of the functional integrity and strength of the extensor mechanism
and articular congruity.
 Figure 4 A and B, AP and lateral radiographs from a 45-year-old man after a
fall from a ladder, with comminuted patellar fracture. C, CT scan reveals extent
of comminution. D, Intraoperative fluoroscopic images showing reduction
sequence with provisional fixation and anterior mesh plate application. E, Final
AP and F, lateral fluoroscopic images showing restoration of the extensor
mechanism and articular congruity. G and H, Final follow-up at 6 months shows
healed patellar fracture. The patient was asymptomatic and pain free.

Tibial Plateau
The three-column model for tibial plateau fractures has become
more widely accepted and used. A study correlated this model with
fracture mechanism: flexion varus, extension varus, hyperextension
varus, flexion valgus, extension valgus, and hyperextension valgus. 26
The flexion varus type pa ern was characterized by a primary
fracture apex located posteromedially and was frequently
associated with concomitant anterior cruciate ligament avulsion
(44.8%). The extension varus pa ern had a characteristic medial
fragment apex at the posteromedial crest or multiple apices
symmetrically around the crest and was commonly completely
articular in nature (65%). The hyperextension varus pa ern is noted
by anteromedial articular impaction, 51% with a fibular avulsion
and 60% with posterior tension failure fragments. The flexion
valgus pa ern was characterized by articular depression
posterolaterally, often (58.9%) with severe comminution of the
posterolateral cortical rim. The extension valgus pa erns only
involved the lateral plateau, with central articular depression
and/or a pure split. The hyperextension valgus pa ern is denoted
by anterolateral articular depression. A moderate positive
association was found between flexion varus fractures and anterior
cruciate ligament avulsions and between hyperextension varus
fractures and fibular avulsions.
For tibial plateau fractures with articular depression, debate
continues regarding the ideal graft to support the articular
fragment once elevated. A multicenter RCT compared autologous
iliac cortical bone graft with bioresorbable hydroxyapatite and
calcium sulfate cement (Cerament bone void filler) in 135 patients
with depressed tibial plateau fractures. 27 There were no significant
differences in functional or pain scores at postoperative week 26.
There was a significant reduction of blood loss and pain levels at
postoperative day 1 in the Cerament bone void filler group. The
rates of fracture healing, defect remodeling, and articular
subsidence were not significantly different in both groups.
The role of soft-tissue injury and MRI in tibial plateau fractures
remains unclear. However, a 2020 study that examined the
outcomes of tibial plateau fractures with MRI identified soft-tissue
injuries compared with those without a soft-tissue injury on MRI. 28
At 12 months postoperatively, there were no differences in
functional outcomes between the patients. For tibial plateau
fractures, restoration of alignment, improving the condylar width,
and articular reduction remain the most important aspects of care;
however, stability of the knee joint must be confirmed as well.

Tibial Shaft
The debate continues regarding the use of infrapatellar and
suprapatellar nailing for tibial fractures. Multiple studies and RCTs
have been performed to compare the clinical outcomes, functional
outcomes, and complications, including the incidence of knee pain.
One of the largest studies included 16 total studies (5 RCTs and 11
observational) with 1,750 patients, of which 810 patients underwent
suprapatellar nailing and 940 infrapatellar nailing. 29 Although
there was no difference in complication rates between the groups,
the suprapatellar nailing group had be er Lysholm scores,
decreased fluoroscopy times, and improved entry point accuracy. A
2019 study more specifically compared the incidence of knee pain in
patients with greater than 12-month follow-up using a numeric
rating scale. 30 The median follow-up for the 262-patient cohort was
3.8 years, and there was no statistical or clinical difference in knee
pain at rest while walking or kneeling.
Intramedullary fixation is increasingly being used for more
proximal and distal tibia fractures. A 2020 study of 43 consecutive
proximal tibia fractures managed with suprapatellar nailing had an
average follow-up of 20.4 months, average Lower Extremity
Functional Scale of 89.4%, and no anterior knee pain. 31 There were
four malunions and one nonunion requiring an additional surgery,
but all fractures eventually united. For extra-articular distal tibial
fractures, a meta-analysis assessed the functional outcomes and
complications of 1,332 patients in 15 studies (including 10 RCTs)
treated with either an intramedullary nail or plate fixation. 32 There
were no differences between the groups in functional outcomes,
union rate, or need for additional procedures. Patients treated with
an intramedullary nail had a higher risk of malunion, higher rate of
anterior knee pain, shorter time to union, shorter time-to-full-
weight-bearing, and lower risk of deep infection.
 Ballistic injuries and open tibial fractures present additional
issues and have higher complication rates. A 2021 multicenter
retrospective study involving 121 patients who sustained a low-
velocity ballistic tibial fracture demonstrated an overall
complication rate of 49%. 33 There was a 14% infection rate, and 26%
of patients underwent an additional procedure. Several studies
have evaluated the timing of soft-tissue coverage in open Gustilo
type III tibial fractures, demonstrating an increased complication
rate with a delay in soft-tissue coverage. A 2019 multicenter study
with 672 patients had a 10% increase in complication rate if there
was a delay in coverage over 7 days. 34 A 2021 study including 296
patients had 32.4% deep infection rate, with the most predictive
factor in multivariate regression being the time from definitive
fixation to flap coverage. 35 No association with increased infection
was noted in patients treated with temporary internal fixation.

Pilon
Although implant design and technology have continued to
advance, particularly the use of fragment-specific or mini-fragment
fixation, the tenants of soft-tissue handling with targeted surgical
approaches to allow fracture reduction and stable fixation remain
paramount in the management of pilon fractures 36 (Figure 5).
Complication rates continue to be high, particularly in patients
with severe soft-tissue injuries, and especially in open injuries.
 Figure 5 Images show a comminuted pilon fracture in a 20-year-old man after
a fall off a roof.A and B, AP and lateral radiographs show a comminuted tibial
plafond fracture with intact fibula. C, Three-dimensional CT scan and D, axial CT
reveal complex intra-articular pathology. Immediate postoperative AP radiograph
(E) and lateral radiograph (F) after open reduction and internal fixation using
mini-fragment, fragment-specific fixation.

Recent literature has focused on some of the risk factors

associated with the development of deep infection, nonunion, and
flap coverage. A single-center, retrospective study of 150 patients
with pilon fractures had a 16.7% deep infection rate. 37 Although
open fractures had a higher infection rate, when analyzed based on
the location of the traumatic wound, there was a higher infection
rate in patients with a medial or anterior wound. Other factors
found to be associated with complications included segmental bone
loss, need for soft-tissue coverage, and use of a posterolateral
approach.
With most of these injuries being managed in a staged manner, a
2021 study tried to determine if overlap of the definitive construct
with external fixator pin sites was an independent risk factor for
infection. 38 One hundred forty-six patients were treated in a staged
manner over a 6-year period at a single center. Fifty-eight patients
(40%) were included with overlap between the definite plate and
external fixator pin site. Twenty-two patients (15%) in the cohort
developed a deep infection, with no significant differences in either
the amount of overlap or the distance from plate to pin site.
A 2019 study tried to assess risk factors for the development of a
tibial plafond nonunion by retrospectively assessing 518 patients at
a single center. 39 Their nonunion rate was 14%, with risk factors
including bone loss, open fracture, lack of medial column fixation,
use of locking plates, and tobacco use. The nonunion and wound
complication rate in open pilon fractures was also assessed in a
retrospective, multicenter study that included 161 patients. 40 The
deep infection rate was 27% and there was association with tobacco
use, type 3B fractures, and male sex. There was a higher rate of
infection in patients treated with acute fixation and those who
underwent soft-tissue coverage greater than 1 week after definitive
fixation. There was a 22% nonunion rate and a 47% rate of
secondary procedures for either revision, removal of deep implants,
or irrigation and debridement.

Ankle
Many techniques have been described to evaluate syndesmotic
injury and confirm anatomic reduction. A 2020 cadaver study found
improved translational reduction accuracy using the anterolateral
articular surface of the distal tibia as a visual landmark compared
with the incisura. 41
Debate continues regarding the optimal fixation construct for
patients with syndesmotic injuries (Figure 6). Multiple RCTs have
tried to assess the outcomes of patients with syndesmotic injuries
treated using suture bu on fixation versus screw fixation. A 2018
study assessing 97 patients with syndesmotic injuries both
clinically and with postoperative CT scans shows improved
outcomes at 2 years in patients treated with suture bu on fixation
compared with a single quadricortical syndesmotic screw. 42
Patients in the suture fixation group had significantly improved
patient-reported outcomes (American Orthopaedic Foot and Ankle
Society scale and Olerud-Molander Ankle scores), lower rate of
tibiofibular widening, and a lower rate of symptomatic, recurrent
syndesmotic diastasis. This increase could have been related to
secondary loss of reduction due to early, routine screw removal. A
multicenter RCT with 103 patients with syndesmotic injuries
treated using either suture bu on fixation or two tricortical
syndesmotic screws showed similar functional outcomes at 1 year
and a higher rate of revision surgery in the screw fixation group
primarily because of implant removal. 43 CT scans obtained 3
months postoperatively demonstrated a higher rate of syndesmotic
malreduction with screw fixation (39% versus 15%); however,
patients treated with suture bu on fixation still had greater
syndesmotic diastasis compared with the uninjured side and less
fibular medialization compared with the screw fixation group. Two
other RCTs that compared patients treated with a suture bu on or a
single tricortical syndesmotic screw showed similar functional and
radiographic outcomes at 2 years; however, at 5-year follow-up,
there were improved functional outcomes and a decreased
incidence of radiographic degenerative changes in patients treated
with suture bu on fixation. 44 , 45
 Figure 6 A and B, AP and lateral radiographs from a 35-year-old man who
sustained an ankle fracture while mountain biking. Following fixation of the fibular
fracture, a stress test revealed syndesmosis instability. C and D, The
syndesmosis was stabilized using a hybrid of flexible suture button fixation and
rigid screw fixation.

Evidence advocating for the safety of early weight bearing after

ankle fractures has also been growing. An RCT comparing patients
with ankle fractures cleared to bear weight at 2 weeks versus 6
weeks demonstrated no increase in complication rate and similar
patient-reported outcomes (Olerud-Molander Ankle score) between
groups. 46 A 2021 systematic review and meta-analysis of 20 studies,
including 1,130 cases, also showed similar complication rates and
patient-reported outcomes in early versus delayed weight-bearing
groups; however, there was an increase in noninfectious
complications with early range of motion before wound healing. 47

Hindfoot
A meta-analysis, with 2,179 patients from 17 RCTs and 10
retrospective studies, comparing the clinical outcomes of displaced
intra-articular calcaneal fractures managed with ORIF using an
extensile lateral or minimal incision approach found more
favorable results using a minimal incision approach. 48 There were
improved radiographic parameters (calcaneal height and Böhler
angle) and patient-reported outcomes (visual analog scale and
American Orthopaedic Foot and Ankle Society scores), with
decreased wound complications, superficial infections, and sural
nerve injuries.
However, a different 2021 study was performed using
postoperative CT scans and radiographs to assess the reduction
quality in displaced intra-articular calcaneal fractures managed
with ORIF using an extensile lateral or sinus tarsi approach. 49
Overall, the posterior facet fracture gap and step-off as well as the
residual varus angulation of the tuberosity were improved in
patients treated with an extensile lateral approach. When separated
based on the Sanders classification, there was no statistically
significant difference in reduction quality based on the approach,
but there was a trend in be er reduction quality with an extensile
lateral approach in Sanders III calcaneal fractures. Overall, the data
regarding reduction appear to favor the sinus tarsi pa ern for
simple intra-articular calcaneus fracture pa erns when surgery can
be performed acutely. For calcaneal fractures with complex articular
fracture fragments, significant tuberosity displacement, and/or
even for simple fracture pa erns done in the subacute period, the
extensile lateral approach facilitates improved reductions and
restoration of morphology.
Subtalar arthrodesis can be performed in conjunction with ORIF
in select patients based on underlying patient factors and fracture
characteristics, including the degree of cartilage injury and
posterior facet comminution. 50 A recent retrospective study
demonstrated a 94.3% fusion rate, defined as bridging bone greater
than 25% of the posterior facet on postoperative CT scan, with this
technique. 50

Midfoot
Controversy still exists regarding the optimal treatment for Lisfranc
injuries, with ORIF and primary arthrodesis being the two most
considered treatment options. A meta-analysis, with 547 patients
from two RCTs and six retrospective studies, comparing these two
treatment options demonstrated similar outcomes and similar rates
of return to work/activity. 51 Patients treated with ORIF had a higher
rate of additional procedures, including implant removal or
secondary fusion, but the overall complication rate was similar
between the treatment groups. A 2020 RCT comparing first
tarsometatarsal joint ORIF using temporary bridge plating with
primary arthrodesis in 48 patients showed similar patient-reported
outcomes and visual analog scale pain scores; however, patients
treated with a temporary bridge plates had a higher incidence of
pos raumatic arthritis despite be er radiographic alignment
(Meary angle). 52
A 2018 study using the PearlDiver database showed that both the
average cost of care ($5005.82 for primary arthrodesis versus
$3961.97 for ORIF) and the complication rate (30.2% for primary
arthrodesis versus 23.1% for ORIF) were higher in patients treated
with primary arthrodesis compared with ORIF; however, this failed
to factor in the costs associated with the higher rate of hardware
removal in the ORIF group (43.6%) compared with the primary
arthrodesis group (18.4%). 53

Summary
Traumatic injuries to the lower extremity remain common with
continuing challenges for the orthopaedic surgeon to restore
anatomy to improve patient health and prevent long-term
disability. Treatment of these fractures requires a thorough
understanding of the native anatomy, fracture characteristics, and
fixation options. Each fracture and patient present unique
challenges, but with adherence to fundamental principles and
nuanced understanding of the type of the fracture, excellent
outcomes can be achieved.

Key Study Points

Primary arthroplasty instead of internal fixation may be warranted in older patients
with femoral neck fractures, especially those presenting with greater than 20° of
posterior tilt.
 For AO 31-A1 and 31-A2 intertrochanteric femoral fractures, there are no differences
in revision surgery rates (including peri-implant fractures, implant failure) between
short or long cephalomedullary nails.
Suprapatellar nailing of tibial fractures may provide some benefits, particularly in
proximal fractures, without an increase in postoperative knee pain, complication rate,
or change in clinical outcomes.
Syndesmotic stabilization using suture button fixation provides some benefits over
screw fixation, and studies have shown similar, if not improved, short-term and
midterm functional outcomes.

Annotated References
1. Koerner M, Westberg J, Martin J, Templeman D: Patient-
reported outcomes of femoral head fractures with a minimum 10-
year follow-up. J Orthop Trauma 2020;34(12):621-625. This is a
retrospective review of 28 femoral head fractures with 10 years of
follow-up. Seven patients required conversion to THA at an
average of 6.4 years, with three later requiring revisions. Oxford
hip score of native hips was 37 at an average of 13.6 years of
follow-up compared with 41 for primary THAs and 31.4 for
secondary THAs. Level of evidence: IV.
2. Gavaskar AS, Srinivasan P, Jeyakumar B, Raj RV, Sharath V,
Narayan DA: Surgical dislocation or the modified Heuter anterior
approach for Pipkin I and II femoral head fracture dislocations. J
Orthop Trauma 2020;34(12):626-631. This retrospective review of
49 patients with Pipkin I and II femoral head fractures treated
surgically with ORIF via modified Heuter or surgical hip
dislocation approaches compared the two groups for blood loss,
surgical time, pain, length of hospital stay, fracture union,
occurrence of pos raumatic hip arthritis, femoral head
osteonecrosis, and functional outcome using the modified Merle
d’Aubigné score and Oxford hip scores. Surgical time, blood loss,
and pain at 24 hours were significantly lower in the modified
Heuter group. The pain at discharge and length of hospital stay
were similar in both groups. All fractures had united. No cases of
osteonecrosis were observed. Functional outcome and
complications were similar in both groups. Level of evidence: III.
3. Pa erson JT, Ishii K, Torne a PIII, et al: Open reduction is
associated with greater hazard of early reoperation after internal
fixation of displaced femoral neck fractures in adults 18-65 years.
J Orthop Trauma 2020;34(6):294-301. A multicenter retrospective
cohort review of femoral neck fractures in patients 18 to 65 years
of age examined (1) which factors are associated with the choice
to perform an open reduction and (2) by adjusting for these
factors, whether the choice of reduction method is associated
with revision surgery. Two hundred thirty-four patients were
reviewed at a median follow-up of 1.5 years. Reduction quality
was not significantly affected by open versus closed approach
(71% versus 69% acceptable, P = 0.378). A total of 35 (33%) versus
28 (22%) revision surgeries occurred after open versus closed
reduction (P = 0.056). Open reduction was associated with a 2.4-
fold greater propensity-adjusted hazard of revision surgery (95%
confidence interval 1.3 to 4.4, P = 0.004). Level of evidence: III.
4. Levack AE, Gausden EB, Dvorzhinskiy A, Lorich DG, Helfet DL:
Novel treatment options for the surgical management of young
femoral neck fractures. J Orthop Trauma 2019;33(suppl 1):S33-S37.
This technique article reviewed the clinical data regarding
conventional fixation constructs and described the technique and
rationale behind two novel alternative treatment options for
femoral neck fractures. The surgical technique and clinical
examples for constructs involving multiple cannulated
screws/Pauwels screw augmented with a fibular strut graft, as
well as a novel fixed-angle locking plate with controlled dynamic
compression, are presented. Level of evidence: IV.
5. HIP ATTACK Investigators Accelerated surgery versus standard
care in hip fracture (HIP ATTACK): An international,
randomised, controlled trial. Lancet 2020;395(10225):698-708. In
this international multicenter RCT, 2,970 patients were
randomized: 1,487 to an accelerated surgical procedure and 1,483
to standard treatment. The median time from hip fracture
diagnosis to the surgical procedure was 6 hours in the accelerated
surgical procedure group and 24 hours in the standard-care
 group (P < 0.0001). Mortality was similar between the groups: 9%
in the accelerated surgical procedure group and 10% in the
standard-care group. Major complications were also similar at
22% in both the accelerated surgical procedure group and the
standard-care group. The authors concluded that, compared with
standard care, an accelerated surgical procedure did not lower
the risk of mortality or major complications. Level of evidence: I.
6. Okike K, Udogwu UN, Isaac M, et al: Not all Garden-I and II
femoral neck fractures in the elderly should be fixed: Effect of
posterior tilt on rates of subsequent arthroplasty. J Bone Joint Surg
Am 2019;101(20):1852-1859. A subset analysis of the FAITH trial,
an international, multicenter study, looked at 555 patients, age
older than or equal to 50 years, with femoral neck fractures
classified as Garden I or II and assessed posterior tilt. Those
patients with greater than or equal to 20° had a higher incidence
of subsequent arthroplasty following internal fixation compared
with patients with less than 20° posterior tilt. Level of evidence:
III.
7. Investigators H, Bhandari M, Einhorn TA, et al: Total hip
arthroplasty or hemiarthroplasty for hip fracture. N Engl J Med
2019;381(23):2199-2208. This was an RCT of 1,495 patients 50 years
of age or older with a displaced femoral neck fracture to undergo
either THA or hemiarthroplasty. The primary end point was a
secondary hip procedure within 24 months of follow-up.
Secondary end points included death, serious adverse events,
hip-related complications, health-related quality of life, function,
and overall health end points. The primary end point occurred in
57 of 718 patients (7.9%) who were randomly assigned to THA
and 60 of 723 patients (8.3%) who were randomly assigned to
hemiarthroplasty (hazard ratio, 0.95; 95% confidence interval, 0.64
to 1.40; P = 0.79). Hip instability or dislocation occurred in 34
patients (4.7%) assigned to THA and 17 patients (2.4%) assigned
to hemiarthroplasty (hazard ratio, 2.00; 99% confidence interval,
0.97 to 4.09). Function, as measured with the total Western
Ontario and McMaster Universities Osteoarthritis Index score,
 pain score, stiffness score, and function score, modestly favored
THA over hemiarthroplasty. Mortality was similar in the two
treatment groups (14.3% among the patients assigned to THA
and 13.1% among those assigned to hemiarthroplasty, P = 0.48).
Serious adverse events occurred in 300 patients (41.8%) assigned
to THA and in 265 patients (36.7%) assigned to hemiarthroplasty.
Level of evidence: I.
8. Chammout G, Kelly-Pe ersson P, Hedbeck CJ, Stark A, Mukka S,
Skoldenberg O: HOPE-trial: Hemiarthroplasty compared with
total hip arthroplasty for displaced femoral neck fractures in
octogenarians – A randomized controlled trial. JBJS Open Access
2019;4(2):e0059. A prospective, randomized, single-blinded trial
included 120 patients with a mean age of 86 years (range, 80 to 94
years) who had sustained an acute displaced femoral neck
fracture <36 hours previously. The patients were randomized to
treatment with hemiarthroplasty (n = 60) or THA (n = 60). The
primary end points were hip function and health-related quality
of life at 2 years. Secondary end points included hip-related
complications and revision surgeries, mortality, pain in the
involved hip, activities of daily living, surgical time, blood loss,
and general complications. No differences between the groups in
terms of hip function, health-related quality of life, hip-related
complications and revision surgeries, activities of daily living, or
pain in the involved hip. Hip function, activities of daily living,
and pain in the involved hip deteriorated in both groups
compared with prefracture values. The ability to regain previous
walking function was similar in both groups. Level of evidence: I.
9. van der Sijp MPL, van Delft D, Krijnen P, Niggebrugge AHP,
Schipper IB: Surgical approaches and hemiarthroplasty outcomes
for femoral neck fractures: A meta-analysis. J Arthroplasty
2018;33(5):1617-1627.e9.
10. Parker MJ, Cawley S: Cemented or uncemented
hemiarthroplasty for displaced intracapsular fractures of the hip:
A randomized trial of 400 patients. Bone Joint J 2020;102-B(1):11-
16. A total of 400 patients with a displaced intracapsular fracture
 of the hip were randomized to receive either a cemented polished
tapered stem hemiarthroplasty or a cementless Furlong
hydroxyapatite-coated hemiarthroplasty. Follow-up was
conducted by a nurse blinded to the implant at set intervals for
up to 1 year from surgery. A total of 115 patients died in the year
after surgery. There was a tendency toward a slightly higher
mortality in those treated with the cementless prosthesis after 1
year (64 versus 51; P = 0.18). For the survivors, there was no
significant difference in pain score at any of the time intervals.
Patients treated using the cemented hemiarthroplasty recovered
mobility be er than those treated with the cementless
hemiarthroplasty (mean decrease in mobility score at 1 year: 1.7
versus 1.1, SD 1.9; P = 0.008). There was a tendency to more
periprosthetic fractures in the cementless group (five versus two
cases; P = 0.45). There were four perioperative deaths in the
cemented group. Level of evidence: I.
11. Hecht G, Saiz AMJr, Shelton TJ, et al: CT scans be er assess
lateral wall morphology of “stable appearing” intertrochanteric
(IT) femur fractures and predict early failure of sliding hip screw
(SHS) fixation. OTA Int 2021;4(3):e140. This is a retrospective
cohort study comparing the efficacy of plain radiographic images
and CT to assess the morphology of the lateral wall component of
intertrochanteric femoral fractures and determine predictors of
early fixation failure. One hundred forty-two adult patients with
intertrochanteric fractures treated with either a sliding hip screw
(SHS) or a cephalomedullary nail (CMN) who had both
preoperative plain radiographs and CT scans with at least 6
weeks of follow-up were reviewed. One hundred forty-two
patients met inclusion criteria, 105 patients were treated with a
CMN and 37 with a SHS. There was a poor correlation between
the assessment of the lateral wall on plain radiographs and CT
scans. Failures in the SHS group were significantly associated
with all CT measurements (P < 0.05) but not with plain film
lateral wall assessment (P = 0.66). Fifteen patients had an early
implant failure (6 CMN, 9 SHS). There were no statistically
 significant associations between any radiographic measurement
(plain images and CT) and CMN failures. Level of evidence: III.
12. Hoffmann MF, Khoriaty JD, Sietsema DL, Jones CB: Outcome of
intramedullary nailing treatment for intertrochanteric femoral
fractures. J Orthop Surg Res 2019;14(1):360. Retrospectively 216
consecutive adult intertrochanteric femoral fractures (OTA/AO
type 31 A3) with intramedullary nail fixation were identified.
After the index procedure, 86% healed uneventfully. Nonunion
development was observed in 6% and 5% had an unscheduled
revision surgery because of implant or fixation failure. Fixation
failure occurred in 11.1% of patients with a neck-shaft angle <125°
compared with 2.6% (4 of 155) of patients with a neck-shaft angle
≥125° (P = 0.021). Level of evidence: III.
13. Felton J, Slobogean GP, Jackson SS, et al: Femoral neck
shortening after hip fracture fixation is associated with inferior
hip function: Results from the FAITH trial. J Orthop Trauma
2019;33(10):487-496. This is a secondary analysis of data from the
FAITH trial. Femoral neck shortening was measured as a
categorical variable and classified into one of the following
groups: no shortening, mild shortening (≤5 mm), moderate
shortening (6 to 10 mm), or severe shortening (>10 mm). The
primary outcome for the current analysis was hip function, as
measured by the Western Ontario and McMaster Universities
Osteoarthritis Index questionnaire, at 24 months after injury.
Two-thirds of patients had no or mild shortening (≤5 mm),
whereas one-third of patients had moderate or severe shortening
(>5 mm). After adjusting for surgical treatment, a greater amount
of femoral neck shortening was found to be associated with
poorer hip function (P < 0.01). Level of evidence: II.
14. Bovbjerg P, Froberg L, Schmal H: Short versus long
intramedullary nails for treatment of intertrochanteric femur
fractures (AO 31-A1 and AO 31-A2): A systematic review. Eur J
Orthop Surg Traumatol 2019;29(8):1823-1831. A meta-analysis
looked at the revision surgery rate, as well as surgical time,
length of hospital stay, and 1-year mortality, between short and
 long intramedullary nails in intertrochanteric femoral fracture
types AO 31-A1 and AO 31-A2. Studies with patients older than
18 years comparing short nail with long nail and at least one of
the clinical outcomes on interest (revision surgery rate, surgical
time, length of hospital stay, 1-year mortality) were included. No
difference in complication rate leading to revision surgery was
found in the individual studies or in the meta-analysis (odds ratio
0.89 [0.49; 1.16]). There is no difference in the length of hospital
stay between the two nail cohorts; a shorter surgical time
inserting a short nail compared with inserting a long nail was
found (P < 0.0001). In the meta-analysis, no difference was noted
in 1-year mortality (odds ratio 1.20 [0.80; 1.79]). Level of evidence:
II.
15. Viberg B, Eriksen L, Hojsager KD, et al: Should pertrochanteric
and subtrochanteric fractures be treated with a short or long
intramedullary nail? A multicenter cohort study. J Bone Joint Surg
Am 2021;103(24):2291-2298. The Danish Multidisciplinary Hip
Fracture Registry was searched to identify patients who had been
aged 65 years and older who had had major revision surgeries,
defined as any revision surgery with the exclusion of simple
hardware removal within 2 years of follow-up. Of 2,245
pertrochanteric fractures, 1,867 were treated with a short
intramedullary nail and 378 were treated with a long
intramedullary nail. The rate of major revision surgeries was 4.0%
in the short intramedullary nail group and 6.3% in the long
intramedullary nail group with an adjusted odds ratio of 1.67
(1.04 to 2.70). Of 909 subtrochanteric fractures, 308 were treated
with a short intramedullary nail and 601 were treated with a long
intramedullary nail. The rate of major revision surgeries was 8.4%
in the short intramedullary nail group and 4.0% in the long
intramedullary nail group, yielding an adjusted odds ratio of 0.45
(0.25 to 0.81). Level of evidence: III.
16. Krappinger D, Wolf B, Dammerer D, Thaler M, Schwendinger P,
Lindtner RA: Risk factors for nonunion after intramedullary
nailing of subtrochanteric femoral fractures. Arch Orthop Trauma
 Surg 2019;139(6):769-777. Seventy-four patients who sustained a
subtrochanteric fracture were treated by femoral intramedullary
nailing at a single level 1 trauma centre within a 6-year period.
Nonunion occurred in 17 of 74 patients (23.0%). Of 15 potential
risk factors analysed, only 3 were found to have a significant
effect on the nonunion rate (P < 0.05): postoperative varus
malalignment, postoperative lack of medial cortical support, and
autodynamization of the nail within the first 12 weeks after
surgery. Accuracy of each of these three parameters to predict
nonunion was >0.70. Furthermore, the nonunion rate significantly
increased with the number of risk factors (no risk factor: 2.9%,
one risk factor: 23.8%, two risk factors: 52.9%, and three risk
factors: 100% [Chi-square test, P = 0.001]). Level of evidence: III.
17. Freigang V, Gschrei F, Bhayana H, et al: Risk factor analysis for
delayed union after subtrochanteric femur fracture: Quality of
reduction and valgization are the key to success. BMC
Musculoskelet Disord 2019;20(1):391. This retrospective
radiomorphometric case-control study compared 61 patients after
subtrochanteric femoral fractures in two groups (uncomplicated
healing within 6 months postoperatively versus delayed union)
concerning radiographic properties. Quality of the reduction,
caput-collum-diaphyseal angle, tip-apex distance, leg-length
shortening, and fracture healing according to the Radiographic
Union Score for Hip were assessed. The mean Radiographic
Union Score for Hip at 6 months postoperatively was 21.32
(±4.57). At that point of time, only 29 of 61 fractures were
radiographically fully consolidated (timely fracture healing), and
32 patients were rated as delayed union. The total revision rate
was 9 of 61 (14.7%), whereof 4 patients required revision for
symptomatic nonunion. The results of the radiomorphometric
measurement showed a significant difference between both
groups concerning the degree of reduction measured according
to Baumgaertner (P = 0.022). The postoperative ipsilateral caput-
collum-diaphyseal angle was different between the two groups (P
= 0.019). After 12 months postoperatively, 48 of 61 fractures
 (78.6%) healed without any further intervention. Level of
evidence: III.
18. Rogers NB, Hartline BE, Achor TS, et al: Improving the
diagnosis of ipsilateral femoral neck and shaft fractures: A new
imaging protocol. J Bone Joint Surg Am 2020;102(4):309-314. All
patients received standard radiographic imaging as well as thin-
cut high-resolution pelvic CT imaging on presentation. Rapid
limited-sequence MRI of the pelvis was obtained to evaluate for
an occult femoral neck fracture. Thirty-seven consecutive patients
with 39 acute, high-energy femoral shaft fractures resulting from
blunt trauma were included. Two femoral shaft fractures (5.1%)
were associated with ipsilateral femoral neck fractures that were
detected on radiographs, and no MRI was performed. None of
the remaining 37 femoral shaft fractures was associated with a
femoral neck fracture that was identified on CT imaging. Thirty-
three of 37 patients (89.2%) underwent pelvic MRI to evaluate the
ipsilateral femoral neck. Four of those 33 patients (12.1%) were
diagnosed with a femoral neck fracture (two complete, two
incomplete) that was not identified on thin-cut high-resolution
CT or radiographic imaging. Level of evidence: III.
19. Bogl HP, Zdolsek G, Michaelsson K, Hoijer J, Schilcher J:
Reduced risk of reoperation using intramedullary nailing with
femoral neck protection in low-energy femoral shaft fractures. J
Bone Joint Surg Am 2020;102(17):1486-1494. Using a national
registry in Sweden, this study identified the reasons for and the
types of revision surgeries that occurred for femoral shaft
fracture patients. The categories of implants were determined
through a review of radiographs as intramedullary nails with and
without femoral neck protection. Revision surgeries related to
peri-implant fractures (including hip fractures) were analyzed as
a subgroup of all major revision surgeries. Among the 897
patients, a total of 82 revision surgeries were performed. In 640
patients who were treated with intramedullary nails with femoral
neck protection, there were 7 peri-implant fractures (no hip
fractures) and 27 major revision surgeries. Among the 257
 patients who were treated with intramedullary nails without
femoral neck protection, 14 peri-implant hip fractures and 24
major revision surgeries were identified. Patients who received
nails with femoral neck protection had a lower hazard for any
peri-implant fracture (multivariable-adjusted cause-specific
hazard ratio, 0.19 [95% confidence interval, 0.07 to 0.5]) and major
revision surgery (multivariable-adjusted cause-specific hazard
ratio, 0.51 [95% confidence interval, 0.28 to 0.92]). Level of
evidence: III.
20. Blair JA, Kusnezov N, Fisher T, Prabhakar G, Bader JO, Belmont
PJ: Early stabilization of femur fractures in the se ing of
polytrauma is associated with decreased risk of pulmonary
complications and mortality. J Surg Orthop Adv 2019;28(2):137-143.
The 2009 to 2012 National Sample Program of the National
Trauma Data Bank was queried for all patients 18 to 65 years with
Injury Severity Scores >15 who underwent definitive fixation of
femoral shaft fractures. Mortality, perioperative complications,
and length of intensive care unit and hospital stay were the
primary outcome measures of interest. Following multivariate
analyses, increased time to surgery was found to portend a
statistically significant increased risk of acute respiratory distress
syndrome, mean ventilator time, length of intensive care unit and
hospital stay, and mortality. Earlier definitive fixation of femoral
shaft fractures in the se ing of polytrauma is associated with
significantly decreased risk of acute respiratory distress
syndrome, mean ventilator time, length of intensive care unit and
hospital stay, and mortality. Level of evidence: III.
21. Fontenot PB, Diaz M, Stoops K, Barrick B, Santoni B, Mir H:
Supplementation of lateral locked plating for distal femur
fractures: A biomechanical study. J Orthop Trauma
2019;33(12):642-648. Intra-articular distal femoral fractures with
metaphyseal comminution (OTA/AO 33-C) were simulated with a
standardized model in 28 synthetic femora and divided into four
groups. Group I was instrumented with a 4.5-mm lateral locked
distal femoral plate alone, group II with a lateral locked plate
 plus a low-profile precontoured 3.5-mm medial distal tibial plate,
group III with a lateral locked plate plus a medial 3.5-mm
reconstruction plate, and group IV with a lateral locked plate
plus a retrograde intramedullary nailing. Specimens were then
axially loaded and cycled to failure or runout. Outcomes of
interest were baseline stiffness, survivability, and cycles to
failure. Groups III and IV have a significantly higher baseline
stiffness (P < 0.001) when compared with groups I and II.
Furthermore, groups III and IV had a higher maximum load to
failure (P < 0.01) when compared with groups I and II. The
survivability in groups III and IV was 71% and 100%, respectively,
whereas no specimens in group I or II survived maximum
loading. There was no significant difference between group III
and IV regarding stiffness, survivability, and cycles to failure.
Level of evidence: IV.
22. Shah JK, Szukics P, Gianakos AL, Liporace FA, Yoon RS:
Equivalent union rates between intramedullary nail and locked
plate fixation for distal femur periprosthetic fractures – A
systematic review. Injury 2020;51(4):1062-1068. One prospective
comparative study, 9 retrospective comparative studies, and 28
retrospective case series with 1,188 patients were included in this
review. No statistically significant differences were found
between intramedullary nailing (IMN) and locking compression
plate when analyzing union rate or time to union. Plating
demonstrated a statistically significant decrease in the overall
complication rate and revision surgery rate when compared with
IMN (P < 0.003). IMN demonstrated a slightly higher percentage
of patients reaching full weight-bearing status and a quicker time
to full weight bearing (100% and 7.6 weeks) when compared with
plating (94% and 15.8 weeks). A higher percentage of patients
treated with IMN returned to preinjury activity when compared
with those treated with plating (70.8% versus 61.6%). Both IMN
and locking compression plate offer unique benefits in terms of
clinical and radiographic outcomes for treatment of
 periprosthetic distal femoral fractures after total knee
arthroplasty. Level of evidence: II.
23. Wadhwa H, Salazar BP, Goodnough LH, et al: Distal femur
replacement versus open reduction and internal fixation for
treatment of periprosthetic distal femur fractures: Systematic
review and meta-analysis. J Orthop Trauma 2022;36(1):1-6. Studies
that assessed complications of periprosthetic distal femoral
fractures with primary DFR or ORIF were included. Fifty-eight
studies with 1,484 patients were included in the meta-analysis.
Complications assessed (incidence rate ratio [95% confidence
interval]: 0.78 [0.59 to 1.03]) and reoperation or revision
(incidence rate ratio [95% confidence interval]: 0.71 [0.49 to 1.04])
were similar between the DFR and ORIF cohorts. Mean knee
range of motion was greater in the ORIF cohort (DFR: 90.47
versus ORIF: 100.36, P < 0.05). Mean Knee Society Score (DFR:
79.41 versus ORIF: 82.07, P = 0.35) and return to preoperative
ambulatory status were similar (incidence rate ratio [95%
confidence interval]: 0.82 [0.48 to 1.41]). Level of evidence: III.
24. Elkin DM, Galloway JD, Koury K, et al: Patella fracture fixation
with a non-locked anterior plating technique: A biomechanical
study. Injury 2021;52(4):686-691. Five matched pairs (10
specimens) of fresh-frozen cadavers were used in this study. A
transverse patellar fracture (OTA 34C1.1) was fixed using either
two 4.0-mm cannulated screw anterior tension band (CATB) or
two 2.0-mm stainless steel nonlocking plates along the anterior
cortex secured with 2.4-mm cortical screws traversing the fracture
site. During cyclic loading, there were no failures in the plate
fixation group, and two of five specimens catastrophically failed
in the CATB group (P = 0.22). Average fracture displacement at
the end of fatigue testing was 0.96 mm in the plate fixation group
and 2.72 mm in the CATB group (P = 0.18). The specimens that
withstood cyclic testing underwent a destructive load. Mean load-
to-failure for the plate fixation specimens was 1,286 N, which was
not significantly different from the CATB group mean of 1,175 N
(P = 0.48). Level of evidence: IV.
25. Kim KS, Suh DW, Park SE, Ji JH, Han YH, Kim JH: Suture
anchor fixation of comminuted inferior pole patella fracture-
novel technique: Suture bridge anchor fixation technique. Arch
Orthop Trauma Surg 2021;141(11):1889-1897. There were 21
patients of inferior pole comminuted fracture and 1 patient of
lower periosteal sleeve avulsion fracture. In all patients, bony
union was achieved at postoperative 4 months. At final follow-up,
mean short form 36 score was 72 ± 15 (30 to 91) points and Knee
injury and Osteoarthritis Outcome Score was 66.7 ± 16 (43 to 97).
The average range of motion was 134° ± 5° (125° to 140°). Level of
evidence: IV.
26. Xie X, Zhan Y, Wang Y, Lucas JF, Zhang Y, Luo C: Comparative
analysis of mechanism-associated 3-dimensional tibial plateau
fracture pa erns. J Bone Joint Surg Am 2020;102(5):410-418. Tibial
plateau fractures treated in a large trauma center were
retrospectively reviewed. The fracture lines and comminution
zones of each fracture were graphically superimposed onto a
three-dimensional template of the proximal part of the tibia.
Fracture characteristics were then summarized on the basis of
the fracture maps. In total, 353 tibial plateau fractures were
included. Level of evidence: III.
27. Hofmann A, Gorbulev S, Guehring T, et al: Autologous iliac
bone graft compared with biphasic hydroxyapatite and calcium
sulfate cement for the treatment of bone defects in tibial plateau
fractures: A prospective, randomized, open-label, multicenter
study. J Bone Joint Surg Am 2020;102(3):179-193. In this study, 135
patients with acute depression and split-depression fractures of
the proximal part of the tibia (OTA/AO types 41-B2 and 41-B3)
were enrolled in a prospective, controlled, randomized,
multicenter trial including 20 hospitals in Germany. Patients
were randomized to receive either autologous iliac bone graft or
Cerament bone void filler for reconstruction of the bone defect.
Age, sex, fixation methods, and fracture pa ern were comparable
in both groups. There were no significant differences (P > 0.05) in
the short form 12 physical component summary or visual analog
 scale scores at postoperative week 26. There was a significant
reduction of blood loss (P = 0.007) and pain levels (P = 0.008) at
postoperative day 1 in the Cerament bone void filler group. The
rates of fracture healing, defect remodeling, and articular
subsidence were not significantly different (P > 0.05) in both
groups. Level of evidence: I.
28. Elsoe R, Motahar I, Mahdi F, Larsen P: Presence of magnetic
resonance imaging verified soft tissue injuries did not
significantly affect the patient-reported outcome 12 months
following a lateral tibial plateau fracture: A 12-month prospective
cohort study of 56 patients. Knee 2020;27(2):420-427. This is a
prospective cohort study of patients treated surgically following a
lateral tibial plateau fracture (AO-41B). Soft-tissue injuries were
evaluated with preoperative MRI scans. The primary outcome
score was the 12-month Knee injury and Osteoarthritis Outcome
Score (KOOS5) divided into groups with and without soft-tissue
injuries. A total of 56 patients were included. Average patient age
was 56 years (range 22 to 86 years). Fifty percent of patients
presented with MRI-verified soft-tissue injuries. At 12 months
postoperatively, the mean KOOS5 score for patients with soft-
tissue injuries was 53.5 (95% confidence interval: 44.8 to 62.1) and
the KOOS5 score for patients without soft-tissue injuries was 59.6
(95% confidence interval: 50.7 to 68.6). No significant difference in
the KOOS5 score between patients with and without soft-tissue
injuries was observed (P = 0.31). Level of evidence: III.
29. Packer T, Naqvi A, Edwards T: Intramedullary tibial nailing
using infrapatellar and suprapatellar approaches: A systematic
review and meta-analysis. Injury 2021;52(3):307-315. One of the
largest and most recent studies included 16 total studies (5 RCTs
and 11 observational) with 1,750 patients, of which 810 patients
underwent suprapatellar nailing and 940 patients underwent
infrapatellar nailing. Although there was no difference in
complication rate between the groups, the suprapatellar nailing
group had be er Lysholm scores, decreased fluoroscopy times,
and improved entry point accuracy. Level of evidence: II.
30. Isaac M, O’Toole R, Udogwu U, Connelly D: Incidence of knee
pain beyond 1 year: Suprapatellar versus infrapatellar approach
for intramedullary nailing of the tibia. J Orthop Trauma
2019;33(9):438-442. This study more specifically compared the
incidence of knee pain in patients with greater than 12-month
follow-up using a numeric rating scale. The median follow-up for
the 262-patient cohort was 3.8 years, and there was no statistical
or clinical difference in knee pain at rest, while walking or while
kneeling. Level of evidence: III.
31. Kulkarni M, Tummala M, Aroor M, Vijayan S, Rao S:
Suprapatellar nailing in proximal third tibial fractures –
Clinicoradiological outcome. Injury 2020;51(8):1879-1886. A study
of 43 consecutive proximal tibia fractures managed with
suprapatellar nail had an average follow-up of 20.4 months,
average Lower Extremity Functional Scale of 89.4%, and no
anterior knee pain. There were four malunions and one nonunion
requiring an additional surgery, but all fractures eventually
united. Level of evidence: IV.
32. Bleeker N, van de Wall B, Ijpma F, et al: Plate vs. nail for extra-
articular distal tibia fractures: How should we personalize
surgical treatment? A meta-analysis of 1332 patients. Injury
2021;52(3):345-357. For extra-articular distal tibial fractures, a
meta-analysis assessed the functional outcomes and
complications of 1,332 patients in 15 studies (including 10 RCTs)
treated with either an intramedullary nail or plate fixation. There
were no differences between the groups in functional outcomes,
union rate, or need for additional procedures. Patients treated
with an intramedullary nail had a higher risk of malunion, higher
rate of anterior knee pain, shorter time-to-union, shorter time-to-
full-weight-bearing, and lower risk of deep infection. Level of
evidence: II.
33. Lee C, Brodke D, Engel J, Schloss M, et al: Low-energy gunshot-
induced tibia fractures: What proportion develop complications?
Clin Orthop Relat Res 2021;479(8):1793-1801. A multicenter
retrospective study involving 121 patients who sustained a low-
 velocity ballistic tibial fracture demonstrated an overall
complication rate of 49%. There was a 14% infection rate, and 26%
of patients underwent an additional procedure. Level of evidence:
IV.
34. Pincus D, Byrne J, Nathens A, Miller A, et al: Delay in flap
coverage past 7 days increases complications for open tibia
fractures: A cohort study of 140 north American trauma centers. J
Orthop Trauma 2019;33(4):161-168. One multicenter study with
672 patients had a 10% increase in complication rate if there was
a delay in coverage more than 7 days. Level of evidence: II.
35. Kuripla C, Torne a P, Foote C, Koh J, et al: Timing of flap
coverage with respect to definitive fixation in open tibia fractures.
J Orthop Trauma 2021;35(8):430-436. A study including 296
patients had 32.4% deep infection rate, with the most predictive
factor in multivariate regression being the time from definitive
fixation to flap coverage. There was no association with increased
infection in patients treated with temporary internal fixation.
Level of evidence: III.
36. Hebert-Davies J, Kleweno C, Nork S: Contemporary strategies
in pilon fixation. J Orthop Trauma 2020;34:S14-S20. Although
implant design and technology have continued to advance,
particularly the use of fragment-specific or mini-fragment
fixation, the tenants of soft-tissue handling, targeted surgical
approaches to allow fracture reduction, and stable fixation still
are critical in the management of pilon fractures. Complication
rates continue to be high, particularly in patients with severe
soft-tissue injuries, and especially in open injuries. Level of
evidence: V.
37. Spitler C, Hulick R, Weldy J: What are the risk factors for deep
infection in OTA/AO 43C pilon fractures? J Orthop Trauma
2020;34(6):189-194. This single-center, retrospective study of 150
patients with pilon fractures demonstrated a 16.7% deep
infection rate. Although open fractures had a higher infection
rate, when analyzed based on the location of the traumatic
wound, there was a higher infection rate in patients with a medial
 or anterior wound. Other factors found to be associated included
segmental bone loss, need for soft-tissue coverage, and use of a
posterolateral approach. Level of evidence: III.
38. Dombrowsky A, Abyar E, McGwin G, Johnson M: Is definitive
fixation overlap with external fixator pin sites a risk factor for
infection in pilon fractures? J Orthop Trauma 2021;35(1):7-12. With
most of these injuries being managed in a staged manner, one
study tried to determine whether overlap of the definitive
construct with external fixator pin sites was an independent risk
factor for infection. One hundred forty-six patients were treated
in a staged manner over a 6-year period at a single center. They
had 58 patients (40%) with overlap between the definite plate and
external fixator pin site. A deep infection developed in 22 patients
in the cohort (15%), with no significant differences in either the
amount of overlap or the distance from plate to pin site. Level of
evidence: III.
39. Haller J, Githens M, Rothberg D, Higgins T, Norks S, Barei D:
Risk factors for tibial plafond nonunion: Medial column fixation
may reduce nonunion rates. J Orthop Trauma 2019;33(9):443-449.
This study tried to assess risk factors for the development of a
tibial plafond nonunion by retrospectively assessing 518 patients
at a single center. Their nonunion rate was 14% with risk factors
including bone loss, open fracture, lack of medical column
fixation, use of locking plates, and tobacco use. Level of evidence:
IV.
40. Olson J, Anand K, Esposito J, et al: Complications and soft-
tissue coverage after complete articular, open tibial plafond
fractures. J Orthop Trauma 2021;35(10):371-376. This is a
retrospective, multicenter study including 161 patients. The deep
infection rate was 27% and associated with male gender, tobacco
use, and type 3B fractures. There was a higher rate of infection in
patients treated with acute fixation and those who underwent
soft-tissue coverage >1 week after definitive fixation. There was a
22% nonunion rate and a 47% rate of secondary procedures for
 either revision, removal of deep implants and irrigation, or
débridement. Level of evidence: IV.
41. Torne a P, Yakavonis M, Veltre D, Shah A: Reducing the
syndesmosis under direct vision: Where should I look? J Orthop
Trauma 2020;34(2):51-55. A cadaver study found improved
translational reduction accuracy using the anterolateral articular
surface of the distal tibia as a visual landmark compared with the
incisura. Level of evidence: I.
42. Andersen M, Frihagen F, Hellund J, et al: Randomized trial
comparing suture bu on with single syndesmotic screw for
syndesmotic injury. J Bone Joint Surg Am 2018;100(1):2-12.
43. Sanders D, Schneider P, Taylor M: Improved reduction of the
tibiofibular syndesmosis with TightRope compared with screw
fixation: Results of a randomized controlled study. J Orthop
Trauma 2019;33(11):531-537. A multicenter RCT with 103 patients
with syndesmotic injuries treated using either suture bu on
fixation or two, tricortical syndesmotic screws showed similar
functional outcomes at 1 year and a higher rate of revision
surgery in the screw fixation group primarily because of implant
removal. CT scans obtained 3 months postoperatively
demonstrated a higher rate of syndesmotic malreduction with
screw fixation (39% versus 15%); however, patients treated with
suture bu on fixation still had greater syndesmotic diastasis
compared with the uninjured side and less fibular medialization
compared with the screw fixation group. Level of evidence: I.
44. Ræder B, Stake I, Madsen J, et al: Randomized trial comparing
suture bu on with single 3.5 mm syndesmotic screw for ankle
syndesmosis injury: Similar results at 2 years. Acta Orthop
2020;91(6):770-775. This RCT comparing patients treated with a
suture bu on or a single, tricortical syndesmotic screw showed
similar functional and radiographic outcomes at 2 years. Level of
evidence: I.
45. Ræder B, Figved W, Madsen J, et al: Be er outcome for suture
bu on compared with single syndesmotic screw for syndesmosis
 injury: Five-year results of a randomized controlled trial. Bone
Joint J 2020;102-B(2):212-219. At 5-year follow-up, there were
improved functional outcomes and a decreased incidence of
radiographic degenerative changes in patients treated with
suture bu on fixation. Level of evidence: I.
46. Park J, Kim B, Kim Y, et al: Early weightbearing versus
nonweightbearing after operative treatment of an ankle fracture:
A multicenter, noninferiority, randomized controlled trial. Am J
Sports Med 2021;49(10):2689-2696. An RCT comparing patients
with ankle fractures cleared to bear weight at 2 weeks versus 6
weeks demonstrated no increase in complication rate and similar
patient-reported outcomes (Olerud-Molander Ankle score)
between groups. Level of evidence: I.
47. Sernandez H, Riehl J, Fogel J: Do early weight-bearing and
range of motion affect outcomes in operative treated ankle
fractures: A systematic review and meta-analysis. J Orthop
Trauma 2021;35(8):408-413. A recent systematic review and meta-
analysis of 20 studies, including 1,130 cases, also showed similar
complication rates and patient-reported outcomes in early versus
delayed weight-bearing groups; however, there was an increase in
noninfectious complications with early range of motion before
wound healing. Level of evidence: I.
48. Seat A, Seat C: Lateral extensile approach versus minimal
incision approach for open reduction and internal fixation of
displaced intra-articular calcaneal fractures: A meta-analysis. J
Foot Ankle Surg 2020;59(2):356-366. A meta-analysis, with 2,179
patients from 17 RCTs and 10 retrospective studies, comparing
the clinical outcomes of displaced intra-articular calcaneal
fractures managed with ORIF using an extensile lateral or
minimal incision approach, found more favorable results using a
minimal incision approach. There were improved radiographic
parameters (calcaneal height and Böhler angle) and patient-
reported outcomes (visual analog scale and American
Orthopaedic Foot and Ankle Society scores), with decreased
 wound complications, superficial infections, and sural nerve
injuries. Level of evidence: I.
49. Busel G, Mir H, Merimee S, et al: Quality of reduction of
displaced intra-articular calcaneal fractures using a sinus tarsi
versus extensile lateral approach. J Orthop Trauma 2021;35(6):285-
288. A study was performed using postoperative CT scans and
radiographs to assess the reduction quality in displaced intra-
articular calcaneal fractures treated with ORIF using an extensile
lateral or sinus tarsi approach. Overall, the posterior facet
fracture gap and step-off as well as the residual varus angulation
of the tuberosity were improved in patients treated with an
extensile lateral approach. When separated based on the Sanders
classification, there was no statistically significant difference in
reduction quality based on the approach, but there was a trend in
be er reduction quality with an extensile lateral approach in
Sanders III calcaneus fractures. Level of evidence: III.
50. Schipper O, Cohen B, Davis W, et al: Open reduction and
primary subtalar arthrodesis for acute intra-articular displaced
calcaneal fractures. J Orthop Trauma 2021;35(6):296-299. Subtalar
arthrodesis can be performed in conjunction with ORIF in select
patients based on underlying patient factors and fracture
characteristics, including the degree of cartilage injury and
posterior facet comminution. A retrospective study
demonstrated a 94.3% fusion rate, defined as bridging bone >25%
of the posterior facet on postoperative CT scan, with this
technique. Level of evidence: IV.
51. Alcelik I, Fenton C, Hannant G, et al: A systematic review and
meta-analysis of the treatment of acute Lisfranc injuries: Open
reduction and internal fixation versus primary arthrodesis. Foot
Ankle Surg 2020;26(3):299-307. A meta-analysis, with 547 patients
from two RCTs and six retrospective studies, comparing these
two treatment options demonstrated similar outcomes and
similar rates of return to work/activity. Patients treated with ORIF
had a higher rate of additional procedures, including implant
 removal or secondary fusion, but the overall complication rate
was similar between the treatment groups. Level of evidence: III.
52. Stodle A, Hvaal K, Brogger H, et al: Temporary bridge plating vs
primary arthrodesis of the first tarsometatarsal joint in Lisfranc
injuries: Randomized controlled trial. Foot Ankle Int
2020;41(8):901-910. An RCT comparing first tarsometatarsal joint
ORIF using temporary bridge plating with primary arthrodesis in
48 patients showed similar patient-reported outcomes and visual
analog scale pain scores; however, patients treated with a
temporary bridge plate had a higher incidence of pos raumatic
arthritis despite be er radiographic alignment (Meary angle).
Level of evidence: I.
53. Barnds B, Tucker W, Morris B, et al: Cost comparison and
complication rate of Lisfranc injuries treated with open reduction
internal fixation versus primary arthrodesis. Injury
2018;49(12):2318-2321.
C H AP T E R 2 5

Pelvic Trauma
L. Henry Goodnough MD, PhD, Conor P. Kleweno MD,
FAAOS

Dr. Kleweno or an immediate family member has received royalties from Globus Medical; serves
as a paid consultant to or is an employee of Stryker; and serves as a board member, owner,
officer, or committee member of Orthopaedic Trauma Association. Neither Dr. Goodnough nor
any immediate family member has received anything of value from or has stock or stock options
held in a commercial company or institution related directly or indirectly to the subject of this
chapter.

ABSTRACT
Pelvic ring, acetabulum, and femoral head injuries are potentially
severe and complex to manage. Injuries to the pelvic ring are
associated with other severe blunt injuries and severe hemorrhage.
Classification systems have been established to characterize all of
these injuries and guide treatment, with injury pa erns often
dictating surgical approaches. Clinical outcomes are improving
with additional clinical experience and advancements in techniques,
yet these injuries can still result in persistent long-term
dysfunction.
Keywords: acetabulum; fracture; pelvic ring; trauma

Introduction
Similar to other anatomic areas, fractures of the pelvis and
acetabulum may present as high-energy injuries, yet increasingly
manifest as fragility fractures in the elderly. High-energy trauma to
the pelvis is not only associated with severe blunt injuries to other
organ systems but is also itself associated with potential life-
threatening hemorrhage requiring prompt diagnosis and
intervention. Classification of pelvic ring injuries focuses primarily
on the diagnosis of mechanically unstable pa erns that would
benefit from surgical intervention. Outcomes of pelvic injuries are
dependent on reestablishing stability, restoration of ring
morphology, and extent of soft-tissue injury. For acetabular
fractures, diagnosis continues to be based on the Letournel
classification. Surgical intervention is indicated for unstable and
displaced fractures to restore hip stability and to mitigate future
risk of pos raumatic arthritis. Long-term outcomes depend on
anatomic reduction, as well as fracture characteristics and patient
factors.
Femoral head fractures occur rarely but are usually associated
with posterior hip dislocations and occasionally clinically
meaningful posterior wall acetabulum fractures. Surgery is
indicated if the fracture fragments compromise the weight-bearing
articular surface or stability of the hip. Both the anterior surgical
approach and surgical hip dislocation are safe and effective
strategies for managing femoral head fractures.

Pelvic Ring Injuries

Pelvic ring disruptions are characterized by a bimodal distribution
of high-energy blunt trauma and geriatric fragility or insufficiency
fractures of the pelvis. Pelvic ring injuries are present in
approximately 9% of high-energy blunt trauma. 1 High-energy
pelvic ring injuries have a mortality rate of approximately 9% to
11%. 2 , 3
Pelvic ring injuries are classified according to either the
mechanism of injury or the implied stability of the injury. The Tile
classification is still used to describe injuries based on perceived
rotational and vertical stability after injury. 4 The Young-Burgess
classification is based on the vector of injury to the pelvic ring. 5 The
AO/Orthopaedic Trauma Association classification system uses
features of the Tile and the Young-Burgess classification systems. 6
Currently, each classification system remains limited in its ability to
predict mortality, associated injuries, 3 and treatment strategies. 7
The AO Spine Sacral Injury Classification is a newer and reliable
way to describe sacral and spinopelvic injuries. Type A lesions are
lower sacrococcygeal injuries. Type B injuries are complete sacral
fractures representing posterior pelvic ring injuries. Type C lesions
describe spinopelvic injuries including nondisplaced (C0), stable
(C1), and unstable, displaced (C3) injuries. 8

Evaluation and Initial Management

The initial evaluation of suspected pelvic ring injuries includes an
AP radiograph of the pelvis in the emergency department. The
presence of a pelvic ring injury often suggests a high-energy
mechanism and serves as a potential predictor of other blunt
injury. Pelvic ring injuries are also associated with hemorrhage
from the chest, abdomen, or long bones. 9 Open wounds to the
perineum, rectum, or vagina and soft-tissue degloving injuries
(Morel-Lavallee lesions) should be identified. A neurovascular
examination should be performed, and in sacral fractures, the
sacral nerve root distributions should be examined.
Patients with pelvic ring injuries can have life-threatening
hemorrhage into the retroperitoneal space. Therefore, in addition
to resuscitation, circumferential wrapping (using a sheet or a pelvic
binder) for volume-expanding injuries can close down the potential
space and allow for tamponade. 10 Circumferential sheets offer the
ability to cut holes for access for external fixation, percutaneous
fixation, or angiography, without having to be removed, which is a
potential advantage over a binder, 11 although both are effective. In
patients who have hypotension or hemodynamic instability with
pelvic ring injury, and without other sources of hemorrhage from
the chest or intraperitoneal space, angiography is an appropriate
next intervention (depending on institutional access). This is a safe
and efficacious technique to stem hemorrhage and should be
available in a timely manner according to the American College of
Surgery guidelines. 12 Retroperitoneal pelvic packing is also an
option to mitigate ongoing hemorrhage but should occur in
conjunction with relative stabilization of the pelvis, such as external
fixation and resuscitation screws. Clinically meaningful pelvic
packing can be technically challenging and is therefore potentially
less generalizable than angiography to control active bleeding.
There remains a lack of high-quality evidence comparing the two
interventions. Newer interventions such as resuscitative
endovascular balloon occlusion of the aorta offer additional
hemorrhage control. Skeletal traction may also be helpful in
selective injury pa erns (eg, vertically unstable pa erns with
complete sacral fractures). External fixation with or without
resuscitative posterior iliosacral screws may be used for damage
control orthopaedics as part of the acute management.
Advanced imaging should consist of a CT scan of the pelvis and
inlet and outlet views of the pelvic ring (obtained either through
plain radiographs or as reconstructions from the CT). 13 The AP
pelvic radiograph alone is inadequate to detect U-type sacral
fractures. 14 In instances of frank hematuria or with blood at the
urethral meatus, a CT cystogram is used to diagnose urethral or
bladder injuries.

Definitive Management
The most common pelvic ring injuries are lateral compression
fractures. Although often the most benign injury of the pelvic ring,
management of type I lateral compression (LC1) injuries remains
controversial. There is evidence that minimally displaced (<10 mm)
LC1 injuries may be managed nonsurgically with unrestricted
weight bearing and early mobilization. 15 Surgical treatment of
patients with minimally displaced LC1 injuries may offer
statistically significant early pain relief, but the clinical significance
is uncertain. 16 A subset of LC1 injuries, including complete zone 2
sacral fractures, and bilateral obturator ring disruptions injuries
may demonstrate further radiographic displacement, 17 and tend to
undergo surgical fixation more often than isolated zone 1 fractures.
18
However, compelling evidence is lacking that subsequent minor
displacement with eventual healing is of clinical consequence
(Figure 1, A through D). Nonetheless, identifying harbingers of
substantial further displacement leading to an unacceptable
malunion, including complete sacral fractures and bilateral
superior and inferior rami fractures, is of interest. 17 Another
indication for surgical management in LC1 injuries is failed
nonsurgical management (Figure 1, E through G). Although
postmobilization radiographs can be used for serial imaging in
patients treated nonsurgically, evidence suggests this intervention
rarely changes management. 15 Whether to fix posterior, anterior, or
posterior with or without anterior aspects of the pelvic ring is also
controversial. 19 Posterior options include percutaneous iliosacral-
style or transsacral-style screws. Anterior treatment options include
percutaneous medullary screw placement, anterior external fixator,
or internal application of an external fixator (INFIX). As with other
types of trauma, a higher level of energy may predispose to more
relevant instability, and similar injuries are more likely to require
surgery, compared with fragility fractures.
 Figure 1 A, AP radiograph of the pelvis demonstrating a right side complete
sacral fracture with superior and inferior rami fractures. B and C, Dynamic AP
fluoroscopic images of the pelvis demonstrating >10 mm displacement with
internal rotation. D, AP radiograph of the pelvis at 6 weeks demonstrating healing
without further displacement. E, AP radiograph of the pelvis demonstrating right
complete sacral fracture with ipsilateral superior and inferior pubic rami fractures
at injury. F, AP radiograph 3 weeks after injury. G, After failure of nonsurgical
management, an AP radiograph of the pelvis obtained immediately after surgery
shows insertion of percutaneous transsacral screws.

Fractures of the posterior ilium with extension into the sacroiliac

joint are potentially unstable and represent a relative indication for
surgery. If displaced, the unstable ilium is manipulated through
closed/percutaneous means or through a lateral window approach
and reduced to the intact portion. Fixation can be achieved either
with screws in the supra-acetabular corridor from the anterior
inferior iliac spine toward the posterior superior iliac spine (Figure
2) or with a bu ress plate placed through a lateral window. If the
iliac fracture exits low and posteriorly, or if there is also a complete
sacroiliac joint injury, then additional fixation is achieved through
iliosacral screws inserted after manipulative reduction. Lateral
compression pelvic fractures are, in general, typically reduced
through indirect manipulation of the anterior ring (Figure 3).

Figure 2 A, AP radiograph of the pelvis demonstrating right fracture of the

posterior ilium through a blastic metastatic lesion with ipsilateral obturator ring
disruption. B, AP radiograph of the pelvis obtained immediately after surgery
demonstrating insertion of percutaneous screws.

Figure 3 A, AP radiograph of the pelvis demonstrating right side obturator ring

fractures, right sacroiliac joint injury, symphysis disruption, and left sacral
fracture. B, AP radiograph of the pelvis after placement of an anterior external
fixator, suprapubic catheter, bilateral iliosacral screws, and a transsacral screw.
 Historically, anterior-posterior compression I injuries with
diastasis less than 2.5 cm were thought to be stable; however, it is
critical to rule out occult instability, and many injuries within this
range are now recommended to be stabilized. The concavity of the
CT gantry can inadvertently reduce symphyseal diastasis and can
mask some occult injuries. 20 Additionally, dynamic instability can
be concealed on static imaging, and therefore dynamic radiographs
or fluoroscopy may be of use. 21 Single-leg stance radiographs
(flamingo views) or examination under anesthesia can be used to
diagnose occult instability. 5 , 21 , 22 For unstable symphysis
disruptions, reduction and fixation of the anterior ring via a
Pfannenstiel/midline rectus split approach can reduce the ring
provided the posterior tension band is intact. Fixation of the
anterior ring alone in these injuries does not always reduce motion
at the sacroiliac joints 23 and can result in fixation failure in the
event of an undetected/underdiagnosed posterior ligamentous
injury. If the sacroiliac joint is well aligned in AP and craniocaudal
planes after reduction of the anterior ring but remains wide, then a
screw-based reduction can be performed along the vector of
placement of a partially threaded lag screw. Otherwise, an open
reduction of an unstable sacroiliac joint can occur through a lateral
window approach (less commonly a prone paramedian approach).
The number and size of screws needed and whether transiliac
fixation is necessary to stabilize the sacroiliac joint remain topics of
ongoing debate.
INFIX is another option for stabilization of the anterior pelvic
ring. 24 Open fractures or urologic injury where definitive anterior
internal fixation represents a risk of infection 25 are instances in
which temporary placement of an anterior internal fixator can be
considered. INFIX application can be more challenging in patients
with very li le abdominal subcutaneous adipose tissue. Lateral
femoral cutaneous nerve injury, heterotopic ossification, and
femoral nerve palsy are described complications after INFIX
application. 26
 Combined mechanism injuries and vertical shear pa erns are
typically considered rotationally and vertically unstable. Even in
displaced injuries, the pelvic ring can be reduced indirectly via
traction or reduction of the anterior pelvic ring, either with an
anterior external fixator or an open reduction with a clamp.
Alternatively, a sacral fracture can be reduced and clamped
through a posterior approach and prone positioning if the patient’s
physiology and soft-tissue envelope permit (Figure 4). (Anterior
access to the sacrum is limited, and thus is not practical for
reduction.) This is often easier to do with zone 1 fracture locations
as there tends to be less comminution. The posterior ring is
typically definitively stabilized with sacral screws. Lumbopelvic
fixation may augment posterior ring fixation if there is lumbopelvic
instability 27 or if patient anatomy precludes multiple points of
transsacral pelvic fixation (Figure 4).

Figure 4 A through C, AP radiograph, outlet ghost reconstruction, and

posterior three-dimensional reconstruction, respectively, of the pelvis
demonstrating left obturator ring disruption and complete left sacral fracture. D,
Inlet fluoroscopic radiograph demonstrating reduction of sacral fracture with a
clamp. E, AP ghost reconstruction of the pelvis demonstrating transsacral
screw, anterior external fixator, and unilateral lumbopelvic fixation.
 Sacral dysmorphism represents a spectrum of anatomic variation
which, when present, merits special technical consideration for safe
screw placement in contending with pelvic ring injuries. 28 The
technical implications of sacral dysmorphism in the injured pelvis
include that it may not be feasible to safely insert a transiliac
transsacral screw. In pelvic ring injuries with complete posterior
injuries in the presence of dysmorphism, percutaneous
lumbopelvic fixation may be a useful adjunct to ensure durable
fixation of the posterior ring.
Sacral U fractures can be subtle in presentation, 14 are associated
with high rates of neurologic injury, and may be indicative of the
need for dedicated lumbopelvic stabilization. U fractures are
composed of a transverse sacral fracture component, along with
bilateral vertical fracture lines. When bilateral sacral alar fractures
are present, a transverse fracture line is highly likely to be present,
29
particularly in the elderly. History of bowel and bladder
incontinence should be excluded. Even in very caudal transverse
fractures, canal compromise may be present, with sacral nerve root
compromise resulting in saddle anesthesia and bowel compromise
(Figure 5). If there is evidence of nerve root compression, sacral
decompression via laminectomies is warranted. Sacral U fractures
without significant kyphotic deformity can be fixed percutaneously
with transsacral screws. Lumbopelvic fixation can be adjunctive in
high-energy sacral U fractures or in dysmorphic sacral U fractures,
and percutaneous techniques are safe and effective.
 Figure 5 Sagittal CT scan (A) and sagittal T2-weighted magnetic resonance
image (B), respectively, of the pelvis demonstrating transverse sacral fracture at
S3 with canal stenosis and associated hematoma.

Geriatric Pelvic Ring Injuries

Geriatric pelvic ring injuries represent unique clinical entities
regarding injury mechanism, perioperative morbidity and
mortality, and approach to treatment. Compared with younger
individuals, geriatric pelvic ring injuries are more likely to be
lateral compression (LC1 or LC2) injuries resulting from a lower
injury mechanism. No high-level evidence has demonstrated
superior outcomes in surgically managed geriatric pelvic ring
injuries compared with those managed without surgery. However,
overall mortality is comparable with the geriatric hip fracture
population. 30 Surgical treatment may be considered in geriatric
patients with fragility fractures of the pelvic ring that are too
painful for early mobilization 31 (Figure 2).
Despite contemporary innovations, unstable pelvic ring injuries
can result in persistent pain and disability over the long term. 32 , 33
The extent of soft-tissue injury also drives outcomes, and persistent
sexual and genitourinary dysfunction are relatively common. 34

Acetabular Fractures
Acetabular fractures also occur in bimodal distribution, with the
incidence in the geriatric population increasing slightly in recent
years. 35 There are high-energy fractures in young individuals, as
well as low-energy falls and geriatric pa erns in patients with poor
bone quality. Associated injuries include blunt head, chest, and
abdominal injuries; 36 ipsilateral lower extremity fracture; and
closed superficial degloving injuries (Morel-Lavallee lesions). 37 An
approximately 30% incidence of concomitant femoral head
dislocation has been reported. 36 Combined acetabular and pelvic
ring injuries have an incidence of 5% to 16% 38 , 39 (Figure 6).

Figure 6 A, AP radiograph of the pelvis demonstrating left transverse-posterior

wall acetabular fracture, pubic symphysis disruption, and bilateral incomplete
sacroiliac joint injuries. Radiographs obtained immediately (B) and 3 months
after fixation (C), respectively.

The Letournel classification remains the most established

method for evaluating acetabular fractures. 40 , 41 Initial evaluation
follows the Advanced Trauma Life Support guidelines, including
identification and initial management of other injuries. Fracture-
dislocations should be reduced expeditiously to mitigate as much
as possible the risk of osteonecrosis and to alleviate pressure on the
peroneal branch of sciatic nerve, which is at risk after posterior
dislocations. Pos raumatic sciatic nerve injury has a documented
incidence of 12%. 40 Skeletal traction is warranted preoperatively in
unstable pa erns, displacement at the articular surface, or with
incarcerated fragments.
The mainstays of radiographic evaluation of acetabular fractures
are an AP radiograph with additional oblique (Judet) views and a
CT scan of the pelvis. The pelvic CT scan can also be used to
 p p
reproduce three-dimensional surface rendered imaging as well as
the Judet ghost reconstructions. 42 , 43 The CT scan is useful in
evaluating marginal impaction, in which articular fragments are
crushed into underlying cancellous bone, as well as incarcerated
intra-articular fragments.
Indications for surgical intervention center around restoring a
stable, concentric hip joint. Nonsurgical management is
appropriate for stable fractures without displacement at the weight-
bearing articular surface. Unstable fractures represent an indication
for intervention as in the absence of a stable hip joint, rapid
progression of arthrosis occurs 40 (Figure 7, A and B). Instability is
commonly associated with posterior wall fractures. The most
reliable way to determine hip stability is examination under
anesthesia, 44 with any subluxation of the femoral head indicating
the need for surgical stabilization. An articular step-off or gap of
greater than 2 mm represents relative surgical indications. 45
 Figure 7 AP radiographs of the pelvis at injury (A) and 10 weeks after injury (B)
in a patient with a small right posterior wall acetabular fracture managed
nonsurgically that went on to develop rapid radiographic arthrosis. Obturator
oblique radiographs of the pelvis demonstrating right transverse posterior wall
acetabulum at injury (C) and immediately after surgery (D).

Typically, fracture pa ern dictates surgical approach, and the

Kocher-Langenbeck and ilioinguinal approaches (and the
variations) are the mainstay posterior and anterior approaches,
respectively. Additional approaches have been described. 40 , 46 - 48
The Kocher-Langenbeck approach is indicated for posterior wall
fractures, posterior column, as well as many transverse (Figure 7, C
and D) and T-shaped fractures. The patient may be positioned
prone or lateral. Prone positioning mitigates the deforming force of
the femoral head displacing the columns. Lateral positioning may
require fewer assistants to retract the gluteal musculature and
allows for a digastric osteotomy of the greater trochanter and
possible surgical dislocation, allowing access to the cranial and
anterior aspects of the posterior wall as well as the femoral head. 46 ,

47

For anterior column family fractures (Figure 8) and associated

both-column fractures, either the ilioinguinal approach or its
modifications such as the modified Stoppa, in conjunction with the
lateral window of the ilioinguinal approach, 49 are commonly used.
The modified Stoppa approach and lateral window are becoming
increasingly common and may be related to surgeon inexperience
with division of the inguinal ligament and lateral repair,
mobilization of the femoral vessels, commercially available
anatomic precontoured plates, and potentially increased incidence
of quadrilateral surface involvement in geriatric individuals. 50

Figure 8 A, AP radiograph of the pelvis demonstrating right anterior column

posterior transverse acetabular fracture. B and C, Clinical photographs
demonstrating modified attachment for the limb positioner. D and E, AP
fluoroscopic images of the right hip demonstrating lateralization of the femoral
head with the limb positioner. F, AP radiograph of the pelvis immediately after
surgery.
 After reduction using manipulative aids 51 (Figure 8), flexible
reconstruction-style small fragment plates and small fragment
screws remain the mainstay of fixation. Posterior wall, column, and
transverse or T-shaped fractures are typically fixed with one or two
bu ress plates on the posterior column and/or wall with balanced
fixation (Figure 9). However, it is critical to include anterior column
screws because they cross and stabilize the primary transverse
fracture lines in transverse and T-shaped fractures (Figure 9). In
anterior column posterior hemi-transverse and associated both-
column fracture pa erns, bu ress plates for the anterior column
fracture along the pelvic brim and intrapelvic infrapectineal
bu ress plates for the posterior column and quadrilateral surface
(Figure 8) with long screws in the posterior column should be used.

Figure 9 AP (A and D), iliac oblique (B and E), and inlet radiographs (C and F)
of the pelvis at injury (A through C) and postoperatively (D through F)
demonstrating a right transverse acetabular fracture, right incomplete sacroiliac
joint injury, and left complete sacral fracture, which were managed
percutaneously.

With improved techniques and imaging, percutaneous reduction

and fixation of acetabular fractures has become more feasible 52 - 54
in certain patients with minimally displaced injury pa erns. The
goal of surgery remains a stable, congruent hip joint. Percutaneous
intervention may be considered in minimally displaced, yet
unstable fractures such as transverse pa erns (Figure 9), in patients
with minimal displacement and soft-tissue injury or with medical
comorbidities precluding open reduction, and in low-energy
pa erns in geriatric individuals who mobilize poorly. Although
long-term outcomes remain unknown, minimally displaced
geriatric fractures managed percutaneously have comparable
functional outcomes and conversion to arthroplasty with those
managed with an open reduction. 55
Certain geriatric acetabular injury pa erns may be appropriate
for acute total hip arthroplasty. Age is a risk factor for
pos raumatic arthritis after acetabular fractures, as are injury
features present in many low-energy fragility pa erns including
marginal impaction, comminuted posterior wall fragments, and
femoral head articular injuries. 56 In a 2020 study of patients older
than 60 years with an acetabular fracture, a nearly 25% conversion
rate to arthroplasty was noted 10 months after surgery. 57 Given the
risk of failure of hip survivorship in geriatric acetabular fractures,
combined approaches for arthroplasty and open reduction and
internal fixation (ORIF) have been described and have proven to be
safe and efficacious. 58 - 60 Drawbacks include the challenge of
achieving acetabular component stability and osseointegration in
comminuted, osteoporotic bone; no high-level evidence exists
favoring arthroplasty over ORIF in this se ing. Moreover,
contemporary outcomes are improving in pos raumatic conversion
arthroplasty after acetabular fracture. 61 Accordingly, ORIF can be
performed in geriatric patients with acetabular fracture, with the
goals of restoring hip offset by neutralizing the medialized
quadrilateral surface and achieving stable fixation of the columns if
the patient accepts the risk of conversion to an arthroplasty in the
future. Outcomes after ORIF of acetabular fractures are
reproducibly affected by several factors specific to patient, injury
type, and surgical technique; these include advanced age, fracture
comminution, marginal impaction, and femoral head damage, all of
which portend a poor prognosis. Anatomic reductions and early
intervention are favorable factors for outcome. 56 , 62 , 63
Complications after acetabular fracture include neurovascular
injury, deep vein thrombosis, and heterotopic ossification. Anterior
approaches can be associated with injury to the lateral femoral
cutaneous nerve (lateral window), obturator nerve (medial
window/Stoppa), or femoral nerve and vessels (middle ilioinguinal
window). Posterior approaches are associated with sciatic nerve
injury. Routine antithrombotic prophylaxis should be administered,
as deep vein thrombosis is common after acetabular fracture.
Heterotopic ossification is most common after extensile exposures
such as the extended iliofemoral approach. Radiation or
chemoprophylaxis for heterotopic ossification prevention is not
recommended given the lack of evidence and potential harm.

Summary
Pelvic ring, acetabular, and femoral head injuries can present either
as high-energy injuries or fragility pa erns in geriatric patients.
Classification systems are designed to identify unstable injuries
and guide treatment. Surgical approaches are predicated on injury
pa erns in pelvic ring injuries, acetabular fractures, and femoral
head fractures. In geriatric acetabular and femoral head fractures,
arthroplasty can be a safe and effective option. Clinical outcomes
continue to improve with further clinical experience and
advancements in techniques.

Key Study Points

Pelvic ring injuries can be associated with life-threatening hemorrhage and severe
blunt injuries. Evidence-based institutional guidelines should be followed.
Management of LC1 injuries remains controversial, but surgery may be beneficial,
particularly in geriatric patients with fragility fracture who are unable to mobilize
because of pain.
For unstable pelvic injury patterns, reduction and fixation of both anterior and
posterior injuries provide durable fixation; in severe injuries or sacral U fractures,
lumbopelvic fixation is indicated.
 Displaced or unstable acetabular fractures warrant anatomic reduction and stable
fixation, although in some geriatric injury patterns, arthroplasty may be an additional
consideration; injury pattern dictates an anterior versus posterior approach.
Femoral head fractures can be safely and effectively managed via either the anterior
approach or by a posterior approach with surgical hip dislocation.

Annotated References
1. Demetriades D, Karaiskakis M, Toutouzas K, Alo K, Velmahos
G, Chan L: Pelvic fractures: Epidemiology and predictors of
associated abdominal injuries and outcomes. J Am Coll Surg
2002;195(1):10.
2. Starr AJ, Griffin DR, Reinert CM, et al: Pelvic ring disruptions:
Prediction of associated injuries, transfusion requirement, pelvic
arteriography, complications, and mortality. J Orthop Trauma
2002;16(8):553-561.
3. Manson T, O’Toole RV, Whitney A, Duggan B, Sciadini M,
Nascone J: Young-Burgess classification of pelvic ring fractures:
Does it predict mortality, transfusion requirements, and non-
orthopaedic injuries? J Orthop Trauma 2010;24(10):603-609.
4. Tile M: Pelvic ring fractures: Should they be fixed? J Bone Joint
Surg Br 1988;70(1):1-12.
5. Burgess AR, Eastridge BJ, Young JW, et al: Pelvic ring
disruptions: Effective classification system and treatment
protocols. J Trauma 1990;30(7):848-856.
6. Meinberg EG, Agel J, Roberts CS, Karam MD, Kellam JF:
Fracture and dislocation classification compendium-2018. J
Orthop Trauma 2018;32(suppl 1):S1-S170.
7. Furey AJ, O’Toole RV, Nascone JW, Copeland CE, Turen C,
Sciadini MF: Surgeon variability in the treatment of pelvic ring
injuries. Orthopedics 2010;33(10):714.
8. Schroeder GD, Karamian BA, Canseco JA, et al: Validation of the
AO Spine Sacral Classification System: Reliability among
surgeons worldwide. J Orthop Trauma 2021;35(12):e496-e501. This
 study demonstrated that the AO Spine Sacral Fracture
Classification System has high interobserver reliability in
classifying sacral fractures.
9. White CE, Hsu JR, Holcomb JB: Haemodynamically unstable
pelvic fractures. Injury 2009;40(10):1023-1030.
10. Rou MLC, Falicov A, Woodhouse E, Schildhauer TA:
Circumferential pelvic antishock sheeting: A temporary
resuscitation aid. J Orthop Trauma 2002;16(1):45-48.
11. Gardner MJ, Osgood G, Molnar R, Chip Rou ML: Percutaneous
pelvic fixation using working portals in a circumferential pelvic
antishock sheet. J Orthop Trauma 2009;23(9):668-674.
12. Velmahos GC, Toutouzas KG, Vassiliu P, et al: A prospective
study on the safety and efficacy of angiographic embolization for
pelvic and visceral injuries. J Trauma 2002;53(2):303-308.
13. Ricci WM, Mamczak C, Tynan M, Streubel P, Gardner M: Pelvic
inlet and outlet radiographs redefined. J Bone Joint Surg Am
2010;92(10):1947-1953.
14. Pa erson JT, Lack WD, Agel J, et al: AP pelvis radiograph is
insufficient for diagnosis of U-type sacral fractures. Emerg Radiol
2021;28(6):1119-1126. The AP pelvic radiograph in the emergency
room is incompletely sensitive for detection of sacral U fractures.
If the patient has persistent posterior pain and a history of blunt
trauma, a pelvic CT should be considered to rule out sacral
fracture. Level of evidence: III.
15. Sembler Soles GL, Lien J, Torne a P: Nonoperative immediate
weightbearing of minimally displaced lateral compression sacral
fractures does not result in displacement. J Orthop Trauma
2012;26(10):563-567.
16. Torne a P, Lowe JA, Agel J, et al: Does operative intervention
provide early pain relief for patients with unilateral sacral
fractures and minimal or no displacement? J Orthop Trauma
2019;33(12):614-618. A prospective multicenter observational
study of 194 unilateral sacral fractures demonstrated statistically
significant improvements in visual analog scale scores for pain
 for patients treated surgically compared with those treated
nonsurgically at 24 hours and 3 months; the clinical significance
of this improvement is uncertain. Level of evidence: II.
17. Bruce B, Reilly M, Sims S: OTA highlight paper: Predicting
future displacement of nonoperatively managed lateral
compression sacral fractures – Can it be done? J Orthop Trauma
2011;25(9):523-527.
18. Vallier HA, Lowe JA, Agel J, et al: Surgery for unilateral sacral
fractures: Are the indications clear? J Orthop Trauma
2019;33(12):619-625. This prospective multicenter observational
study showed that unilateral sacral fractures managed surgically
by multiple surgeons were more likely to be zone 2 sacral
fractures and/or feature posterior cortical displacement than
nonsurgically managed sacral fractures. Level of evidence: II.
19. Parry JA, Funk A, Heare A, et al: An international survey of
pelvic trauma surgeons on the management of pelvic ring
injuries. Injury 2021;52(10):2685-2692. This international survey
study of pelvic trauma surgeons assessed the clinical
management of pelvic ring injuries and found that there were no
areas of moderate to strong agreement in the management of LC-
1 injuries.
20. Gibson PD, Adams MR, Koury KL, Shaath MK, Sirkin MS, Reilly
MC: Inadvertent reduction of symphyseal diastasis during
computed tomography. J Orthop Trauma 2016;30(9):474-478.
21. Sagi HC, Coniglione FM, Stanford JH: Examination under
anesthetic for occult pelvic ring instability. J Orthop Trauma
2011;25(9):529-536.
22. Siegel J, Templeman DC, Torne a P: Single-leg-stance
radiographs in the diagnosis of pelvic instability. J Bone Joint Surg
Am 2008;90(10):2119-2125.
23. Dujardin FH, Roussignol X, Hossenbaccus M, Thomine JM:
Experimental study of the sacroiliac joint micromotion in pelvic
disruption. J Orthop Trauma 2002;16(2): 99-103.
24. Vaidya R, Colen R, Vigdorchik J, Tonnos F, Sethi A: Treatment of
unstable pelvic ring injuries with an internal anterior fixator and
posterior fixation: Initial clinical series. J Orthop Trauma
2012;26(1):1-8.
25. Vaidya R, Martin AJ, Roth M, Nasr K, Gheraibeh P, Tonnos F:
INFIX versus plating for pelvic fractures with disruption of the
symphysis pubis. Int Orthop 2017;41(8): 1671-1678.
26. Vaidya R, Woodbury D, Nasr K: Anterior subcutaneous internal
pelvic fixation/INFIX: A systemic review. J Orthop Trauma
2018;32(6):S24-S30.
27. Sagi HC: Technical aspects and recommended treatment
algorithms in triangular osteosynthesis and spinopelvic fixation
for vertical shear transforaminal sacral fractures. J Orthop Trauma
2009;23(5):354-360.
28. Miller AN, Rou MLC: Variations in sacral morphology and
implications for iliosacral screw fixation. J Am Acad Orthop Surg
2012;20(1):8-16.
29. Bishop JA, Dangelmajer S, Corcoran-Schwar I, Gardner MJ,
Rou MLC, Castillo TN: Bilateral sacral ala fractures are strongly
associated with lumbopelvic instability. J Orthop Trauma
2017;31(12):636-639.
30. Hill RM, Robinson CM, Keating JF: Fractures of the pubic rami.
Epidemiology and five-year survival. J Bone Joint Surg Br
2001;83(8):1141-1144.
31. Slobogean GP, Gaski G, Nascone J, et al: A prospective clinical
trial comparing surgical fixation versus nonoperative
management of minimally displaced complete lateral
compression pelvis fractures. J Orthop Trauma 2021;35(11):592-
598. This prospective clinical trial of <10 mm displaced lateral
compression pelvic ring injuries demonstrated a small
improvement in pain and function outcome for up to 12 months
after surgical compared with nonsurgical treatment, particularly
in patients with >5 mm of posterior pelvic ring displacement.
Level of evidence: II.
32. Hoffmann MF, Jones CB, Sietsema DL: Persistent impairment
after surgically treated lateral compression pelvic injury. Clin
Orthop Relat Res 2012;470(8):2161-2172.
33. Bo A, Odutola A, Halliday R, Acharya MR, Ward A, Chesser
TJS: Long-term patient-reported functional outcome of
polytraumatized patients with operatively treated pelvic
fractures. J Orthop Trauma 2019;33(2): 64-70. This long-term
observational study of patients with surgically treated pelvic ring
injuries demonstrated persistent differences in functional
outcome scores at 11 or 22 years postoperatively compared with
an uninjured population. Level of evidence: IV.
34. Odutola AA, Sabri O, Halliday R, Chesser TJS, Ward AJ: High
rates of sexual and urinary dysfunction after surgically treated
displaced pelvic ring injuries. Clin Orthop Relat Res
2012;470(8):2173-2184.
35. Rinne PP, Laitinen MK, Hu unen T, Kannus P, Ma ila VM: The
incidence and trauma mechanisms of acetabular fractures: A
nationwide study in Finland between 1997 and 2014. Injury
2017;48(10):2157-2161.
36. Ma a JM: Fractures of the acetabulum: Accuracy of reduction
and clinical results in patients managed operatively within three
weeks after the injury. J Bone Joint Surg Am 1996;78(11):1632-1645.
37. Tseng S, Torne a P: Percutaneous management of Morel-
Lavallee lesions. J Bone Joint Surg Am 2006;88(1):92-96.
38. Veerappa LA, Tippannavar A, Goyal T, Purudappa PP: A
systematic review of combined pelvic and acetabular injuries. J
Clin Orthop Trauma 2020;11(6):983-988. This systematic review
determined the incidence of combined pelvic ring and acetabular
injuries to be between 5% and 16%; transverse family and
associated both-column acetabulum fractures were most
commonly associated with pelvic ring injuries, and outcomes are
worse overall than isolated injuries. Level of evidence: V.
39. Halvorson JJ, LaMothe J, Martin CR, et al: Combined
acetabulum and pelvic ring injuries. J Am Acad Orthop Surg
 2014;22(5):304-314.
40. Letournel É, Judet R, Elson R: Fractures of the Acetabulum.
Springer-Verlag, 1993.
41. Beaulé PE, Dorey FJ, Ma a JM: Letournel classification for
acetabular fractures. Assessment of interobserver and
intraobserver reliability. J Bone Joint Surg Am 2003;85(9):1704-1709.
42. Borrelli J, Peelle M, McFarland E, Evanoff B, Ricci WM:
Computer-reconstructed radiographs are as good as plain
radiographs for assessment of acetabular fractures. Am J Orthop
(Belle Mead NJ) 2008;37(9):455-459.
43. Sullivan MP, Telgheder ZL, Kleweno CP: Three-dimensional
computed tomography posterior iliac oblique images enhance
preoperative planning for acetabular fracture surgery. J Surg
Orthop Adv 2021;30(1):50-54. This survey study of orthopaedic
trauma surgeons demonstrated that three-dimensional
reconstructions of computed tomography are useful in
preoperative planning, particularly in posterior acetabulum
fractures.
44. Moed BR, Ajibade DA, Israel H: Computed tomography as a
predictor of hip stability status in posterior wall fractures of the
acetabulum. J Orthop Trauma 2009;23(1):7-15.
45. Torne a P: Displaced acetabular fractures: Indications for
operative and nonoperative management. J Am Acad Orthop Surg
2001;9(1):18-28.
46. Siebenrock K-A, Keel MJB, Tannast M, Bastian JD: Surgical hip
dislocation for exposure of the posterior column. JBJS Essent Surg
Tech 2019;9(1):e2. This study describes the surgical technique for
the surgical dislocation of the hip for exposure of the posterior
column.
47. Moed BR: The modified Gibson posterior surgical approach to
the acetabulum. J Orthop Trauma 2010;24(5):315-322.
48. Tannast M, Keel MJB, Siebenrock K-A, Bastian JD: Open
reduction and internal fixation of acetabular fractures using the
modified Stoppa approach. JBJS Essent Surg Tech 2019;9(1):e3. This
 study presents a description of the Stoppa approach for
acetabulum fractures. Level of evidence: VI.
49. Archdeacon MT, Kazemi N, Guy P, Sagi HC: The modified
Stoppa approach for acetabular fracture. J Am Acad Orthop Surg
2011;19(3):6.
50. Moed BR, Israel HA: Which anterior acetabular fracture surgical
approach is preferred? A survey of the orthopaedic trauma
association active membership. J Orthop Trauma 2020;34(4):216-
220. This survey study of orthopaedic trauma surgeons
demonstrated that the Stoppa approach is increasingly preferred
to the ilioinguinal for anterior acetabular exposure, particularly
among younger surgeons.
51. Goodnough LH, Olsen T, Hidden K, DeBaun MR, Kleweno CP:
Use of an intraoperative limb positioner for adjustable
distraction in acetabulum fractures with femoral head
protrusion: A case report. JBJS Case Connect 2021;11(3). This study
describes the use of a modified intraoperative limb positioner to
provide adjustable distraction of the femoral head in acetabular
surgery.
52. Bishop JA, Rou MLC: Osseous fixation pathways in pelvic and
acetabular fracture surgery: Osteology, radiology, and clinical
applications. J Trauma Acute Care Surg 2012;72(6):1502-1509.
53. Eastman JG, Chip Rou ML: Intramedullary fixation techniques
for the anterior pelvic ring. J Orthop Trauma 2018;32(6):S4-S13.
54. Banaszek D, Starr AJ, Lefaivre KA: Technical considerations and
fluoroscopy in percutaneous fixation of the pelvis and
acetabulum. J Am Acad Orthop Surg 2019;27(24):899-908. This
study describes fluoroscopic views and insertion techniques for
percutaneous fixation of the pelvis and acetabulum.
55. Gary JL, VanHal M, Gibbons SD, Reinert CM, Starr AJ:
Functional outcomes in elderly patients with acetabular fractures
treated with minimally invasive reduction and percutaneous
fixation. J Orthop Trauma 2012;26(5):6.
56. Ferguson TA, Patel R, Bhandari M, Ma a JM: Fractures of the
acetabulum in patients aged 60 years and older: An
epidemiological and radiological study. J Bone Joint Surg Br
2010;92-B(2):250-257.
57. Navarre P, Gabbe BJ, Griffin XL, et al: Outcomes following
operatively managed acetabular fractures in patients aged 60
years and older. Bone Joint J 2020;102-B(12):1735-1742. This
retrospective registry study demonstrated an approximately 24%
conversion rate to total hip arthroplasty in patients older than 60
years with surgically managed acetabular fractures.
58. Chen MJ, Wadhwa H, Bellino MJ: Sequential ilioinguinal or
anterior intrapelvic approach with anterior approach to the hip
during combined internal fixation and total hip arthroplasty for
acetabular fractures. Eur J Orthop Surg Traumatol 2021;31(4):635-
641. This case series of geriatric patients with acetabulum
fracture treated with combined ORIF/total hip arthroplasty, via
an ilioinguinal or Stoppa approach and a separate anterior
approach to the hip, demonstrated good clinical outcomes.
59. Beaulé PE, Griffin DB, Ma a JM: The Levine anterior approach
for total hip replacement as the treatment for an acute acetabular
fracture. J Orthop Trauma 2004;18(9):623-629.
60. Manson T, Schmidt AH: Acetabular fractures in the elderly: A
critical analysis review. JBJS Rev 2016;4(10):e1.
61. Ranawat A, Zelken J, Helfet D, Buly R: Total hip arthroplasty for
pos raumatic arthritis after acetabular fracture. J Arthroplasty
2009;24(5):759-767.
62. Bhandari M, Ma a J, Ferguson T, Ma hys G: Predictors of
clinical and radiological outcome in patients with fractures of the
acetabulum and concomitant posterior dislocation of the hip. J
Bone Joint Surg Br 2006;88-B(12):1618-1624.
63. Tannast M, Najibi S, Ma a JM: Two to twenty-year survivorship
of the hip in 810 patients with operatively treated acetabular
fractures. J Bone Joint Surg Am 2012;94(17):1559-1567.
C H AP T E R 2 6

Spinal Trauma
Sreeharsha V. Nandyala MD, Nicholas T. Spina MD

Neither of the following authors nor any immediate family member has received anything of value
from or has stock or stock options held in a commercial company or institution related directly or
indirectly to the subject of this chapter: Dr. Nandyala and Dr. Spina.

ABSTRACT
Spinal trauma represents a complex set of injuries from the occiput
to the sacrum. These fracture pa erns largely result from high-
energy trauma, yet a growing number of injuries that have resulted
from low-energy mechanisms are being seen in the aging
population (older than 65 years). Initial management includes
physical examination, stabilization, and advanced imaging.
Treatment decisions remain complex and require an understanding
of the mechanism of injury, fracture morphology, and the integrity
of the secondary ligamentous stabilizers of the spine. Several
classification systems have been introduced to establish a common
language between providers and allow for high-quality research.
Injury severity scoring systems have been developed to guide
surgical versus nonsurgical treatment. It is important to provide a
framework for the evaluation and treatment of spine trauma.
Keywords: cervical; lumbar; spine; thoracoulumbar; trauma

Introduction
Spinal trauma creates significant burden to the general population
and healthcare system. Spinal injuries are typically the result of
high-energy blunt trauma or low-energy falls in the growing
population of patients older than 65 years. Treatment decisions are
complex and take into account many considerations including
location of injury, fracture stability, medical comorbidities, other
traumatic injuries, bone health, and the long-term implications of
spinal fusion. It is important for surgeons to be up to date on the
evaluation, diagnosis, and management of cervical and
thoracolumbar spinal trauma.

Evaluation
Any patient being evaluated for spinal trauma should first undergo
standard Advanced Trauma Life Support evaluation in the
emergency department. The force required to generate spinal
fractures is often large, and concomitant head, chest, intra-
abdominal, and other orthopaedic injuries are quite common. The
secondary trauma survey includes spinal assessment after
hemodynamic stability is ensured.
Patients should be examined for signs of blunt trauma, such as
the seat belt sign or abdominal bruising that are associated with
thoracolumbar injuries. The cervical and thoracolumbar spine
should be palpated for areas of tenderness, step-off, or bogginess
between spinous processes that may indicate injury to the posterior
ligamentous process. After inspection and direct palpation, a
proper neurologic examination can be performed with the aid of
the American Spinal Injury Association form to assess light touch,
pinprick sensation, motor strength, deep tendon reflexes,
bulbocavernosus reflex, and perianal sensation. Careful rectal
examination can provide a prognosis of a spinal cord injury (SCI). 1
For example, an intact S4-5 pinprick sensation at 72 hours indicates
favorable return of bladder function. 2 Spinal shock is characterized
by flaccid paralysis, which can be transient. The return of the
bulbocavernosus reflex indicates functional spinal arc reflex
transmission and an end to a spinal shock. 3
Imaging
Obvious spinal injuries may be identified on preliminary chest and
pelvis radiographs obtained in the trauma bay as part of a primary
trauma survey. Plain radiography largely has been supplanted by
CT of the spine. However, in low-energy trauma, initial radiographs
may be obtained. Plain radiographs of the cervical spine may only
be accepted as satisfactory examinations if the cervicothoracic
junction and C7-T1 disk space can be seen. Radiographs should be
obtained in a seated or upright position to avoid missing subtle
instability that may reduce when the patient is supine. Once a
fracture is identified, CT is recommended to be er see and
characterize the nature of the injury. Noncontiguous spinal injuries
occur in up to 20% of traumas, and, therefore, full spinal axis
imaging is required. 4 Providers should consider MRI for any
patient with a neurologic deficit to be er characterize ligamentous
injury in some fracture pa erns or in certain patients in whom a
neurologic examination is not possible.

Spinal Cord Injury

SCI is associated with a chronic loss of function, and treatment
incurs significant healthcare expenditures. The rate of SCI per one
million people has remained relatively consistent over the past 30
years, but the overall yearly cases have been growing in line with
the population. A study that used the US Nationwide Inpatient
Sample database identified an incidence of 54 cases per million
people and 3,363 total cases of SCI in 2012. 5 The most common
sources of injury were falls, motor vehicle collisions, and gunshot
wounds. During 1993 to 2021, a trend existed toward an increasing
number of SCIs associated with falls in patients older than 65 years.
5

SCI pathophysiology is a biphasic mechanism. The first phase

occurs from direct impact or trauma to the spinal cord. The second
phase occurs after the mechanical trauma and is secondary to
ischemia and presumed vascular disruption inciting an
inflammatory response. The trauma is not modifiable, and
therefore much of the ongoing SCI research is aimed at reducing
the inflammatory response in the 48 hours after injury. Two
mechanisms of treatment are being explored—neuroprotective and
neuroregenerative. Neuroprotective treatment reduces the
secondary inflammatory response and the neuroregenerative
enhances the spinal regeneration pathways. Several clinical trials
are currently underway, but significant advances in the standard of
care have not been achieved. 6 The mainstays of treatment consist
of surgical decompression, stabilization, and supportive care
consisting of blood pressure goals for 48 to 120 hours after injury.
The timing of surgical intervention for SCI remains controversial.
However, a growing body of literature supports earlier intervention
as the gold standard of treatment. A large, pooled 2021 analysis of
1,548 patients with SCI between 1997 and 2017 compared those who
had surgery within 24 hours of injury with individuals receiving
care after 24 hours. 7 Significantly greater improvements in motor
score, light touch, pin prick, and overall American Spinal Injury
Association grades were seen at 1 year in the early versus late
group. Using time to surgery as a continuous variable, a steep
decline in total motor score change was noted with increased time
to surgery between 24 and 36 hours with a plateau effect after 36
hours. This study strengthens the authors’ recommendation that
the earlier the time to intervention the greater the likelihood of
improvement.

Cervical Spine Trauma

Upper Cervical Spine Trauma

Upper cervical spine trauma encompasses injuries from the
occipital condyles to the C2-3 disk space. The space available for the
spinal cord is largest in this region and therefore associated SCI is
relatively rare. The upper cervical spine is supported by a complex
ligamentous structure including the tectorial membrane and apical,
alar, and transverse ligaments.
Fractures of the occipital condyle are the most cephalad injuries
treated. Stable injuries can be managed with a cervical collar. The
classification scheme is based on the fracture pa ern: type I
injuries are comminuted fractures; type II injuries are related to
shear stresses, with a fracture line extending to the skull base; type
III injuries are avulsion fractures at the alar ligament a achment
and, if bilateral, may be associated with atlanto-occipital
dissociation.
Atlanto-occipital dissociation is a rare but extremely unstable
injury that requires urgent intervention. Clinical suspicion should
be raised if extreme soft-tissue swelling is seen in the upper cervical
region on CT or plain radiography. The diagnosis is made on CT-
based incongruity of the occipital cervical joint. Multiple
measurements exist to identify this injury, including the Powers
ratio, but the Harris lines are most useful in evaluation. MRI is
useful to assess the ligamentous stabilizers including the alar
ligaments, facet joints, and most importantly the tectorial
membrane. If uncertainty exists based on radiographic evaluation, a
manual traction test may be performed. If more than 2 mm of
translation is seen during manual traction, the injury is deemed
unstable. Stable injuries may be managed with external orthoses,
whereas unstable injuries require occipital cervical stabilization.
Fusion is associated with significant morbidity and loss of motion.
C1 injuries most commonly occur secondary to an axial load,
which results in a burst fracture (Jefferson fracture). Typically, this
is a three-part or four-part fracture with injuries to the anterior and
posterior ring. Stability of C1 fractures is largely based on upright
radiograph or CT measurement of C1 on C2 lateral mass overhang,
the rule of Spence. A more unique and rare injury is seen in an
isolated C1 lateral mass fracture. If significant displacement is seen,
a cock-robin deformity of the neck may result as the occipital
condyle se les into the displaced and widened lateral mass
fracture. Some authors argue for C1 osteosynthesis surgery with C1
lateral mass screws and a cross connector, thereby reestablishing
the ring. 8 Most C1 fractures may be managed with an external
orthosis.
C2 is the most commonly fractured vertebra in patients older
than 70 years. Its odontoid process has a unique blood supply,
placing a fracture at an increased risk for nonunion. Odontoid
fractures have a high risk of mortality in the elderly population akin
to the risk of mortality in hip fractures. The Grauer modification of
the D’Alonso and Anderson classification is the most used
classification for these injuries. Type I fractures are stable and
involve an avulsion injury to the tip of the process. Type II fractures
traverse the base of the dens, which is a watershed blood supply
region between the vertebral and internal carotid systems. Type III
fractures propagate laterally into the bilateral C1-2 joint, creating a
greater surface area for healing, and are typically treated in external
orthosis.
Surgical versus nonsurgical management of type II odontoid
fractures remains controversial. The goal of management is to
prevent C1-2 instability, reduce neck pain, and allow for
mobilization. Some studies have indicated lower rates of mortality
with surgical treatment and higher rates of union. A 2021 long-term
study of 282 consecutively treated patients with an average follow-
up of 39 months showed higher rates of bony fusion in the
surgically treated group, but no difference was seen between
surgical and nonsurgical groups when fibrous and bony fusions
were combined. In addition, no difference in neck pain was seen at
long-term follow-up. 9
Hangman’s fractures are a unique fracture pa ern seen at the C2
vertebrae representing a fracture of the pars interarticularis of C2.
The stability of these fracture pa erns is driven largely by an
associated injury to the C2-3 disk and fracture displacement. If the
C2-3 disk is injured or an atypical pa ern is observed in which the
fracture extends into the posterior body of C2 with significant
angulation, surgical intervention is required. Both C2-3 anterior
fusion and C2-3 or C1-3 posterior fusions are accepted treatments
for this injury. 10

Subaxial Cervical Spinal Trauma

Subaxial cervical trauma represents injuries located between the
C2-3 and C7-T1 disk spaces. These injuries are best characterized
according to their mechanism of injury, fracture morphology, and
associated injury to the tension bands of the spine. The AO Spine
subaxial classification system was published in 2016 with the goal of
establishing a common language description of C-spine injuries
with high interobserver reliability. 11
The classification system is based on fracture morphology, injury
to the facet, neurologic status, and case-specific modifiers that
would affect injury treatment. Type A injuries reflect injuries to the
vertebral body without disruption of the tension bands of the
spine, type B injuries describe pa erns with disruption of either the
posterior tension band—classically flexion-distraction type injuries
—or anterior tension band—classically extension injuries, and type
C injuries represent translational injuries of the spine in any plane.
Facet injuries are unique and therefore required a separate
descriptor based on the severity of injury and extent of the facet
involved. A neurologic status modifier is included based on the
extent of neurocompromise.
The AO Spine classification system creates a common language
but does not have applicability in terms of management
recommendations. The Subaxial Cervical Spine Injury Classification
System was first published in 2007 and a empts to classify and
guide surgical versus nonsurgical treatment based on a novel
scoring system. The system takes into account injury morphology,
discoligamentous integrity, and neurologic status (Table 1).

Table 1
Subaxial Cervical Spine Injury Classification and Severity Score

Injury Morphology Points

Compression 1
Burst 2
Distraction 3
Rotation translation 4
Discoligamentous Complex
Intact 0
Indeterminate 1
Disruption 2
Neurologic Status
Intact 0
Nerve root injury 2
Complete spinal cord injury 2
Incomplete spinal cord injury 3
Continuous cord compression with neurodeficit +1

A summative score no higher than 3 denotes nonsurgical

management and higher than 5 infers surgical stabilization and
decompression if necessary. A score of 4 is indeterminant and left
to the discretion of the treating surgeon. Raters of the scoring
system agreed 93.3% of the time with the treatment algorithm.
Although the Subaxial Cervical Spine Injury Classification and
Severity Score is not always applicable, it provides a framework to
analyze and evaluate the stability of an injury. In general, surgical
treatment is favored if there is discoligamentous disruption and
neurologic compromise. 12
Treatment principles for subaxial trauma are based on the risk
for displacement, progressive kyphosis, neurologic involvement,
and degree of canal compromise. Surgical technique and
recommendations have not changed drastically in the past 5 years.
Nonsurgical treatment consists of brace immobilization (halo vest,
hard cervical collar, and soft collar) based on the severity of injury.
Surgical treatment aims to decompress the cervical spinal elements
and stabilize the spine with utilization of both anterior and
posterior approaches. A 2021 study comparing anterior with
posterior fixation of subaxial spine injuries did not show a
difference in health-related quality of life at 2-year follow-up, but
increased risk of infection with the posterior approach was noted. 13
This study largely parallels what has been wri en with regard to
degenerative cervical pathology.
Anterior-based surgical approaches allow for direct
decompression of the spinal canal when anterior pathology is
present. Diskectomy and fusion may be undertaken in facet injuries
such as unilateral or bilateral facet dislocations when intact
vertebral end plates are present and facet fractures are absent. One
study demonstrated a 13% failure rate of anterior fixation alone in
these injuries, with failure being associated with concomitant end
plate and facet fractures. 14 A recent scoring system, the Posterior
Ligament-Bone Injury Classification and Severity Score, was
published in 2021 in an a empt to be er guide treatment regarding
subaxial fracture-dislocations. It considers the severity of injury to
the posterior ligamentous complex (PLC), severity of the alignment
or displacement of facet joints, and fractures to the lateral mass.
Scores higher than 7 are associated with failure of anterior-only
fixation. 15
Anterior corpectomy and fusion are used when decompression of
the cervical canal is necessary. Recently, the development of
expandable cervical cages has made this procedure technically
easier secondary to obtaining proper tension and fit with
modifiable cage expansion in the space. Single-level corpectomies
often function as stand-alone fixation techniques while most
authors advocate for 360° stabilization in the se ing of multilevel
corpectomy. The posterior approach, which uses lateral mass and
pedicle screw fixation, allows for decompression of the spine over
multiple levels and in reduction of irreducible fracture pa erns via
facet resection (Figure 1).
 Figure 1 Radiograph shows a C7 burst fracture treated with corpectomy and
expandable cage fixation.

Thoracolumbar Trauma

Anatomy and Biomechanics

The thoracolumbar spine has distinct anatomic and biomechanical
zones. The upper thoracic spine (T1-T10) is a rigid segment that is
stabilized by the true ribs and the sternum. In contrast, the lower
lumbar spine (L3-L5) provides flexibility by virtue of the sagi ally
oriented facet joints and lack of extraspinal osseous articulations.
Between these two biomechanically distinct segments, the
thoracolumbar junction (T11-L2) serves as a transition zone and has
more motion when compared with the stiff upper thoracic spine
because the facet orientation becomes progressively more sagi al
and true rib articulations with the sternum are lacking. The risk for
injury is correlated with the spectrum of biomechanical motion
between the thoracolumbar zones. The thoracolumbar junction is
associated with the greatest incidence of fractures (52%) followed
by the lower lumbar spine (32%) and the upper thoracic spine
(16%). 16 In addition, the thoracolumbar zone is subject to a flexion
moment arm because the center of gravity is located anterior to this
region.
The thoracolumbar spine is stabilized by a tension band referred
to as the PLC. This includes the ligamentum flavum, interspinous
ligament, supraspinous ligament, and the facet joint capsules.
Integrity of the PLC confers stability and appropriate sagi al
alignment, which is why it is a major component of the
thoracolumbar fracture classification scoring system.

Classification Systems
The evolution of thoracolumbar trauma classification systems
depicts the progression of understanding, communication, and
management of thoracolumbar fractures. 17 Each proposed
classification identified a weakness and a empted to improve on
the prior systems. 8 A three-column classification system of
thoracolumbar trauma was proposed that improved on the two-
column system. 18 , 19 This new system proposed a commonly
agreed-on nomenclature of four types of injury pa erns with
increasing complexity: compression, burst, seat belt injuries
(flexion-distraction), and fracture-dislocations. This nomenclature
enabled surgeons to communicate the morphologic features of the
fracture and the extent of column involvement.
A more comprehensive thoracolumbar classification was
proposed as part of the AO system. This system proposed 27
unique fracture pa erns and followed the typical AO language with
type A indicating compression, type B indicating distraction, and
type C indicating torsional injuries. 20 , 21 This once again provided a
systematic and unified language with which surgeons could not
only communicate but also publish standardized methodology for
research. 22
In an effort to guide surgical decision-making and
prognostication, the Spine Study Trauma Group published the
Thoracolumbar Injury Classification System (TLICS) score. 23 This
provided a taxonomy based on three main axes: fracture
morphology, integrity of the PLC, and the patient’s neurologic
status. An algorithmic scoring system was created to guide decision
making with regard to nonsurgical and surgical treatment. 24
The scores from these three criteria are then compiled, and
patients who receive a score of 5 or higher should undergo surgical
intervention, whereas those who receive a score of 3 or less should
be treated nonsurgically. A score of 4 designates an indeterminant
cohort of patients for which surgical decision making rests on
patient and surgical factors (Table 2).

Table 2
Thoracolumbar Injury Classification and Severity Score

Injury Morphology Points

Compression 1
Burst 2
Translation/rotation 3
Distraction 4
Posterior Ligamentous Complex
Intact 0
Suspected disruption 2
Disruption 3
Neurologic Status
Intact 0
Nerve root injury 2
Complete spinal cord injury 2
Incomplete spinal cord injury 3
Cauda equina syndrome 3

The TLICS algorithm carries external validity and high

interobserver reliability (Figure 2). Despite this, some controversy
exists regarding the treatment of TLICS 4 cases. Therefore, a
simplified, treatment-oriented classification was proposed based on
the status of spinal stability. 25 , 26 However, this new classification
system is yet to be widely implemented.

Figure 2 Simplified Thoracolumbar Trauma Algorithm based on spinal

instability.(Adapted with permission from Joaquim AF, Patel AA, Schroeder GD,
Vaccaro AR: A simplified treatment algorithm for treating thoracic and lumbar
spine trauma. J Spinal Cord Med 2019;42[4]:416-422.)

Treatment Options
The decision to pursue surgical versus nonsurgical treatment
should be individualized for each patient and should be based on
spinal stability, neurologic function, and morphologic features 17
(Table 3). Nonsurgical treatment is used for neurologically intact
patients with stable fracture pa erns such as those with TLICS
score of 3 or below or type A pa erns in the AO system for a period
of 10 to 12 weeks. Nonsurgical therapy involves symptom
management with pain medications, activity modification, and
optional immobilization. Thoracolumbosacral orthoses are
commonly used to a empt external stabilization. However, their
efficacy is controversial and should be weighed against the cost of
production. 27 , 28 Patients who opt for nonsurgical treatment should
be followed closely with serial imaging and physical examination to
assess for pos raumatic deformity, neurologic function, and pain
improvement.

Table 3
Common Thoracolumbar Fracture Patterns Causing Immediate
or Potentially Delayed Instability

Immediate
Instability
Fracture-dislocation
Burst with complete disruption of posterior elements and kyphosis
Ligamentous Chance-type fracture with malalignment
Delayed instability
a

Compression fracture
Burst fracture with minimal or no posterior element disruption or
malalignment
Bony Chance-type fracture without malalignment
a
Delayed instability present in the form of prolonged pain, pseudarthrosis, or deformity
progression.
Adapted from Abbasi Fard S, Skoch J, Avila MJ, et al: Instability in Thoracolumbar Trauma: Is
a new definition warranted? Clin Spine Surg 2017;30(8):E1046-E1049.

Nonsurgical treatment has been associated with fewer

complications and reduced cost along with equivalent outcomes
when compared with surgical treatment for the management of
stable burst fractures in patients who are neurologically intact. In
addition, the use of a custom-molded thoracolumbosacral orthosis
has not been proven to improve outcomes among patients treated
nonsurgically. 29 - 31 A percentage of nonsurgically treated patients
will require surgery. Nonsurgical treatment failure can be
characterized by new or worsening neurologic findings, increasing
pain, or progressive deformity. In such cases, the decision to
pursue surgical intervention should follow a discussion with the
patient/family after weighing the risk/benefit profile. Clear risk
factors for nonsurgical treatment failure have not been identified in
the literature.
The goals of surgical intervention are to stabilize the spine and
decompress the neural elements. The decision to pursue a
posterior-only or anterior-only technique versus combined surgical
approach should follow the goals of surgery based on the patient’s
neurologic status and fracture morphology. A posterior approach
enables pedicle screw and rod placement for reduction of a sagi al
plane deformity and restoration of the posterior tension band in
patients with PLC disruption. Decompression is achieved
posteriorly either directly or indirectly through fracture fragment
reduction via ligamentotaxis through an intact posterior
longitudinal ligament. The number of segments included in the
construct should be individualized based on patient factors and
fracture morphology. Patients with poor bone quality will benefit
from a long-segment fusion with or without anterior column
support. Short-segment posterior-only constructs limit stiffness at
the expense of a potentially higher rate of instrumentation failure.
32
As such, the McCormack Load-Sharing Score was developed to
assess for vertebral comminution, displacement, and necessary
sagi al plane correction to determine the success of a potential
posterior-only short-segment fixation. Percutaneous posterior
fixation is gaining popularity secondary to the advances in
intraoperative imaging and guidance. However, patient selection is
key because percutaneous fixation has been associated with
increased risk for implantation failure, particularly among patients
with increased body habitus and poor bone density. 33 Kyphoplasty-
assisted fracture reduction with percutaneous fixation also has been
described recently in the literature 34 but has not been universally
accepted as a viable treatment option.
A ventral decompression of the thecal sac or spinal cord may be
required and can be achieved with a transpedicular,
costotransverse, lateral extracavitary approach, or a minimally
invasive retropleural or transpsoas/antepsoas approach, or through
anterior corpectomy with subsequent allograft or cage
reconstruction. Anterior decompression is particularly indicated at
cord-level lesions with neurologic compromise. Care must be taken
in patients with osteoporosis if an anterior-only reconstruction is
pursued because of the risk of subsidence and progressive
kyphosis. A combined anterior/posterior reconstruction is
recommended in such patients. Combined reconstruction also is
indicated for patients with a disrupted PLC and with neurologic
compromise from dorsally displaced fracture fragments requiring
direct decompression particularly at the cord level. 35
Injuries that result in thoracolumbar fracture-dislocation are
typically caused by translation-rotational forces and often are
associated with significant neurologic injury. A posterior approach
with fracture and facet reduction along with instrumented fusion is
likely necessary. Similarly, flexion-distraction injuries (Chance
fractures) also cause significant disruption of the PLC and continue
anteriorly to the disk and body. In contrast to burst fractures,
vertebral body collapse is not generally a sequela, so a
percutaneous short-segment fixation can be used with bony or soft-
tissue–based flexion-distraction injuries. 36

Spinopelvic Dissociation
Spinopelvic dissociation is a devastating injury that requires early
diagnosis and stabilization. There is variation in treatment and
limited evidence-based guidelines because of the variety, rarity, and
complexity of this injury. 37 The initial description of this injury was
included in the spectrum of sacral fractures in which a transverse
sacral fracture was described that created disassociation from the
spine. 38 This injury was thought to be sustained with extreme axial
load incurred after a fall or jump from a height or high-energy
polytrauma. Insufficiency transverse sacral fractures can also be
seen in patients with osteoporosis and can create spinopelvic
dissociation. 39
 Spinopelvic dissociation is associated with neurologic injury that
ranges from complete SCI with cauda equina syndrome to
individual nerve root injury. In addition, recovery of neurologic
function is less likely if the fracture pa ern is present below S4.
Furthermore, kyphosis of greater than 20° is associated with greater
risk for neurologic deficits. 36 In the se ing of spinopelvic
dissociation, CT should demonstrate bilateral vertical sacral
fractures in conjunction with a transverse component. This creates
some variation of a U-shaped fracture pa ern that can include H, T,
and Y type fractures depending on the location of the fracture lines.
Because of the high degree of instability, spinopelvic dissociation
often requires surgical fixation. However, in patients who cannot
tolerate surgery, nonsurgical treatment is recommended. This
carries suboptimal sequelae with skin ulcer formation, venous
thrombosis, and fracture malunion. Surgical treatment can involve
direct or indirect decompression, fracture reduction, and
instrumentation to restore stability and sagi al balance. Direct
decompression is considered in the se ing of cauda equina
syndrome with lumbosacral laminectomy and foraminotomy.
Recovery can be guarded especially if the sacral nerve roots are
injured. 40 A number of indirect reduction maneuvers have been
described to restore sagi al balance and allow for fracture
reduction. 41 , 42 However, these indirect reduction techniques with
skeletal traction and ligamentotaxis should be avoided if bony
fragments are present within the canal or neuroforamen. 40
Surgical stabilization involves a variation of lumbar and iliac
fixation to reestablish the bony connection. 43 , 44 The most
biomechanically stable is bilateral triangular osteosynthesis. 45
Sacral fixation can be compromised because of sacral dysmorphism
and fracture displacement. If direct decompression is not required,
percutaneous fixation techniques can be adopted. Following
fixation, early weight bearing is encouraged. 46

Summary
Spinal trauma requires expeditious diagnosis and management.
The evolution of classification systems demonstrates the
advancement of management and understanding of spinal
fractures. Despite practice variation in management of spinal
trauma, prompt immobilization, resuscitation, and stabilization are
paramount to mitigate complications. Additional high-grade
evidence is required to demonstrate superiority of management
pa erns for spinal trauma. Until this is established, clinical
judgment of the surgeon is essential for appropriate care of
patients with spinal trauma.

Key Study Points

Injury patterns resulting in unstable morphology should be recognized in both the
cervical and lumbar spine.
Common classification schemes used to describe cervical and thoracolumbar injury
patterns should be understood.
Classification schemes to determine surgical versus nonsurgical management in
thoracolumbar burst fractures should be used.

Annotated References
1. Roberts TT, Leonard GR, Cepela DJ: Classifications in brief:
American Spinal Injury Association (ASIA) Impairment Scale.
Clin Orthop Relat Res 2017;475(5):1499-1504.
2. Grauer JN: Orthopaedic Knowledge Update: OKU 12, ed 12.
American Academy of Orthopaedic Surgeons, 2017, xxii, 890 pp.
3. Harrop JS, Chi JH, Anderson PA, et al: Congress of neurological
surgeons systematic review and evidence-based guidelines on the
evaluation and treatment of patients with thoracolumbar spine
trauma: Neurological assessment. Neurosurgery 2019;84(1):E32-
E35. This is a methodologic review of current literature regarding
classification schemes of neurologic impairment following
trauma and assessment of clinical findings predictive of final
neurologic outcome. Level of evidence: V.
 4. Miller CP, Brubacher JW, Biswas D, Lawrence BD, Whang PG,
Grauer JN: The incidence of noncontiguous spinal fractures and
other traumatic injuries associated with cervical spinal fracture:
A 10-year experience at an academic medical center. Spine (Phila
Pa 1976) 2011;36(19): 1532-1540.
5. Jain NB, Ayers GD, Peterson EN, et al: Traumatic spinal cord
injury in the United States 1993-2012. J Am Med Assoc
2015;313(22):2236-2243.
6. Kim YH, Ha KY, Kim SI: Spinal cord injury and related clinical
trials. Clin Orthop Surg 2017;9(1):1-9.
7. Badhiwala JH, Wilson JR, Witiw CD, et al: The influence of
timing of surgical decompression for acute spinal cord injury: A
pooled analysis of individual patient data. Lancet Neurol
2021;20(2):117-126. This pooled meta-analysis of prospective
spinal cord studies assesses time to surgery and outcomes. Early
time to surgery is associated with be er neurologic outcomes.
Level of evidence: II.
8. Shatsky J, Bellabarba C, Nguyen Q, Bransford RJ: A
retrospective review of fixation of C1 ring fractures does the
Transverse Atlantal Ligament (TAL) really ma er? Spine J
2016;16(3):372-379.
9. Rizvi SAM, Helseth E, Harr ME, et al: Management and long-
term outcome of type II acute odontoid fractures: A population-
based consecutive series of 282 patients. Spine J 2021;21(4):627-
637. Long-term follow-up of consecutively treated patients with
type II odontoid fracture demonstrated no difference between
surgical and nonsurgical management with respect to
pseudarthrosis or neck pain at final follow-up. Nonsurgical
management is safe in elderly patients. Level of evidence: III.
10. Turtle J, Kantor A, Spina NT, France JC, Lawrence BD:
Hangman’s fracture. Clin Spine Surg 2020;33(9):345-354. This is a
narrative review of current diagnosis, evaluation, and
management of cervical hangman’s fractures. Level of evidence:
V.
11. Vaccaro AR, Koerner JD, Radcliff KE, et al: AOSpine subaxial
cervical spine injury classification system. Eur Spine J
2016;25(7):2173-2184.
12. Vaccaro AR, Hulbert RJ, Patel AA, et al: The subaxial cervical
spine injury classification system: A novel approach to recognize
the importance of morphology, neurology, and integrity of the
disco-ligamentous complex. Spine (Phila Pa 1976)
2007;32(21):2365-2374.
13. Fröjd Révész D, Norell A, Charalampidis A, Endler P, Gerdhem
P: Subaxial spine fractures: A comparison of patient-reported
outcomes and complications between anterior and posterior
surgery. Spine (Phila Pa 1976) 2021;46(17): E926-E931. This
observational study of prospectively collected data compared
anterior vs posterior treatment of single-segment subaxial injury.
Anterior surgery had higher patient satisfaction and lower
infection rates, yet no difference was shown in Neck Disability
Index score or quality of life compared with posterior surgery.
Level of evidence: III.
14. Johnson MG, Fisher CG, Boyd M, Pi en T, Oxland TR, Dvorak
MF: The radiographic failure of single segment anterior cervical
plate fixation in traumatic cervical flexion distraction injuries.
Spine (Phila Pa 1976) 2004;29(24):2815-2820.
15. Yang JS, Liu P, Liu TJ, et al: Posterior ligament-bone injury
classification and severity score: A novel approach to predict the
failure of anterior-only surgery for subaxial cervical facet
dislocations. Spine (Phila Pa 1976) 2021;46(4):209-215. In a clinical
case series of subaxial cervical fracture-dislocations, a new
classification system based on instability of the injury is
proposed. The proposed scoring system predicts failure of
anterior-alone instrumentation in extremely unstable lateral
mass fractures. Level of evidence: IV.
16. Harbrecht BG, Djurasovic M: Thoracolumbar spine trauma:
Diagnostic and therapeutic considerations for the general
surgeon. Am Surg 2009;75(3):191-196.
17. Dailey AT, Arnold PM, Anderson PA, et al: Congress of
neurological surgeons systematic review and evidence-based
guidelines on the evaluation and treatment of patients with
thoracolumbar spine trauma: Classification of injury.
Neurosurgery 2019;84(1):E24-E7. This methodologic review of the
current literature discusses classification schemes of
thoracolumbar trauma and their respective utility in guiding
surgical versus nonsurgical management. Level of evidence: V.
18. Holdsworth F: Fractures, dislocations, and fracture-dislocations
of the spine. J Bone Joint Surg Am 1970;52(8):1534-1551.
19. Denis F: The three column spine and its significance in the
classification of acute thoracolumbar spinal injuries. Spine (Phila
Pa 1976) 1983;8(8):817-831.
20. Magerl F, Aebi M, Ger bein SD, Harms J, Nazarian S: A
comprehensive classification of thoracic and lumbar injuries. Eur
Spine J 1994;3(4):184-201.
21. Reinhold M, Audige L, Schnake KJ, Bellabarba C, Dai LY, Oner
FC: AO spine injury classification system: A revision proposal for
the thoracic and lumbar spine. Eur Spine J 2013;22(10):2184-2201.
22. Vu C, Gendelberg D: Classifications in brief: AO
Thoracolumbar Classification System. Clin Orthop Relat Res
2020;478(2):434-440. This is a narrative review of the AO
Thoracolumbar Classification System. Level of evidence: V.
23. Vaccaro AR, Lehman RAJr, Hurlbert RJ, et al: A new
classification of thoracolumbar injuries: The importance of injury
morphology, the integrity of the posterior ligamentous complex,
and neurologic status. Spine (Phila Pa 1976) 2005;30(20):2325-2333.
24. Magnusson E, Spina N, Fernando ND: Classifications in brief:
The thoracolumbar injury classification. Clin Orthop Relat Res
2018;476(1):160-166.
25. Abbasi Fard S, Skoch J, Avila MJ, et al: Instability in
thoracolumbar trauma: Is a new definition warranted? Clin Spine
Surg 2017;30(8):E1046-E1049.
26. Joaquim AF, Patel AA, Schroeder GD, Vaccaro AR: A simplified
treatment algorithm for treating thoracic and lumbar spine
trauma. J Spinal Cord Med 2019;42(4):416-422. This narrative
review of the literature proposes a simplified treatment
algorithm to guide the management of thoracolumbar spine
trauma. Level of evidence: V.
27. Hoh DJ, Qureshi S, Anderson PA, et al: Congress of
neurological surgeons systematic review and evidence-based
guidelines on the evaluation and treatment of patients with
thoracolumbar spine trauma: Nonoperative care. Neurosurgery
2019;84(1):E46-E49. This methodologic review of the current
literature on nonsurgical treatment of thoracolumbar spine
trauma provides treatment recommendations and strength of
literature. Level of evidence: V.
28. Wallace N, McHugh M, Patel R, Aleem IS: Effects of bracing on
clinical and radiographic outcomes following thoracolumbar
burst fractures in neurologically intact patients: A meta-analysis
of randomized controlled trials. JBJS Rev 2019;7(9):e9. This meta-
analysis of three studies of patients treated with and without a
brace demonstrated no difference in patient-reported outcomes,
failure rates, or kyphosis angle with or without brace in short-
term and long-term follow-up. Level of evidence: I.
29. Mulcahy MJ, Dower A, Tait M: Orthosis versus no orthosis for
the treatment of thoracolumbar burst fractures: A systematic
review. J Clin Neurosci 2021;85:49-56. This systematic review of
orthosis versus no orthosis in treatment of thoracolumbar burst
fractures showed low to moderate evidence of no difference in
patient-reported outcomes, radiographic measures, and
complication or failure between groups. Level of evidence: II.
30. Linhares D, Sousa-Pinto B, Ribeiro da Silva M, Fonseca JA,
Neves N, Orthosis Study G: Use and cost of orthosis in
conservative treatment of acute thoracolumbar fractures: A
survey of European and North American Experts. Spine (Phila Pa
1976) 2021;46(9):E534-E541. This survey study examines the use
and cost of an orthosis in Europe and North America. More than
 90% of spine specialists still use an orthosis in acute
thoracolumbar fractures. Level of evidence: V.
31. Linhares D, Pinto BS, Ribeiro da Silva M, Neves N, Fonseca JA:
Orthosis in thoracolumbar fractures: A systematic review and
meta-analysis of randomized controlled trials. Spine (Phila Pa
1976) 2020;45(22):E1523-E1531. A review of five studies including
267 participants showed no difference in pain, kyphosis
progression, loss of anterior height, or long-term Oswestry
Disability Index between groups. No evidence was found to
support the benefit of orthosis use. Level of evidence: III.
32. Jindal R, Jasani V, Sandal D, Garg SK: Current status of short
segment fixation in thoracolumbar spine injuries. J Clin Orthop
Trauma 2020;11(5):770-777. This narrative review highlights the
current use of short-segment fixation in thoracolumbar spine
injuries. Level of evidence: V.
33. Pannu CD, Farooque K, Sharma V, Singal D: Minimally invasive
spine surgeries for treatment of thoracolumbar fractures of
spine: A systematic review. J Clin Orthop Trauma 2019;10(suppl
1):S147-S155. This review evaluates roles, indications, and
complications of minimally invasive treatment techniques in
thoracolumbar fractures. Level of evidence: III.
34. Caruso G, Gildone A, Lorusso V, et al: Percutaneous fixation and
balloon kyphoplasty for the treatment of A3 thoracolumbar
fractures. J Clin Orthop Trauma 2019;10(suppl 1);S163-S167. This
review evaluates roles, indications and complications of
minimally invasive treatment techniques in thoracolumbar
fractures. Level of evidence: III.
35. Tan T, Rutges J, Marion T, et al: Anterior versus posterior
approach in traumatic thoracolumbar burst fractures deemed for
surgical management: Systematic review and meta-analysis. J
Clin Neurosci 2019;70:189-197. A systematic review and meta-
analysis of six studies compared an anterior with posterior
approach. The anterior approach had longer surgical times and
higher estimated blood loss. No difference between approaches
 was seen regarding failure rate, revision rate, length of stay, and
hospital charges. Level of evidence: II.
36. Laghmouche N, Prost S, Farah K, Graillon T, Blondel B, Fuentes
S: Minimally invasive treatment of thoracolumbar flexion-
distraction fracture. Orthop Traumatol Surg Res 2019;105(2):347-
350. A single-center retrospective study of percutaneous fixation
for flexion-distraction fractures with possible supplemental
anterior fixation demonstrated bone healing in all patients and
decreased regional kyphosis. Level of evidence: IV.
37. Kaye ID, Yoon RS, Stickney W, Snavely J, Vaccaro AR, Liporace
FA: Treatment of spinopelvic dissociation: A critical analysis
review. JBJS Rev 2018;6(1):e7.
38. Roy-Camille R, Saillant G, Gagna G, Mazel C: Transverse
fracture of the upper sacrum. Suicidal jumper’s fracture. Spine
(Phila Pa 1976) 1985;10(9):838-845.
39. Quacinella MA, Morrissey PB, Parry JA, Mauffrey C: Spinopelvic
dissociation: Assessment, reduction strategies, and fixation
techniques. J Am Acad Orthop Surg 2020;28(24):e1086-e1096. This
narrative review describes current treatment strategies for
spinopelvic dissociation in the literature. Level of evidence: V.
40. Schildhauer TA, Bellabarba C, Nork SE, Barei DP, Rou MLJr,
Chapman JR: Decompression and lumbopelvic fixation for sacral
fracture-dislocations with spino-pelvic dissociation. J Orthop
Trauma 2006;20(7):447-457.
41. Rua i S, Kerschbaumer G, Gay E, Milaire M, Merloz P, Tone i J:
Technique for reduction and percutaneous fixation of U- and H-
shaped sacral fractures. Orthop Traumatol Surg Res 2013;99(5):625-
629.
42. Williams SK, Quinnan SM: Percutaneous lumbopelvic fixation
for reduction and stabilization of sacral fractures with
spinopelvic dissociation pa erns. J Orthop Trauma
2016;30(9):e318-e324.
43. El Dafrawy MH, Shafiq B, Vaswani R, Osgood GM, Hasenboehler
EA, Kebaish KM: Minimally invasive fixation for spinopelvic
 dissociation: Percutaneous triangular osteosynthesis with S2 alar-
iliac and iliosacral screws – A case report. JBJS Case Connect
2019;9(4):e0119. This is a case report of minimally invasive
fixation for spinopelvic dissociation. Level of evidence: IV.
44. Backer HC, Vosseller JT, Deml MC, Perka C, Pu ier M:
Spinopelvic dissociation: A systematic review and Meta-analysis.
J Am Acad Orthop Surg 2021;29(4):e198-e207. This meta-analysis of
379 patients with spinopelvic dissociation systematically
evaluated the incidence, demographics, treatment, clinical
outcome, and complication rates. Level of evidence: II.
45. Schildhauer TA, Ledoux WR, Chapman JR, Henley MB, Tencer
AF, Rou MLJr: Triangular osteosynthesis and iliosacral screw
fixation for unstable sacral fractures: A cadaveric and
biomechanical evaluation under cyclic loads. J Orthop Trauma
2003;17(1):22-31.
46. Mouhsine E, We stein M, Schizas C, et al: Modified triangular
posterior osteosynthesis of unstable sacrum fracture. Eur Spine J
2006;15(6):857-863.
S E CT I ON 4

Shoulder
SECTION EDITOR
Bradford O. Parsons, MD, FAAOS
C H AP T E R 2 7

Shoulder Anatomy,
Biomechanics, Clinical
Evaluation, and Imaging
Alicia K. Harrison MD, FAAOS, Michael L. Knudsen MD

Dr. Harrison or an immediate family member is a member of a speakers’ bureau or has made
paid presentations on behalf of Arthrex, Inc.; has received research or institutional support from
Biomet; and serves as a board member, owner, officer, or committee member of Minnesota
Orthopaedic Society. Neither Dr. Knudsen nor any immediate family member has received
anything of value from or has stock or stock options held in a commercial company or institution
related directly or indirectly to the subject of this chapter.

ABSTRACT
The shoulder is a phenomenal and unique joint. No other
articulation in the human body demonstrates the same degree of
motion, flexibility, and function. The shoulder is composed of four
joints: the glenohumeral joint, acromioclavicular joint,
sternoclavicular joint, and the scapulothoracic joint. Most of the
range of motion of the shoulder is generated by the glenohumeral
joint. The tremendous flexibility of the shoulder comes, however, at
the cost of stability. The complex interplay of the osseous anatomy,
ligaments, muscles, and tendons is critical for the shoulder to
position the arm or hand in space and remain stable. A firm grasp
of shoulder anatomy is critical for the clinician in performing and
interpreting the physical examination as well as the understanding
and application of shoulder imaging.
Keywords: physical examination; shoulder anatomy; shoulder
imaging

Introduction
The complex interplay of flexibility and stability creates motion in
the shoulder unlike that seen in any other joint but is also a
construct at risk for injury or instability. Ideal shoulder mechanics
allow maximum motion, whereas structures including articular
congruity, muscles, and ligaments stabilize the joint through a full
arc of motion. Diagnosing pathologic function requires a thorough
understanding of the anatomy and the ability to perform a
complete physical examination. The shoulder physical examination
is complex but vitally important, and when integrated with
shoulder imaging, creates a powerful diagnostic tool.

Osseous Anatomy

The Scapula
The concavity of the glenoid represents a functional center of the
scapula. The thin body of the scapula expands or broadens laterally
to form the glenoid, which comprises a surface area three to four
times smaller than the humeral head. The radius of curvature,
however, is larger than that of the humeral head. 1 It is this size
mismatch that generates the tremendous range of motion from the
glenohumeral joint. The glenoid surface is nearly perpendicular to
the plane of the scapula, with an average of 1.23° of retroversion. 2
Additionally, the glenoid is oriented 10° to 15° superior to the
medial border of the scapula with a mean inclination of 7°. Primary
features of the scapular anatomy adjacent to the glenoid are the
spinoglenoid notch medially, the scapular spine superiorly, and the
acromion expansion laterally. Medial to the glenoid vault, the
scapular body is remarkably thin and encased in rotator cuff
musculature.
The Humerus
The bony anatomy of the proximal humerus has four parts: the
humeral head, the greater tubercle, the lesser tubercle and the
shaft. The sphere of the articular surface of the humeral head is
directed posteriorly and superiorly. The superior inclination of the
humeral head relative to the humeral shaft ranges from 30° to 55°
and the retroversion relative to the transepicondylar axis of the
elbow ranges from 0° to 55° (mean, 30°). 3 This retrotorsion allows
the humeral head to remain oriented in the plane of the scapula.
The bony anatomy around the articular surface provides specific
a achment points for the ligamentous and tendinous structures
stabilizing the shoulder (Figure 1). The lesser tubercle is anterior to
the humeral head and the greater tubercle is lateral to the humeral
head, with these bony protuberances separated by the
intertubercular groove. This bicipital groove represents an
important surgical landmark for both arthroscopic and open
shoulder surgery.
Figure 1 Photograph of a humeral head cadaver specimen with the
attachments of the capsule, ligaments, and rotator cuff tendons at the
periphery.LHBT = long head of the biceps tendon, SGHL = superior
glenohumeral ligament
The Clavicle
The clavicle is the first bone to begin ossification in embryologic
development and serves as the connection for the shoulder to the
axial skeleton. The osseous anatomy of the clavicle is complex and
can vary substantially. 4 The clavicle is identifiable by its S-shaped
curvature and is cephalad to the caudad bow. Medially, the clavicle
articulates with the clavicular facet of the sternum, which together
create the sternoclavicular joint. Laterally, the clavicle articulates
with the acromion at the acromioclavicular joint.

The Glenohumeral Joint

There is a wealth of literature on the complex interplay of the
glenohumeral joint and the critical balance between mobility and
stability. When all parts of the joint work as intended, the balance
between the inherent instability of a shallow concavity and the
various stabilizing structures facilitates maximum function. The
static and dynamic stabilizers are critical components of the
glenohumeral joint. Static stabilizers consist of articular congruity
and bony version, the glenoid labrum, the glenohumeral ligaments,
and negative intra-articular pressure. Dynamic stabilizers consist of
the rotator cuff muscles, the rotator interval, and the periscapular
muscles.
It is vital to understand the normal osseous anatomy of the
proximal humerus and glenohumeral joint as it pertains to
reconstruction of this anatomy with anatomic shoulder
arthroplasty. The aim of anatomic shoulder arthroplasty is to
restore normal glenohumeral geometry; restoring the following
relationships is particularly important: humeral head to tubercle
height, acromiohumeral interval, and the anatomic center of
rotation (Figure 2). A best fit or perfect circle has been described to
illustrate variability between the anatomic and prosthetic centers of
rotation 5 (Figure 3). Multiple studies have demonstrated that a
change in the center of rotation of greater than 3 mm negatively
affects postoperative range of motion and shoulder biomechanics. 6

, 7

Figure 2 Radiograph shows the glenohumeral geometry important in the

reconstruction of normal anatomy.AHD = acromiohumeral distance, COR =
center of rotation, HTD = humeral head-tubercle distance
 Figure 3 Postoperative radiograph demonstrating perfect circle annotation to
determine center of rotation (COR).

The Acromioclavicular Joint

The acromioclavicular joint is a diarthrodial joint and represents
the primary articulation connecting the upper extremity to the axial
skeleton. The joint is therefore subjected to repetitive stress and
strain and ultimately is at risk of degenerative disease.
Scapulothoracic movement requires 40° to 50° of rotation from the
acromioclavicular and sternoclavicular joints, but only 5° to 8°
occurs at the acromioclavicular joint. 8 The acromioclavicular
ligaments and the coracoclavicular ligaments are the two primary
groups of stabilizing structures for the acromioclavicular joint. The
acromioclavicular ligaments primarily resist posterior translation
and posterior axial rotation. The coracoclavicular ligaments are
critical stabilizers that provide vertical stability and resist superior
and anterior translation as well as anterior axial rotation. 9

The Sternoclavicular Joint

The sternoclavicular joint is the articulation of the clavicle with the
manubrium of the sternum and the superior aspect of the first
costal cartilage. The posterior sternoclavicular ligament connects
the posterior aspect of the medial clavicle to the posterosuperior
manubrium and is the primary anterior-posterior stabilizer. The
anterior sternoclavicular ligament connects the medial clavicle to
the superior anterior edge of the manubrium and prevents superior
displacement. The costoclavicular ligament connects the inferior
aspect of the clavicle to the first rib and acts as the primary restraint
for the sternoclavicular joint. Multiple vital structures rest posterior
to the sternoclavicular joint and are at risk in traumatic injuries.
The vascular structures found posterior to the sternoclavicular joint
include the common carotid artery, internal jugular vein, and the
brachiocephalic trunk. Additionally, the phrenic nerve, vagus nerve,
trachea, and esophagus are found posterior to the medial clavicle
and sternoclavicular joint.

The Scapulothoracic Articulation

The scapular body articulates with the thorax where it rests over the
posterolateral aspect of ribs 2 through 7. 10 Over a large area of the
scapular body, the bony thickness is remarkably thin, measuring
between 10 and 26 mm. 11 Although no bony or ligamentous
structure connects the scapula and the thorax, there are many
muscular a achments to the scapula that serve to stabilize this
unique osseous anatomy. The muscles connecting the scapula to
the axial skeleton that serve as scapular stabilizers include the
trapezius, serratus anterior, rhomboid major, rhomboid minor,
levator scapulae, subclavius, and pectoralis minor muscles. The
muscles connecting the scapula to the remainder of the upper
extremity serve to position the arm in space and include the
supraspinatus, infraspinatus, teres minor, teres major, deltoid, long
and short heads of the biceps brachii, long head of the triceps
brachii, and coracobrachialis. 12

Muscles
The muscular anatomy of the shoulder is perhaps more critically
important than other functional human anatomy, given the
inherent instability of the glenohumeral joint. These muscles serve
to stabilize the shoulder and provide its motion to position the arm
in space.

Rotator Cuff
The rotator cuff complex comprises the muscles and tendons of the
supraspinatus, infraspinatus, subscapularis, and teres minor. When
the arm actively abducts, the rotator cuff must pull the humeral
head into the glenoid concavity to provide a stable fulcrum for the
deltoid to elevate the arm. This complex mechanism is referred to
as concavity compression. 13

Supraspinatus
The supraspinatus arises from the supraspinous fossa superior to
the scapular spine. The footprint or insertion of this muscle was
clarified in a study that identified the footprint as smaller than
previously believed. The triangular supraspinatus footprint was
found to occupy less of the greater tubercle, sharing this area with
the larger trapezoidal infraspinatus footprint. 14 Supraspinatus
activation provides glenohumeral joint abduction, particularly in
the first 10° to 15°. The supraspinatus also resists inferior
translation at the glenohumeral joint by using the weight of the
limb.
Infraspinatus
The infraspinatus originates from the infraspinatus fossa of the
scapula. The inferior aspect of the muscle rests close to the teres
minor but is separated from it by the infraspinatus fascia. The
tendon sweeps laterally over the posterior glenohumeral joint onto
its trapezoidal footprint on the greater tubercle. The infraspinatus
serves a critical function to extend and laterally rotate the humerus.
Together with the teres minor, the infraspinatus externally rotates
the shoulder, a function which is vital to positioning the arm or
hand in space.

Subscapularis
The subscapularis is the largest and strongest rotator cuff muscle
belly and originates from the anterior scapular body. The
subscapularis tendon inserts on the lesser tubercle with the
glenohumeral capsule. The capsule and the subscapularis tendon
are difficult to separate at the lesser tubercle, but the inferior
subscapularis insertion is muscular below the lesser tubercle and at
this site can be more easily separated from the capsule. The
subscapularis acts as an internal rotator of the humeral head and
prevents anterior displacement or translation of the humeral head
on the glenoid.

Teres Minor
The teres minor arises from the posterior aspect of the axillary
border on the scapula adjacent to the teres major and infraspinatus.
The teres minor inserts on the most inferior aspect of the posterior
greater tubercle. The teres minor functions together with the
infraspinatus and posterior deltoid to externally rotate the humeral
head.

Clinical Evaluation
Patient Demographics
Shoulder pain is a relatively common presenting concern in the
general population and therefore in a general medical practice. In a
2020 study, the prevalence of shoulder pain was found to be 42%,
similar to that of low back pain (44%) or knee pain (48%). 15 The
lifetime prevalence has been reported to be as high as 66%. 16
Shoulder disorders vary by age with certain conditions seen more
commonly in youth, middle age, or older age groups.

Patient History
Certain features of the patient history may clue the physician to a
specific diagnosis; therefore, obtaining a thorough patient history is
an integral aspect of the patient encounter. The patient’s report of
pain at the anatomic site may mislead the examiner. A generic
presentation of shoulder pain may in fact have an etiology from the
cervical spine, glenohumeral joint, or multiple periscapular soft
tissues. 17 Certain features of shoulder pain are common across
diagnoses; pain pa erns of common shoulder conditions are
described in a 2017 study. 18 It can be difficult to distinguish cervical
spine versus shoulder disorders based on history alone, although
pain with shoulder abduction is more common in true shoulder
pathology and arm abduction often improves symptoms in patients
with cervical radiculopathy. 19 Additionally, pain on palpation at the
acromioclavicular joint or directly over the bicipital groove with
radiation into the biceps muscle often suggests acromioclavicular
joint and biceps etiologies, respectively. Rotator cuff pathology
often localizes over the anterolateral part of the shoulder, may
radiate down the arm, is worse with overhead activities, and is often
worse at night and interrupts sleep. Radiating pain below the elbow
is much less often because of shoulder pathology, particularly
where sensation of the hand is altered.

Physical Examination
An informed and thoughtful physical examination is critical in the
evaluation of a patient with shoulder concerns. The importance of
the shoulder physical examination has been the focus of recent
work to improve shoulder physical examination skills across many
levels of medical education. 20 , 21 As with any other musculoskeletal
evaluation, key components of the examination include inspection,
palpation, range of motion, strength, and neurovascular
examination. Given the complex interplay of shoulder anatomy and
function, specifically named examination maneuvers are an
important component to aid the examiner in making a thoughtful
diagnosis. Whether the problem is one of rotator cuff pathology,
glenohumeral instability, arthritis, or other mechanical
dysfunction, clinical decision making and treatment options will be
guided by physical examination.

Inspection
Inspection may be one of the most commonly overlooked aspects of
the physical examination. The value of inspecting the surface
anatomy to be examined is essential. It is most helpful to have the
shoulder uncovered to expose the skin, and many clinic gowns can
be draped or tied such that the patient’s modesty is respected and
preserved. The examiner should inspect for symmetry, atrophy,
surgical or traumatic scars, swelling, or erythema. Atrophy of one
or more muscle groups is particularly important to note because
rotator cuff pathology (particularly large or chronic tears) may
present with atrophy of the supraspinatus or infraspinatus fossa
(Figure 4). Deltoid atrophy may be the first sign of axillary nerve
lesions.
 Figure 4 Photograph shows that the inspection of the exposed shoulder from
this angle allows the examiner to note any atrophy of the supraspinatus or
infraspinatus fossa.

Palpation
The acromioclavicular joint or distal clavicle is perhaps the most
accessible structure for palpation. Symptomatic acromioclavicular
arthrosis or a less severe acromioclavicular separation will exhibit
pain on palpation at this site. Another frequent high-yield structure
for palpation is the bicipital groove, which is readily palpated over
the anterior proximal shoulder. The examiner may ensure palpation
at the correct site via internal or external rotation of the site. Pain
on palpation at this site is not uncommon in patients with biceps
tendinopathy. The posterior aspect of the shoulder lends itself well
to palpation at the posterior glenohumeral joint line, which is often
painful in patients with symptomatic glenohumeral arthrosis or
inflammatory rheumatologic conditions. Palpation more medially
over the medial clavicle and the sternoclavicular joint may elicit
pain in patients with symptomatic inflammatory conditions. The
sternoclavicular joint is perhaps not a common feature of the
general shoulder examination, although it is helpful to understand
the localization of this joint when needed. The examiner need only
palpate the suprasternal notch and move slightly lateral to localize
this joint.

Range of Motion
Perhaps more than in most other musculoskeletal examinations,
the precise understanding of both passive and active motion in the
shoulder is critical. The examiner must understand the distinction
between loss of active motion and stiffness. Shoulder stiffness is a
decrease in both active and passive motion, whereas preserved
passive motion in the face of decreased active motion may be a
result of pain or weakness. True stiffness is often seen with
adhesive capsulitis or glenohumeral arthritis. Total active and
passive motion are both evaluated in the plane of the scapula
through forward elevation, abduction, internal rotation, and
external rotation. Extension is less frequently measured but should
be noted where abnormal. A thorough evaluation of motion should
always include a comparison with the patient’s unaffected or
contralateral shoulder because normal ranges vary from patient to
patient. As discussed in a 2020 study, 22 mean forward elevation is
between 157° and 161°, but may reach 180°. External rotation can be
measured with the arm at the side or in 90° of abduction, and elbow
flexed 90°. External rotation is more variable, with a mean of 55° to
61°, but may reach 90°. 22 Internal rotation is measured by the
spinal level reached with the arm internally rotated behind the back
or in 90° of abduction. Full abduction reaching up to 180° involves a
combination of glenohumeral motion (to 120°) and scapulothoracic
motion (60°).

Strength Testing
Manual muscle or strength testing plays a particular role in
evaluating the rotator cuff. The subscapularis is often tested with
the belly press or lift-off tests. 23 The external rotators (teres minor
and infraspinatus) are tested with the arm by the side and elbow
flexed to 90° with the examiner resisting patient shoulder external
rotation. Patients with sizeable rotator cuff tears involving the
external rotators will exhibit weakness in this test. 24 Supraspinatus
evaluation is typically performed using the Jobe test with the arm
abducted to 90° in the scapular plane and the arm internally
rotated. 25 A patient unable to hold the arm in this position or resist
further elevation is concerning for supraspinatus dysfunction.

Provocative Testing
Although there are many named shoulder provocative tests, there
are many more studies on the accuracy, validity, and other
statistical utility of these many tests. Most clinicians agree that any
single provocative test is insufficient to make a specific diagnosis. 26
Given the vast number of provocative tests described, the focus
here will be on those best described and studied for each
pathology.
Rotator cuff disease: A broad meta-analysis found the following
statistical summaries for provocative tests designed to diagnose
rotator cuff disease: Hawkins-Kennedy (sensitivity, 0.8; specificity,
0.56), Neer (sensitivity, 0.72; specificity, 0.60), and painful arc
(sensitivity, 0.53; specificity, 0.76). 26
Superior labrum anterior and posterior (SLAP) tear: Many tests
have been described to diagnose the presence of a SLAP lesion. The
following tests have been best studied: active compression or
O’Brien (sensitivity, 0.67; specificity, 0.37), Speed (sensitivity, 0.20;
specificity, 0.78), Yergason (sensitivity, 12.4; specificity, 95.3), and
crank (sensitivity, 0.34; specificity, 0.75). 26
Biceps pathology is often discussed, but testing and results
depend on the location of the lesion from origin to muscle
insertion. The active compression test is performed primarily for
SLAP or biceps origin lesions, the Speed test performed primarily
for proximal biceps tendon pathology, and the Yergason test is
performed for slightly more distal biceps pain.
Instability: Various tests have been described in the examination
of anterior instability, posterior instability, and multidirectional
instability. The apprehension test, the relocation test, and the load
and shift test are used to demonstrate anterior instability. In the
apprehension test, the patient rests supine and the affected arm is
abducted to 90°. The arm is passively brought into maximum
external rotation. The test is positive when the patient experiences
apprehension or a sense of instability. The relocation test follows,
with the examiner applying a posteriorly directed force at the
humeral head, relieving the patient’s apprehension. Posterior
instability may be demonstrated with the load and shift test, the
jerk test, and the Kim test. In the jerk test, the examiner brings the
patient’s arm into flexion and internal rotation, applying pressure
directing the arm posteriorly across the joint. The examiner’s other
hand applies anterior force through the scapula, and a jerk
indicating reduction of a subluxated humeral head is a positive test.
Likewise, the Kim test moves the patient’s arm to 90° of abduction
in the scapular plane. The examiner applies axial load on the
shoulder through the elbow, and a posterior-inferior–directed force
is applied as the arm is further elevated 45°. Sudden pain indicates
a positive test. In a meta-analysis of shoulder provocative tests the
following tests were well studied: the apprehension test (sensitivity,
65.6; specificity, 95.4), relocation test (sensitivity, 64.6; specificity,
90.2), and surprise tests (sensitivity, 81.8; specificity, 86.1). 26
Multidirectional instability is a challenging problem in which many
patients have a baseline degree of global ligamentous laxity. The
Beighton score is a screening tool for hypermobility, evaluating
apposition of the thumb to forearm, li le finger
metacarpophalangeal hyperextension, elbow and knee
hyperextension, and flexion of the spine to place palms on the floor
(Figure 5).
 Figure 5 Photographs show the examination components of the Beighton
score.A, Thumb-to-forearm apposition. B, Lumbar spine flexion to place palms
on the floor. C, Little finger metacarpophalangeal hyperextension. D, Knee
hyperextension. E, Elbow hyperextension.

Acromioclavicular joint testing most often includes the active

compression test and direct palpation.
Scapular winging tests: Medial winging can be seen when the
patient actively elevates the arm to 90° but can be best illustrated
by having the patient do a wall push-up (Figure 6). Additionally, the
scapular assistance test, during which the examiner pushes
superiorly and laterally on the inferomedial border of the scapula,
can assist with the diagnosis. 27 Lateral winging can be more subtle;
the affected shoulder droops with inferior translation of the scapula
and the inferior angle rotates laterally. Abducting the arm or
having the patient do a resisted shoulder shrug may be er
illustrate the dysfunction.
 Figure 6 Photograph shows medial winging, best illustrated when the patient
actively elevates the arm to 90°.

Imaging
The complex and intricate anatomy of the shoulder requires a
detailed understanding of the imaging techniques used to evaluate
it and the pathology associated with the various imaging findings.
Without the ability to appropriately order and obtain the correct
diagnostic images, interpretation of imaging is limited, which can
interfere with the ability of the physician to arrive at the correct
diagnosis or treatment plan.

Plain Radiographs
The initial recommended imaging evaluation of the shoulder
begins with a plain radiographic series to include the glenohumeral
joint, acromion, and acromioclavicular joint to evaluate for osseous
abnormalities such as fractures, dislocations, arthritis, osseous
lesions, soft-tissue calcifications, and osteophytes or enthesophytes.
These structures and their associated pathologies are best viewed
with a minimum of two orthogonal radiographic projections,
although at least three orthogonal projections are preferred
whenever possible. Typical plain radiographic views include the AP
view, the Grashey (true AP) view, the scapular Y or outlet view, and
the axillary lateral view (Figure 7).
 Figure 7 Radiographic views demonstrating examination of the shoulder.A,
Traditional AP view of a right shoulder. B, Grashey (true AP) view of the right
shoulder shown in A. C, Scapular Y (outlet) view of a right shoulder. D, Axillary
lateral view of a right shoulder.

There are also several specialized radiographic views that may be

used to obtain more specific diagnostic information about the
shoulder joint. Notable specialized views include variations of the
aforementioned standard views, such as the AP view in external
rotation and internal rotation, which can provide different
projections of the proximal humerus to allow for identification of
abnormalities of the proximal humerus, such as a Hill-Sachs
impaction fracture of the posterior humeral head, as is seen in
shoulder dislocation. The Velpeau view is a useful modification of
the axillary view if the patient is unable to tolerate arm abduction
or the positioning required to obtain an axillary image. The
Bernageau view and the West Point view are modified axial
projections that be er assess the anteroinferior glenoid rim in the
context of recurrent instability. The Stryker notch view is useful for
carefully evaluating the posterior aspect of the proximal humerus
and can be help detect a Hill-Sachs lesion. The Zanca view is used
to carefully scrutinize pathology of the acromioclavicular joint and
is typically obtained with a 10° to 15° cephalic tilt and by centering
the beam on the acromioclavicular joint.

Magnetic Resonance Imaging

MRI is useful for the detailed evaluation of the soft-tissue
structures of the shoulder, and to a lesser degree, the osseous
structures. MRI of the shoulder is appropriate whenever there are
findings in the history or physical examination that suggest rotator
cuff tendon abnormalities, injuries of the long head of the biceps
tendon, glenoid labrum tears, episodes of shoulder instability,
neoplasms or masses, glenohumeral cartilage or osteochondral
abnormalities, synovial disorders, occult fractures, infections of the
shoulder joint or bone, mechanical shoulder symptoms, or
prolonged and refractory shoulder pain. Although this list is not
comprehensive, this represents many of the more common
indications for obtaining an MRI.
Magnetic resonance arthrography (MRA) introduces gadolinium-
based contrast dye into the shoulder joint by means of a
fluoroscopically guided injection. The gadolinium dye diffuses
within the glenohumeral joint and provides contrast that increases
the accuracy of the evaluation of glenohumeral joint ligamentous,
cartilaginous, and labral structures. Although it is more invasive, it
is generally well tolerated and is used most commonly in patients
with a history of glenohumeral instability or other clinical suspicion
for a labral tear. A 2020 study suggests that saline MRA of the
shoulder is at least as accurate as gadolinium-based contrast MRA.
28
Of note, the use of arthrography is not required if MRI is being
performed within 3 weeks of a shoulder dislocation event, because
the intra-articular hemarthrosis from the dislocation event will
provide adequate contrast material to highlight a capsulolabral
injury in the acute se ing. In the investigation of surgically proven
labral tears, MRA may be less diagnostic for SLAP tears. A 2019
study found that T1-gadolinium or T2-fluid signal was absent or did
not indicate a SLAP tear in 33% of cases where the tear was seen at
arthroscopy. The fluid signal was absent on imaging in only 8% of
Bankart tears seen at arthroscopy. 29

Ultrasonography
Ultrasonography introduces the ability to dynamically evaluate the
shoulder joint and is an efficient and inexpensive modality in the
evaluation of the painful shoulder. Ultrasonography can be used to
aid in the diagnosis of rotator cuff tears, calcific tendinitis,
subacromial bursitis, acromioclavicular joint arthropathy, and
fractures. Furthermore, it has a role in the evaluation of the
postoperative shoulder, such as monitoring for rotator cuff tendon
repair healing, and a technical role in the use of ultrasound-guided
therapeutic and diagnostic injections. The main limitation of
ultrasonography is that it is highly dependent on user technique
and provides a limited evaluation of the intra-articular pathology
secondary to the depth of the structures. In particular, diagnostic
ultrasonography in experienced hands has good diagnostic
accuracy for rotator cuff disease. A 2021 systematic review
demonstrated ultrasonography had high diagnostic sensitivity and
specificity for supraspinatus tears with statistically equivalent
performance to MRI. 30

Computed Tomography
CT of the shoulder provides be er detail of the cortical and
trabecular bone structures in comparison with MRI. The downside
of CT is the higher radiation exposure to the patient. CT is most
useful when optimal visualization of bony defects is required to
make the diagnosis or to guide clinical decision making. Instances
where CT is most useful include evaluation of complex fractures,
fracture-dislocations, cases of shoulder instability to evaluate for
glenoid or humeral bone loss, evaluation of osseous healing in
fractures, and glenohumeral arthrosis for preoperative planning
purposes in the se ing of planned shoulder arthroplasty. CT can
also be used in the postoperative evaluation of patients to evaluate
for osseous healing in fractures; in bone transfer procedures such
as Latarjet, Bristow, or distal tibial allograft procedures; or to
evaluate for component loosening in shoulder arthroplasty. CT
arthrogram studies are useful to evaluate for rotator cuff tears or
other soft-tissue pathology when MRI is contraindicated, such as in
patients with an implanted defibrillator or pacemaker. 31
CT can also be processed with three-dimensional reconstruction
views to improve the three-dimensional interpretation of the data
and has been shown to improve the reliability and accuracy of
diagnosing degrees of glenoid bone loss in recurrent shoulder
instability. 32 CT has become a particularly important tool in the
evaluation of glenoid deformity and bone loss in arthrosis. CT–
based virtual planning software allows the surgeon to determine
the ideal arthroplasty implants and optimize the implant position.
Such virtual planning is powerful as it allows the surgeon to create
and implement a surgical plan designed to restore premorbid
anatomy and maximize patient outcome and complication-free
survival.

Summary
Bony and soft-tissue anatomy of the shoulder is interesting and
complex. Four primary articulations and their surrounding soft
tissues provide the extreme shoulder motion critical to the function
of the more distal anatomy. The physician must have a solid
understanding of the anatomy and described examination
maneuvers to diagnose pathologic function or investigate patient
symptoms. Diagnostic imaging can support but does not stand
alone in the evaluation of the shoulder. All imaging investigations
for shoulder pain should begin with plain radiographs because of
the broad range of pathologies easily seen on plain radiographs.
Pertinent positive and pertinent negative findings on plain
radiographs will lead the physician to use more advanced imaging
when necessary for further investigation.

Key Study Points

The complex anatomy of the shoulder allows for tremendous range of motion. An
understanding of this anatomy is critical for diagnosis and treatment of shoulder
dysfunction.
Examination of the shoulder requires an assessment of normal or pathologic motion,
strength, and the application of special tests. Any single provocative test is
insufficient to make a specific diagnosis.
Diagnostic imaging supports and greatly aids but does not stand alone in the
evaluation of shoulder dysfunction.

Annotated References
1. Ianno i JP, Gabriel JP, Schneck SL, et al: The normal
glenohumeral relationships: An anatomical study of one hundred
and forty shoulders. J Bone Joint Surg Am 1992;74(4):491-500.
2. Churchill RS, Brems JJ, Kotschi H: Glenoid size, inclination, and
version: An anatomic study. J Shoulder Elbow Surg 2001;10(4):327-
332.
3. Pearl ML: Proximal humeral anatomy in shoulder arthroplasty:
Implications for prosthetic design and surgical technique. J
Shoulder Elbow Surg 2005;14(1 suppl S):99S-104S.
4. Daruwalla ZJ, Courtis P, Fi patrick C, Fi patrick D, Mulle H:
Anatomic variation of the clavicle: A novel three-dimensional
study. Clin Anat 2010;23(2):199-209.
5. Youderian AR, Ricche i ET, Drews M, Ianno i JP:
Determination of humeral head size in anatomic shoulder
 replacement for glenohumeral osteoarthritis. J Shoulder Elbow
Surg 2014;23(7):955-963.
6. Terrier A, Ramonde i S, Merlini F, Piole i DD, Farron A:
Biomechanical consequences of humeral component
malpositioning after anatomical total shoulder arthroplasty. J
Shoulder Elbow Surg 2010;19(8):1184-1190.
7. Favre P, Moor B, Snedeker JG, Gerber C: Influence of component
positioning on impingement in conventional total shoulder
arthroplasty. Clin Biomech 2008;23(2): 175-183.
8. Rockwood CA: Rockwood and Green’s Fractures in Adults, ed 3.
Lippinco , 1991, pp 1181-1239.
9. Fukuda K, Craig EV, Kai-Nan AN, Cofield RH, Chao EYS:
Biomechanical study of the ligamentous system of the
acromioclavicular joint. J Bone Joint Surg 1986;68-A(3):434-439.
10. Lazar MA, Kwon YW, Rokito AS: Snapping scapula syndrome. J
Bone Joint Surg 2009;91(9):2251-2262.
11. Aggarwal A, Wahee P, Harjeet H, Aggarwal AK, Sahni D:
Variable osseous anatomy of costal surface of scapula and its
implications in relation to snapping scapula syndrome. Surg
Radiol Anat 2011;33(2):135-140.
12. Williams PL, Warwick R, eds: Gray’s Anatomy, ed 35. Longman,
1973.
13. Harryman DR II, Sidles JA, Clark JM, McQuade KJ, Gibb TD,
Matsen FA III: Translation of the humeral head on the glenoid
with passive glenohumeral motion. J Bone Joint Surg Am
1990;72(9):1334-1343.
14. Mochizuki T, Sugaya H, Uomizu M, et al: Humeral insertion of
the supraspinatus and infraspinatus: New anatomical findings
regarding the footprint of the rotator cuff. J Bone Joint Surg Am
2008;90(5):962-969.
15. Imagama S, Ando K, Kobayashi K, et al: Shoulder pain has most
impact on poor quality of life among various types of
musculoskeletal pain in middle-aged and elderly people: Yakumo
 study. Mod Rheumatol 2020;30(3):568-572. This prospective cohort
study of 384 patients investigated the severity and effect on
quality of life of various types of pain in healthy volunteers. The
prevalence of shoulder pain, low back pain, sciatica, and knee
pain was 42%, 44%, 16%, and 48%, respectively. Level of evidence:
II.
16. Luime JJ, Koes BW, Hendriksen IJ, et al: Prevalence and
incidence of shoulder pain in the general population; a
systematic review. Scand J Rheumatol 2004;33(2):73-81.
17. Sembrano JN, Yson SC, Kanu OC, et al: Neck-shoulder
crossover: How often do neck and shoulder pathology
masquerade as each other? Am J Orthop (Belle Mead NJ)
2013;42(9):E76-E80.
18. Bayam L, Arumilli R, Horsley I, Bayam F, Herrington L, Funk L:
Testing shoulder pain mapping. Pain Med 2017;18(7): 1382-1393.
19. Gerber C, Fuchs B, Hodler J: The results of repair of massive
tears of the rotator cuff. J Bone Joint Surg Am 2000;82:505-515.
20. Hose MK, Fontanesi J, Woytowi M, Jarrin D, Quan A:
Competency based clinical shoulder examination training
improves physical exam, confidence, and knowledge in common
shoulder conditions. J Gen Intern Med 2017;32(11):1261-1265.
21. McFarland EG, Kibler WB, Murrell GAC, Rojas J: Examination of
the shoulder for beginners and experts: An update. Instr Course
Lect 2020;69:255-272. This review chapter highlights the
complexities of the shoulder examination and diagnosis of
shoulder pathology. Level of evidence: V.
22. Gill TK, Shanahan EM, Tucker GR, Buchbinder R, Hill CL:
Shoulder range of movement in the general population: Age and
gender stratified normative data using a community-based
cohort. BMC Musculoskelet Disord 2020;21(1):676. This
longitudinal cohort study involving 2,024 participants measured
the average range of active shoulder flexion, abduction, and
external rotation. The study provides normative data for active
shoulder range of motion. Level of evidence: II.
23. Gerber C, Krushell RJ: Isolated rupture of the tendon of the
subscapularis muscle: Clinical features in 16 cases. J Bone Joint
Surg Br 1991;73-B:389-394.
24. Cordasco FA, Bigliani LU: Large and massive tears: Technique of
open repair. Orthop Clin North Am 1997;28(2):179-193.
25. Jobe CM: Superior glenoid impingement. Orthop Clin North Am
1997;28:137-143.
26. Hegedus EJ, Goode AP, Cook CE, et al: Which physical
examination tests provide clinicians with the most value when
examining the shoulder? Update of a systematic review with
meta-analysis of individual tests. Br J Sports Med 2012;46(14):964-
978.
27. Kibler WB: The role of the scapula in athletic shoulder function.
Am J Sports Med 1998;26:325-337.
28. Singer AD, Rosenthal J, Umpierrez M, Guo Y, Gonzalez F,
Wagner E: A comparison of saline and gadolinium shoulder MR
arthrography to arthroscopy. Skeletal Radiol 2020;49(4):625-633. A
retrospective cohort study found that saline MRA was accurate,
with no significant differences compared with gadolinium-based
arthrograms in the diagnosis of labral and rotator cuff pathology.
Level of evidence: III.
29. Nacey NC, Fox MG, Bertozzi CJ, Pierce JL, Said N, Diduch DR:
Incidence of gadolinium or fluid signal within surgically proven
glenoid labral tears at MR arthrography. Skeletal Radiol
2019;48(8):1185-1191. A retrospective study found the lack of
surfacing T1-gadolinium or T2-fluid labral signal is unusual in
Bankart tears but relatively common in SLAP tears. Level of
evidence: IV.
30. Farooqi AS, Lee A, Novikov D, et al: Diagnostic accuracy of
ultrasonography for rotator cuff tears: A systematic review and
meta-analysis. Orthop J Sports Med 2021;9(10):23259671211035106.
A systematic review found ultrasonography is a highly sensitive
and specific diagnostic modality for the diagnosis of
supraspinatus tears and demonstrates statistically equivalent
 capability to MRI in the diagnosis of both full-thickness and
partial-thickness rotator cuff tears. Level of evidence: III.
31. Omoumi P, Bafort A, Dubuc J, Malghem J, Vande Berg BC,
Lecouvet FE: Evaluation of rotator cuff tendon tears: Comparison
of multidetector CT arthrography and 1.5-T MR arthrography.
Radiology 2012;264(3):812-822.
32. Bishop JY, Jones GL, Rerko MA, Donaldson C, MOON Shoulder
Group: 3-D CT is the most reliable imaging modality when
quantifying glenoid bone loss. Clin Orthop Relat Res
2013;471(4):1251-1256.
C H AP T E R 2 8

Rotator Cuff Disease, Calcific

Tendinitis, Adhesive Capsulitis,
Throwing Shoulder, and
Instability
Kevin J. Cronin MD, MS, Surena Namdari MD, MSc, FAAOS

Dr. Namdari or an immediate family member has received royalties from Aevumed, DJ
Orthopaedics, Miami Device Solutions/Biederman Motech, and Tigon; is a member of a
speakers’ bureau or has made paid presentations on behalf of DJ Orthopaedics and Miami
Device Solutions; serves as a paid consultant to or is an employee of ACI Clinical, DJ
Orthopaedics, Miami Device Solutions, and Synthes; has stock or stock options held in
Actabond, Aevumed, Coracoid Solutions, Force Therapeutics, HealthExl, MD Valuate, Mediflix,
Orthophor, Parvizi Surgical Innovations, Rothman Institute, RubiconMD, and Tangen; has
received research or institutional support from Arthrex, Inc., DePuy, a Johnson & Johnson, DJ
Orthopaedics, Integra, Roche, Wright Medical Technology, Inc., and Zimmer; and serves as a
board member, owner, officer, or committee member of the Philadelphia Orthopaedic Society.
Neither Dr. Cronin nor any immediate family member has received anything of value from or has
stock or stock options held in a commercial company or institution related directly or indirectly to
the subject of this chapter.

ABSTRACT
Disorders of the shoulder carry a significant disease burden and
societal cost. Recent research continues to evolve current treatment
algorithms for these common conditions. The role of augmentation
and biologics in the management of rotator cuff disease has been
extensively explored. Advances in the management of massive,
irreparable rotator cuff tears such as superior capsular
reconstruction and lower trapezius transfer provide more options
for this difficult-to-treat population. The optimal treatment for a
first-time traumatic, anterior glenohumeral dislocation continues to
be defined, and recent research may favor surgical intervention in
the young, active male patient. The importance of both glenoid and
humeral-sided bone loss and their interplay in recurrent instability
has now been firmly established. These advances, and others, have
significantly shaped the approach to common shoulder disorders.
Keywords: adhesive capsulitis; calcific tendinitis; rotator cuff
disease; shoulder instability; throwing shoulder

Introduction
Chronic shoulder pain is a leading cause of musculoskeletal
disability in the United States and affects up to 8% of all adults. A
significant number of those affected are of working age, leading to
lost productivity and substantial direct and indirect costs to the
healthcare system. Disorders of the shoulder may include
tendinopathies, instability, arthritis, and pathologic adaptations of
the throwing shoulder. Treatment with both nonsurgical and
surgical interventions generally results in favorable outcomes.

Rotator Cuff Tears

In the United States alone, more than 4.5 million patient visits due
to shoulder pain occur each year. 1 Tears of the rotator cuff can
occur from traumatic injuries or chronic degeneration.
Degenerative tears are more common and increase with age. More
than 50% of asymptomatic patients older than 60 years have a full-
thickness or partial-thickness rotator cuff tear on MRI. 2
Additionally, the size of tears progresses over time although it is
difficult to predict which tears progress and how quickly. A 2021
systematic review showed that partial-thickness tears progress to
full-thickness tears at a rate of 3% per year with no difference in
symptomatic or asymptomatic tears. 3 Full-thickness tears progress
over time as well and possibly at an accelerated rate. A study of 34
patients with symptomatic full-thickness tears treated without
surgery showed progression in 82% of patients after a minimum
follow-up of 6 months 4 (Figure 1).

Figure 1 Coronal (A) and sagittal (B) magnetic resonance images from a 52-
year-old healthy female with an atraumatic single tendon full-thickness rotator
cuff tear treated nonsurgically. The patient re-presented 2 years later with
increasing pain and weakness with no new injury. Follow-up magnetic
resonance images (C and D) show significant progression of her tear with
retraction.

Partial-Thickness Tears
There has been renewed interest in the management of partial-
thickness tears, which can be bursal or articular sided. A 2020 study
compared patients treated with either débridement or takedown
and repair for bursal-sided partial-thickness rotator cuff tears.
Although débridement resulted in be er clinical outcome scores at
6 months, there was no difference at final 2-year follow-up.
Additionally, there was no difference in retear or tear progression
on MRI or ultrasonography between the two groups at 2 years. 5
Long-term outcomes for in situ repair are also favorable. A 2019
study evaluated 62 patients with a mean age of 52.3 years 10 years
after in situ repair and found improvement in all outcome scores
and an 87% rate of return to sport. There were no revisions, and the
authors found no difference in outcomes or return to sport between
articular-sided or bursal-sided tears. 6 More recently, some have
advocated for the use of patch augmentation for the management
of partial-thickness tears. Thirty-three patients with chronic,
degenerative partial-thickness tears were prospectively enrolled
and treated with a resorbable, bioinductive collagen patch over the
bursal side of a partial-thickness tear without tear débridement or
takedown. At 2-year follow-up, the American Shoulder and Elbow
Surgeons (ASES) and Constant scores were significantly improved
from baseline. MRI showed that tendon thickness had increased
compared with baseline, and one patient progressed to a full-
thickness tear. 7

Full-Thickness Tears
Although both nonsurgical management with physical therapy and
surgical repair have been shown to improve symptoms in rotator
cuff tears, recent evidence suggests that surgical repair may be
superior over the long term. A 2019 study reported 103 patients
with full-thickness rotator cuff tears less than 3 cm in size
randomized to primary repair or physical therapy. At 10-year
follow-up, the primary repair group had maintained improvements
compared with the nonsurgical group in ASES score, Constant
score, visual analog scale pain score, pain-free abduction, and pain-
free forward flexion. 8
There continues to be significant debate on rotator cuff repair
technique; a gold standard configuration does not exist. A 2020
double-blind randomized controlled trial compared transosseous-
equivalent double-row and single-row repair of small and large full-
thickness rotator cuff tears. These authors found be er functional
outcomes for those undergoing double-row repair with tears
greater than 3 cm but no difference in outcomes between groups
with smaller tears. 9 The authors postulated this difference in
outcomes may be due to a higher retear rate in single-row repairs
with larger tears, although no imaging follow-up was performed in
these patients. Previous studies have shown a higher healing rate
with double-row repairs for larger tears. 10 The debate also
continues regarding kno ed versus knotless repairs. A 2020
systematic review evaluated 552 shoulders from seven studies and
found no difference in retear rates or the location of retears in
knotless or kno ed suture configurations. 11
The routine use of acromioplasty during rotator cuff repair has
been questioned. A 2021 randomized controlled trial compared
patients undergoing rotator cuff repair with and without
acromioplasty. At a mean follow-up of 7.5 years, there was no
difference in patient-reported outcomes, retear rate, or need for
revision surgery. 12 All acromial morphologies were included and
the study was underpowered to detect differences between these
groups. The need for acromioplasty remains an individualized
decision.
Although outcomes after rotator cuff repair are generally
favorable, there has been recent interest in various types of
augmentation to improve results and retear rates. A 2019 study
randomized patients with degenerative, full-thickness small and
medium rotator cuff tears to undergo standard repair or repair with
porcine dermal patch augmentation. At 2-year follow-up, those with
patch augmentation showed a 97.6% rate of healing compared with
59.5% for the nonaugmented group on MRI. However, there were
no clinically significant differences in outcome scores or strength at
final follow-up. 13 The role of platelet-rich plasma in rotator cuff
repair has also been explored. A 2021 meta-analysis evaluated 553
patients in 17 studies, which compared the use of platelet-rich
plasma during rotator cuff repair with standard repair. The results
for outcome scores were mixed; however, the use of pure platelet-
rich plasma did show a slightly reduced retear rate (19.3% versus
25.4%). 14 More data are needed to support the routine use of patch
or biologic augmentation for rotator cuff repair.

Irreparable Rotator Cuff Tear Management

There remains significant controversy in the management of the
irreparable rotator cuff tear. Options include débridement, partial
repair, superior capsular reconstruction (SCR) with various graft
types (Figure 2), multiple different tendon transfers, and, finally,
reverse shoulder arthroplasty. Débridement remains a viable
option in the appropriately selected patient. A 2020 study
retrospectively reviewed outcomes in 26 patients undergoing
débridement for irreparable tears. These authors saw improvement
in ASES and visual analog scale pain score at mean follow-up of 98
months. Six patients (23%) underwent revision surgery during the
follow-up period, and lower preoperative forward elevation was
associated with worse postoperative ASES score and revision to
reverse shoulder arthroplasty. 15
 Figure 2 Preoperative magnetic resonance and arthroscopic images of a
superior capsular reconstruction.Coronal T2 magnetic resonance image shows
massive superior rotator cuff with retraction significant retraction (A). Sagittal T1-
weighted magnetic resonance image of the same patient shows Goutallier grade
IV atrophy of the supraspinatus (B). Superior capsular reconstruction was
performed with a dermal allograft (C).

The SCR was first performed using a fascia lata autograft, and 5-
year outcomes were published in 2019. 16 The study reported 31
patients after arthroscopic SCR and showed improved clinical
outcomes, range of motion, and acromiohumeral distance. Three
patients had graft retear and progressed to cuff tear arthropathy.
The remaining patients had intact grafts on final follow-up and no
progression to cuff tear arthropathy. Graft thickness on MRI did not
differ between 1-year and 5-year follow-up. 16 A similar study
reported 2-year clinical and imaging outcomes after SCR using a
thinner dermal allograft. Although all clinical outcomes improved
from before surgery, the rate of graft retear was higher (50%)
compared with other studies using fascia lata autografts. 17 With the
available data, it is unclear whether SCR with a dermal allograft
provides outcomes superior to lower cost options such as
débridement or partial repair.
Tendon transfers are another option for the irreparable
posterosuperior rotator cuff tear. The latissimus dorsi transfer has
been well studied. A 2020 study of 22 patients with a mean follow-
up of 3.4 years showed significant improvements in clinical
outcome and pain scores. There was, however, a high complication
rate (27%) and a high rate of conversion to reverse shoulder
arthroplasty (13.6%). These authors reported a clinical failure rate
of 41%. A low acromiohumeral distance and high-grade fa y
infiltration preoperatively were risk factors for failure. 18 More
recently, the arthroscopic-assisted lower trapezius transfer has
been explored because of its improved moment arm for active
external rotation (Figure 3). A prospective evaluation of 41 patients
showed improvement in all clinical outcome scores. At 14-month
follow-up, two patients had been converted to reverse shoulder
arthroplasty and two patients sustained a traumatic rupture of the
graft. 19
 Figure 3 Preoperative magnetic resonance and intraoperative images of an
arthroscopic-assisted lower trapezius transfer.Preoperative coronal T2 magnetic
resonance image shows massive posterior superior rotator cuff tear with
retraction (A) and sagittal T1-weighted images show Goutallier grade IV atrophy
of the infraspinatus (B). Intraoperative photograph (C) through a posterior
incision shows Achilles allograft being fixed to the lower trapezius tendon.
Arthroscopic photograph (D) of lower trapezius tendon graft entering the
subacromial space posteriorly and being fixed to the greater tuberosity.

Although data are limited, a subacromial balloon spacer has also

been explored for the management of massive, irreparable tears. A
2021 prospective, nonrandomized study reported 51 patients with a
minimum of 1-year follow-up. There was significant improvement
in the Constant score with only five patients being dissatisfied with
their outcome. Five patients underwent reverse shoulder
arthroplasty, and one patient went on to latissimus dorsi transfer
during the follow-up period. 20
Calcific Tendinitis
Calcific tendinitis is a painful shoulder condition affecting between
3% and 7% of adults. It is most commonly seen in females aged 30
to 60 years and has an association with diabetes and thyroid
disorders. 21 The etiology is controversial though the stages of
progression—formative, resting, and resorptive—are well accepted
22
(Figure 4). The mainstay of treatment is nonsurgical, including
activity modification, rest, physical therapy, and anti-inflammatory
medications. In refractory cases, more invasive options may be
considered such as injections, ultrasound-guided pulse lavage and
needling, or extracorporeal shock wave therapy. Surgical
intervention remains the last option. Evaluation with plain
radiographs is usually sufficient; however, a 2020 MRI study found
that 56% of calcium lesions were associated with partial-thickness
(93%) or full-thickness (7%) rotator cuff tears, specifically lesions
classified as cloudy with soft contour. 23 A 2020 randomized
controlled trial compared ultrasound-guided needling (UGN) with
subacromial corticosteroid injection (CSI) versus high-energy
extracorporeal shock wave therapy in 82 patients. At 1 year, there
were no differences in Constant scores, Disabilities of the Arm,
Shoulder and Hand scores, or visual analog scale for pain; however
the UGN group had more radiographic resorption of the calcific
lesion and required less additional treatment during the follow-up
period. 24 The addition of a CSI to the UGN procedure has been
shown to improve pain at 6 weeks and function at 3 months versus
saline injection control but had no effect on calcium resorption. 25
Platelet-rich plasma injection after UGN was found to have no
benefit over CSI at 1 and 2 years. 26 Although nonsurgical treatment
is frequently successful, patients with calcific lesions larger than 1
cm had a 2.8-fold increased likelihood of requiring surgical
treatment. 27
 Figure 4 Grashey view (A) of a right hand–dominant 49-year-old female with
calcific tendinitis in the resorptive phase. Note the toothpaste consistency of the
large calcium lesion in the supraspinatus. The patient was treated with a
subacromial corticosteroid injection and formal physical therapy. Repeat
radiograph (B) shows near-complete resorption of the calcific lesion.

Adhesive Capsulitis
Adhesive capsulitis, or frozen shoulder, begins as an inflammatory
reaction and synovitis that progresses to fibrotic contracture of the
shoulder capsule. 28 The pathophysiology is poorly understood but
thought to be driven by increased recruitment of inflammatory
cytokines. Elevated fasting glucose levels, hypercholesterolemia,
thyroid disorder, and increased high-sensitivity C-reactive protein
all have been associated with adhesive capsulitis. In a case-control
study of 202 patients, serum high-sensitivity C-reactive protein was
independently associated with adhesive capsulitis when controlling
for diabetes, dyslipidemia, and thyroid-stimulating hormone. 29
Interestingly, a 2021 report has also suggested a link between
severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and
adhesive capsulitis. 30 In refractory cases, more invasive treatments
can be considered. Extracorporeal shock wave therapy has shown
benefit in diabetic patients compared with intra-articular CSIs at
short-term follow-up. 31 More recently, alternative minimally
invasive treatments such as collagenase Clostridium histolyticum
injections and ultrasound-guided percutaneous sectioning of the
coracohumeral ligament have shown early encouraging results,
although further study is needed. 32 , 33 Studies have shown that
although capsular release and manipulation under anesthesia
provide similar functional outcomes, arthroscopic capsular release
results in improved range of motion including forward flexion,
abduction, and external rotation. 34

Throwing Shoulder
The overhead throwing motion generates substantial force across
the glenohumeral joint. The repetitive stress and microtrauma lead
to adaptive changes in a thrower’s dominant arm and can lead to
various pathologic conditions. These changes include increased
external rotation, decreased internal rotation, increased glenoid and
humeral head retroversion, and posterior capsular hypertrophy.

Glenohumeral Internal Rotation Deficit

Increased glenohumeral external rotation, with a concomitant
decrease in internal rotation, is an essential adaptation for high-
level throwers to obtain maximum velocity. However, this decrease
in internal rotation significantly alters the kinematics of the
shoulder and elbow, which may lead to various pathologic
conditions including labral and partial-thickness rotator cuff
tearing as well as injury to the medial ulnar collateral ligament
(MUCL). A 2020 systematic review showed large variations in the
definition of what is pathologic glenohumeral internal rotation
deficit (GIRD), but it is most commonly defined as a greater than
15° to 20° difference in passive internal rotation compared with the
contralateral, nondominant arm. 35 In a study of 26 asymptomatic
professional baseball players, those with a loss of greater than 20°
were compared against those with normal range of motion. The
group with decreased internal rotation showed increased atrophy of
the supraspinatus and infraspinatus, weakness in external rotation,
and an overall decrease in arc of motion. 36
 It is well accepted that posterior capsular hypertrophy and
tightness is one of the main drivers of GIRD pathology. This
hypertrophy translates the humeral head anterosuperior within the
glenoid fossa resulting in internal impingement during hyper
external rotation in the late cocking phase of throwing, leading to
undersurface rotator cuff tears and labral pathology. Additionally,
there has also been recent interest in the effect of GIRD on the
stresses across the elbow. A 2019 study matched 108 high school,
college, and professional pitchers with MUCL injury to 108
asymptomatic control patients. These authors found a strong
relationship between MUCL injury and glenohumeral internal
rotation loss, with 60% of those with MUCL injuries having GIRD
compared with only 30% of the control group. 37

Superior Labrum Anterior-Posterior Tears

Injuries to the biceps-labral complex are the most common injury
seen in the overhead athlete, and their diagnosis and treatment
remain controversial. 38 First described by Andrews in the 1980s,
the superior labrum anterior-posterior (SLAP) tear is seen in those
with repetitive overhead movements and is commonly associated
with biceps tendinosis. 39 A trial of nonsurgical treatment,
including physical therapy and activity modification remains the
best first option. A prospective study showed improvement in 85%
of recreational athletes with a course of rehabilitation. 40 However,
other studies have shown much lower rates of return to sport with
nonsurgical treatment in elite athletes. 41
After nonsurgical management has failed, much debate exists
regarding the optimal surgical management of SLAP tears. The
high rate of repair failure and low rates of return to sport among
athletes have led to increased utilization of biceps tenodesis, even
in the young overhead athlete. A 2019 retrospective review analyzed
34 athletes younger than 25 years who underwent open subpectoral
biceps tenodesis. At 2 years, 77% of the overhead athletes returned
to sport. 42 A 2020 systematic review evaluated 99 athletes with a
mean age of 19.8 years undergoing biceps tenodesis for a type II
SLAP tear. Included studies evaluated both open and arthroscopic
tenodesis as well as revision procedures for failed SLAP repair.
Overall, the return to sport rate was 70% for overhead athletes. 38 A
different systematic review compared 501 athletes with a mean age
of 22 years undergoing arthroscopic SLAP repair or biceps
tenodesis. Those undergoing biceps tenodesis had the highest
return to sport at 84.5% versus 79.5% for those undergoing repair. 43

Scapular Dyskinesis
Optimal scapular position is critical to peak function for overhead
athletes as it provides a key link in the kinetic chain. Scapular
dyskinesia is defined as altered motion of the scapula that
manifests as resting scapular protraction, which can be
asymptomatic or the root cause of pathologies around the shoulder.
44
However, debate remains whether scapular dyskinesis is a cause
or effect of shoulder pathology. A 2020 systematic review and meta-
analysis identified 7 studies of 212 shoulder injuries in 923 athletes.
Scapular dyskinesis displayed a trend toward increased risk of
shoulder injury, but there was no statistically significant link. 45 For
symptomatic scapular dyskinesia, the first-line treatment remains a
dedicated rehabilitation protocol focusing on restoring normal
scapular kinematics. 46

Biceps Pathology
The long head of the biceps tendon is well established as a pain
generator in the shoulder; however, its true role is poorly
understood. Many physical examination maneuvers have been
described to identify biceps pathology. The Speed test, with a
sensitivity of 32% and specificity of 75%, is performed by having the
patient forward elevate against resistance with the elbow extended
and the forearm held in supination. The Yergason test, with a
sensitivity of 43% and specificity of 79%, is considered positive
when pain is elicited when a patient supinates the forearm against
resistance from a pronated position with the elbow flexed to 90°
and the arm at the side. 47 The subpectoral biceps test was recently
described in a 2019 study; a positive examination was associated
with gross pathologic changes of the biceps in 93% of patients.
However, those with a negative test also showed pathologic
changes 65% of the time. 48 To perform the subpectoral biceps test,
the examiner palpates the biceps tendon as it courses under the
pectoralis major tendon with the patient’s arm held in a position of
adduction and internal rotation. Pain on palpation is considered a
positive test and indicative of biceps pathology.
Once the decision to treat the biceps has been made, there
remains considerable debate over the role of tenotomy versus
tenodesis. A 2020 double-blind randomized controlled trial
enrolled 114 patients with an average age of 57.7 years. Patients
were randomized to receive tenotomy or tenodesis and were
followed for 2 years. There were no differences in outcome scores
between groups; however, there was a 4.3-fold higher rate of Popeye
deformity in those undergoing tenotomy. 49 Further subgroup
analysis showed increased pain and cramping in those with a
Popeye deformity and younger patients being less satisfied with the
cosmetic appearance without any decrease in functional outcomes.
50

When deciding whether to perform a tenodesis, multiple

techniques have been described with successful outcomes. Options
include arthroscopic high groove or suprapectoral fixation as well
as open subpectoral techniques. Fixation methods include all-
suture anchors or interference screws. A recent meta-analysis of
biomechanical studies found no difference in ultimate load to
failure, cyclic loading, or construct strength when evaluating
various surgical techniques and locations. 51 In contrast, a 2021
study showed increased load to failure for an all-suture anchor
compared with conventional interference screw in a biomechanical
study evaluating an open subpectoral approach. 52 A 2020
randomized prospective analysis compared low groove arthroscopic
suprapectoral biceps tenodesis with open subpectoral biceps
tenodesis. All procedures used a polyether ether ketone
interference screw. The authors of this study found no difference in
functional outcomes or complication rates between the two
techniques. 53

Instability

Glenohumeral Instability
Stability of the glenohumeral joint relies on a combination of bony
and soft-tissue anatomic structures. Traumatic instability results
from a fall or contact with the arm in the abducted and externally
rotated position, whereas atraumatic instability can be from
generalized ligamentous laxity or repetitive microtrauma.

Anterior Instability
Anterior instability accounts for most instances of glenohumeral
instability and is commonly seen in young athletes. Male athletes
who participate in contact sports are at an elevated risk for both
instability and recurrence. Recent literature has focused extensively
on risk factors for recurrent instability, the role of nonsurgical
versus surgical treatment in the patient with a first-time
dislocation, and the concept of critical glenoid bone loss (Figure 5).
 Figure 5 Algorithm for treatment of glenohumeral instability in the young
patient. HSL, Hill-Sachs lesion

Substantial controversy exists regarding the management of a

patient with a first-time anterior glenohumeral dislocation. Factors
to consider include age, activity level, mechanism of injury,
preexisting ligamentous laxity, and the amount of glenoid bone
loss. In 2020, the ASES Neer Circle used the Delphi approach in an
a empt to reach a consensus in treatment. Seventy-two expert
surgeons evaluated 162 clinical scenarios and only 8 scenarios (5%)
achieved >90% consensus for surgical management and 22
scenarios (14%) for nonsurgical management. 54 This study
highlights the high level of disagreement on treatment strategies,
even in the hands of expert surgeons.
A 2021 multicenter randomized controlled trial evaluated
immobilization versus arthroscopic stabilization after a single
dislocation event without glenoid bone loss. At 2-year follow-up,
there was a significantly increased risk of recurrent instability in
those treated without surgery (19.1% versus 2.3%, P = 0.016)
although there was no difference in final clinical outcome scores. 55
Similarly, the long-term follow-up of a previous randomized,
double-blind trial of arthroscopic stabilization versus arthroscopic
washout for a first-time anterior dislocation was published in 2020.
At 10-year follow-up, the rate of recurrent instability was
significantly higher in the arthroscopic washout group (47% versus
12%, P = 0.002). Unlike the previous study, the Western Ontario
Shoulder Instability Index score was significantly worse in the
arthroscopic washout group. Nine patients (28%) in the
arthroscopic washout group ultimately underwent stabilization
surgery. 56 These results may suggest worse long-term outcomes in
those treated nonsurgically after a first-time dislocation event.
Failure of initial treatment continues to be a clinical concern. A
2021 study of 217 shoulders found an 11.5% failure rate of
arthroscopic stabilization at mean follow-up of 42 months. Failure
was associated with glenoid bone loss greater than 14.5%, Hill-
Sachs volume greater than 1.3 cm2, and duration of instability
symptoms greater than 3 months. Those with recurrent instability
had significantly worse clinical outcome scores. 57 Because of these
relatively high failure rates, some have recently advocated for a
more aggressive approach with open stabilization or primary bone
block procedures such as the Latarjet. A 2021 study randomized
those with recurrent anterior shoulder instability to either open or
arthroscopic stabilization. At 15-year minimum follow-up, the
overall failure rate was 13.3%, with no difference between
arthroscopic or open stabilization. 58 A 2021 systematic review
compared arthroscopic Bankart repair versus the Latarjet approach
for recurrent anterior stability. A total of 7 studies with 3,275
shoulders were reviewed. Arthroscopic Bankart repair was
associated with a higher risk of recurrent instability; however, there
were no differences in Rowe score or the need for revision surgery.
59
The risk factors for failure after a primary Latarjet procedure have
been reviewed. A 2020 study analyzed 358 shoulders over a 10-year
period that underwent a primary Latarjet procedure for anterior
instability. At a mean follow-up of 6 years, recurrence was seen in
17 shoulders (4.7%) with an additional 28 shoulders (8.2%) defined
as clinical failures due to poor outcome scores. Risk factors for
recurrent instability included initial atraumatic dislocation and
bilateral instability, whereas clinical failure was associated with
female sex and bilateral instability. 60 A 2021 single-institution
study evaluated early complications with the Latarjet procedure.
The study authors observed 15 complications in 190 procedures for
a rate of 9.0%, with 6 patients requiring revision surgeries.
Complications included those not typically encountered after
arthroscopic procedures such as graft and hardware failure (4.7%)
as well as nerve injuries (3.2%). 61
In addition to glenoid-sided bone loss, the importance of
humeral-sided bone loss has recently been explored. The Hill-Sachs
lesion can result from a single dislocation or multiple instability
events, and it has recently been identified as a predictor of
recurrence. 57 A 2021 randomized controlled trial looked at 108
patients with recurrent anterior instability and an engaging Hill-
Sachs lesion with less than 15% glenoid bone loss. Arthroscopic
Bankart repairs with or without remplissage to treat the Hill-Sachs
defect were performed. Rates of recurrent instability were
significantly higher in those without remplissage (18% versus 4%, P
= 0.027). There were no differences in clinical outcomes or need for
revision surgery between groups. Hill-Sachs lesions greater than 20
mm or greater than 15% of humeral head diameter were associated
with recurrent instability. 62 Similarly, a 2020 systematic review
compared arthroscopic Bankart repair with and without
remplissage as well as arthroscopic Bankart repair with remplissage
and the Latarjet procedure. When comparing arthroscopic Bankart
repair with and without remplissage, there was a significant
difference in recurrence rate (3.2% versus 16.8%, P < 0.05) but no
difference in need for revision or clinical outcomes. Although there
was no difference in recurrence rate when comparing arthroscopic
Bankart and remplissage with the Latarjet procedure, there was a
significantly higher rate of complications with the Latarjet
procedure. 63

Posterior Instability
Posterior glenohumeral instability clinically manifests as posterior
shoulder pain and is commonly seen in athletes. There are two
unique pathomechanical processes resulting in posterior
instability. The first is most often encountered in contact athletes
and results from a posteriorly directed axial force and repetitive
microtrauma leading to posteroinferior labral tearing. The second
distinct pathology is seen in overhead throwers and is the result of
capsular contractures and imbalances of the dynamic stabilizers
leading to posterosuperior labral tearing.
A 2021 retrospective review evaluated 143 patients with posterior
instability with a minimum 5-year follow-up. These authors
determined nonsurgical management to be a viable option for most
patients. 64 When nonsurgical management fails to result in
improvement in pain and dysfunction, surgery is considered. A
2021 systematic review evaluated 1,153 shoulders in 1,100 patients
undergoing both arthroscopic and open stabilization of posterior
shoulder instability. These authors showed an overall return to
sport of 94% for contact athletes and 88% for throwers. Overall, 68%
returned to their preinjury function. 65 A 2021 retrospective study
evaluated factors associated with failure after arthroscopic
stabilization for posterior instability. The authors reported an
association between smaller glenoid width and a greater percentage
of glenoid bone loss in those with failed stabilization. Cutoffs of
11% and 15% of posterior glenoid bone loss resulted in a 10-fold
and 25-fold, respectively, higher surgical failure rate. 66

Multidirectional Instability
Multidirectional instability (MDI) was first described by Neer in
1980 and was defined as involuntary inferior subluxation secondary
to redundancy of the ligaments and the inferior portion of the joint
capsule. 67 A classic study later refined this definition by discussing
the difference between laxity and instability in the unbalanced
shoulder. 68 However, li le consensus exists on a true definition of
MDI, making it difficult to study outcome measures. The gold
standard for treatment remains a long course of guided
rehabilitation to strengthen the rotator cuff and periscapular
muscles. One study evaluated 43 patients with MDI and observed
an improvement in functional status, shoulder muscle strength,
and scapular positioning after a 12-week supervised rehabilitation
program. 69 When patients fail to progress in therapy and continue
to be symptomatic, open or arthroscopic surgery may be
considered. A 2019 study evaluated 36 shoulders in 35 patients with
MDI who underwent 360° circumferential labral repair. At final
follow-up, 22% of patients continued to have pain and 25%
experienced recurrent instability. 70

Muscle Ruptures
The pectoralis major tendon is made up of a clavicular and sternal
head that combine to insert on the proximal humerus, just lateral to
the bicipital groove. Tears are typically seen in young, active males
following an eccentric contraction. A retrospective, single-surgeon
case series reviewed 104 surgical cases of pectoralis major rupture
and identified 96% of the tears occurring at or between the
musculotendinous junction and tendinous insertion. 71 A 2019
systematic review and meta-analysis compared surgical techniques
and outcomes of pectoralis major repair. Although low quality of
included studies limited this review, these authors found a
transosseous suture or suture anchor technique to be more likely to
result in a good/excellent outcome compared with a unicortical
bu on technique. 72 Return to work and return to sport is of
particular concern in this young, active population. A 2019
systematic review analyzing 536 patients showed a 90% return to
sport, with 74% returning to their preinjury level. In the same
study, 95% returned to work at a mean of 6.9 months
postoperatively. 73

Summary
Disorders of the shoulder constitute a large portion of
musculoskeletal complaints and affect many working-age adults. A
thorough understanding of the pathoanatomy of various shoulder
conditions improves diagnostic evaluation and helps to guide
treatment strategies. Recent a ention on the treatment of massive
irreparable rotator cuff tears has focused on defining the role of
SCR and various tendon transfers. The mainstay of treatment for
calcific tendinitis and adhesive capsulitis remains nonsurgical. The
patient experiencing a first-time traumatic anterior dislocation
continues to provide a treatment challenge although recent
evidence may favor more aggressive early treatment. The
importance of both glenoid-sided and humeral-sided bone loss and
the relationship between the two in the position of apprehension
has been well established and must be considered when
determining appropriate treatment options. Both arthroscopic
Bankart repair and open Latarjet stabilization result in similar
outcomes although their complication profiles are significantly
different.

Key Study Points

Long-term, randomized, prospective studies continue to show the value and
superiority of surgical repair compared with nonsurgical management for full-
thickness rotator cuff tears.
The mainstay of treatment for adhesive capsulitis and calcific tendinitis is
nonsurgical, with activity modification, physical therapy, over-the-counter anti-
inflammatory agents, and CSIs.
Treatment options for massive, irreparable rotator cuff tears include débridement,
partial repair, SCR with various graft types, multiple different tendon transfers,
reverse shoulder arthroplasty, and balloon spacers. The appropriate treatment
remains a patient-specific decision, and there is no one-size-fits-all approach.
Recent evidence suggests that it may be appropriate to intervene surgically after a
first-time dislocation event in a young, active patient to prevent further recurrence
and the risk of significant bone loss.

Annotated References
1. Mather RC III, Koenig L, Acevedo D, et al: The societal and
economic value of rotator cuff repair. J Bone Joint Surg Am
2013;95(22):1993-2000.
2. Sher JS, Uribe JW, Posada A, Murphy BJ, Zlatkin MB: Abnormal
findings on magnetic resonance images of asymptomatic
shoulders. J Bone Joint Surg Am 1995;77(1):10-15.
3. Tsuchiya S, Davison EM, Rashid MS, et al: Determining the rate
of full-thickness progression in partial-thickness rotator cuff
tears: A systematic review. J Shoulder Elbow Surg 2021;30(2):449-
455. This systematic review evaluated partial-thickness rotator
cuff tear progression based on serial MRI or ultrasonography.
Symptomatic and asymptomatic tears progressed at 0.26% and
0.32% per month, respectively. Level of evidence: IV.
4. Kim YS, Kim SE, Bae SH, Lee HJ, Jee WH, Park CK: Tear
progression of symptomatic full-thickness and partial-thickness
rotator cuff tears as measured by repeated MRI. Knee Surg Sports
Traumatol Arthrosc 2017;25(7):2073-2080.
5. Zhang Y, Zhai S, Qi C, et al: A comparative study of arthroscopic
debridement versus repair for Ellman grade II bursal-side
partial-thickness rotator cuff tears. J Shoulder Elbow Surg
2020;29(10):2072-2079. A retrospective cohort study comparing
arthroscopic débridement versus repair for bursal-sided partial-
thickness rotator cuff tears showed improved outcomes in the
débridement group at 6 months but no difference at 2 years.
Level of evidence: III.
6. Rossi LA, Atala NA, Bertona A, et al: Long-term outcomes after
in situ arthroscopic repair of partial rotator cuff tears. Arthroscopy
2019;35(3):698-702. This retrospective series of 62 patients with 10-
year follow-up after in situ repair of partial-thickness tears
showed low revision rates and excellent clinical outcomes. Level
of evidence: IV.
7. Schlegel TF, Abrams JS, Angelo RL, Getelman MH, Ho CP,
Bushnell BD: Isolated bioinductive repair of partial-thickness
rotator cuff tears using a resorbable bovine collagen implant:
Two-year radiologic and clinical outcomes from a prospective
multicenter study. J Shoulder Elbow Surg 2020;30(8):1938-1948. A
prospective, multicenter study of bioinductive patch
 augmentation of 33 partial-thickness tears is presented. Clinical
outcomes were improved at 2-year follow-up with patients
progressing to full-thickness tear. Level of evidence: IV.
8. Moosmayer S, Lund G, Seljom US, et al: At a 10-year follow-up,
tendon repair is superior to physiotherapy in the treatment of
small and medium-sized rotator cuff tears. J Bone Joint Surg Am
2019;101(12):1050-1060. A prospective, randomized trial
compared physical therapy with arthroscopic repair for small and
medium sized tears. At 10 years, Constant score, ASES score,
visual analog scale score pain, and pain-free abduction and
flexion were superior in the repair group. Level of evidence: I.
9. Imam M, Sallam A, Ernstbrunner L, et al: Three-year functional
outcome of transosseous-equivalent double-row vs. single-row
repair of small and large rotator cuff tears: A double-blinded
randomized controlled trial. J Shoulder Elbow Surg
2020;29(10):2015-2026. A prospective, randomized trial compared
transosseous-equivalent double-row with single-row repair for
full-thickness tears. Double-row repair showed superior
outcomes in tears greater than 3 cm but no benefit for smaller
tears. Level of evidence: I.
10. Gartsman GM, Drake G, Edwards TB, et al: Ultrasound
evaluation of arthroscopic full-thickness supraspinatus rotator
cuff repair: Single-row versus double-row suture bridge
(transosseous equivalent) fixation. Results of a prospective,
randomized study. J Shoulder Elbow Surg 2013;22(11):1480-1487.
11. Kunze KN, Rossi LA, Beletsky A, Chahla J: Does the use of
kno ed versus knotless transosseous equivalent rotator cuff
repair technique influence the incidence of retears? A systematic
review. Arthroscopy 2020;36(6):1738-1746. This systematic review
evaluated the knotless versus kno ed rotator cuff repairs. No
differences were found in the incidence or location of retears.
Level of evidence: IV.
12. Waterman BR, Newgren J, Gowd AK, et al: Randomized trial of
arthroscopic rotator cuff with or without acromioplasty: No
 difference in patient-reported outcomes at long-term follow-up.
Arthroscopy 2021;37(10): 3072-3078. A prospective, randomized
trial evaluated acromioplasty with and without repair of full-
thickness rotator cuff repairs. At a mean 7.5-year follow-up, there
was no difference in patient-reported outcomes, retears, or need
for revision surgery. Level of evidence: II.
13. Avanzi P, Giudici LD, Capone A, et al: Prospective randomized
controlled trial for patch augmentation in rotator cuff repair: 24-
month outcomes. J Shoulder Elbow Surg 2019;28(10):1918-1927. A
prospective, double-blind, randomized trial evaluated the
addition of a porcine dermal patch after single-row repair of full-
thickness tears. MRIs were obtained at 2-year follow-up, which
showed superior healing rates for the augmented group (97.6%
versus 59.6%). Level of evidence: II.
14. Ryan J, Imbergamo C, Sudah S, et al: Platelet-rich product
supplementation in rotator cuff repair reduces retear rates and
improves clinical outcomes: A meta-analysis of randomized
controlled trials. Arthroscopy 2021;37(8):2608-2624. A systematic
review investigated clinical and imaging outcomes of rotator cuff
repairs augmented with platelet-rich product. Analysis showed
reduction in retear rates with platelet-rich product augmentation,
with pure platelet-rich product having the most dramatic effect.
Level of evidence: IV.
15. Ho JC, Kane L, Stone MA, Romeo AA, Abboud JA, Namdari S:
Arthroscopic debridement of irreparable rotator cuff tears:
Predictors of failure and success. J Shoulder Elbow Surg
2020;29(4):e118-e123. A retrospective review of 26 patients
undergoing débridement for irreparable rotator cuff tears
showed good midterm outcomes with poor preoperative forward
elevation as a negative prognostic factor. Level of evidence: IV.
16. Mihata T, Lee TQ, Hasegawa A, et al: Five-year follow-up of
arthroscopic superior capsule reconstruction for irreparable
rotator cuff tears. J Bone Joint Surg Am 2019;101(21):1921-1930. A 5-
year outcomes study of 30 patients undergoing superior capsule
reconstruction (SCR) with fascia lata autograft showed 27 healed
 grafts with excellent clinical outcomes. Three patients (10%) in
whom the procedure failed progressed to severe cuff tear
arthropathy. Level of evidence: IV.
17. Lacheta L, Horan MP, Schairer WW, et al: Clinical and imaging
outcomes after arthroscopic superior capsule reconstruction with
human dermal allograft for irreparable posterosuperior rotator
cuff tears: A minimum 2-year follow-up. Arthroscopy
2020;36(4):1011-1019. A retrospective case series of 22 patients
with retained active forward elevation undergoing superior
capsule reconstruction (SCR) with 3 mm dermal allograft showed
high satisfaction and low failure rates at short-term follow-up.
Level of evidence: IV.
18. Muench LN, Kia C, Williams AA, et al: High clinical failure rate
after latissimus dorsi transfer for revision massive rotator cuff
tears. Arthroscopy 2020;36(1):88-94. A retrospective review of 22
patients undergoing latissimus dorsi transfer for irreparable
rotator cuff tears after failed repair is presented. The authors
showed a high clinical failure rate (41%) and conversion to
reverse shoulder arthroplasty (14%) at final follow-up. Level of
evidence: IV.
19. Elhassan BT, Sanchez-Sotelo J, Wagner ER: Outcome of
arthroscopically assisted lower trapezius transfer to reconstruct
massive irreparable posterior-superior rotator cuff tears. J
Shoulder Elbow Surg 2020;29(10):2135-2142. In a retrospective case
series, the authors evaluated arthroscopically assisted lower
trapezius transfers for irreparable posterior-superior rotator cuff
tears, including those with pseudoparalysis, showing
improvement in functional outcomes in 90% of patients. Level of
evidence: IV.
20. Familiari F, Nayar SK, Russo R, et al: Subacromial balloon
spacer for massive, irreparable rotator cuff tears is associated
with improved shoulder function and high patient satisfaction.
Arthroscopy 2021;37(2):480-486. A prospective evaluation of 51
patients with irreparable tears undergoing subacromial balloon
spacer showed improved outcomes and high satisfaction.
 Implant survival was 87% at 4 years, with 3 patients undergoing
reverse shoulder arthroplasty and 1 patient undergoing
latissimus dorsi transfer. Level of evidence: IV.
21. Greis AC, Derrington SM, McAuliffe M: Evaluation and
nonsurgical management of rotator cuff calcific tendinopathy.
Orthop Clin North Am 2015;46(2):293-302.
22. Uhthoff HK, Loehr JW: Calcific tendinopathy of the rotator cuff:
Pathogenesis, diagnosis, and management. J Am Acad Orthop Surg
1997;5(4):183-191.
23. Brinkman JC, Zaw TM, Fox MG, et al: Calcific tendonitis of the
shoulder: Protector or predictor of cuff pathology? A magnetic
resonance imaging-based study. Arthroscopy 2020;36(4):983-990. A
retrospective review of MRI of patients with calcific tendinitis
showed a 56% incidence of concomitant rotator cuff tears with
most being partial tears. Level of evidence: IV.
24. Louwerens JKG, Sierevelt IN, Kramer ET, et al: Comparing
ultrasound-guided needling combined with a subacromial
corticosteroid injection versus high-energy extracorporeal
shockwave therapy for calcific tendinitis of the rotator cuff: A
randomized controlled trial. Arthroscopy 2020;36(7):1823-1833.e1.
A prospective, randomized trial of ultrasound-guided needling
(UGN) versus extracorporeal shock wave therapy showed
improvement in pain and function in both groups at 1 year. The
UGN was more effective in eliminating the radiographic finding
of calcific deposits. Level of evidence: II.
25. Darrieutort-Laffite C, Varin S, Coiffier G, et al: Are corticosteroid
injections needed after needling and lavage of calcific tendinitis?
Randomised, double-blind, non-inferiority trial. Ann Rheum Dis
2019;78(6):837-843. A randomized, double-blind trial evaluating
the addition of corticosteroid injection (CSI) to ultrasound-
guided needling (UGN) of calcific tendinitis is presented. CSI
improved pain at 1 and 6 weeks but did not affect resorption
rates. Level of evidence: I.
26. Oudelaar BW, Huis In ‘t Veld R, Ooms EM, Schepers-Bok R,
Nelissen R, Vochteloo AJH: Efficacy of adjuvant application of
platelet-rich plasma after needle aspiration of calcific deposits for
the treatment of rotator cuff calcific tendinitis: A double-blinded,
randomized controlled trial with 2-year follow-up. Am J Sports
Med 2021;49(4):873-882. This randomized, double-blind trial
compared corticosteroid injection (CSI) to platelet-rich plasma
with ultrasound- guided needling (UGN) of calcific tendinitis.
The CSI group had improved scores at 6 weeks but no difference
at 2 years and a lower complication profile compared with
platelet-rich plasma. Level of evidence: I.
27. Drummond Junior M, Ayinon C, Rodosky M, Vyas D, Lesniak B,
Lin A: Predictive factors for failure of conservative management
in the treatment of calcific tendinitis of the shoulder. JSES Int
2021;5(3):469-473. A retrospective review of 293 patients treated
for calcific tendinitis is presented. These authors found lesions
larger than 1 cm to more likely require surgical intervention. Of
those undergoing surgical débridement, 83% required a
concomitant rotator cuff repair. Level of evidence: III.
28. Redler LH, Dennis ER: Treatment of adhesive capsulitis of the
shoulder. J Am Acad Orthop Surg 2019;27(12):e544-e554. A
comprehensive review of pathophysiology, physical examination,
radiographic findings, treatment options, and clinical outcomes
of adhesive capsulitis is presented. Level of evidence: V.
29. Park HB, Gwark JY, Jung J, Jeong ST: Association between high-
sensitivity C-reactive protein and idiopathic adhesive capsulitis. J
Bone Joint Surg Am 2020;102(9):761-768. A retrospective case-
control study showed elevated serum C-reactive protein to be
associated with idiopathic adhesive capsulitis when controlling
for diabetes and dyslipidemia. Level of evidence: III.
30. Ascani C, Passare i D, Scacchi M, et al: Can adhesive capsulitis
of the shoulder be a consequence of COVID-19? Case series of 12
patients. J Shoulder Elbow Surg 2021;30(7):e409-e413. A case series
of 12 patients with recent mild or asymptomatic COVID-19
infection presenting with adhesive capsulitis is presented. Ten of
 12 patients had no other risk factors for adhesive capsulitis. Level
of evidence: IV.
31. El Naggar T, Maaty AIE, Mohamed AE: Effectiveness of radial
extracorporeal shock-wave therapy versus ultrasound-guided low-
dose intra-articular steroid injection in improving shoulder pain,
function, and range of motion in diabetic patients with shoulder
adhesive capsulitis. J Shoulder Elbow Surg 2020;29(7):1300-1309. A
randomized trial of extracorporeal shock wave therapy versus
corticosteroid injection (CSI) for patients with diabetes and with
adhesive capsulitis showed superiority of the extracorporeal
shock wave therapy group at short-term follow-up. Level of
evidence: II.
32. Fi patrick J, Richardson C, Klaber I, Richardson MD:
Clostridium histolyticum (AA4500) for the treatment of adhesive
capsulitis of the shoulder: A randomised double-blind, placebo-
controlled study for the safety and efficacy of collagenase – Single
site report. Drug Des Devel Ther 2020;14:2707-2713. Single-site
results from a multicenter double-blind randomized trial showed
no difference over placebo in range of motion at final follow-up.
Level of evidence: II.
33. Wahezi S, Yerra S, Rivelis Y, et al: Sonographically guided
percutaneous sectioning of the coracohumeral ligament for the
treatment of refractory adhesive capsulitis: Proof of concept. Pain
Med 2020;21(12):3314-3319. This pilot cadaver study evaluated the
safety of ultrasound-guided percutaneous incision of the
coracohumeral ligament using an ultrasonic probe for adhesive
capsulitis. Level of evidence: V.
34. Forsythe B, Lavoie-Gagne O, Patel BH, et al: Efficacy of
arthroscopic surgery in the management of adhesive capsulitis: A
systematic review and network meta-analysis of randomized
controlled trials. Arthroscopy 2020;37(7):2281-2297. This systematic
review of randomized controlled trials evaluated 4,042 shoulders
treated for adhesive capsulitis. No treatment was superior for
range of motion, pain, or functional status, although surgical
 treatment after failed nonsurgical management ranked highest.
Level of evidence: II.
35. Kirsch JM, Bakshi NK, Ayeni OR, Khan M, Bedi A: Clinical
outcomes and quality of literature addressing glenohumeral
internal rotation deficit: A systematic review. HSS J
2020;16(3):233-241. A systematic review of clinical outcomes for
GIRD showed low-quality studies and a lack of high-quality
evidence to guide treatment decisions. Level of evidence: IV.
36. Yamaura K, Mifune Y, Inui A, et al: Relationship between
glenohumeral internal rotation deficit and shoulder conditions in
professional baseball pitchers. J Shoulder Elbow Surg
2020;30(9):2073-2081. A prospective evaluation of professional
baseball pitchers identified a correlation between atrophy of the
supraspinatus and infraspinatus in those with GIRD. Level of
evidence: III.
37. Ostrander R, Escamilla RF, Hess R, Wi e K, Wilcox L, Andrews
JR: Glenohumeral rotation deficits in high school, college, and
professional baseball pitchers with and without a medial ulnar
collateral ligament injury. J Shoulder Elbow Surg 2019;28(3):423-
429. A retrospective case-control study of baseball pitchers with
and without ulnar collateral ligament injury is presented. Those
with GIRD greater than 18° and total motion loss greater than 5°
were more likely to have an ulnar collateral ligament injury. Level
of evidence: II.
38. Fran TL, Shackle AG, Martin AS, et al: Biceps tenodesis for
superior labrum anterior-posterior tear in the overhead athlete: A
systematic review. Am J Sports Med 2021;49(2):522-528. A
systematic review evaluating biceps tenodesis for isolated SLAP
tears in overhead athletes showed encouraging functional
outcomes and high rates of return to sport. Level of evidence: IV.
39. Andrews JR, Carson WGJr, McLeod WD: Glenoid labrum tears
related to the long head of the biceps. Am J Sports Med
1985;13(5):337-341.
40. Shin SJ, Lee J, Jeon YS, Ko YW, Kim RG: Clinical outcomes of
non-operative treatment for patients presenting SLAP lesions in
diagnostic provocative tests and MR arthrography. Knee Surg
Sports Traumatol Arthrosc 2017;25(10):3296-3302.
41. Christensen GV, Smith KM, Kawakami J, Chalmers PN: Surgical
management of superior labral tears in athletes: Focus on biceps
tenodesis. Open Access J Sports Med 2021;12:61-71. A
comprehensive review of surgical management of SLAP lesions
in athletes is presented. Level of evidence: V.
42. Griffin JW, Cvetanovich GL, Kim J, et al: Biceps tenodesis is a
viable option for management of proximal biceps injuries in
patients less than 25 years of age. Arthroscopy 2019;35(4):1036-
1041. A retrospective case series of 45 patients younger than 25
years undergoing biceps tenodesis for biceps-labral pathology,
including SLAP tears, with minimum 2-year follow-up showed
low revision rates and satisfactory return to sport (73% overall
and 56% at same level). Level of evidence: IV.
43. Abdul-Rassoul H, Defazio M, Curry EJ, Galvin JW, Li X: Return
to sport after the surgical treatment of superior labrum anterior
to posterior tears: A systematic review. Orthop J Sports Med
2019;7(5):2325967119841892. This systematic review evaluating
return to sport for superior labrum anterior to posterior (SLAP)
lesions showed biceps tenodesis to have a slightly higher rate of
return to sport (84.5%) compared with SLAP repair (79.5%). Level
of evidence: IV.
44. Kibler WB, Sciascia A: Evaluation and management of scapular
dyskinesis in overhead athletes. Curr Rev Musculoskelet Med
2019;12(4):515-526. The evaluation and management of scapular
dyskinesis in the overhead athlete is reviewed. Level of evidence:
V.
45. Hogan C, Corbe JA, Ashton S, Perraton L, Frame R, Dakic J:
Scapular dyskinesis is not an isolated risk factor for shoulder
injury in athletes: A systematic review and meta-analysis. Am J
Sports Med 2021;49(10):2843-2853. A systematic review and meta-
 analysis showed a trend toward an increased risk of injury in
those with scapular dyskinesis but no statistically significant link.
Level of evidence: IV.
46. Jildeh TR, Ference DA, Abbas MJ, Jiang EX, Okoroha KR:
Scapulothoracic dyskinesis: a concept review. Curr Rev
Musculoskelet Med 2021;14(3):246-254. A thorough review of
clinical examination and current treatment modalities for
scapular dyskinesis is presented. Level of evidence: V.
47. Holtby R, Razmjou H: Accuracy of the Speed’s and Yergason’s
tests in detecting biceps pathology and SLAP lesions:
Comparison with arthroscopic findings. Arthroscopy
2004;20(3):231-236.
48. Dwyer C, Kia C, Apostolakos JM, et al: Clinical outcomes after
biceps tenodesis or tenotomy using subpectoral pain to guide
management in patients with rotator cuff tears. Arthroscopy
2019;35(7):1992-2000. A retrospective review evaluating
preoperative subpectoral tenderness in patients with rotator cuff
tears and its association with intraoperative biceps pathology is
presented. A positive subpectoral biceps test correlated with
gross pathologic changes in 93% of patients. Level of evidence:
III.
49. MacDonald P, Verhulst F, McRae S, et al: Biceps tenodesis
versus tenotomy in the treatment of lesions of the long head of
the biceps tendon in patients undergoing arthroscopic shoulder
surgery: A prospective double-blinded randomized controlled
trial. Am J Sports Med 2020;48(6):1439-1449. A randomized,
double-blind trial comparing tenotomy versus tenodesis showed
good outcomes in both groups with a higher incidence of Popeye
deformity with tenotomy. Level of evidence: I.
50. Woodmass JM, McRae SM, Lapner PL, et al: Effect of age,
gender, and BMI on incidence and satisfaction of a Popeye
deformity following biceps tenotomy or tenodesis: Secondary
analysis of a randomized clinical trial. J Shoulder Elbow Surg
2021;30(8):1733-1740. Secondary analysis of a randomized,
 double-blind trial comparing tenotomy versus tenodesis found
increased pain and cramping, but no outcome differences in
those with self-reported Popeye deformity. Younger patients with
Popeye deformities were less satisfied. Level of evidence: II.
51. Dekker TJ, Peebles LA, Preuss FR, Goldenberg BT, Dornan GJ,
Provencher MT: A systematic review and meta-analysis of biceps
tenodesis fixation strengths: Fixation type and location are
biomechanically equivalent. Arthroscopy 2020;36(12):3081-3091. A
systematic review and meta-analysis evaluating biomechanical
outcomes of biceps tenodesis techniques found no significant
differences in technique or location. Level of evidence: IV.
52. Smuin DM, Vanna a E, Ammerman B, Stauch CM, Lewis GS,
Dhawan A: Increased load to failure in biceps tenodesis with all-
suture suture anchor compared with interference screw: a
cadaveric biomechanical study. Arthroscopy 2021;37(10):3016-3021.
A cadaver study of open subpectoral biceps tenodesis with an all-
suture anchor showed increased load to failure compared with a
conventional interference screw. Level of evidence: V.
53. Forsythe B, Zuke WA, Agarwalla A, et al: Arthroscopic
suprapectoral and open subpectoral biceps tenodeses produce
similar outcomes: A randomized prospective analysis.
Arthroscopy 2020;36(1):23-32. A randomized controlled trial
comparing arthroscopic suprapectoral technique versus open
subpectoral technique for biceps tenodesis found no differences
in outcomes or complications in 75 patients at 1-year follow-up.
Level of evidence: I.
54. Tokish JM, Kuhn JE, Ayers GD, et al: Decision making in
treatment after a first-time anterior glenohumeral dislocation: A
Delphi approach by the Neer Circle of the American Shoulder
and Elbow Surgeons. J Shoulder Elbow Surg 2020;29(12):2429-2445.
A survey of 72 experts from the Neer Circle using the Delphi
process found minimal consensus for recommending treatment
of the patients with a first-time anterior dislocation. Level of
evidence: V.
55. Minkus M, Konigshausen M, Maier D, et al: Immobilization in
external rotation and abduction versus arthroscopic stabilization
after first-time anterior shoulder dislocation: A multicenter
randomized controlled trial. Am J Sports Med 2021;49(4):857-865.
A randomized controlled trial of immobilization versus
arthroscopic repair of patients with first-time anterior
dislocations without bone loss showed no difference in functional
outcomes but a significantly higher rate of recurrence (19.1%
versus 2.3%) in the nonsurgical group. Level of evidence: I.
56. Yapp LZ, Nicholson JA, Robinson CM: Primary arthroscopic
stabilization for a first-time anterior dislocation of the shoulder:
Long-term follow-up of a randomized, double-blinded trial. J
Bone Joint Surg Am 2020;102(6): 460-467. A randomized
controlled trial compared arthroscopic washout versus Bankart
repair in patients with first-time anterior dislocations without
bone loss. At 10-year follow-up, the sham surgery group had
lower Western Ontario Shoulder Instability Index scores and
higher rates of recurrent instability and further surgery. Level of
evidence: I.
57. Dekker TJ, Peebles LA, Bernhardson AS, et al: Limited
predictive value of the instability severity index score: Evaluation
of 217 consecutive cases of recurrent anterior shoulder instability.
Arthroscopy 2021;37(5):1381-1391. A retrospective review of 217
consecutive patients undergoing arthroscopic stabilization for
recurrent anterior instability is presented. The authors describe a
failure rate of 11.5%, which correlated with glenoid bone loss
>14.5% and Hill-Sachs volume >1.3 cm3. There was no association
with the Instability Severity Index Score and failure. Level of
evidence: III.
58. Bo oni CR, Johnson JD, Zhou L, et al: Arthroscopic versus open
anterior shoulder stabilization: A prospective randomized
clinical trial with 15-year follow-up with an assessment of the
glenoid being “On-Track” and “Off-Track” as a predictor of
failure. Am J Sports Med 2021;49(8): 1999-2005. A 15-year follow-
up analysis of a randomized controlled trial comparing
 arthroscopic with open stabilization suggested higher failure
rates with off-track lesions. Level of evidence: I.
59. Imam MA, Shehata MSA, Martin A, et al: Bankart repair versus
Latarjet procedure for recurrent anterior shoulder instability: A
systematic review and meta-analysis of 3275 shoulders. Am J
Sports Med 2021;49(7):1945-1953. A systematic review and meta-
analysis compared Bankart repair with Latarjet procedure for
recurrent anterior instability showing a lower risk of recurrence
but more complications with the Latarjet procedure and no
difference in clinical outcomes. Level of evidence: IV.
60. Di Giacomo G, Peebles LA, Midtgaard KS, de Gasperis N, Scarso
P, Provencher CMT: Risk factors for recurrent anterior
glenohumeral instability and clinical failure following primary
latarjet procedures: An analysis of 344 patients. J Bone Joint Surg
Am 2020;102(19):1665-1671. A retrospective review found
atraumatic dislocation, bilateral instability, and female sex to be
risk factors for recurrence or clinical failure. Level of evidence: IV.
61. Hendy BA, Padegimas EM, Kane L, et al: Early postoperative
complications after Latarjet procedure: A single-institution
experience over 10 years. J Shoulder Elbow Surg 2021;30(6):e300-
e308. A retrospective review of 190 Latarjet procedures noted a
9% 90-day complication rate and 4.2% revision surgery rate.
Fixation with only one screw and increased screw divergence
angle were associated with graft failure. Level of evidence: IV.
62. MacDonald P, McRae S, Old J, et al: Arthroscopic Bankart repair
with and without arthroscopic infraspinatus remplissage in
anterior shoulder instability with a Hill-Sachs defect: A
randomized controlled trial. J Shoulder Elbow Surg
2021;30(6):1288-1298. A randomized controlled trial showed
significantly greater risk of recurrent instability in those who did
not have a remplissage procedure in conjunction with an
arthroscopic Bankart repair with any size Hill-Sachs lesion and
minimal glenoid bone loss (<15%). Level of evidence: I.
63. Hurley ET, Toale JP, Davey MS, et al: Remplissage for anterior
shoulder instability with Hill-Sachs lesions: A systematic review
and meta-analysis. J Shoulder Elbow Surg 2020;29(12):2487-2494. A
systematic review of 12 trials found that those patients with Hill-
Sachs lesions and subcritical glenoid bone loss have lower rates
of recurrent instability with Bankart and remplissage compared
with Bankart repair alone. Bankart repair and remplissage
resulted in similar recurrence rates and outcomes but lower
morbidity and few complications compared with the Latarjet
procedure. Level of evidence: III.
64. Lee J, Woodmass JM, Bernard CD, et al: Nonoperative
management of posterior shoulder instability: What are the long-
term clinical outcomes? Clin J Sport Med 2022;32(2):e116-e120. A
retrospective review is presented of those treated nonsurgically
for posterior instability at minimum 5-year follow-up.
Symptomatic arthritis was seen in 8% of patients. Level of
evidence: IV.
65. Gouveia K, Kay J, Memon M, Simunovic N, Bedi A, Ayeni OR:
Return to sport after surgical management of posterior shoulder
instability: A systematic review and meta-analysis. Am J Sports
Med 2022;50(3):845-857. A systematic review and meta-analysis of
32 studies showed 88% return to sport with 68% at preinjury level
after surgical intervention for posterior instability. Level of
evidence: IV.
66. Arner JW, Ruzbarsky JJ, Midtgaard K, Peebles L, Bradley JP,
Provencher MT: Defining critical glenoid bone loss in posterior
shoulder capsulolabral repair. Am J Sports Med 2021;49(8):2013-
2019. A retrospective case-control study found a tenfold higher
rate of surgical failure with 11% posterior glenoid bone loss in
those with posterior instability. Level of evidence: III.
67. Neer CSII, Foster CR: Inferior capsular shift for involuntary
inferior and multidirectional instability of the shoulder. A
preliminary report. J Bone Joint Surg Am 1980;62(6):897-908.
68. Lippi S, Matsen F: Mechanisms of glenohumeral joint stability.
Clin Orthop Relat Res 1993;291:20-28.
69. Watson L, Balster S, Lenssen R, Hoy G, Pizzari T: The effects of a
conservative rehabilitation program for multidirectional
instability of the shoulder. J Shoulder Elbow Surg 2018;27(1):104-
111.
70. Wall A, McGonigle O, Gill TJ: Arthroscopic circumferential
labral repair for patients with multidirectional instability: A
comparative outcome study. Orthop J Sports Med
2019;7(12):2325967119890103. A retrospective cohort study of 36
shoulders undergoing 360° labral repair matched to 31 patients
with anterior labral repair showed no difference in outcomes.
Level of evidence: III.
71. Kowalczuk M, Rubinger L, Elmaraghy AW: Pectoralis major
ruptures: Tear pa erns and patient demographic characteristics.
Orthop J Sports Med 2020;8(12):2325967120969424. A retrospective
case series of 104 pectoralis major ruptures showed 94% to occur
at the musculotendinous junction and tendinous insertion.
Chronic tears accounted for 64% of cases but a graft was only
required in four cases. Level of evidence: IV.
72. Gupton M, Johnson JE: Surgical treatment of pectoralis major
muscle ruptures: A systematic review and meta-analysis. Orthop J
Sports Med 2019;7(2):2325967118824551. A systematic review and
meta-analysis of pectoralis major ruptures showed equivalent
outcomes for transosseous, unicortical bu on, and suture anchor
techniques. Level of evidence: IV.
73. Yu J, Zhang C, Horner N, et al: Outcomes and return to sport
after pectoralis major tendon repair: A systematic review. Sports
Health 2019;11(2):134-141. A systematic review and meta-analysis
showed a return to sport rate of 90% at a mean of 6.1 months
postoperatively after pectoralis major repair. Level of evidence:
IV.
C H AP T E R 2 9

Shoulder Arthritis and

Arthroplasty
Melissa A. Wright MD, Anand M. Murthi MD, FAAOS

Dr. Wright or an immediate family member has received research or institutional support from
Zimmer and serves as a board member, owner, officer, or committee member of American Shoulder
and Elbow Surgeons. Dr. Murthi or an immediate family member has received royalties from
Aevumed, DePuy, a Johnson & Johnson Company, Globus Medical, and Ignite Orthopaedics;
serves as a paid consultant to or is an employee of Aevumed, DePuy, a Johnson & Johnson
Company, Globus Medical, Ignite Orthopaedics, Immertec, WRS-Work Rehabilitation Solutions,
and Zimmer; has stock or stock options held in Aevumed, Catalyst Orthoscience, Ignite
Orthopaedics, and VTail; has received research or institutional support from Catalyst, Stryker,
and Zimmer; and serves as a board member, owner, officer, or committee member of American
Academy of Orthopaedic Surgeons, American Shoulder and Elbow Surgeons, Association of
Clinical Elbow and Shoulder Surgeons, and MidAtlantic Shoulder and Elbow Society.

ABSTRACT
There are numerous causes and disease processes that lead to
symptomatic degenerative joint disease about the shoulder.
Common disorders include acromioclavicular joint arthritis,
glenohumeral joint osteoarthritis, inflammatory arthritis,
osteonecrosis, instability arthropathy, pos raumatic arthropathy,
and rotator cuff arthropathy. Each disorder has characteristic
presentations, examination findings, radiographic characteristics,
and treatment strategies. The past decade has seen great strides in
diagnostics, preoperative planning, and implant designs. With the
increase in both anatomic and reverse shoulder replacement, care
with surgical planning and indications will lead to fewer
complications and be er outcomes.
Keywords: acromioclavicular; arthroplasty; pos raumatic;
rheumatoid; shoulder arthritis

Introduction
Shoulder reconstruction has advanced significantly over the past
decade, with improved anatomic shoulder arthroplasty designs, the
expanded use of reverse shoulder arthroplasty (RSA), and a be er
understanding of arthroplasty fixation and failure. Understanding
the many etiologies of arthrosis about the shoulder helps the
surgeon guide treatment and plan proper surgical approaches for
good patient outcomes.

Arthritis of the Acromioclavicular Joint

Arthritis of the acromioclavicular (AC) joint is a common cause of
anterior and superior shoulder pain and often exists in conjunction
with other shoulder pathology. Radiographic changes do not always
correlate with clinical symptomatology, and the symptoms of AC
joint arthritis are largely nonspecific. Incidentally identified AC
joint arthritis does not require treatment. A 2019 study of 114
patients with degenerative changes of the AC joint on MRI found
that 90% remained asymptomatic over 7 years. 1 A careful physical
examination including visual inspection, palpation, and provocative
maneuvers alone can help identify clinically relevant AC joint
arthritis. The cross-body adduction stress test is the most sensitive
for AC joint arthritis (77%), whereas the O’Brien active
compression test is most specific (95%). 2 Radiographic imaging is
sufficient to diagnose AC joint arthritis. The joint can be visualized
on chest radiographs and standard shoulder radiographs. However,
the AC joint is best visualized on the Zanca view (10° to 15°
cephalad tilt and 50% penetration). 3
For symptomatic AC joint arthritis, treatment begins with
nonsurgical modalities such as activity modification, NSAIDs, and
cortisone injections. A 2021 scoping review a empted to compare
differences in outcome after surgical and nonsurgical management
of AC joint arthritis and found no comparative studies. Fifteen
studies of surgical management and four of nonsurgical
management found improvement in patient-reported outcomes,
with low complication rates across all studies. 4
Surgical intervention for symptomatic AC joint arthritis involves
distal clavicle excision (DCE), which can be performed
arthroscopically or open. A systematic review of 17 studies
comparing open versus arthroscopic DCE found no difference in
patient-reported outcome scores, with possible faster return to
activities after arthroscopic DCE if performed in isolation. 5 The
goal of DCE is to remove the pathology while minimizing
destruction of the joint capsule and risk of instability. Safe
resection length varies based on the individual, but should be less
than 10 mm. Persistent pain, the most common complication after
DCE, can be related to either inadequate resection or overresection
and subsequent instability.
DCE is often performed in conjunction with rotator cuff repair
(RCR). A systematic review evaluated patients undergoing
arthroscopic RCR with and without DCE and found no difference in
patient-reported outcomes, range of motion, pain, or repeat surgery
between the groups. 6 Additionally, there is low risk (1.1%) of
repeat surgery to perform DCE after RCR if not performed initially,
and therefore routine DCE is not recommended with RCR unless
the patient is specifically symptomatic at the AC joint. 7

Arthritis of the Glenohumeral Joint

Numerous disease processes and injury pa erns can result in a
degenerative glenohumeral joint. The most common disorders
include osteoarthritis, inflammatory arthritis, osteonecrosis, rotator
cuff arthropathy (RCA), pos raumatic arthritis, and
postcapsulorrhaphy arthropathy. Each disorder has characteristic
presentations, examination findings, radiographic characteristics,
and treatment strategies.
 Osteoarthritis is the most common degenerative process in the
shoulder. 8 Classic presentation includes progressive atraumatic
pain, loss of motion, morning stiffness, and a concomitant loss of
strength. Radiographic signs of glenohumeral osteoarthritis include
osteophyte formation, loss of joint space, subchondral sclerosis,
and osseous cyst formation (Figure 1, A). Posterior glenoid wear
and posterior humeral head subluxation are common in later stages
of the disease. Surgical treatment includes arthroscopic
débridement, capsular release, surface replacement or
hemiarthroplasty, and total shoulder arthroplasty (TSA) (reverse
and anatomic).

Figure 1 True AP radiographs demonstrating the classic findings of

glenohumeral osteoarthritis (A), inflammatory arthritis (B), rotator cuff
arthropathy (C), and osteonecrosis (D).

Inflammatory arthritis, most commonly rheumatoid arthritis, is

an inflammatory process characterized by a synovial disease that
erodes the glenohumeral articulation. 9 Painful motion,
polyarticular disease, and loss of motion are common. The
radiographic findings include periarticular erosions, subchondral
cysts, osteopenia, and central glenoid wear, with medialization of
the humeral head in advanced disease (Figure 1, B). The physician
must be aware of the possible coexistence of joint infection because
these patients are often on immunosuppressive medication and the
clinical manifestations of rheumatoid arthritis are similar to those
of infectious arthritis. Patients with rheumatoid arthritis and
preserved joint space may benefit from arthroscopic synovectomy,
whereas those with later-stage disease benefit from arthroplasty.
RCA describes a particular type of glenohumeral arthritis that
develops in the se ing of a massive chronic rotator cuff tear.
Patients often have pseudoparalysis, with li le active elevation or
abduction of the shoulder. Radiographs demonstrate proximal
migration of the humeral head and superior glenoid wear with loss
of glenohumeral joint space (Figure 1, C). Acetabularization of the
acromion can occur with end-stage RCA. Treatment for RCA was
revolutionized by the development of the RSA.
Osteonecrosis is a less frequent disease of the shoulder, often
found in younger patients with deep, unexplained shoulder pain. It
may be idiopathic or pos raumatic, or it may result from steroid
usage, alcoholism, sickle cell disease, lupus, vascular compromise,
and chemotherapy or irradiation. 10 Disruption of the vascular
supply to the humeral head leads to cartilage collapse and a loss of
normal glenohumeral congruity, with subsequent pain, stiffness,
and advanced glenohumeral arthritis (Figure 1, D). Treatment is
guided by assessment of the etiology of the osteonecrosis and
reversal of the offending cause, if possible, followed by
radiographic assessment of subchondral collapse and glenoid
involvement. Classification is based on a modified Ficat scheme.
Core decompression is performed as an early intervention before
significant subchondral collapse, whereas hemiarthroplasty may
benefit patients with unipolar disease, and TSA is reserved for
shoulders in which the glenoid has become involved. 10
Pos raumatic arthritis is a mixed group of disorders resulting
from osseous, cartilaginous, or soft-tissue trauma. Tuberosity
malunion, intra-articular fractures, and iatrogenic injury secondary
to stabilization procedures (postcapsulorrhaphy) all can lead to
glenohumeral arthrosis. Severe stiffness, particularly in external
rotation, is noted in these conditions.

Presentation and Evaluation

The patient with significant glenohumeral arthritis usually presents
with pain and loss of function. The history should include a
description of the onset of the problem, any injuries, previous
surgeries, a empts at nonsurgical management, and the nature and
progression of functional difficulties. Systemic or polyarticular
manifestations of sepsis, degenerative joint disease, or rheumatoid
arthritis may provide helpful clues. A past history of steroid use or
alcohol abuse may suggest osteonecrosis, whereas past injury,
fractures, or stabilization surgery suggest pos raumatic or
postcapsulorrhaphy arthropathy.
Physical examination of the shoulder begins with a thorough
inspection for deformity, atrophy, scars, effusions, and swelling.
Palpation of bony prominences (AC joint), bicipital groove,
tuberosities, deltoid, and any areas of swelling is necessary.
Evaluating range of motion in all planes (forward elevation,
abduction, internal and external rotation), both passive and active,
helps differentiate acquired stiffness versus weakness, which may
indicate rotator cuff disease. Strength testing of the deltoid, rotator
cuff, and scapular stabilizers includes testing of subscapularis
function (lift-off, belly press, bear hug). Crepitus with motion is
common in degenerative joint disease. Finally, a thorough
neurovascular evaluation is performed, focusing on the axillary
nerve (deltoid strength and lateral deltoid sensation).

Radiographic Imaging
Standard views include an AP view in the plane of the scapula
(Grashey view), a standard AP view, scapular Y, and a true axillary
view (Figure 2). These views will show humeral head and glenoid
morphology, loss of glenohumeral joint space, and the relative
positions of the humeral head and glenoid. The presence of
osteophytes, deformity, subluxation, and erosion can be noted. A
chronic massive rotator cuff tear likely exists in the case of proximal
migration (Figure 1, C).
 Figure 2 True AP (A), AP (B), axillary (C), and scapular Y (D) views of the
shoulder are the four views typically obtained when performing a radiographic
evaluation of glenohumeral arthritis.

CT can be performed to quantify bone quality and geometry in

complex arthritis cases. The Walch classification of glenoid
morphology is based on wear pa erns and version and is best
assessed on CT scan (Figure 3). CT scans can also be used for three-
dimensional preoperative planning and the creation of patient-
specific implants.
 Figure 3 Illustrations of the glenohumeral joint demonstrating the Walch
classification, based on version and wear pattern.A, Type A1: centered humeral
head with minor concentric glenoid erosion. B, Type A2: centered humeral head
with major concentric glenoid erosion. C, Type B1: posterior humeral subluxation
with eccentric erosion. D, Type B2: posterior humeral subluxation with eccentric
erosion with a biconcave glenoid. E, Type C: severe retroversion greater than
25°.(Reprinted from Sears BW, Johnston PS, Ramsey ML, Williams GR:
Glenoid bone loss in primary total shoulder arthroplasty: Evaluation and
management. J Am Acad Orthop Surg 2012;20[9]:604-613.)

Imaging of the rotator cuff by MRI, CT arthrogram, or

ultrasonography is performed if it will affect patient management.
However, rotator cuff assessment from patient history, physical
examination, and radiographs is usually sufficient in the se ing of
glenohumeral arthrosis.

Nonsurgical Management
Nonsurgical management of glenohumeral arthritis is
recommended initially and includes activity modification, anti-
inflammatory medications, and physical therapy as first-line
treatment strategies. Physical therapy can preserve motion and
optimize function; however, a empts at therapy in the se ing of
substantial stiffness may worsen symptoms. Secondary treatment
strategies include corticosteroid injections, local analgesics, and
transdermal analgesics. Treatment options, such as acupuncture,
electrical stimulation, ultrasound therapy, and oral supplements,
may provide benefit but are not well studied. The use of disease-
modifying antirheumatic drugs has decreased the incidence of
shoulder arthroplasty in patients with rheumatoid/inflammatory
arthritis. 9

Joint-Preserving Treatment
Joint-preserving surgical treatment for shoulder arthritis is an
option for mild disease, especially in younger adults in whom
implant longevity is a concern or in situations in which the arthritis
is localized to a focal area of chondral loss. Cartilage-preserving
options include capsular release, glenohumeral débridement, and
synovectomy. Cartilage restoration procedures include
microfracture of focal chondral lesions, osteochondral autograft,
autologous chondrocyte implantation, osteochondral allograft, and
glenoid biologic resurfacing. A 2021 study showed good 10-year
follow-up in young patients with glenohumeral osteoarthritis who
underwent an arthroscopic comprehensive arthritis management
procedure, 11 which focuses on glenohumeral chondroplasty,
synovectomy, loose body removal, humeral osteoplasty with
excision of the inferior osteophyte, capsular release, subacromial
and subcoracoid decompression, axillary nerve decompression, and
biceps tenodesis. The survivorship rate at minimum 10-year follow-
up was 63.2%. 11

Hemiarthroplasty
Hemiarthroplasty was developed more than 50 years ago for the
management of nonreconstructible proximal humeral fractures. 12
The current indications for hemiarthroplasty include treatment of
primary glenohumeral osteoarthritis in younger adults in whom the
longevity of a glenoid component is of concern, arthritic conditions
with inadequate glenoid bone stock, rotator cuff tear arthropathy,
inflammatory arthropathy, and osteonecrosis of the humeral head
without secondary involvement of the glenoid.
Hemiarthroplasty must be indicated carefully as studies show
improved survivorship with TSA as well as superior pain relief. 13
One study of patients younger than 55 years with 10-year follow-up
demonstrated 92% implant survival with TSA compared with 72%
for hemiarthroplasty. 14 Clinical success and survivorship of
hemiarthroplasty are likely affected by patient-specific factors
including glenoid morphology.
Hemiarthroplasty with concentric reaming of the glenoid, known
as ream and run, is also an option, but studies demonstrate that
men older than 60 years have be er results than younger adults,
and pain relief is delayed up to 1.5 years postoperatively. 15
Hemiarthroplasty with biologic glenoid resurfacing has shown
favorable short-term results but up to 30% revision rates. 16

Total Shoulder Arthroplasty

Indications and Outcomes
TSA is the most effective surgical treatment for end-stage
glenohumeral arthritis, with more than 95% of patients obtaining
symptomatic relief. TSA rates continue to increase in the United
States, doubling in frequency every 7 years, with TSA survivorship
now greater than 85% at 15-year follow-up. 17 Indications for TSA
include glenohumeral osteoarthritis, inflammatory arthropathy
with an intact rotator cuff, postcapsulorrhaphy arthritis, and failed
hemiarthroplasty. Contraindications include an irreparable rotator
cuff tear, RCA, infection, and neurologic dysfunction.

Implants and Technical Considerations

Reconstruction of the osteoarthritic shoulder a empts to re-create
bony anatomy to restore biomechanics and soft-tissue balance.
Many glenoid component designs exist, with varying degrees of
clinical evidence. A review of more than 1,500 TSAs demonstrated
that cemented all-polyethylene pegged glenoid components had
the lowest revision rate compared with cemented keeled and metal-
backed designs. 18 Newer pegged implants are often designed to
promote biologic osseous fixation around a central polyethylene
peg with deep flanges, but the long-term advantages over a full
cementation technique are unknown.
Advanced glenoid retroversion and posterior wear are difficult to
manage during TSA because of the competition between creating a
balanced joint with version correction and jeopardizing glenoid
component implantation if too much bone is removed. Clinical
studies have shown that correcting retroversion of more than 10°
has a failure rate greater than 40%. 19 Posterior humeral subluxation
is associated with biconcave glenoid wear and also correlates with
poor results. 20 The management of glenoid osseous defects and
retroversion is controversial. Although eccentric, or high side,
reaming is commonly used to address minor version corrections,
there are no clear guidelines regarding the amount of glenoid
version that can safely be corrected. Options other than eccentric
reaming to manage posterior glenoid bone loss include structural
glenoid bone grafting and augmented glenoid components. Recent
studies have shown both short- and intermediate-term good clinical
outcomes using augmented glenoids for deformity and subluxation
correction. 19 Long-term durability remains to be seen.
Glenoid dysplasia is characterized by more than 25° of
retroversion and is commonly associated with dysplastic
development. The dysplastic articulation often maintains stability
through hypertrophy of the posterior soft tissues. TSA can be a
viable option for managing painful dysplasia, but hemiarthroplasty
is used if the glenoid bone stock will not support an implant.
Humeral stem designs are evolving to preserve proximal
metaphyseal bone and increase implant longevity through osseous
ingrowth. Press-fit stems have loosening rates of 5% to 10%, and the
use of proximal ingrowth stems has improved these rates at
midterm follow-up. 21 Ingrowth stems have the disadvantages of
stress shielding, proximal bone resorption, and difficult revision
because of secure ingrowth. Stemless humeral implantation is
another option (Figure 4). One study found excellent short-term
clinical outcomes in a prospective trial of stemless implants. 22 A
2021 study also demonstrated good results with an anatomic
stemless shoulder prosthesis with no clinical differences compared
with a stemmed prosthesis over a mean of 10 years, although
differences in the pa ern of periprosthetic humeral bone
adaptations were noted. 23 Bone-preserving stemless implants
require less surgical time and potentially less blood loss. Revision
surgery may require less bone removal. 24 A surgeon’s choice of a
stemmed or stemless humeral implant should be based on surgical
reproduction of the anatomy and implantation of a stable
prosthesis.

Figure 4 True AP view of stemless (A) and stemmed (B) components used in
total shoulder arthroplasty.

As described in a 2021 study, an anatomic total shoulder

arthroplasty using a stem-free ellipsoid humeral implant has been
developed to create an anatomic chamfer cut-based humeral
replacement. Careful positioning is crucial to prevent overstuffing
the glenohumeral joint, which can result in pain, stiffness, and
rotator cuff dysfunction. At 2-year minimum follow-up, this stem-
free ellipsoid humeral component provides very good results with
high patient satisfaction, clinical improvement in all outcome
measures studied, and no signs of loosening. 25
Computer-assisted or computer-navigated TSA may play a role in
the optimization of component positioning. Trials comparing
glenoid component positioning using patient-specific instruments
versus standard surgical instruments are ongoing.

Reverse Shoulder Arthroplasty

Indications and Outcomes
The modern-day RSA was developed in the 1980s for the
management of RCA. By distalizing and medializing the center of
rotation and using a constrained prosthesis, these implants harness
the deltoid for active forward elevation in rotator cuff-deficient
patients. RSA was approved for use in the United States in 2003 and
has become increasingly popular, with recent studies
demonstrating the long-term reliability of RSA for RCA with a
revision rate of only 8.5% at 10 years in one registry study. 26 Given
its early success, the indications for RSA have expanded.
RSA for primary glenohumeral osteoarthritis has been used in
elderly populations at risk for rotator cuff dysfunction and early
failure following TSA. In a 2020 study of 135 patients older than 70
years undergoing TSA or RSA, there were no differences in patient-
reported outcomes but a revision rate of 3.0% in the RSA group
compared with 6.9% in the TSA group. 27 The use of RSA for
primary glenohumeral osteoarthritis in individuals with significant
glenoid bone loss and/or posterior subluxation has also increased
because of the more secure screw fixation of the metal glenoid
baseplate in RSA. A recent midterm study found good clinical
outcomes and 96% implant survival at minimum 5-year follow-up in
49 shoulders that underwent RSA for primary glenohumeral
osteoarthritis with Walch B and C type glenoids. 28
 The use of RSA for proximal humerus fractures and fracture
sequelae has expanded in recent years. RSA has overtaken
hemiarthroplasty as the preferred method of arthroplasty for most
proximal humerus fractures requiring surgical intervention,
because RSA is less reliant on anatomic tuberosity healing for a
reasonable functional outcome. Comparisons of RSA with
nonsurgical management have been less clearly in favor of RSA,
with a 2019 study finding only a benefit in early pain relief in the
RSA group compared with nonsurgical management. 29 Further
understanding of the specific indications for RSA in the
management of proximal humerus fractures is needed.
Finally, the use of RSA for revision shoulder arthroplasty has
continued to grow. In a 2020 analysis of 542 failed arthroplasties
over 20 years, RSA was the most common final revision implant
(48% of shoulders). 30 Although RSA is a reliable option for failed
shoulder arthroplasty, and can likely offer the best solution in many
situations, RSA in the revision se ing does not perform as well as
primary RSA, with lower subjective shoulder values and a higher
rate of complications. 31

Implant Innovation and Surgical Techniques

With the growing use and expanding indications for RSA since its
approval in the United States in 2003, there has been increased
consideration of implant design and how design can be tailored to
improve patient outcomes.
Decreasing the humeral neck-shaft angle in RSA from the initial
155° to a more anatomic 135° reduced the rate of scapular notching
from 58% to 21% in one prospective randomized controlled trial of
primary RSA. 32 A 2021 computational modeling study compared
the effect of humeral neck-shaft angle, humeral inlay/onlay, glenoid
lateralization, and glenoid eccentricity on glenohumeral range of
motion and found that humeral changes had no effect on global
range of motion but altered the balance between
adduction/abduction and internal/external rotation. 33
Clinical
studies have similarly shown no difference in range of motion or
pain between inlay and onlay humeral implants, but there are
concerns about an increased scapular spine fracture rate with onlay
implants, due to the increased distalization. 34
Glenoid implant design in RSA has also evolved, improving
motion and stability while decreasing complications such as
notching and stress fracture. In the 2021 computer modeling study
described previously, only glenoid lateralization was able to
increase the global glenohumeral range of motion. 33 Clinically,
modern laterally offset glenospheres have demonstrated excellent
patient-reported outcomes with good range of motion and minimal
scapular notching. A 2021 systematic review of 16 clinical studies
comparing a traditional Grammont-style RSA with a lateralized
glenosphere found no difference in clinical outcomes with lower
notching and complication rates in the lateralized RSAs. 35 Glenoid
lateralization may improve implant stability and promote active
external rotation, but it may come with an increased risk of
acromial stress fracture (3.8% versus 2.5% with traditional
medialized implants in one study). 36
The BIO-RSA uses a bone graft to provide lateralization of the
glenosphere in an a empt to decrease notching and improve
motion and stability similar to other lateralized glenospheres. Five-
to 10-year follow-up of 143 patients undergoing a BIO-RSA
procedure found an 83% rate of satisfaction and graft incorporation
in 96% of patients. Only 18% of patients had severe grade scapular
notching. 37
Metal-augmented glenoid baseplates have been developed to not
just allow for lateralization but also correct bony deformity,
version, and inclination through the use of full and half wedges of
various degrees. The limited literature regarding these implants has
generally shown good short-term outcomes. One study of 44
patients undergoing RSA with an augmented baseplate found good
clinical outcomes with improved version from an average 28° to 16°.
There were no cases of baseplate loosening or failure, but there was
a high rate of acromial stress fracture (11.4%). 38 Continued study of
these implants is needed.

Complications After Shoulder Arthroplasty

Although both TSA and RSA provide clear benefit to patients, they
are not without complications, and each implant type bears its own
unique set of potential problems. A large study of 542 failed
arthroplasties undergoing revision over 20 years found that the
overall revision rate for TSA was 6.7% with glenoid loosening the
most common cause, resulting in 37% of all TSA failures. 30 The
glenoid has long been considered the weak link in TSA, and
glenoid loosening remains the leading cause of TSA failure in many
studies regardless of glenoid backing and fixation. 6 , 30 Early small
studies of inset glenoid components have shown minimal glenoid
loosening but larger, long-term prospective studies are needed. 39
Rotator cuff failure is another leading complication and cause of
revision in TSA. 40 , 41 Isolated subscapularis deficiency is less
common than posterior superior rotator cuff failure but can cause
significant disability. Reported rates vary widely because not all
subscapularis deficiency is clinically significant. In one recent
single-institution study, subscapularis failure was responsible for
11% of revision TSA, with trauma cited as the cause in 36% of cases.
42

Infection occurs at a rate of less than 1% in both TSA and RSA. 40

Young, male patients are at highest risk for infection after primary
TSA. 43 Infection can be managed with a single-stage or two-stage
revision or definitively with an antibiotic spacer.
Complication and revision rates reported for RSAs tend to be
lower, although this may be in part due to limited revision options
after failed RSA. The aforementioned study of 542 failed
arthroplasties found that the overall revision rate for RSA was 3.9%,
with instability causing 32% of all RSA failures. 30 Young patients,
revision surgery, and tuberosity resorption increase the risk of
instability, whereas lateralized implants can reduce the risk. 44
Instability has been identified as the primary cause of revision RSA
in other large studies, with acromial and scapular spine fracture
identified as the leading complication. 41 A recent retrospective
multicenter study found a 3.9% rate of acromial and scapular spine
fractures among 6,755 RSAs, with increased risk in females and
those with osteoporosis, with inflammatory arthritis, or who
underwent RCA. 45
Notching is common after RSA and is associated with worse
patient-reported outcomes, function, and range of motion. 46 Care
with implant selection and surgical technique should be used to
reduce the risk of notching and other complications.

Summary
Degenerative joint disease at the shoulder can affect both the AC
and glenohumeral joints. Glenohumeral joint disease has a more
significant functional effect and can be due to numerous causes and
disease processes including osteoarthritis, inflammatory arthritis,
osteonecrosis, pos raumatic arthropathy, and RCA. Careful history
and physical examination with appropriate imaging is key to initial
evaluation. Nonsurgical treatment should be a empted first, and
there is a limited role for joint-preserving surgery in glenohumeral
arthropathy. Shoulder arthroplasty includes hemiarthroplasty,
anatomic TSA, and RSA, each with unique indications, technique
pearls, expected outcomes, and complications. New implant
designs in both TSA and RSA over the past decade may improve
outcomes and limit complications.

Key Study Points

Primary glenohumeral arthritis is very common and successfully managed with TSA
using stemmed and stemless implants.
RSA is growing in popularity for rotator cuff arthropathy and newer indications
including osteoarthritis, fracture, and failed prior arthroplasty.
Complications of shoulder arthroplasty can be mitigated with careful indications and
preoperative planning.
Annotated References
1. Frigg A, Song D, Willi J, Freiburghaus AU, Grehn H: Seven-year
course of asymptomatic acromioclavicular osteoarthritis
diagnosed by MRI. J Shoulder Elbow Surg 2019;28(10):e344-e351.
This retrospective cohort study of 114 patients found that
asymptomatic AC joint arthritis remained asymptomatic in 90%
of cases over 7 years. Level of evidence: III.
2. Chronopoulos E, Kim TK, Park HB, Ashenbrenner D, McFarland
EG: Diagnostic value of physical tests for isolated chronic
acromioclavicular lesions. Am J Sports Med 2004;32(3):655-661.
3. Zanca P: Shoulder pain: Involvement of the acromioclavicular
joint. (Analysis of 1,000 cases). Am J Roentgenol Radium Ther Nucl
Med 1971;112(3):493-506.
4. Soler F, Mocini F, Djemeto DT, Ca aneo S, Saccomanno MF,
Milano G: No differences between conservative and surgical
management of acromioclavicular joint osteoarthritis: A scoping
review. Knee Surg Sports Traumatol Arthrosc 2021;29(7):2194-2201.
This scoping review of 19 studies and 861 shoulders found no
direct comparison studies between surgical and nonsurgical
treatment for AC joint arthritis, but studies of each treatment
individually found both to be effective treatment options. Level
of evidence: IV.
5. Pensak M, Grumet RC, Slabaugh MA, Bach BRJr: Open versus
arthroscopic distal clavicle resection. Arthroscopy 2010;26(5):697-
704.
6. Wang J, Ma JX, Zhu SW, Jia HB, Ma XL: Does distal clavicle
resection decrease pain or improve shoulder function in patients
with acromioclavicular joint arthritis and rotator cuff tears? A
meta-analysis. Clin Orthop Relat Res 2018;476(12):2402-2414.
7. Chalmers PN, Granger E, Ross H, Burks RT, Tashjian RZ:
Preoperative factors associated with subsequent distal clavicle
 resection after rotator cuff repair. Orthop J Sports Med
2019;7(5):2325967119844295. This retrospective study of 894
patients found that only 1.1% of patients undergoing RCR
required subsequent DCE, with females, those with AC joint
pain, and those having surgery on their dominant arm at higher
risk. Level of evidence: III.
8. Khazzam M, Gee AO, Pearl M: Management of glenohumeral
joint osteoarthritis. J Am Acad Orthop Surg 2020;28(19):781-789.
9. Tehlirian CV, Bathon JM: Rheumatoid arthritis, in Klippel JH,
Stone JH, Crofford LJ, eds: Primer on Rheumatic Diseases, ed 13.
Springer, 2008, pp 114-141.
10. Franceschi F, Francesche i E, Pacio i M, et al: Surgical
management of osteonecrosis of the humeral head: A systematic
review. Knee Surg Sports Traumatol Arthrosc 2017;25(10):3270-3278.
11. Arner JW, Elrick BP, Nolte PC, Haber DB, Horan MP, Mille PJ:
Survivorship and patient-reported outcomes after comprehensive
arthroscopic management of glenohumeral osteoarthritis:
Minimum 10-year follow-up. Am J Sports Med 2021;49(1):130-136.
This retrospective study of 38 patients undergoing
comprehensive arthroscopic management procedures for
glenohumeral osteoarthritis found a 10-year procedure survival of
63.2%, with severe joint congruity a predictor of need for
arthroplasty. Level of evidence: III.
12. Neer CS II: The classic: Articular replacement for the humeral
head. 1955. Clin Orthop Relat Res 2011;469(9):2409-2421.
13. Radnay CS, Se er KJ, Chambers L, Levine WN, Bigliani LU,
Ahmad CS: Total shoulder replacement compared with humeral
head replacement for the treatment of primary glenohumeral
osteoarthritis: A systematic review. J Shoulder Elbow Surg
2007;16(4):396-402.
14. Bartelt R, Sperling JW, Schleck CD, Cofield RH: Shoulder
arthroplasty in patients aged fifty-five years or younger with
osteoarthritis. J Shoulder Elbow Surg 2011;20(1):123-130.
15. Gilmer BB, Comstock BA, Je e JL, Warme WJ, Jackins SE,
Matsen FA: The prognosis for improvement in comfort and
function after the ream-and-run arthroplasty for glenohumeral
arthritis: An analysis of 176 consecutive cases. J Bone Joint Surg
Am 2012;94(14):e102.
16. Meaike JJ, Pa erson DC, Anthony SG, Parsons BO, Cagle PJ:
Soft tissue resurfacing for glenohumeral arthritis: A systematic
review. Shoulder Elbow 2020;12(1):3-11. This systematic review of
11 studies of biologic resurfacing of the glenoid with a metallic
humeral component found improvements in pain and motion at
a minimum of 2 years but a high rate of complications and
revision. Level of evidence: III.
17. Weatherby PJ, Efejuku TA, Somerson JS: Complications after
anatomic shoulder arthroplasty: Revisiting leading causes of
failure. Orthop Clin North Am 2021;52(3):269-277. This review
explored the changing complication profile of anatomic shoulder
arthroplasty including the decline in the relative rate of glenoid
loosening and rise in rotator cuff insufficiency. Level of evidence:
V.
18. Fox TJ, Cil A, Sperling JW, Sanchez-Sotelo J, Schleck CD,
Cofield RH: Survival of the glenoid component in shoulder
arthroplasty. J Shoulder Elbow Surg 2009;18(6):859-863.
19. Ianno i JP, Jun BJ, Derwin KA, Ricche i ET: Stepped
augmented glenoid component in anatomic total shoulder
arthroplasty for B2 and B3 glenoid pathology: A study of early
outcomes. J Bone Joint Surg Am 2021;103(19):1798-1806. This
prospective study of 92 patients undergoing anatomic TSA with a
stepped augmented glenoid found restoration of native anatomy
with good short-term clinical and radiographic outcomes. Level
of evidence: II.
20. Ianno i JP, Norris TR: Influence of preoperative factors on
outcome of shoulder arthroplasty for glenohumeral
osteoarthritis. J Bone Joint Surg Am 2003;85(2):251-258.
21. Throckmorton TW, Zarkadas PC, Sperling JW, Cofield RH:
Radiographic stability of ingrowth humeral stems in total
shoulder arthroplasty. Clin Orthop Relat Res 2010;468(8):2122-
2128.
22. Churchill RS, Chuinard C, Wiater JM, et al: Clinical and
radiographic outcomes of the simpliciti canal-sparing shoulder
arthroplasty system: A prospective two-year multicenter study. J
Bone Joint Surg Am 2016;98(7):552-560.
23. Martens N, Heinze M, Awiszus F, Bertrand J, Lohmann CH,
Berth A: Long-term survival and failure analysis of anatomical
stemmed and stemless shoulder arthroplasties. Bone Joint J
2021;103-B(7):1292-1300. This retrospective study of 161 patients
found no difference in clinical or radiographic outcomes between
TSA with stemmed versus stemless humeral components at 10
years. Level of evidence: IV.
24. Holschen M, Frane ki B, Wi KA, Liem D, Steinbeck J: Is
reverse total shoulder arthroplasty a feasible treatment option for
failed shoulder arthroplasty? A retrospective study of 44 cases
with special regards to stemless and stemmed primary implants.
Musculoskelet Surg 2017;101(2):173-180.
25. Goldberg SS, Baranek ES, Korbel KC, Blaine TA, Levine WN:
Anatomic total shoulder arthroplasty using a stem-free ellipsoid
humeral implant in patients of all ages. J Shoulder Elbow Surg
2021;30(9):e572-e582. This retrospective case series of 63
shoulders undergoing shoulder arthroplasty with an ellipsoid
stem-free humeral prosthesis found high satisfaction, good
clinical improvement, and no radiographic loosening at
minimum 2-year follow-up. Level of evidence: IV.
26. Baram A, Ammi boell M, Brorson S, Olsen BS, Amundsen A,
Rasmussen JV: What factors are associated with revision or worse
patient-reported outcome after reverse shoulder arthroplasty for
cuff-tear arthropathy? A study from the Danish shoulder
arthroplasty registry. Clin Orthop Relat Res 2020;478(5):1089-1097.
This Danish Shoulder Arthroplasty Registry study found a
 cumulative 10-year revision rate of 8.5% for RSA performed for
RCA and identified risk factors for revision. Level of evidence:
III.
27. Wright MA, Keener JD, Chamberlain AM: Comparison of
clinical outcomes after anatomic total shoulder arthroplasty and
reverse shoulder arthroplasty in patients 70 years and older with
glenohumeral osteoarthritis and an intact rotator cuff. J Am Acad
Orthop Surg 2020;28(5):e222-e229. This retrospective cohort of 135
patients older than 70 years undergoing reverse or anatomic
shoulder arthroplasty found good clinical outcomes with both
options but a higher revision rate with anatomic shoulder
arthroplasty. Level of evidence: III.
28. Collin P, Herve A, Walch G, Boileau P, Muniandy M, Chelli M:
Mid-term results of reverse shoulder arthroplasty for
glenohumeral osteoarthritis with posterior glenoid deficiency
and humeral subluxation. J Shoulder Elbow Surg 2019;28(10):2023-
2030. This retrospective review of patients undergoing RSA for
glenohumeral osteoarthritis with Walch B and C glenoids found
excellent clinical outcomes at minimum 5 years postoperatively.
Level of evidence: IV.
29. Lopiz Y, Alcobia-Diaz B, Galan-Olleros M, Garcia-Fernandez C,
Picado AL, Marco F: Reverse shoulder arthroplasty versus
nonoperative treatment for 3- or 4-part proximal humeral
fractures in elderly patients: A prospective randomized
controlled trial. J Shoulder Elbow Surg 2019;28(12):2259-2271. This
randomized controlled trial of elderly patients with complex
proximal humerus fractures found only short-term pain relief to
be improved with RSA compared with nonsurgical treatment.
Level of evidence: I.
30. Gauci MO, Cavalier M, Gonzalez JF, et al: Revision of failed
shoulder arthroplasty: Epidemiology, etiology, and surgical
options. J Shoulder Elbow Surg 2020;29(3):541-549. This
retrospective review of 542 failed shoulder arthroplasties
identified glenoid failure and instability as the most common
 causes of revision, with RSA as the most common final implant.
Level of evidence: III.
31. Shields E, Wiater JM: Patient outcomes after revision of
anatomic total shoulder arthroplasty to reverse shoulder
arthroplasty for rotator cuff failure or component loosening: A
matched cohort study. J Am Acad Orthop Surg 2019;27(4):e193-
e198. This matched cohort study found that patients undergoing
revision of an anatomic TSA to reverse TSA had function
comparable with primary RSA but more complications. Level of
evidence: III.
32. Gobezie R, Shishani Y, Lederman E, Denard PJ: Can a functional
difference be detected in reverse arthroplasty with 135 degrees
versus 155 degrees prosthesis for the treatment of rotator cuff
arthropathy: A prospective randomized study. J Shoulder Elbow
Surg 2019;28(5):813-818. This randomized controlled trial of 100
patients undergoing RSA with a 135º or 155º humeral stem found
no difference in range of motion but less notching with the 135°
design. Level of evidence: I.
33. Arenas-Miquelez A, Murphy RJ, Rosa A, Caironi D, Zumstein
MA: Impact of humeral and glenoid component variations on
range of motion in reverse geometry total shoulder arthroplasty:
A standardized computer model study. J Shoulder Elbow Surg
2021;30(4):763-771. This three-dimensional computational
modeling study found that only lateralizing the glenosphere
increased the global range of motion of the shoulder in RSA.
Level of evidence: III.
34. Haidamous G, Ladermann A, Frankle MA, Gorman RA II,
Denard PJ: The risk of postoperative scapular spine fracture
following reverse shoulder arthroplasty is increased with an
onlay humeral stem. J Shoulder Elbow Surg 2020;29(12):2556-2563.
This multicenter retrospective review of RSA found that humeral
onlay stems led to a 10-mm increase in distalization and 2.5 times
increased risk of scapular fracture compared with inlay stems.
Level of evidence: IV.
35. Nunes B, Linhares D, Costa F, Neves N, Claro R, Silva MR:
Lateralized versus nonlateralized glenospheres in reverse
shoulder arthroplasty: A systematic review with meta-analysis. J
Shoulder Elbow Surg 2021;30(7):1700-1713. This systematic review
found a lower rate of scapular notching and complications in
lateralized RSAs compared with traditional Grammont-style
prostheses. Level of evidence: III.
36. King JJ, Dalton SS, Gulo a LV, Wright TW, Schoch BS: How
common are acromial and scapular spine fractures after reverse
shoulder arthroplasty? A systematic review. Bone Joint J 2019;101-
B(6):627-634. This systematic review of 90 articles found a 2.8%
rate of acromial and scapular spine fractures after RSA. Level of
evidence: III.
37. Boileau P, Morin-Salvo N, Bessiere C, Chelli M, Gauci MO,
Lemmex DB: Bony increased-offset-reverse shoulder arthroplasty:
5 to 10 years’ follow-up. J Shoulder Elbow Surg 2020;29(10):2111-
2122. In this cohort study of 142 patients, there were good clinical
and range of motion outcomes at 2 years after RSA with a bony
increased offset baseplate fixation technique. Level of evidence:
IV.
38. Kirsch JM, Patel M, Singh A, Lazarus MD, Williams GR,
Namdari S: Early clinical and radiographic outcomes of an
augmented baseplate in reverse shoulder arthroplasty for
glenohumeral arthritis with glenoid deformity. J Shoulder Elbow
Surg 2021;30(7 suppl):S123-S130. This retrospective study of 44
patients who underwent RSA with an augmented glenoid
baseplate had good deformity correction and clinical outcomes
but a high rate of acromial stress fracture. Level of evidence: IV.
39. Cvetanovich GL, Naylor AJ, O’Brien MC, Waterman BR, Garcia
GH, Nicholson GP: Anatomic total shoulder arthroplasty with an
inlay glenoid component: Clinical outcomes and return to
activity. J Shoulder Elbow Surg 2020;29(6):1188-1196. A
retrospective study of 27 shoulders that underwent anatomic
shoulder arthroplasty with an inlay glenoid component had
 improved clinical outcomes and no radiographic loosening at
short-term follow-up. Level of evidence: IV.
40. Aibinder W, Schoch B, Parsons M, et al: Risk factors for
complications and revision surgery after anatomic and reverse
total shoulder arthroplasty. J Shoulder Elbow Surg
2021;30(11):e689-e701. A large international database was used to
define complication and revision rates for anatomic shoulder
arthroplasty and RSA arthroplasty, as well as risk factors for
complications and revision. Level of evidence: IV.
41. Parada SA, Flurin PH, Wright TW, et al: Comparison of
complication types and rates associated with anatomic and
reverse total shoulder arthroplasty. J Shoulder Elbow Surg
2021;30(4):811-818. This large database analysis quantified
revision and complication rates for anatomic shoulder
arthroplasty and RSA. Level of evidence: IV.
42. Entezari V, Henry T, Zmistowski B, Sheth M, Nicholson T,
Namdari S: Clinically significant subscapularis failure after
anatomic shoulder arthroplasty: Is it worth repairing? J Shoulder
Elbow Surg 2020;29(9):1831-1835. This retrospective review of
patients undergoing revision surgery for subscapularis failure
after TSA found that those undergoing subscapularis repair were
younger and healthier than those revised to RSA, but both
groups did well. Level of evidence: IV.
43. Richards J, Inacio MC, Becke M, et al: Patient and procedure-
specific risk factors for deep infection after primary shoulder
arthroplasty. Clin Orthop Relat Res 2014;472(9):2809-2815.
44. Guarrella V, Chelli M, Domos P, Ascione F, Boileau P, Walch G:
Risk factors for instability after reverse shoulder arthroplasty.
Shoulder Elbow 2021;13(1):51-57. This retrospective multicenter
series of 1,035 RSAs found that younger patients are at higher
risk of instability and patients with lateralized implants are at
lower risk. Level of evidence: III.
45. ASES Complications of RSA Research Group, Mahendraraj KA,
Abboud J, et al: Predictors of acromial and scapular stress
 fracture after reverse shoulder arthroplasty: A study by the ASES
Complications of RSA Multicenter Research Group. J Shoulder
Elbow Surg 2021;30(10):2296-2305. A large multicenter
retrospective study of 6,755 RSAs identified a stress fracture
incidence of 3.9%, with female sex, massive rotator cuff tear
without arthritis, RCA, and osteoporosis all placing patients at
increased risk. Level of evidence: III.
46. Jang YH, Lee JH, Kim SH: Effect of scapular notching on clinical
outcomes after reverse total shoulder arthroplasty. Bone Joint J
2020;102-B(11):1438-1445. This meta-analysis of 11 studies found
that scapular notching is associated with worse clinical outcome
scores and range of motion following RSA. Level of evidence: III.
S E CT I ON 5

Elbow
SECTION EDITOR
Aaron M. Chamberlain, MD, MSc, MBA, FAAOS
C H AP T E R 3 0

Anatomy, Biomechanics,
Physical Examination, and
Imaging of the Elbow
Benjamin Zmistowski MD

Dr. Zmistowski or an immediate family member serves as a paid consultant to or is an employee of

Zimmer and serves as a board member, owner, officer, or committee member of American Shoulder
and Elbow Surgeons.

ABSTRACT
Recent additions to the knowledge of anatomy, biomechanics,
physical examination, and imaging of the elbow provide a be er
understanding of elbow pathology. These advances in knowledge
have the potential to lead to significant advances in treatment
strategies and techniques.
Keywords: biomechanics; CT; elbow; physical examination;
ultrasonography

Introduction
An understanding of the complex anatomy and mechanism for
stable motion of the elbow is critical to effective treatment. The
understanding of these concepts continues to evolve. Much of the
research focus for the elbow is currently on evolving diagnostic
imaging modalities. Where available, new evidence is summarized
and presented in the context of existing knowledge. Significant
research by the pioneers of elbow care provided the foundation for
elbow anatomy, biomechanics, and physical examination. More
recently, innovators in the field have adopted imaging modalities
for utilization in the elbow.

Anatomy

Bone Anatomy
Because of the highly congruous articulation of the ulna and the
trochlea of the humerus, there is significant inherent osseous
stability. The ulnohumeral congruency is exemplified by the 180°
arc of articular coverage (including the bear spot) in the greater
sigmoid notch and the greater than 250° arc of articular coverage of
the trochlea 1 , 2 (Figure 1). These articulations allow the hinge-like
movement achieved in the elbow, with the coronoid process
limiting posterior and anteromedial instability. This inherent
osseous stability also takes contribution from the radiocapitellar
joint providing a secondary restraint to valgus instability. 3 In
addition, the articulation of the proximal radius with the ulna in the
lesser sigmoid notch provides osseous stability while facilitating
forearm pronosupination.
 Figure 1 Three-dimensional reconstruction from a CT scan of an elbow in
extension with a minimally displaced radial head fracture viewing from anterior
(A), medial (B), anterior (ulna only, C), lateral (ulna only, D), anterior (humerus
only, E), and medial (humerus only, F). AM = anteromedial facet, Ca =
Capitellum, CT = coronoid tip, GS = greater sigmoid notch, LS = lesser sigmoid
notch, ME = medial epicondyle, OT = olecranon tip, Tr = trochlea

With these anatomic relationships established, new research has

focused on the relationship between the radius and ulna to help
guide implant design, selection, and surgical reconstruction
techniques. The authors of a 2019 study analyzed 98 cadaver arms
with CT three-dimensional (3D) reconstruction to investigate the
variable anatomy of the radial notch of the ulna (lesser sigmoid
notch). 4 While finding highly variable anatomy, the study authors
noted a trend of the notch extending laterally while moving distal
in the notch. Although not clinically tested, these findings do have
implications for radial head arthroplasty design. Radial head
arthroplasty relies on articulation with the lesser sigmoid notch. In
nonconforming total elbow arthroplasty constructs—which are
commonly used—it is possible that the distal aspect may be
overstuffed, leading to bony erosion or persistent pain.
A 2021 study investigated the relationship between the radial
head and the tip of the coronoid. 5 Using 80 3D reconstructions of
cadaver upper extremity CT scans, the study authors found that the
mean height of the coronoid from the base of the greater sigmoid
notch was 3.6 cm, whereas the tip of the coronoid to the anterior
aspect of the radial head was 4.5 mm. Knowledge of these
relationships provides useful information when reconstructing the
coronoid in elbows where the radial head is intact.

Ligamentous Anatomy
The lateral ligament complex—composed of the lateral ulnar
collateral ligament (LUCL), the annular ligament, radial collateral
ligament, and the accessory lateral collateral ligament—has proven
crucial to elbow stability (Figure 2). Despite repeated investigations
of the LUCL, granular detail of specific components—such as the
annular ligament—remain poorly described. One study
investigated the annular ligament in detail with specific focus on
the superior, inferior, and anterior oblique bands. 6 In reviewing
cadaver specimens—both embalmed and fresh frozen—the study
authors noted three layers to the lateral ligament complex: LUCL
and radial collateral ligament, the superior and inferior oblique
bands with the annular ligament, and the capsule. These bands
broaden the lateral ulnar a achments of the annular ligament.

Figure 2 Anatomy of the medial (A) and lateral (B) collateral ligament
complexes of the elbow.(Reproduced from Tashjian RZ, Katarincic JA: Complex
elbow instability. J Am Acad Orthop Surg 2006;14[5]:278-286.)

The medial ulnar collateral ligament (MUCL)—specifically the

anterior bundle—has been a frequently investigated structure given
its importance in throwing sports (Figure 3). However, in the
se ing of trauma, MUCL incompetence can also contribute to
persistent instability. To be er understand the effect in the se ing
of trauma, the authors of a 2019 study made a detailed assessment
of the insertion of the MUCL relative to the tip of the coronoid in 84
embalmed elbows. 7 They found a variable distance from the tip of
the coronoid to the insertion of the MUCL (1.4 to 13.9 mm) with an
average distance of 7.7 mm. Even for fractures outside of the
anteromedial facet, based upon these findings, a fracture of the
coronoid tip may extend into the insertion of the MUCL. 8 One
study provided an assessment of the origin and insertion sites of
the three bundles: transverse, anterior, and posterior. 9 It was noted
that the transverse bundle—while inserting and originating from
the same bone—had a achments to the anterior bundle in all 10
specimens evaluated. This suggests a biomechanical advantage
provided by the transverse bundle in supporting the anterior
bundle through valgus loads.

Figure 3 Illustration (A) and photograph (B) showing reported insertion sites of
the two distinct heads of the distal biceps tendon.(Reproduced from Sutton KM,
Dodds SD, Ahmad CS, Sethi PM: Surgical treatment of distal biceps rupture. J
Am Acad Orthop Surg 2010;18[3]:139-148.)

In a empts to understand the pathologic process for

degenerative MUCL pathology, the authors of a 2019 study
evaluated the vascular distribution of the MUCL. 10 In 18 cadavers,
the study authors consistently found dense vascularization in the
proximal MUCL with hypovascularity distally. This provided a more
detailed assessment of the MUCL vascular supply than had been
previously described. 11 They also noted a consistent artery—
naming it the recurrent flexor/pronator artery—traveling in line
with the MUCL that appeared to contribute to the proximal
ligament vascularity. These findings may provide explanation for
the discrepancy in outcomes of nonsurgical management for
proximal versus distal MUCL pathology. 12

Tendinous Anatomy
The most common pathologic tendons around the elbow are the
biceps brachialis, triceps brachialis, and the extensor carpi radialis
brevis (ECRB). In a 2020 study, 10 cadaver specimens were used to
assess the lateral ligamentous complex and extensor tendon
origins. 13 The most notable finding in the cadaver analysis was the
broad origin site for the ECRB. The elbows were examined in
extension and the ECRB origin was found to extend distal to the
radiocapitellar joint by 5.9 mm with a achments to the capsule. As
such, ECRB pathology and associated symptoms may extend distal
to radiocapitellar joint.
The distal biceps tendon has seen renewed study over the past
decade with the contention that there are distinct insertion sites for
the short and long heads of the biceps 14 (Figure 3). The clinical
significance of this distinction remains unknown, with authors
advocating for repair of an isolated short head rupture. 15 To further
the possibility of routine endoscopic biceps treatment, anatomic
landmarks to aid in endoscopy have been evaluated. 16 In 20
cadavers, a bare area on the radial tuberosity was described in all
cases. In all cases, the tendon was encased in a bursal sheath but
had a variable number of bundles (two to five). In a separate
analysis of 11 cadavers, the proximal radioulnar space at the level of
the distal biceps insertion was evaluated. 17 It was noted that the
space through which the native distal biceps tendon passes
between the radius and ulna narrows in pronation, especially
distally. Any thickening of the distal biceps tendon, native or
surgically, may create an impingement within this space in
pronation.
Management of the triceps tendon in distal humerus open
reduction and internal fixation or elbow arthroplasty remains
variable and is a topic of debate. In a 2021 histologic analysis of 17
cadaver specimens to assess the footprint of the triceps tendon and
its relationship to bony landmarks, a smaller insertional footprint
was found with histologic analysis in comparison with historical
findings and the study authors’ own gross measurements. 18
Specifically, the distal to proximal footprint was 10.9 mm compared
with the previously reported 13 mm. 19 This provided that the
distance from the tip of the olecranon to the insertion of the triceps
averaged 16.7 mm. This updated knowledge provides surgeons
reassurance during removal of pathologic processes of the
olecranon tip and obtaining extensive exposure in surgery for
degenerative or traumatic pathologies.

Biomechanics

Elbow Motion
The amount of elbow motion required to perform common daily
tasks has historically been described as 30° to 130° of elbow flexion,
50° of supination, and 50° of pronation. 20 However, with modern-
day tasks, such as holding a phone to the ear, greater flexion and
forearm pronation are required. 21 A systematic review has
confirmed the greater need of flexion than previously reported to
achieve modern-day tasks (>140°). 22 A 2020 study revisited this
topic for children and adolescents, finding that for most common
tasks the initial ranges historically reported were accurate.
However, for modern-day tasks—telephone and keyboard use—a
need for greater forearm pronation (up to 65°) and elbow flexion
(approaching 150°) was similar to that of the adult population. 23 It
is now clear that not all desired tasks can be performed within the
range described historically. Rather, a graduated increase in
functional tasks is seen with greater flexion and pronation. Whether
patients can make accommodations when unable to achieve these
end-ranges has yet to be determined.

Center of Rotation
Passing through the geometric centers of the trochlea and
capitellum, the center of rotation for flexion and extension is static
throughout functional ranges of motion. Accurate identification of
the flexion-extension axis is critical when applying dynamic hinged
fixators or reconstructing collateral ligaments. The authors of a 2019
study revisited the center of rotation about the elbow with a focus
on the relationship between the center of rotation and the medial
epicondyle. 24 This was performed to aid in accurate placement of
the humeral bone tunnel for anterior bundle of the MUCL
reconstruction. The center of rotation, defined by the trochlea, was
predictably found on the distal aspect of the anterior medial
epicondyle. This center of rotation was slightly posterior and
proximal to the center of the trochlea when viewing from medial to
lateral. The distance from the ulnohumeral joint to the center of
rotation line was 14.3 mm in the sagi al plane. This knowledge may
guide a surgeon during an MUCL reconstruction when the native
MUCL is not visible in hopes of achieving isometric reconstruction.

Carrying Angle
The carrying angle of the elbow is normally defined as the degree of
cubitus valgus with the elbow in anatomic position—extension and
supination. It has been established that the carrying angle, or
amount of valgus, decreased with elbow flexion. 25 An increased
carrying angle has been implicated as an independent predictor of
subsequent injury in pitchers. 26 The difference in carrying angle
between injured (n = 8) and noninjured pitchers (n = 24) was limited
(17.5° versus 13.1°) and may not be clinically applicable. To further
investigate this, the authors of a 2019 study reported on 52 pitchers
for a single organization who were followed for a season. 27
Although a greater carrying angle was found in the dominant arm
of pitchers, no statistical difference was observed in the carrying
angle of injured versus noninjured pitchers.

Elbow Stability
Stability of the elbow is provided through bony constraint, static
soft-tissue stabilizers, and dynamic stabilizers. 28 Dynamic
stabilizers have primarily been thought to include the brachialis
and triceps. In a 2019 cadaver simulation of an injury resulting in
lateral collateral ligament complex and common extensor tendon
incompetence, the anconeus as a dynamic stabilizer was tested.
Tensioning the anconeus through its anatomic line of pull, the
effect seen from lateral collateral ligament and common extensor
tendon disruption was reversed. 29 On the opposing side of the
elbow, the medial elbow joint space was analyzed with
ultrasonography in 22 healthy males with intact ulnar collateral
ligaments. 30 The medial elbow joint space enlarged significantly
with valgus stress. However, under the same stress with maximal
grip contraction, the medial elbow joint space was no different than
the space without valgus stress. This suggests the common flexor
tendon—likely primarily flexor carpi ulnaris and flexor digitorum
superficialis—dynamically contributes to elbow stability.
In a 2020 cadaver analysis, the effect of tear location on the
significance of a partial anterior bundle MUCL tear was evaluated. 31
Using joint gapping on ultrasonography as a quantitative measure
of joint instability with valgus stress, it was found that partial-
thickness tears in the midsubstance had the greatest effect on
subsequent instability. No effect was seen with distal partial-
thickness tears, whereas proximal partial-thickness tears only
marginally increased gapping with valgus stressing. In contrast, the
posterior-distal aspect of the MUCL has been found to contribute
more to rotation stability and stiffness compared with the proximal
aspect of the ligament. 32 Minimal effect has been seen even at
complete transection of the transverse ligament of the MUCL. 33 In
contrast, studies have found significant contribution of the
posterior bundle of the MUCL to elbow stability. 34 In a cadaver
analysis of the effect of coronoid fracture and MUCL disruption on
posteromedial rotatory instability, a significant increase in joint
gapping was found with simulated anteromedial facet fracture, and
posterior bundle disruption significantly increased joint gapping at
30°, 60°, and 90° of flexion. With reconstruction of the posterior
bundle, elbow stability improved at 90° of flexion. Subsequent
transection of the anterior bundle following posterior bundle
reconstruction only significantly worsened the joint gapping at 30°
of flexion. This demonstrates the importance of the posterior
bundle in resisting posteromedial rotator instability while
demonstrating some benefit of reconstruction. These findings were
reinforced in an analysis of sequential stabilizer disruptions in six
cadavers. 35 The elbow remained congruent with varus force with
lateral collateral ligament disruption and anteromedial coronoid
fracture. When the posterior bundle was subsequently transected,
the elbow subluxated under gravity load. However, before posterior
bundle transection, there were increased contact pressures seen in
the ulnohumeral and radiocapitellar joints without subluxation.
Although playing a minor role, the radial lateral collateral
complex does contribute to elbow stability by resisting varus stress.
36
The importance of the posterolateral capsule in elbow stability
has also been raised. 37 In a cadaver analysis simulating an
Osborne-Co erill lesion, it was noted that the posterolateral
capsule protects against posterior radial head displacement.
Subsequent sectioning of the lateral collateral ligament complex
provided even greater radial head displacement. As such, referring
to the posterolateral capsule as the Osborne-Co erill ligament was
advocated.

Physical Examination
In patients presenting with a symptomatic elbow, a thorough elbow
examination is required to distinguish between potential
pathologies, understand the functional limitations, and guide
further diagnostic imaging and treatment.

Inspection
Often patients present with significant elbow pain with varying
degrees of elbow trauma. Ecchymosis over the elbow can be a guide
toward the pathology. Although fractures can present with global
ecchymosis, characteristic bruising over the posterior elbow or the
antecubital fossa may represent triceps or biceps brachii injury,
respectively. In this se ing, tendon retraction may be grossly
visible. The elbow carrying angle and comparison with the
contralateral side may provide clues about preexisting disease or
gross instability. In addition, localized areas of swelling with or
without surrounding erythema may provide clues toward aseptic or
septic olecranon bursitis or intra-articular pathology.

Palpation
Patients with lateral or medial epicondylitis have characteristic pain
over and just distal to the respective epicondyles that can be
exacerbated by resisted wrist extension or flexion, respectively.
Meanwhile, radial head pathology, early arthritis, and
osteochondral lesions may mimic lateral epicondylitis with
palpation over the lateral elbow. In the se ing of trauma, palpation
of the anatomic locations of the collateral ligaments may help
distinguish the extent of potential injury, especially when concern
for elbow subluxation history exists. Tenderness over the
antecubital fossa, especially exacerbated by resisted forearm
supination, may point to distal biceps pathology. Likewise,
tenderness over the olecranon in the appropriate clinical se ing
may indicate triceps pathology, especially when exacerbated by
resisted elbow extension. As part of a routine elbow examination,
performing the hook test to evaluate for distal biceps pathology can
quickly diagnose a potential surgical injury.
 All of the nerves crossing the elbow may have compression
pathologies about the elbow. However, the most common is the
ulnar nerve within the cubital tunnel. When patients complain of
medial elbow pain or neuropathic pain in the ulnar digits,
performing an assessment of the ulnar nerve is essential. This
includes palpation with Tinel sign and assessment of ulnar nerve
subluxation while taking the elbow passively from extension to
flexion. Radial tunnel syndrome can be more difficult to assess but
may exhibit a Tinel sign and tenderness approximately 3 to 5 cm
distal to the lateral epicondyle potentially exacerbated by resisted
wrist extension.

Motion
In a normal elbow, patients typically are able to achieve full
extension and flexion to 140° with 75° of pronation and 85° of
supination. It is important to recall that the range of motion in the
elbow required for daily activities has been modified recently
because of a change in modern-day activities (talking on a phone
and typing on a computer). 21 A critical portion of the elbow
physical examination is an assessment of both active and passive
elbow motion. Loss of active elbow motion, especially against
gravity, with retention of passive motion may represent weakness
because of neurologic or tendon injury. Rather, loss of passive
motion may represent a traumatic injury or arthritic process. A
critical distinction in assessing motion is the specific ranges
through which pain exists. Pain at the terminal aspects of motion
rather than throughout the arc of motion may be from similar
etiologies (eg, osteoarthritis) but is prognostic and may alter
treatment. In addition, crepitus throughout passive or active range
of motion without arthritis may indicate radiocapitellar plica. In the
se ing of potentially nonsurgical traumatic injuries, such as radial
head fractures, confirmation of ability to achieve near-full range of
motion, especially without blocks to pronation and supination, is
essential.
Strength
Weakness in the elbow is most commonly a critical issue in distal
biceps or triceps brachii tendon pathologies. In the acute se ing
with concern for distal triceps injury, determining the ability to
extend against gravity can guide the need for advanced imaging and
aid in management. This is best performed either supine with the
forearm over the patient’s chest or si ing with the arm brought
overhead. When concerned about distal biceps pathology, testing
resisted forearm supination initiating from a supinated position
can be helpful in quantifying weakness and associated pain,
especially in subacute and chronic injuries.

Instability
When concerned about elbow instability following trauma,
examination may be limited because of significant pain and
swelling. In this se ing, reliance on history and radiologic
assessments is necessary. However, areas of ecchymosis,
tenderness, and laxity if able to relax the patient may help guide
further testing. First, a thorough examination as described
previously, including an initial assessment of comfortable range of
motion, is critical. In the se ing of intact articular surfaces, bony
congruity can provide significant inherent stability. Grossly stable
elbows are typically evident clinically and on early radiographic
assessment. More subtle instability, such as posterolateral rotatory
instability, valgus instability during throwing, or varus
posteromedial rotatory instability, requires greater clinical
suspicion and careful clinical examination. After establishing
concern for MUCL compromise, assessment of stability to valgus
directed force can further clarify the extent of MUCL injury. A
positive milking maneuver or moving valgus stress test 38 should
lead to further advanced imaging (Figure 4). With concern for
posterolateral rotatory instability, a lateral pivot shift test has high
diagnostic accuracy in the sedated patient. However, it has poor
sensitivity in the awake patient given understandable blocking. In
the awake patient, the prone or chair push-up test may have be er
sensitivity. 39 With concern for varus posteromedial rotatory
instability, flexing and extending the forearm parallel to the floor by
abducting the shoulder and providing varus through gravity may
re-create symptoms and should raise concern for significant
pathology in the lateral collateral ligament and anteromedial
coronoid.
Figure 4 Photographs showing physical examination maneuvers of the elbow
to evaluate for medial ulnar collateral ligament pathology.A and B, Milking
maneuver demonstrated by pulling on the patient’s thumb with the forearm
supinated and elbow flexed more than 90°. A positive test is seen with
apprehension and medial elbow pain. C and D, Moving valgus test is
demonstrated by maximally flexing the elbow with the shoulder abducted. Valgus
stress is applied through the elbow while externally rotating maximally at the
shoulder. The elbow is then quickly extended. A positive test re-creates the
patient’s symptoms.(Reproduced from Smith MV, Lamplot JD, Wright RW,
Brophy RH: Comprehensive review of the elbow physical examination. J Am
Acad Orthop Surg 2018;26[19]:678-687.)
Imaging
Qualifying and quantifying the extent of elbow injuries relies
heavily on radiographic modalities. The utility of specific modalities
—especially ultrasonography—remains under investigation.

Radiographs
Plain radiographs and fluoroscopy play an important role in initial
radiographic evaluation of a symptomatic elbow. In all patients
presenting with elbow symptoms, plain radiographs are an
essential part of the evaluation. In a 2020 study, the radiographic
anatomy of the proximal ulna to aid in safe extra-articular
placement of hardware found that from the central trochlear ridge,
the ulnar facets extended dorsally from 6.2 to 9.7 mm on average on
a lateral radiograph. 40 As such, screws placed in this zone and
deviated from center are at risk of articular injury. Such hardware
can be critical in maintaining articular impaction injuries.
Therefore, it is critical to have an understanding of the complex
radiographic anatomy of the sigmoid notch to aid in hardware
placement. Despite a complex understanding of anatomy, four
experienced orthopaedic trauma surgeons were able to correctly
identify a malreduction in a simulated proximal ulna fracture in a
cadaver only 73% of the time on average. 41 Both intraobserver and
interobserver reliability was poor. With this finding, there should
be a low threshold to perform CT when there is concern about
complex fractures of the proximal ulna or potential malreductions
postoperatively.
In the se ing of collateral ligament injury, evaluating the extent
of the injury and need for surgical repair can be clinically
challenging. One study evaluated the use of dynamic fluoroscopy
for potentially aiding in this clinical situation. 42 With dynamic
fluoroscopy and varus stress, it was found that transection of the
LUCL alone resulted in increased angulation of 4.3° to 7.0° under
varus stress. This finding is in comparison with 4.9° to 8.8° of
increased angulation with valgus stress after isolated transection of
the anterior bundle of the MUCL. Angulation increased with varus
stress to 7.9° to 13.4° after transection of the entire lateral collateral
ligament complex. Transection of the entire MUCL showed similar
increase under valgus stress. Angulation increased to more than 20°
angulation with either varus or valgus stress in full extension when
the medial or lateral ligament injuries were coupled with injuries to
the anterior capsule. This analysis establishes the potential utility
for dynamic fluoroscopy to clarify the extent of injured structures
and guide surgical management.

Computed Tomography
As understanding of complex anatomy increased, CT utilization is
only increasing. In 36 patients undergoing arthroscopy for elbow
osteoarthritis, CT improved the interrater reliability for detecting
osteophytes (95% versus 80%) and loose bodies (91% versus 81%)
compared with radiography alone. 43 CT improved the sensitivity of
detecting osteophytes (46% and 98%) and loose bodies (49% versus
98%) compared with radiographs, respectively. However, this
finding was associated with decreased specificity. Previously, the
potential utility of CT and motion simulation to plan arthroscopic
surgery was described. In a new iteration of preoperative planning,
the addition of a 3D-printed color-coded model based on their
planned surgery was compared with planning alone. 44 No
difference in outcomes was found with the addition of the 3D-
printed color-coded model. The analysis was likely underpowered
and needs further demonstration of value, but provides a novel
application of CT preoperative planning for complex elbow
arthroscopy.

Magnetic Resonance Imaging

MRI remains the dominant method for diagnosing tendon injuries
about the elbow. More recently, authors have revisited its utility in
the se ing of elbow dislocations and when assessing the MUCL in
throwing athletes. MRI was used to assess injuries in simple elbow
dislocation in 17 patients, and the lateral collateral ligament
complex was found to be at least partially disrupted in all but one
case, whereas the medial collateral ligament was intact in only two
cases. 45 Complete anterior capsule tears were noted in 12 cases
whereas complete medial and lateral collateral ligament ruptures
were noted in 10 and 9 patients, respectively. In this se ing, there
was high interobserver reliability for reviewing radiologists. Yet, in
a separate review of 30 MRI studies following simple elbow
dislocation, agreement among reviewers was 60% for collateral
ligament injuries. There was high agreement in determining joint
congruity, elbow effusion, and loose bodies. 46 Unfortunately, there
were wide ranges of intraobserver reliability, questioning the
reproducibility of MRI diagnosis in this se ing.
The MUCL provides a vital function in overhead throwers—
especially pitchers. As such, the diagnosis and management of
MUCL pathology has garnered significant a ention. A 2019 study
takes this a step further by assessing MRI findings of asymptomatic
pitchers and a empting to predict future injury. 47 None of the
pitchers had previously been on the disabled list, yet the study
authors found that pitchers who subsequently went on the disabled
list were more likely to have MUCL heterogeneity, humeral-based
MUCL partial tears, and MRI evidence of posteromedial
impingement of their asymptomatic elbow. Translating these
findings to clinical care can be difficult but establishes the at-risk
structures and the predominant pathology in elite pitchers. Several
recently published studies evaluate the utility of MRI in guiding
and predicting clinical management of MUCL pathology. 48 - 50 A
classification system was proposed to define the injury based on
location (proximal, midsubstance, or distal) and degree of injury
(complete versus partial). Excellent interobserver and intraobserver
reliability was demonstrated for this classification system on MRI.
This classification system, especially in identifying distal pathology,
aided in guiding successful nonsurgical or nonsurgical
management. 49 , 50
 In the se ing of persistent elbow pain with normal radiographs,
MRI may also be useful in diagnosing and quantifying the
pathology. This may be true for radiocapitellar plica, 51 chronic
medial or lateral epicondylitis, osteonecrosis, or osteochondral
lesion. This may prove especially helpful in differentiating potential
pathologies in the se ing of lateral elbow pain, especially when
recalcitrant to nonsurgical measures.

Ultrasonography
Ultrasonography provides a low-cost and noninvasive diagnostic
method for elbow pathology. Another important distinction is its
ability to easily provide dynamic testing. The accuracy of
ultrasonography is operator dependent and therefore is not as
widely available as other radiographic modalities.
A common application for ultrasonography in the elbow is to
evaluate MUCL pathology in the throwing athlete. A 2020 study
revisited stress ultrasonography as a potential primary diagnostic
tool for evaluating complete MUCL tears. 52 Stress ultrasonography
accurately predicted complete tears on MRI when joint gapping was
greater than 0.5 mm at 30° of flexion or 1.0 mm at 90° of flexion.
Although fewer clinicians are experienced with ultrasonography, in
this se ing it allows for evaluation of the MUCL with dynamic
evaluation to study the extent of joint gapping under stress.
The distal biceps and triceps brachii tendons are often evaluated
with the use of nonarthrographic MRI. However, in cases where
MRI is not widely available or in patients who are unable to
undergo MRI, ultrasonography may play a diagnostic role. High
sensitivity for partial and complete tears on ultrasonography
compared with findings during surgical intervention has been
demonstrated. 53 In an analysis of 39 cases without surgical
intervention, only a single case had a major discrepancy between
ultrasonography and MRI: a low-grade partial tear on
ultrasonography with a complete tear on MRI.
 For soft-tissue structures about the elbow, especially those
providing elbow stability and benefiting from dynamic testing,
ultrasonography can be an invaluable tool. Its adoption, however,
requires providers who have experience in the techniques and
assessment of this complex anatomy and associated pathologies.

Summary
Accurate diagnosis of elbow pathology can be elusive. This is
because of the many overlying structures and complex anatomy. An
understanding of anatomy and biomechanics helps guide
appropriate physical examination that should subsequently dictate
appropriate imaging utilization. Current and future research will
heavily focus on the best diagnostic imaging of the elbow.
Ultrasonography is an emerging technology with great promise in
specific se ings. Accuracy of ultrasonography is dependent on
experience. With this updated knowledge, improved dissemination
and adoption of these promising technologies is essential.

Key Study Points

Elbow osseous, ligamentous, and tendinous anatomy is complex, and a thorough
understanding of these structures is required for appropriate treatment.
The defined functional elbow range of motion has been updated for modern-day
tasks. To complete all tasks, including phone to the ear and typing on a keyboard, up
to 150° of elbow flexion and 65° of pronation are required.
It is critical that a full routine elbow examination is provided for each patient with
elbow symptoms and includes visual inspection, palpation, and assessment of
motion, strength, and stability.
Imaging of the elbow continues to evolve. Dynamic fluoroscopy in the setting of
elbow instability may aid in quantifying the degree of injury and guiding treatment.
Ultrasonography by an experienced operator also provides a dynamic and
inexpensive modality for radiographically evaluating elbow injuries.

Annotated References
1. Giannicola G, Sedati P, Cino i G, Bulli a G, Polimanti D: The
ulnar greater sigmoid notch “coverage angle”: Bone and cartilage
 contribution. Magnetic resonance imaging anatomic study on 78
elbows. J Shoulder Elbow Surg 2015;24:1934-1938.
2. Shiba R, Sorbie C, Siu DW, Bryant JT, Cooke TDV, Wevers HW:
Geometry of the humeroulnar joint. J Orthop Res 1988;6:897-906.
3. Morrey BF, An KN: Stability of the elbow: Osseous constraints. J
Shoulder Elbow Surg 2005;14:S174-S178.
4. Wegmann K, Knowles N, Lalone E, Müller LP, Athwal GS, King
GJW: Computed tomography analysis of the radial notch of the
ulna. J Hand Surg 2019;44:794.e1-794.e8. A cadaver analysis of 98
arms with 3D CT was performed to be er characterize the lesser
sigmoid notch.
5. Walch A, Garcia-Maya B, Knowles NK, Athwal GS, King GJW:
Computed tomography analysis of the relationship between the
coronoid and the radial head. J Shoulder Elbow Surg
2021;30(12):2824-2831. A 3D CT assessment of 80 cadaver upper
extremity specimens was performed to evaluate the relationship
between the coronoid and the radial head. The authors found
that the tip of the coronoid to the anterior aspect of the radial
head was 4.5 mm.
6. Barnes JW, Chouhan VL, Egekeze NC, Rinaldi CE, Cil A: The
annular ligament – Revisited. J Shoulder Elbow Surg 2018;27:e16-
e19.
7. Rausch V, Wegmann S, Hackl M, et al: Insertional anatomy of
the anterior medial collateral ligament on the sublime tubercle of
the elbow. J Shoulder Elbow Surg 2019;28:555-560. The authors
assessed the insertion of the MUCL to the tip of the coronoid in
84 embalmed elbows. The distance was highly variable (1.4 to 13.9
mm).
8. Ablove R, Moy O, Howard C, Peimer C, S’Doia S: Ulnar coronoid
process anatomy: Possible implications for elbow instability. Clin
Orthop 2006;449:259-261.
9. Camp CL, Jahandar H, Sinatro AM, Imhauser CW, Altchek DW,
Dines JS: Quantitative anatomic analysis of the medial ulnar
 collateral ligament complex of the elbow. Orthop J Sports Med
2018;6:2325967118762751.
10. Buckley PS, Morris ER, Robbins C, et al: Variations in blood
supply from proximal to distal in the ulnar collateral ligament of
the elbow: A qualitative descriptive cadaveric study. Orthop J
Sports Med 2019;7:2325967119S00361. A cadaver assessment of the
vascular distribution of the MUCL is presented. The authors
noted a consistent artery traveling in line with the MUCL that
appeared to be the dominant supply to the proximal ligament.
11. Yamaguchi K, Sweet FA, Bindra R, Morrey BF, Gelberman RH:
The extraosseous and intraosseous arterial anatomy of the adult
elbow. J Bone Joint Surg 1997;79:1653-1662.
12. Frangiamore SJ, Lynch TS, Vaughn MD, et al: Magnetic
resonance imaging predictors of failure in the nonoperative
management of ulnar collateral ligament injuries in professional
baseball pitchers. Am J Sports Med 2017;45:1783-1789.
13. Bernholt DL, Rosenberg SI, Brady AW, Storaci HW, Viola RW,
Hacke TR: Quantitative and qualitative analyses of the lateral
ligamentous complex and extensor tendon origins of the elbow:
An anatomic study. Orthop J Sports Med 2020;8:2325967120961373.
A cadaver assessment of the lateral ligament complex and
extensor tendon origins is presented. The authors found that the
ECRB had a broader origin than previously described with the
origin extending on the capsule over the radiocapitellar joint.
14. Jarre CD, Weir DM, Stuffmann ES, Jain S, Miller MC, Schmidt
CC: Anatomic and biomechanical analysis of the short and long
head components of the distal biceps tendon. J Shoulder Elbow
Surg 2012;21: 942-948.
15. Voleti PB, Berkowi JL, Konin GP, Cordasco FA: Rupture of the
short head component of a bifurcated distal biceps tendon. J
Shoulder Elbow Surg 2017;26:403-408.
16. Bhatia DN: Endoscopic anatomy of distal biceps tendon
insertion and bicipitoradial bursa: A cadaveric study. J Shoulder
 Elbow Surg 2021;30:1759-1767. This cadaver analysis describes
landmarks for endoscopic evaluation of the distal biceps tendon.
17. Bhatia DN, Kandhari V, DasGupta B: Cadaveric study of
insertional anatomy of distal biceps tendon and its relationship
to the dynamic proximal radioulnar space. J Hand Surg
2017;42:e15-e23.
18. Whitaker JJ, Hartke J, Hawayek BJ, Howard CS, Ablove RH:
Histologic evaluation of the triceps brachii tendon insertion:
implications for triceps-sparing surgery. J Hand Surg Am
2021;47(4):386.e1-386.e. This cadaver study revisits the insertion
of the triceps tendon. The authors describe a smaller footprint of
the triceps brachii than has previously been reported.
19. Keener JD, Chafik D, Kim HM, Gala LM, Yamaguchi K:
Insertional anatomy of the triceps brachii tendon. J Shoulder
Elbow Surg 2010;19:399-405.
20. Morrey BF, Askew LJ, Chao EY: A biomechanical study of
normal functional elbow motion. J Bone Joint Surg Am 1981;63:872-
877.
21. Sardelli M, Tashjian RZ, MacWilliams BA: Functional elbow
range of motion for contemporary tasks. J Bone Joint Surg Am
2011;93:471-477.
22. Oosterwijk AM, Nieuwenhuis MK, van der Schans CP, Mouton
LJ: Shoulder and elbow range of motion for the performance of
activities of daily living: A systematic review. Physiother Theory
Pract 2018;34:505-528.
23. Valone LC, Waites C, Tartarilla AB, et al: Functional elbow range
of motion in children and adolescents. J Pediatr Orthop
2020;40:304-309. This analysis confirms previous findings in
adults for functional elbow range of motion for modern tasks
applied to children. Level of evidence: II.
24. Graham KS, Golla S, Gehrmann SV, Kaufmann RA: Quantifying
the center of elbow rotation: Implications for medial collateral
ligament reconstruction. Hand 2019;14:402-407. This study revisits
the center of rotation for the elbow using 3D-reconstructed CT
 scans with specific focus in guiding MUCL reconstruction
surgery.
25. Chao EY, Morrey BF: Three-dimensional rotation of the elbow. J
Biomech 1978;11:57-73.
26. Shah SS, Goldstein JA, Stein S, et al: Increased valgus carrying
angle at the elbow correlates with shoulder and elbow injuries in
professional pitchers: A prospective study. Orthop J Sports Med
2017;5:2325967117S00379.
27. Erickson BJ, Chalmers PN, Zajac J, et al: Do professional
baseball players with a higher valgus carrying angle have an
increased risk of shoulder and elbow injuries? Orthop J Sports
Med 2019;7:2325967119866734. In this prospective analysis, 52
pitchers were followed over a single season to determine whether
the carrying angle at the start of the season was associated with
subsequent injury. Level of evidence: II.
28. Safran MR, Baillargeon D: Soft-tissue stabilizers of the elbow. J
Shoulder Elbow Surg 2005;14:S179-S185.
29. Badre A, Axford DT, Banayan S, Johnson JA, King GJW: Role of
the anconeus in the stability of a lateral ligament and common
extensor origin-deficient elbow: An in vitro biomechanical study.
J Shoulder Elbow Surg 2019;28:974-981. This cadaver model of
elbow instability was used to assess the anconeus as a stabilizer
of the elbow. This model specifically simulated lateral collateral
ligament and common extensor tendon incompetence to test the
anconeus.
30. Pexa BS, Ryan ED, Myers JB: Medial elbow joint space increases
with valgus stress and decreases when cued to perform a
maximal grip contraction. Am J Sports Med 2018;46:1114-1119.
31. Cicco i MC, Hammoud S, Dodson CC, Cohen SB, Nazarian LN,
Cicco i MG: Medial elbow instability resulting from partial tears
of the ulnar collateral ligament: Stress ultrasound in a cadaveric
model. Am J Sports Med 2020;48:2613-2620. In this cadaver study,
the authors used stress ultrasonography to evaluate the effect of
 partial-thickness tears on elbow stability. The greatest effect was
seen with a midsubstance partial-thickness tear.
32. Frangiamore SJ, Bigart K, Nagle T, Colbrunn R, Millis A,
Schickendan MS: Biomechanical analysis of elbow medial ulnar
collateral ligament tear location and its effect on rotational
stability. J Shoulder Elbow Surg 2018;27:2068-2076.
33. Solitro GF, Fa ori R, Smidt K, Nguyen C, Morandi MM, Barton
RS: Role of the transverse ligament of the ulnar collateral
ligament of the elbow: A biomechanical study. JSES Int
2021;5:549-553. This was an analysis of 12 cadaver specimens to
test the effect of transection of the transverse ligament of the
medial collateral ligament complex. Minimal effect was seen with
complete transection.
34. Gluck MJ, Beck CM, Golan EJ, Nasser P, Shukla DR, Hausman
MR: Varus posteromedial rotatory instability: A biomechanical
analysis of posterior bundle of the medial ulnar collateral
ligament reconstruction. J Shoulder Elbow Surg 2018;27:1317-1325.
35. Hwang J-T, Shields MN, Berglund LJ, Hooke AW, Fi simmons
JS, O’Driscoll SW: The role of the posterior bundle of the medial
collateral ligament in posteromedial rotatory instability of the
elbow. Bone Joint J 2018;100-B:1060-1065.
36. Arrigoni P, Cucchi D, Luceri F, et al: Lateral elbow laxity is
affected by the integrity of the radial band of the lateral collateral
ligament complex: A cadaveric model with sequential releases
and varus stress simulating everyday activities. Am J Sports Med
2021;49:2332-2340. This is a cadaver model assessment of the
importance of the radial band of the lateral collateral ligament in
contributing to elbow stability. The authors found that the effect
of the radial band was not substantial, but it did play a role in
resisting varus stress.
37. Edwards DS, Arshad MS, Luokkala T, Kedgley AE, Wa s AC:
The contribution of the posterolateral capsule to elbow joint
stability: A cadaveric biomechanical investigation. J Shoulder
Elbow Surg 2018;27:1178-1184.
38. O’Driscoll SWM, Lawton RL, Smith AM: The “Moving Valgus
Stress Test” for medial collateral ligament tears of the elbow. Am
J Sports Med 2005;33:231-239.
39. Regan W, Lapner PC: Prospective evaluation of two diagnostic
apprehension signs for posterolateral instability of the elbow. J
Shoulder Elbow Surg 2006;15:344-346.
40. Githens TC, Campbell ST, Salazar B, et al: Understanding the
radiographic anatomy of the proximal ulna and avoiding
inadvertent intraarticular screw placement. J Orthop Trauma
2020;34:102-107. Using elbow cadaver specimens, the authors
investigated the radiographic anatomy of the proximal ulna with
specific focus of the articular projection on the lateral radiograph.
This aids in extra-articular hardware placement.
41. Kubik J, Schneider P, Buckley R, Korley R, Duffy P, Martin R:
Evaluating the utility of the lateral elbow radiograph in central
articular olecranon reduction: An anatomic and radiographic
study. J Orthop Trauma 2018;32:e81-e85.
42. Schne ke M, Bergmann M, Wegmann K, et al: Determination of
elbow laxity in a sequential soft-tissue injury model: A cadaveric
study. J Bone Joint Surg Am 2018;100:564-571.
43. Alnusif NS, Matache BA, AlQahtani SM, et al: Effectiveness of
radiographs and computed tomography in evaluating primary
elbow osteoarthritis. J Shoulder Elbow Surg 2021;30:S8-S13. This
study compared the utility of plain radiography versus CT prior
to elbow arthroscopy in identifying and localizing loose bodies
and osteophytes. CT provided improved sensitivity with
decreased specificity. Level of evidence: I.
44. Shigi A, Oka K, Tanaka H, Shiode R, Murase T: Utility of a 3-
dimensionally printed color-coded bone model to visualize
impinging osteophytes for arthroscopic débridement
arthroplasty in elbow osteoarthritis. J Shoulder Elbow Surg
2021;30:1152-1158. This study evaluated 16 patients, 8 in each
study arm, undergoing elbow arthroscopy. The study authors
compared the outcome of CT-based preoperative planning alone
 versus preoperative planning, with the 3D printed model
displaying the architecture of osteophytes requiring excision.
Level of evidence: III.
45. Luokkala T, Temperley D, Basu S, Karjalainen TV, Wa s AC:
Analysis of magnetic resonance imaging-confirmed soft tissue
injury pa ern in simple elbow dislocations. J Shoulder Elbow Surg
2019;28:341-348. Using 17 cases of simple elbow dislocations with
subsequent MRI, the authors investigated frequency and pa ern
of injured structures: lateral and medial collateral ligaments,
anterior capsule, and common extensor tendon.
46. Schne ke M, Schüler S, Hoffend J, et al: Interobserver and
intraobserver agreement of ligamentous injuries on conventional
MRI after simple elbow dislocation. BMC Musculoskelet Disord
2017;18:85.
47. Garcia GH, Gowd AK, Cabarcas BC, et al: Magnetic resonance
imaging findings of the asymptomatic elbow predict injuries and
surgery in major league baseball pitchers. Orthop J Sports Med
2019;7:2325967118818413. MRI findings of 41 asymptomatic
pitchers without prior injury were correlated with subsequent
injury in this retrospective analysis. The authors characterize the
preinjury MRI findings that predict subsequent injury. Level of
evidence: III.
48. Ramkumar PN, Frangiamore SJ, Navarro SM, et al:
Interobserver and intraobserver reliability of an MRI-based
classification system for injuries to the ulnar collateral ligament.
Am J Sports Med 2018;46:2755-2760.
49. Ramkumar PN, Haeberle HS, Navarro SM, Frangiamore SJ,
Farrow LD, Schickendan MS: Clinical utility of an MRI-based
classification system for operative versus nonoperative
management of ulnar collateral ligament tears: A 2-year follow-
up study. Orthop J Sports Med 2019;7:2325967119839785. This is a
follow-up study of 58 athletes who underwent treatment for
MUCL injuries. An MRI classification system based on the
location and extent of injury guided management without
 crossovers from nonsurgical to surgical treatment. Level of
evidence: III.
50. Ramkumar PN, Haeberle HS, Navarro SM, Frangiamore SJ,
Farrow LD, Schickendan MS: Prognostic utility of an magnetic
resonance imaging-based classification for operative versus
nonoperative management of ulnar collateral ligament tears: one-
year follow-up. J Shoulder Elbow Surg 2019;28:1159-1165. This was
an early follow-up study of patients treated for MUCL injury
based on an MRI classification developed by the authors.
Location and extent of MUCL injury was a major determinant
between surgical and nonsurgical management.
51. Lee HI, Koh KH, Kim J-P, Jaegal M, Kim Y, Park MJ: Prominent
synovial plicae in radiocapitellar joints as a potential cause of
lateral elbow pain: Clinico-radiologic correlation. J Shoulder Elbow
Surg 2018;27:1349-1356.
52. Park JY, Kim H, Lee JH, et al: Valgus stress ultrasound for
medial ulnar collateral ligament injuries in athletes: Is
ultrasound alone enough for diagnosis? J Shoulder Elbow Surg
2020;29:578-586. The authors prospectively evaluated the
diagnostic utility of stress ultrasonography for MUCL pathology.
They found that joint gapping of 0.5 and 1.0 mm at 30º and 90º of
flexion, respectively, was diagnostic of complete MUCL tear.
Level of evidence: III.
53. de la Fuente J, Blasi M, Martínez S, et al: Ultrasound
classification of traumatic distal biceps brachii tendon injuries.
Skeletal Radiol 2018;47:519-532.
C H AP T E R 3 1

Elbow Degenerative Conditions

and Nerve Disorders
Robert L. Brochin MD, Joseph F. Styron MD, PhD, FAAOS,
Jason C. Ho MD

Dr. Brochin or an immediate family member is a member of a speakers’ bureau or has made paid
presentations on behalf of DJ Orthopaedics. Dr. Styron or an immediate family member is a
member of a speakers’ bureau or has made paid presentations on behalf of Acumed, LLC,
Axogen, and EXSOmed and serves as a paid consultant to or is an employee of Acumed, LLC,
Axogen, and EXSOmed. Dr. Ho or an immediate family member serves as a paid consultant to or
is an employee of Biedermann Motech.

ABSTRACT
There are several etiologies of elbow pain and stiffness, including
but not limited to primary elbow osteoarthritis, pos raumatic
elbow arthritis, and inflammatory arthropathies that affect the
elbow. It is important for orthopaedic surgeons to review these
etiologies and focus on treatment options and their appropriate
application with a current review of the literature. An
understanding of two nerve compression syndromes about the
elbow, cubital tunnel and radial tunnel syndromes, is also
important.
Keywords: cubital tunnel syndrome; elbow arthritis; rheumatoid
arthritis; total elbow arthroplasty

Introduction
Elbow motion is necessary for upper extremity function and the
ability to position the hand in space. Functional elbow range of
motion (ROM) for activities of daily living has been classically
defined to be a 100° functional arc, with a range of 30° to 130°, and
50° for both pronation and supination, with more recent data
supporting flexion arcs of 130°, and up to 149° of flexion for certain
activities. 1 The elbow is a constrained synovial hinge joint. Because
of this constraint, it is intolerant of trauma and has a high
propensity for stiffness and degeneration. Conditions that may
cause pain and limit the elbow’s functional ROM include primary
elbow osteoarthritis, pos raumatic elbow arthritis, and
inflammatory arthropathies, specifically rheumatoid arthritis.

Etiologies
Elbow arthritis is mostly caused by three etiologies: primary
osteoarthritis, pos raumatic arthrosis, and inflammatory
arthropathies. Primary elbow osteoarthritis is relatively rare,
occurring in less than 2% of the population. 2 It is generally
accepted that strenuous manual labor is a significant predisposing
factor, and weightlifters and throwing athletes are thought to be
specifically predisposed. 2 Biomechanical studies have shown more
force is transmi ed across the radiocapitellar joint than the
ulnohumeral joint (55% versus 45%) with an applied axial load. 3 Up
to three times the weight of an individual can be transmi ed across
the humeroulnar and humeroradial joints with heavy labor. 4
Previous elbow trauma is a known risk factor for the
development of secondary pos raumatic elbow arthrosis. Prior
studies have shown pos raumatic arthritis as high as 80% in distal
humeral fractures at 12 years or more follow-up after open
reduction and internal fixation, with other studies showing 35% to
45% with distal humeral fractures or fracture-dislocations than with
isolated radial head (5%) and olecranon fractures (9%) at mean 19-
year follow-up. 5 , 6 For isolated proximal ulna fractures managed
surgically, a preoperative Regan and Morrey type 3 coronoid
process fracture and a postoperative joint surface incongruity of
greater than 2 mm were found to be associated with the
development of arthritis. 7 Although few long-term studies exist,
elbow fractures occurring in childhood are thought to predispose
individuals to osteoarthritis because of deformities related to
epiphyseal plate injury or incomplete reduction of fractures.
Rheumatoid arthritis is the most common inflammatory
arthropathy that affects the elbow. The elbow is involved in the
disease process of 20% to 65% of patients with rheumatoid arthritis.
8
Unlike primary elbow osteoarthritis, elbow rheumatoid arthritis
usually involves diffuse and symmetric joint space narrowing and
cartilage destruction. 8 As the disease progresses to more advanced
stages, joint destruction may lead to subluxation, dislocation, bony
fragmentation, and ultimately joint ankylosis (Figure 1). The use of
disease-modifying antirheumatic drugs for the management of
rheumatoid arthritis has been shown to decrease the radiographic
progression of joint destruction in patients with rheumatoid
arthritis. 9
 Figure 1 A, AP and lateral elbow radiographs from a patient with early
rheumatoid arthritis with symmetric joint space narrowing and cartilage
destruction. B, AP and lateral elbow radiographs from a patient with advanced
rheumatoid arthritis with complete joint destruction and dislocation.(Courtesy of
Jason C. Ho, MD.)

Evaluation
When evaluating patients with elbow arthritis, a thorough history
should be obtained because it may offer insight into the etiology of
their elbow complaint (eg, previous trauma, rheumatologic history).
Complete physical examination includes a thorough assessment of
elbow ROM. Flexion/extension assessment is typically performed
with the arm parallel to the floor and the hand in full supination. It
is particularly important to assess where in the arc of motion pain
occurs. Pain primarily at the extremes of ROM suggests impeding
bone or tissue, which is more responsive to joint-preserving
procedures. Pain that occurs throughout the flexion/extension arc,
along with pain with resisted flexion/extension, is more likely
indicative of articular cartilage destruction. Pronation/supination
should also be assessed, although in most patients with primary
elbow arthritis this will be preserved. A full upper extremity
neurologic examination should be performed, with particular
a ention paid to the ulnar nerve because medial osteophytes at the
cubital tunnel or a tight ulnar retinaculum may compress the nerve.
Plain radiographs of the elbow are necessary at a minimum to
evaluate the severity of the disease. CT scans can be particularly
helpful in identifying areas of bony impingement if surgical
intervention is considered. A 2021 study has shown that when
compared to plain radiographs, elbow CT scans have greater
sensitivity and higher interrater agreement in detecting
osteophytes and loose bodies when correlating imaging findings
with intraoperative findings 10 (Figure 2). Nerve conduction studies
can be considered to evaluate the severity of nerve impingement if
neurologic symptoms are present.
 Figure 2 Example of AP and lateral plain radiographs (A) and three-
dimensional CT scan showing anterior and posterior views of the elbow (B) of a
38-year-old man who works as a laborer with primary elbow osteoarthritis
demonstrating the mechanical blocks to elbow range of motion including
osteophytes and loose bodies.(Courtesy of Jason C. Ho, MD.)

Nonsurgical Treatment
In patients with preserved and functional arc of motion and
relatively minor pain and disability related to the elbow,
nonsurgical treatment is appropriate. The mainstays of nonsurgical
treatment for elbow arthritis include activity modification and
physical therapy to delay progression and maintain ROM, oral
NSAIDs, and intra-articular injections such as corticosteroid for
pain relief. There is limited evidence comparing the efficacy of the
various nonsurgical treatment modalities, but some authors
maintain that the most important aspect of nonsurgical treatment
is activity modification to delay progression after explaining the
natural history of the disease process.
Intra-articular injections other than corticosteroid, such as
hyaluronic acid, have been described for elbow arthritis. Hyaluronic
acid has not been found to be useful in the treatment of patients
with pos raumatic elbow arthritis, with patients experiencing no
beneficial effects at 6-month follow-up. 11 Furthermore, hyaluronic
acid is not FDA approved for the treatment of patients with elbow
osteoarthritis, and its use would be off-label. Platelet-rich plasma
has been proposed as treatment for patients with osteoarthritis of
various joints; however, to the authors’ knowledge there has not
been a study specifically looking at its efficacy in managing elbow
osteoarthritis.

Surgical Treatment
Surgical treatment in patients with elbow arthritis should be
reserved for those with moderate to severe pain and significant
functional impediments. Surgery may be indicated for either pain
and/or limited ROM, and surgical indications should be
individualized. For example, a person whose occupation involves
heavy labor may tolerate more limited ROM versus a high-level
athlete.
When surgery is indicated, surgical options are based on the
goals of the intervention and the severity of the disease process.
Surgical options include both arthroscopic and open joint
débridement and soft-tissue releases, interpositional arthroplasty,
elbow arthroplasty, and elbow arthrodesis. Each procedure and its
indications will be discussed in more detail in the next paragraphs.

Débridement, Synovectomy, Capsular

Release, and Loose Body Removal
In patients in whom nonsurgical treatment has failed, the most
common procedures a empt joint preservation because joint
replacement surgeries are reserved for more advanced pathology or
patients with limited activity goals. The goals of joint-preserving
surgery include the removal of marginal osteophytes that impede
elbow ROM and removal of loose bodies and may include anterior
and posterior capsular release if joint contractures are present.
Pathologic synovium and pannus resection can also be therapeutic
in patients with rheumatoid arthritis. At the time of surgery, the
ulnar nerve is released or transposed if symptoms are present.
Although data in the literature have been mixed, some authors
have advocated a prophylactic ulnar nerve release even when
preoperative ulnar nerve symptoms are not present if a significant
flexion contracture exists, with the hypothesis that increased
postoperative ROM would produce new-onset ulnar nerve
compression symptoms. 12 , 13
One study found that there was a higher rate of postoperative
ulnar nerve symptoms in patients who underwent elbow
contracture release without cubital tunnel release at the time of
surgery if patient had preoperative flexion less than or equal to 100°
compared with patients with preoperative flexion greater than or
equal to 100°, although their results did not reach significance. 12
These procedures may be performed arthroscopically or in an open
fashion. Débridement is generally considered to be most reliable
when peripheral osteophytes cause pain at terminal flexion and
extension with limitation of motion, but the central portion of the
joint is preserved.
Open Techniques
The classic open treatment for patients with mild to moderate
elbow arthritis is the Outerbridge-Kashiwagi procedure, which
involves a transhumeral approach via a triceps split with distal
humeral fenestration to remove impinging osteophytes from the
olecranon, coronoid, and their corresponding fossae. In the largest
long-term follow-up study, this procedure was found to result in
li le or no pain in a li le more than one-half of patients (55%). 14
The addition of the release of the collateral ligaments to enable
joint subluxation to assess the articular surface and allow for more
extensive osteophyte excision has been termed débridement
arthroplasty. Mean 5-year outcomes for this procedure have shown
recurrence of mild arthritis, but with durable pain relief and
improved ROM. 15 A modified Outerbridge-Kashiwagi procedure
has been described in which the triceps was elevated rather than
split to access the olecranon and a trephine used to remove
osteophytes encroaching on the olecranon and coronoid fossae.
This modification was called ulnohumeral arthroplasty. 16 At an
average of 80 months, mean flexion/extension arc improved
significantly from 79° to 101°, 76% of patients had no pain, and
75.5% of patients had excellent or good Mayo Elbow Performance
Scores (MEPS). 13 A medial column over-the-top approach, with or
without a lateral column approach, has also been investigated
specifically to treat pos raumatic elbow stiffness. These dual
approaches have demonstrated an improvement in ROM at mean
1.5 years, although a relatively high rate of additional procedures
was reported, including manipulation under anesthesia and
subsequent revision contracture releases. 17
Open synovectomy alone has been investigated in patients with
rheumatoid arthritis. Long-term follow-up has demonstrated
survivorship of synovectomy for rheumatoid arthritis after 10, 15,
and 20 years at 97%, 75%, and 70%, respectively, with an overall
recurrence of synovitis of 31%. 18
Arthroscopic Techniques
Arthroscopic techniques for the management of elbow arthritis
have been developed and are gaining favor. An arthroscopic
procedure with three-dimensional reshaping of the bones of the
elbow joint, removal of loose bodies, and capsulectomy has been
described and is known as arthroscopic osteocapsular arthroplasty.
19
This is a technically demanding procedure that involves four key
steps: (1) establishing a view, (2) creating a space in which to work,
(3) bone removal, and (4) capsulectomy (Figure 3). In this technique
prior to osteocapsular arthroplasty the ulnar nerve is released
through a limited posteromedial skin incision. Advocates of this
procedure find that it provides comparable results to similar open
procedures with quicker recovery and be er cosmetic results. 19
Other authors have compared arthroscopic débridement, with and
without capsulectomy, and have shown greater improvement in
ROM with capsulectomy without a difference in rate of
complications. 20 According to a 2019 study, no difference has been
shown in efficacy of arthroscopic débridement in primary versus
pos raumatic elbow arthritis, with improvement in pain, ROM, and
functional score in both groups. 21
 Figure 3 Clinical images of an elbow arthroscopy.A, The anterior joint looking
from lateral to medial with a coronoid spur (*) and its subsequent débridement
and distal humeral osteoplasty (^) (B). C, The posterior elbow joint with a large
olecranon spur (**) and its subsequent débridement (D).(Courtesy of Jason C.
Ho, MD.)

Open Versus Arthroscopic Débridement

As arthroscopic débridement has become more popular, several
authors have investigated whether a difference in outcomes exists
when compared with open procedures. In a 2019 series from a
single institution comparing 35 consecutive open débridements
with 52 consecutive arthroscopic osteocapsular arthroplasties at a
mean follow-up of approximately 3 years, both procedures
demonstrated similar significant improvements in ROM, MEPS,
and visual analog scale score. 22 Both groups demonstrated inferior
outcomes when preoperative ulnohumeral joint narrowing was
measured at <2 mm. A 2020 systematic review of the literature
found no difference in functional outcomes and similar
improvements in ROM between open and arthroscopic procedures,
leading to the conclusion that both are effective and reliable
techniques. 23

Elbow Interposition Arthroplasty

In more advanced cases of primary or pos raumatic elbow arthritis
where joint débridement may not reliably produce a satisfactory
outcome, arthroplasty is usually considered. Débridement alone is
unlikely to be reliable when there is pain throughout the arc of
motion and radiographs/CT demonstrate extensive joint
destruction with a loss of cartilage and narrowing of the entire joint
space. Total elbow arthroplasty (TEA) will be discussed in the next
paragraphs, but because of concerns with implant longevity in
active patients other procedures have been developed that maintain
the native bony architecture of the elbow while a empting to
provide pain relief. A technique has been described in which the
joint is exposed with a triceps-on technique, the joint is thoroughly
débrided of osteophytes, and the humeral articulation is resurfaced
with allograft such as fascia lata, Achilles tendon, or a similar
synthetic substance. 24 This procedure has been advocated in the
se ing of severe primary or pos raumatic elbow arthritis or stage
II or IIA rheumatoid arthritis in young, high-demand patients.
Other authors have found mixed results, with fewer than one-half
of patients having good or excellent results at mean 6-year follow-
up with a high rate of revision, leading to the conclusion that this
procedure should be reserved only for young, active patients who
may not tolerate TEA. 25 Some recent studies have reported more
favorable results for pos raumatic and rheumatoid cases, with
most patients having significantly improved MEPS and excellent or
good results at short-term follow-up when performing
interpositional arthroplasty as a salvage procedure in lieu of TEA 26

(Figure 4).

Figure 4 Clinical images from a patient with elbow arthritis (A), with a dermal
allograft (B) used as an interposition arthroplasty.(Reproduced with permission
from Ahmed P, Debbarma I, Ameer F: Management of elbow arthritis by
interposition arthroplasty with abdominal dermal graft. J Clin Orthop Trauma
2020;11[suppl 4]:S610-S620.)

Total Elbow Arthroplasty

TEA is generally reserved for severe elbow arthritis for which joint
preservation is unlikely to provide a satisfactory outcome.
Historically TEA was performed most commonly for inflammatory
arthropathies, but this indication has become less prevalent with
the advent of disease-modifying antirheumatic drugs. From 1997 to
2006, TEA performed for inflammatory conditions decreased from
43% of all TEAs in a single state to 19%. 27 Similarly, a study of all
TEAs performed in Germany from 2005 to 2014 revealed a decrease
of 20% to 2.6% in TEAs performed for inflammatory conditions. 28
The same studies found that over time, elbow trauma has become
the most common indication for TEA, surpassing arthritic
conditions. 27 , 28 Although the incidence of TEA performed for
inflammatory conditions has decreased because of disease-
modifying antirheumatic drugs, evidence has demonstrated that
this may be the most reliable indication for TEA in terms of
patient-reported outcomes. A 2019 meta-analysis comparing results
of TEA for rheumatoid arthritis versus pos raumatic elbow
arthritis demonstrated higher MEPS in the rheumatoid arthritis
group with decreased rate of mechanical failure. 29
The literature regarding outcomes of TEA performed for primary
elbow osteoarthritis is sparse. In a case series of 18 patients with a
mean age of 68 years and a mean follow-up of 8.9 months, a 16.6%
rate of major complications requiring a revision surgery was
reported. In patients without mechanical failure, pain scores were
significantly improved, but there was no significant clinical change
in elbow ROM. 30 A study of the outcomes of a single TEA implant
in 11 patients older than 65 years with primary osteoarthritis
demonstrated significant reductions in pain and ROM
improvement with minimal complications at mean follow-up of 57.6
months, leading to the conclusion that TEA is a reasonable option
in elderly patients with primary osteoarthritis. 31
Generally, surgeons are hesitant to perform TEA in younger
patients because of concerns with implant longevity related to
activity demands. Some authors limit patient weight-bearing to 5 to
10 lb, which is an amount generally reported in the literature. This
concern is further reflected by reported long-term survivorship of
TEA. The Norwegian Arthroplasty Registry has reported 5-, 10-, 15-,
and 20-year overall survivorship for TEA as 92%, 81%, 71%, and
61%, respectively. 32 The Australian registry reported revision rates
of 10%, 15%, and 19% at 3, 6, and 9 years, respectively. This 2019
study found that the most common reasons for revision were
infection (35% of revisions) and aseptic loosening (34% of
revisions). 33 The study of the nationwide German registry found an
increase in rate of revision from 10.3% to 17.1% over this 9-year
study period. 28 In a case series examining TEAs in patients younger
than 50 years, 82% of patients experienced a complication and over
half experienced mechanical failures at a mean of 3.2-year follow-
up, leading the authors to caution surgeons against placing TEAs in
younger high-demand patients. 34
TEA implant design may affect outcomes. There are four general
types of TEA designs: unlinked, linked semiconstrained,
semiconstrained condylar-bearing, and convertible. The main
differences between implant styles lies in the level of constraint.
The unlinked design is unconstrained and was designed to
overcome mechanical loosening seen in linked and hinged
prostheses. Nonconstrained TEAs do not impart intrinsic stability
and rely on the integrity of the elbow’s native stabilizers, mainly
the collateral ligaments and posterior capsule and surrounding
musculature. Because it relies on a preserved soft-tissue envelope,
this type of implant has been mainly used in the management of
rheumatoid arthritis. At minimum 10-year follow-up for
unconstrained TEA performed in patients with rheumatoid
arthritis, the survivorship was 87.8% and 70.7% at 5 and 10 years,
respectively, with a rate of aseptic loosening of 26.8%. 35 Linked
semiconstrained designs, such as the Coonrad-Morrey Elbow
(Zimmer), are some of the most commonly used and extensively
studied (Figure 5). Because of its linked design, the elbow
collaterals do not need to be competent for its use. Theoretically, its
semiconstrained design allows for some varus/valgus movement
and axial rotation, which reduces stress at the bone-cement
interface. Although this theoretical advantage exists, high rates of
aseptic loosening are still reported with this type of implant,
especially in reference to the ulnar component. Semiconstrained
condylar-bearing designs were created to decrease polyethylene
edge loading and decrease bushing wear. They have promising
results at short-term (4-year) follow-up, 36 but long-term outcome
studies are needed. Convertible designs exist in which the surgeon
may choose between a semiconstrained and nonconstrained
prosthesis based on the integrity of the collateral ligaments, and
condition of the radial head and surrounding soft tissue. Based on
the available literature, it is difficult to ascertain superiority of one
design rationale over another. The Australian registry study found
no difference in rates of revision among the various implant
designs. 33

Figure 5 Postoperative AP and lateral radiographs demonstrating the use of a

semiconstrained total elbow arthroplasty (Coonrad-Morrey Elbow; Zimmer) for
the treatment of advanced elbow rheumatoid arthritis.Preoperative radiographs
of this patient are presented in Figure 1, B(Courtesy of Jason C. Ho, MD.)

Recently, elbow hemiarthroplasty with distal humeral

replacement has emerged as an alternative to TEA (Figure 6). This
has been investigated extensively for the management of distal
humeral fractures, but few data exist to support its use to manage
elbow arthritis. Hemiarthroplasty is theoretically advantageous for
use in young patients because it allows for preservation of radial
and ulnar bone stock and does not require strict postoperative
activity limitations given the absence of an ulnar component. A
2019 study reporting hemiarthroplasty in 16 elbows in patients with
an average age of 45 years noted marked improvement in ROM at a
mean follow-up of 51 months, but excellent or good results based
on MEPS were obtained in just over half of the patients. 37
Additional surgery was necessary in one-third of the patients, and
two patients required conversion to TEA. Although literature
surrounding elbow hemiarthroplasty for distal humeral fracture
has been promising, additional research is needed before it can be
considered a reliable option for elbow arthritis in a young
population.

Figure 6 Five-year follow-up AP and lateral radiographs of posttraumatic elbow

arthritis after open reduction and internal fixation (A) managed with elbow
hemiarthroplasty (B).(Reprinted with permission from Werthel JD, Schoch B,
Adams J, Steinmann S: Outcomes after hemiarthroplasty of the elbow for the
management of posttraumatic arthritis: Minimum 2-year follow-up. J Am Acad
Orthop Surg 2019;27[19]:727-735.)

Nerve Disorders
The two most common nerve disorders involving the elbow are
cubital tunnel and radial tunnel syndromes involving the ulnar and
radial nerves, respectively. These syndromes arise from several
areas of entrapment. Other etiologies include previous trauma or
surgery. These may coincide with elbow arthritides or may occur in
isolation.

Cubital Tunnel Syndrome

Cubital tunnel syndrome is the second most common upper
extremity compressive neuropathy after carpal tunnel syndrome. 38
If left untreated, cubital tunnel syndrome may lead to permanent
loss of sensation, muscle weakness, and/or joint contractures in the
ulnar nerve distribution. The ulnar nerve may be compressed at
several sites proximal, at, or distal to the elbow. The cubital tunnel,
which is the most common site of entrapment, is defined as the
space occupied by the ulnar nerve posterior to the medial
epicondyle of the distal humerus and covered by the Osborne
ligament. Proximally, the nerve may be entrapped at the arcade of
Struthers 6 to 10 cm proximal to the medial epicondyle, which is a
band of thickened connective tissue extending from the medial
triceps to the intermuscular septum. Distally in the forearm the
ulnar nerve may be entrapped in the deep fascia or between the two
heads of the flexor carpi ulnaris or the fascia of the flexor digitorum
superficialis. Elbow trauma may contribute to cubital tunnel
syndrome; pos raumatic cubital tunnel syndrome has been
reported to occur after 1% to 10% of elbow dislocations, and after
12% of distal humeral fractures. 38 Rarely, a space-occupying lesion
also may be a cause (Figure 7). When considering a differential
diagnosis for ulnar nerve symptoms such as paresthesia of the
ulnar side of the hand, nerve root (C8/T1) radicular compression
and more distal compression at Guyon canal in the wrist must also
be considered.
 Figure 7 Clinical photographs showing surgical treatment of cubital tunnel
syndrome.A, Image shows a decompressed ulnar nerve (U) with a ganglion cyst
(*) in the cubital tunnel causing ulnar neuritis. B, The ganglion is resected.
Humerus (H) and forearm (FA) are marked for orientation. C, A ganglion cyst (^)
is noted compressing the posterior interosseus nerve (P) just as the nerve is
going under the supinator (S) of a 25-year-old patient with posterior interosseous
nerve palsy and after resection (D). Note the severe nerve compression in panel
D as demonstrated by the hour-glassing and erythema at the site of
compression. The patient made a full motor recovery by 6 weeks
postoperatively.(Courtesy of Joseph F. Styron, MD, PhD, FAAOS.)

Patients will most commonly report altered sensation of the volar

ring and small fingers of the affected extremity. As the process
progresses, hand weakness and loss of fine hand manipulation may
also be reported. Prolonged elbow flexion may exacerbate these
symptoms. Complaints of pain are less common but may be
experienced along the course of the ulnar nerve in the
posteromedial elbow and ulnar forearm. If pain about the elbow is
the main complaint, other etiologies such as medial epicondylitis or
ulnohumeral arthritis should be considered. A careful physical and
neurologic examination should be performed. Sensation of the ring
and small fingers should be assessed with two-point discrimination
or Semmes-Weinstein monofilament testing. On inspection, muscle
atrophy may be evident in the first web space where the first dorsal
interosseous muscle, supplied by the ulnar nerve, provides the
most bulk. Classic examination findings include the Wartenberg
sign, which occurs when the patient is unable to adduct the small
finger because of dysfunction of the third palmar interosseous
muscle, and the Froment sign, which is obligate thumb
interphalangeal flexion with key pinch to compensate for a
weakened adductor pollicis muscle, also supplied by the ulnar
nerve. Electrodiagnostic studies may aid in the diagnosis, but
normal results do not exclude its presence because of diagnostic
error a ributable to variable elbow position, skin temperature, and
soft-tissue bulk about the elbow. 38
The severity of the syndrome may be classified as mild disease
(limited to intermi ent paresthesias and subjective weakness),
moderate disease (intermi ent paresthesias and objective
weakness), and severe disease (persistent paresthesias and
objective weakness with or without intrinsic muscle atrophy).
Choice of initial treatment is usually based on severity at
presentation. Nonsurgical treatment is appropriate for mild and
sometimes moderate disease and includes night splinting, therapy,
elbow pads, NSAIDs, and activity modification. In a prospective
study of a 3-month course of rigid night splinting to maintain the
elbow at 45°, 88% of patients were successfully treated (did not
require surgery) at mean 2-year follow-up. 39 However, a
randomized controlled trial comparing night splinting and nerve
gliding exercises with no intervention in patients with mild to
moderate symptoms found that at 6-month follow-up 89.5% of
patients improved regardless of the type of nonsurgical
intervention received, with the remainder of patients proceeding to
surgical treatment. 40
 Regardless of nonsurgical treatment choice, most authors agree
nonsurgical treatment should be reserved for those with mild or
moderate symptoms and surgical treatment is appropriate in those
with mild/moderate disease in whom nonsurgical treatment has
failed and those with advanced disease. There are several surgical
treatment methods available for cubital tunnel syndrome including
open or endoscopic in situ decompression, ulnar nerve
transposition, and medial epicondylectomy. In situ decompression
consists of releasing the Osborne ligament, the superficial and deep
fascia of the flexor carpi ulnaris distally, and the fascia between the
medial triceps and medial intermuscular septum proximally
resulting in approximately 6 cm of decompression (Figure 7). The
endoscopic technique allows for a smaller incision and more
extensive decompression. A retrospective cohort study comparing
open and endoscopic techniques found improved short-term
results in return to full activity and duration of postoperative pain,
but no significant difference in long-term results. 41 Several
techniques have been described for ulnar nerve transposition
including submuscular, intramuscular, and subcutaneous
transposition. In general, they all involve circumferential release of
the nerve with relocation anterior to the medial epicondyle with
stabilization to soft-tissue structures. Randomized controlled trials
have found equivalent results at 1-year follow-up for simple
decompression versus transposition, with significantly fewer
complications in the simple decompression group. 42 There are
relatively limited data regarding long-term outcomes. A 2021 study
found that at minimum 5-year follow-up simple in situ
decompression resulted in a significantly higher revision surgery
rate (25%) versus anterior subcutaneous decompression (12%).
Most of the revisions (78%) for the in situ decompression group
were performed within 3 years of the index surgery. It was also
concluded that younger age and female sex were independent
predictors of the need for revision surgery. 43
Medial epicondylectomy as a treatment for cubital tunnel
syndrome was developed with the rationale that it would remove at
least four sites of compression: the medial intermuscular septum,
the medial epicondyle, the aponeurosis of the flexor carpi ulnaris,
and the cubital tunnel retinaculum. 44 Early results demonstrated it
to be effective at relieving ulnar nerve symptoms, but results were
tempered by medial elbow pain and elbow instability. 44 This was
a ributed to detachment of the anterior bundle of the elbow
medial collateral ligament. A modification to the procedure was
proposed, whereby the medial epicondyle is exposed with
visualization and protection of the anterior bundle of the medial
collateral ligament and osteotomized obliquely between the coronal
and sagi al planes to create a flat surface on which the nerve is
allowed to glide. Good or excellent outcomes were reported in 93%
of patients at 2-year follow-up, with 3 of 27 patients reporting
medial elbow pain and 1 patient with a 30° flexion contracture. 45 A
prospective randomized study comparing medial epicondylectomy
to ulnar nerve transposition found no differences in motor power or
nerve conduction rates with nerve conduction velocity studies at
mean 4.5-year follow-up, but did find higher patient satisfaction in
the medial epicondylectomy, with 92% of patients reporting they
would have the procedure again versus 68% in the nerve
transposition group. 46

Radial Tunnel Syndrome

Radial tunnel syndrome is a compressive neuropathy of the
posterior interosseous nerve, a branch of the radial nerve. This is an
uncommon pathology, with an annual incidence of only 0.03%. 47
The radial tunnel is the anatomic boundary of the radial nerve
about the elbow measuring approximately 5 cm in length and
bounded laterally by the brachioradialis, extensor carpi radialis
longus, and extensor carpi radialis brevis, medially by the biceps
tendon and brachialis with the floor composed of the elbow joint
capsule. There are several described sites of posterior interosseous
nerve compression in the radial tunnel. The most common site of
compression is the tendinous edge of the superficial supinator
muscle, known as the arcade of Frohse. 48 Other sites of
compression are the tendinous edge of the extensor carpi radialis
brevis, the radial recurrent artery (leash of Henry), and fibrous
bands distal to the radial head.
Radial tunnel syndrome is diagnosed clinically. Patients typically
present with lateral forearm pain that must be distinguished from
lateral epicondylitis. Patients may report tenderness in the mobile
wad area that worsens with activity. 49 On physical examination,
palpation over the mobile wad approximately 2 to 5 cm distal to the
lateral epicondyle elicits maximal tenderness. Provocative tests aim
at placing tension on the radial nerve to elicit pain and include
resisted forearm supination, resisted wrist extension, and resisted
long finger extension. Although it is largely a clinical diagnosis,
radiographs of the elbow should be obtained to exclude an osseous
abnormality of prior trauma as a source of compression. MRI can
be considered, although results are typically negative. When
findings are present they may include denervation edema of
muscles innervated by the posterior interosseous nerve, thickened
extensor carpi radialis brevis edge, prominent radial recurrent
vessels, swelling of the posterior interosseous nerve, or
compressive space-occupying lesions 49 (Figure 7). Electrodiagnostic
studies are generally inconclusive because of the composition of
the posterior interosseous nerve and should not be used to
establish a diagnosis.
The mainstay of treatment for radial tunnel syndrome is
nonsurgical and includes activity modifications, NSAIDs, and
temporary splinting. Generally, these should be trialed for up to 1
year before invasive treatments are considered. Corticosteroid
injections may be both diagnostic and therapeutic. A 2019 study
demonstrated that a single corticosteroid injection in the proximal
forearm at the point of maximal tenderness produced significantly
improved pain and disability scores at 2 weeks, 3 months, and 1
year. In this series of 40 patients, 57% achieved clinically important
difference in the Quick Disabilities of the Arm, Shoulder and Hand
score, and 23% of patients went on to surgical treatment. 50 When
nonsurgical treatment fails, surgery usually involves the release of
the most common sites of compression through one of several
approaches to the posterior interosseous nerve.

Summary
Primary osteoarthritis, pos raumatic arthritis, and inflammatory
arthritis of the elbow are debilitating conditions that may limit the
functional use of the upper extremity and cause substantial
disability. Treatment should be focused on the individual’s loss of
ROM, pain, or both. A proper understanding of the etiology and
level of dysfunction is necessary to apply the appropriate available
treatments. This is similar for the treatment of patients with nerve
compression pathologies about the elbow.

Key Study Points

The three most common etiologies of elbow arthrosis are primary osteoarthritis,
posttraumatric arthritis, and rheumatoid arthritis.
Treatment options for the various etiologies must take into account patient age,
activity level, degree of pathology, and expectations.
Elbow débridement, open or arthroscopic, may be effective in the management of
mild to moderate elbow arthritis. Interposition arthroplasty and TEA should be
reserved for more advanced cases in appropriately indicated patients.
TEA should be reserved for patients who will be compliant with activity restrictions.
Given the relatively poor outcomes and aseptic loosening in TEA performed for
younger, more active patients, alternative treatment options should be considered.
Patients should be counseled on the expected longevity of the implant and potential
need for future revision surgery.
Cubital tunnel syndrome should be managed based on degree of pathology. Both in
situ decompression and ulnar nerve transposition are effective surgical treatments.
Radial tunnel syndrome should be managed nonsurgically, with surgery reserved for
patients not responsive to extensive nonsurgical treatment.

Annotated References
1. Sardelli M, Tashjian RZ, MacWilliams BA: Functional elbow
range of motion for contemporary tasks. J Bone Joint Surg Am
2011;93(5):471-477.
 2. Cheung EV, Adams R, Morrey BF: Primary osteoarthritis of the
elbow: Current treatment options. J Am Acad Orthop Surg
2008;16(2):77-87.
3. Chadwick EKJ, Nicol AC: Elbow and wrist joint contact forces
during occupational pick and place activities. J Biomech
2000;33(5):591-600.
4. Hwang JT, Kim Y, Shields MN, et al: Effects of axial forearm
instability on force transmission across the elbow. J Shoulder
Elbow Surg 2019;28(1):170-177. This study of 10 cadaver upper
limbs investigated the relative force across the radiocapitellar
and ulnohumeral joints with various types of injuries simulated.
Level of evidence: IV.
5. Gui on TG, Zurakowski D, Van Dijk NC, Ring D: Incidence and
risk factors for the development of radiographic arthrosis after
traumatic elbow injuries. J Hand Surg Am 2010;35(12):1976-1980.
6. Doornberg JN, Van Duijn PJ, Linzel D, et al: Surgical treatment
of intra-articular fractures of the distal part of the humerus:
Functional outcome after twelve to thirty years. J Bone Joint Surg
Am 2007;89(7):1524-1532.
7. Rochet S, Obert L, Lepage D, Lemaire B, Leclerc G, Garbuio P:
Proximal ulna comminuted fractures: Fixation using a double-
plating technique. Orthop Traumatol Surg Res 2010;96(7):734-740.
8. Studer A, Athwal GS: Rheumatoid arthritis of the elbow. Hand
Clin 2011;27(2):139-150.
9. Finckh A, Liang MH, Van Herckenrode CM, De Pablo P: Long-
term impact of early treatment on radiographic progression in
rheumatoid arthritis: A meta-analysis. Arthritis Care Res
2006;55(6):864-872.
10. Alnusif NS, Matache BA, AlQahtani SM, et al: Effectiveness of
radiographs and computed tomography in evaluating primary
elbow osteoarthritis. J Shoulder Elbow Surg 2021;30(7):S8-S13. The
authors present a radiographic study of arthritic elbows
comparing plain radiographs and two-dimensional CT scans for
preoperative assessment of osteophyte and loose body location,
 demonstrating that CT has greater sensitivity and superior
interrater percentage agreement in detecting osteophytes and
loose bodies. Level of evidence: I.
11. van Brakel RW, Eygendaal D: Intra-articular injection of
hyaluronic acid is not effective for the treatment of post-
traumatic osteoarthritis of the elbow. Arthroscopy
2006;22(11):1199-1203.
12. Williams BG, Sotereanos DG, Bara ME, Jarre CD, Venouziou
AI, Miller MC: The contracted elbow: Is ulnar nerve release
necessary? J Shoulder Elbow Surg 2012;21(12):1632-1636.
13. Antuña SA, Morrey BF, Adams RA, O’Driscoll SW:
Ulnohumeral arthroplasty for primary degenerative arthritis of
the elbow: Long-term outcome and complications. J Bone Joint
Surg Am 2002;84(12):2168-2173.
14. Minami M, Kato S, Kashiwagi D: Outerbridge-Kashiwagi’s
method for arthroplasty of osteoarthritis of the elbow — 44
elbows followed for 8–16 years. J Orthop Sci 1996;1(1):11-15.
15. Oka Y: Debridement arthroplasty for osteoarthrosis of the
elbow: 50 patients followed mean 5 years. Acta Orthop Scand
2000;71(2):185-190.
16. Morrey BF: Primary degenerative arthritis of the elbow:
Treatment by ulnohumeral arthroplasty. J Bone Joint Surg Br
1992;74(3):409-413.
17. Tan V, Daluiski A, Simic P, Hotchkiss RN: Outcome of open
release for post-traumatic elbow stiffness. J Trauma
2006;61(3):673-678.
18. Ishii K, Inaba Y, Mochida Y, Saito T: Good long-term outcome of
synovectomy in advanced stages of the rheumatoid elbow. Acta
Orthop 2012;83(4):374-378.
19. O’Driscoll SW, Blonna D: Osteocapsular arthroplasty of the
elbow. JBJS Essent Surg Tech 2013;3(3):e15.
20. Isa AD, Athwal GS, King GJW, MacDermid JC, Faber KJ:
Arthroscopic debridement for primary elbow osteoarthritis with
 and without capsulectomy: A comparative cohort study. Shoulder
Elbow 2018;10(3):223-231.
21. Carlier Y, Desmoineaux P, Lenoir H, Vidil A: Prospective
comparative analysis of arthroscopic debridement for primary
and post-traumatic elbow osteoarthritis. Orthop Traumatol Surg
Res 2019;105(8):S217-S220. This prospective multicenter study
investigated the relative efficacy of arthroscopic elbow
débridement for primary versus pos raumatic elbow
osteoarthritis, demonstrating similar efficacy for both groups.
Level of evidence: III.
22. Kwak JM, Kholinne E, Sun Y, Lim S, Koh KH, Jeon IH: Clinical
outcome of osteocapsular arthroplasty for primary osteoarthritis
of the elbow: Comparison of arthroscopic and open procedure.
Arthroscopy 2019;35(4):1083-1089. This retrospective comparative
trial investigated the clinical outcomes of open versus
arthroscopic osteocapsular arthroplasty for patients with primary
elbow osteoarthritis. The open group demonstrated greater
improvements in flexion limitation; otherwise, the groups were
comparable in MEPS and visual analog scale score
improvements. Level of evidence: III.
23. Guerrero EM, Bullock GS, Helmkamp JK, et al: The clinical
impact of arthroscopic vs. open osteocapsular débridement for
primary osteoarthritis of the elbow: A systematic review. J
Shoulder Elbow Surg 2020;29(4):689-698. The authors of this
systematic review investigated arthroscopic versus open
débridement for the management of primary elbow
osteoarthritis, demonstrating that both open and arthroscopic
débridement are effective, both reliably improving flexion,
extension, and functional outcome scores. Level of evidence: IV.
24. Chen DD, Forsh DA, Hausman MR: Elbow interposition
arthroplasty. Hand Clin 2011;27:187-197.
25. Larson AN, Morrey BF: Interposition arthroplasty with an
achilles tendon allograft as a salvage procedure for the elbow. J
Bone Joint Surg Am 2008;90(12):2714-2723.
26. Ahmed P, Debbarma I, Ameer F: Management of elbow
arthritis by interposition arthroplasty with abdominal dermal
graft. J Clin Orthop Trauma 2020;11(suppl 4):S610-S620. A series of
18 arthritic elbows (mean patient age, 34.3 years) managed with
dermal allograft interposition arthroplasty by a single surgeon
demonstrated improved elbow range of motion and MEPS at
mean 22-month follow-up. Level of evidence: IV.
27. Gay DM, Lyman S, Do H, Hotchkiss RN, Marx RG, Daluiski A:
Indications and reoperation rates for total elbow arthroplasty: An
analysis of trends in New York State. J Bone Joint Surg Am
2012;94(2):110-117.
28. Klug A, Gramlich Y, Buckup J, Schweigkofler U, Hoffmann R,
Schmidt-Horlohé K: Trends in total elbow arthroplasty: A
nationwide analysis in Germany from 2005 to 2014. Int Orthop
2018;42(4):883-889.
29. Wang JH, Ma HH, Chou TFA, et al: Outcomes following total
elbow arthroplasty for rheumatoid arthritis versus post-traumatic
conditions: A systematic review and meta-analysis. Bone Joint J
2019;101-B(12):1489-1497. A meta-analysis investigating the
outcomes of total elbow arthroplasty for the management of
rheumatoid arthritis and pos raumatic elbow arthritis including
679 TEAs is presented. The rheumatoid arthritis group was
associated with a higher risk of septic loosening, but had a higher
MEPS. There is no difference found in range of motion;
Disabilities of the Arm, Shoulder and Hand score; aseptic
loosening; deep infection; perioperative fracture; or ulnar
neuropathy. Level of evidence: IV.
30. Schoch BS, Werthel JD, Sánchez-Sotelo J, Morrey BF, Morrey M:
Total elbow arthroplasty for primary osteoarthritis. J Shoulder
Elbow Surg 2017;26(8):1355-1359.
31. Naqui SZ, Rajpura A, Nu all D, Prasad P, Trail A: Early results
of the Acclaim total elbow replacement in patients with primary
osteoarthritis. J Bone Joint Surg Br 2010;92(5):668-671.
32. Krukhaug K, Hallan G, Dybvik E, Lie SA, Furnes ON: A
survivorship study of 838 total elbow replacements: A report
from the Norwegian Arthroplasty Register 1994-2016. J Shoulder
Elbow Surg 2018;27(2):260-269.
33. Viveen J, van den Bekerom MPJ, Doornberg JN, et al: Use and
outcome of 1,220 primary total elbow arthroplasties from the
Australian Orthopaedic Association National Joint Arthroplasty
Replacement Registry 2008–2018. Acta Orthop 2019;90(6):511-516.
An analysis of the Australian Orthopaedic Association National
Joint Replacement Registry investigated the trends of TEA use
and survivorship, reporting the most common reasons for
revision were infection and aseptic loosening. Level of evidence:
IV.
34. Schoch B, Wong J, Abboud J, Lazarus M, Ge C, Ramsey M:
Results of total elbow arthroplasty in patients less than 50 years
old. J Hand Surg Am 2017;42(10):797-802.
35. Kodama A, Mizuseki T, Adachi N: Kudo type-5 total elbow
arthroplasty for patients with rheumatoid arthritis: A minimum
ten-year follow-up study. Bone Joint J 2017;99-B(6):818-823.
36. Hastings H, Lee DH, Pietrzak WS: A prospective multicenter
clinical study of the Discovery elbow. J Shoulder Elbow Surg
2014;23(5):e95-e107.
37. Werthel JD, Schoch B, Adams J, Steinmann S: Outcomes after
hemiarthroplasty of the elbow for the management of
pos raumatic arthritis: Minimum 2-year follow-up. J Am Acad
Orthop Surg 2019;27(19):727-735. A case series with minimum 2-
year follow-up of 16 elbows that underwent elbow
hemiarthroplasty for pos raumatic arthritis reported high rates
of revision surgery, but good or excellent MEPS and 57% of
patients with surviving implants. Level of evidence: IV.
38. Staples JR, Calfee R: Cubital tunnel syndrome: Current
concepts. J Am Acad Orthop Surg 2017;25(10):e215-e224.
39. Shah CM, Calfee RP, Gelberman RH, Goldfarb CA: Outcomes of
rigid night splinting and activity modification in the treatment of
 cubital tunnel syndrome. J Hand Surg Am 2013;38(6):1125-1130.e1.
40. Svernlov B, Larrson M, Rehn K, Adolfsson L: Conservative
treatment of the cubital tunnel syndrome. J Hand Surg Eur Vol
2009;34(2):201-207.
41. Dü mann S, Martin KD, Sobo ka S, et al: Open vs retractor-
endoscopic in situ decompression of the ulnar nerve in cubital
tunnel syndrome: A retrospective cohort study. Neurosurgery
2013;72(4):605-616.
42. Biggs M, Curtis JA: Randomized, prospective study comparing
ulnar neurolysis in situ with submuscular transposition.
Neurosurgery 2006;58(2):296-303.
43. Hutchinson DT, Sullivan R, Sinclair MK: Long-term reoperation
rate for cubital tunnel syndrome: Subcutaneous transposition
versus in situ decompression. Hand (N Y) 2021;16(4):447-452. This
retrospective multicenter cohort study compared subcutaneous
ulnar nerve transposition versus in situ decompression for
cubital tunnel syndrome with minimum 5-year follow-up,
demonstrating statistically significant higher long-term revision
surgery rate for the in situ decompression group. Level of
evidence: IV.
44. Kaempffe FA, Farbach J: A modified surgical procedure for
cubital tunnel syndrome: Partial medial epicondylectomy. J Hand
Surg Am 1998;23(3):492-499.
45. Osei DA, Padegimas EM, Calfee RP, Gelberman RH: Outcomes
following modified oblique medial epicondylectomy for
treatment of cubital tunnel syndrome. J Hand Surg Am
2013;38(2):336-343.
46. Geutjens GG, Langstaff RJ, Smith NJ, Jefferson D, Howell CJ,
Barton NJ: Medial epicondylectomy or ulnar nerve transposition
for ulnar neuropathy at the elbow? J Bone Joint Surg Br
1996;78(5):777-779.
47. Dang AC, Rodner CM: Unusual compression neuropathies of
the forearm, part I: Radial nerve. J Hand Surg Am
2009;34(10):1906-1914.
48. Konjengbam MK, Elangbam J: Radial nerve in the radial tunnel:
Anatomic sites of entrapment neuropathy. Clin Anat
2004;17(1):21-25.
49. Levina Y, Dantuluri PK: Radial tunnel syndrome. Curr Rev
Musculoskelet Med 2021;14(3):205-213. This review article
highlights the natural history, etiology, presentation, and
management of radial tunnel syndrome. Level of evidence: V.
50. Marchese J, Coyle K, Cote M, Wolf JM: Prospective evaluation of
a single corticosteroid injection in radial tunnel syndrome. Hand
(N Y) 2019;14(6):741-745. This prospective study of 40 patients
with clinical diagnosis of radial tunnel syndrome given a single
corticosteroid injection with 1-year follow-up demonstrated
improved Quick Disabilities of the Arm, Shoulder and Hand and
visual analog scale scores at 12 weeks and 1 year. Level of
evidence: IV.
C H AP T E R 3 2

Tendinopathy, Throwing Injuries,

and Elbow Ligament
Reconstruction
Noah J. Quinlan MD, Peter Chalmers MD, FAAOS

Dr. Chalmers or an immediate family member has received royalties from DePuy, a Johnson &
Johnson Company; is a member of a speakers’ bureau or has made paid presentations on behalf
of DePuy, a Johnson & Johnson Company; and serves as a paid consultant to or is an employee
of DePuy, a Johnson & Johnson Company and DJ Orthopaedics. Neither Dr. Quinlan nor any
immediate family member has received anything of value from or has stock or stock options held
in a commercial company or institution related directly or indirectly to the subject of this chapter.

ABSTRACT
The elbow is constrained by dynamic and static stabilizers. A
variety of mechanisms from chronic degradation to acute trauma
may lead to predictable pa erns of injury to these structures.
Tendon injuries about the elbow range from tendinopathy to acute
rupture and primarily affect the flexor/pronator mass (medial
epicondylitis), extensor/supinator mass (lateral epicondylitis), distal
biceps, or triceps. Although acute ruptures are often managed with
surgical repair or reconstruction, tendinopathy is managed
nonsurgically and primarily responds to activity modification.
Although tendon injures about the elbow occur in a variety of
se ings, ligament injuries are seen with more specific mechanisms.
Throwing leads to injuries about the elbow because of medial
tension, lateral compression, and posterior shear forces. Valgus
overload about the elbow may lead to ulnar collateral ligament
injuries, which can have a significant effect on throwing efficacy in
addition to causing pain. When refractory to nonsurgical measures,
treatment entails reconstruction with good results. Lateral
collateral ligament injury and associated posterolateral rotatory
instability is more commonly seen following a traumatic injury
such as a dislocation. Similarly, when refractory to nonsurgical
treatment, good results can be seen with reconstruction in
appropriately indicated patients.
Keywords: distal biceps injury; elbow tendinopathy; throwing
injuries; ulnar collateral ligament

Introduction
It is important to review current concepts regarding tendon and
ligament injuries about the elbow. Although frank tendon rupture
may be managed surgically, a number of tendinopathies about the
elbow are managed with nonsurgical measures. Unfortunately,
recovery with both surgical and nonsurgical treatment can be a
lengthy process. Recovery from tendinopathy may ultimately be
self-limiting regardless of treatment. Throwing injuries lead to a
predictable pa ern of injury based on forces on the elbow, and
physicians should perform careful evaluation for accurate diagnosis
and optimal treatment. Although patients with partial injury are
typically treated with a course of nonsurgical measures,
reconstruction is indicated for full-thickness tears in patients for
whom nonsurgical treatment has failed.

Tendinopathy

Medial Epicondylitis
Medial epicondylitis, or golfer’s elbow, is a condition caused by
repetitive microtrauma and gradual degradation of the flexor
pronator mass. Originating at the medial epicondyle, the common
tendon of the flexor carpi ulnaris, palmaris longus, pronator teres,
flexor carpi radialis, and flexor digitorum superficialis is
responsible for wrist flexion and forearm pronation. Those most
commonly affected by the condition participate in a profession,
activity, or sport where these motions are repetitive. Onset is often
insidious and exacerbated by activity in the fourth to sixth decades
of life, but can be acute with eccentric contraction of the muscles
causing a strain or even rupture. The muscle mass also serves as a
dynamic stabilizer to valgus stress at the elbow. 1
Physical examination is critical to evaluate the etiology of medial-
sided elbow pain. Medial epicondylitis is exacerbated with flexion
and pronation of the wrist. Patients often experience tenderness
during palpation over the flexor pronator muscle mass just distal to
the medial epicondyle. Evaluation for alternative or concomitant
etiologies such as ulnar collateral ligament (UCL) tears, ulnar
neuritis, or osteoarthritis is imperative. Consideration should be
given to medial epicondyle apophysitis or avulsion in the skeletally
immature population. 1
Imaging is rarely helpful as radiographs are often normal.
Ultrasonography may reveal diseased tendon but requires an
experienced technician. MRI is the gold standard for soft-tissue
evaluation although it is often unnecessary unless there is concern
for rupture. A 2021 study demonstrated that abnormal signal in the
common flexor tendon on MRI was only seen in 66% of clinically
diagnosed cases of medial epicondylitis, and this finding was
associated with persistent pain at follow-up. 2 Electromyography or
nerve conduction studies can be performed if needed to evaluate
for concomitant ulnar nerve pathology.
Management for most medial epicondylitis cases is nonsurgical,
consisting of rest, ice, and nonsteroid anti-inflammatory drugs
(NSAIDS). Physical therapy for strengthening with gradual
progression to activity over the course of weeks to months is
typical, with most cases resolving without further intervention.
Recent focus has been on alternative nonsurgical modalities
including injections (steroid, autologous whole blood, platelet-rich
plasma [PRP]), splinting, kinesiology taping for counterforce brace
treatment, and extracorporeal shock wave therapy. 1
Few recent studies are specific to medial epicondylitis, as most
involve both medial and lateral tendinopathies. A 2020 meta-
analysis evaluating PRP compared with corticosteroid for both
medial and lateral elbow epicondylitis reported that corticosteroid
may provide more pain relief within the first 3 months, but PRP
may have be er pain relief after 6 months. Neither provided
functional benefit over the other. 3 A 2019 study reported on
ultrasound-guided tenotomy for common extensor, common flexor,
and triceps tendinopathy. Overall, there was a 70% satisfaction rate.
However, specific to the common flexors, no difference in pain or
function was reported. 4 A 2019 randomized controlled trial (RCT)
compared PRP against lidocaine as tenotomy adjuvants for
epicondylitis and found no difference in pain or function. 5 A 2019
study compared PRP with ultrasound-guided percutaneous
tenotomy for either medial or lateral epicondylitis. Again, there
were no differences in pain or function in this mixed cohort. 6 These
findings suggest that PRP likely does not have a role in the
management of this condition. Ultimately, medial epicondylitis is a
self-limiting process best managed with activity modification, and
its course is largely unaltered by treatment modalities based on the
available evidence to date.
Surgical intervention is reserved for refractory chronic cases
(longer than 6 months), or high-level athletes with rupture. In
either case, the procedure entails débridement of the tendon with
subsequent repair or rea achment with transosseous suture or
anchor. Concomitant procedures may include microfracture of the
epicondyle and ulnar nerve decompression or transposition.
Postoperatively, range of motion starts after appropriate soft-tissue
healing, followed by strengthening starting at 6 weeks, and return
to sport-specific activity at 3 months. 1

Lateral Epicondylitis
Lateral epicondylitis, or tennis elbow, is more common than medial
epicondylitis. It most often presents in middle-aged women but is
common in both women and men. Pain occurs over the lateral
aspect of the elbow near the origin of the long wrist extensors in the
absence of elbow instability or nerve-related symptoms. Similar to
medial epicondylitis, it is a ributed to progressive microtrauma of
the long wrist extensors with gradual degradation and fibrosis of
the tendons. Specifically, the extensor carpi radialis brevis and
extensor digitorum communis are affected and thought to be the
source of symptoms. 7 Aside from repetitive activity, few other risk
factors are known, although a 2019 study identified an association
between high total cholesterol levels and lateral epicondylitis. 8 A
2019 study also found pain sensitization was associated with
presenting Disabilities of the Arm, Shoulder and Hand (DASH)
score, symptom duration, and DASH score after 1 year of
nonsurgical management. 9
Patients typically report pain over the dorsum of the forearm that
is worse with wrist extension activities. Repetitive activities such as
typing, writing, or sports may exacerbate symptoms. On
examination, pain may be elicited with direct palpation over the
origin of the wrist extensors at the lateral epicondyle as well as with
resisted wrist extension in elbow extension. Evaluating for
instability or nerve-related syndromes is critical to distinguish
lateral epicondylitis from other diagnoses such as radial tunnel
syndrome. 7
Imaging is rarely helpful except in ruling out other causes of
lateral elbow pain. Radiographs are often negative. MRI and
ultrasonography may identify tendon degeneration with signal or
concomitant ligamentous injuries (Figure 1). As such, the diagnosis
of lateral epicondylitis is largely made on clinical examination and
history. A 2020 study evaluated ultrasound changes in patients with
chronic lateral epicondylitis, comparing the contralateral arm and
healthy control patients. The affected arms exhibited greater
tendon thickness, Doppler activity, and bone spurs. However, the
differences were small and although they may help confirm clinical
suspicion, are not diagnostic. Importantly, there was no correlation
with symptoms, outcomes, or duration. 10

Figure 1 Magnetic resonance image shows common extensor interstitial

tearing and edema.

A number of treatment modalities have been proposed, although

no one treatment has been shown to be most effective in the long
term. Although some treatment modalities may alleviate symptoms
for a period, it is not uncommon for symptoms to recur. Lateral
epicondylitis is largely a self-limiting condition based on activity
that may take 9 to 12 months to resolve, regardless of additional
intervention. Therefore, initial treatment is primarily focused on
activity modification, physical therapy, and gradual return to
activity as tolerated. Various braces have been described such as
counterforce brace treatment and wrist extension splinting. A 2019
RCT compared counterforce brace treatment with placebo brace
treatment for lateral epicondylitis. Although both improved pain
and function, counterforce brace treatment had be er frequency of
pain at rest at 6 and 12 weeks, pain at rest level at 2 weeks, and
elbow function at 26 weeks so it may be beneficial in the short term.
11
Another 2019 RCT evaluated patients without a brace, with a
forearm band, and with an elbow sleeve for lateral epicondylitis.
Both braces improved pain and grip strength, with no significant
difference between them. They each helped with proprioception,
but at different degrees of flexion. 12 These findings suggest that
brace treatment can reduce symptoms of lateral epicondylitis.
Injections into the muscle origin or proximal muscle tissue have
been described including corticosteroid, PRP, autologous blood,
prolotherapy, and saline. These have limited evidence-based
success and potentially only short-term benefits. Steroid injections
pose a risk of weakening the lateral collateral ligament complex and
skin changes including thinning and depigmentation. 7 Innovative
injectable solutions are an active area of investigation. A 2019 study
evaluated an injectable gel with cross-linked bioengineered
recombinant human type 1 collagen combined with autologous
PRP. In patients with chronic lateral epicondylitis, there was 59%
reduction in the Patient-Rated Tennis Elbow Evaluation score at 6
months. They also noted improvement in the 12-item Short-Form
Healthy Survey, grip strength, and ultrasonographic appearance of
the tendon without any adverse effects. 13 Although these results
are promising, randomized studies should be performed before
this treatment can be recommended.
A 2020 RCT of 119 patients with lateral epicondylitis receiving
PRP, autologous blood, or saline found no significant differences in
outcomes or grip strength. 14 Interestingly, a 2020 meta-analysis
reviewing 15 RCTs incorporating normal saline injection for lateral
epicondylitis found significant improvement in pain, function, and
outcome scores at minimum 6-month follow-up. 15 This would
indicate the physical injection, as opposed to what is injected, may
be the significant intervention.
 Extracorporeal shock wave therapy has been proposed although a
2020 meta-analysis found no clinical differences. In subgroup
analysis, the study authors noted a greater effect in patients with
symptoms over 6 months compared with 3 months. Even when
effective, results did not last beyond 24 weeks. 16 A 2019 RCT of 24
patients with lateral epicondylitis evaluated iontophoresis with
dexamethasone and lidocaine compared with a control group.
Although both groups improved, iontophoresis had greater
improvement in pain and function. 17
Percutaneous techniques have also been described. A previously
mentioned 2019 study reported on ultrasound-guided tenotomy for
a variety of pathologies. Specific to the common extensors, the
study authors found significantly improved short-term and long-
term pain, as well as physical function. 4 A 2021 study reported on
ultrasonic percutaneous tenotomy in 20 patients with minimum 7-
year follow-up. Satisfaction was 100% with no recurrence of
symptoms and a significant improvement in outcome scores. 18
Another RCT of 101 patients undergoing dry needling compared
with corticosteroid injection found that, at minimum 6-month
follow-up, both groups improved though dry needling appeared
slightly more effective based on the Patient-Rated Tennis Elbow
Evaluation score. 19
A 2019 meta-analysis reviewed all nonsurgical options for lateral
epicondylitis. Over the short term, corticosteroid appeared to be
most effective. Over the midterm, laser therapy and local
botulinum toxin improved pain. Over the long term, extracorporeal
shock wave therapy provided pain relief. Laser therapy was the only
modality to improve grip strength. The study authors noted that
these all have minimal effects on the course of lateral epicondylitis
but are associated with adverse events. In patients treated with
placebo, many improved between short-term and midterm follow-
up. 20
Surgical intervention should be reserved for refractory cases. The
procedure entails débriding the diseased portion of the tendon
with or without rea achment to the origin. Débridement may be
done either arthroscopically or open. 7
Care should be taken not to violate the lateral collateral ligament
complex and introduce iatrogenic instability. A 2021 study
compared patients with lateral epicondylitis who underwent
débridement with those who had concomitant lateral ulnar
collateral ligament (LUCL) reconstruction for a suspected
component of posterolateral rotatory instability (PLRI) in their
clinical presentation. Both groups improved over time in visual
analog scale score and Mayo Elbow Performance Score (MEPS). 21
There is also the question of the involvement of the lateral capsule.
A 2021 study evaluated arthroscopic lateral capsule resection with
and without extensor carpi radialis brevis débridement. Both
cohorts demonstrated similar improvement, leading to the
conclusion that the lateral capsule may be a key factor. 22
Ultimately, results of surgical intervention for lateral epicondylitis
are mixed, and there is suspicion that patients improve primarily
because it entails a period of enforced immobility and therapy. 7

Distal Bicep Injuries

Distal biceps ruptures occur at a disproportionate rate in middle-
aged men and are often the result of forced rapid eccentric elbow
contraction. 23 A 2021 study of the demographics of distal biceps
tears reported this disproportionate rate in men, as well as noting a
bimodal occurrence in elite athletes and middle age. Prodromal
symptoms were reported in 10% of cases. 24 Injuries are often labor
related and accompanied by a pop with immediate weakness of
elbow flexion and supination. Although often an acute event, tears
may occur in a chronic se ing secondary to degeneration,
hypovascularity, or impingement. A number of risk factors for
rupture have been reported, including obesity, smoking, anabolic
steroids, statins, wild-type transthyretin cardiac amyloidosis,
corticosteroid injection, chronic prednisone administration, and
Cushing disease. 23 These all suggest that systemic metabolic
factors increase the risk for tendon rupture.
Anatomically, the distal biceps has two insertion heads. Both
insert on the more dorsal aspect of the bicipital tuberosity of the
radius. The short head a aches distally, whereas the long head
a aches posteriorly and deep. Of note, the bicipital aponeurosis,
also called the lacterus fibrosus, is a band of connective tissues
arising from the biceps distally and fans medially to a ach on the
forearm flexor/pronator mass as well as the ulna. Awareness of this
structure is important because if it remains intact despite a distal
biceps rupture, the examiner may mistakenly think that the distal
biceps is intact. 23
Early detection of these injuries is critical as acute surgical
intervention is favored. On examination, patients will have
weakness with elbow flexion and forearm supination. There may
also be swelling and bruising in the antecubital fossa, with an
appreciable gap at the expected location of the tendon. Nerve
injuries rarely accompany ruptures. Various tests have been
described but in combination the hook test, passive forearm
pronation, and biceps crease interval (ie, reverse Popeye deformity)
have been shown to be most sensitive and specific. 23 If there is any
uncertainty, MRI should be performed (Figure 2). Flexion-
abduction-supination view has been advocated by some authors. A
2020 study found that it was no more specific or sensitive than
standard MRI in detecting biceps pathology in patients without
complete tears, though it was be er at grading severity of injury. 25
Ultrasonography may also be valuable. A 2019 study found MRI to
be more sensitive and specific than ultrasonography for distal
biceps tears, although they were similar when only considering
partial tears. 26
 Figure 2 Magnetic resonance image showing retracted distal biceps rupture.

Nonsurgical treatment is reserved for low-demand patients,

those with high risk, chronic ruptures with acceptable deficiencies,
and those with partial tears involving less than 50% of the tendon
insertion. 23 Nonsurgical treatment can also be considered on the
nondominant side where supination power is less important for
activities of daily life. In a 2021 cadaver study, supination moment
arm significantly decreased after 75% of the distal biceps tendon
was detached suggesting this may be a cutoff for repair. 27 A 2020
MRI study of patients with partial distal biceps tears found that
most (34%) were isolated partial long head ruptures though there
was a greater likelihood of involvement of the short head in
traumatic cases. Smoking was associated with atraumatic cases. 28
Numerous factors may play a role in treatment decision making. A
2021 retrospective review of 60 patients with distal bicep tears, both
complete and incomplete, who were treated either surgically or
nonsurgically had similar outcomes. This was a heterogenous
population, but it demonstrated that individualized treatment
decisions can yield similar results. 29
Surgical repair is typically favored for acute ruptures (less than 6
weeks) in appropriate candidates as failure to repair may lead to
30% flexion and 50% supination weakness. Numerous techniques
have been described for repair with a focus around single versus
dual incision approaches. Single incision is associated with a higher
risk of nerve injury, whereas dual incision has a higher rate of
heterotopic ossification. The arm should be supinated during the
volar approach to avoid injury to posterior interosseous nerve
(PIN). 23 A 2021 MRI study demonstrated that supination increases
the distance of the PIN from the trajectory and start point of the
guidewire for bicortical bu on fixation. 30 A 2019 study evaluating
single incision cortical bu on fixation versus dual incision suture
over bony bridge fixation found that single incision had a 20%
greater supination torque at median 28 months follow-up. 31 In
cases of severe retraction, a 2020 study described a two-incision
anterior technique. One incision was used to retrieve the tendon,
whereas the other was used for rea achment with a cortical bu on.
When compared with patients who underwent a single incision
repair, there were no differences in strength (both were weaker
with supination compared with contralateral side), motion, or
outcomes. 32 Concomitant repair of the biceps aponeurosis, if it is
also torn, has been advocated as it may strengthen the repair up to
50% with faster return to activity. 23 A 2019 study comparing biceps
repair with biceps and aponeurosis repair found a faster return to
activity, but otherwise no differences. 33
A number of fixation techniques have been described including
transosseous tunnels, suture anchor, suspensory cortical bu ons,
or interosseous screws. Biomechanically, suspensory cortical
fixation appears to have the greatest strength, but there are no clear
clinical differences. 23 A 2021 meta-analysis of biomechanical
studies suggested that constructs with a cortical bu on had the
greatest load to failure. Failure load improved with a locking stitch,
but this also increased the odds of failure within the tissue. 34
Regarding unicortical compared with bicortical fixation, a 2020
cadaver study found no difference in strength of an intermedullary
compared with a bicortical bu on. 35 Clinically, a 2019 study of
distal biceps repairs with an intramedullary cortical bu on
observed no differences in motion or strength compared with the
contralateral side, with good to excellent outcome scores.
Heterotopic ossification was observed in 46% of cases, but only one
was symptomatic. There was one rerupture and one asymptomatic
bu on migration. 36 Regarding other fixation methods, a 2019
cadaver study comparing all-suture anchors with titanium screw
anchors found no difference in load to failure, stiffness, or mode of
failure (anchor pullout). 37
Delayed surgical fixation is also more difficult as the tendon may
retract and its course may fill with scar tissue. Chronic ruptures
may be managed with nonanatomic repair to the brachialis or
coronoid, anatomic repair (particularly if the bicipital aponeurosis
is intact), and graft reconstruction. A 2020 study reported results of
chronic distal biceps tears (longer than 4 weeks) treated with
single-incision anatomic repair with a suture bu on in high flexion.
As a result, patients’ initial flexion contractures ranged from 50° to
90° of flexion; however, at mean 26 months follow-up all had full
motion, strength, and improved outcome scores. 38 A 2020 study
comparing patients undergoing allograft reconstruction for chronic
tears with primary repair found no differences in complications,
range of motion, or outcome scores. 39 A 2019 study evaluated
delayed primary repair, defined as over 21 days, to reconstruction
with semitendinosus autograft. There were no differences in
strength, motion, DASH score, or Single Assessment Numeric
Evaluation. However, the primary repair did score be er on the
Patient-Rated Elbow Evaluation and MEPS, suggesting that primary
repair is preferable if possible. 40
Regarding outcomes, a 2021 study of patients who underwent
distal biceps repair reported 93% returned to sport. Delayed time to
fixation, suture anchor compared with bu on, and dominant arm
injury were associated with lower likelihood of returning to sport at
the same or higher level. Single compared with double incision was
associated with a longer time to return. 41 A 2021 study of 35
National Football League players who underwent distal biceps
repair reported that 33 returned to sport, and there was no
subsequent difference in length of career or performance compared
with control patients. 42 However, this is in contrast to another 2021
study of 25 National Football League players reporting 84% return
to sport, with precipitous decline to 56% at 2 years. Compared with
control patients, those with distal biceps repairs had shorter careers
and played fewer games per season, but did not show differences in
performance. 43
Rehabilitation involves a period of immobilization followed by
passive range of motion. Active range of motion begins at 2 weeks
with light strengthening at 6 weeks. A 2021 RCT evaluated early
range of motion as tolerated compared with 6 weeks of splint
immobilization following distal biceps repair. There were no
significant findings of worse outcomes in the early mobilization
group, indicating that this is a safe practice. 44 A 2020 systematic
review of distal biceps repair reported average time to return to
work was just over 14 weeks, with 89% returning to work. 45
Complications following distal biceps repair or reconstruction
include nerve injury (lateral antebrachial cutaneous nerve [LABCN]
and PIN most commonly), heterotopic ossification, synostosis,
proximal radius fracture, rerupture, infection, stiffness, weakness,
vascular injury, complex regional pain syndrome, and lateral
epicondylitis. 23 A 2020 systematic review of 3,091 distal biceps
repairs reported the overall complication rate to be 25%. This was
divided into 4.6% major complications (ie, PIN, median nerve,
rerupture, synostosis) and 20.4% minor complications (LABCN,
superficial radial nerve, heterotopic ossification, infection). LABCN
injury was the most common at 9% and was most often treated with
cortical bu on fixation. Radioulnar synostosis was only seen in one
dual incision case. 46 A retrospective review of 784 distal biceps
repairs compared complications of single and dual incision
techniques. LABCN was the most common complication and was
significantly more frequent with single incision. However, dual
incision was associated with a higher rate of PIN palsy, heterotopic
bone, and revision surgery. The overall rerupture rate was 1.9%. 47
Distal Triceps Injuries
Distal triceps injuries are relatively uncommon. They typically
occur with a discrete event such as a fall onto an outstretched hand,
traumatic blow, or eccentric load while the muscle is contracting.
Patients may feel a pop with subsequent ecchymosis and swelling
about the olecranon. A palpable defect may be present. Passive
range of motion is usually preserved though weakness with elbow
extension may be appreciated. 48 A 2021 study compared distal
triceps ruptures due to a fall as opposed to direct injury. Compared
with direct injury, falls were more likely to be a partial tear, involve
additional ligamentous injuries, and have bony involvement
(fracture or contusion). 49 These injuries are most common in men
and athletes, though risk factors include anabolic steroid use,
weightlifting, local steroid injection, hyperparathyroidism, renal
disease, Marfan syndrome, hypocalcemic tetany, osteogenesis
imperfecta, olecranon bursitis, rheumatoid arthritis, and type 1
diabetes. 48
The triceps tendon is a confluence of the three muscle heads—
lateral, long, and medial. The tendon inserts on the olecranon but
has a lateral expansion that inserts on the anconeus fascia. The
insertion is large so if there is a partial tear, or the lateral expansion
remains intact, the patient may present with partially preserved
extensor strength leading the examiner to falsely believe the tendon
is intact. Injury can occur anywhere along the tendon and muscle,
though avulsion typically occurs at the tendon-bone interface.
Partial tears are most often on the medial side. 48
Radiographs are often normal, though enthesophytes may be
appreciated. These may fracture and retract in cases of triceps
rupture. MRI remains the gold standard for diagnosis though
ultrasonography is equally effective with an experienced technician.
48

Treatment is largely dictated by tear width. A patient’s functional

and medical status should also be considered. A previously
mentioned 2019 study reported ultrasound-guided tenotomy for a
variety of pathologies. Specific to the triceps, no improvement in
short-term pain, long-term pain, or physical function was found. 4
Partial tears less than 50% are typically managed nonsurgically,
which entails a few weeks of immobilization at approximately 30°
elbow flexion followed by progressive motion. Full-thickness tears
and partial tears over 50% are often managed with surgical repair.
Ideally this occurs within the first 2 to 3 weeks after injury. A
number of techniques for fixation have been described, primarily
with bone tunnels, suture anchor, or direct repair to a periosteal
sleeve. If the lateral expansion is disrupted, it should be repaired as
well to augment the construct. In chronic or revision cases,
allografts with or without bone plugs, autografts, and anconeus
rotation flaps have been described. 48
Postoperatively, the elbow is typically immobilized in
approximately 30° of flexion for 2 weeks. This is followed by 2 to 4
weeks of progressive active elbow flexion with passive extension.
Active range of motion and gradual progression of strengthening
starts at approximately 6 weeks postoperatively. Heavy lifting
should be avoided until at least 3 months postoperatively. 48
Outcomes of distal triceps repair are quite good. Patients
typically regain strength though may lose a few degrees of elbow
extension. Chronic injuries appear to do worse. Complications
include bursitis, flexion contracture, rerupture, and symptomatic
fixation. 48 A 2021 study of patients undergoing distal triceps repair
reported that 93% returned to work at an average of 2.2 months
postoperatively. Of those, 89% returned to work of same intensity,
although it took longer to return to higher intensity jobs. Overall,
96% were satisfied and only one patient required revision. 50 A 2019
study of 69 distal triceps injuries managed with surgical repair
reported on demographics and outcomes. Enthesopathy was more
common in partial ruptures and with overuse mechanisms causing
rupture indicating a degree of chronicity. Repairs were a mix of
bone tunnels, direct repair, and suture anchor with no differences
in outcome scores or complications. There was a 22% complication
rate. Those with enthesopathy were more likely to have
complications. 51

Throwing Injuries

Background/Etiology
Throwing injuries follow a predictable pa ern based on the
supraphysiologic valgus stress placed on the elbow during
throwing, particularly with the late cocking and early acceleration
phases. This stress leads to medial-sided tension, lateral-sided
compression, and posterior shear forces that may injure the static
and dynamic stabilizers of the elbow. 52 Although UCL injuries
have become popularized in the literature, other common injuries
to be aware of include ulnar neuritis, flexor pronator injury, medial
epicondylar apophysitis, valgus extension overload syndrome with
posterior impingement, olecranon stress fracture, and
osteochondritis dissecans lesion of the capitellum. 53

In an effort to implement UCL injury prevention programs, the

following risk factors have been identified: younger age, increased
throwing (pitch count, longer season, year-round play), high pitch
velocity, and pitching while fatigued. 54 A 2021 ultrasound study
reported that after 100 pitches the elasticity of the UCL significantly
increased. This may be interpreted as pathologic laxity that may
lead to injury. 55 Pitch type may also play a role as a 2020 study
found that medial elbow torque is significantly higher with fastballs
compared with curveballs. 56

Evaluation/Physical Examination
Patient symptoms should first be clearly understood. These
symptoms may include pain, mechanical symptoms, or altered
function. Physical examination should include observation,
palpation, motion, strength, stability, and specific examination
maneuvers.
 Throwing athletes with medial-sided elbow pain should be
thoroughly evaluated for UCL injuries, as well as other sources of
pain. Specific to UCL injuries, patients rarely report an acute pop or
event. Symptoms include medial elbow pain particularly with
valgus load or palpation, tightness, and reduced throwing efficiency
(ie, velocity, control). Frank instability, swelling, ecchymosis, and
weakness are rare. Patient age should be taken into consideration,
as physeal injuries occur in pediatric patients. 52
Range of motion is not affected in UCL injuries, although it is not
uncommon for pitchers to have some degree of flexion contracture
in their throwing arm. If there is limited, blocked, or painful range
of motion then posteromedial impingement, loose bodies, or
olecranon stress fracture are considered. The flexor pronator mass
should be assessed as noted in a previous section. Nerve-related
symptoms, particularly ulnar nerve compression or subluxation,
should be investigated. If additional nerve symptoms are noted, the
neck should be evaluated. 52
The entire throwing kinetic chain should be evaluated as well as
the extremity proximal to the elbow. 52 Shoulder and scapular
motion may contribute to elbow injuries. A 2019 study comparing
shoulder motion among pitchers found that those with UCL tears
had greater glenohumeral internal rotation loss, external rotation
gain, and total rotational motion deficit. 57
Specific to the UCL, pain may be re-created with valgus stress
specifically with late cocking or early acceleration-type movement.
Two key physical examinations have been described. With the
milking maneuver, the patient’s arm is brought into abduction,
external rotation, and 90° of elbow flexion. The patient’s thumb is
grasped and pulled posteriorly to create a valgus moment on the
elbow. The moving valgus stress test involves the patient’s arm
being brought into the same position as the milking maneuver;
however, the elbow is taken through a range of flexion/extension
with persistent posterior force creating a valgus stress at the elbow.
Pain or apprehension with either of these maneuvers indicates a
positive test. 52
Additional specialty tests are as follows. The arm bar test
involves the patient abducting the shoulder, extending the elbow,
internally rotating the arm, and placing it on the examiner’s
shoulder. The examiner applies downward pressure on the
humerus to create maximal extension. A positive test elicits pain
around the olecranon, which is indicative of valgus extension
overload with posteromedial impingement. 52 A 2020 cadaver study
demonstrated that the moving valgus stress test resulted in more
elongation of the UCL than static tests. Overall, the greatest change
in length was seen during extension movement around 90° of
flexion. 58 This would suggest improved sensitivity with dynamic
testing. It can also be useful to test the degree of elbow flexion the
patient exhibits in the late cocking phase, which most pitchers
know as their slot angle and varies from more extended in
submarine or sidearm pitchers to more flexed in over-the-top
pitchers.
Radiocapitellar issues may be elucidated with palpation as well
as pronation/supination particularly with elbow extended. The
elbow flexion test may be used to assess for ulnar nerve
compression. The arm is held maximally abducted, flexed at the
elbow, and pronated with the wrist extended. A positive test is
noted if sensory issues occur in the ulnar nerve distribution when
the position is held and the ulnar nerve compressed at the cubital
tunnel for at least 30 seconds. 52

Imaging
Imaging should start with radiographs that may be normal in a
number of common elbow throwing conditions. However, patients
should be evaluated for joint-space narrowing, intra-articular
bodies, osteochondritis dissecans lesions, cysts, osteophytes,
calcifications, chondrosis, physeal injuries, and olecranon fractures.
Stress radiographs are largely unhelpful. 52 A 2020 study of stress
radiographs in throwing athletes with medial-sided elbow pain did
find that joint gapping was associated with UCL injury severity.
However, excess opening in the injured compared with uninjured
side was not associated with injury. Additionally, 22% of cases had
increased gapping on the uninjured side. 59
Ultrasonography and stress ultrasonography have been
described, but are operator dependent. A 2019 cadaver study found
dynamic stress ultrasonography to be as reliable as stress
radiography in the se ing of anterior bundle UCL transection. 60 A
2020 study of valgus stress ultrasonography reported cutoffs for
diagnosing complete UCL rupture. At 30° of flexion, 0.5 mm medial
gapping had a sensitivity of 88% and specificity of 62%. At 90° of
flexion, 1 mm of medial gapping had a sensitivity of 81% and
specificity of 66%. 61
MRI is the gold standard for evaluation of UCL and other soft-
tissue injuries. Intra-articular gadolinium increases sensitivity and
specificity for identifying UCL tears, particularly in the se ing of a
partial tear 52 (Figure 3).

Figure 3 Coronal MRI sections demonstrating partial-thickness (A) and full-

thickness (B) ulnar collateral ligament tears.

Finally, electromyography studies should be obtained if there is

any concern for nerve-related symptoms. 52
Nonsurgical Management
Regarding UCL injuries, nonsurgical measures are initially
recommended for all patients. This includes a period of rest from
throwing, typically 3 months, during which a shoulder and elbow
strengthening program may be implemented. If the patient is pain
free, a gradually progressive throwing program should be followed.
Success of this protocol ranges widely in the literature. 54 In a 2021
study of professional baseball players with partial UCL injuries,
return to play for pitchers and position players was 82% and 90%,
respectively. There were no differences in performance metrics
compared with uninjured control patients. The reinjury rate was
11%, although none required reconstruction. 62
Additional measures are being investigated, such as PRP and
autologous blood injections, although there is evidence to support
them. 54 In a 2019 study, professional baseball players treated
nonsurgically for UCL injury were evaluated, comparing those who
had and had not received a PRP injection. Ultimately 54% returned
to play, but the PRP group had a longer delay in return to throwing
and play. Tear grade and location were not associated with return to
play or progression to surgery. 63 Thus, the role of PRP in the
nonsurgical management of UCL tears remains unclear.

Elbow Ligament Reconstruction

Ulnar Collateral Ligament Reconstruction

Anatomy
The UCL is composed of three bundles: anterior, posterior, and
oblique. Although multiple dynamic and static stabilizers
contribute to elbow constraint, the UCL is critical for valgus
stability. From 20° to 120° of elbow flexion, the anterior bundle of
the UCL is the key restraint to valgus stress. Injuries to the UCL are
a ributed to valgus stress, causing excessive medial tension and are
most commonly seen in throwing athletes. Because elbow flexion
with throwing is typically under 120° of flexion, the anterior bundle
of the UCL is of primary concern. 52
The anterior bundle is composed of an anterior and posterior
band. The structure runs from the face of the medial epicondyle of
the humerus to the sublime tubercle of the ulna. Although the UCL
is the key stabilizer to valgus stress, the joint capsule and flexor
pronator mass provide additional restraint. 52 The UCL appears to
respond to stress as a 2021 ultrasonography study of professional
pitchers reported UCL thickness was associated with peak throwing
velocity. Additionally, both UCL thickness and valgus laxity
increased during the season and decreased during the offseason. 64
Regarding pathoanatomy, a 2020 cadaver study of medial elbow
laxity found that complete tears demonstrated the most laxity,
followed by midsubstance tears, those consistent with the T sign,
and proximal tears. Distal partial tears had the least laxity. 65

Indications
Surgical intervention may be considered for patients wanting to
return to sport at a high level without evidence of arthritis or
alternative etiology for pain and after a trial of nonsurgical
management has failed. A minimum 3-month trial of nonsurgical
measures is recommended, although this may be abbreviated in
high-level athletes because of additional timing constraints.
Patients must also be willing to participate in the extensive
postoperative rehabilitation regimen because this is critical for
success. 54
Certain tears may be more amenable to nonsurgical treatment. A
2019 study reported that patients with UCL tears that were distal or
complete were significantly more likely to undergo surgical
intervention (odds ratios: 48 and 5, respectively). 66 Distal tears may
be less successfully managed nonsurgically, as a 2019 cadaver study
with India ink noted that the proximal UCL has a more dense blood
supply than distally. 67
Technique
Surgical intervention focuses on reconstruction specifically of the
anterior bundle of the anterior band of the UCL. The graft is
typically autologous palmaris longus or gracilis, although toe
extensors, plantaris, portions of Achilles tendon, and allograft have
been used. Evaluation for a palmaris longus preoperatively is
critical as it may be absent unilaterally in 16% and bilaterally in 9%.
Failure to preoperatively recognize congenital absence of the
palmaris can lead to inadvertent harvest of the median nerve, a
disastrous complication. Graft size depends on surgical technique,
although for reference, at least a 15-cm graft is preferred for the
modified Jobe technique. 54 In a 2019 study, professional baseball
players undergoing UCL reconstruction with hamstring autograft
were compared with a cohort that underwent reconstruction with
palmaris autograft. There was no difference in rate of or time to
return to play or performance time. However, the hamstring group
sustained significantly more lower extremity injuries, whereas the
palmaris group trended toward more upper extremity injuries. 68
Another 2019 study of pitchers undergoing UCL reconstruction
with hamstring autograft reported no differences based on the side
from which the graft was harvested (drive leg versus plant leg) in
terms of return to sport rate or time, subsequent ipsilateral or
contralateral hamstring injury, and performance metrics. 69
Multiple techniques for reconstruction have been described,
including a variety of fixation constructs (Figure 4). The most
commonly described are the modified Jobe; docking; and David
Altcheck, Neal ElA rache, Tommy John (or DANE TJ) techniques.
The modified Jobe technique entails anterior elevation of the flexor
pronator mass without transection to access the UCL. This
approach requires transposition of the ulnar nerve. A muscle-
spli ing approach between the flexor carpi ulnaris and anterior
flexor pronator mass has also been described and may avoid ulnar
nerve transposition. Once exposed, a Y-shaped tunnel is drilled in
the medial epicondyle and a V shape in the sublime tubercle of the
ulna. The graft is passed and tied on itself. The docking technique
uses the similar muscle-spli ing approach as described previously.
Tunnels again are similarly drilled although the two proximal
humerus holes are smaller. The graft edges are docked into the
humerus and tied over the bony bridge. The DANE TJ technique
uses similar docking in the humerus but an interference screw in
the ulna. Multiple other various fixation methods have been
described including use of interference screws and cortical bu ons.
54
Some authors suggest simultaneous arthroscopic evaluation;
however, this is probably only needed if there are concerns for
anterior compartment issues as posterior issues may be addressed
through the same surgical incision without violation of any
musculotendinous units. Nerve transposition remains
controversial. Transient ulnar neuritis is a common complication
regardless of transposition. 54

Figure 4 Intraoperative photograph shows an example of ulnar collateral

ligament reconstruction.
 A number of studies have evaluated and compared clinical
outcomes of these techniques. A 2021 meta-analysis comparing the
modified Jobe and docking techniques found no difference in
outcomes when controlling flexor pronator mass preservation
versus detachment and ulnar nerve transposition. 70 A 2019 study of
UCL reconstructions by a variety of techniques in professional
pitchers showed a return to sport rate of 80%. Neither graft nor
technique affected rate of return to play, rate of return to same level
of play, subsequent elbow surgery, or rate of revision UCL
reconstruction. Additionally, ulnar nerve transposition at the time
of reconstruction did not affect outcomes. 71
There have been some investigations on the use of an internal
brace as an augment. A 2019 cadaver study evaluated the strength
of the native UCL compared with palmaris graft using the docking
technique with and without an internal brace. Stiffness and
ultimate failure torque were lower for reconstruction without a
brace compared with the native UCL. However, these parameters
were comparable between reconstruction with the internal brace
and native UCL. 72 A 2019 study reported on amateur athletes who
underwent UCL repair with internal brace augmentation. The
decision to repair, as opposed to reconstruction, was made based
on ligament quality on imaging and at time of surgery. At
minimum 1-year follow-up, 92% had returned to the same level of
competition or higher at mean 6.7 months. 73

Rehabilitation
Rehabilitation is critical. Postoperatively the elbow should be
immobilized at 90° for 5 to 7 days to allow wound healing. Range of
motion is then progressed with a goal to return to full motion by 6
weeks. This is followed by a period of isotonic strengthening with
progression to isotonic lifting and throwing plyometrics at week 12.
A throwing program may begin at 16 weeks to gradually increase
distance and repetitions. Position players may progress from there
to game situations, whereas pitchers then begin throwing from the
mound, again with gradual progression of velocity and repetitions.
Phases should not be advanced until the patient is pain free.
Position players may return to play as early as 6 months, whereas
pitchers usually require at least 10 months and can take 12 to 18
months before returning to play. 54
Different techniques for return to throwing have been suggested
but should be carefully considered. For example, the crow hop may
be recommended in some rehabilitation programs; however, based
on a 2021 study this actually increases torque across the medial
elbow compared with standing throws up to 60 feet. 74 A 2020 study
found that pitches thrown at 50% and 75% perceived effort were
significantly faster and generated more elbow torque than pitches
actually thrown at velocities of 50% and 75% for individuals. This is
important as pitches thrown with a 10% reduction in maximal
velocity demonstrated 13% less maximal torque. The study authors
suggest implementing a radar gun to measure pitch velocity during
return to pitching. 75

Outcomes
Outcomes of primary reconstruction are quite good as return to
sport rates in the literature are often higher than 80%. Pitchers
appear to lose some velocity compared with preoperative findings,
but they are not different compared with age-matched control
patients. There are some misconceptions that UCL reconstruction
may improve performance, and this has repeatedly been
demonstrated to be false. Counseling patients in this regard is
critical. Average return to play is close to 1 year. Overall, the
revision rate is approximately 1% though it has been reported
higher in Major League Baseball (MLB) at 9%. No technique is
clearly superior. Outcomes after revision are worse with more
complications. 54
A number of studies have been performed on throwing athletes,
particularly baseball players. A 2021 meta-analysis of UCL
reconstructions by a variety of techniques found that on average
players returned to a throwing program at 16.7 weeks, mound at 7.4
months, and competition at 12.2 months with 85.7% returning to
preinjury level or higher. 76 A 2021 study of MLB pitchers
undergoing UCL reconstruction found no difference between
preoperative and postoperative pitch velocity, movement, angle, or
performance metrics. 77 Regarding player’s perception, a 2021 study
of MLB and Minor League pitchers who had undergone UCL
reconstruction reported that only 56% perceived no changes in their
pitching mechanics, and only 54% believed their velocity improved.
Additionally, 20% sustained a setback in their rehabilitation, and
only 61% would undergo the procedure again if indicated. 78 Tear
location may play a role, as a 2020 study of MLB players undergoing
UCL reconstruction found that only 71% of those with proximal
tears were able to return to sport compared with 100% of distal
tears. Pitchers with distal tears had higher utilization upon return
with similar performance compared with those with proximal tears.
79
Although most research has focused on throwing, a 2020 study of
position professional baseball players undergoing UCL
reconstruction found that 77% returned to hi ing in a game and
75% returned to fielding in a game. On average, swings began at
150 days, ba ing practice at 195 days, and game hi ing at 323 days.
Utilization was lower postoperatively with fewer at-bats, but there
was no difference in performance. 80 This procedure is also
performed in amateur athletes. A 2021 systematic review of
adolescent baseball players and javelin throwers undergoing UCL
reconstruction reported 84% return to sport at the same level or
higher with a 3.9% complication rate and 1.8% revision surgery rate.
81

Revision reconstruction is widely believed to have worse

outcomes. A 2019 systematic review of high-level baseball players
undergoing revision UCL reconstruction reported rate of return to
sport at preinjury level at 63% at a range of 1.3 to 1.7 years. 82 A 2020
study of 38 pitchers undergoing revision reconstruction reported
that 47% returned to preoperative level of competition for at least 1
year, initiating throwing at 6.3 months and return to competition at
12.8 months. 83
 The most common complications after UCL reconstruction are
transient ulnar neuritis, donor-site issues, wound breakdown,
weakness, and pain. 54 A 2019 meta-analysis reported the prevalence
of postoperative ulnar neuropathy to be 12%, though fewer than 1%
required revision surgery. Ulnar nerve transposition resulted in a
higher rate of ulnar neuropathy than when it was left in situ. 84
However, this remains controversial in the literature.

Lateral Collateral Ligament Reconstruction

Anatomy
The lateral collateral ligament of the elbow is a Y-shaped complex
of four ligaments: LUCL, radial collateral ligament, annular
ligament, and the accessory ligament. This complex resists varus,
external rotation, and posterior directed stresses. When injury
occurs, a sheet of tissue that is the confluence of these structures
typically avulses off the humerus and results in PLRI. The
mechanism of injury is most commonly trauma either with frank
dislocation or valgus stress when the arm is axially loaded and
supinated. Injury may also be iatrogenic from surgery, steroid
injections, or chronic varus deformity leading to ligament
a enuation. Although bony anatomy is key to elbow stability at
extremes of flexion and extension, the collateral ligaments are
crucial from approximately 20° to 120° of flexion. 85

Indications
Patients with posterolateral instability may complain of pain,
particularly with activities requiring elbow extension and
supination though this can be hard to elicit on examination.
Mechanical symptoms such as clicking, subluxation, or
dislocation may also be reported. Focused examination should
include valgus and varus stress at 30°, PLRI test, lateral pivot shift
test, and chair pushup test. Radiographs may show posterior
subluxation of the radial head but otherwise may be normal. MRI is
the gold standard, but injury of the lateral collateral ligament can
be difficult to fully appreciate 85 (Figure 5).

Figure 5 A and B, Magnetic resonance images show lateral collateral ligament

tears.

Nonsurgical treatment should be a empted in all cases except

when gross instability is present. This entails therapy, activity
modification, brace treatment, and NSAIDs. Unfortunately, many
cases of PLRI remain symptomatic given that many activities of
daily life involve varus force on the elbow. 85 A 2021 systematic
review found the most common indication for lateral collateral
ligament reconstruction was chronic PLRI after a trauma (86%), and
specifically a dislocation (61%). 86

Technique
Acute tears may be directly repaired. Most tears are avulsions from
the humeral origin, so repair involves rea achment to the humerus
typically with suture anchor or transosseous suture. The anatomic
point of the lateral collateral ligament is just posterior to the tip of
the lateral epicondyle. 85 A 2019 cadaver study provided an in-depth
analysis of the anatomy of the lateral collateral ligament complex.
Notably, the LUCL origin is 10.7 mm distal to the lateral epicondyle
and the insertion is 3.3 mm distal to the supinator crest apex. 87
 Alternatively, chronic tears often require reconstruction with
either autograft, allograft, or synthetic graft (Figure 6). A variety of
techniques have been described, including transosseous fixation,
suture anchors, interference screws, and docking. In a 2021
systematic review, docking (86%) and autograft (61%) were
reported to be the most common techniques; however, there is no
consensus on optimal technique in terms of outcomes. The only
significant findings were that autografts had a higher MEPS than
allograft although there was no difference in QuickDASH score.
Primary compared with revision reconstruction demonstrated the
same finding. 86 The surgical approach is either posterior with the
patient in lateral decubitus position or through a modified Kocher
technique with the patient supine. Correcting underlying osseous
abnormalities or alignment is critical to prevent recurrence. 85

Figure 6 A and B, Intraoperative photographs show an example of lateral ulnar

collateral ligament reconstruction.

A few recent publications have focused on the use of an internal

brace with suture tape. A 2020 cadaver study evaluated repairs,
repairs with suture tape augmentation, reconstruction, and
reconstruction with suture tape augmentation. For primary repair,
augmentation led to higher load to failure and improved rotation
stiffness. For reconstruction, augmentation led to higher load to
failure and less displacement. 88 Clinically, a 2019 study of patients
with posterolateral elbow instability secondary to dislocation
treated with LUCL repair and suture tape augmentation
demonstrated no signs of instability at 10-month median follow-up.
89
It remains unclear whether an internal brace is necessary, as good
outcomes have been obtained without the brace and no
comparative clinical studies exist.

Rehabilitation
Rehabilitation protocols vary widely in the literature. A 2019
systematic review of LUCL reconstructions reported averages of
immobilization for 3 weeks (range, 0 to 9 weeks), active range of
motion starting at 8 weeks (range, 0 to 12 weeks), and return to
work/lifting/sport at 32 weeks (range, 12 to 52 weeks). 87 Typically,
active motion can begin at 2 weeks in a hinged brace while
instructing patients to avoid supination extension, with
strengthening starting at 12 weeks and return to work and sports at
4 to 5 months.

Outcomes
A 2021 systematic review of LUCL reconstructions reported, based
on MEPS, excellent results in 48%, good in 33%, fair in 16%, and
poor in 3%. Range of motion returned to normal in 93% of patients
postoperatively compared with 81% preoperatively. Return to full
level of function occurred in 84%, and 40% returned to sport.
Although 49% reported persistent pain, 87% were satisfied. The
overall complication rate was 22%. Complications included
recurrent instability, flexion contracture, ulnar neuropathy,
pos raumatic osteoarthritis, deep vein thrombosis, infection, and
symptomatic heterotopic ossification. Recurrent instability was the
most common at 15%. This was significantly higher in revision
compared with primary reconstruction, though it was not affected
by graft type. 86
Summary
Carefully evaluating patients to ensure appropriate diagnosis is
critical. Additionally, for most of the pathologies presented,
nonsurgical measures may be an appropriate first step. Particularly,
tendinopathies about the elbow are self-limiting conditions
unaffected in the long term by various treatment modalities.
Similarly, ligamentous injuries may be managed nonsurgically, but
when nonsurgical treatment has failed surgical intervention in
appropriately indicated patients can yield excellent results. Frank
discussion with patients about their symptoms and goals will help
guide treatment decisions.

Key Study Points

Medial and lateral epicondylitis are overuse-related syndromes that appear to be
self-limited. Numerous modalities have been investigated, although none is clearly
most effective. Activity modification is critical for resolution.
Distal biceps and triceps ruptures are best managed with acute surgical intervention
in appropriately indicated patients.
Throwing injuries follow a predictable pattern of injury because of medial tension,
lateral compression, and posterior shear forces.
Ulnar collateral ligament reconstruction is indicated in throwing athletes if symptoms
are refractory to nonsurgical measures. Outcomes indicate a high rate of return to
sport at a similar level, but reconstruction does not improve performance.
Lateral collateral ligament reconstruction in the setting of posterolateral rotatory
instability refractory to nonsurgical measures has good outcomes.

Annotated References
1. Rami GA, Dan ker N, Ahmad CS: Injuries and conditions
affecting the elbow flexor/pronator tendons. Clin Sports Med
2020;39(3):549-563. Review article covering anatomy, pathology,
evaluation and management of flexor/pronator injuries about the
elbow.
2. Bae KJ, Park C, Ahn JM, Kang Y, Gong HS: Magnetic resonance
imaging evaluation of patients with clinically diagnosed medial
epicondylitis. Skeletal Radiol 2021;50(8): 1629-1636. A
 p y
retrospective review of 83 patients undergoing MRI of the elbow
for medial epicondylitis reported signal change in the common
flexor tendon as the most common finding and was associated
with follow-up pain. Level of evidence: IV.
3. Huang K, Giddins G, Wu LD: Platelet-rich plasma versus
corticosteroid injections in the management of elbow
epicondylitis and plantar fasciitis: An updated systematic review
and meta-analysis. Am J Sports Med 2020;48(10):2572-2585. A
systematic review and meta-analysis of 20 prospective studies
compared PRP and corticosteroid injections. Specific to elbow
epicondylitis, PRP seemed to have more effect over the long term,
whereas corticosteroid had more improvement in the short term.
Level of evidence: I.
4. Stover D, Fick B, Chimenti RL, Hall MM: Ultrasound-guided
tenotomy improves physical function and decreases pain for
tendinopathies of the elbow: A retrospective review. J Shoulder
Elbow Surg 2019;28(12):2386-2393. A retrospective review of 131
patients who underwent ultrasound-guided tenotomy for all
elbow tendinopathies demonstrated improved pain and quality
of life with a satisfaction rate of 70%. Level of evidence: IV.
5. Martin JI, Atilano L, Merino J, et al: Platelet-rich plasma versus
lidocaine as tenotomy adjuvants in people with elbow
epicondylopathy: A randomized controlled trial. J Orthop Surg
Res 2019;14(1):109. An RCT of 71 patients with elbow
tendinopathy comparing ultrasound-guided tenotomy with either
PRP or lidocaine found no significant differences in clinical
outcomes. Level of evidence: II.
6. Boden AL, Sco MT, Dalwadi PP, Mautner K, Mason RA,
Go schalk MB: Platelet-rich plasma versus Tenex in the treatment
of medial and lateral epicondylitis. J Shoulder Elbow Surg
2019;28(1):112-119. This is a retrospective review of 62 patients
who underwent either PRP injection or ultrasound-guided
percutaneous tenotomy for medial and lateral epicondylitis.
Although both groups improved, there was no difference
between them. Level of evidence: III.
 7. Meunier M: Lateral epicondylitis/extensor tendon injury. Clin
Sports Med 2020;39(3):657-660. Review article covering evaluation
and management of lateral epicondylitis/extensor tendon injury.
8. Lee SH, Gong HS, Kim S, Kim J, Baek GH: Is there a relation
between lateral epicondylitis and total cholesterol levels?
Arthroscopy 2019;35(5):1379-1384. A retrospective review
comparing 289 patients with lateral epicondylitis and 1,077
healthy patients found the incidence of hypercholesterolemia
and total cholesterol levels to be associated with lateral
epicondylitis. Level of evidence: III.
9. Roh YH, Gong HS, Baek GH: The prognostic value of pain
sensitization in patients with lateral epicondylitis. J Hand Surg
Am 2019;44(3):250.e1-250.e7. A prospective study of 131 patients
with lateral epicondylitis evaluated pain sensitization, finding
that it was associated with symptom severity, duration, and
disability at 1 year. Level of evidence: IV.
10. Krogh TP, Fredberg U, Ammi bøll C, Ellingsen T: Clinical value
of ultrasonographic assessment in lateral epicondylitis versus
asymptomatic healthy controls. Am J Sports Med 2020;48(8):1873-
1883. Ultrasonographic evaluation of 60 patients with lateral
epicondylitis compared with 264 healthy patients reported
increased tendon thickness, mean color Doppler activity, and
bone spurs in the lateral epicondylitis cohort. Level of evidence:
III.
11. Kroslak M, Pirapakaran K, Murrell GAC: Counterforce bracing
of lateral epicondylitis: A prospective, randomized, double-
blinded, placebo-controlled clinical trial. J Shoulder Elbow Surg
2019;28(2):288-295. An RCT that compared counterforce bracing
in 17 patients with placebo bracing in 14 patients observed a
number of similar improvements in both groups. However, the
counterforce brace had be er short-term pain frequency and
severity. Level of evidence: II.
12. Barati H, Zarezadeh A, MacDermid JC, Sadeghi-Demneh E: The
immediate sensorimotor effects of elbow orthoses in patients
 with lateral elbow tendinopathy: A prospective crossover study. J
Shoulder Elbow Surg 2019;28(1):e10-e17. This RCT of patients with
lateral epicondylitis compared no brace to forearm band, to
elbow sleeve. Both types of braces improved pain and grip
strength, with no difference between them. Level of evidence: II.
13. Farkash U, Avisar E, Volk I, et al: First clinical experience with a
new injectable recombinant human collagen scaffold combined
with autologous platelet-rich plasma for the treatment of lateral
epicondylar tendinopathy (tennis elbow). J Shoulder Elbow Surg
2019;28(3):503-509. Prospective evaluation of 40 patients with
lateral epicondylitis found improved pain, outcome scores, grip
strength, and ultrasound tendon appearance following injections
of cross-linked bioengineered recombinant human type I
collagen combined with autologous PRP. Level of evidence: IV.
14. Linnanmäki L, Kanto K, Karjalainen T, Leppänen OV, Lehtinen
J: Platelet-rich plasma or autologous blood do not reduce pain or
improve function in patients with lateral epicondylitis: A
randomized controlled trial. Clin Orthop Relat Res
2020;478(8):1892-1900. An RCT of 119 patients with lateral
epicondylitis receiving injection of PRP, autologous whole blood,
or saline found no difference in pain or outcomes scores. Level of
evidence: II.
15. Acosta-Olivo CA, Millán-Alanís JM, Simental-Mendía LE, et al:
Effect of normal saline injections on lateral epicondylitis
symptoms: A systematic review and meta-analysis of randomized
clinical trials. Am J Sports Med 2020;48(12):3094-3102. A meta-
analysis of 15 RCTs including cohorts that received saline
injection for lateral epicondylitis noted improvement in pain and
function at minimum 6-month follow-up. Level of evidence: I.
16. Yoon SY, Kim YW, Shin I, Moon HI, Lee SC: Does the type of
extracorporeal shock therapy influence treatment effectiveness in
lateral epicondylitis? A systematic review and meta-analysis. Clin
Orthop Relat Res 2020;478(10):2324-2339. A meta-analysis of 12
RCTs including extracorporeal shock wave therapy for lateral
 epicondylitis found no significant benefit compared with control
patients in terms of grip strength or pain. Level of evidence: I.
17. da Luz DC, de Borba Y, Ravanello EM, Daitx RB, Döhnert MB:
Iontophoresis in lateral epicondylitis: A randomized, double-
blind clinical trial. J Shoulder Elbow Surg 2019;28(9):1743-1749.
This RCT investigated 24 patients with lateral epicondylitis
receiving iontophoresis either with dexamethasone and gel
lidocaine or with the base gel. Although both groups improved,
the dexamethasone and lidocaine group showed be er results in
pain and function. Level of evidence: I.
18. Ang BFH, Mohan PC, Png MA, et al: Ultrasonic percutaneous
tenotomy for recalcitrant lateral elbow tendinopathy: Clinical and
sonographic results at 90 months. Am J Sports Med
2021;49(7):1854-1860. A retrospective review of 20 patients treated
with ultrasonic percutaneous tenotomy for lateral epicondylitis
reported 100% satisfaction, with improvements in pain and
outcome scores. Level of evidence: IV.
19. Uygur E, Aktaş B, Yilmazoglu EG: The use of dry needling vs.
corticosteroid injection to treat lateral epicondylitis: A
prospective, randomized, controlled study. J Shoulder Elbow Surg
2021;30(1):134-139. This is an RCT of 108 patients with lateral
epicondylitis treated with either steroid injection or dry needling.
Both showed improved outcome scores, but steroid injection
appeared to have superior results up to 6 months. Level of
evidence: II.
20. Lian J, Mohamadi S, Chan JJ, et al: Comparative efficacy and
safety of nonsurgical treatment options for enthesopathy of the
extensor carpi radialis brevis: A systematic review and meta-
analysis of randomized placebo-controlled trials. Am J Sports Med
2019;47(12):3019-3029. This is a meta-analysis of 36 RCTs
involving nonsurgical management for lateral epicondylitis. At
short-term follow-up steroid injection was favorable; at midterm
follow-up laser therapy and botulinum toxin injection were
favorable; and at long-term follow-up extracorporeal shock wave
therapy was favorable. Level of evidence: I.
21. Noh YM, Kong GM, Moon SW, et al: Lateral ulnar collateral
ligament (LUCL) reconstruction for the treatment of recalcitrant
lateral epicondylitis of the elbow: A comparison with open
débridement of the extensor origin. JSES Int 2021;5(3):578-587.
This is a retrospective review of patients with lateral epicondylitis
treated with isolated débridement or with LUCL reconstruction.
Although both groups improved, results were more rapid in the
reconstruction group. Level of evidence: III.
22. Paksoy AE, Laver L, Tok O, Ayhan C, Kocaoglu B: Arthroscopic
lateral capsule resection is enough for the management of lateral
epicondylitis. Knee Surg Sports Traumatol Arthrosc 2021;29(6):2000-
2005. This is a retrospective study of 38 patients treated
arthroscopically for lateral epicondylitis with either lateral
capsular resection and débridement or capsular resection alone.
There were no differences between groups. Level of evidence: IV.
23. Albishi W, Agenor A, Lam JJ, Elmaraghy A: Distal biceps
tendon tears: Diagnosis and treatment algorithm. JBJS Rev
2021;9(7). Review article covering distal biceps injuries, anatomy,
evaluation, and management.
24. Luokkala T, Sidharthan SK, Karjalainen TV, Paloneva J, Wa s
AC: Distal biceps tendon repairs and reconstructions-an analysis
of demographics, prodromal symptoms and complications. Arch
Orthop Trauma Surg 2021; January 23 [Epub ahead of print]. A
retrospective review of 228 distal biceps ruptures reported a
bimodal pa ern for age at presentation and surgical treatment is
most commonly direct repair. There was a 12% adverse event
rate, and 10% had prodromal symptoms. Level of evidence: IV.
25. Schenkels E, Caekebeke P, Swinnen L, Peeters J, van Riet R: Is
the flexion-abduction-supination magnetic resonance imaging
view more accurate than standard magnetic resonance imaging in
detecting distal biceps pathology? J Shoulder Elbow Surg
2020;29(12):2654-2660. This is a retrospective review of MRI in 50
patients with biceps pathology and 50 healthy elbows. Half of
each group had normal views, whereas the other half had flexion-
 abduction-supination technique. There was no difference in
detecting partial distal biceps tears. Level of evidence: IV.
26. Lynch J, Yu CC, Chen C, Muh S: Magnetic resonance imaging
versus ultrasound in diagnosis of distal biceps tendon avulsion.
Orthop Traumatol Surg Res 2019;105(5): 861-866. This is a
retrospective study of 31 distal biceps tears managed surgically.
Preoperative MRI was more accurate, sensitive, and specific in
diagnosis. Level of evidence: III.
27. Tomizuka Y, Schmidt CC, Davidson AJ, et al: Partial distal
biceps avulsion results in a significant loss of supination force. J
Bone Joint Surg Am 2021;103(9):812-819. This is a cadaver study of
18 specimens with sequential distal biceps release. Distal release
caused a decrease in supination moment arm.
28. Nicolay RW, Lawton CD, Selley RS, et al: Partial rupture of the
distal biceps brachii tendon: A magnetic resonance imaging
analysis. J Shoulder Elbow Surg 2020;29(9):1859-1868. This is a
retrospective review of MRI of 77 patients with partial distal
biceps ruptures. The most common finding was a partial long
head rupture with the short head intact. Trauma was associated
with short head involvement. Level of evidence: IV.
29. Berthold DP, Muench LN, Cusano A, et al: Clinical and
functional outcomes after operative and nonoperative treatment
of distal biceps brachii tendon ruptures in a consecutive case
series. Orthop J Sports Med 2021;9(6):2325967120984841. This is a
retrospective review of 60 patients with distal biceps rupture
managed surgically and nonsurgically. Both groups improved
and achieved satisfactory outcomes. Level of evidence: III.
30. Luthringer TA, Bloom DA, Klein DS, et al: Distance of the
posterior interosseous nerve from the bicipital (radial) tuberosity
at varying positions of forearm rotation: A magnetic resonance
imaging study with clinical implications. Am J Sports Med
2021;49(5):1152-1159. An MRI study evaluated the location of the
PIN in relation to proposed distal biceps cortical bu on fixation
 through a single-incision approach. Supination was the safest
position to avoid nerve injury. Level of evidence: IV.
31. Stockton DJ, Tobias G, Pike JM, Daneshvar P, Goe TJ:
Supination torque following single- versus double-incision repair
of acute distal biceps tendon ruptures. J Shoulder Elbow Surg
2019;28(12):2371-2378. This is a retrospective review of 37 patients
with distal biceps rupture treated with a single-incision or
double- incision technique, noting greater supination torque in
the single-incision group at follow-up. Level of evidence: III.
32. DeAngelo N, Thomas RA, Kim HM: Primary repair of severely
retracted nonchronic distal biceps tendon rupture using 2-
incision anterior-approach repair. JSES Int 2020;4(2):231-237. This
is a retrospective review of 20 patients treated surgically for distal
biceps rupture with anterior approach cortical bu on technique.
Patients requiring a second incision to retrieve a retracted tendon
had no difference in outcomes. Level of evidence: III.
33. Conlin CE, Naderipour A, ElMaraghy A: Outcome of distal
biceps tendon repair with and without concomitant bicipital
aponeurosis repair. Orthop J Sports Med
2019;7(8):2325967119865500. This is a retrospective study of 24
patients with distal biceps rupture, of whom 13 had
supplemental bicipital aponeurosis repair and returned to
recreational activity faster. Level of evidence: III.
34. Taylor AL, Bansal A, Shi BY, Best MJ, Huish EGJr, Srikumaran
U: Optimizing fixation for distal biceps tendon repairs: A
systematic review and meta-regression of cadaveric
biomechanical testing. Am J Sports Med 2021;49(11):3125-3131.
Meta-regression of 14 studies evaluating distal biceps repair
techniques in cadavers showed cortical bu on fixation to be
stronger than suture anchor repair with less risk of type 2 failure
compared with interference screw or fixation without implants.
35. Caekebeke P, Duerinckx J, Bellemans J, van Riet R: A new
intramedullary fixation method for distal biceps tendon ruptures:
A biomechanical study. J Shoulder Elbow Surg 2020;29(10):2002-
 2006. A cadaver study comparing bicortical bu on with
intramedullary fixation demonstrated comparable tendon-bone
displacement, load to failure, and breakout through the cortex.
36. Siebenlist S, Schmi A, Imhoff AB, et al: Intramedullary cortical
bu on repair for distal biceps tendon rupture: A single-center
experience. J Hand Surg Am 2019;44(5):418.e1-418.e7. A
retrospective study of 28 patients treated with intramedullary
cortical bu on fixation for distal biceps repair reported excellent
motion, strength, and outcome scores. Heterotopic ossification
was seen in 46% of cases, but only one was symptomatic. Level of
evidence: IV.
37. O o A, Mehl J, Obopilwe E, et al: Biomechanical comparison of
onlay distal biceps tendon repair: All-suture anchors versus
titanium suture anchors. Am J Sports Med 2019;47(10):2478-2483. A
cadaver study comparing all-suture anchors with titanium
anchors for distal biceps repair demonstrated similar peak load
and stiffness. At a proximal position, all-suture anchors had
slightly more displacement with cyclic loading though unclear if
this is clinically important.
38. Zeman CA, Mueller JD, Sanderson BR, Gluck JS: Chronic distal
biceps avulsion treated with suture bu on. J Shoulder Elbow Surg
2020;29(8):1548-1553. This is a retrospective review of 21 primary
repairs for chronic distal biceps tendon ruptures managed with a
single incision and suture bu on. At follow-up, patients had full
motion and strength with significantly improved outcome scores
and pain. Level of evidence: IV.
39. Hendy BA, Padegimas EM, Harper T, et al: Outcomes of chronic
distal biceps reconstruction with tendon grafting: A matched
comparison with primary repair. JSES Int 2020;5(2):302-306. In a
retrospective study, 46 patients who underwent distal biceps
reconstruction with allograft were compared with 92 matched
patients undergoing primary repair. At mean 5 years, there was
no difference in outcome scores or motion. Level of evidence: IV.
40. Frank T, Seltser A, Grewal R, King GJW, Athwal GS:
Management of chronic distal biceps tendon ruptures: primary
repair vs. semitendinosus autograft reconstruction. J Shoulder
Elbow Surg 2019;28(6):1104-1110. In a retrospective review, 19
delayed distal biceps ruptures managed with tendon
reconstruction were compared with 16 delayed primary repairs.
Patient-Rated Elbow Evaluation and Mayo Elbow Performance
index were be er in the repair group. Level of evidence: III.
41. Gowd AK, Liu JN, Maheshwer B, et al: Return to sport and
weightlifting analysis following distal biceps tendon repair. J
Shoulder Elbow Surg 2021;30(9):2097-2104. A retrospective review
of 61 patients with distal biceps repair found a 93% return to
sport rate. Days from injury to surgery, suture anchor as opposed
to bu on, and dominant-side surgery were factors associated
with lower likelihood of return. Level of evidence: IV.
42. McGinniss A, Guinand LA, Ahmed I, Vosbikian M: Distal
biceps ruptures in National Football League players: Return to
play and performance analysis. J Shoulder Elbow Surg
2021;30(7):1647-1652. This is a retrospective review of 35
professional football players who had a surgically managed distal
biceps rupture. The rate of return to sport was 94%. Offensive
linemen played fewer games per season compared with control
patients; otherwise no differences were seen. Level of evidence:
III.
43. Pagani NR, Leibman MI, Guss MS: Return to play and
performance after surgical repair of distal biceps tendon ruptures
in National Football League athletes. J Shoulder Elbow Surg
2021;30(2):346-351. A retrospective review of 25 professional
football players who underwent distal biceps repair reported an
84% rate of return to sport, although they had shorter career
lengths and played fewer games per season. Level of evidence:
IV.
44. Bergman JW, Silveira A, Chan R, et al: Is immobilization
necessary for early return to work following distal biceps repair
using a cortical bu on technique?: A randomized controlled trial.
 J Bone Joint Surg Am 2021;103(19):1763-1771. This is an RCT of 101
patients treated with primary repair who underwent early
mobilization or 6 weeks of immobilization. The early
mobilization group had be er passive supination and
QuickDASH scores without other differences. Level of evidence:
I.
45. Rubinger L, Solow M, Johal H, Al-Asiri J: Return to work
following a distal biceps repair: A systematic review of the
literature. J Shoulder Elbow Surg 2020;29(5):1002-1009. This is a
systematic review of 40 studies evaluating distal biceps repairs.
Overall, 89% of patients returned to work at mean 14 weeks.
Level of evidence: IV.
46. Amarasooriya M, Bain GI, Roper T, Bryant K, Iqbal K, Phadnis J:
Complications after distal biceps tendon repair: A systematic
review. Am J Sports Med 2020;48(12):3103-3111. A systematic
review of 72 studies on primary distal biceps repairs reported a
25% complication rate with the most common being lateral
cutaneous nerve injury. Fixation did not affect rerupture or PIN
injury rate. Level of evidence: I.
47. Dunphy TR, Hudson J, Batech M, Acevedo DC, Mirzayan R:
Surgical treatment of distal biceps tendon ruptures: An analysis
of complications in 784 surgical repairs. Am J Sports Med
2017;45(13):3020-3029.
48. Walker CM, Noonan TJ: Distal triceps tendon injuries. Clin
Sports Med 2020;39(3):673-685. Review article covering anatomy,
evaluation, and management of distal triceps injuries.
49. Lee JH, Ahn KB, Kwon KR, Kim KC, Rhyou IH: Differences in
rupture pa erns and associated lesions related to traumatic
distal triceps tendon rupture between outstretched hand and
direct injuries. Clin Orthop Relat Res 2021;479(4):781-789. This is a
retrospective review of 22 traumatic distal triceps ruptures.
Indirect injury due to a fall was less likely to lead to full-thickness
rupture compared with direct injury. Indirect injuries had a
 higher likelihood of associated ligamentous and bone injuries.
Level of evidence: III.
50. Agarwalla A, Gowd AK, Jan K, et al: Return to work following
distal triceps repair. J Shoulder Elbow Surg 2021;30(4):906-912. A
retrospective review of 81 distal triceps repairs found 93%
returned to work by average 2.2 months postoperatively and 89%
returned to work at the same intensity. Patients with more
intense jobs and workers’ compensation patients took longer to
return. Level of evidence: IV.
51. Waterman BR, Dean RS, Veera S, et al: Surgical repair of distal
triceps tendon injuries: Short-term to midterm clinical outcomes
and risk factors for perioperative complications. Orthop J Sports
Med 2019;7(4):2325967119839998. This is a retrospective review of
69 distal triceps ruptures. The most common mechanism was
direct trauma, and direct bone tunnels was the most common
fixation method. Overall complication rate was 22%, which was
not associated with age, tear degree, or technique. Level of
evidence: IV.
52. Cicco i MC, Cicco i MG: Ulnar collateral ligament evaluation
and diagnostics. Clin Sports Med 2020;39(3):503-522. This review
article covers ulnar collateral ligament injuries including
anatomy and evaluation as well as thorough differential for
medial-sided elbow symptoms in a throwing athlete.
53. Patel RM, Lynch TS, Amin NH, Gryzlo S, Schickendan M:
Elbow injuries in the throwing athlete. JBJS Rev 2014;2(11):e4.
54. Cain ELJr, Ochsner MGIII: Ulnar collateral ligament
reconstruction. Clin Sports Med 2020;39(3):523-536. This review
article covers anatomy, evaluation, and management of ulnar
collateral ligament injuries.
55. Ha ori H, Akasaka K, Otsudo T, Hall T, Sakaguchi K, Tachibana
Y: Ulnar collateral ligament laxity after repetitive pitching:
Associated factors in high school baseball pitchers. Am J Sports
Med 2021;49(6):1626-1633. Ultrasound evaluation of high school
 baseball pitchers found that strain ratio of the UCL decreased
after 100 pitches, indicating increased laxity.
56. Lizzio VA, Gulledge CM, Smith DG, et al: Predictors of elbow
torque among professional baseball pitchers. J Shoulder Elbow
Surg 2020;29(2):316-320. Sensor evaluation of 12 professional
pitchers showed higher elbow torque with fastballs than
curveballs and increased body mass index was associated with
decreased elbow torque.
57. Ostrander R, Escamilla RF, Hess R, Wi e K, Wilcox L, Andrews
JR: Glenohumeral rotation deficits in high school, college, and
professional baseball pitchers with and without a medial ulnar
collateral ligament injury. J Shoulder Elbow Surg 2019;28(3):423-
429. This is a retrospective evaluation of 216 pitchers either with
or without UCL injury. Those with UCL injury had shoulder
rotation and motion deficits compared with those without. Level
of evidence: II.
58. Wigton MD, Schimoler PJ, Kharlamov A, Miller MC, Frank DA,
DeMeo PJ: The moving valgus stress test produces more ulnar
collateral ligament change in length during extension than
during flexion: A biomechanical study. J Shoulder Elbow Surg
2020;29(6):1230-1235. A cadaver study evaluating the moving
valgus stress test noted more elongation of the UCL compared
with a static test.
59. Molenaars RJ, Medina GIS, Eygendaal D, Oh LS: Injured vs.
uninjured elbow opening on clinical stress radiographs and its
relationship to ulnar collateral ligament injury severity in
throwers. J Shoulder Elbow Surg 2020;29(5):982-988. A
retrospective review of valgus stress radiographs demonstrated
joint gapping was associated with UCL injury severity. However,
excess opening compared with the contralateral side was not
associated with injury severity. Level of evidence: III.
60. Hendawi TK, Rendos NK, Warrell CS, et al: Medial elbow
stability assessment after ultrasound-guided ulnar collateral
ligament transection in a cadaveric model: Ultrasound versus
 stress radiography. J Shoulder Elbow Surg 2019;28(6):1154-1158.
Stress radiographs and ultrasound in cadavers identified
increased joint gapping with UCL transection. There were no
differences between modalities.
61. Park JY, Kim H, Lee JH, et al: Valgus stress ultrasound for
medial ulnar collateral ligament injuries in athletes: Is
ultrasound alone enough for diagnosis? J Shoulder Elbow Surg
2020;29(3):578-586. Prospective imaging of 146 athletes with
medial elbow pain reported degree of UCL injury on MRI was
associated with joint gapping on ultrasound proposing a cutoff of
0.5 mm at 30° of elbow flexion and 1 mm at 90°. Level of evidence:
III.
62. Walker CM, Genuario JW, Houck DA, Murayama S, Mendez H,
Noonan TJ: Return-to-play outcomes in professional baseball
players after nonoperative treatment of incomplete medial ulnar
collateral ligament injuries: A long-term follow-up study. Am J
Sports Med 2021;49(5):1137-1144. A retrospective review of 27
professional baseball players treated nonsurgically for UCL
injuries reported an 85% rate of return to play, of which 78%
reached a higher level of play. There were no differences in
performance metrics. Reinjury rate was 11%. Level of evidence:
III.
63. Chauhan A, McQueen P, Chalmers PN, et al: Nonoperative
treatment of elbow ulnar collateral ligament injuries with and
without platelet-rich plasma in professional baseball players: A
comparative and matched cohort analysis. Am J Sports Med
2019;47(13):3107-3119. A retrospective review of 544 baseball
players treated nonsurgically for UCL injuries found those that
received PRP had longer delay in return to throwing and play.
There were no differences compared with those that did not
receive PRP over time. Level of evidence: III.
64. Chalmers PN, English J, Cushman DM, et al: The ulnar
collateral ligament responds to stress in professional pitchers. J
Shoulder Elbow Surg 2021;30(3):495-503. Prospective ultrasound
evaluation of 185 professional pitchers found UCL thickness was
 associated with peak velocity and prior UCL reconstruction. UCL
thickness and valgus laxity increased during the season and
decreased during off season.
65. Cicco i MC, Hammoud S, Dodson CC, Cohen SB, Nazarian LN,
Cicco i MG: Medial elbow instability resulting from partial tears
of the ulnar collateral ligament: Stress ultrasound in a cadaveric
model. Am J Sports Med 2020;48(11):2613-2620. A cadaver study of
simulated UCL tears found full-thickness tears followed by
midsubstance partial tears had the biggest change in joint space
on stress ultrasound, whereas distal tears had the least amount of
change.
66. Ramkumar PN, Haeberle HS, Navarro SM, Frangiamore SJ,
Farrow LD, Schickendan MS: Prognostic utility of an magnetic
resonance imaging-based classification for operative versus
nonoperative management of ulnar collateral ligament tears:
One-year follow-up. J Shoulder Elbow Surg 2019;28(6):1159-1165. A
retrospective review of 80 baseball players with UCL injuries
reported a higher odds of surgical treatment for distal and
complete tears. Level of evidence: IV.
67. Buckley PS, Morris ER, Robbins CM, et al: Variations in blood
supply from proximal to distal in the ulnar collateral ligament of
the elbow: A qualitative descriptive cadaveric study. Am J Sports
Med 2019;47(5):1117-1123. A cadaver study evaluating vascularity
about the medial epicondyle with India ink noted relatively
dense blood supply about the proximal as opposed to distal UCL.
68. Erickson BJ, Chalmers PN, D’Angelo J, Ma K, Dines JS, Romeo
AA: Do outcomes or subsequent injuries differ after ulnar
collateral ligament reconstruction with palmaris versus
hamstring autograft? Am J Sports Med 2019;47(6):1473-1479. A
retrospective review of 195 professional baseball players who
underwent UCL reconstruction with hamstring autograft
compared with palmaris autograft found no difference in return
or metrics, though they were more likely to sustain a
contralateral leg injury. Level of evidence: III.
69. Erickson BJ, Chalmers PN, D’Angelo J, et al: Side of hamstring
harvest does not affect performance, return-to-sport rate, or
future hamstring injuries after ulnar collateral ligament
reconstruction among professional baseball pitchers. Am J Sports
Med 2019;47(5):1111-1116. A retrospective review of 191 baseball
players who underwent UCL reconstruction with hamstring
autograft comparing whether the tendon was taken from the
drive or landing leg found no differences in return to sport,
subsequent injury, or performance. Level of evidence: III.
70. Looney AM, Wang DX, Conroy CM, et al: Modified Jobe versus
docking technique for elbow ulnar collateral ligament
reconstruction: A systematic review and meta-analysis of clinical
outcomes. Am J Sports Med 2021;49(1):236-248. A meta-analysis of
21 UCL reconstructions found no significant differences between
docking and modified Jobe technique when the flexor pronator
mass was preserved and ulnar nerve transposition was not
performed. Level of evidence: I.
71. Griffith TB, Ahmad CS, Gorroochurn P, et al: Comparison of
outcomes based on graft type and tunnel configuration for
primary ulnar collateral ligament reconstruction in professional
baseball pitchers. Am J Sports Med 2019;47(5):1103-1110. A
retrospective review of 566 professional pitchers who underwent
UCL reconstruction reported 80% return to play, which was not
affected by graft or technique type. Level of evidence: III.
72. Bernholt DL, Lake SP, Castile RM, Papangelou C, Hauck O,
Smith MV: Biomechanical comparison of docking ulnar collateral
ligament reconstruction with and without an internal brace. J
Shoulder Elbow Surg 2019;28(11):2247-2252. A cadaver study
evaluating UCL reconstruction with internal brace augmentation
observed greater stiffness and failure torque compared with
autograft repairs without it. With the internal brace, values were
similar to the native UCL.
73. Dugas JR, Looze CA, Capogna B, et al: Ulnar collateral ligament
repair with collagen-dipped fibertape augmentation in overhead-
throwing athletes. Am J Sports Med 2019;47(5):1096-1102. A
 retrospective review of 111 overhead athletes treated with UCL
repair with internal brace augmentation reported 92% return to
play at mean 6.7 months. Level of evidence: IV.
74. Lizzio VA, Smith DG, Guo EW, et al: The effect of the crow hop
on elbow stress during an interval throwing program. Am J Sports
Med 2021;49(2):359-363. Sensor evaluation of 20 baseball players
found crow hop throws generated greater elbow torque than
standing throws at distances up to 60 feet.
75. Lizzio VA, Smith DG, Jildeh TR, et al: Importance of radar gun
inclusion during return-to-throwing rehabilitation following
ulnar collateral ligament reconstruction in baseball pitchers: A
simulation study. J Shoulder Elbow Surg 2020;29(3):587-592. Sensor
evaluation of 37 pitchers observed that pitches thrown at 50% or
75% effort were significantly faster and generated more elbow
torque than pitches actually thrown at 50% or 75% velocity.
76. Anderson MJJ, Crocka WK, Mueller JD, et al: Return-to-
competition criteria after ulnar collateral ligament
reconstruction: A systematic review and meta-analysis. Am J
Sports Med 2021;50(4):1157-1165. A meta-analysis of 15 studies
evaluating UCL reconstruction in throwing athletes reported on
mean return progress. Overall, 86% returned to preinjury level or
higher at average 12.2 months. Level of evidence: IV.
77. Pla BN, Zacharias AJ, Uhl T, Freehill MT, Conley CE, Stone AV:
Pitch break and performance metrics remain unchanged in
pitchers who returned to the same level of play after ulnar
collateral ligament reconstruction in Major League Baseball
pitchers. J Shoulder Elbow Surg 2021;30(10):2406-2411. A
retrospective review of 46 patients who underwent UCL
reconstruction found no change in pitch velocity, movement, or
angle compared with preoperative findings. Level of evidence: IV.
78. Camp CL, Jensen AR, Leland DP, Flynn N, Lahti J, Conte S:
Players’ perspectives on successfully returning to professional
baseball after medial ulnar collateral ligament reconstruction. J
Shoulder Elbow Surg 2021;30(5): e245-e250. A retrospective
 review of 530 professional pitchers who underwent UCL
reconstruction found that 56% of pitchers reported no change in
pitching mechanics and 54% thought their velocity was faster
than before the injury. During recovery, 20% of pitchers
experienced a setback.
79. Erickson BJ, Carr J, Chalmers PN, Vellios E, Altchek DW: Ulnar
collateral ligament tear location may affect return-to-sports rate
but not performance upon return to sports after ulnar collateral
ligament reconstruction surgery in professional baseball players.
Am J Sports Med 2020;48(11):2608-2612. A retrospective review of
25 pitchers who underwent UCL reconstruction found players
with distal as opposed to proximal tears were more likely to
return to sport and had higher utilization postoperatively. Level
of evidence: III.
80. Erickson BJ, Chalmers PN, D’Angelo J, et al: Timing of return to
ba ing milestones after ulnar collateral ligament reconstruction
in professional baseball players. Am J Sports Med 2020;48(6):1465-
1470. A retrospective review of 141 UCL reconstructions in
professional position players found only 77% were able to return
to hi ing in a game and 75% fielding in a game. Ultimately
players had fewer at-bats, hits, and runs postoperatively. Level of
evidence: IV.
81. Hadley CJ, Edelman D, Arevalo A, Patel N, Cicco i MG, Dodson
CC: Ulnar collateral ligament reconstruction in adolescents: A
systematic review. Am J Sports Med 2021;49(5):1355-1362. A
systematic review of 9 studies evaluating adolescent throwing
athletes reported 84% return to sport at the same level or higher.
There was a 4% complication rate and 2% revision surgery rate.
Level of evidence: IV.
82. Glogovac G, Grawe BM: Outcomes with a focus on return to play
for revision ulnar collateral ligament surgery among elite-level
baseball players: A systematic review. Am J Sports Med
2019;47(11):2759-2763. A systematic review of 5 studies evaluated
revision UCL reconstruction with a return to sport rate of 63%,
which ranged from 1.3 to 1.7 years. Level of evidence: V.
83. Andrews JR, Venkateswaran V, Christensen KD, et al: Outcomes
after ulnar collateral ligament revision reconstruction in baseball
players. Am J Sports Med 2020;48(13):3359-3364. A retrospective
review of 65 baseball players who underwent UCL revision
reconstruction reported 50% returning to their prior level of play
at mean 12.7 months. Level of evidence: IV.
84. Clain JB, Vitale MA, Ahmad CS, Ruchelsman DE: Ulnar nerve
complications after ulnar collateral ligament reconstruction of
the elbow: A systematic review. Am J Sports Med 2019;47(5):1263-
1269. A meta-analysis of 17 studies evaluating UCL
reconstruction found a 12% rate of postoperative ulnar
neuropathy, although the rate of revision surgery was 0.8%. Ulnar
nerve transposition had a higher rate of neuropathy compared
with no handling of the nerve. Level of evidence: V.
85. Fedorka CJ, Oh LS: Posterolateral rotatory instability of the
elbow. Curr Rev Musculoskelet Med 2016;9(2):240-246.
86. Badhrinarayanan S, Desai A, Watson JJ, White CHR, Phadnis J:
Indications, outcomes, and complications of lateral ulnar
collateral ligament reconstruction of the elbow for chronic
posterolateral rotatory instability: A systematic review. Am J
Sports Med 2021;49(3):830-837. A systematic review of 17 studies
involved LUCL reconstruction for PLRI, which most often
occurred in the se ing of trauma. A variety of grafts and
techniques were used with an overall complication rate of 22%,
which was most commonly recurrent instability. Level of
evidence: V.
87. Camp CL, Fu M, Jahandar H, et al: The lateral collateral
ligament complex of the elbow: Quantitative anatomic analysis of
the lateral ulnar collateral, radial collateral, and annular
ligaments. J Shoulder Elbow Surg 2019;28(4):665-670. A cadaver
study described LUCL anatomy, noting the origin to be 10.7 mm
distal to the lateral epicondyle and the insertion 3.3 mm distal to
the apex of the supinator crest.
88. Melbourne C, Cook JL, Della Rocca GJ, Loftis C, Konicek J,
Smith MJ: Biomechanical assessment of lateral ulnar collateral
ligament repair and reconstruction with or without internal brace
augmentation. JSES Int 2020;4(2):224-230. A cadaver study
evaluated repair, repair with augmentation, reconstruction with
palmaris, and reconstruction with augmentation. Augmentation
had a higher load to failure, reduced displacement
(reconstruction group only), and be er rotational stiffness (repair
alone).
89. Greiner S, Koch M, Kerschbaum M, Bhide PP: Repair and
augmentation of the lateral collateral ligament complex using
internal bracing in dislocations and fracture dislocations of the
elbow restores stability and allows early rehabilitation. Knee Surg
Sports Traumatol Arthrosc 2019;27(10):3269-3275. A retrospective
review of 17 patients treated with LUCL repair with suture tape
augmentation reported no signs of residual instability with
excellent range of motion. All returned to preinjury activity level
and there was only one revision surgery for heterotopic
ossification. Level of evidence: IV.
S E CT I ON 6

Hand and Wrist

SECTION EDITOR
Jeffrey G. Stepan, MD, MSc Martin I. Boyer, MD, FAAOS
C H AP T E R 3 3

Anatomy, Clinical Examination,

and Imaging of the Hand and
Wrist
Martin I. Boyer MD, FAAOS, Jeffrey G. Stepan MD, MSc

Dr. Boyer or an immediate family member has received royalties from ExsoMed, LLC; serves as a
paid consultant to or is an employee of ExsoMed; and serves as a board member, owner, officer,
or committee member of the American Society for Surgery of the Hand. Neither Dr. Stepan nor
any immediate family member has received anything of value from or has stock or stock options
held in a commercial company or institution related directly or indirectly to the subject of this
chapter.

ABSTRACT
Recent publications outlining the bony and vascular anatomy of the
hand and wrist have led surgeons to a deeper understanding of
both osteology and microvasculature, whereas progress in
neuroimaging and in vivo functional imaging of bone, articular
cartilage, and tendon has led to real-time advances in treatment of
patients. There have been important advances made in these fields
that are related directly to the care of patients.
Keywords: cartilage imaging; flexor tendon gap; hand and wrist
anatomy; neuroimaging

Introduction
Topics related to the anatomy of the hand and wrist that have been
investigated over the past several years fall into several groups:
bony and vascular anatomy, kinematics of the carpus, bony and
soft-tissue anatomy of the hand and forearm, neuroanatomy and
diagnostic neuroimaging, anatomic imaging of cartilage and dense
regular connective tissue, soft-tissue imaging and diagnosis of
infection, and the diagnosis of hand and wrist fractures.

Evolution of Hand and Wrist Anatomic

Knowledge

Bony Anatomy
Since its popularization in the early 2000s, reconstruction of the
middle phalanx after proximal interphalangeal joint dorsal fracture-
dislocation has increased in popularity. In a 2019 study, laser
scanning technology of the dorsal distal hamate articular surface
was used to demonstrate the lack of similarity in shape between the
volar middle phalangeal base and the articular surfaces of the
dorsal distal hamate. 1 The study authors urged a detailed
understanding of hamate morphology before using this
reconstructive technique. In a 2020 study, direct measurement of 40
hands (160 phalanges and 40 hamates) was used to observe that the
middle phalangeal base and distal articular surface of the hamate
are not anatomically identical; these differences may prevent
anatomic reconstruction 2 (Figure 1). Variation in morphology of the
hook of the hamate has been noted, especially in Caucasian
females. 3 Taken together, these studies add to the understanding of
the utility of middle phalangeal reconstruction following
irreducible dorsal fracture-dislocations, and to the understanding
of the osteology of the hamate palmarly and dorsally.
 Figure 1 Clinical photographs of hamate specimens identifying variability in
distal articular anatomy.A, Right hamate specimens. B, Left hamate specimens.
(Reprinted from Drain J, Mehta S, Goyal KS: An analysis of hamate morphology
relevant to hemi-hamate arthroplasty. J Hand Surg Am 2020;45[7]:657.e1-
657.e6, Figure 5, with permission from Elsevier.)

Investigators in the Netherlands used four-dimensional CT to

assess proximal carpal row motion in patients with Madelung
deformity and documented decreased lunate and triquetrum
motion during in vivo wrist motion. This 2021 study demonstrated
the usefulness of four-dimensional CT in the evaluation of carpal
motion, and also increased the understanding of carpal motion in
patients with Madelung deformity. 4
Osteology of the radius and ulna, especially as related to forearm
rotation, was evaluated in a 2020 study by several Canadian
surgeons using CT evaluation of cadaver forearms. They found that
rotational anatomy varies significantly between individuals but
demonstrated similar anatomy side-to-side, allowing for its use in
the correction of malunions, or in the treatment of patients with
traumatic bone loss. 5

Neurovascular Anatomy
In a 2019 study, micro-CT angiographic scanning of the scaphoid
was used to assess internal vascularity. Two distinct scaphoid types
(full and slender) were found to exist, and the vascular supply for
each was dissimilar. It was proposed that central axis
interfragmentary screw insertion is best in terms of minimizing
disruption of vascularity, and that antegrade insertion (dorsal to
volar) was also of substantial benefit. 6
Investigators at the University of Buenos Aires used dissection of
52 fresh-frozen cadaver proximal interphalangeal joints to
investigate proximal interphalangeal neuroanatomy and found
consistent articular neuroanatomy at the palmar aspect of the joint.
They hypothesized that denervation techniques for the proximal
interphalangeal joint based on these studies might improve results
(perhaps of nonanatomic hemihamate autografts) 7 (Figure 2).
 Figure 2 Illustration of the various patterns of proximal interphalangeal joint
innervation.A, Pattern 1. B, Pattern 2.(Reprinted from Pastrana MJ, Zaidenberg
EE, Palumbo D, Cesca FJ, Zaidenberg CR: Innervation of the proximal
interphalangeal joint: An anatomical study. J Hand Surg Am 2019;44[5]:422.e1-
422.e5, Figure 2 (panel A) and FIgure 5 (panel B), with permission from
Elsevier.)

A 2020 study that will be of use for hand surgeons treating

patients with acute injury involved 24 fresh-frozen cadavers that
were dissected to demonstrate a new surface landmark for the
location of bifurcation of the radial and ulnar digital nerves of the
thumb. This study’s usefulness lies in its assistance in the
evaluation of patients with penetrating injuries to the thenar
eminence as well as providing a guide for surgical exploration of
the radial and ulnar digital nerves of the thumb 8 (Figures 3 and 4).

Figure 3 Clinical photographs of surface landmarks to identify the thumb

bifurcation of the radial and ulnar digital nerves.A, Index metacarpophalangeal
joint flexed to 90°. B, The distal interphalangeal joint in full extension and
proximal interphalangeal joint flexed until the index finger meets skin. C, The
bifurcation of the radial and ulnar digital nerves is predicted to bifurcate within
this U.(Reprinted from Wu K, Aibinder WR, Richards RS, Suh N: A new surface
landmark for thumb digital nerve bifurcation: a cadaveric study. J Hand Surg Am
2020;45[4]:362.e1-362.e4, Figure 1, with permission from Elsevier.)
Figure 4 Clinical photograph of anatomic dissection of the bifurcation U.The
bifurcation is found within the U with a type 1 pattern: proper thumb radial digital
nerve and common digital nerve to the first web space. The thumb ulnar digital
nerve and index radial digital nerve branch from the common digital nerve to the
first web space more distal.(Reprinted from Wu K, Aibinder WR, Richards RS,
Suh N: A new surface landmark for thumb digital nerve bifurcation: A cadaveric
study. J Hand Surg Am 2020;45[4]:362.e1-362.e4, Figure 3, with permission
from Elsevier.)
Soft-Tissue Anatomy
Also related to anatomy of the palm of the hand is a review article
that described current understanding of the anatomy of the
retinacular elements of the hand (the palmar fascia). 9 A coherent
and consistent nomenclature is outlined for the palmar,
palmodigital, and digital fascia, as well as the transverse carpal
ligament and the flexor retinacula of the thumb and fingers.
Anomalous forearm musculature was also reviewed, with the six
most common anomalous muscles of the forearm (aberrant
palmaris longus, anconeus epitrochlearis, palmaris profundus,
flexor carpi radialis brevis, accessory head of flexor pollicis muscle,
and anomalous radial wrist extensors) described in detail. Imaging
in addition to history and physical examination were recommended
to diagnose anomalies in these muscles and surgical excision if
symptomatic. 10
Another study related to upper extremity muscular anatomy
found that pectoral muscle hypoplasia was necessary but
insufficient for the diagnosis of Poland syndrome. The authors
cautioned that accurate diagnosis of syndromes associated with
pectoral muscle deficiency has implications regarding inheritance
and associated anomalies. 11

Clinical Examination of the Hand and Wrist:

Current Concepts
An interesting 2019 retrospective clinical and radiographic
assessment of the soft tissue in fingers with purulent infections of
the flexor tendon sheath showed that a differential assessment of
volar versus dorsal soft-tissue thickness at the level of the proximal
phalanx was highly predictive of intrasynovial infection. 12 In cases
of purulent infection, the ratio of volar to dorsal thickness was
always greater than 1.
 A study assessing the clinical examination of patients presenting
with wrist pain after a fall (occult distal radius fractures)
demonstrated that distal radial tenderness was highly effective in
the diagnosis of distal radius fractures in the absence of plain
radiographic abnormalities. 13 The importance of palpation of the
injured extremity was stressed.

Advances in Imaging of the Upper Extremity

Neuroimaging of peripheral nerves was reviewed in detail in a 2019
study that discusses the advances in magnetic resonance
neurography and ultrasonography in the diagnosis of compression
neuropathies as well as nerve tumors and lesions of the brachial
plexus. 14
Similar imaging subspecialization in the diagnosis of articular
cartilage disorders following extra-articular and intra-articular
fractures of the distal radius by means of biochemical and
morphologic nonenhanced MRI was evaluated in a 2020 study. 15
This technique was shown to be useful for the diagnosis of articular
cartilage damage following fractures without the need for
intravenous or intra-articular contrast agents. The authors of a 2021
study evaluated the efficacy of MRI in the preoperative assessment
of elbow osteochondritis dissecans lesions and found this
technique to be of significant value when correlated with surgical
findings. 16
A 2021 study demonstrated the usefulness of MRI and
ultrasonography in the diagnosis of flexor tendon repair site gaps,
potentially allowing for modifications in rehabilitation protocols so
that the danger of intrasynovial flexor tendon repair site rupture is
mitigated. 17 In addition, a pocket-sized ultrasonography device was
used to diagnose fractures of the distal radius and to gauge
reduction accuracy. 18

Summary
Relevant studies on the anatomy and imaging of the hand, wrist,
and upper extremity will provide the surgeon a deeper
understanding of the diagnosis and treatment of traumatic and
nontraumatic conditions of the upper extremity.

Key Study Points

There is substantial variability in the anatomy of the dorsal hamate that is relevant to
the reconstruction of proximal interphalangeal joint fracture-dislocations.
New descriptions of proximal interphalangeal joint neuroanatomy may allow for
greater success of denervation procedures in the management of painful arthritis.
Advances in imaging of nerves, cartilages, and flexor tendons have direct
implications on the care and rehabilitation of injured patients.

Annotated References
1. Sollaccio DR, Navo P, Ghiassi A, Orr CM, Patel BA, Lewton KL:
Evaluation of articular surface similarity of hemi- hamate grafts
and proximal middle phalanx morphology: A 3D geometric
morphometric approach. J Hand Surg Am 2019;44(2):121-128. The
authors used osteologic samples from two separate bone banks
to obtain three-dimensional virtual renderings of the dorsal
distal hamate and volar middle phalanx base in 25 cadavers. The
authors found a wide variation in articular morphology of the
hamate that was not found in the volar middle phalangeal base.
The authors conclude that there is no uniform similarity in shape
between the volar base of the middle phalanx and dorsal hamate
and note that hamate morphology should be considered while
performing a hemihamate procedure.
2. Drain J, Mehta S, Goyal KS: An analysis of hamate morphology
relevant to hemi-hamate arthroplasty. J Hand Surg Am
2020;45(7):657.e1-657.e6. This cadaver study from a separate
osteologic collection used 40 cadaver hamates and 160 matched
middle phalanx specimens (index through small finger). The
authors measured features of the hamate and middle phalanx
specimens as relevant to hemihamate reconstruction finding the
 distal articular surface of the hamate to have a smaller axial ridge
angle, a smaller articular sagi al inclination, with a large surface
area compared with the volar base of the middle phalanx. This
knowledge may improve harvest and inset during hemihamate
reconstruction.
3. Huang JI, Thayer MK, Paczas M, Lacey SH, Cooperman DR:
Variations in hook of hamate morphology: A cadaveric analysis. J
Hand Surg Am 2019;44(7):611.e1-611.e5. This study evaluated 2,000
hamate bones to evaluate the hook of the hamate. The mean
height was 9.8 mm with less than 4% of the population having
hamate hooks larger than 7 mm. Knowledge in this variation of
size of hamates may be important for surgical surface anatomy
and interpretation of imaging studies.
4. Peymani A, de Roo MGA, Dobbe JGG, Streekstra GJ, McCarroll
HR, Strackee SD: Carpal kinematics in Madelung deformity. J
Hand Surg Am 2021;46(7):622.e1-622.e12. The authors evaluated 9
wrists with Madelung deformity and 18 healthy wrists and
created four-dimensional imaging during flexion-extension and
radioulnar deviation. They found that there was decreased
rotation of the lunate and triquetrum during flexion-extension
and less translation of the lunate during radioulnar deviation.
The study demonstrated the capability of four-dimensional
imaging on wrist kinematics and the decreased mobility of the
lunate and triquetrum in wrists with Madelung deformity.
5. Daneshvar P, Willing R, Lapner M, Pahuta MA, King GJW:
Rotational anatomy of the radius and ulna: Surgical implications.
J Hand Surg Am 2020;45(11):1082.e1-1082.e9. The authors created
three-dimensional models of the radius and ulna from 98 cadaver
forearms to analyze the rotation of the ulna and the ulna. The
biceps was 44° supinated from the distal radius central axis (136°
opposite the radial styloid) and the volar cortex of the distal
radius was 13° supinated compared with the distal radius central
axis.
6. Morsy M, Sabbagh MD, van Alphen NA, Laungani AT, Kadar A,
Moran SL: The vascular anatomy of the scaphoid: New
 discoveries using micro–computed tomography imaging. J Hand
Surg Am 2019;44(11):928-938. This study investigated the
intraosseous vascular anatomy of 13 scaphoids using micro-CT
imaging and three- dimensional reconstruction, finding that all
specimens received inflow from the dorsal ridge supplying 83%
of the scaphoid, whereas four scaphoids had a supplemental
network from the volar vessels at the waist. A separate network
was identified by vessels entering at the volar aspect of the
scaphoid tubercle supplying the remainder of the scaphoid
(missing in one specimen).
7. Pastrana MJ, Zaidenberg EE, Palumbo D, Cesca FJ, Zaidenberg
CR: Innervation of the proximal interphalangeal joint: An
anatomical study. J Hand Surg Am 2019;44(5):422.e1-422.e5. The
authors studied 52 fresh-frozen fingers of 6 male and 4 female
cadavers injected with colored latex to describe innervation of the
proximal interphalangeal joint. The joint was innervated by one
articular branch of the palmar digital nerve on each side of the
finger, and less frequently a distal branch from the same nerve
was found. Dorsal articular branches were only found in the
small finger.
8. Wu K, Aibinder WR, Richards RS, Suh N: A new surface
landmark for thumb digital nerve bifurcation: A cadaveric study.
J Hand Surg Am 2020;45(4):362.e1-362.e4. Using 24 fresh-frozen
cadavers, the authors found a bifurcation U where in 92% of
specimens the radial and ulnar digital nerves of the thumb
bifurcated. This bifurcation U is located in the area where the
index finger pulp touches the thenar eminence with the index
finger metacarpophalangeal joint flexed to 90°. They also found
that in most of the specimens the index radial digital nerve either
trifurcated (with the radial and ulnar digital nerves of the thumb)
or branched from a common digital nerve (with the ulnar digital
nerve of the thumb).
9. Godfrey J, Rayan GM: Anatomy of the volar retinacular elements
of the hand: A unified nomenclature. J Hand Surg Am
2018;43(3):260-270.
10. Andring N, Kennedy SA, Iannuzzi NP: Anomalous forearm
muscles and their clinical relevance. J Hand Surg Am
2018;43(5):455-463.
11. Baas M, Burger EB, Sneiders D, Galjaard RJH, Hovius SER, van
Nieuwenhoven CA: Controversies in Poland syndrome:
Alternative diagnoses in patients with congenital pectoral muscle
deficiency. J Hand Surg Am 2018;43(2):186.e1-186.e16.
12. Yi A, Kennedy C, Chia B, Kennedy SA: Radiographic soft tissue
thickness differentiating pyogenic flexor tenosynovitis from other
finger infections. J Hand Surg Am 2019;44(5):394-399. This
retrospective review of 60 patients with finger infections and
radiographs (30 with pyogenic flexor tenosynovitis and 31 with
other finger infections) analyzed the different soft-tissue
thickness on radiographs between the two groups. Given all
finger infections had diffuse swelling, the authors found
significantly greater volar soft-tissue thickness in patients with
pyogenic flexor tenosynovitis. In their series, patients with a
differential between volar and dorsal soft-tissue thickness greater
than 7 mm had a sensitivity and specificity of 84% and 74%,
respectively, for diagnosing pyogenic flexor tenosynovitis. Level
of evidence: IV.
13. Glickel SZ, Hinojosa L, Eden CM, Balutis E, Barron OA,
Catalano LW: Predictive power of distal radial metaphyseal
tenderness for diagnosing occult fracture. J Hand Surg Am
2017;42(10):835.e1-835.e4.
14. Holzgrefe RE, Wagner ER, Singer AD, Daly CA: Imaging of the
peripheral nerve: Concepts and future direction of magnetic
resonance neurography and ultrasound. J Hand Surg Am
2019;44(12):1066-1079. This article reviews the strengths and
limitations of ultrasound and magnetic resonance neurography
with regard to imaging of neural structures and for the diagnosis
in specific conditions or injuries. Also discussed are new
technologies and future directions of nerve imaging.
15. Tarabin N, Gehrmann S, Mori V, et al: Assessment of articular
cartilage disorders after distal radius fracture using biochemical
and morphological nonenhanced magnetic resonance imaging. J
Hand Surg Am 2020;45(7):619-625. The authors assessed
radiocarpal articular cartilage damage after distal radius fractures
with the use of multiparametric MRI using 3T MRI in 14 patients
with distal radius fractures and in 12 healthy volunteers. The
study found greater cartilage degradation in patients with distal
radius fractures compared with control patients; there was no
difference in patients with extra-articular or intra-articular
articular fractures. Level of evidence: IV.
16. Broughton JS, Obey MR, Hillen TJ, Smith MV, Goldfarb CA:
Magnetic resonance imaging in osteochondritis dissecans of the
humeral capitellum: Preoperative assessment of lesion size and
lateral wall integrity. J Hand Surg Am 2021;46(6):454-461. This
study compared preoperative MRI findings of osteochondritis
dissecans and intraoperative findings. There was no significant
difference in mean lesion size between preoperative MRI and
intraoperative measurements, and use of the lateral wall sign on
MRI is accurate in the identification of lateral wall involvement.
Level of evidence: II.
17. Renfree KJ, Dahiya N, Kransdorf MJ, Zhang N, Patel KA, Drace
PA: Comparative accuracy of 1.5T MRI, 3T MRI, and static
ultrasound in diagnosis of small gaps in repaired flexor tendons:
A cadaveric study. J Hand Surg Am 2021;46(4):287-294. In this
study, the authors compared different imaging techniques to
identify small gaps in flexor tendon repair in 160 fresh-frozen
cadaver digits with repairs of varying gap sizes. Both 1.5T and 3T
MRI had lower mean error than ultrasonography for small gap
sizes 2 mm or less with ultrasonography overestimating gap size;
however, they performed equally well for gaps 4 to 6 mm in size.
The authors recommended MRI over ultrasonography for
evaluation of gaps after flexor tendon repair.
18. Lau BC, Robertson A, Motamedi D, Lee N: The validity and
reliability of a pocket-sized ultrasound to diagnose distal radius
fracture and assess quality of closed reduction. J Hand Surg Am
2017;42(6):420-427.
C H AP T E R 3 4

Bone and Soft-Tissue Infections

and Vascular Conditions of the
Hand and Wrist
Bilal Mahmood MD, Warren C. Hammert MD

Dr. Hammert or an immediate family member serves as a board member, owner, officer, or
committee member of the American Society for Surgery of the Hand. Neither Dr. Mahmood nor
any immediate family member has received anything of value from or has stock or stock options
held in a commercial company or institution related directly or indirectly to the subject of this
chapter.

ABSTRACT
Hand and wrist infections are a common reason for emergency
department and urgent care visits. Evidence does not support the
use of prophylactic antibiotics in routine soft-tissue hand surgeries.
A high level of suspicion is required for the diagnosis of atypical
and fungal infections. Upper extremity vascular disorders are not as
common as many conditions seen by hand surgeons and
orthopaedic surgeons but are important to understand to provide
optimal treatment. In broad terms, these conditions fall into two
categories: vasospastic and occlusive disorders. There is a
substantial amount of overlap between these categories, but
following the principles for workup and advanced imaging with
angiography when surgery is considered will help to inform
treatment options to provide optimal care.
Keywords: hand infection; hand ischemia; prophylactic antibiotics;
soft tissue infections; vasospasm

Introduction
Hand and wrist infections are a common reason for emergency
department and urgent care visits. The use of routine antibiotic
prophylaxis in soft-tissue hand surgery cases is unnecessary.
Appropriate management of common, atypical, and fungal
infections of the hand and wrist requires early diagnosis,
appropriate antibiotic and antifungal coverage, and surgical
débridement as needed. With some conditions, such as necrotizing
fasciitis, delayed management can be limb-threatening or life-
threatening.

Soft-Tissue Infections

Surgical Site Infection and Indications for

Antibiotic Prophylaxis
Antibiotic prophylaxis is a common practice across multiple
surgical specialties; however, no relationship has been found
between risk of surgical site infection and antibiotic prophylaxis in
soft-tissue hand surgery. In a study of multistate commercial
insurance claims, no difference in risk for postoperative surgical
site infection was found between patients who had received
antibiotic prophylaxis and those who had not. 1 A 2020 study of 312
Veterans Affairs patients undergoing carpal tunnel release also
reported no difference in risk for surgical site infections in regard
to prophylactic antibiotic use, or an operating room versus
procedure room se ing. 2
Infection rates after soft-tissue hand surgery are consistently less
than 1%. Building on previous literature, the authors of one study
reported on 454,987 Medicare patients undergoing carpal tunnel
release, reporting an infection rate of 0.32%. 3 A number of other
studies agree with these low infection rates in soft-tissue hand
surgery, with or without antibiotic prophylaxis. 4 - 6 Even in patients
with prosthetic joints, according to a 2020 study there is no known
risk of a prosthetic joint infection after clean hand surgery. 7 It can
be concluded that the rate of surgical site infection in soft-tissue
hand surgery is low, without evidence to support the routine use of
preoperative antibiotics.
Factors associated with an increased risk of surgical site infection
after carpal tunnel release include male sex, age younger than 65
years, body mass index higher than 30 kg/m2, tobacco and alcohol
use, diabetes, inflammatory arthritis, vascular disease, chronic liver
disease, chronic kidney disease, chronic lung disease, and
depression. 3 In data from a 2019 study looking specifically at
hemoglobin A1c levels in patients with diabetes undergoing
primary open carpal tunnel release, elevated hemoglobin A1c levels
higher than 7.8 were found to be associated with an increased risk
of postoperative surgical site infection. 8

Hand Cellulitis and Abscesses

In patients presenting to the emergency department with cellulitis,
hand involvement is an independent risk factor for inpatient
hospitalization. 9
Community-acquired methicillin-resistant
Staphylococcus aureus remains a common cause of hand soft-tissue
infection, although polymicrobial infections are on the rise. 10 One
study recommended empiric coverage for community-acquired
methicillin-resistant S aureus if local prevalence rates exceed 10% to
15%. 11 Unfortunately, multidrug-resistant methicillin-resistant S
aureus is also being reported, with young age, intravenous drug use,
and nosocomial infection as risk factors. 12
Drainable fluid collections require intervention. Abscesses may
be evaluated with ultrasonography, with a sensitivity as high as
96.7%. MRI may also be used with 89% sensitivity and 80%
specificity for a soft-tissue abscess. In cases where ultrasonographic
evaluation is difficult or access to MRI is limited, CT can be valuable
in evaluating for an abscess. 13 Early administration of antibiotics
should be provided; antibiotics do not need to be held until
decompression. Following surgical decompression, no difference
has been demonstrated between different soaks or daily dressing
change techniques.

Flexor Tenosynovitis
The four Kanavel signs are used to clinically diagnose flexor
tenosynovitis, but only 54% of patients with pyogenic flexor
tenosynovitis may present with all of these signs. 14 There are
conflicting studies on which Kanavel signs are most sensitive or
specific. 15 , 16 Inflammatory markers such as white blood cell count,
erythrocyte sedimentation rate, and C-reactive protein are used as
adjuncts, but are not sensitive enough to use as a screening tool to
rule out flexor tenosynovitis. 17 Kanavel signs are not uniformly
present in children and adolescents.
Patients presenting early (less than 24 hours of symptoms) or
with mild symptoms may undergo a trial of intravenous antibiotic
therapy alone. 18 When nonsurgical management fails or a patient
presents late or with significant findings, surgery is indicated. A
systematic review reported excellent outcomes in 74% of patients
treated with limited incisions and closed catheter irrigation
compared with 26% of patients treated with open surgical drainage.
19
Patients must be counseled on the possibility of repeat surgery,
with another study showing a 14.2% rate of requiring additional
surgical intervention. 20
The ideal route and duration of antibiotic administration in flexor
tenosynovitis has not been determined. 19 The most common
pathogens identified are S aureus and beta-hemolytic Streptococcus. 21
Worse outcomes are associated with older age, delay in antibiotic
treatment, and medical comorbidities. 15
Septic Arthritis
Untreated septic arthritis erodes the articular cartilage. An
inflamed joint needs to be evaluated appropriately and treated in a
timely manner. Cases of atraumatic, inflamed joints have a wider
differential diagnosis that includes crystalline arthropathy or
rheumatoid disease. Joint-fluid analysis is helpful for diagnosis,
although this can be difficult to obtain. One study reviewed 104
patients with inflamed wrists. Over a 2-year period, five patients
had confirmed septic arthritis; of these, only two had undergone
successful aspiration. 22 According to a 2019 study, if a minimal
amount of fluid is aspirated, the greatest diagnostic lead may come
from a cell count and the percentage of polymorphonuclear
leukocytes. 18 After a septic joint is identified, surgical treatment,
which may be open or arthroscopic, with irrigation or débridement
is the standard of care. A course of intravenous antibiotics, possibly
with a course of oral antibiotics to follow, is pursued. S aureus is the
most common organism involved.

Necrotizing Fasciitis
There are approximately 600 to 1,200 cases of necrotizing fasciitis
yearly in the United States, and the extremities are most commonly
affected. 18 Mortality rates can vary from 5.4% to 11.1% and
amputation rates are approximately 25% when the infection is
based in the extremity. 23 , 24 Independent risk factors for death
include heart disease, white blood cell count greater than 30,000/µL,
and creatinine level greater than 2 mg/dL. 23
Young, healthy individuals may have monomicrobial infection
with group A beta-hemolytic Streptococcus. Vibrio species are also
common. Patients with diabetes or other immunosuppressive
conditions are more likely to have polymicrobial infections
involving aerobic and anaerobic organisms. 18
The initial diagnosis of necrotizing fasciitis is based on clinical
findings in combination with imaging and laboratory results. The
Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score
was developed to help in diagnosis. 25 As shown in Table 1, an
LRINEC score higher than 8 indicates greater than 75% chance of a
patient having necrotizing fasciitis. In a study of atypical pathogens
such as Vibrio, however, all mortality cases had a LRINEC score of
less than 6. 26 In these cases, a LRINEC score of 2 or higher along
with hemorrhagic bullae or blister skin lesions are important
predictors of necrotizing fasciitis. 27 The most common risk factors
for necrotizing fasciitis include intravenous drug use, smoking,
trauma, and diabetes. 28 CT findings may show the presence of
fascial air, edema, fluid tracking, lymphadenopathy, and
subcutaneous edema. MRI findings are similar to those of
nonnecrotizing soft-tissue infections. A definitive diagnosis can be
made in the operating room with a fascial biopsy.

Table 1
Laboratory Risk Indicator for Necrotizing Fasciitis Score

Laboratory Marker Results Score

C-reactive protein (mg/dL) ≥15 4
White blood cell (1/mm 3) 15,000-25,000 1
≥25,000 2
Hemoglobin (g/dL) 11.0-13.5 1
<11.0 2
Sodium (mmol/L) <135 2
Creatinine (mg/dL) >1.6 2
Glucose (mg/dL) >180 1
Data from Wong CH, Khin LW, Heng KS, Tang KC, Low CO: The LRINEC (Laboratory Risk
Indicator for Necrotizing Fasciitis) score: A tool for distinguishing necrotizing fasciitis from
other soft tissue infections. Crit Care Med 2004;32(7):1535-1541.

After a necrotizing fasciitis soft-tissue infection has been

identified, treatment is emergent aggressive débridement. Serial
débridement every 24 to 48 hours is usually necessary. Intensive
care is needed to monitor vital signs and broad-spectrum
intravenous antibiotics are administered until definitive culture
results are available.
Bite Wounds and Fight Bites
The hand is the most common site for bite injuries. Fight bites are
sustained from a clenched-fist injury resulting from striking
another person in the mouth. These wounds may overlie the
metacarpophalangeal or proximal interphalangeal joints; rates of
traumatic arthrotomy may approach 100%. 29 Eikenella corrodens is
the classically described pathogen in human fight bites, but
Viridans group streptococci, S aureus, and enterococci are also
common pathogens. Broad-spectrum antibiotics are the first line of
treatment, and the treating surgeon should have a low threshold for
irrigation and débridement formally in the operating room.
Workup should include radiographs to evaluate for a fracture or
broken tooth fragment. Extensor tendon injuries should also be
considered.
Dog bites are the most common animal bites in the United
States. Dog bites result in larger and more traumatic wounds than
cat bites. The smaller and innocuous wounds from cat bites may be
deeper because of the cat’s sharp needle-like teeth. Common
pathogens with both cat and dog bites include S aureus,
Streptococcus, Bacteroides, and Pasteurella multocida. Pasteurella is
more commonly isolated from cat bites. Antibiotic therapy should
be targeted to gram-positive, gram-negative, and anaerobic
organisms. Formal irrigation and débridement should be
considered based on the extent of injury.

Osteomyelitis
Osteomyelitis of the hand is uncommon, representing fewer than
10% of all hand infections. 30 The most common bone involved is
the distal phalanx. 31 Open injuries or penetrating trauma are the
most common cause of osteomyelitis of the hand. In children and
immunocompromised patients, hematogenous spread can occur
more commonly. 18 Osteomyelitis can be associated with substantial
morbidity, with delayed presentation of greater than 6 months
resulting in an amputation rate of 86%. 31 Patients with diabetes are
more likely than those without diabetes to present with
osteomyelitis.
The most common infecting organisms are S aureus and
Staphylococcus epidermidis. Clinical findings include pain, warmth,
erythema, and drainage. Radiographs show osteolysis, osteopenia,
osteosclerosis, or periosteal reactions; they can often be negative
early, in which case MRI is considered superior in sensitivity and
specificity. White blood cell count is not always elevated, and C-
reactive protein level is a more sensitive laboratory test.
In early osteomyelitis, consideration for management with
intravenous antibiotics alone until a clinical and laboratory
response is obtained can be pursued. In children, there is evidence
that only oral antibiotics may be needed. 32 Surgical management
still has a significant role because it allows for obtaining deep
cultures and débridement of necrotic bone. If the infection cannot
be eradicated following antibiotic therapy and multiple trips to the
operating room for débridement, amputation is the definitive
treatment. Despite aggressive and appropriate surgical and medical
management, the amputation rate can be as high as 39%. 31

Atypical and Fungal Infections

Atypical and fungal infections of the hand are seen in
immunocompromised patients but may also occur in
immunocompetent patients. Specific pathogens are found in the
southwest United States, Ohio-Mississippi River Valley, or tropical
climates. In patients who are gardeners, bird or sheep handlers, or
who participate in fishing/boating activities, atypical hand
infections may develop. A detailed history and social history are of
particular importance with atypical and fungal infections.
Obtaining cultures for fungi and acid-fast bacilli should be done
during intraoperative treatment.
Mycobacterium tuberculosis can cause tenosynovial tuberculosis
with rice bodies in the hand and wrist. Risk factors include patient
age older than 60 years, malnutrition, low socioeconomic status,
alcohol abuse, diabetes, immunosuppression, exposure to
tuberculosis, and local steroid injection. 33
Nontuberculous mycobacterial infections are often diagnosed
late because of a low clinical suspicion and their indolent
presentation. 34 Mycobacterium marinum may present as a chronic
flexor tenosynovitis related to aquatic injuries. The aquatic
environment may also result in other pathogens, such as Vibrio
species, Aeromonas hydrophila, and Erysipelothrix rhusiopathiae.
Mycobacterium avium may be seen in bird handlers or in patients
with HIV. Mycobacterium leprae (Hansen disease) is a chronic
peripheral nerve infection that can be transmi ed through
southwestern armadillos.
Fungal infections are rare and more commonly affect
immunocompromised patients; these infections can be superficial
or deep. A review of 10 patients with fungal tenosynovitis showed 8
patients to be immunocompromised, with an average delay of
diagnosis of 6 months and a 30% recurrence rate. 35 Mucormycosis
infections can occur in immunocompetent as well as
immunocompromised patients and are typically a result of grossly
contaminated wounds involving soil or agricultural facilities.
Coccidioidomycosis occurs in the southwestern United States, and
findings can include synovitis, arthritis, and osteomyelitis of the
hand. Histoplasmosis and blastomycosis are endemic to the area
around the Ohio-Mississippi River valley and should be considered
a possibility in chronic hand infection refractory to antibiotic
therapy. Based on a review of 100 patients, obtaining fungal and
acid-fast bacillus cultures was recommended in all patients
undergoing débridement for hand infections. 36

Nontraumatic Vascular Conditions of the

Upper Extremity
Chronic upper extremity vascular disorders can be broadly
categorized as vasospastic disease and occlusive disease. Although
there is substantial overlap in both categories, there are important
differences. Regardless of the category, the choice of treatment
depends on the presence or absence of collateral circulation and the
underlying sympathetic muscle tone.
Vasospastic disease is subdivided into primary and secondary
disease. One example of primary vasospasm would be Raynaud
disease (a spasm occurs without an underlying etiology). Secondary
vasospasm is associated with an underlying condition, such as
collagen vascular disease, with scleroderma being a common
underlying cause. Vasospasm is common in the northern climates,
with 10% to 15% of people reporting sensitivity to cold and up to
25% reporting digital blanching and numbness. 37
Occlusive disease is generally a result of embolism, thrombosis,
or aneurysm. Any of these conditions can result in showering of
emboli distally and resultant vasospasm.

Circulation
In the evaluation of upper extremity circulation, it is important to
also evaluate the macrocirculation and microcirculation.
Macrocirculation is the ability to regulate blood flow to meet the
metabolic requirements of the tissue to maintain cellular viability.
When this process is compromised, termed vascular incompetency,
the result is pain, cold intolerance, and potential tissue loss.
Microcirculation has two components: nutritional blood flow and
thermoregulatory blood flow. Under normal conditions,
approximately 80% to 90% of the circulation passes through the
thermoregulatory beds. This is the area in the fingertips where
arteriovenous connections are located along the distal phalanx.
Nutritional blood flow is responsible for the remaining 10% to 20%
of the circulation and provides the cellular metabolic needs
through the tissue to maintain viability. 38 In response to cooling or
aerobic exercise, the increase in sympathetic tone closes the
arteriovenous shunts, which decreases thermoregulatory flow and
diverts the remaining blood flow to the capillary nutrient beds
unobstructed, and preserves nutritional blood flow in the presence
of decreased overall blood flow.

Physical Examination and Diagnostic Tests

The appearance of the digits, ulceration at the fingertips, and laxity
of the skin should be noted. The color of the digits may change
during the physical examination, sometimes appearing pale, ashen,
or gray or white to purple to red. In patients with darker skin, such
color changes will be apparent in the fingernail beds. The warmth
of the digits is important to assess and note any differences in each
digit on both hands. Palpation of the radial and ulnar pulse as well
as digital pulses, if present, provides helpful information. An Allen
test can be performed at the wrist level as well as the digital level. A
handheld Doppler device should be available to listen for flow in
these vessels and determine the extent of distal flow. This can be
used to assess antegrade flow as well as retrograde flow.
A noninvasive vascular test can help determine the anatomy as
well as the capability to respond to stress, evaluating total blood
flow at baseline and after warming. There are multiple noninvasive
options, but the two most common are segmental arterial pressures
(digital brachial indices) and digital plethysmography (pulse
volume recordings).
The digital brachial indices are obtained with occlusive cuffs,
similar to a blood pressure cuff, to measure the ratio of the
pressure in the brachial artery and the digital artery. A normal ratio
is 0.9, and a ratio less than 0.7 indicates inadequate arterial inflow
and supports the need for intervention. 39 The pulse volume
recordings are waveforms and when the circulation is
compromised, the waveforms are fla ened. 40 An arteriogram
(angiogram) is the definitive test to assess circulation and evaluate
for occlusion. This can also be performed with intra-arterial
vasodilators, which helps in understanding the vasospastic
component. Magnetic resonance angiography and CT angiography
often do not provide adequate detail in the digits to make
treatment decisions.

Nonsurgical Treatment
Most patients with vasospastic disease can be treated nonsurgically,
with only a small percentage requiring more than medications.
Calcium channel blockers, tricyclic antidepressants, selective
serotonin reuptake inhibitors, alpha-2 agonists, and
phosphodiesterase inhibitors all have been demonstrated to
provide distal vasodilation and potential relief of symptoms.
Prostacyclin can be used in refractory cases and is effective because
it can cause platelet inhibition and vasodilation. These medications
are often used to treat patients with pulmonary hypertension.
These medications, particularly prostacyclin, are best prescribed by
a medical physician rather than a hand surgeon.
A nonsurgical treatment alternative with variable effectiveness is
botulinum toxin A. The mechanism of action is thought to be
relaxation of the smooth muscle in the vessel walls, resulting in
blood vessel dilation and increased nutritional blood flow, although
the exact mechanism has not been determined. In addition, use of
this medication is off-label. Typically, 100 units are injected into
each hand. although there is no evidence regarding optimal dose,
100 units seems to be an effective dose. Additionally, the
medication is supplied in 100-unit vials. In a study reporting on 20
patients with scleroderma who were treated with 100 units of
botulinum toxin, 16 patients reported improvement in pain and
Disabilities of the Arm, Shoulder and Hand (DASH) scores, 13
reporting improvement in cold intolerance and grip strength, and
18 reporting improvement in pinch strength at 8 to 12 weeks. 41 One
study reported 40 patients (25 with limited scleroderma and 15 with
diffuse scleroderma) with each patient receiving botulinum toxin in
one hand and saline in the other. 42 Evaluation was with Doppler
imaging, patient-reported outcomes, and clinical examination. At 1
month, there was a greater decrease in blood flow in the hands with
botulinum toxin, likely because of differences in the patients with
long-standing disease and diffuse scleroderma. More recently, the
authors of a 2021 study reported a retrospective series of 20 patients
(31 hands). All had abnormal digital brachial index and pulse
volume recordings prior to the injection. All patients had
immediate pain relief and decreasing opioid requirements after the
injections and reported significant improvement on DASH scores
(49 prior to injection, 26 at 6 weeks) with maintenance of the
improvement at 6 months (DASH score of 29) after injection. 43

Surgical Treatment
The mainstay of surgical treatment for vasospastic disease is
peripheral sympathectomy. This can be at the digital level, or at the
level of radial and ulnar arteries, and the superficial palmar arch.
The concept involves circumferentially stripping the adventitia
around the arteries. The preferred technique includes the
modification of exploring the ulnar artery through the Guyon canal.
Prior to surgical treatment of vasospastic disease, an arteriogram
should be obtained because there is a high incidence of associated
occlusive disease. The authors of a 2019 study reviewed 110 upper
extremity angiograms performed from 1996 to 2017 and created a
classification system 44 (Table 2).

Table 2
Classification of Angiographic Findings

Types Subtypes
0—Normal A—Superficial palmar arch occluded
1—Impaired palmar arch B—Deep palmar arch occluded
2—Impaired ulnar artery C—Both superficial and deep palmar arches
occluded
3—Impaired radial artery —
4—Impaired radial and ulnar —
arteries
Reprinted from Leyden J. Burn MB, Wong V, Leon DS, Kaizawa Y, Chung L, Chang L: Upper
extremity angiographic patterns in systemic sclerosis: Implications for surgical treatment. J
Hand Surg Am 2019;44(11):990.e1-990.e7, with permission from Elsevier.

They noted that 57% of patients had a nonpatent ulnar artery at

the wrist (type 2) and 77% of those had a nonpatent superficial
palmar arch (type 2A). In the event occlusion is noted on the
angiogram, bypass tends to relieve the sympathetic discharge
(Leriche sympathectomy) and improve the distal circulation.
Reconstruction of an occluded ulnar or radial artery typically
requires a graft; the choice of graft (arterial or venous) appears to
affect the outcome. Vein grafts are readily available but must be
reversed or the valves removed, and they typically have a size
mismatch and thinner walls when compared with the artery. The
use of arterial grafts has evolved from cardiac surgery based on the
concept of higher long-term patency rates with arterial grafts in
comparison with venous grafts. Graft length is limited and the
artery is expendable, but there are no valves so reversal is not
necessary; diameter and wall thickness are similar and some
arteries have similar branching pa erns. The most common arterial
grafts are the descending branch of the lateral femoral circumflex
artery, the thoracodorsal artery, the deep inferior epigastric artery,
and the subscapular artery. These tend to have a predictable length
of 10 to 15 cm and a diameter of 2 to 3 mm. The descending branch
of the lateral femoral circumflex artery tends to have multiple
branches, which may enable multiple end-to-end anastomoses in
the palm if needed. 45 A systematic review of 16 studies compared
arterial and venous grafts of 145 patients (152 grafts). There were
120 ulnar artery grafts, 31 radial artery grafts, and one patient in
whom both grafts were used. Of the 19 arterial grafts, there was
100% patency at 18 months. Of the 133 vein grafts, there was a
58.5% patency rate at 37 months, with all patients reporting
reduction of cold sensitivity, decreased pain, and digital
ulcerations. 46
One study reported 36 hands in 27 patients with connective
tissue disorders. Sympathectomy alone was performed on 26 hands
and sympathectomy plus bypass on 9 hands. 47 At a median follow-
up of 2.8 years, the sympathectomy plus bypass group had be er
resolution of digital ulcers.
Occlusive disease results from thrombosis or aneurysm. Ulnar
artery thrombosis, commonly referred to as hypothenar hammer
syndrome, is typically the result of repetitive blunt trauma to the
ulnar aspect of the wrist. Because the ulnar artery is more
superficial in location, the trauma results in either periadventitial
thickening with subsequent intimal disruption and thrombosis, or
disruption of the internal elastic lamina and subsequent aneurysm
formation. Depending on the collateral circulation, treatment can
be resection of the thrombosed segment (to prevent the distal
microemboli and subsequent vasospasm), known as Leriche
sympathectomy. In the absence of adequate collateral circulation,
reconstruction with a graft is indicated with choices determined as
previously described. According to one study, ultrasonography
showed occlusion of 14 of 18 vein grafts at 118 months, but there
was no difference in DASH scores or grip strength. 48 Those with
occluded grafts had more cold intolerance. Another study reported
11 patients with arterial reconstruction with descending branch of
lateral femoral circumflex artery, with 9 of the 11 grafts patent at 63
months. Nine of 11 patients reported improvement in symptoms
and when these findings were compared with those of a historical
cohort of 32 venous grafts, only 9 grafts were patent at 85 months. 49
The authors of a 2020 study reported 15 patients treated over 14
years with ligation, direct repair, or vein graft reconstruction. 50
Outcomes assessed were DASH, Cold Intolerance Symptom
Severity, and Patient-Reported Outcomes Measurement
Information System Pain Interference, with similar patient-
reported outcomes across all treatments. Six patients had complete
symptom relief, six reported partial relief, one had temporary
resolution and recurrence, and two had no improvement. 50

Summary
An understanding of bone and soft-tissue infections is vital for the
practicing hand surgeon. The evidence against routine prophylactic
antibiotic use in soft-tissue hand surgery is inherently related to the
management of bone and soft-tissue infections in a empts to
minimize antibiotic resistance. An increasing number of soft-tissue
infections of the hand are polymicrobial. Gram-negative pathogens
are more commonly seen in immunocompromised patients.
Atypical and fungal infections can occur in immunocompromised
or immunocompetent patients.
Understanding the principles for workup of patients with
nontraumatic upper extremity vascular disorders will enable the
surgeon to differentiate between primary vasospastic or occlusive
disease. Vasospastic disease can often be managed medically, but
when symptoms persist or digital ulcerations are present, surgery is
often recommended. Occlusive disease is often managed with
surgery to remove the thrombosed segment and reconstruct with a
graft when indicated.

Key Study Points

Prophylactic antibiotics are not indicated for routine soft-tissue hand surgery.
Necrotizing fasciitis may be life threatening and requires immediate and emergent
débridement when identified.
Workup for patients with chronic vascular disease includes noninvasive studies and
angiography to determine optimal treatment.
In cases refractory to medical treatment without tissue loss, botulinum toxin may
provide good relief of symptoms and improve nutritional blood flow.
Surgical treatment, including sympathectomy and bypass when indicated, can
provide relief, but ongoing medical treatment is important as this treats the result and
not the underlying cause.

Annotated References
1. Li K, Sambare TD, Jiang SY, Shearer EJ, Douglass NP, Kamal
RN: Effectiveness of preoperative antibiotics in preventing
 surgical site infection after common soft tissue procedures of the
hand. Clin Orthop Relat Res 2018;476:664-673.
2. Halvorson AJ, Sechriest VFII, Gravely A, DeVries AS: Risk of
surgical site infection after carpal tunnel release performed in an
operating room versus a clinic-based procedure room within a
Veterans Affairs medical center. Am J Infect Control 2020;48:173-
177. The authors reported no significant differences in surgical
site infection rates for carpal tunnel release performed in the
operating room or procedure room environments. They also did
not note any difference in surgical site infection in patients who
received prophylactic antibiotics versus those who did not. Level
of evidence: III.
3. Werner BC, Teran VA, Deal DN: Patient-related risk factors for
infection following open carpal tunnel release: An analysis of
over 450,000 Medicare patients. J Hand Surg Am 2018;43:214-219.
4. Harness NG, Inacio MC, Pfeil FF, et al: Rate of infection after
carpal tunnel release surgery and effect of antibiotic prophylaxis.
J Hand Surg Am 2010;35:189-196.
5. Bykowski MR, Sivak WN, Cray J, et al: Assessing the impact of
antibiotic prophylaxis in outpatient elective hand surgery: A
single-center, retrospective review of 8,850 cases. J Hand Surg Am
2011;36:1741-1747.
6. Tosti R, Fowler J, Dwyer J, et al: Is antibiotic prophylaxis
necessary in elective soft tissue hand surgery? Orthopaedics
2012;35:e829-833.
7. Warnick E, Ilyas AM: Prophylactic antibiotics prior to hand
surgery in patients with prosthetic joints. Hand 2020;17:298-301.
In this retrospective review, the authors note no relationship
between prosthetic joint infection and hand surgery with or
without the use of prophylactic antibiotics. They conclude that
there is no indication for antibiotic prophylaxis in a patient with a
total joint arthroplasty to achieve prophylaxis against a prosthetic
joint infection. Level of evidence: III.
 8. Cunningham DJ, Baumgartner RE, Federer AE, Richard MJ,
Mithani SK: Elevated preoperative hemoglobin A1c associated
with increased wound complications in diabetic patients
undergoing primary, open carpal tunnel release. Plast Reconstr
Surg 2019;144:632e-638e. In this retrospective cohort study, the
authors note that in patients with diabetes undergoing open
primary carpal tunnel release with a hemoglobin A1c value of 7.8
or higher, there was a higher rate of postoperative wound
complications compared with patients with diabetes with a lower
hemoglobin A1c value. Level of evidence: III.
9. Volz KA, Canham L, Kaplan E, Sanchez LD, Shapiro NI,
Grossman SA: Identifying patients with cellulitis who are likely
to require inpatient admission after a stay in an ED observation
unit. Am J Emerg Med 2013;31:360-364.
10. Kistler JM, Thoder JJ, Ilyas AM: MRSA incidence and antibiotics
trends in urban hand infections: A 10-year longitudinal study.
Hand 2019;14(4):449-454. The authors conclude that the annual
incidence of methicillin-resistant S aureus in hand infections
declined from 2005 to 2014, but that it remains the most common
pathogen. There has been an increase in the number of
polymicrobial infections. Methicillin-resistant S aureus resistance
to clindamycin and levofloxacin has increased. Level of evidence:
III.
11. Harrison B, Ben-Amo O, Sammer DM: Methicillin- resistant
Staphylococcus aureus infection in the hand. Plast Reconstr Surg
2015;135:826-830.
12. Tosti R, Trionfo A, Gaughan J, Ilyas AM: Risk factors associated
with clindamycin-resistant, methicillin-resistant Staphylococcus
aureus in hand abscesses. J Hand Surg Am 2015;40:673-676.
13. Whitaker CM, Low S, Gorbachova T, Raphael JS, Williamson C:
Imaging and laboratory workup for hand infections. Hand Clin
2020;36:285-299. In this review, the authors summarize the
workup for hand infections, including laboratory workup (such
as white blood cell count, erythrocyte sedimentation rate, C-
 reactive protein, procalcitonin, and interleukin-6 levels) and
helpful imaging (radiography, ultrasonography, CT, and MRI).
14. Dailiana ZH, Rigopoulos N, Varitimidis S, Hantes M, Bargiotas
K, Malizos RN: Purulent flexor tenosynovitis: Factors influencing
the functional outcome. J Hand Surg Eur Vol 2008;33(3):280-285.
15. Pang HN, Teoh LC, Yam AK, Lee JY, Puhaindran ME, Tan AB:
Factors affecting the prognosis of pyogenic flexor tenosynovitis. J
Bone Joint Surg Am 2007;89(8):1742-1748.
16. Kennedy CD, Lauder AS, Pribaz JR, Kennedy SA:
Differentiating between pyogenic flexor tenosynovitis and other
finger infections. Hand 2017;89:1742-1748.
17. Bishop GB, Born T, Kakar S, Jawa A: The diagnostic accuracy of
inflammatory blood markers for purulent flexor tenosynovitis. J
Hand Surg Am 2013;38(11):2208-2211.
18. Koshy JC, Bell B: Hand infections. J Hand Surg Am 2019;44:46-54.
In this review article, the authors discuss a variety of hand
infections and in particular focus on identifying serious hand
infections that require urgent or emergent treatment. A
discussion on necrotizing fasciitis, flexor tenosynovitis, deep
space infection, septic arthritis, cellulitis, abscesses, bites, and
osteomyelitis is presented.
19. Giladi AM, Malay S, Chung KC: A systematic review of the
management of acute pyogenic digital flexor tenosynovitis. J
Hand Surg Eur Vol 2015;40:720-728.
20. Muller CT, Uckay I, Erba P, Lipsky BA, Hoffmeyer P, Beaulieu
JY: Septic tenosynovitis of the hand: Factors predicting need for
subsequent debridement. Plast Reconstr Surg 2015;136:338e-343e.
21. Karagergou E, Rao K, Harper RD: Parameters affecting the
severity and outcome of pyogenic digital flexor tenosynovitis. J
Hand Surg Eur Vol 2014;40:100-101.
22. Skeete K, Hess EP, Clark T, Moran S, Kakar S, Rizzo M:
Epidemiology of suspected wrist joint infection versus
inflammation. J Hand Surg Am 2011;36:469-474.
23. Anaya DA, McMahon K, Nathens AB, Sullivan SR, Foy H, Bulger
E: Predictors of mortality and limb loss in necrotizing soft tissue
infections. Arch Surg 2005;140(2):151-157.
24. Psoinos CM, Flahive JM, Shaw JJ, et al: Contemporary trends in
necrotizing soft-tissue infections in the United States. Surgery
2013;153(6):819-827.
25. Wong CH, Khin LW, Heng KS, Tang KC, Low CO: The LRINEC
(Laboratory Risk Indicator for Necrotizing Fasciitis) score: A tool
for distinguishing necrotizing fasciitis from other soft tissue
infections. Crit Care Med 2004;32(7):1535-1541.
26. Tsai YH, Hsu RW, Huang KC, Huang TJ: Laboratory indicators
for early detection and surgical treatment of vibrio necrotizing
fasciitis. Clin Orthop Relat Res 2010;468(8):2230-2237.
27. Chao WN, Tsai SJ, Tsai CF, et al: The laboratory risk indicator
for necrotizing fasciitis score for discernment of necrotizing
fasciitis originated from Vibrio vulnificus infections. J Trauma
Acute Care Surg 2012;73:1576-1582.
28. Angoules AG, Kontakis G, Drakoulakis E, Vren os G, Granick
MS, Giannoudis PV: Necrotizing fasciitis of upper and lower
limb: A systematic review. Injury 2007;38(suppl 5):S19-S26.
29. Shewring DJ, Tricke RW, Subramanian KN, Hnyda R: The
management of clenched fist ‘fight bite’ injuries of the hand. J
Hand Surg Eur Vol 2015;40:819-824.
30. Waldvogel FA, Medoff G, Swar MN: Osteomyelitis: A review of
clinical features, therapeutic considerations and unusual aspects.
N Engl J Med 1970;282:198-206.
31. Reilly KE, Linz JC, Stern PJ, Giza E, Wyrick JD: Osteomyelitis of
the tubular bones of the hand. J Hand Surg Am 1997;22:644-649.
32. Kargel JS, Sammer DM, Pezeshk RA, Cheng J: Oral antibiotics
are effective for treatment of hand osteomyelitis in children.
Hand 2018;15(2):220-223.
33. Al-Qa an MM, Al-Namla A, Al-Thunayan A, Al-Omawi M:
Tuberculosis of the hand. J Hand Surg Am 2011;36:1413-1421.
34. Sotello D, Garner HW, Heckman MG, Diehl NN, Murray PM,
Alvarez S: Nontuberculous mycobacterial infections of the upper
extremity: 15-year experience at a tertiary care medical center. J
Hand Surg Am 2018;43:387.e1-387.e8.
35. O’Shaughnessy MA, Tande AJ, Vasoo S, Enzler MJ, Berbari EF,
Shin AY: A rare diagnosis: Recognizing and managing fungal
tenosynovitis of the hand and upper extremity. J Hand Surg Am
2017;42:e77-e89.
36. Kazmers NH, Fryhofer GW, Gi ings D, Bozentka DJ, Steinberg
DR, Gray BL: Acute deep infections of the upper extremity: The
utility of obtaining atypical cultures in the presence of purulence.
J Hand Surg Am 2017;42: 663.e1-663.e8.
37. Pauling JD, Hughes M, Pope JE: Raynaud’s phenomenon – an
update on diagnosis, classification and management. Clin
Rheumatol 2019;38(12):3317-3330. This review article describes
Raynaud disease, which is a clinical diagnosis when there is no
identifiable underlying cause. This may include vasospasm as
well as cold intolerance. Raynaud phenomenon, or secondary
Raynaud, is a result of an underlying condition, most a
commonly connective tissue disorder, with systemic
sclerosis/scleroderma being the most common cause. This can
result in severe vasospasm and microangiopathy with finger tip
ulcerations and eventually tissue loss or necrosis. Management is
dependent on the underlying cause and clinical symptoms.
38. Fagrell B, Svedman P, Ostergren J: The influence of hydrostatic
pressure and contralateral cooling on capillary blood cell velocity
and transcutaneous oxygen tension in fingers. Int J Microcirc Clin
Exp 1982;1(2):163-171.
39. Zimmerman NB: Occlusive vascular disorders of the upper
extremity. Hand Clin 1993;9(1):139-150.
40. Kleinart JM, Gupta A: Pulse volume recording. Hand Clin
1993;9(1):13-46.
41. Uppal L, Dhaliwal K, Butler PE: A prospective study of the use
of botulinum toxin injections in the treatment of Raynaud’s
 syndrome associated with scleroderma. J Hand Surg Eur Vol
2014;39(8):876-880.
42. Bello RJ, Cooney CM, Melamed E, et al: The therapeutic efficacy
of botulinum toxin in treating scleroderma- associated
Raynaud’s phenomenon: A randomized, double-blind, placebo-
controlled clinical trial. Arthritis Rheumatol 2017;69(8):1661-1669.
43. Goldberg SH, Akoon A, Kirchner HL, Deegan J: The effects of
botulinum toxin A on pain in ischemic vasospasm. J Hand Surg
Am 2021;46(6):513e1-513e12. The authors report on botulinum
toxin use in 31 hands, noting immediate pain relief and
decreased opioid requirements after the injections. An
improvement in DASH scores was maintained over the 6-month
follow-up. Level of evidence: IV.
44. Leyden J, Burn MB, Wong V, et al: Upper extremity angiographic
pa erns in systemic sclerosis: Implications for surgical
treatment. J Hand Surg Am 2019;44(11):990.e1-990.e7. The authors
report angiogram findings over a 20-year period for patients with
scleroderma and describe a classification system for impaired
circulation. Level of evidence: IV.
45. Masden DL, McClinton MA: Arterial conduits for distal upper
extremity bypass. J Hand Surg Am 2013;38(3): 572-577.
46. Masden DL, Seruya M, Higgins JP: A systematic review of the
outcomes of distal upper extremity bypass surgery with arterial
and venous conduits. J Hand Surg Am 2012;37(11):2362-2367.
47. Shammas RL, Hwang BH, Levin LS, Richard MJ, Ruch DS,
Mithani SK: Outcomes of sympathectomy and vascular bypass for
digital ischaemia in connective tissue disorders. J Hand Surg Eur
Vol 2017;42(8):823-826.
48. Endress RD, Johnson CH, Bishop AT, Shin AY: Hypothenar
hammer syndrome: Long-term results of vascular reconstruction.
J Hand Surg Am 2015;40(4):660-665.
49. de Niet A, Van Uchelen JH: Hypothenar hammer syndrome:
Long-term follow-up after ulnar artery reconstruction with the
 lateral circumflex femoral artery. J Hand Surg Eur Vol
2017;42(5):507-510.
50. Demetri L, Lans J, Go lieb R, Dyer GSM, Eberlin KR, Chen NC:
Long term patient-reported outcomes after surgery for
hypothenar hammer syndrome. Hand (N Y) 2020;15(3):407-413.
The authors reported on 15 patients with ulnar artery thrombosis
over 15 years who were treated with excision, direct repair, or
grafting, with similar patient-reported outcomes across groups,
with 12 of 15 reporting at least some improvement in symptoms.
Level of evidence: IV.
C H AP T E R 3 5

Neuropathies and Hand Arthritis

Jeffrey G. Stepan MD, MSc, Christina M. Nypaver Cebulko
MD

Neither of the following authors nor any immediate family member has received anything of value
from or has stock or stock options held in a commercial company or institution related directly or
indirectly to the subject of this chapter: Dr. Stepan and Dr. Nypaver Cebulko.

ABSTRACT
Neuropathies and degenerative arthritis are very common
pathologic conditions that affect the upper extremity. These
progressive conditions can have a detrimental effect on the function
and quality of life of patients. It is critical to understand the risk
factors of these conditions, patient presentation and examination,
and the best diagnostic practices to be able to provide optimal
treatment for successful outcomes. The orthopaedic surgeon
should be knowledgeable about common nerve conditions and
hand arthritis for the most up-to-date evidence on which to base
treatment decisions as well as any novel techniques or findings.
Keywords: carpal tunnel syndrome; cubital tunnel syndrome;
interphalangeal joint arthrodesis/arthroplasty; osteoarthritis;
metacarpophalangeal joint arthroplasty

Introduction
Common nontraumatic pathologies of the upper extremity include
compressive and idiopathic neuropathies, and arthritis of the hand.
An understanding of demographic information related to each
condition, including incidence and risk factors, patient
presentation, physical examination findings, and diagnostic
considerations, as well as treatment options, potential
complications, and outcomes, is important to provide the best
treatment.

Upper Extremity Neuropathies

Carpal Tunnel Syndrome

Carpal tunnel syndrome, or compression of the median nerve at the
wrist, is the most prevalent compression neuropathy of the upper
extremity. It more commonly affects the middle-aged and older
population with a mean age at diagnosis of 50 years, and it is more
common in women than men (approximately 4:1). Other risk factors
for the development of carpal tunnel syndrome include pregnancy,
menopause, obesity, hypothyroidism, diabetes mellitus, renal
failure, alcoholism, inflammatory arthritis, amyloidosis, and high
hand/wrist repetition rate. 1 , 2 Despite identifying these risk factors,
there is still no uniform consensus on the precise mechanism by
which carpal tunnel syndrome develops.
The diagnosis of carpal tunnel syndrome is made with a clinical
history and physical examination, as well as adjunct diagnostic
testing. The classic patient will describe nocturnal paresthesias in
the median nerve distribution (thumb, index finger, long finger,
and radial side of the ring finger), although this can be variable.
Patients may also describe a burning, painful sensation in the hand
and wrist as well as loss of hand dexterity and muscle atrophy,
particularly in more severe cases. These symptoms gradually
worsen as nerve compression continues and injury progresses.
Abnormal sensibility testing and positive provocative examination
maneuvers such as the Phalen test, Tinel sign, and Durkin
compression test are supportive of the diagnosis but should not be
used in isolation to make the diagnosis.
 Nerve conduction studies (NCS) and needle electromyography
(EMG) can be useful diagnostic tools to help confirm carpal tunnel
syndrome. Focal demyelination of the median nerve is manifested
by delayed conduction velocities across the wrist on NCS and may
assist in ruling out other possible sites of nerve compression. The
presence of thenar atrophy and/or muscle fibrillations on needle
EMG can help determine the severity of disease and therefore
influence prognosis.
There have been more recent advances in and support of
ultrasonography as a reproducible, rapid, and painless alternative
to electrodiagnostics. Diagnosis is made by the identification of an
enlarged, hypoechoic median nerve at the carpal tunnel inlet
(Figure 1). The cross-sectional area (CSA) of the nerve is measured
with a diagnostic cut-off value of 11 mm2. 3 , 4 When compared with
electrodiagnostics, one study found a positive correlation (r = 0.81)
between increased nerve CSA and distal motor and distal sensory
latency values on NCS. 5 Additional studies have reported on the
inter-rater and intrarater reliability among examiners when
measuring nerve CSA as well as suggested superiority of
ultrasonography over NCS/EMG, promoting its use as a reliable
and accurate diagnostic tool. Another study 6 found moderate
agreement among examiners of varying levels of experience when
measuring the CSA of the median nerve (Lin concordance
correlation coefficient of 0.59), with experienced examiners having
excellent intra-rater reliability. Additionally, a 2019 prospective
cohort series demonstrated that ultrasonography had a lower false-
positive rate than NCS (23% compared with 43%) in asymptomatic
patients as measured by the six-item carpal tunnel symptoms scale
(CTS-6), which relies on history and physical examination alone to
make the diagnosis 7 (Table 1).
 Figure 1 Ultrasonographic image demonstrating an enlarged cross-sectional
median nerve at the entrance to the carpal tunnel in a patient with carpal tunnel
syndrome.N = median nerve, T = flexor digitorum tendons.(Reprinted from
Wiesler ER, Chloros GD, Cartwright MS, Smith BP, Rushing J, Walker FO: The
use of diagnostic ultrasound in carpal tunnel syndrome. J Hand Surg Am
2006;31[5]:726-732, Figure 3, With permission from Elsevier.)

Table 1
The Carpal Tunnel Syndrome Scoring System a

Finding Points
Numbness predominantly or exclusively in median nerve distribution 3.5
Nocturnal symptoms 4
Thenar atrophy or weakness 5
Positive Phalen test 5
Loss of two-point discrimination (>5 mm) 4.5
Positive Tinel sign 4
a
This scoring system uses six history or clinical examination findings. The corresponding
point values for all positive findings are added together to obtain a total score. A score of 12
points is defined as positive for carpal tunnel syndrome.
With permission from Fowler JR, Munsch M, Tosti R, Hagberg WC, Imbriglia JE: Comparison
of ultrasound and electrodiagnostic testing for diagnosis of carpal tunnel syndrome: study
using a validated clinical tool as the reference standard. J Bone Joint Surg Am
2014;96(17):e148, Table 1. https://journals.lww.com/jaaos/pages/default.aspx.
 There also has been recent controversy regarding the necessity of
adjunct diagnostic testing, particularly electrodiagnostics, given the
reliability of the CTS-6 scoring system. One study prospectively
compared CTS-6 (as well as other clinical diagnostic questionnaires)
with NCS in 408 wrists in 250 patients and reported that although
NCS had a high sensitivity (94%), CTS-6 had the highest specificity
(99% compared with 50% for NCSs), suggesting that
electrodiagnostics are actually not ideal confirmatory tests. 8
Further research is needed in this area, which is challenging given
the current lack of an objective gold standard diagnostic tool.
Nonsurgical management in the form of therapy, bracing the
wrist in a neutral position particularly at nigh ime, and
corticosteroid injection should be considered as initial treatment
options for mild to moderate symptoms. 2 A 2021 double-blind
randomized clinical trial reported on the efficacy of corticosteroid
injection. 9 A total of 111 patients with idiopathic carpal tunnel
syndrome were randomized to one of two steroid injection groups
(40 and 80 mg of methylprednisolone) or a saline placebo group.
Ultimately, 90% of the trial participants went on to have carpal
tunnel surgery within 5 years of injection; however, there were
some notable findings. Surgical treatment was less likely in the
higher dose steroid group compared with placebo (84% versus 97%)
and time from injection to surgical treatment was significantly
longer after steroid injection compared with saline (6 months
versus 3 months).
Surgical treatment involves releasing the transverse carpal
ligament, decompressing the median nerve. Historically this
procedure is performed via a standard, open approach; however,
other techniques have been developed including endoscopic and
ultrasonography-guided carpal tunnel release, facilitated by a
retractable blade or a thread device, respectively. Patients
undergoing endoscopic carpal tunnel release have been shown to
return to work faster, with less postoperative pain and pain
medication use; however, this technique has been reported to have
a higher procedural cost as well as an increased risk for iatrogenic
nerve injury. 10 - 12 However, a 2021 study evaluated the cost-
effectiveness of endoscopic versus open techniques in patients
undergoing unilateral carpal tunnel release and determined that
endoscopic carpal tunnel release is actually more cost-effective if
performed under local anesthesia when considering earlier return-
to-work parameters. 13 Conversely, a 2020 study reported that
patients who underwent endoscopic carpal tunnel release had a
higher rate of revision surgery within 1 year after the index
procedure compared with those who had an open release (6.5%
versus 4.4%). 14 There has also been recent advocacy of “wide awake,
local anesthesia, no tourniquet,” or WALANT, surgical release,
which spares the patient the possible complications of intravenous
anesthesia as well as tourniquet pain, whereas others claim that
there is no difference in outcomes or patient satisfaction when
compared with monitored anesthesia care and a local anesthetic. 15 -
17
Cost-effectiveness by se ing and surgical technique continues to
be evaluated in the literature. 18
Although studies including large randomized controlled trials
continue to question the superiority of the different techniques,
there has been no definitive evidence to suggest a best approach
when considering long-term outcomes. Postoperative complications
of all surgical techniques include a 0.5% incidence of nerve, arterial,
or tendon injury; complex regional pain syndrome; and infection
(<1%). 19
Recurrent carpal tunnel syndrome after surgical release can occur
from a number of causes including improper diagnosis, incomplete
release, secondary nerve compression, scar formation, and
adhesions. A thorough history and examination as well as a
diagnostic workup are indicated to determine the most likely
etiology and therefore treatment. The authors of a 2020 study
looked at risk factors for and rate of revision carpal tunnel release.
14
They reported a revision rate of 1.5% and a median time to
secondary surgery of 1.23 years, with risk factors being older age,
male sex, bilateral release, and endoscopic release. Revision median
nerve neurolysis can be performed alone or in combination with
local soft-tissue flaps or allograft wraps, although, similar to
primary release techniques, there does not appear to be a superior
method. 20

Cubital Tunnel Syndrome

Cubital tunnel syndrome, or compression of the ulnar nerve at the
elbow, is the second most common compression neuropathy, with
an incidence of approximately 30 per 100,000 person-years. 21 It is
more common in the older and male population. Patients will
typically present with progressive paresthesias in the ulnar digits of
the hand (small finger and ulnar aspect of the ring finger) and
eventual motor weakness and atrophy of the hypothenar and
intrinsic muscles. Vague elbow pain can be an additional
presenting symptom. Patients also tend to present with a more
severe presentation than with carpal tunnel syndrome.
Cubital tunnel syndrome is similarly diagnosed by clinical
history and examination with diagnostic testing as adjuncts.
Careful examination of sensation in the ulnar nerve distribution,
specifically the dorsal ulnar cutaneous nerve, is paramount. Given
its anatomic origin, branching from the ulnar nerve proper 6 cm
proximal to the wrist, preservation of sensation indicates a more
distal compression site (Guyon canal), whereas absence of
sensation is more likely to indicate compression at the level of the
elbow. Positive provocative examination maneuvers such as
symptom exacerbation by prolonged elbow flexion, Tinel sign at the
elbow, Wartenberg sign (weakness in small finger active
adduction), Froment sign (obligate thumb interphalangeal flexion
with pinch from a weak adductor pollicis), and the scratch collapse
test (obligate shoulder internal rotation after lightly scratching the
area of compression coupled with resisted shoulder external
rotation) also support the diagnosis of cubital tunnel syndrome,
though the la er has been reported to be very operator dependent.
22
NCS and EMG can be helpful to confirm the diagnosis,
demonstrating delayed conduction velocities across the elbow and
possible muscle atrophy and fibrillations in distal ulnarly
innervated muscles; however, their reported sensitivity in the
literature is only 60% to 80%. As with carpal tunnel syndrome,
ultrasonography and uniquely MRI are being increasingly
recognized as diagnostic aids in lieu of electrophysiologic studies.
Diagnosis is made by measuring the CSA of the ulnar nerve 1 cm
proximal to the medial epicondyle, with a cutoff value of 11.0 mm2.
23 , 24
Ultrasonography also can be helpful in determining ulnar
nerve instability because physical examination assessment has
been found to be poorly correlated with intraoperative findings of
instability (12% compared with 88% with ultrasonography). 25
Patients without atrophy or dense sensory loss should initially be
treated with nonsurgical modalities including therapy, extension
bracing at nigh ime and elbow padding, and anti-inflammatory
medication. If these interventions fail in these patients, surgical
treatment can be considered. The most appropriate surgical
intervention is still debated, ranging from simple in situ
decompression to ulnar nerve transposition. There are various
degrees of in situ decompression from simply unroofing the cubital
tunnel to circumferential neurolysis extending from the proximal
arcade of Struthers to the distal Osborne fascia. If nerve
subluxation or dislocation is present or affects a younger patient,
many surgeons advocate for transposition of the ulnar nerve. 26
Similarly with in situ decompression, an anterior transposition of
the ulnar nerve can be performed by various techniques including
subcutaneous, intramuscular, or submuscular, with a multitude of
different methods to secure the nerve anteriorly. Transposition
typically requires a more extensive dissection to prevent tethering
of the nerve. Potential tethering structures include branches of the
medial antebrachial cutaneous nerve and ulnar artery, the medial
intermuscular septum, the flexor-pronator muscle origin, and flexor
digitorum superficialis fascia.
A recent Cochrane review 27 reported 70% of patients with good
or excellent results after both in situ and anterior transposition
techniques but with insufficient evidence to recommend one
method over the other, although many studies have compared the
rates of reoperation and complication rates between the two
methods. 28 , 29 Some studies have reported higher rates of
secondary surgery and complications in patients undergoing
anterior transposition. 30 , 31 Endoscopic techniques are also
increasingly being used, the benefits of which can include be er
scar satisfaction and reduced early postoperative pain among
patients; however, symptom relief and return-to-work parameters
have been similar when compared with in situ decompression. 32 , 33
Complications of surgical intervention include incomplete release,
nerve injury (ulnar nerve or branches of the medial antebrachial
cutaneous nerve), nerve instability, and infection.
In patients with weakness and atrophy from long-standing
cubital tunnel syndrome, a ention has been given to nerve transfer
procedures to improve recovery of intrinsic function. Patients with
severe cubital tunnel syndrome with significant intrinsic weakness
and atrophy (as well as electrodiagnostic evidence of axonal loss)
may benefit from a supercharge end-to-side anterior interosseous
nerve to ulnar motor nerve transfer. 34 , 35 A 2020 study reported
outcomes in the first cohort of patients undergoing this procedure.
34
The study authors evaluated improvement in first dorsal
interosseous Medical Research Council grade and time to
reinnervation, changes in pinch and grip strength, as well as
Disabilities of the Arm, Shoulder and Hand (DASH) scores. Thirty-
nine of the included 42 patients had successful improvement of
intrinsic function from baseline, 33 of whom improved to a Medical
Research Council grade of three or higher. First dorsal
interosseous, pinch, and grip strength as well as DASH scores were
significantly improved from baseline at a mean follow-up of 11.2
months. Age was the only identified risk factor for failure. This
study also noted that additional research is needed to be er
understand ideal standard outcome measures (objective intrinsic
function) as well as more clearly delineate indications for the
procedure.
 Recurrent cubital tunnel syndrome can occur for the same stated
reasons as recurrent carpal tunnel syndrome, which can be
challenging to diagnose and treat. Recent literature suggests,
however, that a significant percentage of patients (77%) can
experience symptom improvement after revision cubital tunnel
decompression. This procedure should therefore be considered in
patients with recurrent disease, but with appropriate counseling
that outcomes have been shown to be inferior compared with
primary surgery. 36 , 37 If an obvious area of compression cannot be
identified, submuscular transposition is recommended. 38

Radial Tunnel Syndrome

Radial tunnel syndrome is a controversial diagnosis that involves
the compression of the posterior interosseous nerve in the proximal
forearm. It is a much rarer compression neuropathy, occurring in
approximately 0.03% of the general population, although some
think that it is more common than this. The mean age at diagnosis
is 30 to 50 years, and it occurs more frequently in women than men
in some studies.
The most common symptom on initial presentation is a deep
aching, often nocturnal pain in the proximal forearm overlying the
mobile wad, but distal to the lateral humeral epicondyle
(approximately 5 cm distal). Patients will have focal tenderness to
palpation in this area, but with preserved muscle strength and
intact sensation in the posterior interosseous innervated muscles
and superficial radial sensory nerve distribution, respectively. Pain
may be worsened with resisted supination of the forearm and/or
resisted wrist hyperextension. Electrodiagnostic studies are almost
always normal unless the nerve is injured, making the diagnosis a
clinical one. However, adjunct studies such as ultrasonography or
MRI can be used if a space-occupying lesion or mass that could be
compressing the nerve is suspected. Caution should be used when
implementing ultrasonography as a diagnostic tool because the
posterior interosseous nerve can normally appear fla ened as it
enters the supinator. 39 Corticosteroid injection can be diagnostic as
well as therapeutic. Radial tunnel syndrome is a diagnosis of
exclusion, as other more common diagnoses should be ruled out
first, most notably lateral epicondylitis, which often is a concurrent
diagnosis.
Nonsurgical treatment of radial tunnel syndrome includes
therapy, anti-inflammatory agents, and previously mentioned
corticosteroid injection that can provide long-lasting relief. A 2019
study looked at patient-reported outcomes via the QuickDASH in
35 patients with a clinical diagnosis of radial tunnel syndrome who
also underwent corticosteroid injection. The study authors found
that 57% of patients achieved a minimal clinically important
difference at 1 year follow-up compared with baseline, suggesting
potential long-term benefits of injection alone. 40 Patients should be
warned about a transient wrist drop if the injection is mixed with an
anesthetic. Surgical decompression may be offered if nonsurgical
treatment fails. The decompression is performed through a variety
of approaches (anterior, posterior, or muscle-spli ing). Exploration
and neurolysis should aim toward completely releasing the radial
nerve at its bifurcation, with notable compression structures
including the leading edge of the supinator (arcade of Frohse),
vascular structures (leash of Henry), and a fibrous edge of the
extensor carpi radialis brevis. Although this is traditionally
performed open, endoscopic decompression techniques have been
recently described. Success of treatment, or pain relief, varies
widely in the literature with both nonsurgical modalities and after
surgical release (anywhere from 10% to 95% after surgical
treatment). Therefore, decompression should be considered as a
last resort after exhaustive nonsurgical management and after other
diagnoses have been excluded.

Pronator Syndrome
Pronator syndrome is compression of the median nerve in the
proximal forearm, which occurs much less frequently than carpal
tunnel syndrome. Demographically, it occurs in the middle-aged
population and is more predominant in women. The symptoms of
pronator syndrome often can overlap with carpal tunnel syndrome,
which can make it challenging to diagnose.
Electrodiagnostic studies often are negative in patients with
pronator syndrome, and thus the diagnosis must be suspected and
made by careful clinical history and physical examination. Patients
frequently present with an aching pain in the proximal volar
forearm and paresthesias in the median nerve distribution
(including the sensory distribution of the palmar cutaneous branch
on the thenar eminence) that is worsened with elbow flexion and
forearm supination or forearm pronation. Tenderness and eventual
paresthesias with compression at the distal edge of the pronator
teres are highly suggestive of the diagnosis. 41 A positive Tinel sign
and motor weakness in the distal median and anterior interosseous
innervated muscles may or may not be present.
Most patients with pronator syndrome can initially be treated
nonsurgically, given a high reported rate of improvement in the
literature with nonsurgical treatment. Anti-inflammatory agents,
activity modification, therapy, and corticosteroid injection (which
also can be diagnostic) are the mainstays of early treatment.
Surgical decompression is indicated when the aforementioned
options have failed to provide relief of constant or worsening
symptoms. Decompression is commonly performed in patients who
do not improve after carpal tunnel release and have provocative
symptoms as described previously. Pronator release is performed
through an open approach with identification of all possible
compressive structures and releasing them if indicated. A 2020
review article on pronator syndrome discusses the relevant
anatomy as well as treatment outcomes. 41 The study authors
identified the potential structures as the superficial and deep heads
of the pronator teres, the lacertus fibrosus, fibrous arch of the flexor
digitorum superficialis, and the ligament of Struthers and Gan er
muscle (accessory head of the flexor pollicis longus) when
anatomically present. A simultaneous carpal tunnel release can be
performed if both diagnoses are suspected. The success rate of
pronator release varies from 71% to 93%.

Parsonage-Turner Syndrome
Idiopathic brachial plexopathy or neurologic amyotrophy, also
known as Parsonage-Turner syndrome, is a rare neurologic
condition with an incidence of 2 to 3 cases per 100,000 person-years.
The pathophysiology of the condition is not completely understood,
but it is thought to be caused by an autoimmune reaction that is
triggered by a stressor such as viral illness, surgery, or trauma. It is
characterized by antecedent shoulder pain followed by weakness in
the affected nerves (suprascapular, dorsal scapular, axillary, and
anterior and posterior interosseous nerves) over a course of days to
weeks.
Patients will initially present with shoulder pain (71%) followed
by a complex picture of upper extremity weakness that can mimic
multiple compression mononeuropathies or a brachial plexus
injury. 42 Therefore, a high suspicion and a detailed history
including the timeline of symptoms are essential in making the
diagnosis. Electrodiagnostic studies will demonstrate unique
pa erns of denervation in brachial plexus nerve root and peripheral
nerve distributions, making them very helpful in confirming the
diagnosis. Equally as useful, MRI will show paralleled
hyperintensity (edema), fascicular thickening, and/or intrinsic
constrictions in the brachial plexus or involved peripheral nerves
and sporadic intramuscular signal intensity or atrophy of affected
muscle groups. 43
Given its poorly understood etiology, a definitive treatment
strategy has not been recommended. Although steroids and
immunoglobulins have been trialed in the past, a Cochrane review
reported there was no significant evidence in the literature to
support the routine use of steroids when treating idiopathic
brachial plexitis. 44 Recovery rates are variable (66% to 90%);
however, initial recovery may not begin until 1 year after symptom
onset and maximum recovery may not occur for 2 to 3 years.
Physical therapy may improve ultimate strength. Surgical
intervention in the form of nerve exploration, neurolysis with or
without interpositional nerve grafting or nerve transfers, and the
timing of such procedures is controversial given the prolonged,
natural reinnervation time. Late surgical reconstruction should be
reserved as a salvage procedure for patients with poor outcomes at
maximum recovery.

Arthritis of the Hand

Osteoarthritis (OA) and rheumatoid arthritis (RA) are some of the
most common conditions seen by hand surgeons. Women are more
commonly affected with regard to basal joint, distal interphalangeal
(DIP) joint, and proximal interphalangeal (PIP) joint arthritis;
however, with metacarpophalangeal (MCP) joint arthritis there is
less of a difference between men and women. These conditions
commonly impair activities of daily living. Nonsurgical
management such as splints, nonsteroidal anti-inflammtory drugs
(NSAIDs), and corticosteroid injections are the first line of
management. These nonsurgical management options often can
provide good symptomatic relief for patients, delaying or obviating
the need for surgical management. In patients in whom
nonsurgical treatment fails, arthrodesis or arthroplasty are the
mainstays of treatment. There also has been increasing interest in
joint denervation for treatment of arthritis pain. Most research has
focused on denervation of the carpometacarpal (CMC) joint;
however, there are limited studies evaluating denervation at the
MCP, PIP, and DIP joints. 45 The type of surgery must be
individualized for each patient depending on the location of
arthritis, patient risk factors, and patient functional demands.

DIP Joint Osteoarthritis

DIP joint OA is the most common location of osteoarthritis in the
hand, with prevalence increasing with age. 46 Patients with DIP joint
OA often present for cosmetic concerns such as deformity,
Heberden nodes, or with an overlying mucous cyst rather than a
painful joint or decreased hand function. Patient education and
reassurance are often all that is needed. For patients with a painful
deformity, however, splinting and corticosteroid injections may
provide relief.
In patients with significant DIP joint OA in whom nonsurgical
treatment has failed and who continue to have pain, DIP joint
arthrodesis is the gold standard. Joint preparation of the fusion
surfaces of the base of the distal phalanx and the condylar head are
important for successful fusion, with higher fusion rates than
percutaneous in situ arthrodesis. 47 There are a variety of techniques
such as wires, lag screws, plates, and headless compression screws
each of which have high fusion rates at approximately 90% to 95%.
Headless compression screws have gained popularity over recent
years as joint-specific implants have been developed; there are still
few studies directly comparing these techniques. Headless
compression screws, however, limit the amount of flexion in which
the joint can be fused. A recent review article highlights the
advantages and disadvantages of each fixation method in DIP joint
arthrodesis. 48 Another study on the effect of immobilization of the
DIP joint on grip strength showed that simulated fusion decreased
grip strength by 12% to 25%, with increasingly decreased grip
strength with immobilization of the ulnar digits. 49 Although this
study was in healthy control patients, it may be important to
counsel patients regarding the potential of decreased grip strength,
especially when fusing the DIP joints of ulnar digits.
DIP arthroplasty is not commonly performed and would only be
indicated for a small subset of patients without deformity with
sufficient bone stock. A 2020 study compared screw arthrodesis
with silicone arthroplasty in 48 patients (78 fingers). 50 Although
outcomes were similar between the groups, there was a 13% rate of
conversion to arthrodesis and a 21% reoperation rate in the
arthroplasty group. There was a 15% reoperation rate in the
arthrodesis group (all six were for removal of prominent screw
heads) which may have been avoided with different fixation
techniques. DIP arthrodesis remains the surgical treatment of
choice for surgical management of DIP joint OA.

PIP Joint Arthritis

PIP joint arthritis commonly presents with pain and swelling of the
joint, limiting the range of motion and function of the hand.
Patients may present with bony protuberances on the dorsal aspect
of the joint, referred to as Bouchard nodes. Similarly to DIP joint
OA, the radiographic findings in PIP joint arthritis often do not
correlate with patient symptoms, and nonsurgical management
such as splints, NSAIDs, and corticosteroid injections may be
offered. Loss of function and pain at the PIP joint are often more
limiting for patients given that the PIP joint accounts for a larger
portion of the total arc of motion of the finger compared with the
DIP joint. Surgical management for PIP joint arthritis consists of
arthroplasty or arthrodesis. The decision for PIP joint arthroplasty
versus arthrodesis depends on multiple factors such as patient
preferences, comorbidities, stability of the joint, and patient
functional requirements. A 2020 study noted a calculated annual
growth rate of 2.4% in PIP joint arthroplasty from 2005 to 2013 in an
analysis of the Medicare database, whereas revision procedures
were unchanged during this time period. 51 Arthroplasty has
consistently been shown to have higher revision rates than
arthrodesis, but the higher revision rate must be weighed against
the ability to maintain some motion at the joint. Traditional
teaching is that border joints are necessary for pinch and are not
good candidates for arthroplasty; however, a study compared
arthroplasty (63 patients) with arthrodesis (14 patients) of the index
finger PIP joint, showing equal pinch strengths between the
groups. 52 Reoperation rates for the arthroplasty group, however,
were three times higher than the arthrodesis group (63% versus
21%).
 As with DIP joint arthrodesis, fusion of the PIP joint can be
performed via various surgical techniques, including tension band
construct, 90-90 wiring, plate and screws, intramedullary-linked
screw device, and headless compression screws. A study comparing
these techniques (with the exception of headless compression
screws) showed that the intramedullary-linked screw device had the
highest ultimate strength in all planes compared with the rest of
these techniques; however, these specialized devices are often more
expensive. 53 Similarly, a 2019 study found compression wiring to be
more stable than tension band wiring. 54 Although optimal fusion
position varies with particular tasks for each finger, the ideal
position of fusion is generally accepted to be similar to that of the
cascade of the hand from: 40° for the index, 45° for the long finger,
50° for the ring, and 55° for the small finger. A study published in
2020 evaluated 94 patients after PIP joint fusion, noting that most
fusions were in a more extended position than the cascade. Despite
this, 75% of patients were satisfied with the fusion angle. Of the
25% not satisfied, equal numbers of patients complained of the
joints either being too straight or too flexed. 55
There are many variables that may affect the results after PIP
joint arthroplasty, which include surgical approach, implant type,
and postoperative therapy. Surgery can be performed from a volar
or dorsal approach to the PIP joint. Although some surgeons
advocate for a volar approach because it does not disrupt the
extensor mechanism and allows for earlier range of motion, a 2021
retrospective review study compared 88 PIP joint arthroplasties
from a volar (n = 45) or dorsal (n = 43) approach. After controlling
for preoperative patient factors and range of motion, there was no
difference in postoperative range of motion (56° for volar versus 54°
for dorsal) or complications between the dorsal or volar approach. 56
The final range of motion was less than in the case series of volar
approach PIP joint arthroplasty. The patients obtained 72° of
postoperative motion with early range of motion and only splinting
for 7 days after surgery. 57 Despite these data, comparative studies
on surgical approach or postoperative therapy protocols are
lacking, and it is unclear exactly how variables affect surgical
outcomes after arthroplasty.
Common implant types for PIP joint arthroplasty include
silicone, metal-on-polyethylene, and pyrolytic carbon (PC)
implants. Because the metal-on-polyethylene and PC implants are
unconstrained, these usually are not recommended for patients
with RA arthritis secondary to lack of joint stability from the
destructive nature of the disease in the PIP joint. In patients with
OA, both silicone and PC implants are widely used. Midterm data
from multiple centers have shown high revision rates after PC
implants. A 2020 study evaluated 29 PIP joint PC implants with an
average follow-up of 6.4 years. The surgical revision rate was 24%
with a 13.8% removal rate. Eight other patients were indicated for
removal but chose not to proceed. 58 This experience is similar to
that of multiple other centers with mid- to long-term follow-up that
reported similar reoperation rates of approximately one-third of
patients, including a 14% to 21% revision rate largely secondary to
dislocation or pain and stiffness. 59 , 60
Silicone arthroplasty remains a popular option for both PIP joint
OA and RA. Despite high rates of implant failure, silicone
arthroplasty has shown lower revision rates and higher implant
retention in long-term studies (Figure 2). A study published in 2019
reviewed 45 silicone arthroplasties in 25 patients with PIP joint OA
over a median 3-year follow-up. High satisfaction rates were noted,
with 91% of patients indicating they would have the surgery
performed again despite a revision rate of 20% mostly secondary to
instability, persistent pain, and symptomatic implant failure. 61 This
was slightly higher than previously reported literature noting
implant survivorship of 90% at 10 years for PIP joint OA. 62
 Figure 2 AP radiograph of proximal interphalangeal joint silicone implant failure
without clinical deformity or limitation of range of motion of the finger.(Reprinted
from Proubasta IR, Lamas CG, Natera L, Millan A: Silicone proximal
interphalangeal joint arthroplasty for primary osteoarthritis using a volar
approach. J Hand Surg Am 2014;39[6]:1075-1081, Figure 3, With permission
from Elsevier.)

In a study evaluating 299 consecutive primary PIP joint

arthroplasties over a 14-year period, risk factors for revision
included age younger than 60 years (72% 10-year implant survival
rate versus 86% in patients older than 60 years) and pos raumatic
OA. Although only 23 silicone implants were placed, there were
significantly lower revision rates than either metal and
polyethylene surface replacement or PC arthroplasty. 63 When
counseling patients for surgery, it is important to understand the
higher revision rates for implant arthroplasty compared with
arthrodesis, as well as between silicone, PC, and metal and
polyethylene implants. Patient selection, counseling, and
expectations are critical in achieving a good outcome after surgery.

MCP Joint Arthritis

The MCP joint is less commonly affected by arthritis than the PIP,
DIP, or thumb CMC joint. MCP joint arthritis can be caused by a
variety of etiologies including pos raumatic, degenerative OA, RA,
or crystalline arthropathy. As with arthritis of the other joints in the
fingers, the mainstay of treatment is nonsurgical management with
splints, NSAIDs, and corticosteroid injections. After nonsurgical
management has failed, the thumb MCP joint is often managed
with arthrodesis to provide a stable post for pinch given that much
of the thumb functional range of motion is through the CMC joint.
This differs in the other fingers in which arthroplasty often is
favored to maintain range of motion. Arthroplasty options also
include silicone, metal and polyethylene, and PC implants, with
patient factors and the presence of OA versus inflammatory
arthritis being key considerations in treatment choice.
For patients with inflammatory arthritis at the MCP joint, often a
semiconstrained implant such as silicone arthroplasty is used;
however, surface replacement arthroplasty is also an option. A 2020
study reviewed 73 patients with inflammatory arthritis who
underwent 252 MCP silicone arthroplasties over a 14-year period.
The implant survival rate was 92% at 5 years and 70% at 10 years. 64
This is comparable with long-term outcomes published recently by
a different study regarding surface replacement arthroplasty in
patients with RA. In a 2022 article, the study authors examined 80
MCP arthroplasties with metal and polyethylene in 27 patients.
Rates of survival were similar: 95% at 5 years, 80% at 10 years, and
69% at 20 years. 65 The overall reoperation rate, however, was lower
in the silicone group at 9.1% compared with 36% in the metal and
polyethylene implants. 64 , 65
The survival rate is higher and the revision rate is lower in
patients with noninflammatory arthritis after MCP arthroplasty
than in patients with inflammatory arthritis, likely secondary to a
more stable soft-tissue envelope around the MCP joint. A study
published in 2019 reported long-term follow-up (average of 8.3
years) of 35 patients who underwent silicone MCP arthroplasty for
OA. A 97% clinical survivorship rate was reported despite the fact
that 12.5% of the implants were fractured. 66 Two separate studies
have recently analyzed their results of pyrolytic carbon implants in
patients with OA. Similar results were obtained, with 5-year
survival rates of greater than 90%, and in a separate study, the 15-
year implant survival rate was 88% 67 , 68 (Figure 3). A study in 2022
also evaluated the results of metal and polyethylene surface
arthroplasty in patients with noninflammatory arthritis. The
survival rate was similar to that of their patients with rheumatoid
arthritis, with a 5-year survival rate of 90% and a 15-year survival
rate of 79%. 65
 Figure 3 Images showing AP and lateral radiographs of pyrolytic carbon
implants of the metacarpophalangeal joints with bony erosion (A) and dislocation
(B).(Reprinted from Wall LB, Stern PJ: Clinical and radiographic outcomes of
metacarpophalangeal joint pyrolytic carbon arthroplasty for osteoarthritis. J Hand
Surg Am 2013;38[3]:537-543, Figure 3, With permission from Elsevier.
Reprinted from Wanderman N, Wagner E, Moran S, Rizzo M: Outcomes
following acute metacarpophalangeal joint arthroplasty dislocation: An analysis
of 37 cases. J Hand Surg Am 2018;43[3]:289.e1-289.e6, Figure 1, With
permission from Elsevier.)

Although most patients do not undergo revision surgery and are

happy with the outcomes, one study described a series of MCP
arthroplasty dislocations in 17 pyrocarbon, 11 surface replacement
arthroplasties with metal and polyethylene, and 9 silicone implants.
Only one patient had a preoperative diagnosis of OA, whereas 36
had a diagnosis of inflammatory arthropathy at the MCP joint. The
average time to dislocation was 1.3 years with soft-tissue deficiency
and laxity being by far the most common underlying etiology of the
dislocation. Eighteen implants were managed with soft-tissue
reconstruction to provide additional stability with a low success
rate of 28% as most patients went on to have recurrent instability.
Of the patients who underwent revision arthroplasty (often with
soft-tissue stabilization), 71% of these revisions were successful
without recurrent instability. Revision arthroplasty to silicone also
compared favorably to nonconstrained implants. Most patients who
were initially treated nonsurgically eventually elected to undergo
revision surgery. 69
Although implant arthroplasty has been the mainstay of surgical
treatment for MCP joint OA, a 2022 study described a novel
technique using the dorsal capsule as an interposition
arthroplasty70 (Figure 4). They reported their results in eight
patients with an average of 29 months follow-up with good results
without any revision surgery. Additional data must be analyzed,
but this may be a good option for patients without severe OA at the
MCP joint because it does not preclude later implant arthroplasty.
70

Figure 4 A and B, Intraoperative photographs showing dorsal capsule

interposition arthroplasty with distally based capsular flap and the capsular flap
interposed into the metacarpophalangeal joint secured to the volar plate.
(Reproduced with permission from Walker KL, Johnson AN, Marchessault JA:
Dorsal capsule interpositional arthroplasty of the metacarpophalangeal joint.
Hand (N Y) 2020;17[1]: 68-73, Figures 1 and 5.)

Summary
Neuropathy and degenerative arthritis are nontraumatic pathologic
conditions of the upper extremity that will frequently be presented
to the hand surgeon. It is essential to perform an appropriate
history and physical examination and to recognize common clinical
presentation pa erns. Diagnosis may be confirmed with applicable,
supportive tests or imaging studies. Most mildly symptomatic
compression neuropathies can be managed nonsurgically with
activity modification, therapy, medication, bracing, and
corticosteroid injection. Moderate to severe, worsening, or
persistent cases (particularly if there is motor involvement) may
require surgical decompression to prevent further nerve
deterioration. Parsonage-Turner syndrome is thought to be a
triggered autoimmune neurologic condition with an insidious onset
of shoulder pain followed by polyneuropathy in unique nerve
distributions; treatment is controversial and recovery occurs over
an extended period of time. As with neuropathy, degenerative
arthritis of the hand MCP, PIP, and DIP joints can be managed
without surgery on initial presentation. Persistent symptoms
affecting quality of life may necessitate surgical intervention in the
form of arthrodesis or arthroplasty.

Key Study Points

Compression neuropathies are common and occur at distinct anatomic locations in
the upper extremity. They are diagnosed by means of thorough clinical history and
examination and supportive diagnostic tests, including ultrasonography and
electrodiagnostic studies (EMG/NCS). New techniques (endoscopic, WALANT,
nerve transfer procedures, etc) for the surgical treatment of compression
neuropathies continue to evolve and be evaluated in current literature.
Osteoarthritic conditions of the hand, notably the MCP, PIP, and DIP joints, can
almost always be initially managed with nonsurgical management.
Arthrodesis is the gold standard for surgical treatment of DIP OA with varying fixation
methods.
Arthroplasty (with silicone, metal-on-polyethylene or pyrolytic carbon implants) or
arthrodesis can be performed for the PIP joint; however, arthroplasty has been
shown to have higher revision rates.
MCP joint arthritis is less common than in the PIP and DIP joints and is traditionally
surgically treated with arthroplasty, with the exception of the thumb (arthrodesis).

Annotated References
1. Stevens JC, Beard CM, O’Fallon WM, Kurland LT: Conditions
associated with carpal tunnel syndrome. Mayo Clin Proc
 1992;67(6):541-548.
2. Graham B, Peljovich AE, Afra R, et al: The American Academy of
Orthopaedic Surgeons evidence-based clinical practice guideline
on: Management of carpal tunnel syndrome. J Bone Joint Surg Am
2016;98(20):1750-1754.
3. Pan TJ, White RJ, Zhang C, Hagberg WC, Imbriglia JE, Fowler
JR: Baseline characteristics of the median nerve on ultrasound
examination. Hand (N Y) 2016;11(3):353-356.
4. Wiesler ER, Chloros GD, Cartwright MS, Smith BP, Rushing J,
Walker FO: The use of diagnostic ultrasound in carpal tunnel
syndrome. J Hand Surg Am 2006;31(5):726-732.
5. Pulikko il BJ, Schub M, Kadow TR, Wang W, Fowler JR:
Correlating median nerve cross-sectional area with nerve
conduction studies. J Hand Surg Am 2016;41(10):958-962.
6. Fowler JR, Hirsch D, Kruse K: The reliability of ultrasound
measurements of the median nerve at the carpal tunnel inlet. J
Hand Surg Am 2015;40(10):1992-1995.
7. Fowler JR, Byrne K, Pan T, Goi RJ: False-positive rates for nerve
conduction studies and ultrasound in patients without clinical
signs and symptoms of carpal tunnel syndrome. J Hand Surg Am
2019;44(3):181-185. This prospective cohort series showed that
ultrasonography had a lower false-positive rate than NCS (23%
compared with 43%) as measured by the CTS-6 tool and therefore
recommended it as the preferred diagnostic test for carpal tunnel
syndrome. Level of evidence: II.
8. Wang WL, Buterbaugh K, Kadow TR, Goi RJ, Fowler JR: A
prospective comparison of diagnostic tools for the diagnosis of
carpal tunnel syndrome. J Hand Surg Am 2018;43(9):833-836.e2.
9. Hofer M, Ranstam J, Atroshi I: Extended follow-up of local
steroid injection for carpal tunnel syndrome: A randomized
clinical trial. JAMA Netw Open 2021;4(10):e2130753. This
randomized clinical trial sorted patients with idiopathic carpal
tunnel syndrome into steroid injection and saline injection
groups and determined that steroid injection reduced surgery
 rates (84% compared with 97%) and delayed the need for surgery
(3 to 6 months).
10. Koehler DM, Balakrishnan R, Lawler EA, Shah AS: Endoscopic
versus open carpal tunnel release: A detailed analysis using time-
driven activity-based costing at an academic medical center. J
Hand Surg Am 2019;44(1): 62.e1-62.e9. These authors evaluated
the costs of endoscopic versus open carpal tunnel release at an
academic medical center via time- driven activity-based costing
(TDABC) and determined that endoscopic carpal tunnel release
was 44% more expensive. Level of evidence: II.
11. Withers JA, Lalchandani GR, Halvorson RT, Immerman I,
Rahgozar P: Opioid use following open versus endoscopic carpal
tunnel release: A population study. Plast Reconstr Surg Glob Open
2021;9(2):e3399. This study compared narcotic use in patients who
underwent open versus endoscopic carpal tunnel release and
found that perioperative opioid use was higher in patients who
underwent open release (higher likelihood of filling prescription
and filled more quantities).
12. Miles MR, She y PN, Bhayana K, Yousaf IS, Sanghavi KK, Giladi
AM: Early outcomes of endoscopic versus open carpal tunnel
release. J Hand Surg Am 2021;46:868-876. Short-term outcomes
between open and endoscopic carpal tunnel release were
compared and showed that no technique was superior; however,
patients who underwent open release had lower postoperative
PROMIS scores, a higher odds of remaining on pain medication,
and lower odds of returning to work by the first postoperative
visit. Level of evidence: IV.
13. Barnes JI, Paci G, Zhuang T, Baker LC, Asch SM, Kamal RN:
Cost-effectiveness of open versus endoscopic carpal tunnel
release. J Bone Joint Surg Am 2021;103(4): 343-355. This study
evaluated the cost-effectiveness of open versus endoscopic carpal
tunnel release under local anesthesia. It was determined that
endoscopic release is associated with lower societal costs (earlier
return to work, higher quality- adjusted life-years) but is more
 expensive from a payor perspective and is cost-effective only if
performed in an office se ing. Level of evidence: I.
14. Westenberg RF, Oflazoglu K, de Planque CA, Jupiter JB, Eberlin
KR, Chen NC: Revision carpal tunnel release: Risk factors and
rate of secondary surgery. Plast Reconstr Surg 2020;145(5):1204-
1214. This aimed to determine the rate of revision carpal tunnel
release over a 14-year period; 1.5% of patients underwent revision
surgery with a median time to surgery of 1.23 years. Endoscopic
release, male sex, smoking, RA, and staged or simultaneous
bilateral release were risk factors for revision surgery. Level of
evidence: III.
15. Rhee PC, Fischer MM, Rhee LS, McMillan H, Johnson AE: Cost
savings and patient experiences of a clinic-based, wide- awake
hand surgery program at a military medical center: A critical
analysis of the first 100 procedures. J Hand Surg Am
2017;42(3):e139-e147.
16. Aultman H, Roth CA, Curran J, et al: Prospective evaluation of
surgical and anesthetic technique of carpal tunnel release in an
orthopedic practice. J Hand Surg Am 2021;46(1):69.e1-69.e7. This
prospective study that examined different types of anesthesia
(monitored anesthesia care versus WALANT) as well as
technique (mini-open versus endoscopic) in patients undergoing
carpal tunnel release and its effect on patient satisfaction with
postoperative pain/pain control and opioid use. There were
minimal differences in these outcomes between surgical
technique as well as anesthesia type. Level of evidence: IV.
17. Ayhan E, Akaslan F: Patients’ perspective on carpal tunnel
release with WALANT or intravenous regional anesthesia. Plast
Reconstr Surg 2020;145(5):1197-1203. This study compared
patients’ intraoperative experience during open bilateral carpal
tunnel release under WALANT on one side with intravenous
regional anesthesia on the contralateral side. The study found
that WALANT offered a be er intraoperative experience, with
83.3% of patients preferring WALANT if reoperation was
necessary.
18. Rogers MJ, Stephens AR, Yoo M, Nelson RE, Kazmers NH:
Optimizing costs and outcomes for carpal tunnel release surgery:
A cost-effectiveness analysis from societal and health-care system
perspectives. J Bone Joint Surg Am 2021;103(23):2190-2199. This
was a retrospective cost-effective analysis comparing open carpal
tunnel release in a procedure room (OCTR/PR), open carpal
tunnel release in an operating room (OCTR/OR), and endoscopic
carpal tunnel release in an operating room (ECTR/OR). Open
carpal tunnel release in a procedure room was found to be the
most cost-effective. Level of evidence: III.
19. Harness NG, Inacio MC, Pfeil FF, Paxton LW: Rate of infection
after carpal tunnel release surgery and effect of antibiotic
prophylaxis. J Hand Surg Am 2010;35(2):189-196.
20. Pace GI, Zale CL, Gendelberg D, Taylor KF: Self-reported
outcomes for patients undergoing revision carpal tunnel surgery
with or without hypothenar fat pad transposition. Hand (N Y)
2018;13(3):292-295.
21. Osei DA, Groves AP, Bommarito K, Ray WZ: Cubital tunnel
syndrome: Incidence and demographics in a national
administrative database. Neurosurgery 2017;80(3):417-420.
22. Montgomery K, Wolff G, Boyd KU: Evaluation of the scratch
collapse test for carpal and cubital tunnel syndrome - a
prospective, blinded study. J Hand Surg Am 2020;45(6):512-517.
These authors aimed to define the sensitivity, specificity, and
interrater reliability of the scratch collapse test for carpal and
cubital tunnel syndrome with electrodiagnostic testing and the
CTS-6 scoring system as reference standards. Sensitivity was poor
and specificity was good for both diagnoses. Interrater agreement
was fair. Level of evidence: II.
23. Terayama Y, Uchiyama S, Ueda K, et al: Optimal measurement
level and ulnar nerve cross-sectional area cutoff threshold for
identifying ulnar neuropathy at the elbow by MRI and
ultrasonography. J Hand Surg Am 2018;43(6):529-536.
24. Wiesler ER, Chloros GD, Cartwright MS, Shin HW, Walker FO:
Ultrasound in the diagnosis of ulnar neuropathy at the cubital
tunnel. J Hand Surg Am 2006;31(7):1088-1093.
25. Ru er M, Grandizio LC, Malone WJ, Klena JC: The use of
preoperative dynamic ultrasound to predict ulnar nerve stability
following in situ decompression for cubital tunnel syndrome. J
Hand Surg Am 2019;44(1):35-38. These authors reported a
correlation between physical examination and ultrasound and the
ability to accurately assess ulnar nerve instability, which was
determined intraoperatively. Physical examination was poorly
correlated with intraoperative findings of instability (12%)
compared with ultrasound (88%). Level of evidence: II.
26. Henn CM, Patel A, Wall LB, Goldfarb CA: Outcomes following
cubital tunnel surgery in young patients: The importance of
nerve mobility. J Hand Surg Am 2016;41(4):e1-e7.
27. Caliandro P, La Torre G, Padua R, Giannini F, Padua L:
Treatment for ulnar neuropathy at the elbow. Cochrane Database
Syst Rev 2016;11(11):CD006839.
28. Dunn JC, Goddard R, Eckhoff MD, Waterman BR, Nesti LJ,
Kilcoyne KG: Retrospective, nonrandomized analysis of
subcutaneous anterior transposition versus in situ
decompression of the ulnar nerve of military service members. J
Shoulder Elbow Surg 2019;28(4):751-756. This study evaluated
subjective and objective functional outcomes of subcutaneous
anterior transposition versus in situ decompression of the ulnar
nerve for cubital tunnel syndrome. Patients who underwent in
situ decompression had a lower mean DASH score with an
average follow-up of approximately 6 years. There was no
difference in reoperation rate.
29. Van Nest D, Ilyas AM: Rates of revision surgery following in situ
decompression versus anterior transposition for the treatment of
idiopathic cubital tunnel syndrome. J Hand Microsurg
2020;12(suppl 1):S28-S32. This study compared rates of revision
surgery following in situ decompression versus anterior
 transposition of the ulnar nerve for cubital tunnel syndrome. The
revision rate was 3.2% for in situ decompression and 2.2% for
anterior transposition. Risk factors for revision included younger
age, increased nerve conduction velocity, and decreased duration
of symptoms. Level of evidence: III.
30. Zhang D, Blazar P, Earp BE: Rates of complications and
secondary surgeries of mini-open carpal tunnel release. Hand (N
Y) 2019;14(4):471-476. The rates and types of complications and
secondary surgeries after mini-open carpal tunnel release were
examined and were low in the short term. Patients with diabetes
mellitus, chronic kidney disease, and cervical radiculopathy
should be counseled regarding risks of complications and
secondary surgery. Level of evidence: IV.
31. Hutchinson DT, Sullivan R, Sinclair MK: Long-term reoperation
rate for cubital tunnel syndrome: Subcutaneous transposition
versus in situ decompression. Hand (N Y) 2021;16(4):447-452. This
study compared long-term revision rates between in situ ulnar
nerve decompression and anterior subcutaneous transposition
for cubital tunnel syndrome. They reported a 25% long-term
reoperation rate for in situ decompression and 12% for anterior
subcutaneous transposition. Younger age and female sex were
predictors of need for revision.
32. Krejčí T, Večeřa Z, Krejčí O, Šalounová D, Houdek M, Lipina R:
Comparing endoscopic and open decompression of the ulnar
nerve in cubital tunnel syndrome: A prospective randomized
study. Acta Neurochir (Wien) 2018;160(10):2011-2017.
33. Dü mann S, Martin KD, Sobo ka S, et al: Open vs retractor-
endoscopic in situ decompression of the ulnar nerve in cubital
tunnel syndrome: A retrospective cohort study. Neurosurgery
2013;72(4):605-606.
34. Dengler J, Dolen U, Pa erson JMM, et al: Supercharge end-to-
side anterior interosseous-to-ulnar motor nerve transfer restores
intrinsic function in cubital tunnel syndrome. Plast Reconstr Surg
2020;146:808-818. This study reported patients who underwent
 supercharge end-to-side anterior interosseous nerve-to-ulnar
motor nerve transfer for severe cubital tunnel syndrome.
Thirty- nine of the included 42 patients had successful
improvement of intrinsic function from baseline. First dorsal
interosseous, pinch, and grip strength as well as DASH scores
were significantly improved from baseline at a mean follow-up of
11.2 months. Age was the only identified risk factor for failure.
Level of evidence: IV.
35. Power HA, Kahn LC, Pa erson MM, Yee A, Moore AM,
Mackinnon SE: Refining indications for the supercharge end-to-
side anterior interosseous to ulnar motor nerve transfer in cubital
tunnel syndrome. Plast Reconstr Surg 2020;145(1):106e-116e.
Author guidelines for patient selection, surgical technique, and
postoperative rehabilitation for supercharge end-to-side anterior
interosseous nerve-to-ulnar motor nerve transfer procedure were
presented. Level of evidence: V.
36. Natroshvili T, Walbeehm ET, van Alfen N, Bartels RHMA:
Results of reoperation for failed ulnar nerve surgery at the elbow:
A systematic review and meta-analysis. J Neurosurg
2018;130(3):686-701.
37. Aleem AW, Krogue JD, Calfee RP: Outcomes of revision surgery
for cubital tunnel syndrome. J Hand Surg Am 2014;39(11):2141-
2149.
38. Goldfarb CA, Su er MM, Martens EJ, Manske PR: Incidence of
re-operation and subjective outcome following in situ
decompression of the ulnar nerve at the cubital tunnel. J Hand
Surg Eur Vol 2009;34(3):379-383.
39. Raeburn K, Burns D, Hage R, Tubbs RS, Loukas M: Cross-
sectional sonographic assessment of the posterior interosseous
nerve. Surg Radiol Anat 2015;37(10):1155-1160.
40. Marchese J, Coyle K, Cote M, Wolf JM: Prospective evaluation of
a single corticosteroid injection in radial tunnel syndrome. Hand
(N Y) 2019;14(6):741-745. Patient-reported outcomes were
presented using the QuickDASH in patients with a clinical
 diagnosis of radial tunnel syndrome who also underwent
corticosteroid injection. The authors found that 57% of patients
achieved a minimal clinically important difference at 1 year of
follow-up compared with baseline.
41. Adler JA, Wolf JM: Proximal median nerve compression:
Pronator syndrome. J Hand Surg Am 2020;45(12):1157-1165. This
article reviewed pronator syndrome including relevant anatomy,
presentation and differential diagnosis, work-up, treatment
options, and outcomes.
42. Milner CS, Kannan K, Iyer VG, Thirkannad SM: Parsonage-
Turner syndrome: Clinical and epidemiological features from a
hand surgeon’s perspective. Hand (N Y) 2016;11(2):227-231.
43. Sneag DB, Rancy SK, Wolfe SW, et al: Brachial plexitis or
neuritis? MRI features of lesion distribution in Parsonage-
Turner syndrome. Muscle Nerve 2018;58(3):359-366.
44. van Alfen N, van Engelen BGM, Hughes RAC: Treatment for
idiopathic and hereditary neuralgic amyotrophy (brachial
neuritis). Cochrane Database Syst Rev 2009;2009(3):CD006976.
45. Zhu SL, Chin B, Sarraj M, Wang E, Dunn EE, McRae MC.
Denervation as a treatment for arthritis of the hands: A
systematic review of the current literature [published online
ahead of print March 1, 2021]. Hand (N Y). These authors
presented joint denervation as a less invasive option for surgical
treatment of hand arthritis; in all pooled studies, joint
denervation improved pain and hand function at follow-up with a
complication rate of 18.8%.
46. Wilder FV, Barre JP, Farina EJ: Joint-specific prevalence of
osteoarthritis of the hand. Osteoarthritis Cartilage 2006;14(9):953-
957.
47. Renfree KJ: Percutaneous in situ versus open arthrodesis of the
distal interphalangeal joint. J Hand Surg Eur Vol 2015;40(4):379-
383.
48. Wu JC, Calandruccio JH, Weller WJ, Henning PR, Swigler CW:
Arthritis of the thumb interphalangeal and finger distal
 interphalangeal joint. Orthop Clin North Am 2019;50(4):489-496.
This is a review article that explores demographics, patient
presentation and physical examination, and treatment methods
including surgical considerations when treating thumb and
digital interphalangeal osteoarthritis.
49. Wu F, Mehta SS, Dickson D, Catchpole D, Ng CY: Effect of
immobilization of the distal interphalangeal joint of fingers on
grip strength. J Hand Surg Eur Vol 2018;43(5):554-557.
50. Neukom L, Marks M, Hensler S, Kündig S, Herren DB,
Schindele S: Silicone arthroplasty versus screw arthrodesis in
distal interphalangeal joint osteoarthritis. J Hand Surg Eur Vol
2020;45(6):615-621. Outcomes and patient satisfaction were
compared between DIP joint silicone arthroplasty and screw
arthrodesis. Pain was low and patients were satisfied with their
outcomes in both groups; however, arthroplasty patients were
less satisfied with the appearance. Twenty-one percent of
arthroplasties and 15% of arthrodeses required reoperation. Level
of evidence: III.
51. Madden MO, Palmer JR, Ameri BJ, Vakharia RM, Landes J,
Roche MW: Trends in primary proximal interphalangeal joint
system and revisions for osteoarthritis of the hand in the
medicare database. Hand (N Y) 2020;15(6):818-823. This is a
retrospective review of the PearlDiver database, which showed
that there has been increased use of primary PIP arthroplasty
with decreased revision rates in the United States between 2005
and 2013.
52. Vitale MA, Fruth KM, Rizzo M, Moran SL, Kakar S: Prosthetic
arthroplasty versus arthrodesis for osteoarthritis and
pos raumatic arthritis of the index finger proximal
interphalangeal joint. J Hand Surg Am 2015;40(10):1937-1948.
53. Capo JT, Melamed E, Shamian B, et al: Biomechanical evaluation
of 5 fixation devices for proximal interphalangeal joint
arthrodesis. J Hand Surg Am 2014;39(10):1971-1977.
54. Millrose M, Zach A, Kim S, Güthoff C, Eisenschenk A,
Vonderlind HC: Biomechanical comparison of the proximal
interphalangeal joint arthrodesis using a compression wire. Arch
Orthop Trauma Surg 2019;139(4):577-581. A biomechanical study
compared the stability of compression wiring with intraosseous
wiring to tension band wiring for PIP joint arthrodesis. The
stability of the compression wires was statistically significantly
superior to that of intraosseous wires; tenson band wires showed
intermediate stability.
55. Kemper LT, de Jong TR, Brink SM, Verhaegen PDHM: Patient
satisfaction with the angle of fusion of the proximal
interphalangeal joint. J Hand Surg Eur Vol 2020;45(5):521-522. This
study evaluated patient satisfaction with PIP joint arthrodesis
angles. Seventy-five percent of patients were satisfied with their
fusion angle. Satisfied patients had a median fused angle of 10°
more extension compared with the cascade of the hand,
suggesting that patients actually prefer their fusion in a more
extended position than previously thought.
56. Tranchida GV, Allen ST, Moen SM, Erickson LO, Ward CM:
Comparison of volar and dorsal approach for pip arthroplasty.
Hand (N Y) 2021;16(3):348-353. Range of motion and complication
rates were compared between volar and dorsal approaches for
PIP joint arthroplasty and it was found that the overall
complication rates between groups were similar, and although
the dorsal approach group had a greater gain in range of motion,
there was no difference in postoperative range of motion between
groups.
57. Proubasta IR, Lamas CG, Natera L, Millan A: Silicone proximal
interphalangeal joint arthroplasty for primary osteoarthritis
using a volar approach. J Hand Surg Am 2014;39(6):1075-1081.
58. Mora AN, Earp BE, Blazar PE: Midterm clinical and radiographic
follow-up of pyrolytic carbon PIP arthroplasty. J Hand Surg Am
2020;45(3):253.e1-253.e6. This article reported clinical and
radiographic outcomes of pyrolytic carbon arthroplasty of the PIP
joint. With a mean follow-up of 6.4 years, there was a revision rate
 of 24.1%. Strength, range of motion, and pain relief were
satisfactory. Level of evidence: IV.
59. Wagner ER, Weston JT, Houdek MT, Luo TD, Moran SL, Rizzo
M: Medium-term outcomes with pyrocarbon proximal
interphalangeal arthroplasty: A study of 170 consecutive
arthroplasties. J Hand Surg Am 2018;43(9):797-805.
60. Dickson DR, Nu all D, Wa s AC, Talwalkar SC, Hayton M, Trail
IA: Pyrocarbon proximal interphalangeal joint arthroplasty:
Minimum five-year follow-up. J Hand Surg Am 2015;40(11):2142-
2148.e4.
61. Naghshineh N, Goyal K, Giugale JM, et al: Proximal
interphalangeal joint silicone arthroplasty for osteoarthritis:
Midterm outcomes. Hand (N Y) 2019;14(5):664-668. This
retrospective cohort study evaluated functional and subjective
outcomes after PIP joint silicone arthroplasty. Patients reported
significant pain relief, increase grip and key pinch strength, and
high satisfaction rates (84%).
62. Bales JG, Wall LB, Stern PJ: Long-term results of Swanson
silicone arthroplasty for proximal interphalangeal joint
osteoarthritis. J Hand Surg Am 2014;39(3):455-461.
63. Wagner ER, Robinson WA, Houdek MT, Moran SL, Rizzo M:
Proximal interphalangeal joint arthroplasty in young patients. J
Am Acad Orthop Surg 2019;27(12):444-450. Outcomes of PIP
arthroplasty were compared in patients older than and younger
than 60 years. Younger patients had a higher revision rate and a
lower 10-year implant survival rate, with the most common
complication being dislocation. Pos raumatic arthritis also
increased the likelihood of revision. Level of evidence: III.
64. Notermans BJW, Lans J, Arnold D, Jupiter JB, Chen NC: Factors
associated with reoperation after silicone metacarpophalangeal
joint arthroplasty in patients with inflammatory arthritis. Hand
(N Y) 2020;15(6):805-811. Risk factors associated with reoperation
after silicone MCP joint arthroplasty were described. The overall
reoperation rate was 9.1%; patients who underwent single-digit
 arthroplasty and who did not have preoperative MCP joint
subluxation had a higher trend for increased rates of revision.
65. Claxton MR, Wagner ER, Rizzo M: Long-term outcomes of MCP
surface replacement arthroplasty in patients with rheumatoid
arthritis. Hand (N Y) 2022;17:271-277. These authors reported
outcomes in surface replacement arthroplasty of the MCP joint
with a mean follow-up of 9.5 years. Arc of motion, grip strength,
and pain significantly improved following surgery. There was a
36% reoperation rate; however, only 16% underwent revision
arthroplasty.
66. Morrell NT, Weiss A-PC: Silicone metacarpophalangeal
arthroplasty for osteoarthritis: Long-term results. J Hand Surg Am
2018;43(3):229-233.
67. Wall LB, Stern PJ: Clinical and radiographic outcomes of
metacarpophalangeal joint pyrolytic carbon arthroplasty for
osteoarthritis. J Hand Surg Am 2013;38(3):537-543.
68. Dickson DR, Badge R, Nu all D, et al: Pyrocarbon
metacarpophalangeal joint arthroplasty in noninflammatory
arthritis: Minimum 5-year follow-up. J Hand Surg Am
2015;40(10):1956-1962.
69. Wanderman N, Wagner E, Moran S, Rizzo M: Outcomes
following acute metacarpophalangeal joint arthroplasty
dislocation: An analysis of 37 cases. J Hand Surg Am
2018;43(3):289.e1-289.e6.
70. Walker KL, Johnson AN, Marchessault JA: Dorsal capsule
interpositional arthroplasty of the metacarpophalangeal joint.
Hand (N Y) 2022;17:68-73. A retrospective review of patients
undergoing MCP joint dorsal capsule interposition arthroplasty
with a mean follow-up of 29 months demonstrated that patients
had good pain relief, and all returned to work without requiring a
second surgery.
C H AP T E R 3 6

Ligament Injuries of the Wrist

Nichole A. Joslyn MD, Sanjeev Kakar MD, FAAOS, FAOA

Dr. Kakar or an immediate family member serves as a paid consultant to or is an employee of

Arthrex, Inc. and has stock or stock options held in Sonex Healthcare. Neither Dr. Joslyn nor any
immediate family member has received anything of value from or has stock or stock options held
in a commercial company or institution related directly or indirectly to the subject of this chapter.

ABSTRACT
A thorough understanding of the complex anatomy and kinematics
of the wrist is necessary to diagnose and treat wrist pathologies.
Carpal instability can be defined as a symptomatic condition
involving abnormal carpal motion during loading activities of the
wrist. It is important for the orthopaedic surgeon to review carpal
instability pa erns, diagnostic modalities, and discuss current
treatment options.
Keywords: carpal instability; lunotriquetral ligament; perilunate
instability; scapholunate ligament

Introduction
The understanding of the complex articular system of the carpus
continues to evolve. Various injuries to the carpus can sometimes
lead to malalignment and instability. There are four major pa erns
of instability of the wrist: dissociative (within the same carpal row),
nondissociative (between rows, eg, radiocarpal and/or midcarpal),
complex (features of both dissociative and nondissociative
instability, ie, perilunate dislocations), and adaptive (not caused by
an intrinsic wrist ligament pathology, eg, a distal radius malunion,
Madelung deformity).
The wrist is a fascinating, complex, multiarticular system. The fine
movements of the eight carpal bones are dependent on their
structural bony architecture, intrinsic and extrinsic ligaments, and
crossing flexor and extensor tendons. When any one of these is
compromised, the motion and loading of the wrist and hand may be
impaired. Although this may suggest carpal instability, it is
important to understand that not all carpal malalignment should be
considered unstable.

Assessment of Carpal Instability

Carpal instability is a symptomatic condition involving abnormal
carpal motion during loading activities of the wrist. It is helpful to
consider a six-category system 1 when formulating a treatment plan
(Table 1).

Table 1
Analysis of Carpal Instability

Chronicity Severity Etiology Location Direction Pattern

Acute (<1 Dynamic Congenital Radiocarpal VISI Carpal
wk) DISI instability
dissociative
— Static Traumatic Intercarpal — —
— — Inflammatory Midcarpal Ulnar Carpal
Radial instability
nondissociative
Subacute — Arthritis Carpometacarpal — —
(1-6 wk)
Chronic — Neoplastic Specific bone Ventral Carpal
(>6 wk) Iatrogenic Specific ligament Dorsal instability
Miscellaneous Proximal complex
Combination Distal Carpal
Rotary instability
Combinations adaptive
DISI = dorsal intercalated segmental instability, VISI = volar intercalated segmental instability
Reprinted from Larsen CF, Amadio PC, Gilula LA, Hodge JC: Analysis of carpal instability: I.
Description of the scheme. J Hand Surg Am 1995;20(5):757-764, with permission from
Elsevier.

When further assessing patients with carpal instability, SCARCE

is a mnemonic that helps the practitioner consider the numerous
factors that may be involved. S stands for critical Secondary
Stabilizer integrity, C for Carpal alignment, A for Acuity of injury, R
for Reducibility of the carpus, C for quality of the articular Cartilage,
E for Extent of ligament injury (ie, partial versus complete). 2

Carpal Instability Dissociative

Carpal instability dissociative is a disruption between bones of the
same carpal row. Scapholunate and lunotriquetral dissociation are
two of the most commonly seen conditions within this category.

Scapholunate Ligament Injury

Scapholunate ligament dissociation most commonly occurs after a
fall on an outstretched wrist and is the most frequent carpal
instability pa ern. 3 , 4 This may occur as an isolated injury, or in
conjunction with other injuries (eg, perilunate injuries or distal
radius fractures). Up to 30% of distal radius fractures are associated
with variable degrees of carpal ligament disruption. 5 The injury may
also occur secondary to inflammatory or septic arthritis, or
iatrogenically with excessive capsular excision, for example, during a
dorsal ganglion excision.
The scapholunate ligament is composed of the palmar,
membranous, and dorsal regions. Partial injuries may result in
dynamic instability when the wrist is loaded. 6 Injury to the entire
scapholunate ligament when associated with injury to one or more
critical secondary stabilizers (long radiolunate ligament, dorsal
intercarpal ligament, and/or radiopalmar scaphotrapezio trapezoid
[STT] ligament complex) may result in postural deformity such as
diastasis of the scapholunate joint, scaphoid rotatory subluxation, or
dorsal intercalated segment instability (DISI). 7 - 9 Without a direct
tether to the lunate, and with the load and flexion of the radial
column, the scaphoid collapses into flexion and pronation around
the radioscaphocapitate ligament. The lunate and triquetrum may
extend when detached from the scaphoid, where there is a type 1
lunate. This flexion and extension differential allows the distal
carpal row to translate dorsally. If left untreated, this may progress
to progressive pos raumatic arthritis, termed scapholunate
advanced collapse. 10

Physical Examination
Diagnosis is made through a combination of history (often a fall
onto an outstretched hand, complaints of a clunking sensation),
physical examination, and imaging modalities. Most patients with
an acute injury or chronic synovitis will have pain directly over the
scapholunate interval (flexing the wrist, and palpating just distal to
the Lister tubercle). There may also be associated swelling in this
area. The scaphoid shift test and scapholunate ballo ement tests are
also helpful examination maneuvers 11 and should be compared with
the contralateral side.

Radiographs
PA, lateral, and 45° pronated oblique views of the injured wrist and
contralateral wrist should be obtained during the initial patient
evaluation. Gilula lines should be inspected for continuity, and
intercarpal spacing should be evaluated. Carpal alignment can be
measured by the radiolunate angle (normal −20° to + 15°),
scapholunate angle (normal 30° to 70°), radioscaphoid angle (normal
35° to 65°), ulnar variance, carpal height ratio (carpal height/capitate
length normal range of 1.57 +/− 0.05), and ulnar translocation ratio
(articular surface of the radius/distance from the radial styloid to the
proximal ulnar corner of the lunate, normal 0.87 +/− 0.04). Further
imaging modalities may be needed depending on the suspected
pathology.
If dynamic instability is suspected, a clenched-pencil PA view
provides a comparison view of both wrists while loading the
scapholunate interval with grip force. 12 , 13 A motion series can help
evaluate the mobility and reducibility of the carpus, and often
includes a PA radiograph taken in neutral, radial, ulnar deviation,
and lateral views in extension and flexion. A scapholunate gap
greater than 5 mm is considered widened and is also referred to as
scapholunate diastasis. 14 , 15 However, this can be a normal finding,
especially in a patient with hyperlaxity, and should always be
compared with the contralateral side. When the scaphoid rotates
into flexion and pronation (rotatory subluxation of the scaphoid), a
ring sign is seen on a PA radiograph. In more severe stages of
instability, the scaphoid may be flexed on a lateral radiograph and
the lunate extended. Dorsal intercalated segment instability is
defined by a radiolunate angle greater than 15°. 16 As discussed in a
2019 study, patients may also have dorsal scaphoid translation and
should alert the practitioner to additional ligament injury. 17
Additional imaging modalities can be helpful. CT can be
reforma ed into three-dimensional views of the wrist to be er
understand the amount and displacement of the carpus. This can be
done in real time using four-dimensional CT (three-dimensional and
time) scanning. 18 , 19 MRI technology continues to improve and can
assess ligament integrity and cartilage injury. A study published in
2021 suggests that MRI was 95.4% accurate for surgically relevant
scapholunate ligament tears, and 100% accurate for complete
lunotriquetral tears. 20 3T MRI studies have shorter acquisition times
than 1.5T systems and three-dimensional imaging scores superior to
two-dimensional scans when assessing the scapholunate,
lunotriquetral, and triangular fibrocartilage complex ligaments. 21
Real-time MRI has been used to investigate dynamic instabilities,
but its use in clinical practice is unclear.
Although these additional imaging modalities may aid in
diagnosis and planning treatment, arthroscopy can be a useful tool
in the management of carpal instability because it allows for
assessment of the degree of ligamentous injury, evaluation of
reducibility of the carpus, the health of the cartilage, and associated
secondary stabilizer injury. These factors are of critical importance
when deciding treatment.

Treatment
It is important to consider the gradation of injury when developing
a treatment algorithm for scapholunate ligament injury. The Garcia-
Elias staging system 22 provides an overview of some of the available
treatment options.

Garcia-Elias Stage 1: Partial Scapholunate Ligament Rupture

Partial ruptures of the scapholunate ligament typically involve the
palmar and membranous portions and tend to spare the dorsal
fibers in most stage 1 cases. There is no carpal malalignment.
Surgical treatment options include percutaneous Kirschner-wire
stabilization of the scapholunate joint, arthroscopic débridement of
torn ligament edges with electrothermal ligament shrinkage, or
arthroscopic capsulodesis. 23 , 24

Garcia-Elias Stage 2: Scapholunate Dissociation, Reparable

There is complete disruption of the scapholunate ligament, without
postural deformity of the scaphoid or lunate in stage 2. These
patients may present with dynamic diastasis of the scapholunate
joint during wrist loading. Treatment options include arthroscopic-
guided closed reduction with percutaneous stabilization, open
repair of the scapholunate ligaments if performed within 6 weeks of
injury 4 (augmented with either Kirschner wire, temporary screw
placement, or suture stabilization), and arthroscopic capsulodesis.
Arthroscopic dorsal and palmar ligament repairs have been
described also. 25 , 26

Garcia-Elias Stage 3: Scapholunate Dissociation, Irreparable,

Normally Aligned Scaphoid and Lunate
In stage 3, the scapholunate ligament is completely disrupted and
nonrepairable and carpal alignment is maintained. Treatment
options include a capsulodesis or reconstruction.
 A dorsal capsulodesis has been described to help prevent the
scaphoid from collapsing into flexion and pronation. Three methods
have gained popularity. The Bla procedure is performed by
creating a checkrein of a proximally based strip of the dorsal capsule
to prevent scaphoid flexion. 6 , 27 The Mayo capsulodesis takes half of
the dorsal intercarpal ligament, releasing it from the triquetrum and
redirecting and inserting it onto the dorsum of the lunate. 28 The
Szabo procedure involves advancement of the dorsal intercarpal
ligament from its dorsal ridge on the scaphoid to a more radial
position on the scaphoid neck. 29 , 30 Long-term results for these
three capsulodesis options have been satisfactory, although carpal
collapse may still occur. A shortcoming common to all capsulodesis
procedures is that they are all nonanatomic.
Soft-tissue reconstruction of the dorsal scapholunate ligament has
been described by taking a strip of either the dorsal intercarpal
ligament or dorsal radiocarpal ligament, preserving the triquetral
a achment, débridement of the cortices of the scaphoid and lunate
down to bleeding bone, and then reinserting onto the dorsal and
ulnar corner of the proximal scaphoid with a bone anchor. A review
of this technique showed that, at 86 months, it did not reliably
prevent collapse or scapholunate advanced collapse arthritis. 29

Garcia-Elias Stage 4 Scapholunate Dissociation With Rotatory

Subluxation of the Scaphoid, Reducible
Stage 4 involves the complete loss of the scapholunate ligament,
with additional injury to the critical stabilizers. This allows the
scaphoid to flex, pronate, and potentially subluxate dorsally;
however, the lunate remains normally aligned. Because the carpus is
reducible, treatment options have included tendon graft
reconstruction of the dorsal scapholunate ligament complex,
volar/dorsal scapholunate graft reconstruction, scapholunate axis
graft reconstruction, or screw fixation.
The Brunelli technique involves reducing the scaphoid, passing a
distally based strip of the flexor carpi radialis tendon through the
scaphoid and anchoring it to the dorsal rim of the distal radius with
Kirschner wire stabilization. 31 The loss of wrist flexion and the
propensity for the development of radio-scaphoid osteoarthritis led
to various modifications. The three-ligament tenodesis was one of
these modifications. The procedure did not cross the radiocarpal
joint and reconstructed the STT ligaments, the dorsal portion of the
scapholunate ligament, and dorsal scaphotriquetral ligament.
The reduction-association of the scapholunate joint procedure
involves removal of the articular cartilage between the scaphoid and
lunate, reduction of the scaphoid and lunate, and transfixion with a
headless screw, performed either open or arthroscopically. 32 , 33
Some series have demonstrated promising results, 34 although
concerns have been raised regarding hardware failure and carpal
collapse. 35 Another concern was raised in a 2019 study 36 that
demonstrated the high variability of the location of the rotation axis
of the scapholunate joint, and its variation with different motions of
the wrist, indicating that a fixed axis is nonanatomic.
Other techniques use the axis methodology but incorporate a
tendon graft. The scapholunate axis method uses a tendon graft
passed between the scaphoid and lunate along the axis of rotation in
the sagi al plane. It is secured in the scaphoid with an interference
screw, and in the lunate with a graft anchor. 37 The
scapholunotriquetral technique uses a strip of the flexor carpi
radialis passed through the scaphoid axis as in the three-ligament
tenodesis, but then a second tunnel is drilled through the center of
the lunate and through the triquetrum. It is secured with an
interference screw in the triquetrum and the tail of the graft is
brought dorsally to reconstruct a portion of the dorsal intercarpal
ligament. 38
With improved understanding of scapholunate joint mechanics,
recent techniques have been proposed to reconstruct both the
dorsal and volar components of the scapholunate interosseous
ligament, as well as some of the secondary stabilizers. 39 Open and
arthroscopic box techniques have been described, wherein a loop of
tendon graft is tunneled through dorsal-volar channels in each bone
and sutured. 40 , 41 In one such box technique, a palmaris longus
tendon graft is passed through the scaphoid and lunate, superficial
to the volar capsule and tied over the dorsal intercarpal ligaments. 41
- 44

One study described a scapholunate reconstruction with tendon

graft augmented with synthetic tape to increase the strength of the
reconstruction 44 (Figure 1). A 2021 three-center study of nine
patients showed favorable early clinical, patient-reported, and
radiologic outcomes at a mean follow-up of 33.7 months. 42 This
article suggests that the added synthetic tape obviates the need for
Kirschner wires and has earlier rehabilitation compared with
traditional immobilization, 42 , 43 although longer term follow-up is
needed.

Figure 1 Intraoperative photographs of the scapholunate 360° technique.A,

Ligament-sparing capsulotomy. B, Reduction of scapholunate interval. C, Final
volar view demonstrating reconstruction of the volar scapholunate and long
radiolunate ligaments, D, Dorsal view demonstrating reconstruction of the dorsal
scapholunate ligament and a distal tether to prevent scaphoid flexion.(Courtesy of
Sanjeev Kakar, MD, FAAOS, FAOA.)
Garcia-Elias Stage 5: Scapholunate Dissociation With Rotatory
Subluxation and Dorsal Intercalated Segment Instability
Stage 5 includes rupture of the scapholunate ligament as well as one
or more critical lunate stabilizers, with scaphoid and lunate
instability with normal cartilage. Because the lunate is unstable,
reconstruction of the scapholunate ligaments alone is inadequate.
Therefore, it is important to not only reconstruct the scapholunate
ligament, but also to address the critical stabilizers. Treatment
options include scapholunate 360° reconstruction (which also
reconstructs the long radiolunate ligament 42 - 44 ), spiral tenodesis,
and anatomic front and back repair. Spiral tenodesis 45 starts similar
to the three-ligament tenodesis by tunneling flexor carpi radialis
graft through the scaphoid and anchoring it to the lunate. It is then
run through a dorsopalmar tunnel across the triquetrum to the floor
of the carpal tunnel and inserted onto the radial styloid with a bone
anchor or tunnel. Modifications have been described by using a strip
of extensor carpi radialis longus instead of flexor carpi radialis. The
anatomic front and back repair procedure 46 reconstructs the dorsal
scapholunate, dorsal intercarpal, the radiopalmar STT, and the long
radiolunate ligaments. A 2020 study reported on 10 patients
followed for a minimum of 24 months and noted a median
scapholunate gap of 3 mm, scapholunate angle of less than 70° in all
but one patient, improved grip strength, and preserved wrist range
of motion. One patient required revision surgery for ulnocarpal
impaction. 46 As with other reconstruction techniques, longer term
follow-up studies are needed.

Garcia-Elias Stage 6: Scapholunate Dissociation With Irreducible

Carpal Collapse and Normal Cartilage
Stage 6 manifests with the inability to reduce the carpus and
therefore soft-tissue reconstructions should be avoided. Treatment
options include proximal row carpectomy and partial fusions
(scaphoid-trapezium-trapezoid arthrodesis, scaphocapitate
arthrodesis). STT arthrodesis has evolved to include a radial
styloidectomy, to prevent symptomatic radioscaphoid impingement.
47
Garcia-Elias Stage 7: Scapholunate Dissociation With Irreducible
Carpal Collapse and Degenerative Arthritis
Stage 7 involves scapholunate advanced collapse wrist degenerative
changes. Treatment options include arthroscopic or open radial
styloidectomy with or without a partial wrist denervation (anterior
and posterior interosseous neurectomies), 48 radioscaphoid-lunate
fusion with distal scaphoidectomy (if the midcarpal joint cartilage is
without degeneration), 49 scaphoidectomy and midcarpal fusion, 50
total wrist arthroplasty, and total wrist arthrodesis.

Lunotriquetral Ligament Injury

Lunotriquetral ligament injuries often occur from a backward fall
onto an outstretched hand, with impact focused on the hypothenar
region. The long and short radiolunate ligaments hold the lunate in
position, whereas the pisiform pushes the triquetrum dorsally.
Other concomitant injuries may occur, including peripheral
triangular fibrocartilage complex tears, ulnotriquetral ligament
injuries, or ulnocarpal impaction. The lunotriquetral ligament
similarly has three components (volar, membranous, and dorsal)
and, as opposed to the scapholunate ligament, the volar portion is
the strongest.

Diagnosis
Patients will often present with point tenderness directly over the
dorsal aspect of the joint, aggravated by ulnar deviation of the wrist
and forearm supination. A positive ballo ement test is
pathognomonic. There are, however, a multitude of possible ulnar-
sided wrist pathologies that could confound this finding; therefore it
is critical that the examiner perform a thorough assessment of the
wrist. 51 , 52

Radiographs
Wrist radiographs may appear normal. However, if there is
disruption of the normal convexity of the proximal carpal row in the
PA film, lunotriquetral ligament injury should be suspected. A
seagull sign can be appreciated on the PA view. Volar intercalated
segment instability (VISI) malalignment may be seen on lateral
films. Additional imaging modalities include MRI and CT to help
delineate the carpal instability, as described earlier. Arthroscopy
can help with the diagnosis of intercarpal ligament injury, its
location (dorsal, membranous, palmar, or complete), lunotriquetral
joint reducibility, cartilage quality, and to diagnose additional
pathologies such as hamate arthrosis lunotriquetral ligament injury
or ulnar impaction. 53

Treatment
In order to help guide treatment, lunotriquetral ligament injuries
have been classified into three stages. 54

Acute Lunotriquetral Injury Without Carpal Collapse

Treatment options include splint or cast immobilization (with a pad
beneath the pisiform and over the dorsal distal radius to augment
immobilization of the lunotriquetral joint), arthroscopic-assisted
percutaneous lunotriquetral pinning or screw stabilization, or open
repair. 55 , 56

Chronic Lunotriquetral Injury Without Carpal Collapse

Treatment options include arthroscopic débridement,
electrothermal shrinkage, open repair with capsulo- desis (only if
the quality of the lunotriquetral ligament is suitable), ligament
reconstruction, or lunotriquetral arthrodesis. The success of these
procedures is variable. Ligament reconstruction has been described
using a distally based strip of extensor carpi ulnaris tendon passed
through drill holes in the lunate and triquetrum. Fusion of the
lunotriquetral joint has variable union rates (26% to 100%). One
study comparing ligament reconstruction with a distally based strip
of the extensor carpi ulnaris tendon with lunotriquetral fusion
showed higher subjective and objective outcomes with the ligament
reconstruction. 56
Chronic Lunotriquetral Dissociation With Carpal Collapse
This injury is due to complete lunotriquetral ligament disruption, as
well as other extrinsic ligaments including the dorsal radiocarpal
and ulnar arcuate ligaments. The carpus collapses into a VISI
malalignment. Fusion of the lunotriquetral or soft-tissue
reconstructions may not provide reliable symptom relief because
they are unsuccessful in reducing VISI. Treatment options include
radiolunate fusion 57 (with or without triquetrum excision) or
midcarpal fusion.

Nondissociative Carpal Instability

Nondissociative carpal instability or carpal instability
nondissociative (CIND) occurs when there is dysfunction between
the radiocarpal or midcarpal joints. There are three types of CIND:
radiocarpal, combined radiocarpal-midcarpal (proximal row
instability), or, rarely, midcarpal instability. Proximal row instability
can be further divided into CIND-DISI (extension of the proximal
row with dorsal capitate subluxation) and CIND-VISI (flexion of the
proximal row with volar subluxation of the capitate). 58
In nondissociative radiocarpal instability, the carpus tends to
translate ulnarly. It is most commonly seen in patients with
congenital anomalies such as Madelung deformity, or in
inflammatory arthritis. Pos raumatic instability is less common and
occurs when there is disruption of the proximal carpal row extrinsic
ligaments or a radial styloid fracture with ulnar subluxation of the
carpus. Two types of ulnar translocation have been described. 59
Type I involves disruption of the radiocarpal ligaments (dorsal
radiocarpal, long radiolunate, short radiolunate,
radioscaphocapitate) causing displacement of the entire carpus
including the scaphoid, resulting in an increased distance between
the radial styloid and scaphoid. In type II instability, the scaphoid
remains in place, and the scapholunate joint is widened as the
lunotriquetral complex translocates ulnarly. Treatment for ulnar
translocation of the carpus often includes radiocarpal fusion, as
ligament reconstructions have been disappointing. 60
Proximal row instability is the most common CIND pa ern and
involves disruption of the ligaments crossing the radiocarpal and
midcarpal joints (hence the term combined radiocarpal and
midcarpal instability). It is commonly seen in patients with
ligamentous laxity or as a result of disruption of the dorsal
radiocarpal, triquetrohamate, and STT ligaments, and most
frequently presents as CIND-VISI. Patients may complain of a
painful “clunk” when moving the wrist into ulnar deviation (eg,
pouring milk from a carton). Rarely, patients may present with
CIND-DISI, which is usually caused by traumatic disruption of the
dorsal intercarpal and long radiolunate ligaments.
Given that CIND-VISI is the most common form of proximal row
instability, radiographs will usually show a VISI pa ern. Dynamic
fluoroscopy can be helpful as well as traction views to rule out
disruptions within the joints of the proximal carpal row. Stress
views including the anterior drawer test, posterior drawer test,
forced ulnar deviation, and forced radial deviation can also be used
to determine the nature of extrinsic ligament injury. Arthroscopy
can be helpful to examine the injured ligaments but also to rule out
lunotriquetral injury, which in itself can result in volar flexion of the
lunate.
In symptomatic patients, a course of nonsurgical treatment is
warranted, including 6 to 8 weeks of immobilization in a pisiform
boost splint and avoidance of activities that produce the “catch-up
clunk.” Patients should then undergo dedicated hand therapy
including proprioception training and concomitant activation of the
flexor carpi ulnaris and extensor carpi ulnaris muscles to prevent
excessive flexion of the proximal carpal row. 61 If patients remain
symptomatic despite nonsurgical treatment, treatment options
include capsular shrinkage (to the palmar midcarpal and dorsal
radiocarpal capsule), soft-tissue ligament reconstruction (eg,
plication of dorsal radiocarpal and dorsal intercarpal ligaments or
an STT ligament reconstruction), and intercarpal arthrodesis (STT,
triquetrohamate, radiolunate, or four-corner fusion). A
biomechanical study compared radiolunate arthrodesis with
triquetrohamate arthrodesis, and although both procedures
eliminated wrist clunking, the radiolunate fusion decreased
scaphoid flexion, whereas the triquetrohamate fusion altered
proximal row motion in several directions. 62
Patients with CIND-DISI should also undergo a period of
nonsurgical treatment and therapy that involves proprioceptive
training of their extensor carpi radialis longus, extensor carpi
radialis brevis, and extensor carpi ulnaris muscles to prevent
excessive extension of the proximal carpal row. In patients with
refractory symptoms, treatment may involve a transverse midcarpal
dorsal capsulodesis to reinforce the dorsal intercarpal ligaments. 29
Pure midcarpal instability is when the midcarpal joint is unstable
but not the radiocarpal joint, and includes capitolunate instability
pa ern. 63 , 64 These patients can initially be treated with hand
therapy and activity modification. Surgical treatment options
include obliteration of the space of Poirier with nonabsorbable
sutures or dorsal reinforcement of the midcarpal capsule using a
dorsal capsulodesis. 65

Carpal Instability Complex

When an injury shares features of both carpal instability
dissociative and CIND, this form of instability is referred to as
carpal instability complex. Acute carpal fracture-dislocations fall
under this category. There are six types of wrist dislocations: dorsal
perilunate dislocations, dorsal perilunate fracture-dislocations,
palmar perilunate dislocations, radiocarpal dislocation, axial
dislocation, and isolated carpal bone dislocations. These are
typically the result of a high injury mechanism and a heightened
degree of vigilance is needed for assessment and management. It is
important to obtain a complete set of wrist radiographs, and
dislocations need to be reduced in the emergency department as
quickly as possible. A thorough neurovascular examination is
critical because acute carpal tunnel syndrome is not infrequent. 66
Postreduction radiographs and a CT scan should be obtained to
understand the personality of the injury and for surgical planning.
The term perilunate instability not dislocated refers to a lesser or
greater arc injury in which there was no dislocation of the capitate
from the lunate on the radiographs. 29 The surgeon should have a
high index of suspicion when assessing these injuries.

Dorsal Perilunate Dislocation

Dorsal perilunate and palmar-lunate dislocations represent different
stages of the same injury and their management is similar. After a
closed reduction has been performed, postreduction radiographs
(including a scaphoid view) and CT scans should be obtained.
Unless medically contraindicated, surgery is indicated to ensure the
carpus is anatomically aligned. This may be via arthroscopic-
assisted closed reduction and stabilization (using Kirschner wires or
cannulated screws) or by open reduction and repair of the injured
ligaments. 67 - 69 Given the devastating nature of these injuries,
patients should be aware before surgery that the recovery can be
prolonged and outcomes can be unpredictable. One study
retrospectively reviewed 30 patients (14 perilunate and 16 perilunate
fracture-dislocations) with a mean follow-up of 18 years and found
the average Mayo Wrist Score was 70 and grip strength was 70% of
the contralateral arm. Radiographic arthritis was seen in 70% of
patients despite the patients having good functional outcomes. 70

Dorsal Perilunate Fracture-Dislocation

Approximately 60% of all perilunate dislocations are associated with
a scaphoid fracture (Figure 2). Typically, the proximal fragment will
remain a ached to the lunate; however, there are rare instances in
which there is a concomitant scapholunate dissociation. 71 In
addition, there can be other carpal fractures including the capitate
and/or triquetrum. Treatment options include either arthroscopic or
open reduction and internal fixation of the fractures and
stabilization of the carpus. One study compared arthroscopic-
assisted reduction and fixation with open reduction and fixation of
transscaphoid perilunate fracture-dislocations with a minimum
follow-up of 2 years and reported that the Disabilities of the Arm,
Shoulder and Hand scores and a flexion-extension arc were be er in
the arthroscopy group. 72

Figure 2 Radiographs showing a dorsal transscaphoid perilunate fracture-

dislocation.A, PA radiograph. B, Lateral radiograph.(Courtesy of Sanjeev Kakar,
MD, FAAOS, FAOA.)

Palmar Perilunate Dislocation

Palmar dislocation of the capitate relative to the lunate is very rare.
If it is not associated with a lunate fracture, scapholunate
dissociation or scaphoid fracture is invariably present.

Radiocarpal Dislocation
There are two types of radiocarpal dislocations. Type I are rare and
are those without a radial styloid fracture with injury to the
radiocarpal ligaments. Type II, the most common, are associated
with a radial styloid fracture (containing the origin of the palmar
radio-scaphoid and radioscaphocapitate ligaments). For type I
injuries, the palmar and dorsal radiocarpal ligaments are repaired
and the carpus immobilized with a dorsal spanning plate for
approximately 12 weeks. In general, type II injuries yield be er
outcomes if the radial styloid can be reduced and fixed. In a study
on 26 patients with radiocarpal dislocations, 3 underwent an acute
arthrodesis (2 radioscapholunate fusions and 1 total wrist fusion).
Those who underwent open reduction and internal fixation and
ligament repair had be er subjective patient outcomes than those
undergoing acute fusion. 73

Axial Fracture-Dislocation
This injury is often related to a high-energy crush mechanism,
whereby the wrist divides into two axial columns. One remains
normally aligned, and the other shifts radially (axial radial) or
ulnarly (axial ulnar). The metacarpals follow the displacement of
their corresponding carpal bones, leading to an intermetacarpal
dissociation. Significant soft-tissue injury is common. Again, as with
all carpal dislocations, a thorough neurovascular examination is
important. Débridement of devitalized muscle, skin, and soft tissue
is often the first step, followed by surgical stabilization of the carpus
and associated bone and soft-tissue injuries because many of these
are open injuries. Radial axial injuries have the worst prognosis. 74

Isolated Carpal Bone Dislocation

Isolated carpal bone dislocations are rare; however, dislocation of
each carpal bone has been reported. In contrast to axial carpal
dislocations, isolated dislocations do not result in pancarpal
instability. Palmar dislocation of the scaphoid has been described
and there can either be an anterolateral dislocation of the proximal
pole (type I) or a scaphoid dislocation with axial disruption of the
capitate-hamate joint (type II).
Carpal Instability Adaptive
Within this type of instability, carpal malalignment is not caused by
an intrinsic or extrinsic carpal ligament injury but rather the
response of the carpus to distortions of the anatomy of the distal
radius or carpus itself. The most common carpal instability adaptive
pa ern is secondary to a dorsally displaced distal radius malunion,
which will result in increased flexion of the midcarpal joint to reach
a neutral wrist position. The primary cause of this malalignment is
the radius deformity, and treatment should focus on correction of
the malunion, assuming the carpal malalignment is reducible and
not fixed.
Adaptive carpal malalignment can be secondary to a scaphoid
nonunion or humpback deformity, STT arthritis (erosion of the
distal scaphoid leads to its shortening with compensatory extension
of the proximal carpal row, especially with a type 1 lunate), and
Kienböck disease, where lunate collapse can lead to proximal
migration of the capitate and scaphoid flexion and pronation. The
etiology of the adaptive carpal instability should be identified and
corrected if possible.

Summary
Carpal instability is a complex disorder for which a myriad of
different types and causes exist. Having a detailed understanding of
carpal kinematics, anatomy, and analyzing carpal instability by its
chronicity, severity, etiology, location, direction, and pa ern can
help classify the diagnosis and aid in formulating a treatment plan.

Key Study Points

Carpal instability is a symptomatic condition involving abnormal carpal bone motion
during loading activities of the wrist.
Carpal instability dissociative is a disruption between bones of the same carpal row.
Scapholunate and lunotriquetral ligament injuries are the most common conditions
within this category.
Carpal instability nondissociative occurs when there is dysfunction between rows.
There are three types of CIND: radiocarpal, combined radiocarpal-midcarpal
 (proximal row), or midcarpal.
When carpal instability dissociative and CIND occur concomitantly, this is referred to
as carpal instability complex.
Treatment of carpal instability adaptive should be directed toward correcting the
underlying cause, when possible.

Acknowledgment
The authors would like to thank Sco Wolfe, MD, for his assistance
with the preparation of this chapter.

Annotated References
1. Larsen CF, Amadio PC, Gilula LA, Hodge JC: Analysis of carpal
instability: I. Description of the scheme. J Hand Surg Am
1995;20(5):757-764.
2. Kakar S, Wolfe SW: Carpal instability, in Wolfe SW, Hotchkiss
RN, Pederson C, Kozin S, Cohen M, eds: Green’s Operative Hand
Surgery, ed 8. Elsevier, Inc., 2021. This chapter details the
anatomy, biomechanics and types of carpal instability ranging
from their pathogenesis to treatment options.
3. Kitay A, Wolfe SW: Scapholunate instability: Current concepts in
diagnosis and management. J Hand Surg Am 2012;37(10):2175-
2196.
4. Rohman EM, Agel J, Putnam MD, Adams JE: Scapholunate
interosseous ligament injuries: A retrospective review of
treatment and outcomes in 82 wrists. J Hand Surg Am
2014;39(10):2020-2026.
5. Geissler WB: Arthroscopic management of scapholunate
instability. J Wrist Surg 2013;2(2):129-135.
6. Nathan R, Bla G: Rotary subluxation of the scaphoid. Revisited.
Hand Clin 2000;16(3):417-431.
7. Padmore CE, Stoesser H, Langohr GDG, Johnson JA, Suh N:
Carpal kinematics following sequential scapholunate ligament
sectioning. J Wrist Surg 2019;8(2):124-131. This cadaver sectioning
 study details the role of various carpal ligaments and notes the
importance of the scapholunate ligament as the primary stabilizer
of this joint as well as the function of the STT and
radioscaphocapitate ligaments.
8. Pérez AJ, Jethanandani RG, Vutescu ES, Meyers KN, Lee SK,
Wolfe SW: Role of ligament stabilizers of the proximal carpal row
in preventing dorsal intercalated segment instability: A cadaveric
study. J Bone Joint Surg Am 2019;101(15):1388-1396. This cadaver
study notes that in order to have extension of the lunate (DISI),
injury to the scapholunate ligament as well as another secondary
stabilizer ligament is required.
9. Short WH, Werner FW, Green JK, Masaoka S: Biomechanical
evaluation of ligamentous stabilizers of the scaphoid and lunate. J
Hand Surg Am 2002;27(6):991-1002.
10. Watson HK, Ballet FL: The SLAC wrist: Scapholunate advanced
collapse pa ern of degenerative arthritis. J Hand Surg Am
1984;9(3):358-365.
11. Watson HK, Ashmead D, Makhlouf MV: Examination of the
scaphoid. J Hand Surg Am 1988;13(5):657-660.
12. Lawand A, Foulkes GD: The “clenched pencil” view: A modified
clenched fist scapholunate stress view. J Hand Surg Am
2003;28(3):414-420.
13. Lee SK, Desai H, Silver B, Dhaliwal G, Paksima N: Comparison of
radiographic stress views for scapholunate dynamic instability in
a cadaver model. J Hand Surg Am 2011;36(7):1149-1157.
14. Mann FA, Wilson AJ, Gilula LA: Radiographic evaluation of the
wrist: What does the hand surgeon want to know? Radiology
1992;184(1):15-24.
15. Schimmerl-Me SM, Me VM, To erman SM, Mann FA, Gilula
LA: Radiologic measurement of the scapholunate joint:
Implications of biologic variation in scapholunate joint
morphology. J Hand Surg Am 1999;24(6): 1237-1244.
16. Braun N, Berger RA, Wolfe SW: Defining DISI and VISI. J Hand
Surg Eur Vol 2021;46(5):566-568. This article provides the rationale
 for and definitions of DISI and VISI.
17. Chan K, Vutescu ES, Wolfe SW, Lee SK: Radiographs detect
dorsal scaphoid translation in scapholunate dissociation. J Wrist
Surg 2019;8(3):186-191. This article describes methods of
evaluating dorsal translation of the proximal pole of the scaphoid
on the distal radius in chronic scapholunate instability. Level of
evidence: III.
18. Goelz L, Kim S, Güthoff C, et al: ACTION trial: A prospective
study on diagnostic accuracy of 4D CT for diagnosing Instable
ScaphOlunate DissociatioN. BMC Musculoskelet Disord
2021;22(1):84. In this prospective study, the authors describe the
role of four-dimensional CT scanning to detect early scapholunate
ligament injury.
19. Sulkers GS, Schep NW, Maas M, van der Horst CM, Goslings JC,
Strackee SD: The diagnostic accuracy of wrist cineradiography in
diagnosing scapholunate dissociation. J Hand Surg Eur Vol
2014;39(3):263-271.
20. Daunt N, Couzens GB, Cutbush K, Green J, Ross M: Accuracy of
magnetic resonance imaging of the wrist for clinically important
lesions of the major interosseous ligaments and triangular
fibrocartilage complex; correlation with radiocarpal arthroscopy.
Skeletal Radiol 2021;50(8):1605-1616. This study shows the excellent
correlation between MRI and arthroscopy in the diagnosis of
common soft-tissue disorders of the wrist.
21. Götestrand S, Björkman A, Björkman-Burtscher IM, et al:
Visualization of wrist ligaments with 3D and 2D magnetic
resonance imaging at 3 Tesla. Acta Radiol 2021;63(3): 368-375. The
authors compare the ability of three-dimensional versus two-
dimensional MRI in the assessment of wrist ligaments.
22. Andersson JK, Garcia-Elias M: Dorsal scapholunate ligament
injury: A classification of clinical forms. J Hand Surg Eur Vol
2013;38(2):165-169.
23. Burn MB, Sarkissian EJ, Yao J: Long-term outcomes for
arthroscopic thermal treatment for scapholunate ligament
 injuries. J Wrist Surg 2020;9(1):22-28. This prospective study
details the favorable outcomes of thermal shrinkage of low-grade
scapholunate ligament injuries with a minimum of 5 years of
follow-up. Level of evidence: IV.
24. Crespo Romero E, Arias Arias A, Domínguez Serrano D, et al:
Arthroscopic electrothermal collagen shrinkage for partial
scapholunate ligament tears, isolated or with associated
triangular fibrocartilage complex injuries: A prospective study.
Musculoskelet Surg 2020;105(2):189-194. This retrospective study
details the efficacy of thermal shrinkage in the management of
scapholunate or triangular fibrocartilage complex injuries.
25. Del Piñal F: Arthroscopic volar capsuloligamentous repair. J
Wrist Surg 2013;2(2):126-128.
26. Wahegaonkar AL, Mathoulin CL: Arthroscopic dorsal capsulo-
ligamentous repair in the treatment of chronic scapholunate
ligament tears. J Wrist Surg 2013;2(2): 141-148.
27. Megerle K, Bertel D, Germann G, Lehnhardt M, Hellmich S:
Long-term results of dorsal intercarpal ligament capsulodesis for
the treatment of chronic scapholunate instability. J Bone Joint Surg
Br 2012;94(12):1660-1665.
28. van Kampen RJ, Bayne CO, Moran SL: A new technique for volar
capsulodesis for isolated palmar scapholunate interosseous
ligament injuries: A cadaveric study and case report. J Wrist Surg
2015;4(4):239-245.
29. Gajendran VK, Peterson B, Slater RRJr, Szabo RM: Longterm
outcomes of dorsal intercarpal ligament capsulodesis for chronic
scapholunate dissociation. J Hand Surg Am 2007;32(9):1323-1333.
30. Szabo R: Dorsal intercarpal ligament capsulodesis, in AY S, ed.
Epub-Advances in Scapholunate Ligament Treatment. American
Society for Surgery of the Hand, 2014, pp. 84-96.
31. Brunelli GA, Brunelli GA: Carpal instability with scapholunate
dissociation treated using the flexor carpi radialis and scaphoid-
trapezoid ligament repair: Foundations, technique and results of
 preliminary series [French]. Rev Chir Orthop Reparatrice Appar Mot
2003;89(2):152-157.
32. Koehler SM, Guerra SM, Kim JM, Sakamoto S, Lovy AJ,
Hausman MR: Outcome of arthroscopic reduction association of
the scapholunate joint. J Hand Surg Eur Vol 2016;41(1):48-55.
33. Rosenwasser MP, Miyasajsa KC, Strauch RJ: The RASL
procedure: Reduction and association of the scaphoid and lunate
using the Herbert screw. Tech Hand Up Extrem Surg 1997;1(4):263-
272.
34. Lombardi J, Rodriguez R, Rosenwasser M: Reduction and
association of scaphoid and lunate for scapholunate instability, in
AY S, ed: Epub-Advances in Scapholunate Ligament Treatment.
American Society for Surgery of the Hand, 2014, pp 153-162.
35. Larson TB, Stern PJ: Reduction and association of the scaphoid
and lunate procedure: Short-term clinical and radiographic
outcomes. J Hand Surg Am 2014;39(11): 2168-2174.
36. Best GM, Mack ZE, Pichora DR, Crisco JJ, Kamal RN, Rainbow
MJ: Differences in the rotation axes of the scapholunate joint
during flexion-extension and radial-ulnar deviation motions. J
Hand Surg Am 2019;44(9):772-778. While assessing carpal motion
in healthy volunteers, this study demonstrates that there is no
fixed anatomic scapholunate axis during wrist motion.
37. Yao J, Zlotolow DA, Lee SK: ScaphoLunate Axis method. J Wrist
Surg 2016;5(1):59-66.
38. Ross M, Loveridge J, Cutbush K, Couzens G: Scapholunate
ligament reconstruction. J Wrist Surg 2013;2(2):110-115.
39. Henry M: Reconstruction of both volar and dorsal limbs of the
scapholunate interosseous ligament. J Hand Surg Am
2013;38(8):1625-1634.
40. Corella F, Del Cerro M, Ocampos M, Simon de Blas C,
Larrainzar-Garijo R: Arthroscopic scapholunate ligament
reconstruction, volar and dorsal reconstruction. Hand Clin
2017;33(4):687-707.
41. Ho PC, Wong CW, Tse WL: Arthroscopic-assisted combined
dorsal and volar scapholunate ligament reconstruction with
tendon graft for chronic SL instability. J Wrist Surg 2015;4(4):252-
263.
42. Kakar S, Logli AL, Ramazanian T, Gaston RG, Fowler JR:
Scapholunate ligament 360° procedure. Bone Joint J 2021;103-
B(5):939-945. This multicenter study details the short-term
favorable outcomes of the scapholunate 360° procedure,
emphasizing the importance of addressing the volar and dorsal
scapholunate ligaments, when injured and the need for longer
term follow-up. Level of evidence: III.
43. Kakar S, Greene RM, Denbeigh J, Van Wijnen A: Scapholunate
ligament internal Brace 360 tenodesis (SLITT) procedure: A
biomechanical study. J Wrist Surg 2019;8(3):250-254. This
biomechanical study shows that the addition of synthetic tape to
tendon graft in the scapholunate 360° procedure adds greater
construct stability than just tendon graft alone.
44. Kakar S, Greene RM: Scapholunate ligament internal Brace 360-
degree tenodesis (SLITT) procedure. J Wrist Surg 2018;7(4):336-
340.
45. Chee KG, Chin AY, Chew EM, Garcia-Elias M: Antipronation
spiral tenodesis—a surgical technique for the treatment of
perilunate instability. J Hand Surg Am 2012;37(12):2611-2618.
46. Sandow M, Fisher T: Anatomical anterior and posterior
reconstruction for scapholunate dissociation: Preliminary
outcome in ten patients. J Hand Surg Eur Vol 2020 ;45(4):389-395.
This study details the favorable outcomes of the ANAFAB
procedure in the short term in the management of chronic
scapholunate ligament injury. Level of evidence: IV.
47. Hom S, Ruby LK: A empted scapholunate arthrodesis for
chronic scapholunate dissociation. J Hand Surg Am 1991;16(2):334-
339.
48. O’Shaughnessy MA, Wagner ER, Berger RA, Kakar S: Buying
time: Long-term results of wrist denervation and time to repeat
 surgery. Hand (N Y) 2019;14(5):602-608. This retrospective study
details the outcomes of partial wrist denervation for myriad
chronic wrist disorders. Level of evidence: IV.
49. Garcia-Elias M, Lluch A, Ferreres A, PapiniZorli I, Rahimtoola
ZO: Treatment of radiocarpal degenerative osteoarthritis by
radioscapholunate arthrodesis and distal scaphoidectomy. J Hand
Surg Am 2005;30(1):8-15.
50. Traverso P, Wong A, Wollstein R, Carlson L, Ashmead D,
Watson HK: Ten-year minimum follow-up of 4-corner fusion for
SLAC and SNAC wrist. Hand (N Y) 2017;12(6): 568-572.
51. Kleinman WB: Physical examination of the wrist: Useful
provocative maneuvers. J Hand Surg Am 2015;40(7): 1486-1500.
52. Kakar S, Garcia-Elias M: The “Four-Leaf Clover” treatment
algorithm: A practical approach to manage disorders of the distal
radioulnar joint. J Hand Surg Am 2016;41(4): 551-564.
53. Meaike J, Meaike J, Kakar S. Outcomes following surgical
treatment of hamate arthrosis lunotriquetral ligament injuries.
Hand (N Y) 2021; September 22 [Epub ahead of print]. This study
reports the outcomes of 19 patients who underwent surgical
treatment of HALT lesions and noted improvement in Mayo Wrist
Scores from 54 to 71 and pain improvement. The study also
underscores the importance of other concomitant wrist injuries
with HALT lesions. Level of evidence: IV.
54. Viegas SF, Pa erson RM, Peterson PD, et al: Ulnar-sided
perilunate instability: An anatomic and biomechanic study. J
Hand Surg Am 1990;15(2):268-278.
55. Omokawa S, Fujitani R, Inada Y: Dorsal radiocarpal ligament
capsulodesis for chronic dynamic lunotriquetral instability. J Hand
Surg Am 2009;34(2):237-243.
56. Shin AY, Weinstein LP, Berger RA, Bishop AT: Treatment of
isolated injuries of the lunotriquetral ligament. A comparison of
arthrodesis, ligament reconstruction and ligament repair. J Bone
Joint Surg Br 2001;83(7):1023-1028.
57. Halikis MN, Colello-Abraham K, Taleisnik J: Radiolunate fusion.
The forgo en partial arthrodesis. Clin Orthop Relat Res
1997;341:30-35.
58. Dobyns JH, Linscheid RL, Macksoud W: Proximal carpal row
instability nondissociative. Orthop Trans 1985;9:574.
59. Wright TW, Dobyns JH, Linscheid RL, Macksoud W, Siegert J:
Carpal instability non-dissociative. J Hand Surg Br 1994;19(6):763-
773.
60. Rayhack JM, Linscheid RL, Dobyns JH, Smith JH: Pos raumatic
ulnar translation of the carpus. J Hand Surg Am 1987;12(2):180-189.
61. Mulders MAM, Sulkers GSI, Videler AJ, Strackee SD, Smeulders
MJC: Long-term functional results of a wrist exercise program for
patients with palmar midcarpal instability. J Wrist Surg
2018;7(3):211-218.
62. Shiga SA, Werner FW, Garcia-Elias M, Harley BJ: Biomechanical
analysis of palmar midcarpal instability and treatment by partial
wrist arthrodesis. J Hand Surg Am 2018;43(4):331-338.e2.
63. Louis DS, Hankin FM, Greene TL, Braunstein EM, White SJ:
Central carpal instability-capitate lunate instability pa ern:
Diagnosis by dynamic displacement. Orthopedics 1984;7(11):1693-
1696.
64. Overstraeten LV, Camus EJ, Wahegaonkar A, et al: Anatomical
description of the dorsal capsulo-scapholunate septum (DCSS)—
Arthroscopic staging of scapholunate instability after DCSS
sectioning. J Wrist Surg 2013;2(2):149-154.
65. Johnson RP, Carrera GF: Chronic capitolunate instability. J Bone
Joint Surg Am 1986;68(8):1164-1176.
66. Wickramasinghe NR, Duckworth AD, Clement ND, Hageman
MG, McQueen MM, Ring D: Acute median neuropathy and carpal
tunnel release in perilunate injuries. Can we predict who gets a
median neuropathy? J Hand Microsurg 2015;7(2):237-240.
67. Herzberg G, Comtet JJ, Linscheid RL, Amadio PC, Cooney WP,
Stalder J: Perilunate dislocations and fracturedislocations: A
multicenter study. J Hand Surg Am 1993;18(5):768-779.
68. Minami A, Kaneda K: Repair and/or reconstruction of
scapholunate interosseous ligament in lunate and perilunate
dislocations. J Hand Surg Am 1993;18(6):1099-1106.
69. Trumble T, Verheyden J: Treatment of isolated perilunate and
lunate dislocations with combined dorsal and volar approach and
intraosseous cerclage wire. J Hand Surg Am 2004;29(3):412-417.
70. Krief E, Appy-Fedida B, Rotari V, David E, Mertl P, MaesClavier
C: Results of perilunate dislocations and perilunate fracture
dislocations with a minimum 15-year follow-up. J Hand Surg Am
2015;40(11):2191-2197.
71. Cheng CY, Hsu KY, Tseng IC, Shih HN: Concurrent scaphoid
fracture with scapholunate ligament rupture. Acta Orthop Belg
2004;70(5):485-491.
72. Oh WT, Choi YR, Kang HJ, Koh IH, Lim KH: Comparative
outcome analysis of arthroscopic-assisted versus open reduction
and fixation of trans-scaphoid perilunate fracture dislocations.
Arthroscopy 2017;33(1):92-100.
73. Yuan BJ, Dennison DG, Elhassan BT, Kakar S: Outcomes after
radiocarpal dislocation: A retrospective review. Hand (N Y)
2015;10(3):367-373.
74. Shannon SF, Boe CC, Shin AY: Comparison of outcomes between
axial radial and axial ulnar carpal injuries. J Hand Surg Eur Vol
2018;43(7):712-717.
C H AP T E R 3 7

Tendon Injuries and

Tendinopathies of the Hand and
Wrist
Kendrick Au MD, MSc, Nina Suh MD, FAAOS

Dr. Suh or an immediate family member serves as a paid consultant to or is an employee of Shire.
Neither Dr. Au nor any immediate family member has received anything of value from or has
stock or stock options held in a commercial company or institution related directly or indirectly to
the subject of this chapter.

ABSTRACT
Tendon injuries of the hand and wrist can be challenging for
surgeons, therapists, and patients. Recent advancements in surgical
technique, surgical materials, anesthesia, and postoperative
protocols have helped improve patient outcomes. Research
continues to focus on maximizing tendon strength and gliding to
maximize early motion for all types of tendon injuries. Despite
these evolutions, patients should be counseled on the challenging
rehabilitation process and imperfect functional results.
Tendinopathies of the hand and wrist involve tenosynovitis of the
six extensor compartments and stenosing flexor tenosynovitis.
These pathologies are often distinguished on a thorough history
and physical examination. They generally follow a similar course of
treatment, as recent literature continues to provide guidance for
optimizing nonsurgical and surgical modalities.
Keywords: early active motion; extensor tendon injuries; flexor
tendon repair; tendinopathies

Introduction
Tendon injuries and tendinopathies of the hand and wrist
encompass a wide spectrum of pathologies of both the flexor and
extensor tendons. Flexor and extensor tendon injuries typically
involve a traumatic mechanism that can occur in the presence of a
laceration or avulsion. These injuries are often managed surgically
and do pose specific challenges given the intricate anatomic and
biomechanical considerations. In contrast, tendinopathies of the
hand and wrist are often from overuse or inflammatory origins.
These conditions can often be successfully managed nonsurgically,
with surgical release reserved for patients refractory to nonsurgical
measures.

Flexor Tendon Injury

Pathology and Anatomy

The hand contains a total of nine finger flexor tendons: four flexor
digitorum superficialis (FDS) tendons, four flexor digitorum
profundus (FDP) tendons, and one flexor pollicis longus tendon.
The FDS muscle has two heads and originates from the anterior
aspect of the medial epicondyle. At the level of the midforearm, the
FDS muscle divides to send a deep layer of tendons to the li le and
index fingers and a superficial layer of tendons to the long and ring
fingers. Approaching the insertion on the base of the middle
phalanx, the FDS tendon dives deep to the FDP tendon as it splits
into a radial and ulnar slip at the Camper chiasm. The FDP muscle
arises from the volar and medial aspects of the proximal ulna and
interosseous membrane. It travels in the deepest aspect of the
forearm to a ach to the proximal aspect of the distal phalanx. The
flexor pollicis longus tendon originates from the volar aspect of the
middle third of the radial shaft and lateral interosseous membrane
and a aches at the proximal aspect of the distal phalanx of the
thumb. All nine tendons pass through the carpal tunnel in a
consistent topography. The FDS tendons to the ring and long
fingers are the most superficial, followed by the FDS tendons to the
li le and index fingers. Immediately beneath them, the FDP and
flexor pollicis longus tendons will be found.
The pulley mechanism of the flexor tendon sheath aids in flexor
tendon excursion and efficiency. It is composed of five annular
pulleys and three cruciate pulleys. The annular pulleys are stiffer
and ensure the intimate contact between tendon and the
underlying bone is preserved. Recent literature has further
supported the existence of an A0 pulley located just proximal to the
A1 pulley, composed of transverse fascicular fibers of the palmar
aponeurosis, that can be a source of persistent triggering after an
A1 pulley release. 1 The thumb pulley system is arranged in a
similar fashion, classically containing an A1, A2, and oblique (A0)
pulley.
As knowledge of flexor tendon anatomy has evolved, this has
facilitated a distinction of five anatomic zones (I through V) for the
fingers and three (I through III) for the thumb (Figure 1).
Classically zone II has been labeled “no man’s land.” However,
anatomic considerations and technique evolutions have challenged
the historically poor results of repair in this zone.
 Figure 1 Illustration showing the location of the flexor tendon zones in the
thumb (A) and fingers (B).(From Klifto CS, Capo JT, Sapienza A, Yang SS,
Paksima N: Flexor tendon injuries. J Am Acad Orthop Surg 2015;26[2]:e26-e35,
Figure 2B. https://journals.lww.com/jaaos/pages/default.aspx.)

Diagnostic Evaluation
The evaluation of a flexor tendon injury should start with a
thorough history and physical examination. Careful inspection of
patients with a flexor tendon injury may reveal a penetrating wound
and loss of the inherent tone of the tendon. This may manifest in
the loss of the normal cascade of the hand, with the injured digit
assuming a more extended posture. In this circumstance, there may
be an absence of the tenodesis effect of digital flexion with wrist
extension. When a empting to narrow the diagnosis of tendon
injury, the examiner should also isolate each individual tendon
during examination. To isolate the FDS tendon, the adjacent digits
are held in an extended position while active proximal
interphalangeal (PIP) joint flexion is evaluated. During this
maneuver, FDP function is effectively blocked as it originates from
a common muscle belly. Meanwhile, FDP integrity is evaluated by
stabilizing the middle phalanx in extension while distal
interphalangeal (DIP) joint flexion is a empted.
 Accompanying an examination of each individual tendon, a
thorough neurovascular examination should always be performed.
The close proximity of the neurovascular bundle puts it at risk in
the presence of a flexor tendon injury. A neurologic examination
using light touch, static two-point discrimination, and/or
monofilament testing is preferred. Capillary refill of the volar
digital pulp and nail bed can be used to assess vascularity. A digital
Allen test, Doppler examination, or pulse oximetry can also be
performed.
For zone I flexor tendon injuries, radiographs are typically
obtained to assess for the presence and location of a bony avulsion
injury to the distal phalanx.

Tendon Repair
The objectives of flexor tendon repair are to promote intrinsic
healing potential, maximize strength, and ensure tendon glide to
allow for early active motion to limit adhesion formation. There
should be less than 3 mm of gapping at the repair site and the
tendon should have well-coapted ends. Apart from these factors,
many surgical techniques and materials can be used to bolster the
strength and glide of the tendon depending on location of injury
and tissue quality.

Zone I
Injury to the FDP tendon can occur from either a laceration or
avulsion in this area. An avulsion injury is often referred to as a
jersey finger and generally results from a hyperextension
mechanism of the DIP joint. The Leddy and Packer classification is
commonly used to describe five pa erns of FDP avulsion (Figure 2).
Type I injuries are the most urgent, as the FDP tendon retracts into
the palm and the vincular blood supply of the tendon has been
disrupted. These injuries should typically be addressed within 10
days of injury because the tendon can undergo necrosis and
myostatic contracture. 2 Type II injuries have a small fleck of bone
accompanying an FDP avulsion, with tendon retraction to the level
of the PIP joint. In type III injuries, there is a large bone fragment
a ached to the FDP tendon stump that prevents retraction
proximal to the A4 pulley. Type IV and V injuries were added to the
original classification and describe a separation of the FDP tendon
from a bony avulsion fragment and a bony avulsion of FDP with a
distal phalanx fracture, respectively. Early exploration of these
injuries is often advocated because it can be a challenge to
distinguish certain types clinically. However, type II injuries, for
example, have been shown to have good outcomes even when
repaired 3 months after injury. 2
 Figure 2 Schematic illustration showing the Leddy and Packer classification of
zone I flexor tendon injuries.PIP = proximal interphalangeal, VBP = vinculum
brevis profundus, VLP = vinculum longum to the profundus tendon.(From
Ruchelsman DE, Christoforou D, Wasserman B, Lee SK, Rettig ME: Avulsion
injuries of the flexor digitorum profundus tendon. J Am Acad Orthop Surg
2011;19[3]:152-162, Figure 3.
https://journals.lww.com/jaaos/pages/default.aspx.)

Although it is possible to have an intratendinous rupture

enabling an end-to-end repair, avulsion injuries are far more
common and require tendon-to-bone reduction. Purely tendinous
injuries (types I and II) can be fixed with either a pullout bu on
technique, suture anchors, or suturing over a bone bridge.
Classically, the pullout bu on technique is used and involves core
suture placement with the free ends of the suture being passed
through the distal phalanx and tied over a sterile bu on on the
dorsum fingernail. The disadvantages of the pullout bu on
construct are the external sutures, nail plate deformity, and higher
infection rate. The use of a bone suture anchor offers an alternative
that may avoid the associated morbidity associated with the pullout
bu on construct. Clear clinical superiority has not been
demonstrated between techniques; however, patients receiving
suture anchors have shown to have a quicker return to work. 3
Types III through V injuries are less common but are generally
managed with open reduction and fixation of the bony fragment. In
type IV injuries, the tendon is typically repaired to bone after
fixation. Occasionally a dorsal blocking pin may be required to
maintain joint congruity.

Zone II
Traditionally repair of tendons in zone II have resulted in poor
results. However, changes in surgical technique and postoperative
motion protocols have dramatically changed outcomes over the
past few decades. Modern surgical principles are anchored in
maximizing tendon strength to prevent tendon gap formation while
allowing for tendon glide to achieve early active motion. Many
clinical decisions and technical factors play an additional role in
building strength within a tendon repair. The most studied aspect
has been suture technique, with studies to support that a minimum
of four core sutures should be used to allow for early active motion.
4
There have been many applied techniques to execute four core
suture repairs without consensus of a superior technique.
Techniques using more than four core sutures have also been
described, and although these repairs have superior biomechanical
strength, these techniques may require more tissue handling,
increased knot burden, and meticulous placement of suture.
Regardless of the suture strategy, ensuring that suture purchase is
between 7 and 10 mm from the tendon edge, there is a sufficiently
sized lock (2 mm in diameter, if used), there is adequate tensioning
(10% tendon shortening), and at least 3 knots are thrown for most
sutures will also effectively improve repair strength. 5 , 6 Typically, 3-
0 and 4-0 suture diameter is the most commonly used. In cyclic
loading and linear testing 3-0 suture has been shown to be stronger
and as such are generally recommended. 7
 In an a empt to mitigate suture pull-through, a mesh suture
design has recently been studied. It is composed of multiple
polypropylene filaments, and the open braid design allows for a
larger suture diameter that collapses on tying, which creates a
smaller strand and lower knot profile. According to a 2019 study,
mesh repairs had a significantly higher yield and ultimate force
required for gap formation in cadaver testing compared with
braided poly-blend suture. 8 Peripheral epitendinous repairs have
been shown to increase strength and reduce gapping to core suture
techniques. However, if a strong multistrand repair is achieved,
some surgeons have gone without supplemental peripheral
augmentation, with positive results indicating it may not be as
critical to tendon repair as previously thought. 9
Tendon glide after flexor tendon repair can be affected by the
major annular pulleys (A2 and A4) and the FDS tendon. In recent
years, it has been understood that the A2 pulley can be released up
to two-thirds of its length and the A4 can be released entirely
without causing clinically significant bowstringing. Recent cadaver
research has shown that FDP repairs between the A2 and A4 pulley
will slide proximally under the A2 pulley with full active flexion,
suggesting A2 pulley venting will be required in these
circumstances. The length between the repair and A4 pulley can be
used as a guide to the amount of venting of the A2 pulley required
for tendon glide. 10 In addition, to reduce the diameter of contents
passing through the pulleys, some studies have suggested resecting
a slip of the FDS tendon or only repairing one slip of FDS in the
event of a complete laceration. 11 , 12
Once the repair is completed it is important to evaluate the
quality and glide of the repair. This can be done at three separate
points when going from full extension to flexion. In full extension
the repaired tendon is evaluated for any visible gap formation.
Next, as the finger is brought into midflexion, the tendon is
examined to ensure adequate glide is achieved. Last, the finger is
brought into full flexion to confirm that the repair does not cluster
along the pulleys and venting is sufficient. 12

Tendon Reconstruction
In a delayed presentation of a flexor tendon injury without tendon
retraction, primary repair and satisfactory clinical outcomes may
still be achieved. However, in the event of dramatic tissue loss from
trauma, neglected tendinous injury involving tendon retraction, or
failed tendon repair, primary end-to-end repair of the tendon is
generally not possible. 13 Heroic efforts to complete an end-to-end
repair may risk contracture and quadriga; therefore, tendon
reconstruction should be considered. Reconstruction can be
accomplished as a single-stage or two-stage procedure, with options
of intrasynovial or extrasynovial donor tendons. Prior to proceeding
with tendon reconstruction, careful preoperative planning to
evaluate for tendon availability and length requirements is needed.
The finger should also be supple and free of contracture. When the
reconstruction involves an isolated FDP tendon, the intact FDS
tendon should not be sacrificed as a donor. The functional
satisfaction of an FDS-only finger should be discussed with the
patient prior to undertaking the complex process of a tendon
reconstruction.
Single-stage reconstruction is a viable option in scenarios with a
substantial loss of flexor tendon tissue but with preservation of
pulley system and tendon sheath. Staged tendon grafting is more
commonly used and allows for the management of concomitant
injuries to the surrounding structures such as the pulley system,
bone, skin, and neurovascular structures. Under these conditions, a
silicone spacer is affixed to the distal and proximal ends of the
remaining tendon to create a sufficient space and path within the
tendon sheath to allow for eventual passage of a tendon graft
during the second stage. As part of the first stage, the A2 and A4
pulleys are typically reconstructed using a graft belt loop
reconstruction or shoelace reconstruction. 14 Generally, it is advised
to wait 6 to 8 weeks prior to commencing the second stage to allow
for a formation of a pseudosheath and to regain range of motion
prior to grafting. Extrasynovial grafts are commonly used for both
immediate or staged reconstruction and include palmaris longus,
extensor digiti minimi, and extensor indicis proprius. Traditionally,
a Pulvertaft weave technique has been used for the suture
technique in combining the graft to the remaining tendon. It offers
sufficient strength and stiffness, but does require ample length of
donor tendon and considerable diameter of both tendons and
results in a relatively bulky repair. Side-to-side suture techniques
have been introduced as an alternative method to mitigate some of
the challenges with the Pulvertaft weave. There have been various
described methods of tendon and suture configuration with the
side-to-side technique, but proponents of this technique advocate
for its simplicity compared with the Pulvertaft weave. Recent
biomechanical studies have also shown that the side-to-side
techniques demonstrated a higher load to failure and less bulkiness
when compared with the Pulvertaft technique. 15 , 16

Rehabilitation
The advancements in tendon repair have afforded rehabilitation to
begin within days after repair completion. The benefits of early
motion have subsequently been supported in the literature,
showing increasing tendon repair site strength and excursion. 17
Early motion enhances the restoration of the flexion-extension arc
and total active motion. To date, there have been various active
motion protocols implemented that range from place and hold
techniques to true active flexion. A 2019 systematic review
demonstrated that the place and hold exercises provided be er
outcomes than passive flexion protocols, but there currently is
insufficient evidence to recommend a specific active protocol. 17
Complications of tendon repair can include tendon adhesions,
which can be a major factor in the plateau of motion recovery after
tendon repair. Tenolysis may be beneficial, but it should only be
a empted after at least 3 months following repair and after a
thorough trial of appropriate hand therapy. The technical tips
described earlier are the best guard against re-rupture of the repair
site. However, if re-rupture is encountered up to 3 weeks
postoperatively, repeat repair can be a empted. If it occurs outside
the 3-week window, the success of a repeat repair is less
predictable, and the surgeon should be prepared for reconstructive
options.

Extensor Tendon Injuries

Pathophysiology and Anatomy

The extrinsic extensor muscles originate in the forearm and are
divided into superficial and deep muscular components. The
superficial group includes the extensor carpi radialis longus, the
extensor carpi radialis brevis, the extensor digitorum communis,
the extensor digiti minimi, and the extensor carpi ulnaris (ECU).
The deep group is composed of the abductor pollicis longus (APL),
the extensor pollicis brevis (EPB), the extensor pollicis longus, and
the extensor indicis proprius. At the level of the wrist, the extrinsic
extensor tendons travel through six dorsal compartments on the
way to the dorsal hand. At this level, the extrinsic tendons that
cross the wrist are responsible for wrist extension. After the
tendons course through these fibro-osseous tunnels, they become
more superficial and fla er. The complexity increases distally
whereby the intrinsic muscles (lumbricals and interosseous
muscles) coalesce into the extensor mechanism. The extrinsic
tendons traverse the metacarpophalangeal (MCP) joint dorsally and
are responsible for MCP extension. However, transverse fibers of
the interossei travel volar to the MCP joint axis and are primarily
responsible for MCP joint flexion. At the level of the PIP joint, the
common extensor tendon trifurcates into two lateral bands and a
central slip, whereas the intrinsic muscles also swing inward and
contribute to both tributaries. The central slip inserts at the base of
the middle phalanx to extend the PIP joint. The lateral bands merge
with slips from the intrinsic muscles to form the conjoined lateral
bands, which coalesce to form the terminal tendon, inserting at the
distal phalanx. The terminal tendon is responsible for DIP joint
extension. The knowledge of this complex system can help with
understanding diagnoses, treatment, and rehabilitation for these
injuries. To help easily identify and guide treatment of these
injuries, the extensor mechanism can be divided into eight zones
along its course (Figure 3).
 Figure 3 Photograph shows the extensor tendon zones of injury.(Reproduced
from Desai MJ, Wanner JP, Lee DH, Gauger EM: Failed extensor tendon repairs:
extensor tenolysis and reconstruction. J Am Acad Orthop Surg 2019;27[15]:563-
574, https://journals.lww.com/jaaos/pages/default.aspx.)

Diagnosis and Evaluation

Similar to flexor tendon injuries, suspected extensor tendon injuries
should start with a thorough examination. Open wounds should be
evaluated for the size and location of wounds, the resting cascade of
the hand should be inspected for loss of posture, and a
neurovascular examination should be completed. In patients with a
terminal tendon disruption, the DIP is often found in obligate
flexion, whereas the PIP may have compensatory hyperextension.
Extensor lag of the affected digit may also be noticed in digits at all
levels. Wrist and digital motion should also be included in the
evaluation, with assessment of each extensor tendon individually so
that the juncturae tendinum do not mask an injury. The Elson test
is a common special test that is often used in the diagnosis of
central slip injuries. The PIP joint is placed in a flexed position,
often over the edge of a table, and the patient is asked to extend the
PIP joint of the involved finger against resistance. A central slip
injury is inferred in the absence of PIP extension with
compensatory hyperextension of the DIP, as the intact lateral bands
overexert extension force on the DIP joint when a empting to
extend the affected digit.
Radiographs of the affected digit can be obtained if osseous
injury is suspected. Both static and dynamic ultrasonography may
also be used as a clinical adjunct for equivocal examinations. 18

Treatment
Treatment of extensor tendons generally is guided by the zone of
injury but has three main overarching treatment strategies:
nonsurgical management with splinting, primary repair, or tendon
grafts.

Zone 1
This injury is often caused by a sudden forced flexion of the
extended DIP joint. This results in disruption of the terminal
tendon, frequently referred to as a mallet finger. This injury has
been classified into four main types (Table 1) to help guide
management. Type I injuries can be managed nonsurgically with an
extension-based splint for 6 to 8 weeks followed by gentle active
flexion range of motion and a period of nigh ime spli ing.
Although there are a variety of splints, the evidence would suggest
that patient compliance may be the most important factor for a
good outcome. A 2021 study evaluating 26 consecutive patients with
type I mallet finger injuries showed compliance was only 65.4%
even with a comprehensive instructed splinting regimen for each
patient, highlighting the challenge for this treatment for patients. 19
Type II injuries are considered open injuries and can be managed
with primary repair with figure-of-8 sutures through the tendon or
dermatotenodesis depending on the amount of distal tendon
available. Subsequently the patient’s finger can be placed in an
extension-based splint until the repair is stable. Type III injuries
generally require coverage and because of the tendon substance
loss often require a tendon graft. Type IV injuries either can be
managed with closed reduction and splinting or may require
Kirschner wire fixation and splinting depending on the articular
involvement and stability of the joint. A 2020 randomized clinical
trial evaluating bony mallet injury involving more than one-third of
the joint without subluxation randomized patients to either
nonsurgical management versus extension-block pinning. 20 A total
of 28 patients completed the protocol. No significant difference was
found in active extension lag or patient-reported outcomes. A
slightly improved arc of motion was found in the splinting group;
however, secondary subluxation developed in three patients in this
group, highlighting the potential for secondary subluxation with
the splinting group and the need for close radiographic follow-up if
that treatment pathway is selected. 20

Table 1
Doyle Classification of Mallet Finger Injuries

Type Description
I Closed injury ± small dorsal avulsion fracture
II Open injury (laceration)
III Open injury involving skin and tendon substance
IV Mallet finger
A: Distal phalanx physeal injury (pediatric)
B: Fracture involving 20%-50% of articular surface (adult)
C: Fracture involves >50% articular surface (adult)
Reproduced with permission from Wolfe SW, Hotchkiss RN, Pederson WC, Kozin SH:
Green’s Operative Hand Surgery, ed 6. Elsevier Inc, 2010.

Zone 2
Zone 2 injuries occur in the interval between the DIP and PIP
joints. Often these injuries occur from either a crush injury or
laceration. In general, lacerations involving less than 50% of the
tendon can be managed with splinting and active motion therapy,
whereas primary suture repair is recommended for tendon
lacerations greater than 50%.

Zone 3
Zone 3 injuries occur at the level of the PIP joint, resulting in a
central slip injury. This injury can produce a boutonnière
deformity: loss of extension at the PIP joint with hyperextension at
the DIP. The Elson test as mentioned previously is an examination
to assist in the diagnosis of this injury type. In general, patients
with closed injuries in this zone can be treated with splinting of the
PIP in extension for 3 to 6 weeks while leaving the surrounding
joints mobile, followed by 6 weeks of nigh ime splinting. Flexion
exercises of the DIP joint can aid in correction of the boutonnière
deformity because it can tighten the triangular ligament and help
draw the lateral bands dorsal, correcting the deforming force at the
PIP joint. Relative motion flexion orthosis has also been discussed
in the correction of the boutonnière deformity from a central slip
injury, although comparable outcome studies have yet to be
published. The splint keeps the MCP joint flexed, loosening the
intrinsic lateral band tightness and allowing them to migrate
dorsal. The lateral slips from the long extensors typically tighten
with MCP flexion and pull the lateral bands dorsally. 21
Acute surgical indications of zone 3 injuries are limited but
include displaced, irreducible avulsion fractures of the middle
phalanx and an unstable PIP joint with loss of extension. Even in
open injuries, as the proximal tendon edge typically does not
retract, a trial of splinting initially can be implemented.

Zone 4
Injuries between the PIP and MCP are managed based on the
ability to extend on physical examination. Those that do not have
extension deficits can be splinted with the PIP joint in extension
after soft-tissue management. If an extension deficit is detected,
then surgical repair of the tendon should be considered. The
patient’s finger should be splinted in extension to protect the repair
for 3 weeks.

Zone 5
Management strategy for zone 5 injuries depend on whether the
injury is closed, open, or from a bite wound. Closed injuries may be
placed in an MCP-based extension splint for 4 to 6 weeks until the
tendon is healed. However, tendons with more than 50% laceration
should be repaired to restore extension strength. If an injury to the
sagi al bands is encountered, it should be repaired to help restore
extensor digitorum communis stability and prevent subluxation.
Patients with bite injuries should have a thorough débridement and
washout prior to tendon repair. Because the digit is usually in
flexion at the time of injury, the tendon end is often more proximal
in the wound.

Zone 6
The diagnosis of extensor tendon injuries in this zone can be
challenging as the juncturae tendinum may allow for digit
extension even with complete laceration of the extensor tendon. As
the tendons move more proximal, they become thicker and
amenable to core and epitenon suturing techniques, if primary
repair is possible. Because these tendons do function as if quadrigia
is present, the surgeon should take care not to overtighten or
excessively shorten the tendon as it may affect tendon excursion.

Zone 7
At this level, injuries can involve multiple tendons as they converge
at the wrist. Care must be taken to leave a portion intact or repair
the retinaculum to protect against bowstringing. Unique to this
zone is the subluxation of the ECU in the context of closed
traumatic rupture of the sixth dorsal compartment. In the event of
painful, symptomatic subluxation, a new compartment can be
fashioned using a portion of the extensor retinaculum. Moreover,
nontraumatic rupture at this level can also occur, particularly to the
extensor pollicis longus tendon from prior distal radius fractures
(usually nondisplaced). Extensor indicis proprius tendon transfer is
usually the most suitable option for reconstruction, as the
a ritional wear of the tendon prohibits primary repair.

Zone 8
Injuries at this level can present a challenge to repair as it is close
to the muscle-tendon junction. The proximal tendon origin often
needs to be located in the intramuscular belly to support core
suture repair in the proximal end of the injury. In the case of
multiple tendon lacerations, restoration of independent thumb and
wrist extension should be prioritized.
Tendon Reconstruction
Although the extensor tendon anatomy does not have a tendon
sheath as does the flexor tendon system, it does have additional
anatomic considerations of its own. As the tendons travel distally,
they become quite thin and flat, susceptible to suture pullout. The
excursion of the extensor tendon in more distal zones is also quite
limited with only 1 to 2 mm in the terminal tendon and a 1-mm gap
in zones 1 through 5, leading to 20° of extension loss. 22 Because the
extensor tendons are quite superficial in nature, they can be
vulnerable to soft-tissue injury and segmental tendon loss often
accompanying dorsal hand trauma. In general, tendon
reconstructive options can be broadly divided into three categories:
intercalary grafting (autograft or allograft), local tissue
reconstruction, and free tissue transfer (composite grafts). Tendon
transfers are also an option in certain circumstances.
In zone 1, the terminal tendon can be reconstructed using local
tissue from a hemilateral band technique whereby a distally based
flap is created from each lateral band that is then sutured to the
distal residual digit of the terminal tendon. 23 Other options using
intercalary tendon graft typically involve the use of palmaris
longus. Multiple techniques have been described, commonly
suturing to the terminal tendon or passing through drill tunnels.
Similarly, the palmaris longus can also be used as a primary
tendon graft in zone 3 injuries. In a 2019 study, 17 patients were
retrospectively reviewed with open zone 3 injuries. These injuries
were managed with débridement, primary tendon graft (palmaris
longus or a strip of ipsilateral flexor carpi radialis), and soft-tissue
coverage (if required), with immediate short arc motion therapy.
Mean range of motion was 75° at the PIP joint, with 10 patients
achieving an excellent outcome. 24 When soft-tissue loss is
combined with extensor tendon tissue loss, soft-tissue coverage is
often required. Recent evidence suggests immediate reconstruction
of the tendon with single-staged flaps had fewer surgical
procedures, faster return to maximum range of motion, and a
greater likelihood of return to work. 25

Rehabilitation
Although there is a general consensus that early active motion
appears to lead to earlier return to function and mobility, it is
unclear in the current literature which orthotic device is superior in
facilitating active motion. A 2021 international inquiry survey of
hand therapy for zone V and VI injuries found that of 992
individual responses, 83% used a program with early active motion
with only 8% using early passive motion and 7% using
immobilization. 26 The two most commonly used methods for early
active motion were relative motion extension (43%) and
palmar/interphalangeal joints free (25%), with the relative motion
extension orthosis preferred for earlier recovery of hand function
and motion. The relative motion flexion splint keeps the affected
tendon of the injured digit in 15° to 20° less relative motion than
the adjacent tendons from a shared muscle. As such, it experiences
less force regardless of the position of the digit from full extension
to full flexion, in effect, relaxing the repair regardless of the MCP
and interphalangeal joint positions. A 2020 randomized clinical
trial comparing early active motion programs in 42 patients with
zones V to VI extensor tendon repairs showed that patients using a
relative motion extension orthosis had be er early hand function,
total active motion, and orthosis satisfaction compared with
controlled active motion with a static wrist-hand-finger orthosis. 27

Extensor Tendinopathies

de Quervain Tenosynovitis
de Quervain tenosynovitis is a common tendinopathy involving the
first dorsal extensor compartment. This compartment is located on
the most radial aspect of the distal radius with the contents of the
APL and EPB tendons within the fibro-osseous tunnel. However,
anatomic variations exist as the APL tendon may have multiple
slips and/or the EPB tendon may be within a separate
subcompartment. In a 2019 study evaluating the anatomy of 130
patients undergoing first dorsal compartment release for de
Quervain tenosynovitis, the study authors identified multiple (one
to four) slips of APL in 78% of patients, whereas 55% of patients
had a subcompartment for EPB, and 8% had three
subcompartments. 28 Branches of the superficial radial nerve are
also often encountered during surgical release; in 61% of patients in
the aforementioned study at least one branch was encountered in
the incision. Those who are affected by de Quervain tenosynovitis
have shown to have tendon sheaths up to five times thicker with
accumulation of mucopolysaccharides and increased vascularity,
because of a myxoid degeneration process rather than acute
inflammation.
Diagnosis is generally achieved from the clinical history and
physical examination. Patients present with complaints of radial-
sided wrist pain that is exacerbated by thumb motion or radial and
ulnar deviation of the wrist. There is often swelling in the vicinity of
the radial styloid and tenderness with palpation along the first
extensor compartment. The Eichhoff and Finkelstein maneuvers
have been described as special examinations to confirm the
diagnosis of de Quervain tenosynovitis. The Eichhoff maneuver is
performed by asking the patient to gently grasp the thumb in the
palm while the wrist is ulnarly deviated by the examiner. Pain over
the first compartment region is considered a positive finding. The
Finkelstein maneuver involves passive flexion of the thumb with
ulnar deviation of the wrist. The Finkelstein test has been shown to
have higher specificity and produced fewer false-positive results,
causing less discomfort for patients. 29 The wrist hyperflexion and
abduction of the thumb maneuver has been described as an
additional diagnostic tool and found to have be er sensitivity (0.99
versus 0.89) and specificity (0.28 versus 0.14) than the Eichhoff test
alone. 30 The test reproduces the patient’s symptoms with resisted
thumb abduction in a maximally flexed wrist. Radiographs are often
performed during the course of investigation for de Quervain
tenosynovitis; they can be helpful to identify concurrent pathology
but have not been shown to alter the course of treatment.
The initial management of de Quervain tenosynovitis starts with
activity modification, a short course of immobilization, hand
therapy, and NSAIDs. Corticosteroid injections into the tendon
sheath of the first dorsal compartment are often combined with the
aforementioned modalities. A prospective study of 49 patients with
de Quervain tendinopathy receiving a single corticosteroid injection
found that 82% of patients were symptom free for the first 6 weeks,
and more than 50% were without symptoms at the 1-year mark. 31 A
cohort found that 73.4% of patients experienced sufficient symptom
relief within 2 injections. 32 A 2020 prospective randomized trial of
20 patients showed that combining immobilization (thumb spica
cast or splint for 3 weeks) with corticosteroid injections did not
contribute to improved patient outcomes. 33 However, a similar
prospective study of 67 patients found 3 weeks of thumb spica cast
wear combined with corticosteroid injection had a larger
improvement in pain scores and functional ability, compared with
corticosteroid alone. 34 When looking at the utility of multiple
injections, a 2021 national database study of 33,420 patients with de
Quervain tenosynovitis found that a single injection was successful
in 71.6% of patients, with 19.7% receiving a repeat injection. A
second injection had a 66.3% success rate and a third injection was
successful in 60.5% of patients, suggesting a possible benefit to
repeat injections. The study authors found a higher success rate in
patients with diabetes than those without diabetes, but the rate was
only 2%. 35 Risks associated with corticosteroid injection included
skin pigmentation and atrophy, tendon rupture, and transient
elevation in blood glucose.
If patients continue to have symptoms after nonsurgical
management, surgical release of the first compartment is
considered. The patient should be counseled regarding the
possibility of prolonged recovery, incomplete resolution of
symptoms, and numbness in the superficial radial nerve
distribution. After an incision is made over the first compartment,
care is taken to protect any superficial branches of the radial nerve
or lateral antebrachial cutaneous nerves. The sheath of the first
compartment should be released on the dorsal aspect of the first
extensor compartment to limit the possibility of volar tendon
subluxation. The surgeon should also be vigilant to evaluate for a
separate septum of the EPB tendon and release if encountered.
Early movement to promote tendon gliding should be encouraged.
In a 2021 national database study, only 11.6% of patients
ultimately required surgery. 35 As depression, anxiety, and pain
catastrophizing have been associated with worse pain and function
in patients with de Quervain tenosynovitis, a 2019 cross-sectional
study evaluated the psychological variables independently
associated with worse outcomes in this patient population. In 229
patients awaiting first compartment decompression for de Quervain
tenosynovitis, this study found those who were more prone to
negative perceptions of the consequences of de Quervain
tenosynovitis and pain catastrophizing were associated with having
worse pain and reduced function at baseline. 36 This suggests a
biopsychosocial framework approach when treating patients with
this condition may prove beneficial and perhaps may reduce the
number of patients ultimately choosing surgical decompression or
perhaps improve surgical outcomes. 36

Intersection Syndrome
Tenosynovitis of the second extensor compartment tendons
(extensor carpi radialis longus and extensor carpi radialis brevis) is
known as intersection syndrome. It typically occurs at the area
where the first compartment tendons cross superficial to the second
compartment approximately 6 to 7 cm proximal to the wrist joint.
The extensor carpi radialis longus tendon travels distally to a ach
to the base of the second metacarpal, and the extensor carpi radialis
brevis tendon a aches to the base of the third metacarpal. The
diagnosis can be made typically on clinical history and examination.
This disorder is more common in athletes who perform repetitive
wrist extension movements such as rowers, cyclists, and
weightlifters. Patients typically present with pain, swelling, and
occasionally a grinding or squeaking sensation over an area
typically 6 to 7 cm proximally to the radial styloid; a distinctive
difference from the more distal location of patients with pain
associated with de Quervain tenosynovitis (Figure 4). Symptoms of
intersection syndrome are usually aggravated by wrist motion,
particularly wrist extension and radial deviation. On examination,
pain is generated with direct palpation over the area of intersection
and with resisted wrist extension.

Figure 4 Illustration demonstrating the anatomy of the first (blue arrow) and
second (yellow arrow) dorsal extensor compartments.Intersection syndrome
(black arrow) occurs at a point more proximal than de Quervain syndrome (blue
arrow).(From Adams JE, Habbu R: Tendinopathies of the hand and wrist. J Am
Acad Orthop Surg 2015;23[12]:741-750, Figure 2.
https://journals.lww.com/jaaos/pages/default.aspx.)

Most cases of intersection syndrome can be managed with

nonsurgical measures including activity modification, temporary
immobilization with the wrist in neutral extension, physiotherapy
for stretching exercises, and anti-inflammatory agents. In refractory
cases, corticosteroid injections into the tendon sheath of the second
compartment over the area of maximal tenderness may provide
relief; however, evidence for this is currently lacking. Surgical
release of the second compartment is rarely required but may be an
option for patients with persistent symptoms. It typically involves
release of the second compartment distal to the point of
intersection along the extensor retinaculum and removal of any
inflamed tenosynovium or adhesions.

ECU Tenosynovitis
Inflammation of the ECU tendon is a common cause of ulnar-sided
wrist pain. The close proximity of the ECU tendon to other ulnar-
sided wrist structures, in particular the triangular fibrocartilaginous
complex, can present a challenge in the diagnosis of ECU
tenosynovitis. The ECU provides static stabilization to the wrist and
also functions to ulnar deviate the wrist when the forearm is in
pronation and extend the wrist when the forearm is in supination.
The two main pathologies specific to the ECU tendon involve either
tenosynovitis or instability, with the two occasionally occurring
simultaneously. When examining the ECU, it is important to
delineate the pain associated with these various pathologies as the
treatment differs.
Clinical history is important in these patients because some can
be born with asymptomatic subluxation representing a normal
anatomic variant. Patients with symptomatic ECU subluxation often
describe a traumatic event, commonly occurring in racquet sports,
and a painful snapping during supination. However, patients
presenting with ECU tenosynovitis typically describe a repetitive,
overuse injury without a specific identifiable event.
On physical examination, patients with ECU tendinitis typically
have provocative pain with palpation directly over the ECU, resisted
ulnar deviation with the forearm in pronation, and/or resisted wrist
extension with the forearm in supination. Patients may also have
altered sensation in the distribution of the dorsal sensory branch of
the nerve as it travels in close proximity of the sheath. The synergy
test is a special test that can be helpful in differentiating ECU
pathology from intra-articular pathology (eg, triangular
fibrocartilaginous complex). 37 The patient rests their elbow on a
table with the forearm in supination and digits extended. The
examiner grasps the patient’s thumb and long finger and asks the
patient to radially deviate against resistance. The examiner’s other
hand gently palpates the ECU and flexor carpi ulnaris. The presence
of pain suggests an extra-articular ECU tendon pathology. Tendon
instability can be assessed by evaluating the tendon while moving
the wrist from extension and supination to flexion and ulnar
deviation. A positive test can often demonstrate visual subluxation
of the tendon or an audible snap can be heard.
Imaging is generally recommended to help distinguish other
causes of ulnar-sided wrist pain. Typically radiographs are helpful
to assess for any fracture-dislocations, distal radioulnar joint
arthritis, or ulnar carpal impaction. More advanced imaging, such
as dynamic ultrasonography or MRI, may provide further insight in
discerning ECU tenosynovitis from ECU subsheath disruption and
instability. In addition, MRI can help evaluate intra-articular soft-
tissue causes of ulnar-sided wrist pain such as triangular
fibrocartilaginous complex pathology. Diagnostic and therapeutic
injections may also be considered when clinical examination and
imaging are equivocal.
The initial treatment is nonsurgical and may include rest, activity
modification, a short course of immobilization, physical therapy,
and anti-inflammatory agents. Immobilization can be considered
particularly in the se ing of ECU instability, where the wrist is
placed in a cast in pronation and slight radial deviation.
Corticosteroid injection into the tendon sheath may be considered,
but care should be taken to avoid injection into the tendon
substance. Surgical intervention is reserved for patients with
chronic symptoms, refractory to at least 2 to 3 months of quality
nonsurgical management. The approach is through a dorsal
longitudinal incision over the sixth extensor compartment,
protecting any superficial sensory branches of the ulnar nerve. The
compartment is released longitudinally and a retinacular flap can
be created for eventual repair, although controversy exists whether
that is necessary to prevent postoperative ECU instability. In the
se ing of surgery for ECU subluxation, the tendon is typically
stabilized by creating a pulley from the extensor retinaculum after
the ECU has been released from the sheath. There have been many
described techniques, but a common technique involves an ulnarly
based flap of extensor retinaculum elevated from the fourth
extensor compartment. This flap is then placed volarly under the
ECU tendon and then turns dorsally to suture onto itself on the
radial side of the ECU tendon (Figure 5).

Figure 5 Illustration demonstrating the extensor carpi ulnaris (ECU) subsheath

reconstruction using an ulnarly based flap of extensor retinaculum elevated from
the fourth extensor compartment.(From Adams JE, Habbu R: Tendinopathies of
the hand and wrist. J Am Acad Orthop Surg 2015;23[12]:741-750, Figure 5.
https://journals.lww.com/jaaos/pages/default.aspx.)

Flexor Tendinopathies

Stenosing Flexor Tenosynovitis

Stenosing flexor tenosynovitis, also known as trigger finger, is a
local thickening of the A1 pulley and flexor tendons causing a
mechanical mismatch for smooth tendon gliding within a stenotic
sheath during digit flexion. It is a very common flexor tendon
pathology, with an increased prevalence with associated medical
conditions such as rheumatoid arthritis or diabetes. Patients may
complain of pain at the level of the A1 pulley with associated
symptoms of progressive triggering, and eventually locking of the
affected digit. Often, as these symptoms progress, patients may
avoid flexion of the digit to prevent the locking sensation, which
can lead to grip weakness and digit stiffness. At its most severe, the
digit can become locked in a fixed flexed position requiring manual
release using the contralateral hand.
On physical examination, a nodule may be palpable on the
proximal edge of the A1 pulley. Patients are often able to
demonstrate the triggering and/or locking of the affected digit. In
patients with long-standing stenosis, joint contracture of the PIP or
interphalangeal joint and grip weakness may be present. In the
event patients lack the catching and clicking sensations,
ultrasonography may be considered to confirm the diagnosis.
Nonsurgical management strategies of trigger finger may include
physical therapy, orthotics, NSAIDs, and corticosteroids. A 2019
systematic review demonstrated clinically important change in the
stage of stenosing tenosynovitis with the use of an orthotic device
with recommendations to immobilize a sole joint (MCP), while
leaving the PIP and DIP joints free, for 6 to 10 weeks. In other
reviews, orthoses are reported to have a 40% to 87% relief rate;
however, compliance is variable because some orthotics are quite
cumbersome for activities of daily living. 38 As such, corticosteroid
injection into the flexor tendon sheath is a common first-line
nonsurgical management of trigger finger. Corticosteroid injection
has shown a 60% to 90% response rate with a higher recurrence rate
in diabetic mellitus, multiple digits affected, and other associated
tendinopathies. 38 There is also a fading probability of successful
subsequent injection with a recurrence of triggering. There is
significant variability among surgeons concerning the type of
steroid used. A 2021 retrospective review evaluating 210 patients
showed that there was a higher rate of additional injections with
the use of triamcinolone when compared with dexamethasone and
methylprednisolone. 39
However, those who had a
methylprednisolone injection had a surgical release performed
earlier and more frequently than the other two groups. The dosage
of steroid is also widely variable. A 2020 randomized controlled
trial comparing 10 mg versus 20 mg of triamcinolone in 191 patients
with low-grade triggering showed equivalent efficacy in reducing
symptoms at 6 weeks with either low-dose or high-dose steroid. 40
The complications of steroid injections include skin
depigmentation, skin thinning, fat necrosis, tendon weakening, or
elevated glucose levels in patients with diabetes. A 2020
retrospective study has also investigated the risk of infection in
trigger finger release surgery following corticosteroid injection.
Interestingly, there was a small (0.7%) but statistically significant
increased rate of deep infection after trigger release surgery with a
preoperative corticosteroid injection. The risk of infection did
appear to be time dependent and greater when the injections were
performed within 90 days of surgery, and most notably 31 to 90
days postinjection. 41
If the trigger finger is refractory to nonsurgical management,
surgery is considered. The surgical options include both open and
percutaneous release of the A1 pulley. Open release is the standard
and generally has a high rate of excellent outcomes. The open
release technique can use either transverse, oblique, or longitudinal
incisions. A 2019 randomized controlled trial showed no significant
differences between longitudinal versus transverse incisions in scar
quality and improvement in patient outcomes between these two
incision types. 42 Regardless of the incision, once through skin,
blunt dissection is used to identify the location of both digital
neurovascular bundles and protect them throughout the surgical
procedure. In the thumb, the radial digital nerve crosses the A1
pulley from ulnar to radial and is at risk during open release. The
A1 pulley is then sharply incised under direct visualization. If
residual triggering is encountered after the A1 pulley release, the
proximal superficial palmar aponeurosis (the so-called A0 pulley)
can be released or structural changes in the FDS or FDP should be
evaluated.
Percutaneous release of the A1 pulley is generally best done with
the MCP in slight hyperextension to allow the neurovascular
bundles of the digit to fall more dorsally. Because of the dangerous
location of the neurovascular bundles of the thumb, index, and li le
fingers, the long and ring fingers are generally the best candidates
for percutaneous release. Hypodermic needles, a knife blade, or
special percutaneous devices with or without ultrasonographic
guidance can be used, without particular evidence of superiority.
The proximal edge of the A1 pulley is landmarked, and the
instrument is inserted and a sweeping motion performed in a
proximal to distal direction. At the conclusion of the procedure, the
patient is asked to reproduce the triggering to ensure an adequate
release. Complications are rare but do include neurovascular
bundle injury, stiffness, wound complication, and bowstringing.

Summary
Management of flexor and extensor tendon injuries of the hand and
wrist has vastly improved in recent years. This can be a ributed to
basic science and clinical research directed at evaluating
improvements in repair strength, glide, and rehabilitation
protocols. This should not undermine the continued challenge that
these injuries can have on patients, therapists, and surgeons. These
injuries require a great deal of commitment and persistence to
maximize results. Unfortunately, despite current best techniques
and efforts, functional outcomes of some tendon injuries, especially
zone II flexor tendon injuries, continue to have imperfect results.
The surgical technique and subsequent patient outcomes for
extensor tendon injuries tend to be more predictable. Current
research continues to help bring forth new augments to aid in
tendon repair strength and glide, while also unifying therapy
protocols to promote early motion and limit adhesion formation.
The diagnosis and management of tendinopathies of the hand and
wrist is generally more straightforward. These pathologies can also
require commitment and patience from the patient during the
course of treatment, but generally have a more predictable course.
Similar to tendon injuries, recent research in tendinopathies of the
hand and the wrist continue to work toward identifying the optimal
regime of nonsurgical modalities and surgical techniques.

Key Study Points

Anatomy of the flexor and extensor tendon system is imperative to ensure
restoration of function. When core sutures can be implemented, a minimum of four
core sutures should be used to allow for early active motion protocols. Increasing
the number of core suture and adding epitendinous sutures can increase the
strength of tendon repair.
Flexor tendon repair in the location of the annular pulleys can negatively affect
tendon glide. Venting or release of the affected pulley may be useful surgical
techniques.
Early active motion protocols after tendon repair with selective use of orthosis has
been a key advancement in preventing tendon adhesion and reducing the need for
tendon tenolysis.
In chronic flexor or extensor tendon injuries, tendon reconstruction in a single or
staged technique is preferred over primary repair.
Tendinopathies of the hand and wrist involving the flexors and extensors are
generally diagnosed with history and physical examination. The treatment for these
pathologies involves a combined approach of multiple nonsurgical modalities. Most
patients tend to respond to nonsurgical measures; however, those with refractory
symptoms can be offered a surgical procedure to release the affected tendon
sheath.

Annotated References
1. Wu RT, Walker ME, Peck CJ, et al: Differential pulley release in
trigger finger: A prospective, randomized clinical trial. Hand
2021; March 1 [Epub ahead of print]. This randomized controlled
trial of 31 fingers randomized initial release of either the A1 or A0
 pulley. Of those who had initial A0 release, 47% demonstrated
complete resolution of symptoms, whereas 46% of those with
initial release of the A1 pulley had complete resolution. There was
no statistically significant difference between groups, and all
patients had complete resolution after release of both pulleys.
Level of evidence: II.
2. Netscher DT, Badal JJ: Closed flexor tendon ruptures. J Hand
Surg Am 2014;39(11):2315-2323.
3. McCallister WV, Ambrose HC, Katolik LI, Trumble TE:
Comparison of pullout bu on versus suture anchor for zone I
flexor tendon repair. J Hand Surg Am 2006;31(2):246-251.
4. Prowse P, Nixon M, Constantinides J, Hunter J, Henry A,
Feldberg L: Outcome of zone 2 flexor tendon injuries: Kleinert
versus controlled active motion therapy regimens. Hand Ther
2011;16(4):102-106.
5. Tang JB, Zhou X, Pan ZJ, Qing J, Gong KT, Chen J: Strong digital
flexor tendon repair, extension-flexion test, and early active
flexion: Experience in 300 tendons. Hand Clin 2017;33(3):455-463.
6. Wu YF, Tang JB: Recent developments in flexor tendon repair
techniques and factors influencing strength of the tendon repair.
J Hand Surg Eur Vol 2014;39(1):6-19.
7. Barrie KA, Tomak SL, Cholewicki J, Merrell GA, Wolfe SW:
Effect of suture locking and suture caliber on fatigue strength of
flexor tendon repairs. J Hand Surg Am 2001;26(2):340.
8. Wallace SJ, Mioton LM, Havey RM, Muriuki MG, Ko JH:
Biomechanical properties of a novel mesh suture in a cadaveric
flexor tendon repair model. J Hand Surg Am 2019;44(3):208-215.
This cadaver study compared 3-0 and 4-0 braided suture with a
novel 1-mm mesh suture, using a 40-strand core repair. Mesh
suture had a significantly higher yield and ultimate force values
and with a higher force required to produce repair gaps. Level of
evidence: V.
9. Giesen T, Reissner L, Besmens I, Politikou O, Calcagni M: Flexor
tendon repair in the hand with the M-Tang technique (without
 peripheral sutures), pulley division, and early active motion. J
Hand Surg Eur Vol 2018;43(5):474-479.
10. Altman PR, Fisher MWA, Goyal KS: Zone 2 flexor tendon repair
location and risk of catching on the A2 pulley. J Hand Surg Am
2020;45(8):775.e1-775.e7. This cadaver study evaluated excursion
of the FDP and FDS tendons between the A2 and A4 pulleys. The
study found a suture placed just distal to the A2 pulley with the
finger fully flexed traveled 1.6 ± 1.9 mm distal to the proximal
edge of the A4 pulley with passive extension. Venting the A4
pulley 50% and 100% increased FDP excursion a maximum of 0.9
and 1.9 mm, respectively.
11. Zhao C, Amadio PC, Zobi ME, An KN: Resection of the flexor
digitorum superficialis reduces gliding resistance after zone II
flexor digitorum profundus repair in vitro. J Hand Surg Am
2002;27(2):316-321.
12. Tang JB: Flexor tendon injuries. Clin Plast Surg 2019;46(3):295-
306. A single-surgeon review of the key anatomic and technical
elements for flexor tendon repair is presented. The review
specifically discusses zone 2 repair, focusing on key
developments to make it successful.
13. Munz G, Pogge i A, Cenci L, Rizzo AR, Biondi M, Pfanner S: Up
to five-week delay in primary repair of zone 2 flexor tendon
injuries: Outcomes and complications. J Hand Surg Eur Vol
2021;46(8):818-824. This study evaluated the outcomes of delayed
primary repair of flexor tendons in zone 3. The tendons were
repaired with a six-strand core suture or double Tsuge suture and
peripheral suture. Overall, excellent, and good results using Tang
criteria were in 27 of 31 fingers and thumbs. Level of evidence: IV.
14. Tang JB, Chang J, Elliot D, Lalonde DH, Sandow M, Vögelin E:
IFSSH Flexor Tendon Commi ee report 2014: From the IFSSH
Flexor Tendon Commi ee (Chairman: Jin Bo Tang). J Hand Surg
Eur Vol 2014;39(1):107-115.
15. Koopman JE, Hundepool CA, Duraku LS, Kreulen M, Zuidam
JM: Biomechanical study comparing Pulvertaft, double side-to-
 side, and locking side-to-side tendon suture techniques. J Hand
Surg Am 2021;46(3):246.e1-246.e7. This cadaver study compared
Pulvertaft technique with a double side-to-side and locking side-
to-side tendon suture techniques. Overall, single-sided locking
and double-sided nonlocking side-to-side reconstructions offer a
suitable alternative to the Pulvertaft technique because of higher
strength and less bulkiness.
16. Rivlin M, Eberlin KR, Kachooei AR, et al: Side-to-side versus
Pulvertaft extensor tenorrhaphy—a biomechanical study. J Hand
Surg Am 2016;41(11):e393-e397.
17. Neiduski RL, Powell RK: Flexor tendon rehabilitation in the 21st
century: A systematic review. J Hand Ther 2019;32(2):165-174. This
is a systematic review to assess current evidence to support a
type of exercise regimen during flexor tendon rehabilitation. The
review shows moderate to strong evidence that place and hold
exercises provide be er outcomes than passive flexion protocols
in patients with two-strand to six-strand repairs. However, the
review did have methodologic limitations from the current
evidence. Level of evidence: I.
18. Dezfuli B, Taljanovic MS, Melville DM, Krupinski EA, Sheppard
JE: Accuracy of high-resolution ultrasonography in the detection
of extensor tendon lacerations. Ann Plast Surg 2016;76(2):187-192.
19. Ayhan E, Kuzucu Y, Aslaner EE, Tuna Z: Evaluating stack splint
use for mallet finger. J Hand Surg Asian Pac Vol 2021;26(1):47-51.
In this prospective study, 26 patients with a closed mallet injury
were instructed to wear a stacked splint for 24 hours a day for the
first 6 weeks of treatment, with a 10-minute vent period allowed
per day. Nine patients declared they only wore the splint for less
than 4 weeks, with an overall compliance of 65.4% in the study
protocol. Comprehensive instructions for splinting did not
improve compliance, and it did not lead to favorable outcomes
with an overall satisfaction of 52.9% in those that completed the
study protocol. Level of evidence: III.
20. Thillemann JK, Thillemann TM, Kristensen PK, Foldager-Jensen
AD, Munk B: Splinting versus extension-block pinning of bony
mallet finger: A randomized clinical trial. J Hand Surg Eur Vol
2020;45(6):574-581. This randomized controlled trial aimed to
compare nonsurgical splinting versus extension-block pinning of
bony mallet fingers without subluxation but with involvement of
more than one-third of the joint surface. At 6-month follow-up of
a total of 32 patients, there was no statistical difference in active
extension lag at the DIP or in patient-reported outcomes and
pain scores. Range of motion and flexion at the DIP were be er in
the splinting group, but secondary subluxation did develop in
three patients. Level of evidence: I.
21. Merri WH, Wong AL, Lalonde DH: Recent developments are
changing extensor tendon management. Plast Reconstr Surg
2020;145(3):617e-628e. This summary article reviews key recent
developments in extensor tendon management. It illustrates the
use of relative motion flexion and extension splinting and wide
awake, local anesthesia, no tourniquet surgery on the outcomes
of various extensor tendon injury zones.
22. Türker T, Capdarest-Arest N, Schmahl DT: Zone I extensor
reconstruction with tendon salvaged from another finger. J Hand
Surg Am 2014;39(5):976-980.
23. Savvidou C, Thirkannad S: Hemilateral band technique for
reconstructing gap defects in the terminal slip of the extensor
tendon. Tech Hand Up Extrem Surg 2011;15(3):177-181.
24. Desai MJ, Wanner JP, Lee DH, Gauger EM: Failed extensor
tendon repairs: Extensor tenolysis and reconstruction. J Am Acad
Orthop Surg 2019;27(15):563-573. This review article discusses the
anatomy and surgical options for failed extensor tendon repairs.
The article reviews the options of reconstruction based on
extensor tendon zones, ranging from tenolysis, tendon grafting,
and local and free tissue reconstruction.
25. Lies S, Horowi A, Lee G, Zhang A: Review of the optimal
timing and technique for extensor tendon reconstruction in
 composite dorsal hand wounds. Plast Aesthetic Res 2019;6:18. A
database review of literature on optimal management of
composite hand defects showed immediate cutaneous tendinous
flaps had fewer revision surgeries, faster return to maximum
ROM, and great chance of returning to work over secondary
staged reconstructions. However, there were significantly more
complications seen in immediate reconstruction, particularly
with donor site morbidity.
26. Hirth MJ, Howell JW, Feehan LM, Brown T, O’Brien L:
Postoperative hand therapy management of zones V and VI
extensor tendon repairs of the fingers: An international inquiry of
current practice. J Hand Ther 2021;34(1):58-75. A survey study of
the International Federation of Societies for Hand Therapy
evaluated preferred approach and practice pa erns in zones V
and VI extensor tendon repairs. Although there were multiple
approaches, therapists believed total active motion achieved with
the relative motion extension/early active motion approach was
superior to other methods. Level of evidence: V.
27. Colloco SJF, Kelly E, Foster M, Myhr H, Wang A, Ellis RF: A
randomized clinical trial comparing early active motion
programs: Earlier hand function, TAM, and orthotic satisfaction
with a relative motion extension program for zones V and VI
extensor tendon repairs. J Hand Ther 2020;33(1):13-24. Forty-two
participants with zones V-VI extensor tendon repairs were
randomized to a controlled active motion or relative motion
extension orthosis. Those using a relative motion extension
program and orthosis had be er early hand function, total active
motion, and orthosis satisfaction compared with the controlled
active motion group. Level of evidence: I.
28. Ma on JL, Graham JG, Lutsky KF, Takei TR, Gallant GG,
Beredjiklian PK: A prospective evaluation of the anatomy of the
first dorsal compartment in patients requiring surgery for de
Quervain’s tenosynovitis. J Wrist Surg 2019;8(5):380-383. This
prospective cohort study evaluated 130 patients undergoing first
compartment release for de Quervain tenosynovitis. There was
 only a single compartment in 37%, and a sensory branch of the
radial nerve was encountered in more than 50% of patients.
Tendon instability occurred in 9% of cases. Level of evidence: II.
29. Wu F, Rajpura A, Sandher D: Finkelstein’s test is superior to
Eichhoff’s test in the investigation of de Quervain’s disease. J
Hand Microsurg 2018;10(2):116-118.
30. Goubau JF, Goubau L, Van Tongel A, Van Hoonacker P,
Kerckhove D, Berghs B: The wrist hyperflexion and abduction of
the thumb (WHAT) test: A more specific and sensitive test to
diagnose de Quervain tenosynovitis than the Eichhoff’s test. J
Hand Surg Eur Vol 2014;39(3):286-292.
31. Earp BE, Han CH, Floyd WE, Rozental TD, Blazar PE: De
quervain tendinopathy: Survivorship and prognostic indicators of
recurrence following a single corticosteroid injection. J Hand Surg
Am 2015;40(6):1161-1165.
32. Oh JK, Messing S, Hyrien O, Hammert WC: Effectiveness of
corticosteroid injections for treatment of de Quervain’s
tenosynovitis. Hand 2017;12(4):357-361.
33. Ippolito JA, Hauser S, Patel J, Vosbikian M, Ahmed I:
Nonsurgical treatment of de Quervain tenosynovitis: A
prospective randomized trial. Hand 2020;15(2):215-219. Twenty
patients were randomized to receive either corticosteroid
injection alone versus corticosteroid injection with 3 weeks of
immobilization. In this small study, immobilization increased
costs, hindered activity, and did not contribute to improved
patient outcomes. Level of evidence: II.
34. Mardani-Kivi M, Karimi Mobarakeh M, Bahrami F, Hashemi-
Motlagh K, Saheb-Ekhtiari K, Akhoondzadeh N: Corticosteroid
injection with or without thumb spica cast for de Quervain
tenosynovitis. J Hand Surg Am 2014;39(1): 37-41.
35. Hassan K, Sohn A, Shi L, Lee M, Wolf JM: De Quervain
tenosynovitis: An evaluation of the epidemiology and utility of
multiple injections using a national database. J Hand Surg Am
2021;47(3):284.e1-284.e6. This national database study found
 33,420 patients with the diagnosis of de Quervain tenosynovitis.
Overall, 53.3% of patients were treated with injections and 11.6%
of patients required surgical management. With one injection,
71.9% had a successful outcome but subsequent injections also
had a high rate of success.
36. Blackburn J, Van Der Oest MJW, Selles RW, et al: Which
psychological variables are associated with pain and function
before surgery for de Quervain’s tenosynovitis? A cross-sectional
study. Clin Orthop Relat Res 2019;477(12):2750-2758. A cross-
sectional study reviewed 229 patients who underwent surgery for
de Quervain tenosynovitis. More negative perceptions of the
consequences of de Quervain tenosynovitis and worse pain
catastrophizing were associated with worse pain and reduced
function at baseline in patients awaiting surgical decompression
of de Quervain tenosynovitis.
37. Ruland RT, Hogan CJ: The ECU synergy test: An aid to diagnose
ECU tendonitis. J Hand Surg Am 2008;33(10):1777-1782.
38. Lunsford D, Valdes K, Hengy S: Conservative management of
trigger finger: A systematic review. J Hand Ther 2019;32(2):212-
221. This is a systematic review of current evidence of nonsurgical
management of trigger finger. All studies included showed a
similar result regardless of the joint immobilized; therefore, only
a sole joint should be immobilized for 6 to 10 weeks. Level of
evidence: I.
39. Roberts JM, Behar BJ, Siddique LM, Brgoch MS, Taylor KF:
Choice of corticosteroid solution and outcome after injection for
trigger finger. Hand 2021;16(3):321-325. A survey review from a
single institution showed that trigger finger injections using
triamcinolone had higher rate of additional injections when
compared with dexamethasone and methylprednisolone. Patients
who had a methylprednisolone injection had a surgical release
performed earlier and more frequently.
40. Leung LTF, Hill M: Comparison of different dosages and
volumes of triamcinolone in the treatment of stenosing
 tenosynovitis: A prospective, blinded, randomized trial. Plast
Surg 2020;29(4):265-271. One hundred ninety-one patients were
randomized to receive two separate doses/volumes of
triamcinolone for trigger finger injections. There was no
difference in success rate of complete trigger resolution at 6
weeks between the low dose/volume versus the higher regime.
Level of evidence: I.
41. Ma on JL, Lebowi C, Graham JG, Lucenti L, Lutsky KF,
Beredjiklian PK: Risk of infection in trigger finger release surgery
following corticosteroid injection. J Hand Surg Am 2020;45(4):310-
316. This is a retrospective evaluation of 1,857 patients
undergoing trigger release surgery. There was a 2.1% rate of
infection overall with a small but statistically significant increase
in deep infection with corticosteroid, especially in the 31- to 90-
day postinjection period. Level of evidence: III.
42. Kazmers NH, Holt D, Tyser AR, Wang A, Hutchinson DT: A
prospective, randomized clinical trial of transverse versus
longitudinal incisions for trigger finger release. J Hand Surg Eur
Vol 2019;44(8):810-815. This prospective, randomized study
assessed incision type for trigger finger release and the effect on
scar quality or outcome. There was no significant difference in all
assessments for scar formation and patient-reported outcome at
either 8 or 54 weeks. Level of evidence: II.
C H AP T E R 3 8

Hand and Wrist Injuries,

Fractures, and Reconstruction
Abhiram R. Bhashyam MD, PhD, Jerry I. Huang MD, FAAOS

Dr. Huang or an immediate family member has received royalties from Arthrex, Inc.; is a member
of a speakers’ bureau or has made paid presentations on behalf of Arthrex, Inc., DePuy, a
Johnson & Johnson Company, and DJ Orthopaedics; serves as a paid consultant to or is an
employee of Acumed, LLC; has received research or institutional support from Acumed, LLC; and
serves as a board member, owner, officer, or committee member of the American Association for
Hand Surgery and the American Society for Surgery of the Hand. Neither Dr. Bhashyam nor any
immediate family member has received anything of value from or has stock or stock options held
in a commercial company or institution related directly or indirectly to the subject of this chapter.

ABSTRACT
Many principles of upper extremity trauma have remained
unchanged for some time. Traumatic injury to the upper extremity
may consist of injuries to bone, soft tissues, vessels, and/or nerves
with associated contamination. Goal-directed approaches are
critical to systematically reconstruct the upper extremity while
minimizing complications and maximizing function. Diagnostic
strategies, treatment modalities, approaches, algorithms, and
evaluation of outcomes are important areas of further study.
Keywords: hand fractures; mangled hand; replantation; wrist
fractures

Introduction
Diagnostic strategies, treatment modalities (including fixation
options), and outcome evaluation remain active areas of
investigation in the management of fractures of the hand and wrist
(Table 1). Indications for replantation, particularly artery-only distal
finger replantation, continue to evolve based on published
outcomes. Further prospective studies are needed to provide
treatment guidance, especially for different patient populations.

Table 1
Summary of Common Hand and Wrist Fractures With Surgical
Indications and Fixation Options

Fracture
Common Surgical Indications Fixation Options
Type
Distal
radius Unacceptable radiographic fracture alignment External
fractures (shortening >5 mm, radial inclination <15°, dorsal fixation
angulation >10° or volar angulation >25°, articular Kirschner
step-off >2 mm, disruption of the lateral wires
radiocarpal alignment) Plate fixation
Volar or dorsal radiocarpal instability
Distal radioulnar joint instability

Scaphoid
fractures Displaced fractures (as >1 mm of translation, Kirschner
>10° angular displacement, radiolunate angle wires
>15°, scapholunate angle >60°, or intrascaphoid Headless
angle >35°) compression
Nonunions screws
Plate fixation

Metacarpal
fractures Scissoring with composite flexion Kirschner
Extensor lag wires
External
fixation
Plate fixation
Intramedullary
headless
screw fixation
(retrograde
and
antegrade)
Fracture
Common Surgical Indications Fixation Options
Type
Phalangeal
fractures Scissoring with composite flexion Kirschner
Extensor lag wires
External
fixation
Plate fixation
Intramedullary
headless
screw fixation

Distal Radius Fractures

Fractures of the distal radius often originate in the metaphyseal
region and can extend into the radiocarpal or distal radioulnar
joint. Distal radius fractures almost always heal, but several
surgical techniques can improve alignment with the goal of
improving function in appropriately selected patients.
Furthermore, distal radius fractures are not all the same, and a
single method of treatment is unlikely to be uniformly effective.
Each fracture demands careful analysis of the fracture pa ern,
directions of displacement, fragment size, and predicted instability.
1
It is still unclear which patients predictably benefit from surgery
or which surgical technique for management of these injuries is
best. In general, nonsurgical management is likely to be successful
in patients with extra-articular distal radius fractures with well-
maintained radiocarpal alignment after closed reduction. Typical
indications for surgical treatment include persistent unacceptable
angulation or shortening and fractures with significant intra-
articular displacement or comminution.

Goals of Treatment
The overarching goal in the treatment of patients with distal radius
fractures is to help the patient have a painless, stable wrist that is
functional; that is, allowing return to normal activities within a
physiologic range of motion. Stability evaluation includes
assessment of potential radiocarpal dislocation or distal radioulnar
joint instability that may require additional treatment. 2 , 3 Standard
AO principles are used as the surgical tactic: (1) fracture reduction
to restore anatomic relationships; (2) fracture fixation providing
absolute or relative stability, depending on the type of fracture,
patient, or injury; (3) preservation of blood supply (soft tissues and
bone); and (4) early and safe mobilization.

Surgical Indications
General indications for surgical intervention include unacceptable
radiographic fracture alignment (shortening greater than 5 mm,
radial inclination less than 15°, dorsal angulation greater than 10°
or volar angulation greater than 25°, articular step-off greater than 2
mm, disruption of the lateral radiocarpal alignment), volar or
dorsal radiocarpal instability, or distal radioulnar joint instability. 4
However, there continues to be considerable debate about surgical
versus nonsurgical management of distal radius fractures,
especially in lower demand older age patients. Two recent studies
found that clinical, radiographic, and patient-reported outcome
measures in younger patients were be er with surgical fixation
compared with nonsurgical management in well-reduced distal
radius fractures at 1-year follow-up. 5 , 6 Even in the elderly
population, two subsequent randomized controlled trials found
that although outcomes were similar at 1-year follow-up, patients
who underwent surgical treatment had faster recoveries, were more
satisfied with their function, and had similar rates of complications.
7 , 8
Concurrently, a large retrospective database study conducted in
2019 found that comorbidities were more strongly associated with
developing complications than patient age. 9 In total, these findings
highlight the importance of individualized patient care.

Treatment Options and Fixation Methods

There are a variety of options to treat patients with distal radius
fractures. Closed reduction and casting are indicated for fractures
that are stable with minimal metaphyseal comminution,
shortening, angulation, or displacement. Close weekly follow-up is
required to evaluate for secondary displacement over 2 to 3 weeks
while swelling subsides. Closed reduction and percutaneous
pinning (typically with Kirschner wires [K-wires]) is indicated for
simple intra-articular or extra-articular fractures with mild
comminution and no osteoporosis, or for fractures in children with
open growth plates. External fixation can be used in highly
comminuted fractures that are more difficult to fix rigidly,
especially when soft-tissue contamination is present. Open
reduction and internal fixation is typically indicated for unstable
distal radius fractures. Multiple variations of open reduction and
internal fixation have been described, including a volar plate
through a volar approach, dorsal plate through dorsal approach,
fragment-specific fixation, or a dorsal spanning plate. Fragment-
specific fixation refers to a treatment approach for complex articular
fractures characterized by independent fixation of each major
fracture component with an implant specific for that fragment
based on its size and location. 1 Recent studies have highlighted the
value of advanced imaging in the characterization of dorsal articular
fragments to aid with preoperative planning in terms of surgical
approach, fixation strategy, and intraoperative evaluation. 3 , 10
Specifically, one article described the location of injury in a series of
13 patients with dorsal Barton fracture-dislocations, whereas
another article characterized the morphology and size of the dorsal
ulnar corner fragment. The use of dorsal spanning plates for
fixation of distal radius fractures is versatile, and typical indications
include metadiaphyseal comminution of the radius, the need for
weight bearing through the upper extremity, polytrauma,
augmented fixation, carpal instability, or salvage of prior failed
treatment. 11 In terms of fixation method, the Wrist and Radius
Injury Surgical Trial randomized 187 patients to internal fixation,
external fixation, or percutaneous pinning compared with 117
patients who preferred nonsurgical treatment. Although recovery
was fastest for internal fixation, by 12 months there was no
meaningful difference in outcome. 2 Similar findings also were
 g g
reported in a network meta-analysis comparing outcomes after
treatment of distal radius fractures in adults using external fixation,
intramedullary nailing, K-wires, casting, or plate fixation. 12
Increasingly, hybrid and arthroscopic-assisted approaches are
being used. Arthroscopy can be a helpful adjunct to diagnose
concomitant carpal ligament or triangular fibrocartilage complex
injuries, or to facilitate anatomic reduction of the joint surface. 13
Arthroscopic assistance is especially helpful in radial styloid and
die-punch fracture pa erns where percutaneously placed K-wires
can be manipulated under arthroscopic visualization to reduce and
stabilize articular fragments. These K-wires can then be replaced
with percutaneously placed cannulated screws, or the K-wires can
be kept in place to support the subchondral area of the distal radius
to maintain the articular reduction in combination with a volar or
dorsal plate. Regardless of treatment approach, recent studies have
highlighted the role for dorsal tangential fluoroscopic views and
assessment of carpal alignment in relation to the volar cortex of the
distal radius to evaluate dorsal screw penetration, fixation
placement, and fracture reduction. 4 , 14

Outcomes
Outside of surgical indications and tactics, the recent literature on
distal radius fracture treatment has focused on the incidence of
complications and patient-reported outcomes. In terms of flexor
tendon irritation, multiple studies have highlighted the value of the
Soong classification in terms of plate placement. However, a 2020
study reported that prediction of isolated flexor tendinopathy was
not independently predicted by the Soong classification as fracture
reduction was a significant confounder. 15 Regardless, rates of flexor
tendon irritation at 24 months of follow-up have decreased in more
recent studies, presumably because of improved plate placement,
plate design, and fracture reduction. 16
Finally, there has been significant investigation into clinical and
patient-reported outcomes following distal radius fracture
treatment. A retrospective cohort study of 647 distal radius
fractures found a low complication rate. Risk factors for a
complication included diabetes, obesity, intra-articular fracture
malalignment, and plate prominence. 17 In the Wrist and Radius
Injury Surgical Trial, the most predictive factors for patient-
reported outcome were pain at enrollment, education, age, and
number of comorbidities. 2 In addition, patient-reported outcomes
have also been shown to be associated with injury mechanism and
general health as patients with high-energy injury mechanism and
low health-related quality of life scores were independently
associated with inferior wrist function. 18

Scaphoid Fractures
The scaphoid is almost completely covered with hyaline cartilage,
creating an environment with limited periosteum and vascular
supply. Because of the lack of periosteum, the scaphoid heals
almost completely by primary bone healing. Combined with the
limited blood supply, scaphoid fractures have a higher risk for
nonunion and osteonecrosis. Nondisplaced or occult scaphoid
fractures can be challenging to diagnose, and a 2019 study
suggested that immediate MRI for diagnosis may lead to cost
savings, improved diagnostic accuracy, and higher patient
satisfaction—albeit this study was performed in the United
Kingdom and cost-effective analyses may be region-specific. 19
Given the propensity and frequency of scaphoid nonunion,
management of scaphoid fractures is best categorized into two
groups: acute fractures and nonunions. 20 Current best evidence
suggests that nondisplaced, acute (<4 weeks from injury), and/or
distal pole fractures can be managed nonsurgically with adequate
protection. Displacement is typically defined as greater than 1 mm
of translation, greater than 10° angular displacement, radiolunate
angle greater than 15°, scapholunate angle greater than 60°, or
intrascaphoid angle greater than 35°. Scaphoid waist fractures with
less than 2 mm of displacement may be initially managed with cast
immobilization, but these injuries should be followed closely with
immediate conversion to surgical fixation when suspected
development of a nonunion is confirmed. 21 In general, fracture
displacement is based on CT. In contrast, displaced fractures are
prone to nonunion and are best treated surgically. Factors
associated with development of nonunion include delayed
diagnosis or treatment, inadequate immobilization, proximal
fracture, initial and progressive fracture displacement,
comminution, and presence of associated carpal injuries (eg,
perilunate injuries). 22 Evaluation of healing with advanced imaging
(CT) is frequently performed during the management of acute
scaphoid fractures and nonunions; however, reliability may not
always be improved compared with conventional radiographs. 23

Goals of Treatment
The primary goal of treatment of patients with scaphoid fracture is
to facilitate healing of the fracture to allow the patient to have a
painless, stable wrist that is functional, allowing for return to
normal activities with physiologic range of motion. In terms of
surgery, this equates to the a ainment of an anatomic reduction
with stable rigid fixation, except in cases of distal pole nonunion,
where excision of the distal pole nonunion fragment may allow for
the patient to have a painless, stable functional wrist.

Treatment Options and Fixation Methods

Scaphoid fractures can be managed via a percutaneous or open
approach. Indications for percutaneous fixation include
nondisplaced scaphoid waist fractures, displaced scaphoid waist
fractures that can be closed reduced, and nondisplaced proximal
pole fractures. Volar and/or dorsal open approaches can be used to
facilitate fracture reduction and fixation based on fracture
characteristics and surgeon preference. Arthroscopy is increasingly
used to aid with percutaneous fracture reduction, bone grafting,
and fixation. 24
 Common fixation strategies include K-wires, headless
compression screws, and plates. Headless compression screws may
be inserted along the central axis of the scaphoid or perpendicular
to the fracture plane within the middle third of the scaphoid based
on fracture anatomy and surgeon preference. A 2020 retrospective
cohort study comparing clinical and radiographic outcomes
between K-wire and cannulated compression screw fixation in the
management of scaphoid nonunions found no difference in bony
healing or functional outcomes at the time of final follow-up. 25
Plate fixation of scaphoid fractures is relatively more recent and
typically indicated in se ings of significant comminution or
segmental bone loss that is managed with bone grafting. Union
rates between plate fixation and cannulated compression screws are
similar, although the rate of hardware removal was higher for the
plate fixation group. 26

Bone Grafting
Bone graft is typically used in the management of scaphoid
nonunions. Bone grafts can be divided based on two characteristics:
(1) structural versus nonstructural, and (2) vascularized versus
nonvascularized. Structural bone graft is typically used in the
correction of humpback deformity or segmental defects within the
scaphoid, but there is significantly more debate regarding the need
for vascularized versus nonvascularized bone graft. Common
sources for nonvascularized graft include the distal radius and iliac
crest. Vascularized bone grafts are either pedicled (eg, 1,2-
intercompartmental supraretinacular artery) or free (eg, medial
femoral condyle/medial femoral trochlea [MFT]). A 2019
retrospective cohort study of 109 patients compared the use of
structural iliac crest, 1,2-intercompartmental supraretinacular
artery, and MFT bone grafts to manage scaphoid nonunions. Union
rates and mean time to union were similar for all three groups. 27
Another study reported 35 consecutive scaphoid nonunions
managed with nonvascularized bone grafting and demonstrated
healing in 33 of 35 patients by 12 weeks. 28 In addition, a 2020
national database study comparing rates of revision surgery after
management of scaphoid nonunions using vascularized versus
nonvascularized bone grafts found similar rates of revision surgery,
suggesting that nonvascularized bone grafting may be a reasonable
first option. 29 These results highlight the value of careful patient
selection when deciding on the type of bone graft to use.
Proximal pole reconstruction after scaphoid nonunion has
historically been a challenging problem to manage. Recent
literature has highlighted the utility of two new bone grafts: the
proximal hamate nonvascularized bone graft and the MFT
osteochondral free flap. A 2019 case study illustrated the use of the
proximal pole of the hamate as a replacement arthroplasty in
se ings where the proximal pole scaphoid nonunion has
undergone collapse with bone loss and/or osteonecrosis. 30 A
subsequent 2020 morphologic study demonstrated the proximal
hamate was a good fit for the proximal scaphoid in most of the
cases. 31 A separate case series of 11 patients with 2-year follow-up
after MFT osteochondral free flap reconstruction for the scaphoid
proximal pole demonstrated radiographic union with improvement
in functional and patient-reported outcomes in all patients. 32

Metacarpal Fractures
Hand fractures comprise a significant percentage of all fractures
managed each year and are a common cause of emergency
department visits. Current research has focused on comparative
studies of different fixation methods. There is still some debate
about early active range of motion versus traditional
immobilization in patients treated both surgically and
nonsurgically. 33

Goals of Treatment
The primary goal in treatment of patients with metacarpal fractures
is to restore clinical alignment to facilitate normal hand function. A
simple clinical maneuver to assess for rotational malalignment and
clinically significant shortening involves assessing for extensor lag
or scissoring while asking the patient to fully extend their fingers
and then flexing to make a full composite fist.

Fixation Methods
A variety of fixation methods and techniques are used to manage
metacarpal fractures. Selection of any individual fixation method is
highly dependent on patient characteristics, including bone quality
and activity level, as well as fracture characteristics. Commonly
used fixation methods include (1) closed reduction and casting, (2)
closed reduction and percutaneous pinning (K-wires) or external
fixation, and (3) open reduction and internal fixation with plates.
More recently, intramedullary headless screw (IMHS) fixation of
metacarpal fractures has gained popularity. Intramedullary screw
fixation was reported to be safe and reliable in a clinical series of 91
patients. 34 In a 2021 prospective randomized trial comparing IMHS
with mini plate fixation, no significant differences were found in
clinical outcomes. 35 A 2021 anatomic study provides guidance on
optimal screw size for IMHS fixation of metacarpal fractures. 36

Phalangeal Fractures
Phalangeal fractures are common, and fracture-dislocations of the
digits are high-energy injuries that can sometimes be missed on
initial presentation. With timely diagnosis, phalangeal fractures
and dislocations can often be managed with closed reduction and
immobilization. Although open hand fractures have historically
been considered an indication for surgery, recent studies have
suggested that antibiotic timing is the most important factor in
preventing infection. 37

Goals of Treatment
As with metacarpal fractures, the goal in the treatment of patients
with phalangeal fractures is restoration of clinical alignment.

Fixation Methods
There are multiple fixation methods to manage phalangeal
fractures, including (1) closed reduction and casting, (2) closed
reduction and percutaneous pinning (K-wires) or external fixation,
(3) closed versus open reduction with intramedullary fixation, and
(4) open reduction and internal fixation with plates. Recent studies
have found similar range of motion, patient-reported outcomes,
and complication rates between phalangeal fractures managed with
K-wires, lag screws, or plates. 38 , 39 Recent studies have also started
to report favorable clinical outcomes after intramedullary
cannulated compression screw fixation of unstable phalangeal
fractures in comparison with fixation with K-wire or plate/screw
constructs. 40 A promising recent technique is to use dual antegrade
IMHS for unstable phalangeal fractures. 41

Traumatic Injury of the Hand and Wrist:

Reconstruction and Principles of Treatment
Traumatic injury to an extremity or mangled upper extremity is
characterized by trauma that results in severe injuries to three of
four tissue types (bone, soft tissues, vessels, nerve). These injuries
are typically the result of high-energy trauma. They are often
associated with contamination and segmental loss of critical soft
tissues and/or bone. Goal-directed approaches are critical to
systematically reconstruct the upper extremity while minimizing
complications and maximizing function.

Goals of Treatment
Traumatic injury to the upper extremity should be viewed as a
distraction to initial evaluation, as the primary goal of treatment is
to preserve life over limb. 42 Once the patient is stabilized, detailed
evaluation of the extremity can begin. Early assessment of the
viability of the injured extremity is critical when deciding between
reconstruction versus amputation. Consideration should be given
to primary amputation when the morbidity or limited function that
can be expected following limb salvage outweighs potential
benefits. 43 Although initial management is typically directed
toward limb salvage, in se ings of primary amputation, increasing
a ention has been directed toward neuroma management using
traditional techniques (traction neurectomy, burial into
muscle/bone) versus active techniques (targeted muscle
reinnervation, regenerative peripheral nerve interface, and hybrid
procedures) at the time of the index procedure or in future follow-
up. 44 - 46
Initial management of these challenging injuries is directed at
minimizing infection, minimizing residual disability, and
maximizing final function. Reconstruction in this patient
population is often staged over months to years, requiring careful
consideration of future planned incisions, skeletal fixation,
neurovascular repair, and/or soft-tissue coverage. Strategic
planning is essential to avoid inadvertently eliminating future
surgical options. 47 Given the complexity associated with
management of these injuries, treatment at a high-volume
institution is likely to improve the access to and quality of care. 48

Biomechanics of Hand Function

An understanding of the functional role of each digit and joint in
the upper extremity, as well as its composite function, is invaluable
when planning treatment for the patient with a traumatic injury to
the upper extremity. The joints of the upper extremity position the
hand in space to maximize its function as the effector organ of the
upper extremity. 49 Functionally, the hand can be divided into three
components that facilitate prehension: the thumb, which allows for
opposition and pinch; the index and long finger, fixed rays that act
as stable posts allowing for pinch and precision grip; and the ring
and li le fingers, mobile rays that allow for grasp and power grip.
Four structural principles maximize the ability of a reconstructed
hand to perform basic tasks:

1. A stable thumb—although loss of the thumb can be restored

using a free toe-to-thumb transfer or osteoplastic
reconstruction, thumb salvage should receive the highest
priority 50
2. A stable wrist with two opposing digits that can facilitate pinch
3. Maintenance of a web space between at least two digits to
facilitate prehension
4. Sensate, pain-free digits with enough active range of motion to
facilitate pinch and grasp.

Initial Management
Initial management in the emergency department should include
intravenous antibiotic prophylaxis and tetanus toxoid
administration. If the patient has not received a tetanus booster
within the past 5 years, tetanus immunoglobulin should also be
administered.
Acute-stage procedures may include débridement, bony
stabilization, revascularization, fasciotomy, and temporizing soft-
tissue covering or dressings. Of these, débridement is typically
considered the most critical step in treatment. An oncologic
systematic radical débridement should be performed with the goal
of excising all contaminated and obviously necrotic or devitalized
tissue while preserving critical structures (nerves, vessels, tendons).
At the initial débridement, marginal soft tissues and skin should be
preserved to allow them to declare viability during subsequent
débridement. Similarly, surgical options should be preserved when
possible: (1) uncontaminated bone fragments with intact soft-tissue
a achments should be preserved for future bony stabilization or
reconstruction, (2) critical neurovascular structures and tendons
can be preserved to enhance function of the hand, and (3) spare
parts that may be used for eventual reconstruction should be
identified and preserved (eg, fillet flaps or vascularized muscle).
After débridement, fractures should be stabilized to maintain
proper length, rotation, and alignment. Anatomic reduction and
internal fixation may also be performed depending on the extent of
soft-tissue contamination, fracture characteristics, and other
injuries. Similarly, the choice of fixation is context dependent. 42 In
the se ing of multilevel injuries of the upper extremity, proximal to
distal stabilization may be preferred to restore a stable foundation
on which reconstruction of more distal structures can be
performed. Soft-tissue and intrinsic joint contractures are common
sequelae of hand trauma that can be managed prophylactically with
skeletal fixation (eg, first web space contraction can be prevented
with K-wire fixation or external fixation of the first ray in maximal
palmar and radial abduction for 4 to 6 weeks). Depending on the
clinical context, skeletal defects may be managed with primary
bone grafting versus staged reconstruction using a cement spacer.
Vascular injuries should be expeditiously managed to reestablish
distal perfusion. Vascular shunts may be especially helpful to
temporarily reestablish blood flow in se ings of critical hand
ischemia secondary to injuries at the level of the wrist and
proximally. 42 Definitive vascular reconstruction in the patient with
traumatic injury to the upper extremity often requires a vein graft
because of the zone of injury and the pa ern of segmental vessel
loss that is typically observed. After reconstruction, adequate soft-
tissue coverage is essential to avoid desiccation and vessel
breakdown that can lead to thrombosis or hemorrhage.
Primary nerve reconstruction can be challenging because of the
zone of injury, even in cases where primary coaptation is feasible. If
needed, secondary reconstruction may be performed in a staged
fashion once the zone of neural injury has been determined and the
wound bed is clean and well vascularized with adequate soft-tissue
coverage. Nerve repair or reconstruction must be tension free. For
this reason, there is a low threshold to use nerve grafts or conduits.
When managing soft tissues, primary closure of the skin should
be avoided if there is any tension on the wound. Wounds should be
left open or closed loosely to allow for egress of contaminated
fluids and to minimize soft-tissue tension on the wound periphery
to prevent progressive tissue necrosis. With the emergence of
negative-pressure wound therapy and dermal substitutes,
emergency soft-tissue coverage is less commonly performed than in
the past. Tendons may be repaired in the acute se ing to minimize
retraction. However, tendon injuries are often segmental,
preventing primary end-to-end repair. In this se ing, tendon grafts
or tendon transfer can be performed once the wound bed is
appropriate and the patient will be able to participate in
postoperative rehabilitation. Patients should be carefully observed
for the development of compartment syndrome with a low
threshold to perform fasciotomies, especially in the se ing of crush
or vascular injuries.

Replantation: Indications and Outcomes

Replantation and revascularization are well-accepted procedures
within hand surgery, but not all severed or dysvascular tissues are
appropriate for microvascular reconstruction. A successful outcome
does not simply mean digit or extremity survival, as the goal should
be the restoration of a digit or limb to allow for adequate sensation
and active motion for activities of daily living. 51 Identification of
patients who will have successful and predictable outcomes is an
area of active research.

Indications and Contraindications for

Replantation or Revascularization
Indications and contraindications are general guidelines for
preoperative decision making. Plans must be individualized for
each patient and the clinical situation. Indications for a empted
replantation are broadly divided as absolute or relative based on
age, number of digits involved, level of amputation, and injury
mechanism. Absolute indications include childhood amputation,
any thumb of any mechanism, multiple digits other than the
thumb, and transmetacarpal or wrist-level amputation. Relative
indications include a single digit distal to the flexor digitorum
superficialis insertion, ring avulsion injury, or major limb
amputations (proximal to wrist) with acceptable ischemia time.
Recommended ischemia time before replantation or
revascularization of digits is 12 hours of warm and 24 hours of cold
ischemia time. In more proximal levels of injury, 6 hours of warm
and 12 hours of cold ischemia time are the recommended limits,
although there is still controversy regarding delayed digit
replantation. 52
Absolute contraindications for replantation or revascularization
include severely crushed or mangled parts, significant comorbidity
or associated injury, severe vascular disease, or prolonged ischemia
time for major limb amputation. Relative contraindications include
avulsion mechanism, segmental amputation, or prolonged ischemia
time for digital amputations. The principles of digit replantation
and steps of digit replantation are outlined in Tables 2 and 3,
respectively.

Table 2
Principles of Digit Replantation

1. Initial management at time of injury/at location of referring center: amputated part

should be wrapped in moist gauze, placed in a sealed plastic bag, and placed on ice.
Antibiotic and tetanus prophylaxis should be administered. Cold and warm ischemia
time should be noted to facilitate transfers appropriately.
2. Risks and benefits of replantation/revascularization should be discussed with the
patient and/or family. The potential need for revision amputation and the possibility of
nerve, bone, skin, or vein grafting should be reviewed.
3. Management of the amputated part: bringing the amputated part directly to the
operating room should be considered to perform débridement and preparation before
 patient arrival in the operating room.
4. Adjuncts to care should be facilitated, including a urinary catheter, a regional nerve
block for pain management and sympatholytic effect, and maintenance of patient core
temperature to avoid vasoconstriction.
5. A two-team approach can improve efficiency and efficacy. One team works on the
amputated part while the other works on the structures that are attached to the
patient.

Table 3
Steps of Digit Replantation

1. Preparation: the amputated part should be inspected to identify irreparable damage to

distal vessels, nonviable tissues should be débrided, and structures that will need to
be repaired or reconstructed be identified. Midlateral incisions provide easy
visualization of volar and dorsal structures.
2. Bone fixation: shortening the bone of the amputated digit should be considered to
facilitate débridement and ease soft-tissue repair, especially of neurovascular
structures. Significant intra-articular injury or bone loss requires consideration of
fusion versus arthroplasty. Bony fixation should be expeditious and rigid to facilitate
early active motion.
3. Tendon repair: preplacement of core sutures in the proximal and distal tendons during
structure identification allows this to proceed rapidly.
4. Vascular repair: surgeons differ in the preference between the order of artery and vein
repair. An artery-first technique rapidly revascularizes the part, demonstrates
adequate inflow, and facilitates selection of outflow veins. However, the artery-first
technique results in venous bleeding, making subsequent steps more difficult. Direct
anastomosis is often possible in sharp mechanisms or in settings of local crush
injury with adequate shortening. Vein or arterial grafts may be used in settings of
segmental defect or in large zones of injury. Multiple studies have reported successful
artery-only repair for distal finger amputations when it is not feasible to obtain venous
outflow. Multiple techniques to avoid venous congestion and replant failure have been
described, including dermal pocketing, leech therapy, and external bleeding via
removal of the nail plate or hyponychial area.
5. Nerve repair: the proximal and distal nerve endings are resected until healthy
sprouting fascicles are identified. Repair must be tension-free with a low threshold to
use a nerve graft.
6. Skin coverage: loose skin closure is important to prevent vascular compression and
some areas can be allowed to heal by secondary intention. Other strategies on the
reconstructive elevator may be used as indicated.

Multiple Digit Replantation Technique

The following approach (sequence) should be followed: Two
surgical teams should be used to increase efficiency and improve
outcomes. Digits should be replanted using a structure-by-
structure method. Replantation priority is given to the least
damaged digits and residual limbs. Digits may commonly be
placed in a heterotopic location using a spare parts technique. The
thumb is prioritized.

Aftercare
Replanted or revascularized digits/extremities should be carefully
monitored for continued perfusion and the development of venous
congestion. Perfusion can be assessed clinically through
assessment of skin color, capillary refill, tissue turgor, bleeding
after pinprick, and pulse oximetry. Thrombosis and venous
congestion are typical findings in a failing replant, which can be
managed by removal of constrictive dressings, leech therapy with
antibiotic prophylaxis, or external bleeding methods. 53 , 54
Recommendations for anticoagulation have historically been
variable, but recent studies have identified no protective effect
against digit failure in patients treated with or without
postoperative anticoagulation using heparin. 55 , 56 Aspirin 81 mg
daily for 30 days has been prescribed. Results can be optimized
using individualized, graded rehabilitation programs under the
guidance of an experienced hand therapist. Secondary surgeries are
often required to improve function.

Summary
Many principles of upper extremity trauma have remained
unchanged for some time. Acute management of traumatic injury
to the upper extremity can be daunting, but careful consideration of
the biomechanics of the hand, surgical planning, and meticulous
technique can help to facilitate systematic reconstruction of the
upper extremity while minimizing complications and maximizing
function.
Key Study Points
Fractures of the hand and wrist are not all the same, and a single method of
treatment is unlikely to be uniformly effective.
The primary goal in treating the patient with a traumatic injury to the upper limb is to
preserve life.
Thoughtful, staged surgical planning is necessary to avoid preemptively limiting
options for reconstructions.

Annotated References
1. Medoff RJ: Essential radiographic evaluation for distal radius
fractures. Hand Clin 2005;21(3):279-288.
2. Chung KC, Kim HM, Malay S, Shauver MJ, WRIST Group:
Predicting outcomes after distal radius fracture: A 24-center
international clinical trial of older adults. J Hand Surg Am
2019;44(9):762-771. This is a randomized multicenter study of 187
patients in the Wrist and Radius Injury Surgical Trial
randomized to internal fixation, external fixation, or percutaneous
pinning compared with 117 patients who preferred nonsurgical
management. Primary outcome was 12-month Michigan Hand
Outcomes Questionnaire. Recovery was fastest for internal
fixation, but by 12 months there were no meaningful differences
in outcome. Level of evidence: II.
3. Bhashyam AR, Fernandez DL, Fernandez dell’Oca A, Jupiter JB:
Dorsal Barton fracture is a variation of dorsal radiocarpal
dislocation: A clinical study. J Hand Surg Eur Vol 2019;44(10):1065-
1071. This is a retrospective cohort study involving 111 patients
who sustained a dorsally displaced, intra-articular distal radius
fracture. Thirteen patients had a dorsal Barton fracture that was
best characterized as a dorsal radiocarpal dislocation after CT
analysis. Level of evidence: IV.
4. Dias R, Johnson NA, Dias JJ: Prospective investigation of the
relationship between dorsal tilt, carpal malalignment, and
capitate shift in distal radial fractures. Bone Joint J 2020;102-
 B(1):137-143. This is a prospective analysis of carpal alignment in
250 consecutive patients with 252 distal radius fractures. Carpal
alignment was most strongly associated with dorsal tilt and was
assessed using capitate shift, independent of age or wrist
position. Level of evidence: III.
5. Ochen Y, Peek J, van der Velde D, et al: Operative vs
nonoperative treatment of distal radius fractures in adults: A
systematic review and meta-analysis. JAMA Netw Open
2020;3(4):e203497. This is a systematic review and meta-analysis
comparing the functional, clinical, and radiographic outcomes
after surgical versus nonsurgical management of distal radius
fractures in adults. A total of 23 unique studies involving 2,254
patients were included. The meta-analysis suggested that surgical
management of distal radius fractures improved <1-year
Disabilities of the Arm, Shoulder and Hand scores and grip
strength compared with nonsurgical management, with no
difference in complication rate among adult patients younger
than 60 years. Level of evidence: I.
6. Mulders MAM, Walenkamp MMJ, van Dieren S, Goslings JC,
Schep NWL, VIPER Trial Collaborators: Volar plate fixation
versus plaster immobilization in acceptably reduced extra-
articular distal radial fractures: A multicenter randomized
controlled trial. J Bone Joint Surg Am 2019;101(9):787-796. This is a
multicenter randomized controlled trial comparing the outcomes
of open reduction and volar plate fixation with those of closed
reduction and plaster immobilization in adults with an
acceptably reduced extra-articular distal radius fracture in 92
randomized patients. At all follow-up time points (up to 12
months), surgically treated patients had be er Disabilities of the
Arm, Shoulder and Hand scores. Forty-two percent of
nonsurgically treated patients had a subsequent surgical
procedure. Level of evidence: I.
7. Hassellund SS, Williksen JH, Laane MM, et al: Cast
immobilization is non-inferior to volar locking plates in relation
to QuickDASH after one year in patients aged 65 years and older:
 A randomized controlled trial of displaced distal radius fractures.
Bone Joint J 2021;103-B(2):247-255. This is a randomized
noninferiority trial of 100 patients comparing cast immobilization
with volar locking plate for management of displaced distal
radius fractures in patients older than 65 years. Nonsurgical
treatment was noninferior to surgical treatment based on Quick
Disabilities of the Arm, Shoulder and Hand scores after 1 year,
but patients in the surgical group had a faster recovery and were
more satisfied with their wrist function. Level of evidence: I.
8. Saving J, Severin Wahlgren S, Olsson K, et al: Nonoperative
treatment compared with volar locking plate fixation for dorsally
displaced distal radial fractures in the elderly: A randomized
controlled trial. J Bone Joint Surg Am 2019;101(11):961-969. This is a
randomized controlled trial of 140 elderly patients comparing
volar locking plate fixation with nonsurgical management for
unstable, dorsally displaced distal radius fractures. At 3-month
and 12-month follow-up, Patient-Rated Wrist
Evaluation/Disabilities of the Arm, Shoulder and Hand scores
and grip strength were be er for the volar locking plate group
compared with the nonsurgical group. The complication rates
were similar. Level of evidence: I.
9. Mosenthal WP, Boyajian HH, Ham SA, Conti Mica MA:
Treatment trends, complications, and effects of comorbidities on
distal radius fractures. Hand (N Y) 2019;14(4):534-539. This is a
retrospective database study assessing the likelihood of
complications during management of 155,353 distal radius
fractures in adults. Comorbidities were more strongly associated
with developing complications than age, especially after open
treatment. Level of evidence: IV.
10. Zimmer J, Atwood DN, Lovy AJ, Bridgeman J, Shin AY, Brogan
DM: Characterization of the dorsal ulnar corner in distal radius
fractures in postmenopausal females: Implications for surgical
decision making. J Hand Surg Am 2020;45(6):495-502. This is a
multicenter retrospective cohort study characterizing the dorsal
ulnar corner fragment of distal radius fractures using CT scans in
 80 postmenopausal females. The mean articular surface depth of
this fragment was found to be <5 mm and 24% of the volar-dorsal
width of the radius. Level of evidence: III.
11. Hanel DP, Lu TS, Weil WM: Bridge plating of distal radius
fractures: The Harborview method. Clin Orthop Relat Res
2006;445:91-99.
12. Vannabouathong C, Hussain N, Guerra-Farfan E, Bhandari M:
Interventions for distal radius fractures: A network meta-analysis
of randomized trials. J Am Acad Orthop Surg 2019;27(13):e596-
e605. This is a network meta-analysis of randomized trials
comparing outcomes after management of distal radius fractures
in adults using external fixation, intramedullary nailing, K-wires,
casting, or plate fixation. Open reduction and internal fixation
with a plate demonstrated the most favorable results in terms of
early and sustained functional recovery with reduction in
fracture-healing complications. Level of evidence: I.
13. Yao J, Fogel N: Arthroscopy in distal radius fractures:
Indications and when to do it. Hand Clin 2021;37(2):279-291. This
is a narrative review article summarizing indications, techniques,
and approaches to the use of arthroscopy in distal radius
fractures.
14. Bergsma M, Bulstra AE, Morris D, Janssen M, Jaarsma R,
Doornberg J: A prospective cohort study on accuracy of dorsal
tangential views to avoid screw penetration with volar plating of
distal radius fractures. J Orthop Trauma 2020;34(9):e291-e297. This
is a prospective cohort study involving 50 consecutive patients
undergoing volar plating for distal radius fractures. The study
authors assessed the diagnostic performance of dorsal tangential
views to detect dorsal screw penetration. The dorsal tangential
view has a 52% sensitivity, negative predictive value of 95%, and
accuracy of 95%. Level of evidence: II.
15. DeGeorge BR, Brogan DM, Shin AY: The relationship of volar
plate position and flexor tendon rupture: Should we question the
validity of the Soong classification? Plast Reconstr Surg
 2020;146(3):581-588. This is a retrospective cohort study of 659
distal radius fractures. The reported incidence of isolated flexor
tendinopathy and rupture was 0.9% and 0.3%. The Soong
classification was not an independent predictor, as fracture
reduction was a significant confounder. Level of evidence: III.
16. Hirasawa R, Itadera E, Okamoto S: Changes in the rate of
postoperative flexor tendon rupture in patients with distal radius
fractures. J Hand Surg Asian Pac Vol 2020;25(4):481-488. This is a
retrospective cohort study of 130 patients treated with volar
locked plating for distal radius fractures. Rates of flexor tendon
irritation at 24-month follow-up decreased, presumably because
of improved plate placement based on Soong grade and fracture
reduction. Level of evidence: IV.
17. DeGeorge BR, Brogan DM, Becker HA, Shin AY: Incidence of
complications following volar locking plate fixation of distal
radius fractures: an analysis of 647 cases. Plast Reconstr Surg
2020;145(4):969-976. This is a retrospective cohort study of 647
distal radius fractures managed with volar plate fixation in 636
patients. The incidence of complications including transient
paresthesia, tendon rupture or irritation, and revision surgery
was reported. The overall complication rate was low. Factors
associated with complications were diabetes, obesity, intra-
articular fracture alignment, and plate prominence. Level of
evidence: III.
18. van der Vliet QMJ, Sweet AAR, Bhashyam AR, et al: Polytrauma
and high-energy injury mechanisms are associated with worse
patient-reported outcomes after distal radius fractures. Clin
Orthop Relat Res 2019;477(10):2267-2275. This is a retrospective
cohort study of 265 patients assessing the association between
polytrauma and high-energy injury mechanism with patient-
reported outcomes following management of distal radius
fractures. High-energy injury mechanism and health-related
quality of life scores were independently associated with inferior
wrist function, in addition to previously described factors such as
sex and articular involvement. Level of evidence: III.
19. Rua T, Malhotra B, Vijayanathan S, et al: Clinical and cost
implications of using immediate MRI in the management of
patients with a suspected scaphoid fracture and negative
radiographs results from the SMaRT trial. Bone Joint J 2019;101-
B(8):984-994. This randomized trial compared the clinical and cost
implications of using immediate emergency department MRI in
the acute management of patients with a suspected scaphoid
fracture and negative radiographs. Immediate MRI led to cost
savings, improved diagnostic accuracy, and higher patient
satisfaction. Level of evidence: I.
20. Cooney WP, Dobyns JH, Linscheid RL: Fractures of the
scaphoid: A rational approach to management. Clin Orthop Relat
Res 1980;149:90-97.
21. Dias JJ, Brealey SD, Fairhurst C, et al: Surgery versus cast
immobilisation for adults with a bicortical fracture of the
scaphoid waist (SWIFFT): A pragmatic, multicentre, open-label,
randomised superiority trial. Lancet 2020;396(10248):390-401. This
is a pragmatic, parallel-group, multicenter, open-label,
randomized superiority trial comparing the clinical effectiveness
of surgical fixation versus cast immobilization (followed by
immediate fixation if nonunion was confirmed) in 439 adult
patients older than 16 years. No significant differences in patient-
reported outcomes or complications were observed between the
groups. These findings suggest that scaphoid waist fractures with
less than 2 mm of displacement may be initially treated with cast
immobilization with immediate conversion to surgical fixation
when suspected nonunion is confirmed. Level of evidence: I.
22. Leslie IJ, Dickson RA: The fractured carpal scaphoid. Natural
history and factors influencing outcome. J Bone Joint Surg Br
1981;63-B(2):225-230.
23. Ma on JL, Lutsky KF, Tulipan JE, Beredjiklian PK: Reliability of
radiographs and computed tomography in diagnosing scaphoid
union after internal fixation. J Hand Surg Am 2021;46(7):539-543.
This was a prospective study comparing the reliability of
radiographs alone versus the combination of radiographs and CT
 in determining scaphoid union following open reduction and
internal fixation with a headless compression screw. Surgeons
were more certain in their evaluation of scaphoid healing with
the combination of CT and radiographs, but reliability was not
always improved by the addition of CT to radiographs. Level of
evidence: III.
24. Liu B, Wu F, Ng CY: Wrist arthroscopy for the treatment of
scaphoid delayed or nonunions and judging the need for bone
grafting. J Hand Surg Eur Vol 2019;44(6):594-599. This is a
retrospective cohort study reporting the outcomes of arthroscopy
in the management of delayed or nonunion scaphoid fractures in
25 patients. Based on arthroscopy, stable fractures were managed
with percutaneous screws, whereas unstable fractures underwent
arthroscopic bone grafting followed by percutaneous screw
fixation. Level of evidence: IV.
25. Engel H, Xiong L, Heffinger C, Kneser U, Hirche C: Comparative
outcome analysis of internal screw fixation and Kirschner wire
fixation in the treatment of scaphoid nonunion. J Plast Reconstr
Aesthetic Surg 2020;73(9):1675-1682. This is a retrospective cohort
study comparing clinical and radiographic outcomes between
cannulated compression screw and K-wire fixation of 95 scaphoid
nonunions managed with vascularized bone graft. No significant
difference in bony healing and functional outcomes was
observed. Level of evidence: IV.
26. Schormans PMJ, Kooijman MA, Ten Bosch JA, Poeze M,
Hannemann PFW: Mid-term outcome of volar plate fixation for
scaphoid nonunion. Bone Joint J 2020;102-B(12):1697-1702. This is a
prospective cohort study reporting the outcomes of scaphoid
nonunion treatment using a volar locking plate and cancellous
bone grafting from the ipsilateral iliac crest in 49 patients with
mean follow-up of 38 months. Union was achieved in 96% of
patients with improvements in range of motion and patient-
reported outcomes. Level of evidence: III.
27. Aibinder WR, Wagner ER, Bishop AT, Shin AY: Bone grafting
for scaphoid nonunions: Is free vascularized bone grafting
 superior for scaphoid nonunion? Hand (N Y) 2019;14(2):217-222.
This is a retrospective cohort study comparing the use of
structural iliac crest, 1,2-intercompartmental supraretinacular
artery, and medial femoral condyle bone grafts to treat scaphoid
nonunions in 109 patients. Union rates and mean time to union
were similar for all three groups, potentially highlighting the
value of careful patient selection for this condition. Level of
evidence: IV.
28. Rancy SK, Swanstrom MM, DiCarlo EF, et al: Success of
scaphoid nonunion surgery is independent of proximal pole
vascularity. J Hand Surg Eur Vol 2018;43(1):32-40.
29. Ross PR, Lan W-C, Chen J-S, Kuo C-F, Chung KC: Revision
surgery after vascularized or non-vascularized scaphoid
nonunion repair: A national population study. Injury
2020;51(3):656-662. This is a national database study assessing
rates of revision surgery after management of scaphoid
nonunions using vascularized (358 patients) or nonvascularized
bone grafts (3,819 patients). The failure rate requiring revision
surgery was 5.0% and 6.1%, respectively. These findings suggest
that traditional repair using nonvascularized bone grafting is a
reasonable first option in the management of scaphoid
nonunions. Level of evidence: IV.
30. Chan AHW, Elhassan BT, Suh N: The use of the proximal
hamate as an autograft for proximal pole scaphoid fractures:
Clinical outcomes and biomechanical implications. Hand Clin
2019;35(3):287-294. This is a case report illustrating the use of the
proximal pole of the hamate as a replacement arthroplasty in the
se ing of proximal pole scaphoid nonunions with collapse, bone
loss, and/or osteonecrosis. Level of evidence: V.
31. Kakar S, Greene RM, Elhassan BT, Holmes DR: Topographical
analysis of the hamate for proximal pole scaphoid nonunion
reconstruction. J Hand Surg Am 2020;45(1):69.e1-69.e7. This is an
imaging study comparing the surface topography of the proximal
hamate with the proximal pole of the scaphoid for nonunion
 reconstruction. In most cases, the proximal hamate appeared to
be a suitable donor match.
32. Pet MA, Assi PE, Yousaf IS, Giladi AM, Higgins JP: Outcomes of
the medial femoral trochlea osteochondral free flap for proximal
scaphoid reconstruction. J Hand Surg Am 2020;45(4):317-326.e3.
This is a retrospective cohort study reporting radiographic,
functional, and patient-reported outcomes of MFT osteochondral
free flap reconstruction of the proximal scaphoid in 11 patients at
∼2-year follow-up. All patients experienced fracture union with
improvement in functional and patient-reported outcomes. Level
of evidence: IV.
33. Martínez-Catalán N, Pajares S, Llanos L, Mahillo I, Calvo E: A
prospective randomized trial comparing the functional results of
buddy taping versus closed reduction and cast immobilization in
patients with fifth metacarpal neck fractures. J Hand Surg Am
2020;45(12):1134-1140. This is a randomized controlled trial
comparing functional outcomes of buddy taping versus reduction
and cast immobilization in patients with fifth metacarpal neck
fractures (<70° volar angulation without rotational deformity).
For this indication, functional outcomes and early return to work
were be er for the buddy taping/early mobilization group. Level
of evidence: I.
34. Eisenberg G, Clain JB, Feinberg-Zadek N, Leibman M, Belsky M,
Ruchelsman DE: Clinical outcomes of limited open
intramedullary headless screw fixation of metacarpal fractures in
91 consecutive patients. Hand (N Y) 2020;15(6):793-797. This is a
retrospective cohort study assessing the results of intramedullary
screw fixation for metacarpal fixation in 91 patients. Union rates
were high with excellent outcomes. Level of evidence: IV.
35. Kibar B, Cavit A, Örs A: A comparison of intramedullary
cannulated screws versus miniplates for fixation of unstable
metacarpal diaphyseal fractures. J Hand Surg Eur Vol
2022;47(2):179-185. This is a prospective randomized study
comparing the clinical and radiologic results of retrograde
intramedullary compression screw fixation of intramedullary
 headless cannulated screw compression and plate fixation in 69
patients. At final follow-up, no significant differences in total
active movement, visual analog pain score, Disabilities of the
Arm, Shoulder and Hand scores, or grip strength were observed.
Level of evidence: I.
36. Hoang D, Vu C, Jackson M, Huang JI: An anatomic study of
metacarpal morphology utilizing CT scans: Evaluating
parameters for antegrade intramedullary compression screw
fixation of metacarpal fractures. J Hand Surg Am 2021;46(2):149.e1-
149.e8. This is a cadaver study assessing the morphology of the
metacarpal shafts and feasibility of antegrade intramedullary
compression screw fixation of metacarpal shaft fractures. The
study provides guidance for optimal screw diameter sizes for
each metacarpal. Antegrade screws could be placed in all digits
using limited incisions with minimal violation of the articular
surfaces of the trapezium, capitate, hamate, and metacarpal
bases.
37. Minhas SV, Catalano LW: Comparison of open and closed hand
fractures and the effect of urgent operative intervention. J Hand
Surg Am 2019;44(1):65.e1-65.e7. This is a retrospective database
study comparing the incidence of 30-day postoperative infection
in surgically managed open and closed metacarpal and
phalangeal fractures between patients who were treated urgently
(within 1 day) versus those treated in more delayed fashion (>1
day). Smoking was associated with increased 30-day infection
rate, but patients who were treated more than 1 day after injury
did not have a significantly higher rate of infection. Level of
evidence: II.
38. Kootstra TJM, Keizer J, Bhashyam A, et al: Patient-reported
outcomes and complications after surgical fixation of 143
proximal phalanx fractures. J Hand Surg Am 2020;45(4):327-334.
This is a retrospective cohort study comparing patient-reported
outcome measures and complications between K-wire, lag screw,
and plate fixation of 159 proximal phalangeal fractures (excluding
the thumb). No differences in functional outcomes were
 observed, although unplanned revision surgery was more
common in the plate fixation group. Level of evidence: IV.
39. El-Saeed M, Sallam A, Radwan M, Metwally A: Kirschner wires
versus titanium plates and screws in management of unstable
phalangeal fractures: A randomized, controlled clinical trial. J
Hand Surg Am 2019;44(12):1091.e1-1091.e9. This is a randomized
controlled clinical trial comparing clinical, radiologic, and
functional outcomes of percutaneous K-wires and lateral
titanium plate and screws in the treatment of 40 patients with an
unstable extra-articular proximal and middle phalangeal fracture.
The plate fixation group was associated with higher total active
motion and fewer complications, although union rates and
patient-reported outcomes were similar. Level of evidence: II.
40. Reid AWN, Sood MK: Intramedullary cannulated compression
screws for extra-articular phalangeal fractures. J Hand Surg Asian
Pac Vol 2021;26(2):180-187. This is a systematic review reporting
clinical outcomes of intramedullary cannulated compression
screw fixation of unstable extra-articular phalangeal fractures in a
total of 146 phalangeal fractures. All fractures united with similar
range of motion, complication rate, and patient-reported
outcomes compared with plate/screw and percutaneous K-wire
constructs. Level of evidence: I.
41. Gaspar MP, Gandhi SD, Culp RW, Kane PM: Dual antegrade
intramedullary headless screw fixation for treatment of unstable
proximal phalanx fractures. Hand (N Y) 2019;14(4):494-499. This is
a retrospective case series evaluating the short-term clinical
outcomes of 10 proximal phalangeal fractures fixed using dual
antegrade IMHS fixation. All patients had functional final range
of motion and acceptable grip strength and Quick Disabilities of
the Arm, Shoulder and Hand scores at final follow-up. Level of
evidence: IV.
42. Hanel DP, Chin SH: Wrist level and proximal-upper extremity
replantation. Hand Clin 2007;23(1):13-21.
43. Mathieu L, Bertani A, Gaillard C, et al: Surgical management of
combat-related upper extremity injuries. Chir Main
2014;33(3):174-182.
44. Bhashyam AR, Liu Y, Kao DS: Targeted peripheral nerve
interface: Case report with literature review. Plast Reconstr Surg
Glob Open 2021;9(4):e3532. This is a case series and narrative
review describing current independent and hybrid techniques of
neuroma management in patients with amputations. Level of
evidence: IV.
45. Valerio IL, Dumanian GA, Jordan SW, et al: Preemptive
treatment of phantom and residual limb pain with targeted
muscle reinnervation at the time of major limb amputation. J Am
Coll Surg 2019;228(3):217-226. This is a multi-institutional
retrospective cohort study comparing pain and patient-related
outcomes in patients with and without targeted muscle
reinnervation at the time of major limb amputation. Preemptive
surgical intervention with targeted muscle reinnervation was
associated with decreased phantom limb pain and symptomatic
neuroma-related residual limb pain. Level of evidence: III.
46. Eberlin KR, Ducic I: Surgical algorithm for neuroma
management: A changing treatment paradigm. Plast Reconstr
Surg Glob Open 2018;6(10):e1952.
47. Sabapathy SR, Bhardwaj P: Se ing the goals in the management
of mutilated injuries of the hand-impressions based on the
Ganga Hospital experience. Hand Clin 2016;32(4):435-441.
48. Kurucan E, Thirukumaran C, Hammert WC: Trends in the
management of traumatic upper extremity amputations. J Hand
Surg Am 2020;45(11):1086.e1-1086.e11. This is a retrospective
database study investigating yearly trends of traumatic upper
extremity amputations and evaluation of disparities in access to
care. The study authors reported a higher incidence of
replantation at high-volume hospitals, especially in younger
patients with private insurance. They suggest that patients with
traumatic amputations may benefit from treatment at high-
 volume institutions to improve access to care. Level of evidence:
II.
49. Kapandji AI: The Physiology of the Joints, ed 6. Elsevier, 2010.
50. Pet MA, Ko JH, Vedder NB: Reconstruction of the traumatized
thumb. Plast Reconstr Surg 2014;134(6):1235-1245.
51. Brown PW: Less than ten–surgeons with amputated fingers. J
Hand Surg Am 1982;7(1):31-37.
52. Harbour PW, Malphrus E, Zimmerman RM, Giladi AM: Delayed
digit replantation: What is the evidence? J Hand Surg Am
2021;46(10):908-916. This is a systematic review assessing the
potential and outcomes of delayed digital replantation. The study
authors identified substantial limitations in the current literature
regarding ischemia time cutoffs and the feasibility of delayed
digit replantation. Level of evidence: II.
53. Kayalar M, Güntürk ÖB, Gürbüz Y, Toros T, Sügün TS,
Ademoğlu Y: Survival and comparison of external bleeding
methods in artery-only distal finger replantations. J Hand Surg
Am 2020;45(3):256.e1-256.e6. This is a retrospective cohort study
comparing nail matrix or hyponychial area bleeding with pulp
skin area bleeding (crater method) in 228 artery-only replants.
Digit viability was maintained in 84% of patients treated with nail
bed bleeding and 76.9% of patients with the crater method. Level
of evidence: IV.
54. Lim R, Lee E, Lim J, Chong AKS, Sebastin SJ, Foo A: External
bleeding versus dermal pocketing for distal digital replantation
without venous anastomosis. J Hand Surg Eur Vol. 2019;44(2):181-
186. This is a retrospective cohort study comparing two methods
of venous decongestion after artery-only distal digital
replantation in 43 total digits (external bleeding versus dermal
pocketing). No difference in digital survival was observed with
either method. Level of evidence: IV.
55. Retrouvey H, Solaja O, Bal er HL: Role of postoperative
anticoagulation in predicting digit replantation and
revascularization failure: A propensity-matched cohort study.
 Ann Plast Surg 2019;83(5):542-547. This is a propensity-matched
retrospective cohort study assessing whether the use of
postoperative therapeutic anticoagulation reduced the risk of
digit replantation and revascularization failure. Use of
anticoagulation (postoperative therapeutic heparin or dextran)
did not have a protective effect against digit failure. Level of
evidence: III.
56. Nishijima A, Yamamoto N, Gosho M, et al: Appropriate use of
intravenous unfractionated heparin after digital replantation: A
randomized controlled trial involving three groups. Plast Reconstr
Surg 2019;143(6):1224e-1232e. This is a prospective, randomized,
single-blind, three-arm controlled clinical trial comparing
survival of digit replantation with the following postoperative
anticoagulation: no heparin, low-dose heparin, and high-dose
heparin. No significant differences were observed between
groups among the 101 included fingers. In subgroup analysis,
success rate with heparin was effective in patients aged 50 years
or older. Level of evidence: II.
S E CT I ON 7

Hip and Femur

SECTION EDITOR
Calin Stefan Moucha, MD, FAAOS
C H AP T E R 3 9

Anatomy and Biomechanics,

Evaluation, Clinical Examination, and
Imaging of the Hip
Mitchell C. Weiser MD, MEng, FAAOS, Ferdinand J. Chan MD,
FAAOS

Dr. Weiser or an immediate family member serves as a board member, owner, officer, or committee member of the
American Academy of Orthopaedic Surgeons. Neither Dr. Chan nor any immediate family member has received
anything of value from or has stock or stock options held in a commercial company or institution related
directly or indirectly to the subject of this chapter.

ABSTRACT
The hip is a complex diarthrodial ball-and-socket joint, allowing for
multiaxial rotatory movement in flexion-extension, abduction-adduction, and
internal-external rotation. Knowledge of the anatomy, ossification, and
biomechanical principles of the native hip joint is critical to understanding
the pathologic basis of hip injuries and disorders in both the pediatric and
adult patient population. This knowledge empowers the physician to
appropriately apply and interpret physical examination maneuvers and
imaging studies to aid in diagnosing common hip maladies.
Keywords: hip anatomy; hip joint; hip physical examination; imaging

Introduction
The hip joint is composed of the femoral head and the acetabulum, which
articulate as a ball-in-socket diarthrodial joint capable of multiaxial rotatory
motion. In addition to the bony anatomy, the hip joint is supported by soft
tissue, including the acetabular labrum and hip capsule, which contribute to
the primary stabilization of the articulation of the femoral head in the
acetabulum. This is further reinforced with the hip musculature serving as
dynamic secondary stabilizers. It is an oversimplification to understand the
hip as a pure ball-and-socket joint because the femoral head is not a true
sphere in shape and the socket of the acetabulum is not a true hemisphere (it
is horseshoe shaped). Anatomic variations in acetabular inclination, version,
and dome coverage combined with variations in proximal femoral
architecture and version add further complexity to the idealized hip joint
articulation. Another level of complexity to this articulation is again added
when considering dynamic pelvic positioning through the hip-spine
relationship. Understanding the normal hip joint anatomy and its variants,
both benign and pathologic, is fundamental to the practicing orthopaedic
surgeon.

Osseous and Ligamentous Anatomy

The process of hip-joint formation begins early in embryonic development,
beginning during the fourth week of embryonic gestation. By the sixth week
of embryonic development, chondroblasts appear and by the end of the
eighth week, cartilage templates of the femur and acetabulum are complete,
as are microscopic precursors of the acetabular labrum, ligamentum teres,
and transverse acetabular ligament. Ossification of the femur is complete up
to the lesser trochanter by the 16th week, and the primary ossification centers
of the ilium, pubis, and ischium also have appeared. 1
The acetabulum is formed from both the triradiate cartilage and the
acetabular cartilage complex, which is the fusion of the ilium, ischium, and
pubis. The triradiate cartilage forms the nonarticular aspect of the medial
wall of the acetabulum and contributes to 70% of the overall depth of the
socket. 2 The acetabular cartilage complex forms the articular surface of the
acetabulum and is composed mainly of hyaline cartilage. Three secondary
ossification centers of the acetabulum appear between 8 and 9 years of age
along the rim of the acetabulum: anteriorly, superiorly, and posteriorly.
Fusion of these centers occurs by adulthood and contributes to the
development of the acetabular rim. The superior secondary ossification
center is the most common of the three to fail to fuse, which leads to the
radiographic appearance of an os acetabuli. Radiographic closure of the
triradiate cartilage occurs at the median age of 13.9 years. 3 The normal
versional orientation of the acetabulum, with the pelvis in neutral position
while supine with respect to the sagi al plane, is anteverted, that is, the
opening of the acetabulum facing anteriorly. The degree of normal
anteversion occurs on a spectrum and is generally believed to be between 15°
and 20° 4 with a mean of 17.6°. 5 Functional acetabular anteversion is a
dynamic parameter and varies according to pelvic positioning. In patients
with normal spine mobility, posterior pelvic rollback (or tilting), such as that
which occurs with si ing, increases the functional anteversion of the
acetabulum, whereas anterior tilting, such as when standing, decreases the
functional anteversion. The normal relationship between pelvic tilt and
functional acetabular anteversion is a change of 1° in acetabular anteversion
for every 0.8° change in pelvic tilt. 6 Changes in spinal-pelvic mobility can
change the nature of this relationship because of pathologic conditions (such
as lumbar spine stiffness from degenerative diseases) or prior lumbar fusion.
Understanding the nature of the normal and pathologic hip-spine
relationship is critical, particularly when considering implant positioning
targets during total hip arthroplasty. Acetabular coverage of the femoral
head is directly related to the depth of the acetabulum and proper formation
of the acetabular rim. This can be measured radiographically on a supine AP
pelvis radiograph using the center-edge angle of Wiberg. Normal acetabular
superolateral coverage is thought to be between 25° and 35° with an angle
less than 25° representing borderline dysplasia and an angle greater than 40°
representing overcoverage. 4
The primary ossification center of the femur appears in the seventh week of
gestation, and ossification occurs proximally to the greater trochanter and
femoral neck by birth. Secondary ossification centers at the greater
trochanter, and femoral head appears between 4 and 7 months of age. These
ossification centers are connected by a small isthmus that is responsible for
the overall growth and diameter of the femoral neck. The secondary
ossification center of the femoral head contains the physis, which is
responsible for 30% of length of the femur and 13% of the overall length of
the limb. 7 The median age of radiographic closure of the secondary
ossification center of the femoral head occurs at age of 15.4 years and that of
the greater trochanter at 16.8 years. 3 The bony trabecular architecture of the
proximal femur is oriented in a pa ern designed to resist the mechanical
forces placed across it. The formation of these trabecular pa erns is done via
bone remodeling in response to the Wolff law. These trabecular pa erns are
oriented into primary and secondary tensile and compressive groups. This
trabecular ultrastructure leads to the formation of a small triangular area in
the inferior femoral neck femoral neck relatively devoid of trabeculae. This
area is known as the Ward triangle and is bounded by the principal
compressive trabeculae, secondary compressive trabeculae, and primary
tensile trabeculae. The Ward triangle serves as a weak point in the femoral
neck and osteoporotic femoral neck fractures occur commonly through this
area in elderly patients. 8 Proximal femoral orientation is also determined by
application of the Wolff law and progressive bone remodeling during
development. At the time of birth, the mean anteversion of the proximal
femur is 45°, decreasing to 31.1° by 1 year of age, and finally to 15.4° by 16
years of age. 9 Similarly, the neck-shaft angle of the proximal femur also
changes over time, with the mean neck-shaft angle at 1 year of age being
132.6° and decreasing to 127.3° by age 18 years. 9 Disruptions in the
application of physiologic mechanical forces to both the proximal femur and
acetabulum during development lead to pathologic conditions of the hip,
such as developmental dysplasia.
Understanding the blood supply to the femoral head is critical when
considering surgical intervention for hip preservation or trauma procedures.
A silicone injection study demonstrated that the dominant blood supply to
the femoral head comes from superior retinacular vessels via the medial
femoral circumflex artery in most of the anatomic specimens (29 of 36 hips),
although there are some individuals in whom the inferior gluteal artery may
serve as the dominant blood supply (6 of 36 hips). 10 Additionally, some
individuals may have a substantial anastomosis between the medial femoral
circumflex artery and the inferior gluteal artery adjacent to the tendon of the
obturator externus. 11
The hip joint is stabilized by a soft-tissue envelope consisting of the joint
capsule and acetabular labrum. The joint capsule is divided into internal and
external fibers. The internal fibers form the zona orbicularis, which is the
capsular ring that a aches to the base of the femoral head. This structure
provides added stability to the hip joint through a screw-home mechanism in
extension and external rotation and can serve as a checkrein to limit
distraction of the femoral head. 12 It is an important arthroscopic landmark
that divides the hip joint into the central and peripheral compartments. The
zona orbicularis is also thought to play a contributory role in the circulation
of synovial fluid within the hip joint. 12 The external fibers of the capsule run
longitudinally and are divided into three main ligaments: pubofemoral,
ischiofemoral, and iliofemoral. The pubofemoral ligament originates on the
iliopectineal eminence of the superior ramus, wraps around the iliofemoral
ligament, and blends into the insertion of the ischiofemoral ligament along
the inferior femoral neck just distal to the acetabular rim. The pubofemoral
ligament helps control excessive abduction and external rotation during hip
extension. 12 The ischiofemoral ligament originates from the root of the
ischial ramus and traverses the femoral neck superolaterally to insert at the
base of the greater trochanter. It serves to reinforce the capsule in internal
rotation with neutral position of the hip and restrict combined flexion-
adduction positions. 12 The iliofemoral ligament is the largest of the three and
is divided into two bands: medial and lateral, the Y ligament of Bigelow. The
ligament originates from a broad base along the anterior inferior iliac spine
and anterior rim of the acetabulum. The medial limb passes anteriorly along
the femoral neck in a vertical orientation and inserts along the anterior femur
at the level of the lesser trochanter along the intertrochanteric line. The
lateral limb traverses the anterior hip in an oblique orientation and inserts
superior to the intertrochanteric line at the greater trochanteric crest. The
iliofemoral ligament serves to restrict internal rotation in hip flexion and
reinforce the capsule in external rotation and hip extension. 12 The soft-tissue
envelope surrounding the hip joint is richly innervated with proprioceptive
and nociceptive fibers, allowing these structures to serve as important
sources of hip pain when damaged. The hip capsule receives innervation
from all the major nerves surrounding the hip including branches of the
obturator, femoral, sciatic, and superior gluteal nerves, and the nerve to the
quadratus femoris. 13 The complexity of this innervation can lead to hip pain
being felt in the groin, thigh, bu ock, knee, and as far distal as the foot. 14
The acetabular rim blends into the acetabular labrum, a fibroconnective
tissue that extends from the rim of the acetabulum that contributes to the
suction seal of the femoral head within the acetabular cavity. The height of
the labrum is variable along the acetabular rim and has been found to be
between 4 and 8 mm on average. 15 A 2020 study correlated the height of the
labrum with the strength of the suction seal to resist distractive forces, with
labral height less than 6 mm having reduced capability to resist distractive
forces on the femoral head. 16 The labrum consists of type I and III collagen
along its capsular-facing surface, and fibrocartilage along its articular-facing
surface. Most of these collagen fibers have been found to be circumferential
in alignment. 17 The articular surface of the labrum is contiguous with the
articular cartilage of the acetabulum. 18 The inferior aspect of the acetabulum
is bounded by the transverse acetabular ligament, which connects the
anterior and posterior inferior rims of the acetabulum. As such, it has been
reported as a reliable intraoperative landmark to gauge acetabular
anteversion during total hip arthroplasty. 19 The acetabular labrum is also
richly innervated and contains several different types of sensory nerve organs
along its articular-facing side, including nociceptors and mechanoreceptors. 20
The main blood supply to the acetabular labrum was shown in a silicone
injection study to come from a periacetabular periosteal vascular ring that
traverses the osteolabral junction of the labrum flowing outward to the free
edge of the labrum. There is no significant contribution to this vascular
supply from the hip capsule, osseous labral rim, or synovial lining. 21
The ligamentum teres is a soft-tissue structure that connects the femoral
head and acetabulum directly. It is composed of two separate bands,
approximately 30 to 35 mm in length, which connect the fovea capitis of the
femoral head to the transverse acetabular ligament inferiorly and pubic and
ischial acetabular margins medially. It comprises type I, III, and V collagen
fibers and contains an anterior branch of the posterior division of the
obturator artery. 12 The innervation of the ligamentum teres is controversial,
but a 2019 study states there has been histologic evidence for the presence of
free nerve endings and Pacini corpuscles contained within it, suggesting that
it can be a source of pain and play a role in proprioception. 22

Muscular Anatomy
The thigh has three separate muscular compartments: anterior, lateral, and
medial. There are 22 separate muscles that cross the hip joint, and 29 muscles
about the hip joint and proximal thigh that play a role providing motor
function for the joint. The muscles as presented here are grouped by their
functional actions. A full list of the muscles about the hip joint grouped by
their anatomic location and information on their origins and insertions,
innervation, and function is provided in Table 1.

Table 1
Muscular Anatomy of the Hip

Muscle Compartment Origin Insertion Innervation Function

Sartorius Anterior ASIS Proximal Femoral
medial tibia nerve Hip
(pes flexion
anserinus) Abduction
External
rotation

Iliopsoas Anterior Iliac fossa, TPs Lesser Femoral

L1-L5 trochanter nerve Hip
flexion

Rectus femoris Anterior AIIS (direct Superior pole Femoral

head), anterior of the patella nerve Hip
acetabular rim flexion
(indirect head) Knee
extension

Vastus medialis Anterior Distal Superior Pole Femoral

intertrochanteric of the patella nerve Knee
line, linea via medial extension
aspera, medial quadriceps
intermuscular tendon
septum
Muscle Compartment Origin Insertion Innervation Function
Vastus lateralis Anterior Proximal Superior pole Femoral
intertrochanteric of the patella nerve Knee
line, vastus via lateral extension
ridge, lateral quadriceps
intermuscular tendon
septum
Vastus intermedius Anterior Anterior shaft of Superior pole Femoral
femur of the patella nerve Knee
extension

Pectineus Anterior Pectineal line of Pectineal line Femoral

the pubis of the femur nerve Hip
flexion
Hip
adduction
Internal
rotation

Iliocapsularis Anterior Inferior border Distal to the Femoral

of AIIS lesser nerve Dynamic
trochanter hip
capsule
stabilizer
(pulls
capsule
proximal
and
medial)

Adductor longus Medial Anterior pubic Linea aspera Obturator

ramus nerve Hip
adduction
Internal
rotation
Hip
flexion

Adductor brevis Medial Inferior pubic Linea aspera Obturator

ramus nerve Hip
adduction
Internal
rotation
Hip
flexion

Adductor magnus Medial Inferior pubic Linea aspera, Obturator

ramus, ischial adductor nerve Hip
tuberosity tubercle adduction
Hip
extension
Internal
rotation
Muscle Compartment Origin Insertion Innervation Function
Gracilis Medial Inferior pubic Proximal Obturator
symphysis medial tibia at nerve Hip
pes anserinus adduction
Hip
flexion

Semimembranosus Posterior Ischial Posteromedial Tibial nerve

tuberosity tibia and Hip
posterior extension
capsule of the Knee
knee flexion

Semitendinosus Posterior Ischial Proximal Tibial nerve

tuberosity medial tibia at Hip
pes anserinus extension
Knee
flexion

Biceps femoris Posterior Ischial Fibular head Tibial nerve

(long head) tuberosity Hip
extension
Hip
external
rotation
Hip
adduction
Knee
flexion

Tensor fascia lata Tensor gluteal Anterior iliac Iliotibial band Superior
crest gluteal Hip
nerve flexion
Hip
abduction
Internal
rotation

Gluteus maximus Maximus Posterior ilium Iliotibial band, Inferior

gluteal posterior to gluteal gluteal Hip
posterior gluteal tuberosity of nerve extension
line the posterior Hip
femur adduction
External
rotation

Gluteus medius Medius- Iliac wing Greater Superior

minimus between trochanter gluteal Hip
gluteal posterior and nerve abduction
middle gluteal Hip
lines extension
Internal
rotation
 Muscle Compartment Origin Insertion Innervation Function
Gluteus minimus Medius- Iliac wing Greater Superior
minimus between middle trochanter gluteal Hip
gluteal and inferior nerve abduction
gluteal lines Hip
flexion
Internal
rotation

Piriformis Deep gluteal Anterior sacrum Piriformis Nerve to

fossa greater piriformis External
trochanter rotation
Hip
abduction

Superior gemellus Deep gluteal Ischial spine Medial greater Nerve to

trochanter obturator External
internus rotation

Inferior gemellus Deep gluteal Ischial Medial greater Nerve to

tuberosity trochanter quadratus External
femoris rotation

Quadratus femoris Deep gluteal Ischial Quadrate line Nerve to

tuberosity of femur quadratus External
femoris rotation
Hip
adduction

Obturator internus Deep gluteal Posterior Medial greater Nerve to

surface of the trochanter obturator External
obturator internus rotation
membrane, rim
of pubis and
ischium
bordering the
obturator
membrane
Obturator externus Deep gluteal Anterior surface Medial greater Obturator
of the obturator trochanter nerve Hip
membrane, rim adduction
of pubis and External
ischium rotation
bordering the
obturator
membrane
AIIS = anterior inferior iliac spine, ASIS = anterior superior iliac spine, L = lumbar level, TPs = transverse
processes

Anatomic Compartments
There are three anatomic compartments of the thigh: anterior, posterior, and
medial. The gluteal region contains four distinct compartments: (1) the
tensor compartment, which contains the tensor fascia lata and a branch of the
superior gluteal nerve; (2) the medius-minimus compartment, which contains
the gluteus medius and minimus and is supplied by the superior gluteal
nerve and vessels; (3) the deep gluteal compartment, which contains the
short external rotators; and (4) the maximus compartment, which contains
the gluteus maximus and is supplied by the inferior gluteal nerve and
vessels. Although a rare entity, compartment syndrome of each gluteal
compartment has been reported. 23

Muscle Function
The primary flexors of the hip include the iliopsoas, sartorius, tensor fascia
lata, rectus femoris, adductor longus, and pectineus. Secondary flexors of the
hip include adductor brevis, gracilis, and the anterior fibers of the gluteus
minimus. 24
The primary extensors of the hip include gluteus maximus, the posterior
head of the adductor magnus, the long head of the biceps femoris,
semitendinosus, and semimembranosus. Secondary extensors of the hip
include the middle and posterior fibers of the gluteus medius and the
anterior head of the adductor magnus. 24
The primary external rotators of the hip include the gluteus maximus,
piriformis, obturator internus, superior gemellus, inferior gemellus, and
quadratus femoris. The secondary external rotators include the posterior
fibers of the gluteus medius, posterior fibers of the gluteus minimus,
obturator externus, sartorius, and the long head of the biceps femoris. 24
The internal rotators of the hip include the anterior fibers of the gluteus
minimus, the anterior fibers of the gluteus medius, tensor fascia lata,
adductor longus, adductor brevis, pectineus, and the posterior head of the
adductor magnus. 24
The primary adductors of the hip include the pectineus, adductor longus,
gracilis, adductor brevis, and adductor magnus. The secondary adductors
include the long head of the biceps femoris, the posterior fibers of the
gluteus maximus, quadratus femoris, and the obturator externus. 24
The primary abductors of the hip include the gluteus medius, gluteus
minimus, and tensor fascia lata. The secondary abductors include the
piriformis, sartorius, and rectus femoris. 24
The iliocapsularis is a li le-known muscle about the hip joint. It originates
along the inferior border of the anterior inferior iliac spine and broadly along
the anterior hip capsule and inserts just distal to the lesser trochanter. Its
true function remains controversial, but it is thought to play a role in the
stabilization of dysplastic hips and serves as an important landmark in
anterior surgical approaches to the hip joint. 25

Hip Biomechanics
The hip joint is a multiaxial ball-and-socket joint where most of the motion
between the femoral head and acetabulum is rotational, with no detectable
translation. 26 , 27 Hip range of motion is limited by both soft tissue and bony
architecture. In the sagi al plane, hip flexion averages 120° to 125° and hip
extension averages 10° to 15°. 28 , 29 Pelvic rotation accounts for approximately
18% of hip flexion during weight-bearing activities. 30 Conversely, hip flexion
is limited by knee extension secondary to the pull of the hamstrings. 29 Hip
extension is limited by the anterior structures of the hip joint–iliofemoral
ligament, anterior capsule, and hip flexors. 28 , 29 Internal and external rotation
of the hip are also affected by knee and hip positions. External rotation
ranges from 0° to 90°, whereas internal rotation ranges from 0° to 70°. 28 , 31
There is an average of 45° of abduction and 30° of adduction. 32
Normal gait requires approximately 40° to 50° of rotation, 35° of hip flexion,
and 10° of extension. 33 Hip flexion increases to greater than 55° with running.
34
Furthermore, during running, adduction can increase to 20° just before heel
strike; maximum abduction occurs during swing phase after toe-off. 34
There is a compressive force across the femoroacetabular joint that is never
fully unloaded with activities of daily living. 26 This compressive force is the
result of a balance between the moment arm of the body weight and the pull
of the abductors at the greater trochanter that work together to level the
pelvis. 35 During single-leg stance and the swing phase of gait, this
compressive force can be two to four times the body weight. 35 During slow
pace gait, there is a larger force generated by the gluteus minimus and
medius because of the prolonged single-leg stance phase. 36 Stumbling can
generate forces greater than eight times body weight 37 and can have
detrimental effects in patients with arthrosis and specifically those in the
early postoperative period after hip arthroplasty.
Contact pressure is highest in the peripheral articular cartilage, especially
the posterosuperior acetabulum during gait. 36 , 38 Contact pressure is lowest
in the foveal region and inferior aspect of the femoral head. 38 Cartilage
thickness of the femoral head and acetabulum appears to correspond to the
contact pressure experienced at the various locations. 39 Contralateral cane
use decreases peak pressures and measured gluteus electromyographic
readings. 36 Obesity increases the peak hip moments and can lead to injury
and dysfunction. 40

Physical Examination
Obtaining a detailed history is essential to diagnose the cause of a patient’s
hip pain. Key elements include onset, quality, duration, location of
symptoms, and exacerbating/alleviating factors. Medical history such as HIV,
sickle cell anemia, corticosteroid use, and excessive alcohol use should be
elucidated in conditions such as osteonecrosis of the hip. Constitutional
symptoms such as weight changes, fatigue, and fever/chills should be
assessed to rule out infection, malignancy, and inflammatory processes. 41
Changes in activity, training regimens, or trauma should also be assessed.
Previous surgical and nonsurgical interventions should be questioned. As
reviewed in a 2019 study, a patient may grasp the lateral aspect of the hip in a
manner described as the C-sign, which may suggest intra-articular hip
pathology. 42
A comprehensive examination should include examination of the lumbar
spine as well as the knee, as hip pain can be referred from these areas. Pain
location can help narrow the underlying pathology. Anterior groin pain can
be due to intra-articular or extra-articular pathologies. Intra-articular
pathologies include osteoarthritis, inflammatory arthritis, femoral neck stress
fractures, labral tears, femoroacetabular impingement, osteonecrosis, and
loose bodies. Extra-articular pathologies include hip flexor tendinitis/strain,
sports hernia, iliopsoas snapping syndrome, obturator or ilioinguinal nerve
entrapment, and osteitis pubis. Lateral hip pain may be due to greater
trochanteric pain syndrome, abductor tears or dysfunction, external snapping
hip, contusion of the iliac crest (hip pointer), and meralgia paresthetica. 43
Posterior hip pain can be due to extensor or rotator muscle pain, piriformis
syndrome, proximal hamstring rupture, ischiofemoral impingement, nerve
entrapment (sciatic or pudendal nerve), and bu ock claudication. 44 Other
causes of posterior hip pain can also be referred from the sacroiliac joint or
lumbar spine.
A comprehensive physical examination includes gait analysis, inspection,
palpation, range-of-motion testing, provocative maneuvers, and
neurovascular examination. The patient should be assessed in standing,
supine, lateral, and prone positions (for posterior hip pain). Any
discrepancies in leg length should be determined. To compensate for weak
hip abductors, a Trendelenburg gait is seen where there is a compensatory
lateral tilt of the trunk. With bilateral abductor weakness, a waddling gait
may be present.
The clinical examination begins in the supine position with the inspection
for skin abnormalities. Palpation of bony landmarks of the pelvis and hip as
well as palpation of each muscle group and bursal pain should be performed.
Range-of-motion measurements and strength testing should be compared
with those of the contralateral hip. It is helpful to begin with the contralateral
hip to prevent guarding throughout the remainder of the clinical
examination. Any reproducible snapping should be determined.
Provocative maneuvers should be performed for specific pathologies. A
positive FADDIR (flexion, adduction, internal rotation) test can suggest
femoroacetabular impingement or anterior labral tear. Patrick test or FABER
(flexion, abduction, external rotation) test can elicit posterior hip pain
suggesting sacroiliac joint pathology or posterior hip impingement. Groin
pain during the FABER test suggests iliopsoas pathology or intra-articular hip
pathology, such as impingement, labral tear, or osteoarthritis. Resisted hip
flexion or the Stinchfield test increases hip joint reactive forces and can
suggest intra-articular hip pathology. The Ling test is resisted leg extension
and can be helpful in distinguishing true intra-articular hip pain from lumbar
back pain. If the pain in the hip reduces during resisted leg extension, this
can suggest the hip joint as the source of pain. If the pain remains
unchanged, this can be more suggestive of lumbar spine pathology as the
pain generator. A positive Thomas test is seen with hip flexion contractures.
The Ely test is performed in the prone position to assess for rectus femoris
tightness.
Abductor strength can be assessed with the patient in the lateral decubitus
position. The Ober test can be performed to assess for iliotibial band
tightness.
When microinstability of the hip is suspected, a Beighton score should be
a ained to assess for generalized ligamentous laxity. The anterior
apprehension test or the hyperextension, external rotation test can reproduce
anterior hip pain or apprehension. Posterior hip pain can suggest posterior
impingement. When there is less than 3 inches from the lateral knee to the
examination table with FABER testing, laxity of the hip joint may be present.
The abduction-extension-external rotation test and prone external rotation
test can reproduce a patient’s symptoms of microinstability. The examiner
can feel the hip toggle with the axial distraction test; the test can also cause
apprehension or pain for the patient. 45
Imaging

Radiographs
Plain radiographs are the first-line imaging studies for patients with hip pain.
Standard AP radiographs of the hip and pelvis allow for examination of
fractures, joint space narrowing, acetabular version (presence of crossover
sign), and bone quality. Acetabular coverage can be assessed with
measurement of the lateral center-edge angle, Tönnis angle/acetabular
inclination, and femoroepiphyseal acetabular roof index. Anterior coverage
can be assessed on the false profile view. The modified Dunn view is useful to
measure head-neck offset ratio and alpha angle for cam lesions. Radiographs
of the lumbar spine or ipsilateral knee may be helpful if referred pain is
suspected. When lumbar spine pathology is suspected while planning for a
hip replacement, standing AP pelvis as well as flexion and extension views of
the lumbar spine should be obtained.

Ultrasonography
Ultrasonography serves as an inexpensive diagnostic tool to evaluate
periarticular soft tissue of the hip. Dynamic ultrasound can be used to
confirm diagnosis of coxa saltans interna or externa. Ultrasound-guided
injections are useful for intra-articular injections or bursal injections of
iliopsoas tendinitis or ischiofemoral impingement. Ultrasonography is
limited in evaluating the posterior labrum and has a lower sensitivity for
labral tears compared with magnetic resonance arthrograms. 46

Computed Tomography
CT provides high spatial resolution of the cortical, trabecular bone, and joint
anatomy. 47 Axial oblique cuts oriented along the axis of the femoral neck are
best suited to assess femoral offset in femoroacetabular impingement.
Acetabular version as well as femoral torsion can be assessed when selected
cuts of the distal femur are performed. The crossover sign on plain
radiographs can overestimate acetabular retroversion because of variable
appearance of the anterior inferior iliac spine. 48 CT images can be used to
create three-dimensional reconstructions for preoperative planning for cases
of femoroacetabular impingement.

Magnetic Resonance Imaging

MRI is the modality of choice to assess soft-tissue, intra-articular, and bony
pathologies given its high spatial and contrast resolution. Magnetic
resonance arthrography can be used for both diagnostic and therapeutic
purposes. In addition to contrast medium, local anesthetic and anti-
inflammatory medication can be injected into the joint for therapeutic relief.
A recent study demonstrated magnetic resonance arthrography as superior
in sensitivity and specificity to accurately diagnose labral tears and chondral
injuries when compared with conventional MRI. 49 Cartilage mapping is also
possible with advances in imaging techniques. As described in a 2019 study,
T2 mapping, T1 rho, sodium MRI, and delayed gadolinium-enhanced MRI of
cartilage can show signs of early chondral degeneration even in the se ing of
cartilage that is morphologically normal appearing in volume on
conventional MRI. 50

Summary
It is important to understand the complex soft-tissue and bony anatomy of
the hip and pelvis to make an accurate clinical diagnosis. Furthermore, an
understanding of the biomechanics of the hip allows for appropriate surgical
and nonsurgical interventions. A comprehensive physical examination of the
hip, as well as the lumbar spine and knee, is essential to determine a
differential diagnosis. Imaging modalities such as radiography,
ultrasonography, CT, and MRI are available to confirm diagnosis or
complement history and physical examination to aid in the care of patients.

Key Study Points

Multiple muscle groups cross the hip, providing dynamic stability to the hip joint.
Contralateral cane use decreases peak pressures in the hip.
Examination of the lumbar spine and ipsilateral knee is essential when examining a painful hip.
Understanding the anatomy and development of the hip joint is foundational for the understanding
of the pathologic basis of hip joint disorders.

Annotated References
1. Ponseti IV: Growth and development of the acetabulum in the normal
child. Anatomical, histological, and roentgenographic studies. J Bone Joint
Surg Am 1978;60(5):575-585.
2. Portinaro NM, Murray DW, Benson MK: Microanatomy of the acetabular
cavity and its relation to growth. J Bone Joint Surg Br 2001;83(3):377-383.
 3. Parvaresh KC, Upasani VV, Bomar JD, Pennock AT: Secondary ossification
center appearance and closure in the pelvis and proximal femur. J Pediatr
Orthop 2018;38(8):418-423.
4. Tönnis D, Heinecke A: Acetabular and femoral anteversion: Relationship
with osteoarthritis of the hip. J Bone Joint Surg Am 1999;81(12):1747-1770.
5. Reikerås O, Bjerkreim I, Kolbenstvedt A: Anteversion of the acetabulum
and femoral neck in normals and in patients with osteoarthritis of the hip.
Acta Orthop Scand 1983;54(1):18-23.
6. Eftekhary N, Shimmin A, Lazennec JY, et al: A systematic approach to the
hip-spine relationship and its applications to total hip arthroplasty. Bone
Joint J 2019;101-B(7):808-816. This article represents a comprehensive review
of the interplay of spinopelvic parameters in the normal and pathologic
states, how this affects the dynamic stability of a total hip arthroplasty, and
how to evaluate patients with abnormal mechanics.
7. Weinstein SL, Dolan LA: Proximal femoral growth disturbance in
developmental dysplasia of the hip: What do we know? J Child Orthop
2018;12(4):331-341.
8. Yoshihashi AK, Drake AJ III, Shakir KM: Ward’s triangle bone mineral
density determined by dual-energy x-ray absorptiometry is a sensitive
indicator of osteoporosis. Endocr Pract 1998;4(2):69-72.
9. Lee MC, Eberson CP: Growth and development of the child’s hip. Orthop
Clin N Am 2006;37(2):119-132.
10. Kalhor M, Horowi K, Gharehdaghi J, Beck M, Ganz R: Anatomic
variations in femoral head circulation. Hip Int 2012;22(3):307-312.
11. Grose AW, Gardner MJ, Sussmann PS, Helfet DL, Lorich DG: The surgical
anatomy of the blood supply to the femoral head: Description of the
anastomosis between the medial femoral circumflex and inferior gluteal
arteries at the hip. J Bone Joint Surg Br 2008;90(10):1298-1303.
12. Ng KCG, Jeffers JRT, Beaulé PE: Hip joint capsular anatomy, mechanics,
and surgical management. J Bone Joint Surg Am 2019;101(23):2141-2151. This
article is a comprehensive review of the current understanding of the hip
joint capsule anatomy, function, and its role in hip stability. Foundational
knowledge needed to diagnose and treat common hip disorders is
presented.
13. Nagpal AS, Brennick C, Occhialini AP, et al: Innervation of the posterior
hip capsule: A cadaveric study. Pain Med 2021;22(5):1072-1079. This is an
anatomic study of 18 cadaver hips looking specifically at the innervation of
 the hip joint capsule to explain pain pa erns and provide a basis for
interventional pain procedures.
14. Lesher JM, Dreyfuss P, Hager N, Kaplan M, Furman M: Hip joint pain
referral pa erns: A descriptive study. Pain Med 2008;9(1):22-25.
15. Seldes RM, Tan V, Hunt J, Ka M, Winiarsky R, Fi gerald RHJr: Anatomy,
histologic features, and vascularity of the adult acetabular labrum. Clin
Orthop Relat Res 2001;382:232-240.
16. Storaci HW, Utsunomiya H, Kemler BR, et al: The Hip Suction Seal, Part I:
The role of acetabular labral height on hip distractive stability. Am J Sports
Med 2020;48(11):2726-2732. A biomechanical study of 23 fresh-frozen
cadaver hemipelvises is presented. The cadavers were subjected to
distraction of the hip joint, with force needed to achieve distraction,
distance to rupture of suction seal, and peak negative pressure obtained.
These measurements were then correlated with each specimen’s labral
height.
17. Petersen W, Petersen F, Tillmann B: Structure and vascularization of the
acetabular labrum with regard to the pathogenesis and healing of labral
lesions. Arch Orthop Trauma Surg 2003;123(6):283-288.
18. Cashin M, Uhthoff H, O’Neill M, Beaulé PE: Embryology of the acetabular
labral-chondral complex. J Bone Joint Surg Br 2008;90(8):1019-1024.
19. Yoon BH, Ha YC, Lee YK, Jo WL, Lee KM, Koo KH: Is transverse
acetabular ligament a reliable guide for aligning cup anteversion in total
hip arthroplasty?: A measurement by CT arthrography in 90 hips. J Orthop
Sci 2016;21(2):199-204.
20. Kim YT, Azuma H: The nerve endings of the acetabular labrum. Clin
Orthop Relat Res 1995;320:176-181.
21. Kalhor M, Horowi K, Beck M, Nazparvar B, Ganz R: Vascular supply to
the acetabular labrum. J Bone Joint Surg Am 2010;92(15):2570-2575.
22. Perumal V, Woodley SJ, Nicholson HD: Neurovascular structures of the
ligament of the head of femur. J Anat 2019;234(6):778-786. The study
authors present a histologic study of 10 cadaver hips. The ligamentum
teres was cut and sectioned at three different levels. The specimens were
then stained to study the general tissue architecture and neurovascular
structures to identify an anatomic basis for the function of the ligamentum
teres and its ability to be a pain generator.
23. MacLean J, Wustrack R, Kandemir U: Gluteal compartment syndrome.
Tech Orthop 2012;27(1):43-46.
24. Neumann DA: Kinesiology of the hip: A focus on muscular actions. J
Orthop Sports Phys Ther 2010;40(2):82-94.
25. Babst D, Steppacher SD, Ganz R, Siebenrock KA, Tannast M: The
iliocapsularis muscle: An important stabilizer in the dysplastic hip. Clin
Orthop Relat Res 2011;469(6):1728-1734.
26. Bowman KFJr, Fox J, Sekiya JK: A clinically relevant review of hip
biomechanics. Arthroscopy 2010;26(8): 1118-1129.
27. Harding L, Barbe M, Shepard K, et al: Posterior-anterior glide of the
femoral head in the acetabulum: A cadaver study. J Orthop Sports Phys Ther
2003;33(3):118-125.
28. Polkowski GG, Clohisy JC: Hip biomechanics. Sports Med Arthrosc Rev
2010;18(2):56-62.
29. Dewberry MJ, Bohannon RW, Tiberio D, Murray R, Zanno i CM: Pelvic
and femoral contributions to bilateral hip flexion by subjects suspended
from a bar. Clin Biomech (Bristol, Avon) 2003;18(6):494-499.
30. Murray R, Bohannon R, Tiberio D, Dewberry M, Zanno i C: Pelvifemoral
rhythm during unilateral hip flexion in standing. Clin Biomech (Bristol,
Avon) 2002;17(2):147-151.
31. Nordin M: Basic Biomechanics of the Musculoskeletal System, ed 3. Lippinco
Williams & Wilkins, 2001.
32. Roach KE, Miles TP: Normal hip and knee active range of motion: the
relationship to age. Phys Ther 1991;71(9):656-665.
33. Torry MR, Schenker ML, Martin HD, Hogoboom D, Philippon MJ:
Neuromuscular hip biomechanics and pathology in the athlete. Clin Sports
Med 2006;25(2):179-197.
34. Hughes PE, Hsu JC, Matava MJ: Hip anatomy and biomechanics in the
athlete. Sports Med Arthrosc Rev 2002;10(2):103-114.
35. Pauwels F: Biomechanics of the Normal and Diseased Hip: Theoretical
Foundation, Technique, and Results of Treatment. An Atlas. Springer-
Verlag, 1976.
36. Krebs DE, Robbins CE, Lavine L, Mann RW: Hip biomechanics during
gait. J Orthop Sports Phys Ther 1998;28(1):51-59.
37. Bergmann G, Graichen F, Rohlmann A: Hip joint contact forces during
stumbling. Langenbecks Arch Surg 2004;389(1):53-59.
38. Greenwald AS, Haynes DW: Weight-bearing areas in the human hip joint.
J Bone Joint Surg Br 1972;54(1):157-163.
39. Kurrat HJ, Oberländer W: The thickness of the cartilage in the hip joint. J
Anat 1978;126(pt 1):145-155.
40. McMillan AG, Auman NL, Collier DN, Blaise Williams DS: Frontal plane
lower extremity biomechanics during walking in boys who are overweight
versus healthy weight. Pediatr Phys Ther 2009;21(2):187-193.
41. Jennings F, Lambert E, Fredericson M: Rheumatic diseases presenting as
sports-related injuries. Sports Med 2008;38(11):917-930.
42. Lad N, Kropf EJ: Hip pathology evaluation and imaging. Operat Tech
Orthop 2019;29(4):100734. A comprehensive review of evaluation of hip
injuries in athletes is presented. A systematic approach to physical
examination is described, progressing from gait analysis to supine
examination, allowing the clinician to differentiate intra-articular and extra-
articular pathology.
43. Grumet RC, Frank RM, Slabaugh MA, Virkus WW, Bush-Joseph CA, Nho
SJ: Lateral hip pain in an athletic population: differential diagnosis and
treatment options. Sports Health 2010;2(3):191-196.
44. Martin HD: Clinical examination of the patient with posterior hip pain, in
Martin HD, Gómez-Hoyos J, eds: Posterior Hip Disorders: Clinical Evaluation
and Management. Springer International Publishing, 2019, pp 41-49. The
chapter describes six key physical examination tests to differentiate distal
versus proximal sources of extrapelvic posterior hip pain. Differential
diagnosis is dependent on a thorough understanding of hip anatomy and
biomechanics.
45. Safran MR: Microinstability of the hip-gaining acceptance. J Am Acad
Orthop Surg 2019;27(1):12-22. The article provides an in-depth review of
symptomatic microinstability of the hip. This includes specific physical
examination findings as well as treatment options.
46. Troelsen A, Jacobsen S, Bolvig L, Gelineck J, Rømer L, Søballe K:
Ultrasound versus magnetic resonance arthrography in acetabular labral
tear diagnostics: A prospective comparison in 20 dysplastic hips. Acta
Radiol 2007;48(9):1004-1010.
47. Chiamil SM, Abarca CA: Imaging of the hip: A systematic approach to the
young adult hip. Muscles Ligaments Tendons J 2016;6(3):265-280.
48. Zal I, Kelly BT, Hetsroni I, Bedi A: The crossover sign overestimates
acetabular retroversion. Clin Orthop Relat Res 2013;471(8):2463-2470.
49. Schmaranzer F, Kheterpal AB, Bredella MA: Best practices: Hip
femoroacetabular impingement. AJR Am J Roentgenol 2021;216(3):585-598.
The purpose of the article was to provide guidance on best practices for
 imaging of patients with femoroacetabular impingement. Chondrolabral
lesions can be evaluated with unenhanced MRI or magnetic resonance
arthrography.
50. Noguerol TM, Raya JG, Wessell DE, Vilanova JC, Rossi I, Luna A:
Functional MRI for evaluation of hyaline cartilage extracelullar matrix, a
physiopathological-based approach. Br J Radiol 2019;92(1103):20190443. An
extensive review of advances in the MRI sequences that allow for be er
cartilage assessment is presented. The article provides an educational
update on the physical principles behind advanced MRI techniques as well
as a comprehensive review of the strengths and weaknesses of each
approach.
C H AP T E R 4 0

Early Degenerative Conditions

of the Hip
Erik N. Hansen MD, FAAOS, Stephanie E. Wong MD,
Ishaan Swarup MD

Dr. Hansen or an immediate family member has received royalties from Corin U.S.A. and serves
as a paid consultant to or is an employee of Corin U.S.A. Dr. Swarup or an immediate family
member serves as a paid consultant to or is an employee of OrthoPediatrics and serves as a
board member, owner, officer, or committee member of American Academy of Orthopaedic
Surgeons and Pediatric Orthopaedic Society of North America. Neither Dr. Wong nor any
immediate family member has received anything of value from or has stock or stock options held
in a commercial company or institution related directly or indirectly to the subject of this chapter.

ABSTRACT
Morphologic abnormalities of the acetabulum and proximal femur
can result in the development of early degenerative changes of the
hip joint because of pathologic contact and shearing forces at the
labrum and cartilage during physiologic hip motion. The two most
common categories of these prearthritic hip conditions are
femoroacetabular impingement and hip dysplasia. Advances in
surgical treatments focused on treating the structural abnormalities
inherent in these conditions aim to delay the progression of
arthritis and the ultimate need for a total hip arthroplasty.
Keywords: femoroacetabular impingement; hip dysplasia; young
adult hip

Introduction
The healthy hip is a spheroid (ball and socket) joint, which allows
for a great degree of motion, inherent stability, and repetitive high
mechanical loads because of certain anatomic features, including
congruent bony surfaces, thick articular cartilage, and a
surrounding labrum. Morphologically, the labrum forms a
fibrocartilaginous extension of the bony acetabulum, which
increases the containment of the femoral head. In addition to this
function, the labrum also obstructs fluid flow in and out of the joint
through a sealing action, which is often referred to as the suction
effect, that enhances joint stability but also more uniformly
distributes compressive loads to the articular surfaces. The most
favorable mechanical environment of a healthy functioning hip is
one that is free of both impingement and instability.
Developmental and acquired differences in the bony anatomy of
the acetabulum and proximal femur may alter the biomechanical
forces across the articular cartilage and labrum and predispose to
the development of arthritic changes. In developmental dysplasia
of the hip, inadequate bony coverage of the femoral head results in
mechanical overload of the anterolateral acetabular rim and
labrum. In contrast, femoroacetabular impingement (FAI) is
characterized by decreased clearance and abnormal contact
between the femoral head-neck junction and the acetabular rim,
resulting in femoroacetabular abutment, especially in positions of
hip flexion and internal rotation. Both conditions can lead to labral
tears, chondral damage, and the ultimate development of advanced
arthrosis of the joint unless the underlying hip joint
pathomechanics are corrected.

Radiology of the Prearthritic Hip

A systematic approach to imaging of the hip in a young adult is
important to obtain the correct diagnosis, classify the severity of
the condition, and help guide the appropriate treatment. The goals
in obtaining plain films are to characterize the structural anatomy
of the hip, the congruency of the joint, and the integrity of the
cartilage space. In general, a comprehensive initial series of
radiographs for a young adult hip would include AP, Dunn (at
either 45° or 90°), frog-leg lateral, and false-profile views of the
affected hip. 1 The AP radiograph of the pelvis provides information
on the acetabular coverage of the femoral head, head sphericity,
acetabular inclination, horizontal position of the joint center,
amount of joint space present, and version of the acetabulum. It is
important that the AP radiograph be taken in neutral pelvic tilt and
rotation, as alterations in these parameters may affect
interpretation of images. Various lateral views provide additional
information regarding acetabular coverage and femoral head
sphericity.

Femoroacetabular Impingement
In cases of suspected FAI, on the AP radiograph of the pelvis, the
physician should look for signs of acetabular retroversion,
including the crossover, posterior wall, and ischial spine signs. The
crossover sign is positive when any part of the anterior acetabular
wall is more lateral than the posterior wall in the proximal region of
the acetabulum (Figure 1). The posterior wall sign is present when
the posterior acetabular wall is more medial than the center of the
femoral head, indicating reduced posterior wall coverage. The
ischial spine sign is positive when the ischial spine is visible medial
to the pelvic inlet or iliopectineal line. Furthermore, coxa profunda
is when the floor of the acetabular fossa contacts or overlaps the
ilioischial line on an AP view. Protrusio acetabuli is present when
the femoral head crosses the ilioischial line medially. Dunn views
obtained with the hip abducted 20° and flexed either 45° or 90°
provide the best assessment of the anterosuperior femoral head-
neck junction. Additionally, the head-neck offset ratio can be
assessed on these views. The alpha angle used to quantify the
degree of head asphericity and cam impingement is used with
cross-table lateral radiographs 2 and MRI, 3 and it is defined as the
angle subtended by a line down the middle of the femoral neck and
the point at which the excess bone deviates from the normal
sphericity of the head (Figure 2).

Figure 1 Radiographic signs of acetabular retroversion of the right

hip.Crossover sign—note the anterior acetabular wall is more lateral than the
posterior wall in the proximal region of the acetabulum.
 Figure 2 Dunn radiographic view of the right hip demonstrating classic cam
lesion of the head-neck junction.Alpha angle, 77° (normal <55°).

Advanced imaging techniques can be helpful to further delineate

bony and soft-tissue anatomy and corresponding pathology. Low-
dose CT scans can be used to assess femoral and acetabular
version, to be er characterize the bony anatomy of the pelvis in
planning for periacetabular osteotomy, or to help map the shape of
the acetabular rim and femoral head-neck junction prior to
osteoplasty. MRI techniques provide valuable information
regarding the condition of the periarticular soft tissues, including
the labrum, articular cartilage, ligamentum teres, capsule, and the
surrounding musculotendinous structures. Magnetic resonance
arthrography has been shown to be more sensitive in identifying
labral tears and chondral lesions than conventional MRI, although
it has limitations in detecting undetached chondral separations. 4
Other magnetic resonance sequences, such as delayed gadolinium-
enhanced MRI of cartilage and T1rho mapping, are increasingly
being used more in both clinical and research se ings because
these sequences provide more information regarding the health of
a joint by providing an objective measure of the proteoglycan
content of the articular cartilage. 5

Hip Dysplasia
On the AP radiograph of the pelvis, measurements can be made of
acetabular coverage, including the degree of inclination (the Tönnis
angle) and the lateral center-edge (LCEA) angle of Wiberg, with
normal values being between 0° and 10° from the horizontal for the
Tönnis angle and 25° to 35° for the angle of Wiberg (Figure 3, A and
B). A break in the Shenton line is indicative of subtle subluxation of
the hip. The false-profile view, which highlights the anterior center-
edge angle, anterior acetabular coverage, and anterior joint space
narrowing, is taken with the patient standing with the affected hip
against and the ipsilateral foot parallel to the casse e with the
pelvis rotated 65° (Figure 3, C).
 Figure 3 AP radiographs of the pelvis of a young adult patient with
developmental dysplasia of the hip.A, Right hip—Tönnis angle, 17’ (normal 0° to
10°). B, Lateral center-edge angle, 20° (normal 25° to 35°). C, False-profile view,
anterior center-edge angle, 3° (normal >20°).

Femoroacetabular Impingement
FAI is a clinical syndrome that occurs from repetitive, abnormal
contact between the femoral head-neck and the acetabulum, with
morphologic changes at one or both of those involved structures. 6
This abnormal contact during hip range of motion can lead to
mechanical and shear forces on the adjacent cartilage and labrum,
leading to labral tears, cartilage injury, and abnormal bony
remodeling, and potentially future development of hip arthritis. 7
There are three types of FAI, which are classified according to the
morphologic changes to the bone: cam, pincer, and combined or
mixed-type FAI. 7
Cam impingement describes an aspherical femoral head-neck.
The development of cam lesions has a strong association with
adolescent participation in high-impact sports such as football,
soccer, and hockey. 8 , 9 It is thought that repetitive stress to the
proximal femoral physis during skeletal development can cause
reactive bone formation that leads to the development of a cam
lesion. 9 Cam lesions are defined as having an alpha angle greater
than 55°. 7
Pincer impingement is acetabular overcoverage, which can occur
either focally or globally as well as with acetabular retroversion. 9
The earliest description of a pincer lesion was in 1824, which
described a female pelvis with particularly deep position of the
femoral heads within the acetabula, what is currently described as
protrusio acetabuli or global pincer impingement. 6 A LCEA greater
than 40° is consistent with pincer impingement. 7
Combined, or mixed-type, impingement occurs when both cam
and pincer lesions are present.

Labral Tears, Chondrolabral Junction, and

Articular Cartilage Injuries
The acetabular labrum is a protective ring of fibrocartilage that
contributes to hip stability and the hip suction seal. 10 Labral tears
commonly occur in the se ing of FAI (Figure 4, A) and can also
occur in the se ing of hip dysplasia. 11 The acetabular labrum
normally a aches to the articular cartilage of the acetabulum
through a histologic transition zone called the chondrolabral
junction, and this region is vulnerable to injury in FAI. 12 With cam-
type impingement, the bony prominence of the femoral head-neck
impacts the labrum and chondrolabral junction and can lead to
outside-in chondral injuries, as described in a 2019 study. 13
 Figure 4 Arthroscopic views of the hip showing a labral tear (A) and a surgical
repair (B).

There is a high prevalence of labral tears in asymptomatic

patients. In one study, 45 asymptomatic volunteers underwent hip
MRI. 14 The mean age of the patients was 37.8 years of age, and 60%
were men. Labral tears were identified in 69% of hips. Those older
than 35 years were more likely to have a chondral defect and
subchondral cyst.
Classification systems have been developed to describe labral
tears and acetabular cartilage injury that occur as a result of FAI.
One commonly used classification system, the Beck classification,
was originally described for hips undergoing surgical hip
dislocation; it has since been adapted to be used in hip arthroscopy.
15
Table 1 describes the Beck classification of cartilage damage, and
Table 2 shows the Beck classification of labral damage.

Table 1
Beck Classification of Articular Cartilage Damage

Grade Description Criteria

0 Normal Normal cartilage
1 Malacia Irregular chondral surface, fibrillation, softening
2 Debonding Loss of cartilage fixation to subchondral bone, delamination with
wave or carpet phenomenon
3 Cleavage Loss of cartilage fixation to subchondral bone, thinning of cartilage,
cartilage flap or fragmentation
Grade Description Criteria
4 Defect Full-thickness defect

Table 2
Beck Classification of Labral Damage

Grade Description Criteria

0 Normal Normal labrum
1 Degeneration Thinning, fraying, discoloration
2 Full-thickness Complete avulsion from acetabular rim
tear
3 Detached Separation between acetabular and labral cartilage, preserved
labrum attachment to bone
4 Ossified Osseous metaplasia of the labrum, localized or circumferential
labrum

Treatment and Outcomes

Nonsurgical treatment of FAI includes NSAIDs, physical therapy
for core and gluteal muscle strengthening, and intra-articular hip
corticosteroid injection. The UK FASHIoN Trial, a multicenter
randomized clinical trial, investigated nonsurgical treatment of FAI
with physical therapy compared with hip arthroscopy. 16 A total of
348 patients were enrolled, and after 12 months, both groups had
significant improvements in their primary outcomes and hip-
related quality of life, as measured by the 33-item International Hip
Outcome Tool. Although both groups showed improvement, the
group undergoing hip arthroscopy had greater improvement than
those in the physical therapy group.
Modern surgical treatment of FAI includes hip arthroscopy and
surgical dislocation of the hip, both of which may involve labral
repair (Figure 4, B), acetabuloplasty (for those with pincer lesions),
and femoral osteochondroplasty (for those with cam lesions, Figure
5), with or without capsular closure. Hip arthroscopy is performed
on a traction table to facilitate joint distraction and safe access to
the hip joint.
 Figure 5 A and B, Arthroscopic views of the hip showing femoral
osteochondroplasty.

Surgical dislocation of the hip, popularized by Ganz, is a

powerful corrective option for the femoral and acetabular
abnormalities associated with FAI. Often combined with a
trochanteric slide osteotomy, this technique allows circumferential
exposure of the acetabulum and femoral head-neck junction, but
requires meticulous a ention to preserving the deep branch of the
medial femoral circumflex artery so as to avoid the dreaded
complication of osteonecrosis of the femoral head. Given the
potential morbidity associated with surgical dislocation of the hip,
and as advances in arthroscopic technique have been refined, there
has been a growing trend toward the use of hip arthroscopy for
these conditions.
Outcomes after hip arthroscopy are overall very good with the
proper patient selection. A study investigated outcomes after
arthroscopic treatment of FAI in high school and collegiate athletes
and found improvement in hip outcome scores (modified Harris
Hip Score improved from 68.6 to 88.5 points, P = 0.002, Hip
Outcome Score improved from 78.8 to 91.4, P = 0.03). 17 Alpha
angles improved from 76.5° to 51.4° (P = 0.0003). At 1-year follow-
up, 78% had returned to play and 92% were competing at the same
level of competition at a mean of 9.4 months after surgery. In a 2020
study, when comparing competitive athletes to nonathletes, both
groups improved after hip arthroscopy for FAI, with the athletes
achieving a minimal clinically important difference for the Hip
Outcome Score Sports Subscale at higher rates than the
nonathletes. 18
A 2019 systematic review described predictors of outcomes after
hip arthroscopy surgery for FAI. 19 Predictors of positive outcomes
included younger age, male sex, lower body mass index (less than
24.5 kg/m2), Tönnis grade 0, and pain relief from preoperative
intraarticular hip injection. In contrast, negative predictors
included patient age older than 45 years, female sex, higher body
mass index (over 25 kg/m2), Tönnis grade 1 or greater, preoperative
symptoms lasting more than 8 months, chondral defects, and labral
débridement instead of labral repair. Other studies agree with
these findings, with one comparative matched-group analysis
indicating age and sex as significant predictors of outcomes after
hip arthroscopy, with female patients older than 45 years
demonstrating improvement over baseline, however, with worse
scores compared with male patients and younger patients. 20

Hip Dysplasia
Dysplasia refers to a spectrum of abnormalities ranging from hip
subluxation or dislocation to shallowness of the acetabulum (Figure
3). It is usually diagnosed during childhood, but it may present in
older patients if it is not diagnosed or treated at a younger age. Its
relevance to pain and function is underscored in one study, which
found that osteoarthritis developed in all patients with abnormal
LCEAs. 21 However, the relationship was not linear. In another
study, dysplasia was noted to be the strongest predictor of
degenerative change in the contralateral hip for patients
undergoing unilateral total hip arthroplasty (THA). 22 The
relationship between dysplasia and osteoarthritis is well recognized
and related to altered biomechanics, leading to joint degeneration.
The early changes in dysplasia occur at the chondrocyte level, likely
related to these biomechanical alterations. 23 Dysplasia also may
lead to increased stress being placed on secondary stabilizers of the
hip such as the labrum. For example, a 2019 study found an
association between the center-edge angle and increasing severity
of labral pathology. 24 In general, dysplasia is an important topic for
all orthopaedic surgeons to understand because it is managed by
several subspecialties within orthopaedics.

Classification
Hip subluxation and dislocation are characterized by disruption of
the Shenton line, which has been shown to be a reliable
radiographic marker. 25 The LCEA is commonly used to describe
the severity of dysplasia, with angles less than 25° indicating
inadequate coverage. 1 Mild or borderline dysplasia has been
usually defined as LCEA greater than or equal to 18° and less than
or equal to 25°, 26 - 28 with lower LCEAs being classified as more
severe dysplasia. It is important to note that this is a relatively
subjective definition that is not predicated on natural history
studies. More recent studies also have suggested that LCEA may be
too simplistic because the acetabulum is a three-dimensional
structure. 26 Although the LCEA assesses mostly lateral coverage,
anterior coverage can be assessed by the anterior center-edge angle.
An anterior center-edge angle less than 20° has been associated
with structural instability. 1
Additional classification systems have been described for
patients with dysplasia. The Tönnis grade describes the degree of
osteoarthritis and may be useful in deciding between hip
preservation and arthroplasty options. 1 Generally, hip preservation
is more appropriate in patients with a lower Tönnis grade. 29
Furthermore, the Crowe classification and Hartofilakidis
classification have been described for patients with dysplasia
undergoing arthroplasty. These classification systems relate to the
degree of hip subluxation and are useful in preoperative planning
for THA, which is beyond the scope of this chapter. 30
Examination
Physical examination begins with an assessment of the patient’s
gait. An antalgic gait is a common finding; however, a
Trendelenburg gait also can be observed in patients with abductor
weakness. The patient’s foot progression angle also should be
assessed as part of the rotational profile. 31 Hip motion is commonly
assessed with the patient supine. Hip flexion is normally 95° to
120°, 32 but it may be greater in patients with dysplasia. Hip internal
and external rotation is assessed at 90° of flexion. Hip internal
rotation may be increased in patients with dysplasia or increased
femoral anteversion but decreased in patients with retroversion
and FAI. Hip rotation with the patient in the prone position also
may be assessed as part of a patient’s rotational profile 31 and
provides additional insight into contributions from the femur, tibia,
and foot during gait.
Additional tests include the apprehension test, which is
characterized by anterior pain with hip external rotation in
extension. The prone apprehension relocation test also has been
described in patients with dysplasia. 33 The test replicates hip
instability pain when an anteriorly directed force is placed on the
femur with the patient prone. Additionally, an impingement test
with flexion, adduction, and internal rotation should be performed
because impingement may also be noted in patients with dysplasia.
28 , 34
Finally, a lower extremity neurovascular examination is
essential to evaluate for spinal pathology and assess baseline
function.

Treatment and Outcomes

Treatment for dysplasia is largely predicated on symptoms and
severity of dysplasia. Nonsurgical treatment is usually the first-line
treatment for patients with symptomatic dysplasia based on
history, physical examination, and radiographic evaluation. If
nonsurgical management is unsuccessful, surgical treatment is
considered with the goal of correcting the anatomic abnormality.
Surgical management depends on the patient’s symptoms, findings
on plain radiographs and advanced imaging, and skeletal maturity.
It is typically indicated for patients with minimal degenerative
changes (Tönnis grade 2 or lower) and congruency of the hip joint
on functional radiographs, such as abduction-internal rotation
views. Patients with more advanced arthritic changes or
incongruence may have a higher rate of failure with
nonarthroplasty procedures. 35

Nonsurgical Treatment
There are several nonsurgical treatment options for dysplasia.
NSAIDs, activity modification, and physical therapy are often
considered as first-line management. NSAIDs usually manage the
inflammatory cascade, and activity modification focuses on
avoiding exacerbating activities. Physical therapy typically focuses
on strengthening secondary stabilizers of the hip such as the
abductors. 36 In cases of mild dysplasia, these treatments often are
successful as definitive management. 27 , 28 Other nonsurgical
options include intra-articular injections of local anesthetic and/or
steroids. Injections in the se ing of dysplasia may serve diagnostic
and therapeutic purposes, 37 especially when the origin of the pain
may be unclear or confounded by other pathology. Specifically, an
injection may help to differentiate between intra-articular and
extra-articular pain generators; however, additional studies are
needed to validate its prognostic value.

Surgical Treatment
Surgical treatment options generally can be differentiated into
arthroscopic, open, and combined approaches. Hip arthroscopy in
the se ing of severe dysplasia is usually contraindicated because it
may cause iatrogenic instability. 10 Additionally, it does not address
the underlying abnormality of hip dysplasia. However, hip
arthroscopy is a viable treatment option for labral tears or FAI in
the se ing of borderline hip dysplasia. It is important to note that
outcomes after hip arthroscopy in patients with borderline hip
dysplasia are mixed, with some studies demonstrating similar
results compared to patients without dysplasia, 38 , 39 whereas other
studies show worse outcomes. 40
Open treatment options are classically considered for patients
with dysplasia with li le or no degenerative changes. In skeletally
immature patients, redirection and reorientation osteotomies are
considered depending on patient age and hip abnormality. 35
Redirectional osteotomies include Salter, Pemberton, Dega, and
San Diego osteotomies, and they generally reduce the acetabular
volume. Reorientation osteotomies aim to change the acetabular
orientation and include the triple pelvic osteotomy and
periacetabular osteotomy (PAO). In adult patients, the PAO is the
most frequently used procedure for symptomatic dysplasia.
The Bernese PAO was first described in 1988, with the goal of
reorienting the acetabulum including medial and lateral
displacement. 41 Since the original description, a few modifications
have been made to the surgical technique, including abductor-
sparing 42 and rectus-sparing approaches. 43 In this procedure,
separate osteotomies are made in the ischium, superior pubic
ramus, and ilium. The ischial cut is incomplete and allows for
preservation of the posterior column, which adds inherent stability
to the osteotomy. The iliac cut involves a supra-acetabular cut with
minimal dissection of the abductors, as well as a posterior column
cut that splits the column halfway between the greater sciatic notch
and acetabulum. The procedure is performed using mainly AP and
false-profile fluoroscopic views that allow for an adequate view of
the bony anatomy. 35 , 41 Once all cuts have been completed, the
acetabular fragment can be mobilized to achieve appropriate
anterior and lateral coverage as well as version, and the osteotomy
is fixed with 3.5- or 4.5-mm full-threaded screws (Figure 6). In some
patients an arthrotomy is performed to manage other potential
sources of FAI after acetabular correction. 35 Additionally, there
may be indications for combined arthroscopy and PAO in patients
with symptomatic labral injury and labral detachment on MRI 44
(Figure 7). A multicenter, prospective study is underway to assess
the outcomes and costs associated with combined procedures. 45

Figure 6 A, Postoperative AP radiograph of the pelvis of the patient in Figure 1

who underwent periacetabular osteotomy of the right hip for hip dysplasia. B,
False-profile view demonstrating the correction in the anterior center-edge angle.
 Figure 7 T2 Magnetic resonance image of the left hip of a patient with
dysplasia and symptomatic labral tear.A, Axial view. B, Sagittal view.

Although a learning curve is associated with a PAO, various

preoperative, intraoperative, and postoperative measures can be
taken to minimize complications. 46 These measures include
appropriate patient selection, surgical mentorship, knowledge of
pelvic anatomy, blood conservation strategies, and prevention of
venous thromboembolic events. 47 The most common complications
include wound-related issues, heterotopic ossification, and lateral
femoral cutaneous nerve injury, which usually is transient. 46

Outcomes
Outcomes after PAO have been good, with survival rates greater
than 90% at 10 years, 48 approximately 75% at 18 years, 49 and
approximately 30% at 30 years. 50 The Bernese PAO has also been
shown to successfully change the natural history of dysplasia. In a
2019 study, the probability of progression to THA significantly
increased based on a higher initial Tönnis grade. Specifically, the
probability of progression to THA for patients with Tönnis grade 2
osteoarthritis at the time of PAO was 23% and 53% at 5 years and 10
years, respectively. In comparison, progression to THA in patients
with Tönnis grade 1 osteoarthritis was noted to be 2% and 11% at 5
years and 10 years, respectively. 29 Factors associated with poor
outcomes included age older than 25 years, poor or fair hip
congruency, and preoperative joint space width less than 2 mm or
greater than 5 mm49.

Summary
Clinicians and researchers are pushing the frontiers of
understanding of prearthritic conditions of the hip while
simultaneously improving the ability to appropriately tailor
treatment for these young adult patients through advances in
imaging, surgical techniques, and multicenter clinical studies.
Although hip dysplasia and FAI represent two separate
pathomechanisms for the development of hip arthrosis, early
accurate diagnosis and appropriate surgical intervention of these
conditions holds promise for altering the natural history, and
potentially delaying or obviating the need for joint replacement
surgery.

Key Study Points

Developmental skeletal abnormalities of the hip result in increased biomechanical
stresses on critical anatomic structures, including the labrum and the articular
cartilage, which if untreated leads to degeneration, pain, functional limitations, and
ultimately advanced joint arthrosis.
FAI is a constellation of various osseous abnormalities of the acetabulum and
femoral head that lead to abutment and shear damage to the chondrolabral junction.
Continued refinement in defining the appropriate surgical indications as well as
further advances in hip arthroscopy techniques will improve the care provided for
this problem.
Developmental dysplasia of the hip is a multifaceted orthopaedic condition affecting
both the pelvis and femur in predictable ways (eg, shallow, oblique, low-volume
socket especially anterosuperior; long, valgus femoral neck with excessive
anteversion). The degree of dysplasia dictates the treatment recommendations,
though in the absence of arthritic changes, periacetabular osteotomy is one of the
most effective tools to correct the acetabular undercoverage of the femoral head and
alter the natural history of the condition.

Annotated References
1. Clohisy JC, Carlisle JC, Beaulé PE, et al: A systematic approach
to the plain radiographic evaluation of the young adult hip. J Bone
Joint Surg Am 2008;90(suppl 4):47-66.
2. Eijer H, Leunig M, Mahomed MN, Ganz R: Cross-table lateral
radiographs for screening of anterior femoral head-neck offset in
patients with femoro-acetabular impingement. Hip Int
2001;11(1):37-41.
3. Nö li HP, Wyss TF, Stoecklin CH, Schmid MR, Treiber K,
Hodler J: The contour of the femoral head-neck junction as a
 predictor for the risk of anterior impingement. J Bone Joint Surg
Br 2002;84(4):556-560.
4. Leunig M, Podeszwa D, Beck M, Werlen S, Ganz R: Magnetic
resonance arthrography of labral disorders in hips with dysplasia
and impingement. Clin Orthop Relat Res 2004;418:74-80.
5. Melkus G, Beaulé PE, Wilkin G, Rakhra KS: What is the
correlation among dGEMRIC, T1p, and T2* quantitative MRI
cartilage mapping techniques in developmental hip dysplasia?
Clin Orthop Relat Res 2021;479(5):1016-1024. The authors a empt
to determine the correlation between the relaxation values of
three cartilage mapping techniques in 15 patients with
developmental dysplasia of the hip scheduled for PAO. Level of
evidence: II.
6. Matsumoto K, Ganz R, Khanduja V: The history of
femoroacetabular impingement. Bone Joint Res 2020;9(9):572-577.
This article describes the history of FAI including early anatomic
illustrations of FAI.
7. Pun S, Kumar D, Lane NE: Femoroacetabular impingement.
Arthritis Rheumatol 2015;67(1):17-27.
8. Knapik DM, Gilmore A, Liu RW: Conservative management of
minimally displaced (≤2 mm) fractures of the lateral humeral
condyle in pediatric patients. J Pediatr Orthop 2017;37(2):e83-e87.
9. Packer JD, Safran MR: The etiology of primary femoroacetabular
impingement: genetics or acquired deformity? J Hip Preserv Surg
2015;2(3):249-257.
10. McCarthy J, Noble P, Aluisio FV, Schuck M, Wright J, Lee J:
Anatomy, pathologic features, and treatment of acetabular labral
tears. Clin Orthop Relat Res 2003;406:38-47.
11. Guevara CJ, Pietrobon R, Carothers JT, Olson SA, Vail TP:
Comprehensive morphologic evaluation of the hip in patients
with symptomatic labral tear. Clin Orthop Relat Res 2006;453:277-
285.
12. El-Radi MA, Marin-Peña OR, Said HG, Tey-Pons M: Basics in hip
chondrolabral lesions and state of the art. SICOT J 2017;3:73.
13. Kraeutler MJ, Goodrich JA, Fioravanti MJ, Garabekyan T, Mei-
Dan O: The “outside-in” lesion of hip impingement and the
“inside-out” lesion of hip dysplasia: two distinct pa erns of
acetabular chondral injury. Am J Sports Med 2019;47(12):2978-2984.
Ninety-five patients undergoing hip arthroscopy with acetabular
chondral flaps were included in this cohort study. Outside-in
flaps (centrally anchored flaps with a disruption of the
chondrolabral junction) were predictive of FAI compared with
inside-out flaps (intact chondrolabral junctions with detached
central acetabular cartilage), which were predictive of hip
dysplasia. Level of evidence: III.
14. Register B, Pennock AT, Ho CP, Strickland CD, Lawand A,
Philippon MJ: Prevalence of abnormal hip findings in
asymptomatic participants: A prospective, blinded study. Am J
Sports Med 2012;40(12):2720-2724.
15. Beck M, Kalhor M, Leunig M, Ganz R: Hip morphology
influences the pa ern of damage to the acetabular cartilage:
femoroacetabular impingement as a cause of early osteoarthritis
of the hip. J Bone Joint Surg Br 2005;87(7):1012-1018.
16. Griffin DR, Dickenson EJ, Wall PDH, et al: Hip arthroscopy
versus best conservative care for the treatment of
femoroacetabular impingement syndrome (UK FASHIoN): A
multicentre randomised controlled trial. Lancet
2018;391(10136):2225-2235.
17. Nho SJ, Magennis EM, Singh CK, Kelly BT: Outcomes after the
arthroscopic treatment of femoroacetabular impingement in a
mixed group of high-level athletes. Am J Sports Med 2011;39(suppl
1):14S-9S.
18. Clapp IM, Nwachukwu BU, Beck EC, Jan K, Gowd AK, Nho SJ:
Comparing outcomes of competitive athletes versus nonathletes
undergoing hip arthroscopy for treatment of femoroacetabular
impingement syndrome. Am J Sports Med 2020;48(1):159-166. This
cohort study compared outcomes after hip arthroscopy for FAI in
competitive athletes compared with nonathletes and found that
 both groups had clinically meaningful improvement in outcomes;
however, competitive athletes achieved minimal clinically
important differences at higher rates than nonathletes. Level of
evidence: III.
19. Sogbein OA, Shah A, Kay J, et al: Predictors of outcomes after
hip arthroscopic surgery for femoroacetabular impingement: A
systematic review. Orthop J Sport Med 2019;7(6):2325967119848982.
Thirty-nine studies were included in this systematic review,
which identified predictors of outcomes after hip arthroscopy for
FAI. Positive predictors included younger age, male sex, lower
body mass index, Tönnis grade 0, and pain relief from
preoperative injection. Negative predictors were female sex, older
age (older than 45 years), Tönnis grade 1 or higher, chondral
defects, and undergoing labral débridement. Level of evidence:
IV.
20. Frank RM, Lee S, Bush-Joseph CA, Salata MJ, Mather RC, Nho
SJ: Outcomes for hip arthroscopy according to sex and age: A
comparative matched-group analysis. J Bone Joint Surg Am
2016;98(10):797-804.
21. Cooperman D: What is the evidence to support acetabular
dysplasia as a cause of osteoarthritis? J Pediatr Orthop 2013;33:S2-
S7.
22. Wyles CC, Heidenreich MJ, Jeng J, Larson DR, Trousdale RT,
Sierra RJ: The John Charnley Award: Redefining the natural
history of osteoarthritis in patients with hip dysplasia and
impingement. Clin Orthop Relat Res 2017;475(2): 336-350.
23. Hernandez PA, Wells J, Usheva E, et al: Early-onset
osteoarthritis originates at the chondrocyte level in hip dysplasia.
Sci Rep 2020;10(1):627. This is a basic science study evaluating the
histology and cellular morphology in patients undergoing THA.
The authors find that early degeneration in patients with
dysplasia occurs at the chondrocyte level.
24. Møse FB, Mechlenburg I, Hartig-Andreasen C, Gelineck J,
Søballe K, Jakobsen SS: High frequency of labral pathology in
 symptomatic borderline dysplasia: A prospective magnetic
resonance arthrography study of 99 patients. J Hip Preserv Surg
2019;6(1):60-68. This MRI study showed increasing severity of
labral pathology in patients with decreased center-edge angles.
Level of evidence: III.
25. Rhee PC, Woodcock JA, Clohisy JC, et al: The Shenton line in
the diagnosis of acetabular dysplasia in the skeletally mature
patient. J Bone Joint Surg Am 2011;93(suppl 2):35-39.
26. McClincy MP, Wylie JD, Yen Y-M, Novais EN: Mild or borderline
hip dysplasia: Are we characterizing hips with a lateral center-
edge angle between 18° and 25° appropriately? Am J Sports Med
2019;47(1):112-122. This is a cross-sectional study that suggests
that LCEA may be an oversimplistic approach in classifying
dysplasia. Level of evidence: III.
27. Ricciardi BF, Fields KG, Wen el C, Nawabi DH, Kelly BT, Sink
EL: Complications and short-term patient outcomes of
periacetabular osteotomy for symptomatic mild hip dysplasia.
Hip Int 2017;27(1):42-48.
28. Swarup I, Zal I, Robustelli S, Sink E: Outcomes of
periacetabular osteotomy for borderline hip dysplasia in
adolescent patients. J Hip Preserv Surg 2020;7(2):249-255. This is a
retrospective study looking at outcomes after PAO in patients
with borderline hip dysplasia. The study found that more than
90% of patients achieved minimal clinically important difference
in patient-reported outcomes after surgery. Level of evidence: III.
29. Wyles CC, Vargas JS, Heidenreich MJ, et al: Natural history of
the dysplastic hip following modern periacetabular osteotomy. J
Bone Joint Surg Am 2019;101(10):932-938. This is a retrospective
study that assesses the rate of joint degeneration and
arthroplasty after PAO. The authors found an association
between Tönnis grade at time of PAO and progression to
arthroplasty. Level of evidence: IV.
30. Wang Y: Current concepts in developmental dysplasia of the hip
and total hip arthroplasty. Arthroplasty 2019;1(1):2. This article
 reviews concepts relating to THA in patients with dysplasia.
31. Hudson D: The rotational profile: A study of lower limb axial
torsion, hip rotation, and the foot progression angle in healthy
adults. Gait Posture 2016;49:426-430.
32. Tannast M, Kubiak-Langer M, Langlo F, Puls M, Murphy SB,
Siebenrock KA: Noninvasive three-dimensional assessment of
femoroacetabular impingement. J Orthop Res 2007;25(1):122-131.
33. Spiker AM, Fabricant PD, Wong AC, Suryavanshi JR, Sink EL:
Radiographic and clinical characteristics associated with a
positive PART (Prone Apprehension Relocation Test): A new
provocative exam to elicit hip instability. J Hip Preserv Surg
2020;7(2):288-297. The authors describe a new provocative
physical examination maneuver to replicate hip instability
symptoms in patients with anterior acetabular undercoverage,
which correlated specifically to more acetabular anteversion at
the 3-o’clock position measured on CT scan.
34. Garbuz DS, Masri BA, Haddad F, Duncan CP: Clinical and
radiographic assessment of the young adult with symptomatic
hip dysplasia. Clin Orthop Relat Res 2004;418:18-22.
35. Selberg CM, Chidsey B, Skelton A, Mayer S: Pelvic osteotomies
in the child and young adult hip: Indications and surgical
technique. J Am Acad Orthop Surg 2020;28(6):e230-e237. This
review article focuses on various pelvic osteotomies in pediatric
and adult patients with dysplasia.
36. Neumann DA: Kinesiology of the hip: A focus on muscular
actions. J Orthop Sports Phys Ther 2010;40(2):82-94.
37. Deshmukh AJ, Panagopoulos G, Alizadeh A, Rodriguez JA,
Klein DA: Intra-articular hip injection: Does pain relief correlate
with radiographic severity of osteoarthritis? Skeletal Radiol
2011;40(11):1449-1454.
38. Cvetanovich GL, Levy DM, Weber AE, et al: Do patients with
borderline dysplasia have inferior outcomes after hip
arthroscopic surgery for femoroacetabular impingement
 compared with patients with normal acetabular coverage? Am J
Sports Med 2017;45(9):2116-2124.
39. Tang H-C, Dienst M: Surgical outcomes in the treatment of
concomitant mild acetabular dysplasia and femoroacetabular
impingement: A systematic review. Arthroscopy 2020;36(4):1176-
1184. This systematic review describes five studies that report
outcomes after hip arthroscopy for those with FAI and mild hip
dysplasia. At 2 years follow-up, improved patient-reported
outcomes (Hip Outcome Score, modified Harris Hip Score, Short
Form-12 Physical Component Score, Western Ontario and
McMaster Universities Osteoarthritis Index) were described in
four of five studies. There was no difference in secondary
procedure rate when comparing those with mild dysplasia and
those with normal acetabular coverage. Level of evidence: IV.
40. Larson CM, Ross JR, Stone RM, et al: Arthroscopic management
of dysplastic hip deformities: Predictors of success and failures
with comparison to an arthroscopic FAI cohort. Am J Sports Med
2016;44(2):447-453.
41. Ganz R, Klaue K, Vinh TS, Mast JW: A new periacetabular
osteotomy for the treatment of hip dysplasias. Technique and
preliminary results. Clin Orthop Relat Res 1988;232:26-36.
42. Murphy SB, Millis MB: Periacetabular osteotomy without
abductor dissection using direct anterior exposure. Clin Orthop
Relat Res 1999;364:92-98.
43. Novais EN, Kim Y-J, Carry PM, Millis MB: The Bernese
periacetabular osteotomy: Is transection of the rectus femoris
tendon essential? Clin Orthop Relat Res 2014;472(10):3142-3149.
44. Ricciardi BF, Mayer SW, Fields KG, Wen el C, Kelly BT, Sink EL:
Patient characteristics and early functional outcomes of
combined arthroscopic labral refixation and periacetabular
osteotomy for symptomatic acetabular dysplasia. Am J Sports Med
2016;44(10):2518-2525.
45. Wilkin GP, Poitras S, Clohisy J, et al: Periacetabular osteotomy
with or without arthroscopic management in patients with hip
 dysplasia: Study protocol for a multicenter randomized
controlled trial. Trials 2020;21(1):725. This study describes the
protocol for a prospective study investigating outcomes and costs
associated with combined management with arthroscopy and
PAO.
46. Swarup I, Ricciardi BF, Sink EL: Avoiding complications in
periacetabular osteotomy. JBJS Rev 2015;3(11):e4.
47. Allahabadi S, Faust M, Swarup I: Venous thromboembolism
after pelvic osteotomy in adolescent patients: A database study
characterizing rates and current practices. J Pediatr Orthop
2021;41(5):306-311. This retrospective study investigates the rates
of venous thromboembolism after pelvic osteotomies. This study
includes all types of pelvic osteotomies in adolescents and found
a nonnegligible risk of 0.6% for venous thromboembolism within
90 days of surgery. Level of evidence: III.
48. Grammatopoulos G, Wales J, Kothari A, Gill HS, Wainwright A,
Theologis T: What is the early/mid-term survivorship and
functional outcome after Bernese periacetabular osteotomy in a
pediatric surgeon practice? Clin Orthop Relat Res 2016;474(5):1216-
1223.
49. Wells J, Millis M, Kim Y-J, Bulat E, Miller P, Matheney T:
Survivorship of the Bernese periacetabular osteotomy: What
factors are associated with long-term failure? Clin Orthop Relat
Res 2017;475(2):396-405.
50. Lerch TD, Steppacher SD, Liechti EF, Tannast M, Siebenrock
KA: One-third of hips after periacetabular osteotomy survive 30
years with good clinical results, no progression of arthritis, or
conversion to THA. Clin Orthop Relat Res 2017;475(4):1154-1168.
C H AP T E R 4 1

Muscular, Neurovascular, and Soft-

Tissue Conditions of the Hip
Blair S. Ashley MD, Yale A. Fillingham MD, FAAOS

Dr. Fillingham or an immediate family member has received royalties from Exactech, Inc. and Medacta;
serves as a paid consultant to or is an employee of Exactech, Inc., Johnson & Johnson, and Medacta; has
stock or stock options held in Parvizi Surgical Innovations; and serves as a board member, owner, officer, or
committee member of American Academy of Orthopaedic Surgeons and American Association of Hip and
Knee Surgeons. Neither Dr. Ashley nor any immediate family member has received anything of value from or
has stock or stock options held in a commercial company or institution related directly or indirectly to the
subject of this chapter.

ABSTRACT
A variety of pathologies result in acute and chronic hip pain, including
tendinitis, bursitis, and neurovascular and bone maladies. Some of these
diagnoses are related to acute injury or overuse injuries, and others are
because of anatomic abnormalities. Diagnosis can often be challenging
because imaging studies can sometimes underdiagnose problems that are
more dynamic in nature. Ultrasonography studies and physical
examination findings are paramount in diagnosis. Fortunately, most soft-
tissue ailments about the hip respond to anti-inflammatory medication and
physical therapy. When ailments are refractory to nonsurgical measures,
surgery can be considered, and most of these pathologies can be managed
arthroscopically. As always, the whole patient must be considered, and
providers should be screening for psychological factors such as depression
and anxiety that may amplify the symptoms in patients with chronic hip
pain.
Keywords: bursitis; entrapment; snapping hip; syndromes; tendinitis

Introduction
The hip joint is a ball-and-socket joint composed of complex soft-tissue,
muscular, bony, and neurovascular anatomy lending itself to astounding
function, but also the potential for pain and dysfunction from varying
etiologies. Although most orthopaedic surgeons are facile with treating
patients with bone maladies about the hip, it is also imperative to be able
to recognize, diagnose, and manage soft-tissue disorders about the hip.
Conditions such as trochanteric bursitis, iliopsoas tendinitis, and
neurovascular syndromes can present in patients with native as well as
prosthetic hips. Other diagnoses including gluteal muscle/tendon injuries,
snapping hip, and labral injuries can lead to severe hip pain, limiting
patients during activities of daily living as well as recreational and
competitive sports. An improved understanding about the muscular, soft-
tissue, and neurovascular pathologies that can occur around the hip can
help improve the quality of life of patients of all ages.

Muscular Conditions About the Hip

Lateral hip pain has been a notoriously poorly defined entity that is
difficult to manage given nonspecific historical and examination elements
and a paucity of reliable imaging techniques. The understanding of lateral
hip pathology has been improving, with a continued interest in sports
medicine and increased use of advanced ultrasonography techniques by
musculoskeletal radiologists (Table 1).

Table 1
Differential Diagnosis of Soft-Tissue and Neuromuscular Hip Conditions
of the Native and Prosthetic Hip

Bone-Related Nerve Vascular Nonorthopaedic

Soft-Tissue Disorders
Conditions Conditions Conditions Conditions
Bone-Related Nerve Vascular Nonorthopaedic
Soft-Tissue Disorders
Conditions Conditions Conditions Conditions
Femoroacetabular Peritrochanteric Space Low Back Claudication Gynecologic
Impingement Pathology/Greater Pain/Sciatica Gluteal Artery Disorders
Extra-articular Hip Trochanteric Pain Iatrogenic Stenosis
Impingement Syndrome Nerve Injury Osteonecrosis Ovarian
Syndromes Pelvic Nerve conditions
Trochanteric Neuropathy Uterine
Ischiofemoral bursitis Meralgia fibroids
impingement Abductor Paresthetica Malignancy
Subspine strain/tears Pudendal Infection
impingement External snapping Nerve
Iliopsoas hip syndrome Entrapment Gastrointestinal
impingement
Pectineofoveal Adductor Muscle Hernia
impingement Strains Appendicitis
Hip Flexor Problems Inflammatory
Fractures bowel
Internal snapping disease
Femoral neck hip syndrome Diverticulitis
Pertrochanteric Iliopsoas tendinitis Malignancy
Pubic rami
Sacrum Deep Gluteal Syndrome Genitourinary
Iliac wing (Piriformis Syndrome)
Post-Total Hip Renal
Osteitis Pubis Arthroplasty Conditions stones
Infection
Trochanteric Malignancy
bursitis
Iliopsoas tendinitis
Instability/abductor
insufficiency

Peritrochanteric Space Pathology or Greater

Trochanteric Pain Syndrome
Peritrochanteric space pathology and greater trochanteric pain syndrome
(GTPS) are generic terms with significant overlap that encompass
conditions including trochanteric bursitis, abductor tears, and external
snapping hip syndrome. Peritrochanteric space pathology/GTPS presents
as persistent lateral hip pain radiating along the lateral aspect of the thigh
to the knee and occasionally below the knee and/or bu ock. It can be
incredibly debilitating and is quite common, occurring in 15% of women
and 6.6% of men between the ages of 50 and 79 years. 1 The prevalence of
bilateral GTPS was 8.5% in women and 1.9% in men. 1 In a multivariate
model, adjusting for age, sex, and other factors, iliotibial band (ITB)
tenderness, ipsilateral and contralateral knee osteoarthritis, body mass
index, and low back pain were positively related to GTPS. 1 The complex
anatomy of the lateral hip including bursae, muscular sheaths, and
tendinous a achments of the gluteus maximus, ITB, tensor fascia lata,
gluteus medius, and gluteus minimus are prone to overuse injuries,
trauma, and gait alterations. Physical examination reveals point tenderness
in the posterolateral area of the greater trochanter, and maneuvers useful
in differentiating the source of lateral hip pain include the single-leg
stance, resisted external rotation of the hip, hip lag sign, and the
Trendelenburg test. 2 , 3 Imaging modalities are limited in their ability to
definitively diagnose the etiology of predominantly lateral hip pain in most
cases; however, the use of dynamic ultrasonography along with guided
injections and magnetic resonance scans assists in differentiating the
pathology and confirming the diagnosis in patients with lateral hip pain. 3

Trochanteric Bursitis
Bursae enable improved muscle mechanics over the lateral part of the
proximal femur; most people have three to four bursae surrounding the
lateral aspect of their hips. The largest bursa is found between the gluteus
maximus muscle and gluteus medius tendon, which is located directly
lateral to the greater trochanter and most often implicated in trochanteric
bursitis. Increased acetabular anteversion has been associated with gluteal
and trochanteric bursitis. 3 Correlations have also been noted in patients
with trochanteric bursitis and lumbar degenerative disease, and patients
with concomitant lumbar degenerative disease as seen on scintigraphic
imaging have been shown to be less likely to respond to treatment. 4
According to a 2021 study, obesity, smoking, the presence of emotional
distress, fibromyalgia, and hypothyroidism are correlated to an increased
risk of poor clinical outcomes in patients with trochanteric bursitis. 5

Abductor Tears
Abductor tears, typically at the gluteus medius and/or minimus
musculotendinous junction, are a common underlying etiology for lateral
hip pain and are often referred to as the rotator cuff tears of the hip.
Although inflammation of the tendon is not necessarily a major feature, an
element of tendinosis is typically present before tearing. 6 In particular, the
anterolateral part of the gluteus medius tendon is more prone to tears
because of a thin tendinous portion. 3 Relative risk factors for abductor
tears include increased pelvic width, increased body weight moment arm
and abductor moment arm, decreased femoral anteversion and
enthesophyte present with the teardrop distance, and the presence of
enthesophytes being the most predictive. 7 The presence of an
enthesophyte on the greater trochanter had an odds ratio of approximately
21 and a positive predictive value of 94% for having an abductor tendon
tear. 7 , 8 Additionally, as discussed in a 2020 study, patients with
ischiofemoral impingement have a higher prevalence of gluteus
medius/minimus partial-thickness and full-thickness tears and thus may
have a related pathophysiology. 9 Abductor tendon tears can also occur
after undergoing arthroplasty for a femoral neck fracture or following
elective total arthroplasty, and tendon dysfunction with avulsion or failure
of repair following an anterolateral approach can also occur. 10 Abductor
tendon tears should be confirmed with MRI.

External Snapping Hip

The external snapping hip is produced by the ITB snapping over the
prominence of the greater trochanter during flexion and extension.
Snapping hip syndrome is characterized by audible snapping and is
frequently accompanied by pain, weakness, and a resulting loss of range of
motion. 11 Although painless snapping in the hip is common in the general
population, the symptomatic snapping hip with debilitating pain and
weakness is more commonly seen in those who take part in activities such
as ballet and running hurdles. The diagnosis can be made using dynamic
ultrasonography to observe the snapping tendon in real time. Most
patients with snapping hip can be treated nonsurgically; however, surgery
may be indicated if the condition becomes chronically symptomatic.

Treatment
Fortunately, most cases of GTPS are self-limited with nonsurgical
measures. There is a wide variety of nonsurgical treatment options for
peritrochanteric space pathology/GTPS, including home therapy, insoles
and orthotics, formal physical therapy, eccentric physical therapy
injections, shockwave therapy, platelet-rich plasma injections, and drug
therapy. 6 , 12 , 13 Corticosteroid injections have been shown to be the most
effective at pain relief, without any additional benefit derived from image-
guided injections. 12 , 13 Ultrasound-guided and anatomic landmark
injections of the trochanteric bursa have similar 2-week and 6-month
outcomes; however, ultrasound guidance is more expensive and less cost-
effective; thus, anatomic landmark-guided injection remains the method of
choice and should be routinely performed using a sufficiently long needle
of at least 2 inches. 14 The most effective treatment options were
infiltrations with corticosteroids, resulting in symptom resolution in 49% to
100% of patients, and shockwave therapy. 6 , 15 Both adjuncts are excellent to
help improve patient symptomatology to enable be er participation in
physical therapy. 13 Advancements in nonsurgical treatment modalities for
tendinopathy continue to be developed, and some promising avenues
include topical glycerol trinitrate therapy, matrix metalloproteinase-
inhibitor injection, gene or stem cell therapy, autologous tenocyte
injection, and sclerosant injections. 12
Surgical interventions have anecdotally been reported to provide pain
relief when nonsurgical treatment modalities fail. 2 Surgical treatment
modalities vary greatly and depend on the presumed etiology of the GTPS.
Surgery can include bursectomy, ITB release, trochanteric reduction
osteotomy, or gluteal tendon repair. 13 , 15 For patients requiring repair of
abductor tendon tears, most patients reported good to excellent functional
outcomes and pain reduction after both open and endoscopic repair. 16
Intraoperatively, tears of the gluteus medius and partial-thickness tears
were encountered most often, with tears involving both the gluteus medius
and minimus occurring 29% of the time. 16 Complication rates were low for
both the open and endoscopic approaches, but no tendon retears were
documented after endoscopic repair, whereas the retear rate after open
repair was 9%. 16 As discussed in a 2021 study, the anatomy and chronicity
of the lesion, the extent of fa y infiltration, and neurologic integrity of hip
abductor muscles may influence both treatment choice and outcome. 17 For
more challenging cases, reconstruction with a gluteus maximus muscle flap
or Achilles tendon allograft has provided promising short-term results in
small series. 10 For patients with external snapping hip, the endoscopic
release of the ITB or the endoscopic release of the femoral insertion of the
gluteus maximum tendon is the most popular technique and they provide
fewer complications compared with open surgery, a lower recurrence rate,
and good clinical outcomes. 18 A fanlike technique can be used to release
the ITB in a stepwise manner. 19 When intra-articular lesions causing
discomfort can be identified, arthroscopy may play a key role in treatment.
20
There has also been a recent study purporting the success of treatment
using ultrasound-guided release of the external snapping hip using only
local anesthesia. 21 In a cohort of 14 patients with an average age of 43
years, the snapping hip resolved in all patients following ultrasound-
guided release, with significantly improved patient-reported outcome
measures and without complications or recurrences. 21
Adductor Muscle Strains
Adductor muscle strains commonly occur in sports such as hockey, soccer,
or any activity involving eccentric contracture of the adductor musculature.
Any one of the three muscles of the adductor group can be involved, but
the adductor longus is the most likely to be injured. 22 , 23 Patients typically
present with groin pain/strain, which can be debilitating for an athlete.
Strain severity varies from minor strain (grade 1) to a severe strain (grade 3)
in which there is a complete loss of muscle function. 22 Adductor muscle
strains have been associated with hip muscle weakness, particularly if there
is an imbalance of strength between the abductor and adductor
musculature, as well as history of prior injury, excessive practice sessions,
and level of experience of the athlete. 22 , 24 , 25 Core muscle weakness or
delayed onset of transversus abdominis muscle recruitment may increase
the risk of groin strain injury. 24 Injury prevention is ideal by encouraging
patients and athletes to engage in an active hip-strengthening program. 26 ,
27
Some exercises targeting the adductor longus muscle are be er than
others, with exercises having the most to the least muscle activation as
follows: side-lying hip adduction, ball squeezes, side lunges, standing
adduction on a Swiss ball, rotational squats, and sumo squats. 28 When
injury does occur, a multimodal treatment program including heat, exercise
therapy, massage, and return to running program has been shown to be
more effective than exercise therapy alone. 29 If nonsurgical treatment
modalities fail for 6 months or longer, then surgical interventions such as
adductor release and tenotomy have reportedly had limited success. 22

Hip Flexor Problems

Internal Snapping Hip Syndrome (Medial Coxa Saltans or
Iliopsoas Syndrome)
The pathogenesis of internal snapping hip syndrome is multifactorial, and
it is traditionally thought to be caused by the tendon snapping over the
anterior femoral head or the iliopectineal ridge, although labral tears,
cartilage defects, and loose bodies are also possible intra-articular sources.
Patients typically present with pain aggravated by activities including
flexion and rotation. 30 , 31 There is no significant difference between males
and females, although these symptoms are more common in elite athletes
and dancers, especially with hip flexion beyond 90°. 32 When making the
diagnosis, plain radiographs and dynamic ultrasonography are the best
imaging modalities, with MRI being reserved for only unresolved and
challenging cases. 33 , 34 Dynamic ultrasonography is the gold standard, as
its real-time imaging capabilities enable detection of the mechanism of the
abnormal tendon friction during hip movement in a noninvasive way and it
also allows for a diagnosis of additional hip tissue changes that may be
causing the pain. 34 However, dynamic ultrasonography, similar to all
ultrasonography, is limited by operator experience as well as patient
compliance with the requested maneuvers. Recent studies have tried to
define parameters to increase the diagnostic acumen of MRI. Using
minimum-intensity projection protocol, the sagi al opening angle was
shown to be a statistically significant parameter where a sagi al opening
angle of more than 140° correlates with symptomatic iliopsoas tendon
pathology; however, neither pelvic incidence nor coronal angle consistently
was correlated with pathology. 35 As discussed in a 2019 study, the sagi al
opening angle is measured by forming an angle centered at the apex of the
iliopsoas tendons curvature in the sagi al plane and is then determined by
measuring the angle formed between a line tangent to the proximal portion
of the tendon versus the distal portion of the tendon relative to the apex of
the curve. 35 Most cases of internal snapping hip syndrome resolve with
nonsurgical treatment, which includes avoidance of aggravating activities,
stretching, and NSAIDs. 36 In recalcitrant cases, surgery may be indicated.
Arthroscopic and open surgical techniques are both acceptable; however,
there has been a decreased failure rate, fewer complications, and decreased
postoperative pain reported with arthroscopic management. 37 - 39 It is
important for surgeons to be aware that a subset of patients, approximately
18%, have multiple iliopsoas tendons, and failure to release all tendinous
a achments can be a source of recalcitrant cases. 39 , 40

Iliopsoas Tendinitis and/or Bursitis

Iliopsoas tendinitis is poorly understood and can be an underrecognized
cause of anterior groin pain. This condition afflicts both younger, more
active patients as well as patients following total hip arthroplasty and can
result in symptomatic anterior groin pain. Etiologies of iliopsoas tendinitis
following total hip arthroplasty include acetabular component prominence
at the anteroinferior acetabular rim because of component malpositioning,
retained cement, a prominent femoral collar, and excessively long
acetabular screws. 41 - 46 Pain-generating positions and motions include hip
flexion, such as climbing the stairs, ge ing in and out of bed, and rising
from a seated position. 42 The characteristic anterior groin pain can be
reproduced with the Stinchfield test and psoas stretch, although the
findings can be subtle and nonspecific. Imaging modalities such as
dynamic ultrasonography and MRI have been used but are of limited
diagnostic use. 47 Unfortunately, in a series of 63 patients neither physical
examination nor ultrasonographic or MRI findings were associated with a
positive response to peritendinous iliopsoas corticosteroid injections in
patients with suspected iliopsoas tendinitis. 48 This study found that
although many history or examination findings were sensitive for
diagnosing iliopsoas tendinitis that responded to corticosteroid injection
(groin pain, snapping hip, and pain with resisted straight leg raise), none of
these had a specificity greater than 24%. 48 Similarly, it was found that
bursal distension and tendinosis seen on ultrasonography had low
sensitivities of only 67% and 63%, respectively, and similarly low
specificities of 35% and 32%, respectively. 48 MRI findings including bursal
distension, tendon thickening, and tendon heterogeneity had similarly
disappointing sensitivities and specificities for diagnosis. 48

Deep Gluteal Syndrome

Deep gluteal syndrome (DGS), otherwise known as piriformis syndrome, is
a comprehensive term encompassing bu ock and posterior hip pain
related to nondiscogenic sciatic nerve entrapment of the sciatic nerve by
the piriformis muscle, as well as the obturator internus, levator ani,
gemelli, and coccygeal muscles. 3 The borders of the space include the
gluteus maximus posteriorly, the posterior thigh inferiorly, the linea aspera
laterally, and the posterior border of the femoral neck anteriorly. 49
Pathologic processes contributing to DGS include fibrous and fibrovascular
bands, piriformis muscle hypertrophy, insertional pathology of the gemelli
or obturator internus muscles, aberrant course of the sciatic nerve, fibrosis
after surgery, hamstring origin enthesopathies, or muscle strains, among
other anatomic variants or injuries 49 (Table 2). Suspicion of DGS should be
raised when patients endorse posterior hip pain, radicular pain, and
difficulty with si ing for more than 30 minutes, limping, disturbed or loss
of sensation in the affected extremity, lumbago, and pain at night ge ing
be er during the day. 49 Physical examination findings consistent with DGS
include tenderness in the deep gluteal space, positive piriformis test,
Lasègue test, Freiberg sign, Bea y test, flexion, adduction, internal rotation
or FAIR test, seated piriformis stretch test, and a positive Pace sign. 3 , 49
The active piriformis test has a sensitivity of 78% and specificity of 80%,
and the seated piriformis stretch test has a sensitivity of 52% and specificity
of 90%, making them the physical examination maneuvers most helpful in
diagnosing DGS, particularly when used in combination (sensitivity of 91%,
specificity of 80%). 50 Electrodiagnostic and imaging studies can also aid in
diagnosis. Guided injections with patients lying prone using
ultrasonography, CT, or open MRI can have both diagnostic and
therapeutic benefits. Because the subgluteal space is comprised of cellular
and fa y tissue located between the middle and deep gluteal aponeurosis
layers near the fascia, it can be difficult to visualize on MRI, but MRI can be
helpful in excluding intra-articular sources of pathology. 49 As always,
nonsurgical treatment should first be a empted by instructing patients to
avoid provocative activities, anti-inflammatory medications, image-guided
injections, and physical therapy. Open or endoscopic surgical
decompression should be reserved for patients with persistent symptoms
and for those who have evidence of compressive masses on advanced
imaging. 51

Table 2
Subtypes of Deep Gluteal Syndrome and Their Etiologies

Piriformis
syndrome Hypertrophy of the piriformis muscle
Dynamic sciatic nerve entrapment by the piriformis muscle
Anomalous course of the sciatic nerve or attachments of the piriformis
muscle
Sciatic nerve entrapment secondary to fibrosis after open surgery
Trauma or overuse conditions (avulsions, tendinosis, strains, calcifying
tendinosis, or spasm)

Gemelli-obturator
internus syndrome Insertional pathology where the tendon penetrates the nerve
Hypertrophied obturator internus

Quadratus femoral
and ischiofemoral Isolated strains or tears are uncommon
pathology Edema and/or chronic inflammatory changes and adhesions

Hamstring
conditions Hamstring origin enthesopathies
Partial or complete hamstring strain (acute, recurrent, or chronic)
Hamstring tendon pathology including detachment, avulsion fracture,
apophysitis, nonunited apophysis, proximal tendinopathy, calcifying
tendinosis, or chronic inflammatory changes
Congenital fibrotic bands

Gluteal disorders
Gluteal contracture
Gluteal tendinosis with gluteus maximus muscle atrophy
Extra-articular Hip Impingement Syndromes
There are five types of extra-articular hip impingement syndromes,
including ischiofemoral impingement, subspine impingement, iliopsoas
impingement, DGS, and pectineofoveal impingement. 49 The
understanding of these disorders is limited by generally low prevalence
and frequent concomitant pathologies such as femoroacetabular
impingement.

Ischiofemoral Impingement
Ischiofemoral impingement is where the quadratus femoris muscle
becomes compressed between the lesser trochanter and the ischial
tuberosity. Patients with valgus hips can be particularly prone to
ischiofemoral impingement and frequently present with a lack of external
rotation and extension as well as a positive posterior impingement test. 52
Posterior impingement is extra-articular in 92% of hips with increased
femoral version and typically occurs between the ischium and lesser
trochanter at 20° of extension and 20° of external rotation. 52 Diagnosis can
be challenging and greatly relies on history and physical examination.
However, there are some radiographic markers shown to be helpful in
making the diagnosis. Ischiofemoral distances on supine and standing hip
radiographs had good diagnostic performance and provide a promising
screening tool because patients with ischiofemoral impingement had
ischiofemoral distances on supine and standing radiographs of
approximately 20 mm and 19 mm, respectively, compared with 26 mm and
22 mm for unaffected control patients. 53 MRI can also be useful in
diagnosis because measurements of ischiofemoral space and quadratus
femoris space are decreased relative to controls and using a cutoff for
ischiofemoral space of less than or equal to 15 mm has a sensitivity of 77%
and specificity of 81% and using a cutoff of less than or equal to 10 mm for
quadratus femoris space has a sensitivity of 79% and specificity of 74%. 53 , 54
An image-guided injection test of the ischiofemoral space also has both
diagnostic and therapeutic function in guiding management. 55 Although
initial management should always be nonsurgical, refractory cases can be
treated surgically. Surgical options include femoral derotation osteotomy
and/or hip arthroscopy or resection of the lesser trochanter. 52 There have
been promising results with endoscopic partial resection of the lesser
trochanter with excellent improvements in the modified Harris hip scores,
mean visual analog scale scores with an average return to sport of 4.4
months, no loss of iliopsoas muscle strength, and rare complications noted
in multiple small studies. 56 , 57

Subspine Impingement
Subspine impingement is a mechanical conflict between an enlarged or
misoriented anterior inferior iliac spine (AIIS) and the proximal femur,
particularly the distal anterior femoral neck. Interest in subspine
impingement initially began as it was recognized in patients with
femoroacetabular impingement who underwent arthroscopy and had
refractory symptoms. 58 One study used three-dimensional CT
reconstructions to define three types of AIIS variants: in type 1 there was a
smooth ilium wall between the AIIS and the acetabular rim, in type 2 the
AIIS extended to the level of the acetabular rim, and in type 3 the AIIS
extended beyond the acetabular rim. 59 It was also noted that types 2 and 3
were associated with decreased hip flexion and internal rotation,
supporting the rationale for decompression of the AIIS during
arthroscopic management of impingement in patients with abnormal
morphology. 58 , 59 Preoperative recognition of subspine impingement is
important, and certain radiologic features can be noted on MRI. Distal cam
morphology, as evidenced by an osseous bump along the femoral neck
more distal to the head-and-neck junction and proximal to the bony
protuberance of the capsular a achment, was more prevalent in patients
with a clinical and arthroscopic diagnosis of subspine impingement. 58
Other features include signs of impingement on the distal femoral neck,
superior capsular edema, and edema of the joint capsule at the level of the
AIIS. 58 Although there is considerable overlap between subspine
impingement and femoroacetabular impingement, recognition of features
consistent with subspine impingement preoperatively will help to ensure
adequate surgical resection during arthroscopy and hopefully minimize the
number of patients with persistent symptoms following intervention.

Iliopsoas Impingement
Iliopsoas impingement is a mechanical conflict that occurs between the
iliopsoas muscle and the labrum, resulting in distinct anterior labral
pathology, with anteriorly localized labral damage that does not extend to
the anterosuperior portion of the acetabulum. Patients frequently present
with anterior groin pain and intermi ent catching, snapping, or popping of
the hip. Iliopsoas impingement can also occur after total hip arthroplasty
and becomes a frustrating source of persistent anterior groin pain in these
patients. 60 Nonspecific focal tenderness can sometimes be found over the
iliopsoas tendon at the level of the joint. Diagnosis can be challenging
because the symptoms are typically related to movement, thus dynamic
ultrasonography is generally the most useful imaging modality. Whether in
a native or prosthetic hip, nonsurgical management with activity
modification, anti-inflammatory medications, and therapy serves as the
first line of treatment. If pain persists, ultrasound-guided injections can
have both diagnostic and therapeutic benefits, with arthroscopic release of
the iliopsoas tendon being reserved for refractory cases. For patients
undergoing total hip arthroplasty, nonsurgical treatment was successful in
50% of patients. 60 In patients with minimal acetabular component
prominence (defined as <8 mm), iliopsoas release was highly effective,
whereas in patients with ≥8 mm of prominence, revision of the acetabular
component resulted in more predictable pain relief. 60

Pectineofoveal Impingement
Pectineofoveal impingement describes pain occurring when the medial
synovial fold impinges against overlying soft tissue, primarily the zona
orbicularis. It is a relatively rare condition that causes hip or groin pain
along with mechanical symptoms of clicking and predominantly occurs in
young adults and has received very li le a ention in the literature. 49 The
pectineofoveal fold is a fibrous band located anteromedially on the femoral
neck and can be consistently visualized during arthroscopy in the
peripheral compartment of the hip and comes near the zona with rotational
movements and with the labrum during full flexion and external rotation. 61
This abnormal contact ultimately results in a thickened, fibrosed medial
synovial fold. Patients present with ill-defined hip pain aggravated by
rotational movements and occasional mechanical symptoms such as
feelings of hip blockage, but with a notable absence of snapping or
clunking. 61 Although the medial synovial fold is visible on magnetic
resonance arthrogram, its presence on MRI is unpredictable, thereby
complicating diagnosis before arthroscopy. If nonsurgical measures fail,
then arthroscopic resection of the medial synovial fold with a punch or
radiofrequency ablation device has had some good results, although
response to treatment is largely unpredictable and likely further
complicated by its overlap with other impingement syndromes. 61
Deep Gluteal Syndrome
DGS results in pain occurring in the bu ock because of the entrapment of
the sciatic nerve in the deep gluteal space, as described previously.

Neurovascular Issues
Most of the blood supply to the mature femoral head is via the profunda
femoris artery and its contributory branches of the medial femoral
circumflex artery. Osteonecrosis of the femoral head is a concern when
there is an injury to the major arteries or branches during surgery, trauma,
or external compression sources. 62 When musculoskeletal sources of hip,
thigh, and bu ock pain cannot be found on physical examination or
imaging studies, then vascular sources such as claudication, aneurysm,
and/or arterial disease and stenosis should be considered particularly when
vascular calcifications or other historical elements such as symptom relief
with rest are concerning for these diagnoses. Similarly, stenosis of the
gluteal arteries can result in gluteus maximus claudication resulting in
bu ock pain. 63
Neurologic disorders specific to the hip region are relatively uncommon,
but conditions such as low back pathology and sciatica/sciatic nerve
dysfunction often coexist with, and masquerade as, hip pathology.
Iatrogenic nerve injury can also occur during surgical procedures around
the hip, particularly of the sciatic, femoral, lateral femoral cutaneous, and
superior/inferior gluteal nerves. Neuropathy of the pelvic nerves can result
in chronic pelvic pain. The femoral and genitofemoral nerves, ilioinguinal
and iliohypogastric nerves, pudendal nerve, obturator nerve, lateral
femoral cutaneous nerve (LFCN), posterior femoral cutaneous nerve,
inferior cluneal nerves, inferior rectal nerve, sciatic nerve, superior gluteal
nerve, and the spinal nerve roots can be implicated. 64 , 65 Etiologies of
pelvic neuropathy are extensive and include entrapment, inflammation,
trauma, or iatrogenic trauma. Physical examination remains the
cornerstone of diagnosis because there can be many overlying symptoms
with other disorders. Treatment refractory to nonsurgical measures can be
treated by injections, which are typically performed using image guidance
modalities including ultrasonography, MRI, and more recently, CT scan. 64 ,
65

Meralgia Paresthetica
Meralgia paresthetica is a specific term for paresthesias that occur when
the LFCN is compressed or entrapped as it passes under the inguinal
ligament. Temporary or permanent paresthesias related to LFCN trauma
are observed after direct anterior total hip arthroplasty and following other
anterior exposures to the hip, but the variable regional anatomy of the
LFCN also makes it susceptible to noniatrogenic local trauma. 66 , 67 Patients
are sometimes misdiagnosed as having radiculopathy. However, meralgia
paresthetica should be considered when there are only sensory complaints
without motor deficits. Despite the lack of motor involvement, the
associated sensory dysfunctions can be debilitating for patients. 67 , 68 Local
anesthetic injection can be helpful in diagnosis and in treatment. Most
patients improve with nonsurgical treatment including removal of
compressing agents, NSAIDs, and injections. 67 As this condition
disproportionately affects patients with obesity, weight loss is often
indicated. Because of the variable anatomy of the LFCN, where the average
distance of the LFCN from the anterior superior iliac spine is 8.8 mm but
can be as far as 2 cm from the medial tip of the anterior superior iliac spine,
the use of ultrasound guidance is typically recommended. 66 , 67 If
intractable pain persists despite nonsurgical measures, neurolysis or
transection are surgical procedures that can be considered. 67

Pudendal Nerve Entrapment

Pudendal nerve entrapment or pudendal neuralgia is another potential
source of chronic pelvic pain. The pudendal nerve emerges from the S2, S3,
and S4 roots’ ventral rami of the sacral plexus. It carries sensory, motor,
and autonomic fibers; however, an injury to the pudendal nerve causes
sensory deficits more than motor. 69 The Nantes criteria provide a basis for
diagnosis and consist of five essential diagnostic criteria: (1) pain in the
anatomic territory of the pudendal nerve; (2) pain worsened by si ing; (3)
patient is not awakened at night by the pain; (4) no objective sensory loss
on examination; and (5) a positive pudendal nerve block. 70 The physician
should also be aware of certain red flag symptoms that should raise
suspicion for a more nefarious etiology, including waking up at night,
excessively neuropathic nature of pain, and pinpoint pain and should
prompt further investigation with advanced imaging. 70 Pudendal neuralgia
can be categorized into four types based on anatomy: type I is entrapment
that occurs below the piriformis muscle as the pudendal nerve exits the
greater sciatic notch; type II is entrapment that occurs between
sacrospinous and sacrotuberous ligaments and is the most common cause
of nerve entrapment; type III is when entrapment occurs in the Alcock
canal; and type IV occurs when entrapment occurs to the terminal
branches. 69 Most patients improve with nonsurgical management
consisting of manual therapy, stretching, strengthening exercises, aerobic
conditioning, and cognitive behavioral therapy. 71 Neurolysis and
neurectomy can be considered for refractory cases. 71 There have also been
some reports of the success of pulsed high-frequency radiofrequency
treatment applied to the pudendal nerve under ultrasound guidance. 72

Mental Health Association

When evaluating patients with lateral hip pain and other soft-tissue
disorders about the hip, the physician should also be aware of their
baseline psychologic and emotional state. Mood disorders and hip pain
often coexist, and the whole patient must be considered to optimize the
success of treatment. 73 The prevalence of behavioral health disorders such
as anxiety and depression is as high as 19% in American adults and has
been reported to be as high as 50% in patients with prearthritic hip
disorders, including femoroacetabular impingement, acetabular dysplasia,
lateral trochanteric pain syndrome, and/or labral tears. 74 , 75 Women
undergoing hip arthroscopy were also more likely than their male
counterparts to experience depression or anxiety (56% versus 46%,
respectively). 75 Whether the greater preponderance of behavioral health
diagnoses existed before the hip disorders or were spurred by the pain and
dysfunction associated with the disorders is unclear. Regardless, patients
with psychological impairment have been shown to be less likely to achieve
a favorable outcome after arthroscopy, with an odds ratio of 0.74, and they
reported worse postoperative patient-reported outcome scores compared
with nonimpaired patients, with a mean difference of 20 fewer points. 74
Pain catastrophizing is also commonly seen among patients with
prearthritic hip disorders. A 2019 study found that the percentage of
patients with abnormal levels of pain catastrophizing, anxiety, or
depression was 22.0%, 16.0%, and 12.0% for dysplastic dysplasia of the hip,
respectively; 9.1%, 10.9%, and 7.3% for femoroacetabular impingement,
respectively; and 13.0%, 4.3%, and 4.3% for lateral trochanteric pain,
respectively. 76 Perioperative multidisciplinary assessment may be a
beneficial part of comprehensive orthopaedic hip care because patients
with hip pathology often exhibit pain catastrophizing, anxiety, and
depression, but improvements in hip functionality are associated with
decreased severity of these psychological comorbidities. 77
Summary
Hip and bu ock pain can result from myriad muscular, neurovascular, and
soft-tissue conditions that are often difficult to differentiate. Patients can
often have a delayed diagnosis because of a lack of familiarity with these
conditions among physicians. A thorough knowledge of the anatomy
around the hip as well as a thoughtful and pointed physical examination
are paramount to aid in the diagnosis and management of these disorders.
Similarly, it is imperative that physicians recognize that ill-defined hip and
bu ock pain often coexist with mental health illness and recognition and
treatment of pain catastrophizing, depression, and anxiety are necessary to
ensure that patients have the best treatment outcome possible. Although
nonsurgical therapeutic modalities are the mainstay of treatment for these
disorders, surgery is sometimes indicated and thus the surgical options
and indications must continue to be studied to improve understanding of
these conditions and their management.

Key Study Points

Muscular, neurovascular, and soft-tissue conditions about the hip are extremely common
causes for consultation. The complex anatomy of the hip places it at risk for overuse injuries,
trauma, gait alterations, and soft-tissue issues following surgery.
Most of these conditions about the hip are responsive to nonsurgical treatment modalities, such
as NSAIDs, stretching exercises, formal physical therapy, and injections. After a prolonged
attempt of nonsurgical management, surgical options come into play with arthroscopic and
minimally invasive treatments being most popular.
Neurologic impingement around the hip is relatively uncommon, with the three most common
conditions being meralgia paresthetica, DGS, and pudendal nerve entrapment.
Patients complaining of chronic lateral hip pain and other soft-tissue disorders about the hip
should be screened for mood disorders. There is a well-established association between
depression and anxiety and prearthritic hip disorders that, if left untreated, will inhibit the
patient’s recovery.

Annotated References
1. Segal NA, Felson DT, Torner JC, et al: Greater trochanteric pain
syndrome: Epidemiology and associated factors. Arch Phys Med Rehabil
2007;88(8):988-992.
2. Williams BS, Cohen SP: Greater trochanteric pain syndrome: A review of
anatomy, diagnosis and treatment. Anesth Analg 2009;108(5):1662-1670.
3. Kizaki K, Uchida S, Shanmugaraj A, et al: Deep gluteal syndrome is
defined as a non-discogenic sciatic nerve disorder with entrapment in the
 g p
deep gluteal space: A systematic review. Knee Surg Sports Traumatol
Arthrosc 2020;28(10):3354-3364. This is a systematic review article focused
on identifying the DGS disease definition as a nondiscogenic sciatic
nerve disorder with entrapment in the gluteal space, which can be
diagnosed by history, examination and imaging studies. Level of
evidence: IV.
4. Walker P, Kannangara S, Bruce WJM, Michael D, Van der Wall H: Lateral
hip pain: Does imaging predict response to localized injection? Clin
Orthop 2007;457:144-149.
5. Dzidzishvili L, Parrón Cambero R, Mahillo Fernández I, Llanos Jiménez
L: Prognostic factors of trochanteric bursitis in surgical-staged patients:
A prospective study. Hip Int 2021; January 11 [Epub ahead of print].
Trochanteric bursitis is a common source of lateral hip pain where a
lower number of corticosteroid infiltrations, shorter time span from
symptom onset to surgery, nonsmoker status, and the absence of prior
lumbosacral fusion are good prognostic factors. Level of evidence: IV.
6. Torres A, Fernández-Fairen M, Sueiro-Fernández J: Greater trochanteric
pain syndrome and gluteus medius and minimus tendinosis:
Nonsurgical treatment. Pain Manag 2018;8(1):45-55.
7. Hartigan DE, Perets I, Walsh JP, et al: Radiographic risk factors and
signs of abductor tears in the hip. Arthroscopy 2018;34(8):2389-2397.
8. Zhu MF, Smith B, Krishna S, et al: The pathological features of hip
abductor tendon tears – A cadaveric study. BMC Muscoskelet Disord
2020;21(1):778. The primary pathology underlying abductor tendon tears
is degeneration, and the tears most commonly involve the gluteus
minimus tendon alone followed by concurrent gluteus medius and
gluteus minimus tears. Level of evidence: VI.
9. Kheterpal AB, Harvey JP, Husseini JS, Martin SD, Torriani M, Bredella
MA: Hip abductor tears in ischiofemoral impingement. Skeletal Radiol
2020;49(11):1747-1752. Abnormalities of the quadratus femoris muscle
and narrowing of the ischiofemoral and quadratus femoris spaces are
defined as ischiofemoral impingement, and patients affected by these
have a higher prevalence of abductor tears and abductor muscle atrophy
compared with matched controls. Level of evidence: IV.
10. Lachiewicz PF: Abductor tendon tears of the hip: Evaluation and
management. J Am Acad Orthop Surg 2011;19(7):385-391.
11. Nolton EC, Ambegaonkar JP: Recognizing and managing snapping hip
syndrome in dancers. Med Probl Perform Art 2018;33(4):286-291.
12. Barra PA, Brookes N, Newson A: Conservative treatments for greater
trochanteric pain syndrome: A systematic review. Br J Sports Med
2017;51(2):97-104.
13. Reid D: The management of greater trochanteric pain syndrome: A
systematic literature review. J Orthop 2016;13(1):15-28.
14. Mitchell WG, Ke wich SC, Sibbi WL, et al: Outcomes and cost-
effectiveness of ultrasound-guided injection of the trochanteric bursa.
Rheumatol Int 2018;38(3):393-401.
15. Lustenberger DP, Ng VY, Best TM, Ellis TJ: Efficacy of treatment of
trochanteric bursitis: A systematic review. Clin J Sport Med 2011;21(5):447-
453.
16. Alpaugh K, Chilelli BJ, Xu S, Martin SD: Outcomes after primary open
or endoscopic abductor tendon repair in the hip: A systematic review of
the literature. Arthroscopy 2015;31(3):530-540.
17. Kenanidis E, Lund B, Christofilopoulos P: A roadmap to develop clinical
guidelines for open surgery of acute and chronic tears of hip abductor
tendons. Knee Surg Sports Traumatol Arthrosc 2021;29(5):1420-1431.
Abductor tendon tears are increasingly identified as a source of lateral
hip pain, and the anatomy and chronicity of the lesion, the extent of fa y
infiltration, and the neurologic integrity of the abductor musculature
may influence treatment and outcome. Level of evidence: IV.
18. Randelli F, Mazzoleni MG, Fioruzzi A, Giai Via A, Calvisi V, Ayeni OR:
Surgical interventions for external snapping hip syndrome. Knee Surg
Sports Traumatol Arthrosc 2020;29(8):2386-2393. Snapping hip syndrome is
characterized by an audible or palpable snap of the hip joint which can
become symptomatic enough to warrant surgery, and endoscopic
techniques provide fewer complications compared with open surgery
with lower recurrence and good outcomes. Level of evidence: V.
19. Malinowski K, Kalinowski Ł, Góralczyk A, Ribas M, Lund B,
Hermanowicz K: External snapping hip syndrome endoscopic treatment:
“Fan-like” technique as a stepwise, tailor-made solution. Arthrosc Tech
2020;9(10):e1553-e1557. External snapping hip syndrome is thought to be
caused by friction of the ITB over the greater trochanter, which can be
managed with a novel method using a fanlike cut endoscopically.
20. Potalivo G, Bugiantella W: Snapping hip syndrome: Systematic review
of surgical treatment. Hip Int 2017;27(2): 111-121.
21. Villanueva M, Iborra Á, Sanz-Ruiz P, Noriega C: Ultrasound-guided
surgery for lateral snapping hip: A novel ultraminimally invasive surgical
 technique. J Orthop Surg 2021;16(1):322. Ultrasound-guided release of the
lateral snapping hip is a promising intervention for patients in whom
nonsurgical treatment protocols have failed and can be performed under
local anesthesia in an outpatient se ing. Level of evidence: IV.
22. Nicholas SJ, Tyler TF: Adductor muscle strains in sport. Sports Med
2002;32(5):339-344.
23. Kiel J, Kaiser K: Adductor strain, in StatPearls. StatPearls Publishing,
2021. Available at: h p://www.ncbi.nlm.nih.gov/books/NBK493166/.
Accessed July 18, 2021. Injury to the adductor muscle group of the thigh
is a common cause of medial leg and groin pain, and this article seeks to
identify common mechanisms of injury, the typical patient presentation,
treatment options, and multidisciplinary care strategies.
24. Maffey L, Emery C: What are the risk factors for groin strain injury in
sport? A systematic review of the literature. Sports Med 2007;37(10):881-
894.
25. Tyler TF, Fukunaga T, Gellert J: Rehabilitation of soft tissue injuries of
the hip and pelvis. Int J Sports Phys Ther 2014;9(6):785-797.
26. Hölmich P, Uhrskou P, Ulnits L, et al: Effectiveness of active physical
training as treatment for long-standing adductor-related groin pain in
athletes: Randomised trial. Lancet 1999;353(9151):439-443.
27. Hölmich P, Nyvold P, Larsen K: Continued significant effect of physical
training as treatment for overuse injury: 8- to 12-year outcome of a
randomized clinical trial. Am J Sports Med 2011;39(11):2447-2451.
28. Delmore RJ, Laudner KG, Torry MR: Adductor longus activation during
common hip exercises. J Sport Rehabil 2014;23(2):79-87.
29. Weir A, Jansen JACG, van de Port IGL, Van de Sande HBA, Tol JL,
Backx FJG: Manual or exercise therapy for long-standing adductor-related
groin pain: A randomised controlled clinical trial. Man Ther.
2011;16(2):148-154.
30. Byrd JWT: Snapping hip. Operat Tech Sports Med 2005;13(1): 46-54.
31. Winston P, Awan R, Cassidy JD, Bleakney RK: Clinical examination and
ultrasound of self-reported snapping hip syndrome in elite ballet
dancers. Am J Sports Med 2007;35(1):118-126.
32. Ilizaliturri VM, Villalobos FE, Chaidez PA, Valero FS, Aguilera JM:
Internal snapping hip syndrome: Treatment by endoscopic release of the
iliopsoas tendon. Arthroscopy 2005;21(11):1375-1380.
33. Wunderbaldinger P, Bremer C, Matuszewski L, Marten K, Turetschek K,
Rand T: Efficient radiological assessment of the internal snapping hip
syndrome. Eur Radiol 2001;11(9):1743-1747.
34. Piechota M, Maczuch J, Skupiński J, Kukawska-Sysio K, Wawrzynek W:
Internal snapping hip syndrome in dynamic ultrasonography. J Ultrason
2016;16(66):296-303.
35. Bakhsh W, Childs S, Kenney R, Schiffman S, Giordano B: Iliopsoas
snapping hip: Improving the diagnostic value of magnetic resonance
imaging with a novel parameter. Skeletal Radiol 2019;48(6):889-896. The
use of advanced imaging parameters, such as the sagi al opening angle,
improves understanding of the course of the iliopsoas tendon and also
provides diagnostic value with a threshold of greater than 140°
significantly correlating with clinical presentation. Level of evidence: IV.
36. Laible C, Swanson D, Garofolo G, Rose DJ: Iliopsoas syndrome in
dancers. Orthop J Sports Med 2013;1(3):2325967113500638.
37. Khan M, Adamich J, Simunovic N, Philippon MJ, Bhandari M, Ayeni
OR: Surgical management of internal snapping hip syndrome: A
systematic review evaluating open and arthroscopic approaches.
Arthroscopy 2013;29(5):942-948.
38. Hwang D-S, Hwang J-M, Kim P-S, et al: Arthroscopic treatment of
symptomatic internal snapping hip with combined pathologies. Clin
Orthop Surg 2015;7(2):158-163.
39. Via AG, Basile A, Wainer M, Musa C, Padulo J, Mardones R: Endoscopic
release of internal snapping hip: A review of literature. Muscles Ligaments
Tendons J 2016;6(3):372-377.
40. Ilizaliturri VM, Suarez-Ahedo C, Acuña M: Internal snapping hip
syndrome: Incidence of multiple-tendon existence and outcome after
endoscopic transcapsular release. Arthroscopy 2015;31(10):1991-1995.
41. Dora C, Houweling M, Koch P, Sierra RJ: Iliopsoas impingement after
total hip replacement: The results of non-operative management,
tenotomy or acetabular revision. J Bone Joint Surg Br 2007;89(8):1031-1035.
42. Lachiewicz PF, Kauk JR: Anterior iliopsoas impingement and tendinitis
after total hip arthroplasty. J Am Acad Orthop Surg 2009;17(6):337-344.
43. Trousdale RT, Cabanela ME, Berry DJ: Anterior iliopsoas impingement
after total hip arthroplasty. J Arthroplasty 1995;10(4):546-549.
44. Taher RT, Power RA: Iliopsoas tendon dysfunction as a cause of pain
after total hip arthroplasty relieved by surgical release. J Arthroplasty
 2003;18(3):387-388.
45. Brew CJ, Stockley I, Grainger AJ, Stone MH: Iliopsoas tendonitis caused
by overhang of a collared femoral prosthesis. J Arthroplasty
2011;26(3):504:e17-e19.
46. Mayne IP, Kosashvili Y, White LM, Backstein D: Iliopsoas tendonitis
due to the protrusion of an acetabular component fixation screw after
total hip arthroplasty. J Arthroplasty 2010;25(4):659.e5-659.e8.
47. Johnston CA, Wiley JP, Lindsay DM, Wiseman DA: Iliopsoas bursitis
and tendinitis. A review. Sports Med 1998;25(4):271-283.
48. Haskel JD, Kaplan DJ, Fried JW, Youm T, Samim M, Burke C: The
limited reliability of physical examination and imaging for diagnosis of
iliopsoas tendinitis. Arthroscopy 2021;37(4):1170-1178. Iliopsoas tendinitis
can be difficult to diagnose and manage, and unfortunately neither
physical examination nor ultrasound or MRI findings were predictive of
whether a patient will have a positive response to peritendinous
iliopsoas corticosteroid injection. Level of evidence: III.
49. Nakano N, Khanduja V: Medial synovial fold cyst in the hip leading to
pectineofoveal impingement. J Hip Preserv Surg 2017;4(1):93-96.
50. Martin HD, Kivlan BR, Palmer IJ, Martin RL: Diagnostic accuracy of
clinical tests for sciatic nerve entrapment in the gluteal region. Knee Surg
Sports Traumatol Arthrosc 2014;22(4):882-888.
51. Park JW, Lee Y-K, Lee YJ, Shin S, Kang Y, Koo K-H: Deep gluteal
syndrome as a cause of posterior hip pain and sciatica-like pain. Bone Jt J
2020;102-B(5):556-567. This is a comprehensive review of DGS and its
etiology, diagnosis, and treatment. Level of evidence: V.
52. Lerch TD, Zwingelstein S, Schmaranzer F, et al: Posterior extra-articular
ischiofemoral impingement can be caused by the lesser and greater
trochanter in patients with increased femoral version: Dynamic 3D CT-
based hip impingement simulation of a modified FABER test. Orthop J
Sports Med 2021;9(5):2325967121990629. Posterior extra-articular
ischiofemoral hip impingement can be caused by the lesser and greater
trochanter and can be best diagnosed by performing the FABER test in
addition to the posterior impingement test, particularly for female
patients with high femoral version. Level of evidence: IV.
53. Park S, Lee HY, Cuong PM, et al: Supine versus standing radiographs
for detecting ischiofemoral impingement: A propensity score-matched
analysis. AJR Am J Roentgenol 2016;206(6):1253-1263.
54. Singer AD, Subhawong TK, Jose J, Tresley J, Clifford PD: Ischiofemoral
impingement syndrome: A meta-analysis. Skeletal Radiol 2015;44(6):831-
837.
55. Hernando MF, Cerezal L, Pérez-Carro L, Canga A, González RP:
Evaluation and management of ischiofemoral impingement: A
pathophysiologic, radiologic, and therapeutic approach to a complex
diagnosis. Skeletal Radiol 2016;45(6):771-787.
56. Hatem MA, Palmer IJ, Martin HD: Diagnosis and 2-year outcomes of
endoscopic treatment for ischiofemoral impingement. Arthroscopy
2015;31(2):239-246.
57. Aguilera-Bohórquez B, Leiva M, Pacheco J, Calvache D, Fernandez M,
Cantor E: Pain relief and good functional outcomes after hip endoscopy
via posterior approach in patients with ischiofemoral impingement. Knee
Surg Sports Traumatol Arthrosc 2020;29(8):2394-2400. Ischiofemoral
impingement is relatively uncommon and can be managed surgically by
endoscopically resecting the lesser trochanter via a posterior approach
and results in satisfactory outcomes with regard to symptomatic and
functional outcomes. Level of evidence: IV.
58. Guermazi A: Subspine impingement: Diagnostic dilemma for a
possible new form of hip impingement. Radiology 2019;293(2):422-423.
Subspine impingement is a relatively uncommon form of impingement
that is difficult to diagnose and manage and is discussed in this article.
Level of evidence: V.
59. Hetsroni I, Poultsides L, Bedi A, Larson CM, Kelly BT: Anterior inferior
iliac spine morphology correlates with hip range of motion: A
classification system and dynamic model. Clin Orthop 2013;471(8):2497-
2503.
60. Chalmers BP, Sculco PK, Sierra RJ, Trousdale RT, Berry DJ: Iliopsoas
impingement after primary total hip arthroplasty: Operative and
nonoperative treatment outcomes. J Bone Joint Surg Am 2017;99(7):557-
564.
61. Bardakos NV: Hip impingement: Beyond femoroacetabular. J Hip
Preserv Surg 2015;2(3):206-223.
62. Seeley MA, Georgiadis AG, Sankar WN: Hip vascularity: A review of the
anatomy and clinical implications. J Am Acad Orthop Surg 2016;24(8):515-
526.
63. Gómez-Hoyos J, Martin RL, Martin HD: Current concepts review:
Evaluation and management of posterior hip pain. J Am Acad Orthop Surg
 2018;26(17):597-609.
64. Wadhwa V, Sco KM, Rozen S, Starr AJ, Chhabra A: CT-guided
perineural injections for chronic pelvic pain. Radiographics
2016;36(5):1408-1425.
65. Matičič UB, Šumak R, Omejec G, Salapura V, Snoj Ž: Ultrasound-guided
injections in pelvic entrapment neuropathies. J Ultrason 2021;21(85):e139-
e146. Pelvic entrapment neuropathies encompass a group of chronic pain
syndromes secondary to peripheral nerve entrapment at specific
anatomic locations, which are typically diagnosed by physical
examination and/or ultrasound and can respond to nonsurgical and
surgical treatment modalities. Level of evidence: V.
66. Lee S-H, Shin K-J, Gil Y-C, Ha T-J, Koh K-S, Song W-C: Anatomy of the
lateral femoral cutaneous nerve relevant to clinical findings in meralgia
paresthetica. Muscle Nerve 2017;55(5):646-650.
67. Grossman MG, Ducey SA, Nadler SS, Levy AS: Meralgia paresthetica:
Diagnosis and treatment. J Am Acad Orthop Surg 2001;9(5):336-344.
68. Sanjaya A: Meralgia paresthetica: Finding an effective cure. Postgrad
Med 2020;132(1):1-6. Meralgia paresthetica is a common mononeuropathy
of the lower extremity resulting from LFCN entrapment that is typically
self-resolving and rarely requires surgery. Level of evidence: V.
69. Kaur J, Singh P: Pudendal nerve entrapment syndrome, in StatPearls.
StatPearls Publishing, 2021.
h p://www.ncbi.nlm.nih.gov/books/NBK544272/. Accessed July 18, 2021.
Pudendal neuralgia caused by pudendal nerve entrapment is a chronic
neuropathic pain syndrome most commonly defined by perineal pain
exacerbated by si ing and relieved by standing or lying. This paper
explores its diagnosis and treatment.
70. Ploteau S, Cardaillac C, Perrouin-Verbe M-A, Riant T, Labat J-J:
Pudendal neuralgia due to pudendal nerve entrapment: Warning signs
observed in two cases and review of the literature. Pain Physician
2016;19(3):E449-E454.
71. Martin R, Martin HD, Kivlan BR: Nerve entrapment in the hip region:
Current concepts review. Int J Sports Phys Ther 2017;12(7):1163-1173.
72. Ozkan D, Akkaya T, Yildiz S, Comert A: Ultrasound-guided pulsed
radiofrequency treatment of the pudendal nerve in chronic pelvic pain.
Anaesthesist 2016;65(2):134-136.
73. Sunil Kumar KH, Rawal J, Nakano N, Sarmento A, Khanduja V:
Pathogenesis and contemporary diagnoses for lateral hip pain: A scoping
review. Knee Surg Sports Traumatol Arthrosc 2020;29(8):2408-2416. This is a
review exploring peritrochanteric space syndrome and its pathoanatomy,
clinical assessment, and treatment. Level of evidence: IV.
74. Cheng AL, Schwabe M, Doering MM, Coldi GA, Prather H: The effect
of psychological impairment on outcomes in patients with prearthritic
hip disorders: A systematic review and meta-analysis. Am J Sports Med
2020;48(10):2563-2571. Mental health disorders often coexist with
femoroacetabular impingement, and the presence of baseline
psychological impairment is associated with clinically significantly worse
outcomes in patients who undergo hip arthroscopy. Level of evidence: V.
75. Iglinski-Benjamin KC, Xiao M, Safran MR, Abrams GD: Increased
prevalence of concomitant psychiatric diagnoses among patients
undergoing hip arthroscopic surgery. Orthop J Sports Med
2019;7(1):2325967118822451. This retrospective review highlights the
increased prevalence of comorbid psychiatric conditions in patients
undergoing hip arthroscopy compared with the general population, with
depression and anxiety being the most prevalent diagnoses. Level of
evidence: III.
76. Hampton SN, Nakonezny PA, Richard HM, Wells JE: Pain
catastrophizing, anxiety, and depression in hip pathology. Bone Joint J
2019;101-B(7):800-807. Patients with hip pathology exhibit pain
catastrophizing, anxiety, and depression at a high frequency, and it is
important to recognize these features preoperatively as they can often be
modifiable and affect patient outcomes. Level of evidence: IV.
77. Gudmundsson P, Nakonezny PA, Lin J, Owhonda R, Richard H, Wells J:
Functional improvement in hip pathology is related to improvement in
anxiety, depression, and pain catastrophizing: An intricate link between
physical and mental well-being. BMC Muscoskelet Disord 2021;22(1):133.
Patients presenting with hip pathology and complaints often have a high
amount of coexisting psychological symptoms including pain
catastrophizing, anxiety, and depression, and improvements in hip
functionality are associated with decreased severity of psychiatric
comorbidities. Level of evidence: IV.
C H AP T E R 4 2

End-Stage Hip Degeneration

and Hip Reconstruction
Brett L. Hayden MD, Darwin Chen MD, FAAOS

Dr. Hayden or an immediate family member has stock or stock options held in Bristol-Myers
Squibb, Johnson & Johnson, and Pfizer. Dr. Chen or an immediate family member serves as a
paid consultant to or is an employee of DePuy, a Johnson & Johnson Company, Monogram
Orthopedics, and Smith & Nephew.

ABSTRACT
End-stage degenerative joint disease of the hip is a major
musculoskeletal disease characterized by pain, limited mobility,
and poor quality of life. The most common cause of hip
degenerative joint disease is osteoarthritis, followed by secondary
arthritis from inflammatory conditions and pos raumatic arthritis.
Total hip arthroplasty has been shown to be an excellent treatment
for end-stage degenerative joint disease of the hip, with high rates
of satisfaction and sustained long-term implant survivorship. The
execution of a successful total hip arthroplasty relies on diligent
indications and preoperative medical optimization to decrease the
likelihood of postoperative medical and surgical complications.
After removal from the Centers for Medicare & Medicaid Services
inpatient-only procedure list, total hip arthroplasties are more
commonly being performed in outpatient se ings such as short-
stay, ambulatory surgery centers. Surgical approaches are most
often dictated by surgeon preference and training and have
differing risk profiles. Despite excellent results of total hip
arthroplasty, complications such as infection, dislocation, adverse
local tissue reaction, and fractures still persist and can lead to
catastrophic consequences. Developments and innovations in
implant design, fixation technique, bearing surface, and technology
will continue to drive improvements in clinical, radiographic,
patient-reported, and long-term implant survivorship outcomes.
Keywords: hip osteoarthritis; total hip arthroplasty

Introduction
Hip degeneration presents clinically on a spectrum from mild pain
to incapacitating disability. End-stage degenerative joint disease of
the hip is best managed with total hip arthroplasty (THA), which
has demonstrated overall excellent long-term outcomes. It is
important to review recent advances in preoperative evaluation,
intraoperative execution, and postoperative complications of THA.

Hip Osteoarthritis
Osteoarthritis is the most common disease of the joints, afflicting
an estimated 303 million people worldwide. Although any joint can
be affected, the hip and knee are the most commonly involved
joints. Years lived with disability and the prevalence and incidence
of hip and knee osteoarthritis have increased 8% to 10% since 1990.
1
These increased rates are mirrored by increases in US health care
expenditures, as discussed in a 2020 study that found that spending
for osteoarthritis accounted for $80 billion annually. 2 The disability
from hip osteoarthritis involves pain that affects individuals’
quality of life and activities of daily living but has other far-reaching
consequences. Work absences, sleep disturbances, sexual
dysfunction, and increased risk of cardiovascular disease are
additional effects of symptomatic osteoarthritis. 3
Hip osteoarthritis generally presents with pain, primarily in the
groin or thigh, and stiffness that becomes more noticeable with
activities such as walking, navigating stairs, and pu ing on socks
and shoes. As the osteoarthritis worsens, so too does hip range of
motion, particularly in internal and external rotation with hip
flexion contractures common in the later stages of disease.
Radiographs demonstrate joint-space narrowing, subchondral
sclerosis, osteophyte formation, and subchondral cysts (Figure 1).
The treatment of hip osteoarthritis with mild or moderate
symptoms involves oral or topical anti-inflammatory medications,
activity modification, the use of a cane in the contralateral hand, 4
weight loss, and physical therapy for managing pain and to
improve function. Intra-articular steroid injections can also
improve function and reduce short-term pain for patients with
symptomatic osteoarthritis. 5 The mainstay of treatment for severe
hip osteoarthritis is THA.
 Figure 1 Standing AP radiograph of the pelvis from a patient with severe left
hip osteoarthritis.Joint-space narrowing, subchondral sclerosis, osteophyte
formation, and subchondral cysts are present.

Secondary Arthritis
Secondary arthritis of the hip can occur because of a number of
conditions, most commonly inflammatory arthritis (including
rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and
systemic lupus erythematosus), pos raumatic arthritis, and
osteonecrosis.
Inflammatory arthritis is known to cause significant deformities
of the hip such as coxa profunda and protrusio acetabuli (also
known as arthrokatadysis), rapidly destructive bony erosion, and
severe hip ankylosis/autofusion. Advances in the pharmacologic
management of inflammatory arthritis using disease-modifying
antirheumatic drugs and biologic agents have dramatically
improved the systemic symptoms of these patients and reduced the
amount of severe orthopaedic deformities seen currently. Patients
with inflammatory arthritis who undergo THA are at higher risk of
periprosthetic joint infection (PJI) because of immunocompromise
from antirheumatic medications and the disease itself. A consensus
guideline published by the American College of Rheumatology and
the American Association of Hip and Knee Surgeons has outlined
specific recommendations on perioperative medication
management. Most nonbiologic medications can be continued
6

perioperatively; however, biologic agents should be stopped one

cycle before surgery and restarted after surgery once the wound is
sufficiently healed.
Pos raumatic arthritis of the hip results from chondral damage
due to a significant prior injury to the hip. Intra-articular fractures
of the femoral head or acetabulum cause direct cartilage damage
and articular surface incongruity. Expedient and anatomic
restoration of intra-articular surfaces via open reduction and
internal fixation is key to diminish the risk of pos raumatic
arthritis. Traumatic hip dislocation can also cause chondral damage
as well as disruption of the blood supply to the femoral head,
leading to osteonecrosis. Other severe musculoskeletal injuries may
also predispose patients to the development of pos raumatic hip
arthritis due to joint contractures, an altered gait pa ern, and
abnormal hip biomechanics leading to increased joint reactive
forces.
Osteonecrosis of the hip is a condition caused by compromised
blood supply to the femoral head secondary to a number of medical
conditions including sickle cell disease, HIV, alcoholism, high-dose
steroid usage, radiation treatment, and hypercoagulable states, as
well as prior hip trauma. Plain radiographs and MRI are useful for
diagnosis and classification (Ficat and Arlet, Steinberg). Surgical
management should be considered for patients with precollapse
osteonecrosis and intractable pain as well as those who have
definitive femoral head collapse. Core decompression, with or
without bone grafting, may be indicated in early stage
osteonecrosis without femoral head collapse. More extensive
procedures such as proximal femoral osteotomy or vascularized
free fibula transfer are also used, but like all of these hip salvage
procedures, they have mixed results and may affect the ultimate
outcome of subsequent arthroplasty. THA is indicated for patients
with end-stage femoral head collapse and has excellent outcomes.

Total Hip Arthroplasty

Medical Optimization/Risk Stratification

Of the many recent advances in the surgical evaluation and
management of degenerative joint disease of the hip, preoperative
patient optimization has the potential to be the most effective.
Recognizing which patients to operate on and when is of
paramount importance in avoiding dangerous medical
complications from surgery. The most commonly cited risk factors
for complications after THA are smoking, body mass index less
than 35 to 40 kg/m2 and greater than 20 kg/m2, albumin greater than
3.5 g/dL, narcotic/ethanol dependence, hemoglobin A1c less than
8%, hemoglobin greater than 10 g/dL, and preoperative nasal
colonization with Staphylococcus aureus. 7 Identification and
optimization of these modifiable risk factors can enhance early
recovery with documented lower lengths of hospital stay and
increased rates of home discharge. Additional beneficial outcomes
of medical optimization before THA include decreased readmission
rates, postoperative emergency department visits, PJI rates, and
mortality. 6 Some nonmodifiable risk factors have been linked to
poorer outcomes after surgery. In a 2019 study, the authors
assessed demographic and comorbidity variables and found that
the American Society of Anesthesiologists physical classification
system score greater than 3 was a significant risk factor for 30-day
medical complications, surgical complications, readmission,
revision surgery, and mortality rates following primary total joint
arthroplasty (TJA). Peripheral vascular disease was the most
significant risk factor for medical complications and revision
surgery, whereas bleeding disorders were the most significant risk
factor for readmission and overall mortality. 8
Preoperative optimization has been shown to significantly
increase the workload burden on surgeons and other providers. A
survey of members of the American Association of Hip and Knee
Surgeons published in 2020 reported that 153 additional minutes
were spent on preoperative medical optimization work not
accounted for in Current Procedural Terminology or hospital billing
codes. Additionally, 87% of respondents reported a significant
increase in preoperative workload for THA since 2013. 9

Outpatient THA
The Centers for Medicare & Medicaid Services announced in late
2019 that THA would be removed from the inpatient-only
procedure list as of January 1, 2020. 10 As outpatient THA becomes
more prevalent, careful medical optimization and risk stratification
is mandatory to help select which patients and medical
comorbidities may be appropriate for surgery outside the inpatient
se ing. Multiple risk assessment tools have been developed in an
effort to stratify patients into high-risk and low-risk categories for
readmission after outpatient surgery. Scoring systems such as the
outpatient arthroplasty risk assessment and the American Society
of Anesthesiologists score have been shown to identify which
patients can most safely undergo outpatient TJA. 11 Other reports,
however, have refuted the requirement of a formal scoring
assessment tool. Some specific comorbidities have been found to be
associated with an increased risk of overnight observation rather
than same-day discharge, even after medical optimization.
Coronary artery disease, chronic obstructive pulmonary disease,
and benign prostatic hypertrophy/urinary frequency have been
shown to carry the highest risk of overnight stay after THA. The
overall most commonly cited reasons for an unexpected overnight
stay are urinary retention, postoperative nausea and vomiting,
hypotension, pain management, hypoxia, and patient convenience.
12

Surgical Approaches
Surgical approach has been a heavily debated topic in THA over the
past 10 years, with the premise that direction of approach would
affect surgical outcomes. Considering the ubiquitous push for
outpatient and short-stay THA, an optimal surgical approach would
facilitate a decrease in length of hospital stay, enhanced
rehabilitation, and optimizing early recovery. In addition,
decreasing resource utilization in the form of postoperative
physical therapy and nursing has the potential to lower overall cost
and decrease health care expenditures.
Recent studies suggest that different approaches carry different
complication profiles, rather than different long-term outcomes. 13
The anterior approach was highly marketed and rejuvenated in the
early 2000s and was reported in predominantly medium-quality to
low-quality studies. 14 The findings of meta-analyses and systematic
reviews have consistently demonstrated improved early outcomes
in the first 6 weeks postoperatively for the anterior approach
compared with the posterior or lateral approaches. 14 , 15 Despite the
improved early outcomes, other studies have demonstrated a
higher complication rate with the anterior approach, particularly
revision surgeries and PJIs, with no difference in dislocation rates
compared with the posterior approach. 16
Extent of tissue damage, rather than direction of approach, has
been proposed as a more important proxy of level of invasiveness in
THA and has been difficult to study in controlled se ings. Tissue
sparing approaches, in addition to the anterior and mini-posterior
approaches, include the superior capsulotomy/direct superior
approach or other modifications of more extensile approaches, such
as the percutaneously assisted total hip. These approaches to THA
have been reported as safe with excellent short-term outcomes,
although long-term and direct comparison investigations are
warranted. 17 Ultimately, factors such as pain management, patient
selection, surgeon experience, and hospital perioperative resource
utilization may prove to be more important than surgical approach.

Bearing Surfaces
Despite the overwhelming successes of THA, the optimal bearing
surface has yet to be established. As implant survivorship improves
and patient expectations escalate, THA has been performed more
frequently in younger, more active patients. It was once thought
that young patients would benefit from hard-on-hard bearing
surfaces (ceramic-on-ceramic, or metal-on-metal [MoM]) to improve
durability and obviate polyethylene wear–induced osteolysis and
subsequent prosthetic loosening. MoM utilization peaked in 2008
but soon dramatically decreased as failure reports were published.
Failures of MoM surface bearings were widely demonstrated
because of metal wear debris inducing adverse local tissue
reactions (ALTRs). Additionally, excellent in vivo and in vitro
performance of modern, highly cross-linked polyethylene 18
contributed to the decline of hard-on-hard bearing usage. One
recent database study demonstrated a drastic increase in ceramic-
on-polyethylene bearings in association with a significant decrease
in MoM utilization from 2006 to 2016 18 (Table 1). These changes in
bearing utilization have been mirrored by older age groups with a
shift from hard-on-hard to hard-on-soft bearings with a strong
predominance for ceramic on polyethylene as the most common
bearing surface. 19

Table 1
Trends in Bearing Surface Utilization for Total Hip Arthroplasty
in Young Patients From 2006 to 2016
 Bearing Surface 2006 2016
Ceramic on ceramic 37.3% 20.4%
Metal on metal 30.7% 3%
Ceramic on polyethylene 5% 64.8%
Metal on polyethylene 27% 11.7%
Data from Hart CM, Chen C, Hsiue PP, et al: National trends in total hip arthroplasty bearing
surface usage in extremely young patients between 2006 and 2016. Arthroplast Today
2021;10:51-56.

Dual-mobility articulations have seen widespread adoption in the

United States in primary and revision THA for patients at high risk
of instability. These constructs have been shown to improve hip
stability because of larger head size and subsequent increased
jump distance rather than increased range of motion to
impingement. 20 Dual-mobility bearings have been shown to have
lower dislocation rates in primary and revision THA and lower
revision because of instability, with no difference in overall all-
cause revision rate for primary THA compared with standard
bearing surfaces. 21 It is important, however, to distinguish
modularity (or lack thereof) and specific materials among different
dual-mobility bearings because these have implications for wear,
stability, and mechanical complications. A 2020 study reported on
the use of dual mobility in the American Joint Replacement
Registry from 2012 to 2018. It was found that marked dual-mobility
usage increased from 6.7% in 2012 to 12% in 2018, with a particular
increase in revision THA from 19.5% in 2012 to 30.6% in 2019.
Specific factors associated with higher dual-mobility utilization
were younger patient age, female sex, and major teaching and small
hospitals, as well as Western state geography. 22
Complications of dual-mobility bearings include persistent
instability, intraprosthetic dislocation or dissociation, and possible
trunnionosis from the liner/shell interface. Intraprosthetic
dislocation or dissociation of the outer polyethylene heads from the
inner metal or ceramic head, has an incidence as high as 5.2% with
dual-mobility articulations, has been reported to occur after 71% of
closed reduction a empts, and always requires open revision
surgery. 23 Additionally, concerns about increased blood metal ion
levels in the early postoperative period persist for patients with
modular dual mobility compared with control patients with hard-
on-soft bearings, and long-term outcomes studies are needed.

Fixation Methods
Techniques for component fixation in THA have been debated for
many decades and continue to be refined. Overall, the use of
cemented acetabular and femoral components has declined,
particularly in the nonelderly patient populations. There are
notable regional differences in the literature reported for the use of
cemented and noncemented THAs. In North America,
noncemented (press-fit) fixation of primary and revision THA
predominates. 24 The so-called uncemented paradox describes the
phenomenon of a gradual and persistent shift away from cemented
fixation to noncemented fixation, without an evidence-based
justification in the literature. 25 Noncemented acetabular implant
designs are used almost universally in the United States. Modern
registry studies generally demonstrate higher revision rates and
periprosthetic fractures for noncemented THAs, particularly within
the first 3 months postoperatively, though showing no difference in
overall implant survivorship at long-term follow-up. For these
reasons, cemented femoral stems should be considered for patients
older than 75 years and/or those with osteoporotic bone in primary
THA or the management of femoral neck fractures. 24 , 26

Technology in THA
Technology has become a major factor in the field of medicine,
nowhere more so than in the surgical planning and execution of
THA. From preoperative and postoperative patient care, to
templating and planning software, to navigation and robotics,
technology is an important part of THA execution. Virtual office
visits for new and existing patients have permeated daily practice
and have become a practical and simple way to interact with
patients. Routine telemedicine postoperative appointments have
demonstrated high satisfaction and have the potential for
significant healthcare-associated cost savings. 27 Similarly, virtual
visits for routine postoperative physical therapy have been shown
to have excellent outcomes and allow for the possibility for
providers to monitor progress outside the office se ing. Virtual
rehabilitation has the potential to increase compliance and
adherence to exercises, reduce expenses, as well as lead to more
intensive and earlier initiation of physical therapy. 28
Robotic-assisted THA has become available following the
popularity of robotic arm–assisted total knee arthroplasty.
Advocates tout the potential for accurate and precise implant
positioning according to preoperative surgical planning. There have
been conflicting results in the literature for outcomes of robotic-
assisted THA with a paucity of high-quality, level I evidence. A
systematic review and meta-analysis demonstrated lower
intraoperative complications and more accurate implant
positioning for robotic-assisted THA, with no difference in
functional outcome scores, leg-length discrepancy, or revision rates.
29
A 2021 systematic review and meta-analysis similarly
demonstrated more accurate implant positioning, but no difference
in infections, dislocations, complications, or survival rates. 30
Despite promising early results, the high upfront and maintenance
costs, additional radiation exposure of a CT scan, and questionably
improved clinical outcomes pose difficulties with widespread
adoption.

Complications After THA

Periprosthetic Joint Infection

PJI continues to be one of the most devastating causes of failure
after primary and revision THA. The diagnosis and management of
PJI after THA remains one of the most challenging problems in
arthroplasty. Despite recent advances in infection management, the
incidence of PJI after THA has not changed over a 15-year period
(2002 to 2016), as shown by a 2020 Canadian population-based
study. 31 Five-year mortality rates after PJI are comparable with or
worse than those for the two most common cancers (breast and
prostate) in the US Medicare population. 32 In 2018, the
Musculoskeletal Infection Society set forth revised criteria for the
diagnosis of PJI. 33 Major criteria indicating infection include two
positive cultures with the same organism and/or a sinus tract with
intra-articular extension. Minor criteria indicating infection are
calculated based on a scoring system based on serum erythrocyte
sedimentation rate, C-reactive protein and D-dimer, and synovial
white blood cell count, alpha defensin, synovial polymorphonuclear
leukocyte count, and synovial C-reactive protein. Additionally, a
study demonstrated that a synovial fluid white blood cell count of
3,966 cells/µL with a polymorphonuclear leukocyte count of 80%
has shown to be an optimal cutoff value for the diagnosis of chronic
PJI in the hip. 34
Prevention of PJI is critically important. As discussed previously,
medical optimization (including S aureus decolonization, anemia,
smoking cessation, weight loss, diabetic control, nutrition, etc) and
risk stratification may be the most important factors in infection
prevention. Intraoperatively, surgeons can use numerous tactics to
prevent PJI. Topical vancomycin powder before wound closure has
been used in spine surgery for many years with mixed clinical
evidence and is increasingly being used in arthroplasty. A 2019
systematic review and meta-analysis of vancomycin powder placed
in the wound demonstrated a statistically significant decrease in PJI
in primary (odds ratio = 0.44, P = 0.0046) and revision TJA (odds
ratio = 0.28, P = 0.0013). 35 Dilute povidone-iodine lavage combined
with topical vancomycin powder (VIP protocol) has been shown in
two recent studies 36 , 37 to decrease the incidence of PJI in high-risk
patients and is currently undergoing a large multicenter
prospective randomized controlled trial. In two recent studies,
povidone-iodine lavage alone was shown to be superior to both
chlorhexidine gluconate lavage and vancomycin powder 38 and
decreased the risk of acute postoperative PJI after revision TJA. 39
The use of tranexamic acid is also associated with reduced risk of
PJI in primary and revision TJA, presumably because of reduced
blood loss and the need for allogeneic blood transfusion. 40
Extended oral antibiotics after THA may prevent PJI in high-risk
patients. In a large retrospective review of 3,855 patients with TJA,
patients who were deemed high risk received 7 days of
postoperative oral antibiotics, which led to a statistically significant
and clinically meaningful reduction in 1-year infection rates. 41
The management of acute and chronic PJI after THA remains
controversial. Two-stage exchange (removal of implants, antibiotic
spacer, intravenous/oral antibiotics, followed by staged
reimplantation) has historically been considered the gold standard
for chronic PJI in North America. The success rate of two-stage
exchange is highly variable in the literature and ranges between
60% and 95%. 42 There is renewed interest in one-stage exchange for
patients who have susceptible bacteriology and are appropriate
medical hosts, largely because of the morbidity and high-risk
nature of two-stage exchange. Indications for one-stage exchange
include a known and nonresistant organism, absence of systemic
sepsis, and a healthy soft-tissue envelope. Advantages of one-stage
exchange include decreased overall cost, lower morbidity, improved
limb stability, shorter disability time, and improved quality of life.
Débridement, antibiotics, and implant retention with exchange of
modular components (DAIR) has most commonly been used for
acute PJI occurring within 90 days postoperatively as well as acute
hematogenous PJI, but may also have a role in select chronic PJI
cases. The second International Consensus Meeting on
Musculoskeletal Infection recommendations on DAIR include
performing surgery urgently but not emergently, not delaying until
an organism is isolated, exchanging all modular components, using
copious irrigation and antiseptic solutions, and appropriate
antibiotic management postoperatively. 43 Failure rates after DAIR
are highly variable in the literature, between 20% and 70%. With
both DAIR and one-stage exchange, it is recommended to have a
dirty/clean setup with removal of contaminated instruments used
for irrigation and débridement, re-prepping and re-draping of the
limb after irrigation and débridement, and using new sterile
instruments for the remainder of the case.

THA Instability and the Spinopelvic

Relationship
Despite significant advances in many aspects of THA, instability
remains one of the most common causes of revision. In recent
years, the spinopelvic relationship has become an increasingly
understood and well-documented risk factor for dislocation after
THA. Two main spinal issues should be considered. 44 First, spinal
stiffness is defined by less than 10° change in sacral slope from
standing to seated position. In a flexible spine, the pelvis rolls
posteriorly from a standing to si ing position, allowing for
protection against dislocation. In a stiff spine, there is decreased
pelvic roll back, which increases the risk of anterior hip
impingement and thus dislocation. Second, spinal sagi al
imbalance is defined by a difference between pelvic incidence and
lumbar lordosis greater than 10° or an anterior pelvic plane that is
not neutral or vertically aligned. Sagi al imbalance can cause
significant anterior or posterior pelvic tilt, which can drastically
change the functional position of the acetabular implant and allow
it to fall outside of the safe zone in functional positions such as
standing and forward seated.
Even with in-depth knowledge of the spinopelvic relationship,
optimal acetabular cup placement remains challenging and
controversial. In 2021, a novel hip-spine classification system (Table
2) categorized hips in reference to spinal stiffness and deformity
and provided surgeons with inclination and anteversion targets for
cup positioning. 45 Normal spines with normal mobility can be
placed within the traditional parameters for acetabular implant
positioning (inclination 40° to 45°, anteversion 20° to 25°). Patients
who are stuck standing should be placed with slightly higher
inclination and anteversion (45°/25° to 30°), whereas patients who
are stuck si ing should be placed with less than native anatomic
anteversion but with 45°/25° to 30° relative to the functional pelvic
plane. The use of navigation and robotic technology may aid in
precision cup positioning during THA for patients with spinopelvic
issues. The recent introduction of preoperative, image-based three-
dimensional impingement modeling may also guide the surgeon
with respect to the optimal combination of cup and stem position
on a patient-specific basis. Dual-mobility implants should also be
considered and used judiciously in these cases to minimize the risk
of instability.

Table 2
Classification for Spinopelvic Alignment and Mobility in Total Hip
Arthroplasty

Patients, Inclination and

Group Classification Pathology
n (%) Anteversion Targets
1A Normal spinal Normal anatomy 987 (47) Inclination 40°-45°
alignment (PI-LL < and mobility Anteversion 20°-25°
10°) and normal
spinal mobility (>10°
change in sacral
slope from stand to
sit)
1B Normal spinal Stuck standing— 232 (11) Inclination 45°
alignment and stiff stiff spine, needs Anteversion 25°-30°
spine (<10° change more inclination
in sacral slope from and anteversion
stand to sit)
2A Flatback deformity Anterior pelvic tilt: 715 (34) Anterior pelvic tilt:
(PI-LL ≥ 10°) and from hip flexion Inclination 40°-45°
normal mobility contracture, will Anteversion 20°-25°
resolve Posterior pelvic tilt:
postoperatively Inclination 40°
Posterior pelvic Anteversion 20°-25°
tilt: spinal Unless magnitude ≥13°,
deformity will then component target
cause more should be less than native
functional anatomy
component
anteversion
 Patients, Inclination and
Group Classification Pathology
n (%) Anteversion Targets
2B Flatback deformity Stuck sitting— 147 (7) Inclination 40°
and stiff spine spinal deformity Anteversion 25°
and stiff spine will Unless posterior pelvic tilt
cause more magnitude ≥13°, then
functional component target should
component be less than native
anteversion anatomy or inclination 45°
and anteversion 25°-35°
relative to the functional
pelvic plane
PI-LL = pelvic incidence (PI) minus lumbar lordosis (LL)
Reproduced with permission from Vigdorchik J, Sharma A, Buckland A, et al: The 2021 Otto
Aufranc Award: A simple Hip-Spine Classification for total hip arthroplasty. Bone Joint J
2021;103-B(7 suppl B):17-24.

Adverse Local Tissue Reaction

Soft-tissue reactions in the hip due to metallic debris/tribocorrosion
from modular THA implant interfaces have been coined many
terms including metallosis, pseudotumor, adverse reaction to metal
debris, and aseptic lymphocyte-dominated vasculitis-associated
lesion. Perhaps the most accurate and descriptive term for this
phenomenon is adverse local tissue reaction (ALTR). ALTR
encompasses a variable combination of benign aseptic masses,
aseptic lymphocyte-dominated vasculitis-associated lesion, soft and
hard tissue necrosis, and osteolysis associated with THA. 46 Metal
ion debris formation can occur from any modular metal interface
with a THA implant construct. This includes MoM bearing surfaces,
the head-neck junction (trunnionosis), the modular stem junction
(neck-body, bi-body), and the backside of dual-mobility liners.
ALTR was first widely recognized as arising from MoM total hip
and hip resurfacing bearing surfaces consisting of cobalt-chromium
alloy. ALTR arising specifically from the head-neck junction
because of mechanically assisted crevice corrosion is an increasing
recognized failure mode in metal-on-polyethylene THA and has a
reported prevalence as high as 3.2%. 47 Certain modular neck-body
femoral stems (cobalt-chromium alloy neck on titanium alloy body)
are known to cause ALTR and have been subject to manufacturer
recalls. ALTR arising from the interface between a dual-mobility
liner and the acetabular implant is an emerging phenomenon with
few studies 48 and currently unknown clinical significance.
The diagnosis of ALTR can be difficult as it can mimic PJI and be
masqueraded by instability or component loosening. PJI should be
thoroughly evaluated in every case. Although systemic symptoms
such as end organ damage (renal, cardiac) have been reported,
overall it is rare. Serum levels of cobalt and chromium should be
obtained in all cases of suspected ALTR, and threshold values of
cobalt over 1 ng/mL and cobalt-chromium ratios of greater than 2
indicate ALTR. 49 Further workup should include plain radiographs,
obtaining prior surgical reports and implant records, and cross-
sectional imaging in the form of metal artifact reduction sequence
MRI.
The treatment of ALTR is highly variable depending on the
pathology. In cases of trunnionosis with well-fixed and properly
positioned components, a head and liner exchange to a ceramic-on-
polyethylene bearing can be performed. If there is gross trunnion
failure, the femoral implant must be revised. In cases of modular
stem failure (neck-body or bi-body), the femoral implant should be
revised. MoM hip arthroplasty failures commonly require
acetabular revision. The outcomes of revision THA for ALTR are
mixed and the complication and re-revision rate is unfortunately
quite high. 50

Summary
End-stage hip degeneration causes significant disability and
negatively affects patients’ quality of life. THA has been widely
shown to be an excellent treatment to alleviate pain and improve
function for patients with symptomatic hip degeneration. Despite
the overall excellent results, innovations and modifications to the
preoperative, intraoperative, and postoperative care of the patient
undergoing THA continue to improve outcomes. As widespread
adoption of short-stay and outpatient surgery occurs, preoperative
optimization and risk assessment will become even more
important. Improved implant design, selective use of proven
technological advances and preoperative identification of at-risk
patients, particularly for infection and instability, will continue to
drive down complications.

Key Study Points

Hip osteoarthritis is an important public health issue, affecting millions of people
worldwide.
THA is an excellent treatment for end-stage degenerative joint disease due to
osteoarthritis, inflammatory conditions such as rheumatoid arthritis, and
posttraumatic arthritis with excellent clinical, patient-reported, and long-term
outcomes.
The evolution of preoperative workup of patients undergoing THA focuses on
medical optimization of modifiable risk factors.
Important intraoperative factors for limiting complications and improving outcomes
include infection prevention techniques, the use of modern bearing surfaces, and
optimizing hip stability for patients at risk of dislocation.
New technologies and robotic-assisted THA have demonstrated promise, with more
work needed to assess clinical and patient-reported outcomes.

Annotated References
1. GBD 2017 Disease and Injury Incidence and Prevalence
Collaborators: Global, regional, and national incidence,
prevalence and years lived with disability for 354 diseases and
injuries for 195 countries and territories, 1990-2017: A systematic
analysis for the global burden of disease study 2017. Lancet
2018;392:1789-1858.
2. Dieleman JL, Cao J, Chapin A, et al: US health care spending by
payer and health condition, 1996-2016. J Am Med Assoc
2020;323(9):863-884. This report of US health care expenditures
from 1996 to 2016 demonstrated significant increases in the cost
of osteoarthritis up to that of $80 billion in 2016. Level of
evidence: V.
3. Wang H, Bai J, He B, Hu X, Liu D: Osteoarthritis and the risk of
cardiovascular disease: A meta-analysis of observational studies.
Sci Rep 2016;6:39672.
4. Blaunt WP: Don’t throw away the cane. J Bone Joint Surg Am
1956;38-A(3):695-708.
5. American Academy of Orthopaedic Surgeons: Management of
osteoarthritis of the hip evidence-based clinical practice
guideline. 2017. Available at:
h ps://www.aaos.org/globalassets/quality-and-practice-
resources/osteoarthritis-of-the-hip/oa-hip-cpg_6-11-19.pdf.
Accessed March, 2022.
6. Goodman SM, Springer B, Guya G, et al: American College of
Rheumatology/American Association of Hip and Knee Surgeons
guideline for the perioperative management of antirheumatic
medication in patients with Rheumatic Diseases undergoing
elective total hip or total knee arthroplasty. J Arthroplasty
2017;32(9):2628-2638.
7. Dlo CC, Moore A, Nelson C, et al: Preoperative risk factor
optimization lowers hospital length of stay and postoperative
emergency department visits in primary total hip and knee
arthroplasty patients. J Arthroplasty 2020;35(6):1508-1515.e2. The
authors reported their institutional protocol for risk factor
optimization using a multidisciplinary approach. They found that
a nurse navigator screening and focused treatment protocol
reduced length of hospital stay, home discharge, and emergency
department visits compared with historical and contemporary
control cohorts. Level of evidence: II.
8. Gronbeck C, Cote MP, Leiberman JR, Halawi MJ: Risk
stratification in primary total joint arthroplasty: The current state
of knowledge. Arthroplasty Today 2019;5:126-131. The authors
queried the National Surgical Quality Improvement Program
database to assess medical and surgical complications after
primary TJA. They found American Society of Anesthesiologists
 score, peripheral vascular disease, and bleeding disorders to be
risk factors for complications. Level of evidence: III.
9. Grosso MJ, Courtney PM, Kerr JM, Della Valle CJ, Huddleston JI:
Surgeons’ preoperative work burden has increased before total
joint arthroplasty: A survey of AAHKS members. J Arthroplasty
2020;35(6):1453-1457. A survey of acting American Association of
Hip and Knee Surgeons members was performed and it showed
that 98% of respondents spend time on preoperative medical
optimization and that time included 153 additional minutes of
work. Most respondents reported an increase in work burden for
THA. Level of evidence: V.
10. Centers for Medicare & Medicaid Services: CY 2020 hospital
outpatient PPS policy changes and payment rates and
ambulatory surgical center payment system policy changes and
payment rates. 2019. Available at:
h ps://www.federalregister.gov/documents/2019/11/12/2019-
24138/medicare-program-changes-to-hospital-outpatient-
prospective-payment-and-ambulatory-surgical-center. Accessed
March 2022. Centers for Medicare & Medicaid Services policy
changes detailing the removal of THA from the inpatient-only list
are provided.
11. Ziemba-Davis M, Caccaavallo P, Meneghini RM: Outpatient
joint arthroplasty – Patient selection: Update on the outpatient
arthroplasty risk assessment score. J Arthroplasty 2019;34:S40-S43.
The authors report their retrospective review of 2,051 patients
who underwent primary TJA. They examined the outpatient
arthroplasty risk assessment score in predicting accurate
classification of successful same-day discharge. They found that
scores from 0 to 79 were effective in identifying patients who can
undergo outpatient TJA with 98.8% positive predictive value and
99.3% specificity. Level of evidence: III.
12. Berend KR, Lombardi AV, Berend ME, Adams JB, Morris MJ:
The outpatient total hip arthroplasty: A paradigm change. Bone
Joint J 2018;100-B(1 suppl A):31-35.
13. Aggarwal VK, Elbuluk A, Dundon J, et al: Surgical approach
significantly affects the complication rates associated with total
hip arthroplasty. Bone Joint J 2019;101-B(6):646-651. A
retrospective analysis of THAs performed at a single center
demonstrated complication rates varied by the surgical approach.
The anterior approach had the highest complication rate (8.5%),
whereas the posterior approach had the lowest (5.85%). Level of
evidence: III.
14. Meermans G, Konan S, Das R, Volpin A, Hadad FS: The direct
anterior approach in total hip arthroplasty: A systematic review
of the literature. Bone Joint J 2017:99-B(6):732-740.
15. Wang Z, Hou J, Wu C, et al: A systematic review and meta-
analysis of direct anterior approach versus posterior approach in
total hip arthroplasty. J Orthop Surg Res 2018;13:229.
16. Aggarwal VK, Weintraub S, Klock J, et al: A comparison of
prosthetic joint infection rates between direct anterior and non-
anterior approach total hip arthroplasty: A single institution
experience. Bone Joint J 2019;101-B:2-8. A retrospective review of
THAs performed at a single center describing a decreasing
overall incidence of infection over time, but higher PJI rates in
direct anterior versus nonanterior approaches. Level of evidence:
III.
17. LeRoy TE, Hayden BL, Desmarais J, et al: Early outcome
comparison of the posterior approach and the superior approach
for primary total hip arthroplasty. Arthroplasty Today
2020;6(3):508-512. The authors report a retrospective review of
single-surgeon case series of posterior approach and superior
approach for THA. The superior approach group had decreased
length of hospital stay and higher rates of discharge home than
the posterior group. Level of evidence: III.
18. de Steiger R, Lorimer M, Graves SE: Cross-linked polyethylene
for total hip arthroplasty markedly reduces revision surgery at 16
years. J Bone Joint Surg 2018;100(15):1281-1288.
19. Heckmann ND, Sivasundaram L, Stefl MD, et al: Total hip
arthroplasty bearing surface trends in the United States from
2007 to 2014: The rise of ceramic on polyethylene. J Arthroplasty
2018;33(6):1757-1763.
20. Klemt C, Bounajem G, Tirumala V, et al: Three-dimensional
kinematic analysis of dislocation mechanism in dual mobility
total hip arthroplasty constructs. J Orthop Res 2021;39(7):1423-
1432. A biomechanical study on dual mobility compared with
standard 36-mm head THA components found increased jump
distance in dual mobility without a significant increase in range
of motion to impingement. Level of evidence: V.
21. Reina N, Pareek A, Krych AJ, et al: Dual-mobility constructs in
primary and revision total hip arthroplasty: A systematic review
of comparative studies. J Arthroplasty 2019;34(3):594-603. The
authors present a systematic review of prospective and
retrospective studies that compared dual-mobility constructs
with controls for primary and revision THA between 1986 and
2018. They showed lower dislocation rates and revision for
dislocation for dual mobility in primary THA, no difference in all-
cause revision, infection, fracture, and aseptic loosening. Dual-
mobility constructs in revision THA had lower dislocation, re-
revision, revision due to dislocation, and aseptic loosening, with
no differences in infection or fracture. Level of evidence: IV.
22. Heckmann N, Wei man DS, Jaffri H, et al: Trends in the use of
dual mobility bearings in hip arthroplasty: An analysis of the
American joint replacement registry. Bone Joint J 2020;102-B(7):27-
32. A retrospective analysis of the American Joint Replacement
Registry demonstrated increasing utilization of dual mobility in
primary and revision THA across the years studied from 2012 to
2018. Level of evidence: V.
23. Addona JL, Gu A, De Martino I, et al: High rate of early
intraprosthetic dislocations of dual mobility implants: A single
surgeon series of primary and revision total hip replacements. J
Arthroplasty 2019;34:2793-2798. The authors report a single-
surgeon series of THAs and their dislocation rates. The overall
 dislocation rate was 2.8% and the dislocation rate for traditional
femoral heads was 2.1%, for dual mobility 4.5%. Of the dual-
mobility dislocations, 71% had an intraprosthetic dislocation
after closed reduction a empt. Level of evidence: IV.
24. Blankstein M, Lentine B, Nelms NJ: The use of cement in hip
arthroplasty: A contemporary perspective. J Am Acad Orthop Surg
2020;28:e586-e594. An overview of cement techniques and
utilization in THA is presented. Level of evidence: V.
25. Troelsen A, Malchau E, Sillensen N, Malchau H: A review of
current fixation use and registry outcomes in total hip
arthroplasty: The uncemented paradox. Clin Orthop Relat Res
2013;471:2052-2059.
26. Fernández-Fernández R, Cruz-Pardos A, García-Rey E: Revision
total hip arthroplasty: Epidemiology and causes, in Rodríguez-
Merchán E, ed: Revision Total Joint Arthroplasty. Springer, 2020, pp
43-57. This article details failure mechanisms of primary THA,
specifically higher fracture and revision rates for noncemented
fixation in elderly patients.
27. El Ashmawy AAH, Dowson K, El-Bakoury A, et al: Effectiveness,
patient satisfaction, and cost reduction of virtual joint
replacement clinic follow-up of hip and knee arthroplasty. J
Arthroplasty 2021;36(3):816-822. A retrospective review from 2017
to 2018 reported significant cost savings and high patient
satisfaction for virtual joint replacement postoperative office visit
appointments. Level of evidence: V.
28. Dias Correia F, Nogueira A, Magalhães I, et al: Digital versus
conventional rehabilitation after total hip arthroplasty: A single-
center, parallel-group pilot study. JMIR Rehabil Assist Technol
2019;6(1):e14523. A single-center case series that compared
virtual and conventional physical therapy after THA reported
high satisfaction rates and higher adherence with physical
therapy exercises in the virtual group. Level of evidence: IV.
29. Chen X, Xiong J, Wang P, et al: Robotic-assisted compared with
conventional total hip arthroplasty: Systematic review and meta-
 analysis. Postgrad Med J 2018;94:335-341.
30. Ng N, Gaston P, Simpson PM, et al: Robotic arm-assisted versus
manual total hip arthroplasty: A systematic review and meta-
analysis. Bone Joint J 2021;103-B(6): 1009-1020. The authors
present a systematic review/meta-analysis of 17 studies of robotic
arm–assisted versus manual THA. They demonstrated acetabular
component position in safe zone more often and be er Harris
hip score in robotic-assisted THA, with no difference in infection,
dislocation, complication, and survival rates. Level of evidence: I.
31. McMaster Arthroplasty Collaborative (MAC): Risk factors for
periprosthetic joint infection following primary total hip
arthroplasty: A 15-year, Population-Based Cohort Study. J Bone
Joint Surg Am 2020;102(6):503-509. This database study reported
the overall incidence of PJI (1.44%) and risk factors associated
with PJI, including male sex, type 2 diabetes, and discharge to
inpatient convalescent care. Level of evidence: II.
32. Kur SM, Lau EC, Son MS, Chang ET, Zimmerli W, Parvizi J:
Are we winning or losing the ba le with periprosthetic joint
infection: Trends in periprosthetic joint infection and mortality
risk for the medicare population. J Arthroplasty 2018;33:3238-3245.
33. Parvizi J, Tan TL, Goswami K, et al: The 2018 definition of
periprosthetic hip and knee infection: An evidence-based and
validated criteria. J Arthroplasty 2018;33(5):1309-1314.
34. Higuera CA, Zmistowski B, Malcom T, et al: Synovial fluid cell
count for diagnosis of chronic periprosthetic hip infection. J Bone
Joint Surg Am 2017;99(9):753-759.
35. Heckmann ND, Mayfield CK, Culvern CN, et al: Systematic
review and meta-analysis of intrawound vancomycin in total hip
and total knee arthroplasty: A call for a prospective randomized
trial. J Arthroplasty 2019;34: 1815-1822. A systematic review and
meta-analysis of six low-quality retrospective studies
demonstrated decreased rates of PJI in the intrawound
vancomycin group. Level of evidence: III.
36. Iorio R, Yu S, Anoushiravani AA, et al: Vancomycin powder and
dilute povidone-iodine lavage for infection prophylaxis in high-
risk total joint arthroplasty. J Arthroplasty 2020;35(7):1933-1936. A
review of high-risk patients treated with intrawound vancomycin
and dilute povidone-iodine lavage demonstrated reduction in PJI
rates. Level of evidence: III.
37. Buchalter DB, Kirby DJ, Teo GM, et al: Topical vancomycin
powder and dilute povidone-iodine lavage reduce the rate of early
periprosthetic joint infection after primary total knee
arthroplasty. J Arthroplasty 2021;36(1):286-290. Topical
vancomycin power and dilute povidone-iodine lavage reduced
early PJI incidence in primary TKA in both high-risk and overall
cohorts compared to a historical control. Level of evidence: III.
38. Cichos KH, Andrews RM, Wolschendorf F, et al: Efficacy of
intraoperative antiseptic techniques in the prevention of
periprosthetic joint infection: Superiority of betadine. J
Arthroplasty 2019;34(7 suppl):S312-S318. Povidone-iodine,
chlorhexidine gluconate, and vancomycin power were assessed to
determine minimal inhibitory concentration and time to death
against multiple bacteria. All bacterial isolates were eliminated
immediately on contact by povidone-iodine solution. Level of
evidence: V.
39. Calkins TE, Culvern C, Nam D, et al: Dilute betadine lavage
reduces the risk of acute postoperative periprosthetic joint
infection in aseptic revision total knee and hip arthroplasty: A
randomized controlled trial. J Arthroplasty 2020;35(2):538-543. A
randomized controlled trial of patients undergoing aseptic
revision THA and total knee arthroplasty compared patients
receiving normal saline lavage and dilute betadine before wound
closure. There were significantly fewer infections in the betadine
group without wound complications between groups. Level of
evidence: I.
40. Yazdi H, Klement MR, Hammad M, et al: Tranexamic acid is
associated with reduced periprosthetic joint infection after
primary total joint arthroplasty. J Arthroplasty 2020;35(3):840-844.
 The authors report an institutional database study for patients
undergoing TJA from 2013 to 2017. They demonstrate patients
who received tranexamic acid had a lower odds of PJI. Level of
evidence: III.
41. Kheir MM, Dilley JE, Ziemba-Davis M, Meneghini RM: Extended
oral antibiotics prevent periprosthetic joint infection in high-risk
cases: 3855 patients with 1-year follow-up. J Arthroplasty 2021;36(7
suppl):S18-S25. A 1-year review of extended oral antibiotic
protocol for high-risk TJA showed reductions in PJI in the
treatment group. Level of evidence: II.
42. O en MR, Kildow BJ, Sayles HR, et al: Two-stage reimplantation
of a prosthetic hip infection: Systematic review of long-term
reinfection and pathogen outcomes. J Arthroplasty
2021;36(7):2630-2641. The authors perform a systematic review on
the success rate of two-stage exchange. The success rates are
highly variable in the literature, range between 60% and 95%, and
worsen with increased follow-up. Level of evidence: III.
43. Argenson JN, Arndt M, Babis G, et al: Hip and knee section,
treatment, debridement and retention of implant: Proceedings of
international consensus on orthopedic infections. J Arthroplasty
2019;34(2 suppl):S399-S419. This is a summary of proceedings
from the Second International Consensus Meeting on
Musculoskeletal Infection recommendations on DAIR. These
include performing surgery urgently but not emergently, not
delaying until an organism is isolated, exchanging all modular
components when possible, using copious irrigation and
antiseptic solutions, and appropriate antibiotic management
postoperatively to improve outcomes. Level of evidence: V.
44. Sharma AK, Vigdorchik JM: The hip-spine relationship in total
hip arthroplasty: How to execute the plan. J Arthroplasty 2021;36(7
suppl):S111-S120. The authors review the preoperative evaluation
for spinopelvic parameters, report a classification, and describe
techniques for intraoperative management of acetabular
component positioning. Level of evidence: V.
45. Vigdorchik J, Sharma A, Buckland A, et al: A simple Hip-Spine
Classification for total hip arthroplasty. Bone Joint J 2021;103-
B(7):17-24. The authors review spinopelvic parameters for
patients at high risk for instability, develop a classification, and
assess dislocation rates in a single-center cohort. Level of
evidence: II.
46. Hall DJ, Pourzal R, Jacobs JJ: What surgeons need to know
about adverse local tissue reaction in total hip arthroplasty. J
Arthroplasty 2020;35(6 suppl):S55-S59. The authors review ALTRs,
tribocorrosion, diagnostic, and management techniques in THA.
Level of evidence: V.
47. Hussey DK, McGrory BJ: Ten-year cross-sectional study of
mechanically assisted crevice corrosion in 1352 consecutive
patients with metal-on-polyethylene total hip arthroplasty. J
Arthroplasty 2017;32:2546-2551.
48. Sonn KA, Meneghini RM: Adverse local tissue reaction due to
acetabular corrosion in modular dual-mobility constructs.
Arthroplasty Today 2020;6(4)976-980. Authors present three
patients with mechanically assisted crevice corrosion at the
acetabular componentmetal dual-mobility liner interface. Level
of evidence: IV.
49. Kwon YM, MacAuliffe J, Arauz PG, Peng Y: Sensitivity and
specificity of metal ion level in predicting adverse local tissue
reactions due to head-neck taper corrosion in primary metal-on-
polyethylene total hip arthroplasty. J Arthroplasty 2018;33:3025-
3029.
50. Kwon YM, Rossi D, MacAuliffe J, Peng Y, Arauz P: Risk factors
associated with early complications of revision surgery for head-
neck taper corrosion in metal-on-polyethylene total hip
arthroplasty. J Arthroplasty 2018; 33(10):3231-3237.
S E CT I ON 8

Knee
SECTION EDITOR
Sabrina Strickland, MD, FAAOS

Beth Shubin Stein, MD, FAAOS

C H AP T E R 4 3

Ligament Injuries to the Knee

Jacqueline M. Brady MD, FAAOS, FAOA

Dr. Brady or an immediate family member serves as a paid consultant to or is an employee of

Miach.

ABSTRACT
Ligament injuries in the knee are common and can be caused by
low-energy trauma in patients with predisposing factors or high-
energy injuries in traumatic se ings. When knee ligament injuries
render the tibiofemoral joint unstable, the chondral surfaces and
menisci are at risk of ongoing injury from excessive shear forces.
Likewise, recurrent patellofemoral instability can lead to
cumulative chondral injury concerning for later pos raumatic
arthritis. Surgical intervention is warranted when shown to prevent
ongoing instability. Isolated medial collateral ligament and
posterior collateral ligament tears and many first-time
patellofemoral dislocations may be managed nonsurgically, with
physical therapy directed at strength and periarticular mechanics.
Anterior cruciate ligament tears in athletes pursuing sports
involving change of direction, medial patellofemoral ligament
injuries in the se ing of recurrent patellar instability and/or a loose
chondral/osteochondral injury, and multiligamentous knee injuries
should be managed surgically. Primary repairs of the medial
patellofemoral ligament and posterolateral corner injuries have
been shown to have a high rate of failure; therefore reconstruction
or augmentation should be used. Grafts used for collateral and
cruciate ligament reconstruction are placed under resting tension
to gain maximal stability, but medial patellofemoral ligament grafts
are used as a checkrein only, so they are set to a length that
minimizes tension and allows some patellar translation to avoid
medial patellofemoral joint overload. Surgical intervention for any
knee ligament injury should be guided by the native anatomy, and
a careful approach to allow knee motion by optimizing graft
isometry will improve outcomes.
Keywords: knee dislocation; ligament reconstruction; patellar
instability

Introduction
Although full extension is a stable position for the knee in terms of
bony anatomy, the knee joint is not a pure hinge. With range of
motion, the joint surfaces begin to roll and glide. The knee
ligaments are key to maintaining stability of the knee during this
process.

Anatomy

Anterior Cruciate Ligament

The anterior cruciate ligament (ACL) has rotational and
translational roles in stabilizing the knee. It has two bundles
named for their position within the tibial insertion. The
anteromedial bundle is the more vertical bundle, serving to restrain
anterior translation of the tibia relative to the femur. The femoral
footprint of the native ACL is posteriorly located on the lateral wall
of the intercondylar notch, centered on the bifurcate bony ridge.
The tibial footprint is broad, but centered between the tibial spines,
generally in line with an anatomically normal posterior border of
the anterior horn of the lateral meniscus. The Lachman
examination is the most sensitive physical examination for ACL
integrity, and it primarily tests the anteromedial bundle. The
posterolateral bundle serves as a rotational restraint and is linked
to the pivot shift test in the knee. Patient outcomes after ACL
reconstruction surgery have been demonstrated to correlate with
the presence or absence of a pivot shift on examination. 1 , 2

Posterior Cruciate Ligament

The posterior cruciate ligament (PCL) is broad and stout and also
plays translational and rotational roles in stabilization: posterior
translation of the tibia and anteromedial rotation of the tibia
relative to the femur. The two bundles in the PCL are the
anterolateral and posteromedial bundles. The femoral footprint is
very anterior and vertical within the intercondylar notch, abu ing
the articular cartilage. The tibial footprint is very posterior,
originating behind the tibial plateau at the so-called champagne
glass drop-off of the tibia. The PCL rarely sustains a complete tear
in isolation, so a grade 3 PCL injury (full-thickness injury resulting
in more than 10 mm posterior translation of the tibia relative to the
femur on posterior drawer testing) should alert the examiner to the
likely presence of concomitant ligamentous injuries.

Posterolateral Corner
In evolutionary history, the fibula was part of the knee articulation.
It is now separate from the tibiofemoral articulation, but the lateral
tibial plateau remains convex, leading to a need for an intricate
combination of active and static stabilizers in the lateral knee. The
posterolateral corner of the knee includes the lateral collateral
ligament, popliteus tendon and popliteofibular ligament, iliotibial
band, and biceps femoris. Other structures, such as the arcuate
ligament and the posterolateral joint capsule, are described as part
of the posterolateral corner of the knee, but these are not
necessarily included in the surgical reconstruction. This
combination of structures stabilizes the knee against varus load
and external tibial rotation. Injury to this complex can be subtle,
and the dial test is helpful to evaluate the extent of injury when it
can be compared with an uninjured contralateral knee (Figure 1).
 Figure 1 Clinical photographs show how the dial test is used to aid in
diagnosis of knee injuries involving the posterolateral corner.A, Asymmetric
external rotation at 30° of knee flexion suggests injury only to the posterolateral
corner. B, If the external rotation of the injured knee is greater than the uninjured
knee at 90° of knee flexion, this suggests injury to both the posterolateral corner
and the posterior cruciate ligament.

Medial Collateral Ligament

The medial collateral ligament (MCL) has two components:
superficial and deep. The deep MCL has a achments to the medial
meniscus of the knee. The superficial MCL is the primary restraint
to valgus force, originating from the posterior and superior aspects
of the medial femoral epicondyle and inserting 6 cm distal to the
tibiofemoral joint line. MCL injuries are common in isolation, and
the prognosis for recovery without surgical intervention is known
to be be er when the ligamentous injury is proximal. This is
thought to relate to the anatomy of the distal insertion: tibial-side
injuries sometimes result in a situation akin to the Stener lesion in
ulnar collateral ligament injuries of the thumb: the MCL tears from
its tibial insertion and retracts enough to pull out from under the
pes tendon insertion. Although no conclusive data prove this
theory, the inability of the tibial-side MCL to approximate its native
insertion is thought to hamper its potential to scar with an
acceptable degree of stability.

Posterior Oblique Ligament

In recent years, the understanding of the rotational stability of the
medial side of the knee has improved. The posterior oblique
ligament originates from the adductor tubercle of the knee and
a aches to the posterior aspect of the tibia and joint capsule. It
controls anteromedial rotation and aids in stabilizing against
valgus forces. In addition, it plays a minor role in protecting against
posterior tibial translation.

Medial Patellofemoral Ligament

The patella is a sesamoid bone within the extensor mechanism, and
it experiences significant shearing loads in comparison with the
compressive loads experienced by the tibiofemoral joint. With
wider hips than knees, especially in women, humans are
predisposed to lateral patellar tracking, and sometimes frank
instability. The medial patellofemoral ligament (MPFL) is the
primary restraint to lateral patellar translation. 3 It is a thickening
of the joint capsule that originates in the saddle region between the
adductor tubercle and medial epicondyle of the knee and inserts
primarily above the equator of the patella. A reflection to the
quadriceps tendon has been described, and this structure is thus
perhaps more accurately described as the medial patellofemoral
complex. 4 When patients have predisposing anatomy such as
trochlear dysplasia, patella alta, a high tibial tuberosity to trochlear
groove distance, significant genu valgum, or excessive femoral
anteversion, patients can experience a patellar subluxation or
dislocation, almost universally tearing the MPFL. 5

Imaging
When possible, weight-bearing radiographs are preferred to
evaluate the integrity of the joint with dynamic loads. A
comparison view of the uninjured knee can be useful if findings are
subtle or if suspicion remains regarding joint space in the se ing of
chondromalacia or meniscal pathology. In the case of cruciate
ligament injury, a true lateral radiograph can be useful to
determine the position of the tibia relative to the femur under
loads.

Anterior Cruciate Ligament

A Segond fracture on an AP knee radiograph is pathognomonic for
an ACL tear. This finding represents avulsion of the anterolateral
ligament from the tibia (Figure 2). It is not always present in the
se ing of an ACL tear, but when found on plain radiographs
should prompt MRI evaluation of soft-tissue integrity in the knee. 6
Because ACL tears are commonly associated with meniscal and
chondral injuries in the knee, a weight-bearing tunnel view can also
be helpful in evaluating the integrity of the posterior portion of the
tibiofibular joint.
 Figure 2 AP radiograph shows a Segond fracture (arrow), which is an avulsion
of the anterolateral capsule from the tibia that is a pathognomonic finding for
anterior cruciate ligament tear.(Courtesy of Ekaterina Urch, MD.)

Although more common in patients with skeletal immaturity,

ACL injuries can involve tibial spine avulsions in any age range. If
displaced, the tibial spine can be blocked from anatomic reduction
by either the intermeniscal ligament or the anterior horn of the
medial meniscus. Even with anatomic reduction and fixation,
studies have shown residual laxity in the ACL, indicative of initial
intrasubstance injury.
Radiographs also are important to determine alignment when
planning surgical intervention. The posterior tibial slope has
increasingly been recognized as a risk factor for failure of ACL
reconstruction. 7 , 8 Significant coronal plane malalignment,
particularly genu varum, also can cause overload thought to be
responsible for excessive strains on native and reconstructed
ligaments. Particularly in revision situations, standing bilateral
limb length and alignment radiographs, a lateral view of the tibia
and fibula, and CT to evaluate the size and location of the previous
tunnels are important parts of the workup for ACL injuries in the
knee.
MRI is the gold standard for evaluating the ACL. In many cases
bony contusions consistent with a pivot-shift injury mechanism are
visible on the weight-bearing surface of the lateral femoral condyle
and posterolateral tibial plateau (Figure 3). These bony contusions
are predictive of later pos raumatic arthritis. 9 The ACL itself is
generally readily visible on MRI. Complete rupture is generally
plainly evident. Partial injury can be subtle, and the presence of
typical bone bruises helps the evaluator confirm the incompetence
of the ligament in these cases.
 Figure 3 MRI shows bony contusions in the lateral femoral condyle and
posterolateral tibial plateau (arrows), indicating a pivoting injury in the setting of
anterior cruciate ligament tear.

The location of the tibia relative to the femur on any lateral or

sagi al imaging study can hint at chronicity of any ACL tear: when
the tibia is observed to subluxate slightly anteriorly, a more chronic
injury and underlying anatomic factors such as increased posterior
tibial slope and/or posterior horn meniscus pathology are
suspected.

Posterior Cruciate Ligament

Avulsions of the PCL can occur from the femur or from the tibia.
Depending on the size and location of the fragment, CT is helpful
to confirm the nature of the injury when an avulsion is present
because the bony overlap seen on radiography can be confounding.
Whether the PCL is injured in its midsubstance or from an
avulsion, the lack of integrity of the ligament can result in posterior
sag of the tibia relative to the femur, which often is visible on a
lateral radiograph if carefully scrutinized.
The evaluation of PCL injury on MRI can be nuanced in the
se ing of acute injury. Often, an acutely injured ligament will be
read as grade 3 by a radiologist based on full-thickness edematous
signal seen across its midsubstance. The radiographic grade 3 does
not necessarily correlate with a grade 3 posterior drawer test
finding on examination, however, and it is important to realize that
a PCL in continuity may have the potential to scar sufficiently to
render the knee relatively stable. Surgical intervention should be
based on physical examination, although a completely disrupted
PCL seen on MRI can help direct the physical examination. If the
ankle-brachial index is less than 0.9, or the pulses are asymmetric,
contrast-enhanced CT is indicated to evaluate for vascular injury.
Vascular injury is more common in posterior knee dislocations,
likely because of the higher degree of force required to produce the
injury. It also can occur in anterior knee dislocations, however, via
intimal stretch and resultant thrombosis.

Medial Collateral Ligament

MCL injuries can also involve femoral epicondylar avulsions,
termed Pellegrini-Stieda lesions. The presence of this avulsion
fragment does not necessarily mandate surgical intervention, and
those managed nonsurgically can therefore become a chronic
incidental finding on future radiographs.
MRI is helpful in MCL injuries to determine the location of the
injury and the amount of disruption. It is used to confirm the
presence of a tibial-side Stener lesion, in which the distal MCL is
found superficial to the pes insertion as mentioned previously. In
patients with extreme obesity, a substantial amount of MCL stretch
can develop in valgus knees over time, and MRI can help determine
whether the ligament demonstrates any signs of acute injury if the
examination is inconclusive. Finally, the posterior oblique ligament
can be visualized as the capsular layer posterior to the superficial
MCL.

Posterolateral Corner
Posterolateral corner injuries often involve avulsion of the fibular
head. This injury can be a large or small avulsion fragment, and the
physician sometimes needs a high index of suspicion to detect the
avulsion fragment. Any avulsion of the fibular head on radiographs
should raise suspicion that a severe ligamentous injury may be
involved. Because the other lower extremity is generally protective
against a direct varus force, posterolateral corner injuries are rare in
isolation.
The posterolateral corner can be evaluated for its detailed
anatomy on MRI. The popliteofibular ligament is not always plainly
seen on the standard MRI sequences, but when it is, evaluation of
its integrity can contribute to the overall understanding of the knee
injury. The popliteus itself often is ruptured at its
musculotendinous junction rather than its femoral insertion. If the
fibular head is not avulsed, the individual insertions of the lateral
collateral ligament and biceps femoris can be scrutinized.
Importantly, the integrity of the peroneal nerve also can be
evaluated. If numbness or a foot drop is encountered on
examination, MRI can help the surgeon understand whether the
nerve is still in continuity and make plans for any indicated repair.

Multiligamentous Knee Injuries

Multiligamentous knee injuries and tibiofemoral dislocations, once
reduced, can be very subtle on plain radiographs. Capsular
disruptions can result in small avulsion fractures that the untrained
evaluator might miss as a sign of a complex soft-tissue injury
(Figure 4). When present on radiographs from a patient with a
history suspicious for instability, these small avulsions should
prompt a careful evaluation of neurovascular status and
consideration of advanced imaging.

Figure 4 AP radiograph obtained with a portable trauma bay device shows

capsular avulsions (arrows), which can help identify multiligament knee injuries.

Stress view radiographs are useful intraoperatively to help decide

on definitive management of a ligament or ligament complex that
might show only partial injury on advanced imaging (Figure 5).
Stress views also play a role in some surgeons’ outpatient practices
to help quantify the amount of translation of the tibia posteriorly
on a kneeling radiograph (PCL) or to compare sides with varus or
valgus stress in the se ing of suspected MCL or posterolateral
corner pathology. Stress views also can be useful to evaluate the
integrity of a ligament reconstruction once safe to do so
postoperatively.

Figure 5 Intraoperative fluoroscopic stress view used to determine the amount

of laxity in this incompetent posterior cruciate ligament injury.

MRI is a mainstay of evaluation of multiligament knee injuries.

Bony edema can help direct the reviewer to the location of injury by
mechanism. When considering acute versus delayed intervention,
MRI helps rule out urgent associated injuries such as a bucket
handle or avulsed meniscus. When possible, it is most helpful to
perform MRI early in the care of a patient with an associated
fracture, because the level of detail afforded by the study is
compromised by neighboring metal hardware.

Patellofemoral Joint
Radiographic evaluation of the patellofemoral joint consists of a
true lateral radiograph to evaluate patellar height and any trochlear
dysplasia, and an early bilateral flexion axial or Merchant view to
evaluate patellar tracking. Classification of trochlear dysplasia can
be made on the lateral view using the Dejour classification (Figure
6). The crossing sign describes the intersection of the trochlear
groove line with the anterior femur distal to the anterior femoral
cortical line, and this represents a shallow groove. When the
crossing sign is combined with a supratrochlear spur or boss, the
groove is known to be flat. If those two features are combined with
a double contour sign on the anterior distal femur, the medial
trochlea is known to be hypoplastic, leaving the groove convex at its
proximal portion—this is the most severe form of dysplasia.
 Figure 6 Drawings depict the Dejour classification of trochlear dysplasia.
(Reproduced with permission from DeJour D, Saggin P: The sulcus deepening
trochleoplasty – The Lyon’s procedure. Int Orthop 2010;34[2]:311-316.)

Patellar height is generally described using the Caton-

Deschamps ratio, as other measurements are either less reliable
(Blumensaat) or rendered less useful by referencing the tibial
tubercle (Insall-Salvati, which does not change in the se ing of
tibial tubercle osteotomy). Most measurements of patellar height
reference the tibia in some way, rendering a somewhat incomplete
understanding with regard to the role of lateral patellar tracking,
the length of the often-dysplastic trochlea, and any hyperextension
in a joint with ligamentous laxity.
Most patients with patellar instability have chondral or
osteochondral injuries, so MRI is very helpful for identification of
the initial injury, risk stratification for recurrence, and preoperative
planning. MRI has been shown to identify the MPFL injury in most
cases of patellar dislocation, and the ligament is most commonly
injured at the femoral origin in adults and at the patellar
a achment in children and adolescents. 10 The tibial tubercle–to –
trochlear groove distance was initially described on CT, but may be
more appropriately measured on MRI, as the center of the patellar
tendon a achment itself is likely more influential than the center of
the tubercle bone. Studies have correlated CT and MRI for
measurement of the tibial tubercle to trochlear groove distance,
and found that CT overestimates the value by 3 to 4 mm. 11 MRI
demonstrates the three-dimensional anatomy of the trochlea and
provides a be er understanding of how excessive patellar height
might interact with lateral tracking to worsen patellar instability.

Surgery

Anterior Cruciate Ligament

Nearly a century ago, because of high failure rates, ACL repair was
abandoned in favor of ACL reconstruction. After careful,
methodical examination in animals and then humans, in December
2020, the FDA authorized the marketing of a new implant, the
Bridge-Enhanced ACL Repair Implant. 12 The implant is a
bioabsorbable, porcine-based scaffold that is implanted around the
torn ends of the injured ACL and injected with the patient’s own
blood. The rollout of training for the new procedure was delayed by
the COVID-19 pandemic, however, so at the time of this writing,
ACL reconstruction remains the gold standard for surgical
intervention.
Some patients tolerate ACL deficiency with minimal symptoms.
If a patient is not symptomatic at baseline and not participating in
sporting activities requiring cu ing and jumping, nonsurgical
treatment may be pursued preliminarily or definitively. This seems
particularly possible in the skiing population, as demonstrated in a
case series. 13 The secondary restraint to anterior translation of the
tibia is the posterior horn of the medial meniscus. If this is torn at
the time of initial ACL tear, more consideration may be given to
surgical intervention. In addition, some patients do not realize the
nature of the initial injury and manage return to sports with an
ACL-deficient knee. A consistent pa ern for a chronic ACL tear not
treated initially is late tearing of the posterior horn of the medial
meniscus, causing onset of symptoms of instability (Figure 7).

Figure 7 MRI showing chronic anterior cruciate ligament tears, which can
overload the medial meniscus (A), which can cause late tearing in the form of
bucket-handle displacement (B; also called the double posterior cruciate
ligament sign [arrow]).

ACL reconstruction generally is accomplished by creation of

bony sockets or tunnels in the tibia and femur and implanting a
tendon to replace the ligament. Although two bundles have been
described as responsible for the function of the ACL, the double-
bundle ACL reconstruction technique has failed to gain wide
popularity because of the paucity of studies proving clinical
superiority combined with the complexity of potentially revising a
reconstruction that involved four separate bony tunnels/sockets.
Historical evolution of the ACL reconstruction technique involved a
departure from anatomy as instrumentation has been developed
that allows transtibial placement of a femoral tunnel vertically on
the femoral side. This construct could provide translational stability
but often allows rotational instability to persist. Currently,
abundant tools exist for independent (or very careful transtibial)
creation of the femoral and tibial bony a achments of the new
ACL. The femoral socket or tunnel should be placed as far
posteriorly as possible, referencing the bifurcate bony ridge and the
native ligament’s footprint, when possible. The tibial socket or
tunnel can reference the PCL, the intermeniscal ligament, and/or
the anterior horn of the lateral meniscus. All three tools are useful,
as multiligament injuries, scar associated with prior surgery, or
discoid menisci can complicate the use of only one landmark. The
center of the tibial footprint of the ACL has been described to be 10
to 11 mm anterior to the PCL, 9 mm posterior to the intermeniscal
ligament, and in line with the posterior aspect of the anterior horn
of the lateral meniscus. 14
Once the ACL graft is in place, it is tensioned and definitively
secured. The isometric point of the ACL is known to be in early
flexion of the knee. As the graft is moved down the wall of the
notch into a more posterior position, it is more likely to be tighter
in extension. Therefore, although many surgeons still tension and
definitively secure their ACL graft in early flexion, others have
transitioned to full extension to ensure that the patient is not
robbed of this position once the graft is in place.
Graft choice for ACL reconstruction remains a point of lively
discussion. The patellar tendon is often regarded as the gold
standard graft, with the highest return to sports and lowest failure
rates in the literature. However, it is known to be associated with
anterior knee pain, it has been implicated in the presence of long-
term patellofemoral osteoarthritis, and the risk of dreaded patellar
fracture sometimes proves to be a deterrent. Hamstring autograft
has been a long-standing alternative. The semitendinosus and
gracilis tendons can be doubled over a suspensory suture, or the
semitendinosus alone can be quadrupled over two suspensory
sutures. This option often involves smaller incisions and less
anterior knee pain, but an accumulating body of literature in the
rehabilitation of ACL reconstruction has led to a desire to spare the
hamstrings, as they protect the new graft. The newest autograft
option has been quadriceps tendon, with or without associated
patellar bone. The quadriceps tendon is thicker than the patellar
tendon, and the graft harvest site is away from the kneeling zone on
the anterior knee, sparing some of the typical pain that plagues
patients who undergo ACL reconstruction using patellar tendon.
Allograft is an option for reconstruction of any ligament in the
knee, but it has been proven to have a higher failure rate than
autograft in both primary and revision ACL reconstruction se ings.
For a broad, stout MCL or PCL, it remains a viable option, as many
autograft selections would not approach the size or strength of the
native ligament. For multiligament knee injuries, sufficient
autograft to reconstruct every injured structure might not be
available.

Posterior Cruciate Ligament

Isolated PCL injuries may be managed nonsurgically, with physical
therapy focused on quadriceps strengthening. However, given the
amount of force required to tear the native PCL, isolated PCL
injuries are rare, and a high index of suspicion must be maintained
for other ligamentous injuries. If a PCL injury involves a bony
avulsion, this may be effectively repaired in the acute se ing. When
the injury is purely ligamentous, reconstruction is undertaken.
Biomechanical studies indicate that a double-bundle PCL
reconstruction, often accomplished with one tibial tunnel/socket
and two separate a achments on the femur, can provide improved
rotational stability compared with a single-bundle approach. 15 No
clinical study has demonstrated superiority of one technique over
another, although in a 2020 study systematic reviews have indicated
improved results of stress radiography and functional outcome
scores following double-bundle reconstruction. 16 The risks of
tunnel convergence in multiligament surgery and the increased
complexity in the se ing of revision surgery prove deterrents for
many surgeons. Another debate in PCL reconstruction surgery is
the approach to the tibial fixation. One of the contributors to
postoperative laxity is thought to be the “killer turn” associated
with antegrade drilling of a tibial tunnel from anterior to posterior.
This approach, especially when combined with the common error
of making the tibial aperture somewhat anterior relative to its
native anatomy, is thought to create a severe angle as the graft
makes its way to the femur. For this reason, some surgeons prefer a
posteromedial approach and an inlay of the graft on the posterior
tibia. The inlay technique can prove technically difficult from the
standpoint of positioning, especially if the patient is obese.
Regardless of technique for tibial fixation, once the graft is in place,
it is tensioned and definitively secured in 90° of flexion.

Medial Collateral Ligament

MCL injuries are often managed nonsurgically. Even if the initial
examination reveals grade 3 laxity, some improvement can be
expected with appropriate protection. Patients are provided a
hinged knee brace to allow range of motion but protect against
valgus stress, and a repeat examination is undertaken after 6 weeks.
If the examination has not improved, surgical intervention is
undertaken. In acute se ings, MCL repair might be pursued if
urgent surgical intervention is warranted because of the presence of
persistent subluxation of the joint, the presence of a bucket-handle
meniscal tear, or other relevant injury. MRI can be used to localize
the area of MCL injury, and if adjacent to bone, repair can be
effective at restoring stability to the knee. In addition to repair, a
heavy, braided suture may be added to help protect the healing
ligament between two bony anchors. In a more chronic se ing, any
MCL repair is typically augmented with a graft, or a frank
reconstruction is undertaken in the se ing of intrasubstance MCL
injury. Autograft options have been described, mostly using
semitendinosus. The dimensions of the MCL are such that many
surgeons prefer to use an allograft option such as Achilles tendon
to be er re-create the native ligament’s properties. The graft is
fixed to the medial epicondyle, then routed deep to the pes anserine
tendon sheath to be fixed closely to the native ligament, 6 cm distal
to the joint line on the medial tibia. Anchors may be placed at the
proximal tibia to re-create the deep MCL’s a achment. When the
posteromedial corner is involved, as evidenced by excessive
anteromedial rotation and/or extensive capsular disruption, the
posterior oblique ligament is concomitantly reconstructed. A
variety of techniques have been described, most involving a
tendinous limb from the medial epicondyle to the posteromedial
tibia. 17

Posterolateral Corner
The posterolateral corner of the knee is rarely injured in isolation,
in part because the other knee often protects the area from a pure
varus force. MRI helps to guide any surgical intervention by
identifying injury to the individual structures. When a fibular
avulsion is present, or when the popliteus tendon and/or lateral
collateral ligament is peeled off its femoral insertion, repair may be
undertaken. However, posterolateral corner repair has a 40% rate of
failure, indicating that the ability to identify intrasubstance injury
to the structures is incomplete. 18 , 19 In most cases, therefore, a
tendon augmentation or reconstruction is undertaken. This tendon
can either be looped through a drill hole in the fibula alone or
combined with another tendon inserting on the tibia (Figure 8). As
in PCL reconstruction, the additional fixation of the tibial tunnel
seems to improve biomechanical time-zero stability, but clinical
studies have not proven this to be clinically significant. Given that
posterolateral corner injuries most often accompany other ligament
injuries, some surgeons prefer to avoid the prospect of adding
tibial tunnels in a multiligament reconstruction situation to ensure
the integrity of the other grafts.
 Figure 8 Schematic illustration shows techniques for posterolateral corner
reconstruction.A and B, Fibula-based strategies. C, Dual tunnels including tibial
fixation.(Reproduced with permission from Kang KT, Koh YG, Son J, et al: Finite
element analysis of the biomechanical effects of 3 posterolateral corner
reconstruction techniques for the knee joint. Arthroscopy 2017;33[8]:1537-1550,
Figure 1.)

Medial Patellofemoral Ligament

Historically, patients with a first-time patellofemoral dislocation
were treated nonsurgically on a relatively universal basis (unless an
osteochondral fracture or loose intra-articular body dictated
intervention). A high-risk group of patients is emerging as
potentially benefi ing from surgical intervention to prevent
recurrence. 20 The MPFL also has been shown to have a high rate of
failure for primary repair, 21 so surgical intervention most often
involves a reconstruction of the MPFL. Many techniques have been
described, with autograft sources including semitendinosus or
gracilis, a portion of the quadriceps tendon, or the adductor
magnus tendon. Unlike the other ligaments and complexes in the
tibiofemoral joint, the MPFL is relatively small and weak compared
with any graft choices for its reconstruction. In addition, it is a
checkrein, seeing tension less consistently than its cruciate and
collateral ligament counterparts. Unsurprisingly, then, although the
literature indicates a high rate of failure for ACL reconstruction
using allograft, the same has not been shown for MPFL
reconstruction, and allograft remains an option. The tendon graft is
fixed at the femoral origin of the MPFL, at Schoe le point (Figure 9)
on radiographs. This corresponds to the saddle region between the
adductor tubercle and medial epicondyle of the femur. The graft is
likewise fixed to the patella above its equator—or some surgeons
prefer to fix it to the distal quadriceps tendon in part (ie, one limb
of a two-tailed construct) or whole. As the fulcrum of the circle
formed by knee motion, the femoral insertion is the most
important to achieve isometry of the graft and avoid capture of the
knee. Patellar fixation is important to scrutinize to avoid the
dreaded complication of patellar fracture. Any drilling into the
bone should be kept as small as possible, and avoidance of a dorsal
cortical breach can help avoid a stress riser on the tension side of
the bone. Because any graft used is much larger and stronger than
the native ligament, it is also important to avoid overtensioning the
graft to minimize overload of joint-reactive forces and
postoperative pain. This can be achieved in a variety of ways,
depending on technique.
 Figure 9 Illustration shows radiographic landmarks for appropriate placement
of the femoral fixation point of a medial patellofemoral ligament reconstruction.
(Redrawn with permission from Schöttle PB, Schmeling A, Rosenstiel N, Weiler
A: Radiographic landmarks for femoral tunnel placement in medial
patellofemoral ligament reconstruction. Am J Sports Med 2007;35[5]:801-804,
Figure 4.)

Summary
Ligament injuries in the knee rarely heal on their own, and surgical
reconstruction is the gold standard for treatment. A high index of
suspicion must be maintained for concomitant injuries when one
ligamentous injury is identified, especially in the case of PCL and
posterolateral corner injuries. Surgical techniques are based on the
anatomy of the native ligament or ligamentous complex. Careful
a ention to the relevant anatomy and any associated risk factors
will aid in preventing recurrent instability or failure of any ligament
reconstruction.

Key Study Points

ACL tears are common, and surgical intervention is warranted for patients who
experience ongoing symptomatic instability or who wish to pursue jumping and
cutting sports.
PCL tears rarely occur in isolation, but when encountered they can often be
managed without surgical intervention.
MCL tears often exhibit some scarring that may acceptably stabilize the knee; so if
no other factors force early surgical intervention, a period of 6 weeks of brace
treatment will help to determine whether surgery is warranted.
Posterolateral corner and MPFL injuries fare poorly with repair alone, and should be
reconstructed (or in the case of some acute posterolateral corner injuries,
augmented).

Annotated References
1. Kocher MS, Steadman JR, Briggs KK, Stere WI, Hawkins RJ:
Relationships between objective assessment of ligament stability
and subjective assessment of symptoms and function after
anterior cruciate ligament reconstruction. Am J Sports Med
2004;32(3):629-634.
2. Horvath A, Meredith SJ, Nishida K, Hoshino Y, Musahl V:
Objectifying the pivot shift test. Sports Med Arthrosc Rev
2020;28(2):36-40. This review describes the pivot shift test and
objective methods to reduce variability between examiners, as
well as anatomic factors that contribute to its presence. Level of
evidence: V.
3. Desio SM, Burks RT, Bachus KN: Soft tissue restraints to lateral
patellar translation in the human knee. Am J Sports Med
1998;26:59-65.
 4. Loeb AE, Tanaka MJ: The medial patellofemoral complex. Curr
Rev Musculoskeletal Med 2018;11(2):201-208.
5. Askenberger M, Arendt EA, Ekstrom W, Voss U, Finnbogason T,
Janarv PM: Medial patellofemoral ligament injuries in children
with first-time lateral patellar dislocations: A magnetic resonance
imaging and arthroscopic study. Am J Sports Med 2016;44(1):152-
158.
6. Woods GW, Stanley RF, Tullos HS: Lateral capsular sign: x-ray
clue to a significant knee instability. Am J Sports Med 1979;7(1):27-
33.
7. Feucht MJ, Mauro CS, Brucker PU, Imhoff AB, Hinterwimmer S:
The role of the tibial slope in sustaining and treating anterior
cruciate ligament injuries. Knee Surg Sports Traumatol Arthrosc
2013;21(1):134-145.
8. Panigrahi TK, Das A, Mohanty T, Samanta S, Mohapatra SK:
Study of relationship of posterior tibial slope in anterior cruciate
ligament injury. J Orthop 2020;21:487-490. This study compared
MRI of patients with and without ACL tears, and found that the
lateral tibial slope was significantly higher in patients with ACL
tears. Level of evidence: III.
9. Nakame A, Engebretsen L, Bahr R, et al: Natural history of bone
bruises after acute knee injury: Clinical outcome and
histopathological findings. Knee Surg Sports Traumatol Arthrosc
2006;14(12):1252-1258.
10. Kepler CK, Bogner EA, Hammoud S, Malcolmson G, Po er HG,
Green DW: Zone of injury of the medial patellofemoral ligament
after acute patellar dislocation in children and adolescents. Am J
Sports Med 2011;39(7):1444-1449.
11. Camp CL, Stuart MJ, Krych AJ, et al: CT and MRI measurements
of tibial tubercle-trochlear groove distances are not equivalent in
patients with patellar instability. Am J Sports Med 2013;41(8):1835-
1840.
12. Murray MM, Fleming BC, Badger GJ, et al: Bridge-enhanced
anterior cruciate ligament repair is not inferior to autograft
 anterior cruciate ligament reconstruction at 2 years: Results of a
prospective randomized clinical trial. Am J Sports Med
2020;48(6):1305-1315. This randomized trial demonstrates that
bridge-enhanced ACL repair results in similar postoperative
laxity and improved hamstring strength compared with patients
who underwent ACL reconstruction. Level of evidence: I.
13. Hetsroni I, Delos D, Fives G, Boyle BW, Lillemoe K, Marx RG:
Nonoperative treatment for anterior cruciate ligament injury in
recreational alpine skiers. Knee Surg Sports Traumatol Arthrosc
2013;21(8):1910-1914.
14. Chahla J, Moatshe G, Cinque ME, Godin J, Mannava S, LaPrade
RF: Arthroscopic anatomic single-bundle anterior cruciate
ligament reconstruction using bone-patellar tendon-bone
autograft: Pearls for an accurate reconstruction. Arthrosc Tech
2017;6(4):e1159-e1167.
15. Wijdicks CA, Kennedy NI, Goldsmith MT, et al: Kinematic
analysis of the posterior cruciate ligament, part 2: A comparison
of anatomic single- versus double-bundle reconstruction. Am J
Sports Med 2013;41(12):2839-2848.
16. Chahla J, Williams BT, LaPrade RF: Posterior cruciate ligament.
Arthroscopy 2020;36(2):333-335. This review of posterior cruciate
ligament injuries and options for treatment summarizes current
concepts and evidence for interventions in knees with PCL
injuries.
17. Bonasia DE, Bruzzone M, De oni F, et al: Treatment of medial
and posteromedial knee instability: Indications, techniques, and
review of results. Iowa Orthop J 2012;32:173-183.
18. Levy BA, Dajani KA, Morgan JA, Shah JP, Dahm DL, Stuart MJ:
Repair versus reconstruction of the fibular collateral ligament
and posterolateral corner in the multiligament injured knee. Am J
Sports Med 2010;38(4):804-809.
19. Stannard JP, Brown SL, Farris RC, McGwin GJr, Volgas DA: The
posterolateral corner of the knee: Repair versus reconstruction.
Am J Sports Med 2005;33(6):881-888.
20. Lewallen L, McIntosh A, Dahm D: First-time patellofemoral
dislocation: Risk factors for recurrent instability. J Knee Surg
2015;28(4):303-309.
21. Arendt EA, Moeller A, Agel J: Clinical outcomes of medial
patellofemoral ligament repair in recurrent (chronic) lateral
patella dislocations. Knee Surg Sports Traumatol Arthrosc
2011;19(11):1909-1914.
C H AP T E R 4 4

Articular Cartilage of the Knee

Cassandra A. Lee MD, FAAOS

Dr. Lee or an immediate family member is a member of a speakers’ bureau or has made paid
presentations on behalf of Genzyme and Smith & Nephew and serves as a board member, owner,
officer, or committee member of the American Academy of Orthopaedic Surgeons, the American
Orthopaedic Society for Sports Medicine, and the Arthroscopy Association of North America.

ABSTRACT
Knee articular cartilage defects are commonly found incidentally
with a frequency of occurrence correlating to the age of the patient.
Articular cartilage tissue is highly organized with specific
biomechanical properties that make it difficult to re-create. Because
it is aneural and avascular, the innate healing potential is limited.
Symptomatic chondral defects present a clinical challenge to
manage, especially among athletes and other active patients.
Defects are associated with pain and functional impairment that
may progress toward joint degeneration and frank osteoarthritis.
When nonsurgical methodologies fail to improve symptoms,
surgical intervention can facilitate intrinsic repair or use external
factors to regenerate a functional tissue that allows for return to
activity.
Keywords: articular cartilage; cartilage regeneration; joint
preservation; orthobiologic agents

Introduction
Focal articular cartilage defects are common, often incidental
findings occurring in up to two-thirds of patients undergoing knee
arthroscopy. 1 When symptomatic cartilage lesions can cause
disability that is on the spectrum of knee osteoarthritis, with
symptoms ranging from pain and swelling to mechanical
symptoms such as locking and catching to functional impairment.
Osteoarthritis is irreversible and affects up to 35% of patients
between 50 and 59 years of age and increases to more than 55% in
individuals older than 70 years. It has been known since the Roman
era that cartilage is subject to injury, and it has been observed that
partial-thickness articular cartilage injuries cannot be repaired. 2
Articular cartilage lesions result from idiopathic, repetitive
microtrauma, or overt traumatic events. They are highly associated
with injuries such as anterior cruciate ligament tears, 3 meniscus
tears, patellar dislocation, 4 and malalignment. Lesions may appear
to affect only the overlying cartilage, but there is potential to affect
the underlying subchondral bone. Therefore, careful a ention
should be paid to the osteochondral unit as a whole. The natural
history of cartilage defects is not completely understood. Once the
osteochondral unit is damaged, altered joint contact forces may
occur on adjacent chondral surfaces and subchondral bone, leading
to a vicious cycle of propagating an inflammatory response with
release of cartilage degradative enzymes and further joint
degradation, eventually leading to and progressing toward
osteoarthritis. Surgical interventions are performed to decrease
symptoms, improve function, and alter the course and delay the
progression of joint degeneration. Understanding the connective
tissue’s unique biomechanical properties helps to dictate rationale
for treatment. Evaluation, diagnosis, and management of injuries
are discussed.

Microanatomy
Articular cartilage is a highly organized connective tissue with
complex biomechanical properties with substantial durability
whose purpose is to decrease forces through the joints. 5 The half-
life of type II collagen is estimated to be approximately 117 years,
which limits regenerative potential. Mature chondrocytes are
embedded in a structural framework of collagen and matrix,
possessing low anabolic and proliferative activities because of
limited vascular, nerve, and lymphatic supply. Nutrients to the
chondrocytes are delivered by interstitial fluid in a complex
interplay between the intact dense matrix and fluid flow, which
contribute to the biomechanical properties of cartilage as a
viscoelastic tissue. The healing potential for cartilage defects is
limited, and therefore spontaneous healing does not occur. Partial-
thickness tears do not heal, whereas full-thickness osteochondral
defects can fill to some degree with fibrocartilage scar tissue. The
fibrous repair tissue made up of type I collagen has decreased
stiffness with poor wear characteristics compared with native
tissue, often tending toward advancing degeneration and eventually
osteoarthritis.
Management of isolated chondral or osteochondral defects of the
knee can be difficult in young patients because activity, functional
demands, and expectations do not align with viability or longevity
of surgical treatments such as partial or total knee arthroplasty.

Diagnosis
It is challenging to ascertain whether to manage articular cartilage
defects that are found incidentally on advanced imaging or on
diagnostic arthroscopy. Determining if an articular cartilage lesion
is symptomatic may be even more difficult to ascertain when
patients have additional knee pathologies such as meniscus
insufficiency, malalignment, or ligamentous instability. Articular
cartilage defects do not have a specific finding on physical
examination but patients often present with pain and swelling. In
an isolated defect, an effusion may be present with preserved knee
motion. Patients may complain of possible locking of the knee if
there are displaced osteochondral fragments. In larger or bipolar
defects, more mechanical symptoms are present, such as catching
or clicking with knee motion. Examination to assess alignment and
ligamentous stability is also necessary.
Obtaining a detailed history may shed light on a traumatic
etiology such as a fall or twisting injury. Idiopathic or repetitive
microtrauma may present with an insidious onset of pain and
dysfunction.

Imaging
Weight-bearing radiographs such as AP views in full extension, PA
views in 45° of flexion, lateral and patellofemoral views, and full-
length hip-to-ankle AP views are essential to assess joint
degenerative changes, joint-space narrowing, and limb alignment.
Size markers are also necessary if sizing radiographs are obtained
to account for image magnification.
MRI is an effective tool in identifying cartilage lesions, with 3T
MRI showing greater diagnostic accuracy than 1.5T MRI. As
discussed in a 2020 study, cartilage-specific imaging protocols have
improved the quality of imaging, allowing for accurate assessment
of lesions preoperatively and monitoring cartilage after repair
procedures. 6 Intermediate-weighted images (T1-weighted, T2-
weighted, and proton-density–weighted) are most widely used for
visualizing chondral lesions, with proton density images having the
best results; images are directly correlated with the size and
location of the defect according to a 2019 study. More recently, T2
mapping, T1 rho, and diffusion-weighted imaging have been used
more for research rather than clinical use. Understanding the size
of a lesion is helpful in determining treatment options and
prognosis. MRI is also used to assess ligamentous and meniscal
structures for injury.
CT evaluates the subchondral bone as part of the osteochondral
unit. For the patellofemoral joint, the tibial tubercle–to–trochlear
groove distance is measured to determine the need for unloading
with an anteromedialization/medialization osteotomy. In focal,
distal, and lateral patellar lesions or medial, central, and/or
panpatellar cartilage pathology, an anteromedialization tibial
tubercle osteotomy is recommended. In cases of patellar instability
where the tibial tubercle is lateralized (tibial tubercle–to–trochlear
groove distance, >15 mm), medialization with a soft-tissue
stabilization procedure is recommended. When considering
surgical management of chondral defects of the patellofemoral
joint, addition of a tibial tubercle osteotomy results in good to
excellent patient-reported outcomes (PROs) directly correlating
with the size and location of defect, according to a 2019 study. 7 CT
arthrography can be used to assess the stability of an
osteochondritis dissecans lesion/fragment in cases where MRI is
not possible.

Nonsurgical Treatment Options

After an articular defect is determined to be symptomatic,
nonsurgical treatment begins with relative rest, activity
modification, and physical therapy for 3 to 6 months, focusing on
strengthening and stabilization. Oral anti-inflammatory
medications, nutraceutical agents (glucosamine, chondroitin
sulfate), and bracing treatment can also be used. An unloader brace
can be effective in cases with unilateral compartment overload due
to either malalignment or meniscus deficiency. Injectable therapies
such as steroids and/or viscosupplementation or orthobiologic
agents can be explored to decrease the inflammatory response and
improve symptoms. Orthobiologic agents include platelet-rich
plasma (PRP) and mesenchymal stem cells (MSCs) in the form of
bone marrow aspirate concentrate (BMAC) or stromal vascular
fraction (SVF). Many of these agents demonstrate promising early
results, but high-level randomized controlled trials are warranted to
determine if these agents are truly effective. If these measures fail
to provide acceptable pain relief, surgery may be indicated.

Orthobiologic Agents
Viscosupplementation is a procedure that uses hyaluronic acid,
which is a natural glycosaminoglycan that lubricates and provides
some shock absorption via action as an osmotic buffer in joints.
Meta-analyses of viscosupplementation for the management of
osteoarthritis have found statistically significant improvements in
PROs of pain, function, and stiffness, but none of these
improvements met the minimal clinically important improvement
thresholds. 8 , 9
PRP is an autologous plasma product that is a well-proven
treatment for osteoarthritis of the knee. 10 Once centrifuged and
processed, it contains approximately four to five times more
platelets than unprocessed blood while also containing thousands
of proteins including growth factors. It is the potential of these
growth factors and inflammatory mediators released by the
platelets in PRP that makes it so appealing for musculoskeletal
applications. However, because of the varied preparations for the
production of PRP, no standardization of product exists. Current
evidence suggests that direct injection of PRP into the joint can
control the inflammatory environment by preventing activation of
nuclear factor kappa B, 11 which inhibits synthesis of anabolic-
related genes such as type II collagen. PRP also exerts a potent anti-
inflammatory effect because of concentrated levels of interleukin-1
receptor antagonist 12 as well as other growth factor components
that help stimulate growth of autologous chondrocytes and MSCs
and components of the extracellular matrix via synthesis of
proteoglycans and collagen. 13
Many studies have reported positive effects of PRP on patients
with osteoarthritis, including patients who underwent arthroscopic
débridement and microfracture. 14 In trials comparing PRP versus
hyaluronic acid for the management of osteoarthritis, PRP had
longer and be er effectiveness in reducing pain and improving
function. 15 Overall, PRP has shown a tendency toward be er
efficacy in management of the early stages of osteoarthritis as well
as positive effects in the management of all stages of osteoarthritis.
16
 MSCs and growth factors can be derived from BMAC. It has a
higher concentration of chondrogenic cells, MSCs, and growth
factors in comparison to bone marrow itself that are theorized to
improve the healing response by decreasing apoptosis and
inflammation and activate cell proliferation and differentiation. The
mechanism by which BMAC affects osteoarthritis is unknown. In a
prospective placebo-controlled pilot study comparing BMAC with
saline in patients with bilateral knee osteoarthritis, no significant
difference in pain relief and function occurred between both sides.
17
Injection of BMAC with expanded MSCs is currently in phase I/II
clinical trials, and has been shown to have increased clinical and
functional efficacy compared with hyaluronic acid, with no adverse
effects in the long term (4 years follow-up). 18 Studies on BMAC
effects on focal full-thickness cartilage defects have reported more
favorable outcomes when combined with microfracture 19 or
embedded within a hyaluronic acid–based scaffold. 20
MSCs have demonstrated chondrogenic potential but require
special laboratory conditions and weeks for cell expansion.
Adipocyte MSCs secrete anti-inflammatory soluble factors that can
stop cartilage destruction and degradation but also possess
regenerative capacities. They can be derived from an abundant
supply that is easy to harvest with a minimally invasive liposuction
procedure. The lipoaspirate is mechanically or enzymatically
processed. The resultant SVF does not require tissue culture and
expansion; it contains a heterogeneous mixture of stem, progenitor,
and adult cells but not adipocytes and has a very low concentration
of leukocytes. 21 Adipocyte MSCs in SVF secrete soluble factors with
anti-inflammatory, immunomodulatory, and analgesic effects. SVF
is often suspended in PRP for delivery, with multiple case series
showing improved joint function and decreased pain scores with
limited evidence of improved cartilage thickness. 22 A 2020
randomized controlled trial has supported the use of SVF in the
management of knee osteoarthritis, significantly improving
symptoms for 12 months. 23
 Despite promising results in midterm relief of symptoms and
improvement of function, orthobiologics have yet to be consistently
shown to regenerate articular cartilage. 18 Surgical intervention may
provide the best long-term success for regenerating tissue, but
patient expectations should be realistic with regard to having to
undergo extensive rehabilitation and limitation of activity for an
extended period of time during the healing and regenerative
period.

Surgical Treatment Options

Surgical treatment should focus on removing the underlying cause
of inflammation and restoration of the osteochondral unit. The best
choice for a surgical procedure depends on lesion size, depth, and
location, with no clear algorithm existing for surgical decision
making. Traditionally, lesions considered treatable in patients
younger than 40 years are full-thickness lesions (Outerbridge grade
III to IV, or International Cartilage Repair Society grade 3 or 4; size,
>2 cm2). 24 Surgical strategies can be divided into palliative (eg,
chondroplasty, débridement) versus reparative (eg, microfracture,
drilling) versus restorative (eg, osteochondral autograft or allograft
transfer, autologous chondrocyte implantation [ACI]). Long-term
outcomes for these techniques are frequently debated. Realistic
expectations are crucial to patient outcomes.

Débridement and Chondroplasty

Arthroscopic débridement is commonly performed as a first-line
procedure. The goal of surgery is to reduce inflammatory mediators
by débriding unstable chondral flaps and removing loose bodies
within the joint, this may be ideal in patients with degenerative
joint disease, high body mass index, or those who are in-season
athletes. Because of the underlying chondral defect, symptomatic
improvement is often temporary.
Marrow Stimulation and Microfracture
Reparative procedures that penetrate the subchondral bone plate to
fill the cartilage defect with marrow elements and stimulate
fibrocartilaginous repair is known as marrow stimulation (Figures 1
and 2). Initially described as open Kirschner wire drilling of the
subchondral bone, marrow stimulation was refined from an open
technique to the less invasive microfracture arthroscopic technique.
Microfracture is considered the first-line treatment for chondral
defects of the knee because it is minimally invasive with li le
surgical morbidity and low cost. 25 It should be avoided when
subchondral bone deficiency is present. The cartilage defect is
identified under arthroscopic visualization. The edges of the lesion
are débrided to stable, vertical borders of healthy cartilage with
either an arthroscopic shaver or curet. The subchondral plate is
then penetrated with perpendicular holes 2 to 3 mm apart. Cells,
including MSCs, from the bone marrow fill the defect and mature
into a fibrocartilage clot with irregular type I collagen deposition
that has less capacity to resist shear forces when compared with
native cartilage. 26 Postoperatively, rehabilitation involves toe-touch
weight bearing for 6 to 8 weeks with progression toward full weight
bearing at 8 to 12 weeks. For patellofemoral lesions, patients can
bear weight with the knee locked in full extension in the brace.
Passive motion is introduced with the goal to return to full activity
around 6 to 9 months postoperatively.
Figure 1 Schematic drawings showing the microfracture technique.A, The
chondral defect is prepared to remove loose cartilage to stable vertical borders
with a curet. The calcified cartilage layer should be scraped to the level of the
subchondral bone, but to not violate the subchondral bone. B, The subchondral
bone plate is penetrated with an awl or Kirschner wire with 2 to 3 mm spacing
between punches and to a depth of 2 to 4 mm.

Figure 2 Arthroscopic images of the microfracture technique.A, The chondral

defect is prepared, removing loose chondral flaps and scraping the calcified
cartilage layer off to the subchondral bone plate. B, Microfracture holes are
made, spaced 2 to 3 mm apart and 2 to 4 mm deep.
 Short-term outcomes are often favorable for the microfracture
technique. Eighty percent of patients younger than 45 years who
underwent microfracture for management of traumatic full-
thickness defects with no meniscal or ligament injury were
improved at 7-year follow-up, with statistically significant
improvement in function and less pain when compared with
baseline. 25 When translated to modern PROs, clinical and
statistically significant improvements were seen in patients
undergoing microfracture at 5.7 years with males doing be er than
females and isolated femoral defects doing be er than tibial or
multisite lesions. Large lesions (>3.6 cm2) and prior knee surgery
predicted additional knee surgery after microfracture. 27
Smaller lesions respond be er to microfracture treatment in the
first 2 years. Because repair tissue is often fibrocartilage with only
up to 10% hyaline cartilage, durability is limited, resulting in
unpredictable functional outcomes and variable improvement in
symptoms in the longer term beyond 5 years. 28

Augmented Microfracture—Autologous
Matrix-Induced Chondrogenesis and BMAC
Implantation
It is thought that the inconsistency and suboptimal amount of
repair tissue may be due to instability of the fibrin clot that forms
from the marrow elements, which may shrink and detach as a result
of platelet-driven clot retraction. 29 To improve chondrogenic
differentiation and proliferation of the repair tissue, the
microfracture technique is augmented with synthetic or autologous
biologic adjuvants. Matrix-induced chondrogenesis combines
microfracture surgery with a synthetic matrix. In the case of
autologous matrix-induced chondrogenesis, the blood clot arising
from the marrow is covered by a bilayer collagen I/III membrane,
providing additional stability against shear forces within the joint
during motion. In a randomized controlled clinical trial, significant
clinical improvement for the first 2 years was seen in comparing
microfracture alone with that stabilized by the collagen membrane.
For midterm results, progressive degradation of function was
observed in the microfracture group, whereas the collagen
membrane supported group remained stable for 5 years of follow-
up. 30
Other materials have been studied to improve microfracture
outcomes, including a soluble polymer scaffold containing a
protein called chitosan that reinforces the clot by impeding
retraction. In an international multicenter randomized controlled
trial, MRI-evaluated repair tissue was significantly more similar to
native cartilage than microfracture alone over 5 years, although
PROs did not reflect the differences in repair tissue and were
similar between the two groups. 31
Orthobiologic adjuvants such as PRP, BMAC, and hyaluronic acid
have also been used to augment microfracture to improve
chondrogenic differentiation and proliferation.

Autologous Cultured Chondrocytes on

Porcine Collagen Membrane (Matrix-Induced
Autologous Chondrocyte Implantation)
Autologous cultured chondrocytes induce hyaline-like cartilage by
implantation of harvested and cultured chondrocytes. It is a two-
stage procedure requiring a diagnostic arthroscopy with cell biopsy
and open arthrotomy for implantation (Figures 3 and 4). The cell
biopsy is taken from a non–weight-bearing surface of the knee,
typically the superolateral edge of the lateral femoral condyle,
superomedial edge of the medial femoral condyle, or within the
intercondylar notch. The cells are then cultured, expanded, and
amplified in vitro over 4 to 6 weeks. Currently on the third
generation of the technique, each modification sought to improve
chondrocyte induction, conduction, and cellular and tissue
organization within the defect. From a historical perspective, the
first-generation ACI procedure used harvest of adjacent periosteum
that was sewn onto the articular cartilage around a defect to create a
watertight seal so that chondrocytes could be injected under the
periosteal patch. Because the periosteum was biologically active,
there was a significant rate of reoperation for graft hypertrophy,
reaching as high as 50%. The second generation of ACI eliminated
the periosteum harvest, instead using a porcine collagen membrane
that was also sutured to the adjacent articular cartilage to create a
watertight seal that chondrocytes could again be injected under.
The matrix-induced autologous chondrocyte implantation (MACI)
procedure is the third-generation iteration where the chondrocytes
are cultured directly onto a collagen matrix and then implanted.
Overall graft hypertrophy rate of MACI is approximately 5%. The
implantation phase requires a medial or lateral parapatellar
arthrotomy. Once the defect is identified, a custom cu er can be
placed over the lesion or vertical borders of healthy cartilage can be
created with a freehand cut using a new scalpel. The lesion is then
prepared using curets to scrape out the damaged cartilage through
the calcified cartilage layer down to subchondral bone. The implant
is placed cell-seeded side face down within the defect and fixed to
the subchondral bone with fibrin glue under digital pressure.
Figure 3 Schematic drawings showing the matrix-induced autologous
chondrocyte implantation (MACI) technique.A, In the first stage of the procedure,
a full-thickness cartilage biopsy is taken from the intercondylar region of the
lateral trochlea. B, In the staged implantation procedure, an arthrotomy is
performed. The chondral defect is prepared by removing any loose cartilage
flaps, establishing vertical stable native cartilage borders. The calcified cartilage
layer is also removed from the subchondral bone plate. C, A light layer of fibrin
glue is placed on the subchondral bone plate and the MACI membrane is placed
in the prepared bed. Light pressure is held for 3 minutes. A layer of fibrin glue is
used to secure the periphery of the patch to the cartilage.
 Figure 4 Photographs showing the matrix-induced autologous chondrocyte
implantation (MACI) technique.A, Full-thickness defect of the patella is shown. B,
After preparation of the defect, the MACI membrane is implanted and secured
with fibrin glue.

Postoperative rehabilitation consists of toe-touch weight bearing

for 4 to 6 weeks or weight bearing as tolerated in full extension,
depending on the lesion location along the femoral condyles/tibial
plateau or patellofemoral joint, respectively. Immediate passive
motion is started with use of a continuous passive motion machine
for 6 to 8 hours per day for the first 6 weeks postoperatively. As
discussed in a 2020 study, progressive rehabilitation is advanced
with running allowed at 6 to 9 months postoperatively. Return to
rigorous sports activity is allowed at 9 to 12 months. 32
Patients who have large full-thickness defects greater than 4 cm2
with no prior cartilage procedures and minimal subchondral bone
damage are indicated for this procedure. Patients undergoing ACI
who had prior microfracture had significantly higher failure rates
compared with patients who had ACI as a first-line treatment. 33 In
a prospective randomized controlled trial, patients with
symptomatic cartilage defects greater than 3 cm2 treated with
MACI had clinically and statistically significantly improved pain
and function as well as MRI evaluated improved filling of the defect
when compared with microfracture at 5 years. 34
Osteochondral Autograft Transfer or
Osteochondral Allograft Transplantation
Osteochondral grafts can fill full-thickness cartilage defects
immediately with a core of bone and mature hyaline articular
cartilage. Size of the lesion dictates whether an autograft or
allograft option should be used because of donor site morbidity. In
addition, if subchondral bone loss is present, osteochondral
autograft transfer (OAT) (Figure 5) should be considered for
smaller lesions and osteochondral allograft (OCA) transplantation
(Figure 6) should be performed for large lesions. For autograft,
bone and cartilage cores are obtained from relative non–weight-
bearing surfaces of the knee such as the notch or superolateral
trochlea. OCAs are obtained from size-matched, fresh cadaver
tissue and can be optimally matched to the patient’s lesion size.
Although chondrocyte viability is highest when the tissue is stored
at physiologic temperature, 35 fresh refrigerated allografts are used
as opposed to frozen or freeze-dried. Advancement in tissue
procurement, processing, and storage has increased availability and
popularity for allograft use in the management of large lesions. The
recommended time from procurement of graft to transplantation is
28 days, which correlates to chondrocyte viability of at least 70% at
the time of implantation. 36
 Figure 5 Schematic drawings showing the osteochondral autograft transfer
technique.A, The size of the chondral defect is determined. B, The donor
osteochondral cylinder is obtained from a relative non–weight-bearing surface of
the joint, typically at the intercondylar notch or lateral superior trochlea. C, Once
the recipient site is prepared, the osteochondral cylinder graft is inserted in the
recipient site using a press-fit technique.

Figure 6 Schematic drawing showing the osteochondral allograft transfer

technique.A, An arthrotomy is performed to expose the defect. The defect is then
measured. B, The defect site is then prepared to remove the damaged cartilage
by reaming to a depth of 8 to 10 mm into the subchondral bone. C, The same-
size plug is removed from a fresh allograft specimen. It is then prepared to
match the depth of the prepared recipient site. D, The donor cylinder plug is then
inserted into the prepared recipient site with press-fit technique.

Both OAT and OCA procedures require perpendicular access to

the cartilage surface either arthroscopically or mini-open so that the
donor plug is placed flush with the recipient site, re-creating the
normal articular contour and contact pressures. Aggressive
impaction of the chondral surface of the donor plug should be
minimized to avoid injury to chondrocytes. Postoperative
rehabilitation consists of toe-touch weight bearing for 4 to 8 weeks,
depending on the lesion location and number of osteochondral
cylinders placed. Progressive range of motion is encouraged, with
release to full activity at 4 to 6 months.
Up to 90% of patients undergoing osteochondral grafting obtain
good to excellent results up to 10 years postoperatively for lesions
managed in the femoral condyle or tibial plateau, thus being the
preferred management in these locations, especially when
subchondral bone is involved. 37 Minimizing donor site morbidity
and the limited availability of tissue make osteochondral autograft
transfer system (OATS) ideal for small to mid-size chondral or
osteochondral defects up to 4 cm2. However, lesions less than 2 cm2
managed with OATS are associated with superior outcomes.
Because of correlation of increased defect size and age with failure
as well as risk of donor site morbidity, OATS is indicated in a small
subset of patients who have small, unipolar lesions, neutral
alignment, and normal body mass index. 38
OCA can be used in the presence of subchondral bone damage or
loss and in cases of osteochondritis dissecans. OCA can also be
used as a salvage option for failed cartilage repair surgeries. The
survival rate of OCA is greater than 75% after 12.3 years and the
graft survival rate is 85% after 10 years. 39 For large lesions, a
snowman pa ern can be achieved with two intersecting plugs, but a
single plug may produce be er outcomes. Overall, OATS is
associated with limitations and lower long-term success rates,
whereas fresh OCA has been associated with 88% return to sport
and greater than 75% 10-year survival rates for management of
large femoral condyle lesions. 40

Future Directions
New advancements have sought to improve reparative and
regenerative tissue through development of biologic solutions in
the form of allografts, stem cells, and scaffolds. There are few
clinical trials and most data are from animal models.
Biologics have been investigated to optimize osteochondral
integration and incorporation. In a rabbit model, PRP injected in a
defect before OAT placement 41 and platelet-rich fibrin clots placed
into the graft site before OAT placement 42 resulted in improved
integration at the graft interface. Future understanding of BMAC
and PRP mechanisms may help to elucidate timing of using these
biologics as an adjuvant to optimize current grafting techniques.
Minced or particulated cartilage is a technique currently
undergoing clinical investigation for the management of focal
defects, both autologous or allogeneic options. Autologous use of
minced cartilage combined with a scaffold and fixed into the defect
size resulted in higher subjective outcomes and lower risk of intra-
lesional osteophyte when compared against microfracture, but is
currently no longer under investigation. It is known that juvenile
cartilage possesses higher chondrocyte density with superior
cellular activity compared with adult cartilage. Juvenile particulated
cartilage allograft has shown good fill of defects with hyaline-like
filling. 43 Midterm to long-term outcomes supporting the use of this
technology do not exist. Micronized allograft cartilage and
extracellular matrix combined with PRP has also been used as a
scaffold to augment microfracture procedures, providing a matrix
to improve the quality of healing tissue. When compared with
microfracture alone in an equine model, the augmented group had
significantly be er advanced imaging parameters for the repair
tissue. 44
Cryopreserved OCA equivalent implants have also become
available for clinical use. Cryopreservation allows for a longer shelf
life, thereby increasing availability of allografts that offer a
regenerative treatment of full-thickness chondral defects. The
allografts are often perforated or laser cut so that they are
malleable and can conform to match the defect. Animal studies
have shown promise, 45 but few clinical trials exist.
 Placenta-derived tissues are a known source of anti-inflammatory
and immunomodulatory factors. Amniotic suspension allograft
injection for the management of osteoarthritis was shown to have
be er efficacy in terms of patient-reported pain and activity level at
3 and 6 months when compared with hyaluronic acid or saline
injection in a 2019 multicenter randomized controlled trial. 46
Currently still experimental, phase III clinical trials are currently
underway.
For large chondral defects (2 to 4 cm2), OCA or MACI are
currently standard treatment options. However, novel scaffolds
have been developed for management of these challenging larger
defects, such as an acellular aragonite-based scaffold and a
hyaluronic acid–based scaffold with BMAC. The aragonite-based
scaffold is composed of inorganic calcium carbonate found in the
endoskeleton of coral and made into a cell-free, porous, resorbable
biphasic scaffold. In preclinical studies, the implant was resorbed
and replaced with trabecular bone and regenerated hyaline
cartilage. 47 Three-year outcomes data presented in a 2021 study
showed significant improvement in pain and function as well as
satisfactory osteointegration and restoration of the osteochondral
unit in patients implanted with the biphasic aragonite scaffold for
the management of medium-size chondral lesions of the knee (2.6
cm2 [range, 1.0 to 7.5 cm2]). 48 The product is newly FDA approved
for the management of International Cartilage Repair lesions grade
III or above ranging from 1 to 7 cm2 in joints without severe
osteoarthritis of the knee (Kellgren-Lawrence grade 0 to 3).
For the management of large lesions in the patellofemoral joint,
BMAC on a hyaluronic acid–based scaffold showed similar results
in improved clinical outcomes compared with MACI at 3 years 49
and be er outcomes compared with microfracture at 5 years. 20 This
is a single-stage procedure that has also been shown to improve
PROs with near-complete filling of the defects by MRI evaluation. 50
This product is not approved for use in the United States.
Summary
Articular cartilage is a complex tissue that has very li le innate
ability to heal and regenerate. Basic science discoveries will help
advance methods to improve repairing and regenerative chondral
tissue in this rapidly evolving emerging field. New innovations and
surgical technique evaluation will alter treatment algorithms as the
ultimate goal is toward the prevention or delay of osteoarthritis.

Key Study Points

Articular cartilage is a highly organized connective tissue with complex
biomechanical properties that often deteriorates with idiopathic, repetitive
microtrauma, or traumatic events.
Imaging workup should include plain standing radiographs of the knees, scanogram
of the hip to ankle, MRI, and possibly CT to assess alignment, stability, location of
the defect, and alignment.
Orthobiologic agents are used to decrease inflammation and improve symptomatic
articular cartilage lesions. These include hyaluronic acid, PRP, and MSCs (BMAC
and SVF).
Surgical intervention for chondral defects should take into consideration the
osteochondral unit. Reparative techniques include microfracture, which can include
a scaffold to augment the repair tissue. Regeneration of the chondral surface can be
achieved with cell-based treatments such as MACI or transfer of osteochondral
tissue, either autograft or allograft.
Future directions include exploring biologic solutions in the form of allografts, stem
cells, or scaffolds.

Annotated References
1. Curl WW, Krome J, Gordon ES, Rushing J, Smith BP, Poehling
GG: Cartilage injuries: A review of 31,516 knee arthroscopies.
Arthroscopy 1997;13(4):456-460.
2. Hunter W: Of the structure and disease of articulating cartilages:
1743. Clin Orthop Relat Res 1995;317:3-6.
3. Kessler MA, Behrend H, Henz S, Stu G, Rukavina A, Kuster
MS: Function, osteoarthritis and activity after ACL-rupture: 11
 years follow-up results of conservative versus reconstructive
treatment. Knee Surg Sport Traumatol Arthrosc 2008;16(5):442-448.
4. Farr J, Covell DJ, La erman C: Cartilage lesions in
patellofemoral dislocations: Incidents/locations/when to treat.
Sports Med Arthrosc 2012;20(3):181-186.
5. Simon TM, Jackson DW: Articular cartilage: Injury pathways and
treatment options. Sports Med Arthrosc Rev 2006;14:146-154.
6. Fri RC, Chaudhari AS, Boutin RD: Preoperative MRI of
articular cartilage in the knee: A Practical Approach. J Knee Surg
2020;33(11):1088-1099. Articular cartilage can be evaluated with
high accuracy using MRI preoperatively in patients undergoing
surgical intervention. The article describes MRI findings of
normal articular cartilage as well as characteristics for lesions
that are amenable to surgical intervention. Future directions of
MRI with regard to articular cartilage are discussed. Level of
evidence: IV.
7. Sherman SL, Humpherys J, Farr J: Optimizing patellofemoral
cartilage restoration and instability with tibial tubercle
osteotomy. Arthroscopy 2019;35(8):2255-2256. Tibial tubercle
osteotomy is used to address a variety of patellofemoral
pathology including patellar instability or addressing focal
cartilage defects. The osteotomy can alter patellar tracking and
joint contact pressures within the patellofemoral compartment.
Specific types of osteotomies may be indicated for specific lesions
of the joint. Clinical studies have shown good to excellent results
in the long term when osteotomy is performed for instability.
With regard to chondral defects and osteotomy, outcomes are
related to the size and location of the defect. Level of evidence:
IV.
8. American Academy of Orthopaedic Surgeons: Treatment of
Osteoarthritis of the Knee – 2nd Edition Evidence-Based Clinical
Practice Guideline. 2013. h ps://www.aaos.org/globalassets/quality-
and-practice-resources/osteoarthritis-of-the-knee/osteoarthritis-
of-the-knee-2nd-editiion-clinical-practice-guideline.pdf.
 9. Jevsevar D, Donnelly P, Brown GA, Cummins DS:
Viscosupplementation for osteoarthritis of the knee: A
systematic review of the evidence. J Bone Joint Surg Am
2015;97(24):2047-2060.
10. Cole BJ, Karas V, Hussey K, Pilz K, Fortier LA: Hyaluronic acid
versus platelet-rich plasma: A prospective, double-blind
randomized controlled trial comparing clinical outcomes and
effect on intra-articular biology for the treatment of knee
osteoarthritis. Am J Sports Med 2017;45(2):339-346.
11. Sun Y, Feng Y, Zhang CQ, Chen SB, Cheng XG: The regenerative
effect of platelet-rich plasma on healing in large osteochondral
defects. Int Orthop 2010;34(4):589-597.
12. Bendinelli P, Ma eucci E, Doglio i G, et al: Molecular basis of
anti-inflammatory action of platelet-rich plasma on human
chondrocytes: Mechanisms of NF-κB inhibition via HGF. J Cell
Physiol 2010;225(3):757-766.
13. Kruger JPHS, Endres M, Pruss A, Siclari A, Caps C: Human
platelet-rich plasma stimulates migration and chondrogenic
differentiation of human subchondral progenitor cells. J Orthop
Res 2012;30(6):845-852.
14. Gobbi A, Karna ikos G, Mahajan V, Malchira S: Platelet-rich
plasma treatment in symptomatic patients with knee
osteoarthritis: Preliminary results in a group of active patients.
Sports Health 2012;4(2):162-172.
15. Chang KV, Hung CY, Aliwarga , Wang TG, Han DS, Chen WS:
Comparative effectiveness of platelet-rich plasma injections for
treating knee joint cartilage degenerative pathology: A systematic
review and meta-analysis. Arch Phys Med Rehabil 2014;95(3):562-
575.
16. Cook CS, Smith PA: Clinical update: Why PRP should be your
first choice for injection therapy in treating osteoarthritis of the
knee. Curr Rev Musculoskelet Med 2018;11(4):583-592.
17. Shapiro SA, Kazmerchak SE, Heckman MG, Zubair AC,
O’Connor MI: A prospective, single-blind, placebo-controlled
 trial of bone marrow aspirate concentrate for knee osteoarthritis.
Am J Sports Med 2017;45:82-89.
18. Lamo-Espinosa JM, Mora G, Blanco JF, et al: Intra-articular
injection of two different doses of autologous bone marrow
mesenchymal stem cells versus hyaluronic acid in the treatment
of knee osteoarthritis: Long-term follow up of a multicenter
randomized controlled clinical trial (phase I/II). J Transl Med
2018;16(1):213.
19. Gigante A, Cecconi S, Calcagno S, Busilacchi A, Enea D:
Arthroscopic knee cartilage repair with covered microfracture
and bone marrow concentrate. Arthrosc Tech 2012;1:e175-e180.
20. Gobbi A, Whyte GP: Long-term clinical outcomes of one-stage
cartilage repair in the knee with hyaluronic acid–based scaffold
embedded with mesenchymal stem cells sourced from bone
marrow aspirate concentrate. Am J Sports Med 2019;47:1621-1628.
Twenty-three patients with full-thickness chondral defects
underwent a single-stage restoration procedure of a hyaluronic
acid–based scaffold embedded with BMAC. They were followed
prospectively for a minimum of 6 years reporting Tegner,
International Knee Documentation Commi ee, visual analog
scale, and Knee Injury and Osteoarthritis Outcome Score. Long-
term good to excellent clinical outcomes were noted regardless of
small or large, single or multifocal lesions in one to two
compartments of the knee. Patients older than 45 years also had
good outcomes. Level of evidence: IV.
21. Yoshimura K, Shiguera T, Matsumoto D, et al: Characterization
of freshly isolated and cultured cells derived from the fa y and
fluid portions of liposuction aspirates. J Cell Physiol
2006;208(1):64-76.
22. Koh YG, Choi YJ, Kwon SK, Kim YS, Yeo JE: Clinical results and
second-look arthroscopic findings after treatment with adipose-
derived stem cells for knee osteoarthritis. Knee Surg Sports
Traumatol Arthrosc 2015;23:1308-1316.
23. Garza JR, Campbell RE, Tjoumakaris FP, et al: Clinical efficacy
of intra-articular mesenchymal stromal cells for the treatment of
knee osteoarthritis: A double-blinded prospective randomized
controlled clinical trial. Am J Sports Med 2020;48(3):588-598. In a
multisite prospective double-blind randomized placebo-
controlled clinical trial, adult patients with symptomatic knee
osteoarthritis received either high-dose SVF, low-dose SVF, or
placebo in a 1:1:1 randomization ratio. SVF was proceeded by
obtaining tissue via liposuction, processed, and injected in the
same visit. The Western Ontario and McMaster Universities
Osteoarthritis Index was obtained before injection and 6 and 12
months after injection. Intra-articular SVF injection significantly
decreased knee osteoarthritis symptoms and pain for at least 12
months with no serious adverse events reported. Improvements
were dose dependent.
24. Mandelbaum BR, Brown JE, Fu F, et al: Articular cartilage
lesions of the knee. Am J Sports Med 1998;26:853-861.
25. Steadman JR, Briggs KK, Rodrigo JJ, Kocher MS, Gill TJ, Rodkey
WG: Outcomes of microfracture for traumatic chondral defects of
the knee: Average 11-year follow-up. Arthroscopy 2003;19(5):477-
484.
26. Lee YH, Suzer F, Thermann H: Autologous matrix-induced
chondrogenesis in the knee: A review. Cartilage 2014;5:145-153.
27. Weber AE, Locker PH, Mayer EN, et al: Clinical outcomes after
microfracture of the knee: Midterm follow-up. Orthop J Sports
Med 2018;6(2):1-7.
28. Mithoefer K, McAdams T, Williams RJ, Kreuz PC, Mandelbaum
BR: Clinical efficacy of the microfracture technique for articular
cartilage repair in the knee: An evidence-based systematic
analysis. Am J Sports Med 2009;37:2053-2063.
29. Johnson LL: Characteristics of the immediate postarthroscopic
blood clot formation in the knee joint. Arthroscopy 1991;7:14-23.
30. Volz M, Schaumburger J, Frick H, Gri a J, Anders S: A
Randomized controlled trial demonstrating sustained benefit of
 autologous matrix-induced chondrogenesis over microfracture at
five years. In Orthop 2017;41(4):797-804.
31. Shive MS, Stanish WD, McCormack R, et al: BST-CarGel®
treatment maintains cartilage repair superiority over
microfracture at 5 years in a multicenter randomized controlled
trial. Cartilage 2015;6(2):62-72.
32. Flanigan DC, Sherman SL, Chilelli B, et al: Consensus on
rehabilitation guidelines among orthopedic surgeons in the
United States following use of third-generation articular cartilage
repair (MACI) for treatment of knee cartilage lesions. Cartilage
2020;30:1947603520968876. Based on current rehabilitation
protocol, literature review, and discussion with orthopaedic
surgeons, a consensus in rehabilitation practice following MACI
was reached among a panel of US orthopaedic surgeons. Time to
full weight bearing was immediate for patellofemoral patients,
and 7 to 9 weeks in tibiofemoral patients. Range of motion to 90°
should be achieved by week 4 and advanced as tolerated with the
goal being full range of motion around week 7 to 9. A range of
time to return to activities of daily living, work, and sports was
dependent on size and location of the lesion and patient
characteristics. Level of evidence: II.
33. Pestka JM, Bode G, Salzmann G, Südkamp NP, Niemeyer P:
Clinical outcome of autologous chondrocyte implantation for
failed microfracture treatment of full-thickness cartilage defects
of the knee joint. Am J Sports Med 2012;40(2):325-331.
34. Bri berg M, Recker D, Ilgenfri J, Saris DBF, SUMMIT
Extension Study Group: Matrix-applied characterized autologous
cultured chondrocytes versus microfracture: Five-year follow-up
of a prospective randomized trial. Am J Sports Med
2018;46(6):1343-1351.
35. Bugbee WD, Convery FR: Osteochondral allograft
transplantation. Clin Sports Med 1999;18:67-75.
36. Cook JL, Stannard JP, Stoker AM, et al: Importance of donor
chondrocyte viability for osteochondral allografts. Am J Sports
 Med 2016;44(5):1260-1268.
37. Hangody L, Fules P: Autologous osteochondral mosaicplasty for
the treatment of full-thickness defects of the weight-bearing
joints: Ten years of experimental and clinic experience. J Bone
Joint Surg Am 2003;85-A(suppl 2):25-32.
38. Pareek A, Reardon PJ, Maak TG, levy BA, Stuart MJ, Krych AJ:
Long-term outcomes after osteochondral autograft transfer: A
systematic review at mean follow-up of 10.2 years. Arthroscopy
2016;32:1174-1184.
39. Assenmacher AT, Pareek A, Reardon PJ, Macalena JA, Stuart
MJ, Krych AJ: Long-term outcomes after osteochondral allograft:
A systematic review at long-term follow-up of 12.3 years.
Arthroscopy 2016;32(10):2160-2168.
40. Nielsen ES, McCauley JC, Pulido PA, Bugbee WD: Return to
sport and recreational activity following osteochondral allograft
transplantation in the knee. Am J Sports Med 2017;45(7):1608-1614.
41. Altan E, Aydin K, Erkocak O, Senaran H, Ugras S: The effect of
platelet-rich plasma on osteochondral defects treated with
mosaicplasty. Int Orthop 2014;38:1321-1328.
42. Maruyama M, Satake H, Suzuki T, et al: Comparison of the
effects of osteochondral autograft transplantation with platelet-
rich plasma or platelet-rich fibrin on osteochondral defects in a
rabbit model. Am J Sports Med 2017;45:3280-3288.
43. Farr J, Tabet SK, Margerrison E, Cole B: Clinical, radiographic,
and histological outcomes ater cartilage repair with particulated
juvenile articular cartilage: A 2-year prospective study. Am J
Sports Med 2014;42:1417-1425.
44. Cole BJ, Fortier LA, Cook JL, Cross J, Chapman H, Roller B: The
use of micronized allograft articular cartilage (BioCartilage) and
platelet rich plasma to augment marrow stimulation in an equine
model of articular cartilage defects. Orthop J Sports Med 2015;3(7
suppl 2):2325967115S00044.
45. Geraghty S, Kuang JQ, Yoo D, Leroux-Williams M, Vangsness
CT, Danilkovich A: A novel cryopreserved, viable osteochondral
 allograft designed to augment marrow stimulation for articular
cartilage repair. J Orthop Surg Res 2015;10:66-78.
46. Farr J, Gomoll AH, Yanke AB, Strauss EJ, Mowry KC, ASA Study
Group: A randomized controlled single-blind study
demonstrating superiority of amniotic suspension allograft
injection over hyaluronic acid and saline control for modification
of knee osteoarthritis symptoms. J Knee Surg 2019;32(11):1143-
1154. The study is pilot data from 200 patients enrolled in a
multicenter randomized controlled trial on amniotic suspension
allograft versus saline versus hyaluronic acid (1:1:1) for the
management of knee osteoarthritis. PROs were collected to
include Knee Injury and Osteoarthritis Outcome Score, visual
analog scale, Tegner, and quality-of-life measures. Patients
receiving amniotic suspension allograft had significantly greater
improvements in PROs from baseline compared with hyaluronic
acid and saline. Level of evidence: II.
47. Kon E, Filardo G, Robinson D, et al: Osteochondral regeneration
using a novel aragonite-hyaluronate bi-phasic scaffold in a goat
model. Knee Surg Sports Traumatol Arthrosc 2014;22(6):1452-1464.
48. Van Genecthen W, Vuylsteke K, Struijk C, Swinnen L, Verdonk
P: Joint surface lesions in the knee treated with an acellular
aragonite-based scaffold: A 3-year follow-up case series. Cartilage
2021;13(1 suppl):1217S-1227S. Thirteen patients underwent
treatment for a distal femur chondral defect with a cell-free
aragonite-based scaffold. Safety and clinical outcomes were
measured prospectively for 3 years. The primary measure of Knee
Injury and Osteoarthritis Outcome Score pain improved
significantly at 12 and 36 months postimplantation. There was
evidence of integration and remodeling of the implant without
adverse events. Level of evidence: IV.
49. Gobbi A, Chaurasia S, Karna ikos G, Nakamura N: Matrix-
induced autologous chondrocyte implantation versus
multipotent stem cells for the treatment of large patellofemoral
chondral lesions: A nonrandomized prospective trial. Cartilage
2015;6(2):82-97.
50. Gobbi A, Sco i C, Karna ikos G, Mudhigere A, Castro M,
Pere i GM: One-step surgery with multipotent stem cells and
hyaluronan-based scaffold for the treatment of full-thickness
chondral defects of the knee in patients older than 45 years. Knee
Surg Sports Traumatol Arthrosc 2017;25(8):2494-2501.
C H AP T E R 4 5

Meniscal Pathology, Repair, and

Transplant
Jocelyn Wittstein MD, FAAOS, Kendall Bradley MD, Alison
Toth MD, FAAOS

Dr. Wittstein or an immediate family member serves as a board member, owner, officer, or
committee member of the American Orthopaedic Society for Sports Medicine and the Arthroscopy
Association of North America. Dr. Toth or an immediate family member is a member of a
speakers’ bureau or has made paid presentations on behalf of Vericel Corporation; serves as a
paid consultant to or is an employee of Vericel; has received nonincome support (such as
equipment or services), commercially derived honoraria, or other non–research-related funding
(such as paid travel) from Arthrex, Inc., Breg, Mitek, Smith & Nephew, and Stryker; and serves
as a board member, owner, officer, or committee member of the American Orthopaedic Society for
Sports Medicine. Neither Dr. Bradley nor any immediate family member has received anything of
value from or has stock or stock options held in a commercial company or institution related
directly or indirectly to the subject of this chapter.

ABSTRACT
To provide the best treatment options for patients with meniscus
tears, it is important to review the recent literature on meniscal
pathoanatomy, surgical indications in the pediatric and adult
population, outcomes of repair techniques for various tear pa erns,
and allograft transplantation. Indications for repair have expanded
to include radial, root, and cleavage tears. Surgeons should also be
knowledgeable about the indications for repair of and
pathoanatomy of medial meniscus ramp lesions, and outcomes of
meniscal allograft transplant.
Keywords: cleavage tear; meniscal allograft; meniscus tear; ramp
lesion; root tear
Introduction
Management of meniscus tears has taken a divergent path, with
fewer indications for arthroscopic débridement of degenerative
meniscus tears, yet increased emphasis on repair of many defined
tear pa erns. With advances in arthroscopic techniques and
implants, indications for meniscus repair have expanded far
beyond peripheral longitudinal tears. Recent studies support repair
of radial and horizontal cleavage tear pa erns that were once
indicated for débridement. The understanding of both root tear and
ramp lesions and indications for surgical repair has also greatly
expanded. Meniscal allograft transplant remains a viable option for
the unsalvageable meniscus.

Anatomy
Meniscal anatomy has been well described, including meniscal
morphology, variability in a achment sites, and vascularity
originating in the periphery and penetrating the outer two-thirds.
Recent anatomic studies have contributed to a deeper
understanding of capsular and ligamentous a achments about the
medial and lateral menisci.
A 2019 cadaver study examined the posterior a achments to the
medial meniscus. 1 The authors found that the meniscofemoral and
meniscotibial ligaments converged at a common a achment point
on the posterior horn of the medial meniscus. The meniscotibial
ligament a ached to the tibia approximately 6 mm distal to the
posterior chondral surface of the tibial plateau and blended with
the meniscocapsular a achment as it inserted on the posterior horn
(Figure 1). These data may aid in understanding of pathoanatomy
and repair of ramp lesions.
 Figure 1 A and B, Photograph and illustration showing sagittal view of the
posteromedial meniscus anatomy. MTL = meniscotibial ligament, PHMM =
posterior horn of the medial meniscus.(Reproduced with permission from
DePhillipo NN, Moatshe G, Chahla J, et al: Quantitative and qualitative
assessment of the posterior medial meniscus anatomy: defining meniscal ramp
lesions. Am J Sports Med 2019;47[2]:372-378, Figure 2, p. 374.)

A 2019 study of the posterolateral meniscal anatomy defined the

lateral meniscotibial ligament and popliteomeniscal fascicle
a achments. 2 The mobility of the lateral meniscus is evident in its
anatomy, with the lateral meniscotibial a achment extending less
lateral than the superior capsular a achment and only the superior
and inferior popliteomeniscal fascicles a aching to the meniscus in
the region of the popliteal hiatus in absence of capsular a achment
(Figure 2).
 Figure 2 Illustration of the attachments to the posterolateral meniscusincluding
the meniscotibial ligament, posteroinferior popliteomeniscal fascicle (PIF), the
posterosuperior popliteomeniscal fascicle (PSF), and the anterosuperior
popliteomeniscal fascicle (ASF). ACM = tibial articular cartilage margin, aMFL =
anterior meniscofemoral ligament, FCL = fibular collateral ligament, PCL =
posterior cruciate ligament, pMFL = posterior meniscofemoral ligament.
(Reproduced with permission from Aman ZS, DePhillipo NN, Storaci HW, et al:
Quantitative and qualitative assessment of posterolateral meniscal anatomy:
Defining the popliteal hiatus, popliteomeniscal fascicles, and the lateral
meniscotibial ligament. Am J Sports Med 2019;47[8]:1797-1803, Figure 2, p.
1800.)

Imaging
MRI is the modality of choice in the preoperative detection of
meniscal tears. A 2021 meta-analysis evaluating the diagnostic
accuracy of MRI in detection of medial and lateral tears found that
MRI was slightly more accurate for medial-sided tears. 3 This may
be due to greater presence of concomitant injury and complexity of
meniscal a achments about the lateral meniscus. Sensitivity and
specificity for medial tears were 92% and 90%, respectively, versus
80% and 95% in lateral tears.
MRI is also used for preoperative planning and counseling. A
2019 study comparing decision for repair with MRI review only
versus intraoperative decision making found moderate agreement
on tear repairability when looking at all tear types. 4 When looking
specifically at vertical tears and bucket-handle tears, there was 92%
and 90% accuracy for repairability. The mean distance from the
meniscocapsular junction to tear site was 4.1 ± 1.3 mm in tears,
given a repairable decision. When considering repair decisions for
all tear types, it is likely that other factors contribute, including tear
type, chronicity, and activity level.

Nonsurgical Management
It has become increasingly apparent that surgical treatment for the
degenerative meniscus tear is a second-line treatment, particularly
in the se ing of osteoarthritis. A study of 20-year outcomes of
arthroscopic partial meniscectomy in patients aged 50 to 70 years at
time of surgery noted a 15.7% conversion rate to total knee
arthroplasty (TKA), with risk associated with degree of
osteoarthritis at the time of surgery, older age, malalignment, and
lateral meniscal resection. 5 This study suggests arthroscopic partial
meniscectomy should be avoided in the se ing of degenerative
joint disease and other risk factors for poor outcome. The European
Society of Sports Traumatology, Knee Surgery, and Arthroscopy
(ESSKA) 2016 Meniscus Consensus Project noted that arthroscopic
partial meniscectomy for degenerative meniscus tears should be
used as a second-line treatment only after 3 months of failed
nonsurgical treatment with persistent pain or mechanical
symptoms with positive MRI findings and minimal degenerative
joint disease noted on radiographs. 6
 A 2021 study of rates of meniscus débridement and repair in
American Board of Orthopaedic Surgery Part II examinees revealed
that the number of meniscal débridements declined by 60% from
2011 to 2017, with trends toward greater numbers of meniscus
repairs by sports medicine specialists and in patients younger than
30 years and age 30 to 50 years. Meniscal débridement was noted to
decrease in frequency in all age groups, including those older than
50 years. 7 Outcomes of débridement of degenerative meniscus
tears combined with greater understanding of the progression of
knee arthritis in knees with degenerative tears may have influenced
declines in surgical management for degenerative meniscus tears.

Surgical Management
Surgical management of meniscus tears is largely dictated by tear
pa ern and presence or absence of significant osteoarthritis.
Arthroscopic partial meniscectomy is indicated for unstable inner
third white zone tears in the se ing of lesser degrees of
osteoarthritis. The ESSKA 2019 consensus statement on traumatic
meniscus tears notes that repair is the primary recommendation
whenever possible because of the be er clinical and radiographic
outcomes associated with preservation over partial meniscectomy.
The authors did not find strong evidence to support needling or
application of platelet-rich plasma as augmentation for repair, but
noted indications for meniscus repair have expanded to include
tear types previously not repaired. 8 Surgical repair of various tear
types, pediatric meniscus tears, and meniscal transplantation are
reviewed in the following paragraphs.

Bucket-Handle Tears
The gold standard for repair of bucket-handle tears in the red-white
or red zone of the meniscus has been inside-out repairs, but
increasingly all-inside techniques have been used with mixed
results. A 2021 systematic review and meta-analysis revealed an
overall failure rate of 14.8% for arthroscopic repairs of bucket-
handle tears, and identified only medial-sided tears and tears
performed in isolation rather than with ACL reconstruction as
relative risks for failure of repair. 9 The overall failure rate is far less
than reported in a prior systematic review of bucket-handle repairs
that was limited to all-inside implants and did not include inside-
out repairs, which found a 29.3% failure rate. The higher failure rate
may be due to inclusion of older all-inside implant types that had a
high failure rate. 10 Although a significant difference was not
detected for failure rate between all-inside versus inside-out repairs
in the 2021 meta-analysis, a trend toward more failures in the all-
inside repairs was noted. Additionally, bucket-handle tears had a
significantly higher failure rate than simple longitudinal repairs,
but a similar rate when compared with simple radial or horizontal
repairs. 9 A 2019 review of factors predictive of failure of meniscus
repair that included bucket-handle tears as well as simple repairs
found concomitant ACL reconstruction to be a protective factor for
meniscal healing, but it is unclear how generalizable these findings
are to bucket-handle tears. 11
Additionally, a systematic review of studies comparing inside-out
with all-inside repairs included both bucket-handle and simple
repairs, but excluded meniscal arrows and screws, thus including
only modern all-inside implants. 12 This study found no difference
in outcomes between all-inside repair and inside-out repair
including clinical and anatomic failure rates, functional outcome
scores, and complication rates. Clinical failure was noted to be 11%
versus 10% and anatomic failure to be 13% versus 16% for inside-
out versus all-inside repairs, respectively. A 2021 MRI follow-up
study looking at a series of all-inside bucket-handle repairs 2 years
postoperatively found 90% healed and 10% had recurrent bucket-
handle tears. The authors suggest that 90% healing on MRI with
10% anatomic failure is similar to results a ained with inside-out
repair. 13 High-quality studies are particularly lacking for
comparisons of all-inside and inside-out repairs of bucket-handle
tears.
Root Tears
Meniscal root tears have become an increasing area of interest.
Medial and lateral meniscal root tears present differently. Medial
tears occur more often in older patients, with a higher body mass
index, and with more evidence of baseline osteoarthritis. 14 Lateral
meniscal root tears are more likely to occur in the se ing of
concomitant ligament injury and demonstrate less extrusion on
MRI. 14 The meniscus root is an essential component in maintaining
the hoop stresses. There is increasing evidence that meniscal root
repair in patients should be the standard of care. In the absence of
subchondral collapse, greater than 2 cm2 grade 3+ chondral defects,
Kellgren-Lawrence grade of 3 to 4, malalignment greater than 5°,
and instability, meniscal root repair has been found to be effective
at avoiding progression to TKA. In a 2020 study, control patients
matched by age, sex, and Kellgren-Lawrence grade reported 60% of
meniscectomies progressed to TKA at an average of 74 months,
compared with 26.7% of nonsurgical treatment and zero meniscal
root repairs. 15 This study also showed less progression of arthritis.
A 2021 systematic review found that repair improves functional
outcomes scores (Lysholm, Hospital for Special Surgery,
International Knee Documentation Commi ee, and Tegner) and
slows progression, but does not prevent osteoarthritis. 16
Beyond the clinical effectiveness of meniscus root repair
compared with either débridement or nonsurgical treatment, it has
also been found to be cost-effective. In a 2019 meta-analysis of
patients with medial meniscus root tears at 10 years, the cost was
$22,590, compared with $31,528 for meniscectomy and $25,006 for
nonsurgical treatment. 17 In 53% of patients with meniscus repairs,
osteoarthritis subsequently developed, and 33.5% required TKA,
compared with 99.3% of patients with meniscectomies progressing
to osteoarthritis and 51.5% requiring TKA. 17
Although a great deal of emphasis is placed on the prevention of
the progression of osteoarthritis, the meniscus root is also an
important secondary stabilizer to the anterior cruciate ligament
(ACL). In a 2020 study, a posterior medial root tear was found to
increase force on the graft, whereas repair of the tear was not
statistically significant from the intact state. 18 This force on the
graft was further increased in the se ing of increased posterior
tibial slope.

Radial Tears
Radial tears have traditionally been believed to be difficult to
successfully repair. However, more recently there has been a
greater impetus to repair these tears. A 2021 systematic review of 12
studies of 243 tears with a mean follow-up of 35 months noted good
healing or partial healing rates as assessed by second-look
arthroscopy or MRI (62% and 30%, respectively). Patient-reported
outcomes were also improved postoperatively. 19 The repair of
radial tears in the se ing of ACL repair has similar outcomes to
ACL repair without meniscus injury with no significant differences
in pain, range of motion, KT-1000 arthrometer evaluation, or
radiographs at 2 years postoperatively. 20 The 2019 ESSKA
recommends repair of the tears in zone 1 and 2 with or without
ACL repair, and that partial meniscectomy should only be
considered when repair is not possible. 8
There continues to be debate over the best method of repair of
these tears. A 2020 laboratory study of 30 fresh-frozen porcine
meniscus tears were repaired using inside-out and all-inside repair
techniques and underwent cyclic loading and load to failure testing.
The all-inside, all-suture construct performed the best in terms of
displacement under cyclic load and it was comparable to an inside-
out technique. 21 The inside-out technique had the best load to
failure but was not significantly different than the all-inside all-
suture technique. The anchor hybrid repair construct performed
the worst. 21

Horizontal Cleavage Tears

Symptomatic horizontal cleavage tears in the absence of significant
osteoarthritis have been shown to benefit from repair. A 2019 study
assessed Knee Injury and Osteoarthritis Outcome Score and
International Knee Documentation Commi ee scores 8.5 years
after partial meniscectomy to remove flap tears combined with
repair of the cleavage tear component, and noted good results with
a 15% reoperation rate for failed repairs. This study included
younger patients with a median age of 28 years. 22 A 2020 study with
mean patient age of 47 years and mean 3-year follow-up found
complex horizontal medial tears repaired with fibrin clot and
preservation of associated flap tears were associated with 75%
healing rate. Failure was associated with varus malalignment. The
authors concluded that well-aligned knees benefit from medial
meniscus complex horizontal repairs with incorporation of a fibrin
clot. 23

Ramp Lesions of the Medial Meniscus

Medial meniscal ramp lesions are associated with ACL tears and
have been described as sometimes hidden lesions at the
meniscocapsular junction or a tear of the meniscotibial ligament.
Indications for repair are debated in current literature. A 2019
cadaver biomechanical study found no difference in kinematics, in
situ forces in the ACL, and bone contact forces in the medial and
lateral compartments in knees without and with a 25-mm ramp
lesion. 24 In contrast, a 2020 consecutive series of ACL
reconstructions identified ramp lesions in 10% of cases (10 knees)
and noted increased anterior translation on side-to-side KT-2000
arthrometer evaluation versus ACL torn knees without ramp
lesions. The authors noted 4 of 10 cases to be stable, and 6 of 10 to
be unstable and repaired the unstable lesions only. Stable lesions
were noted to be subcentimeter in length. Knees with ramp lesions
were noted to present more chronically with delayed
reconstruction. 25
 Surgical decision making at the time of arthroscopy is dependent
on stability of the posterior horn. A 2020 series of medial meniscus
ramp lesions with ACL tears found that nontreatment of stable
ramp lesions resulted in similar subjective outcomes and revision
surgery rate as ACL reconstructed knees without ramp lesions, and
that repair of unstable ramp lesions resulted in similar subjective
outcomes, but higher reoperation rate. 26 ACL rerupture was not
related to presence of ramp lesions. The authors suggest repair of
stable ramp lesions likely has no clinical benefit.

Pediatric Meniscus Tears

There has been increasing awareness of meniscal injury in children
beyond that of the discoid meniscus, although it is unclear whether
this is due to an increase in recognition or increase in prevalence
because of childhood participation in sports or greater earlier
sports specialization. 27 In a large retrospective study of meniscal
repair surgery reported in 2019, 25% of patients who underwent
surgery were found to have discoid meniscus and nearly all had
ACL tears. 28 Male patients were more likely to have lateral
meniscus tears, posterior horn tears, and concomitant ACL tears. A
larger percentage of medial meniscus tears and anterior horn tears
was found in female patients. More than half of these patients
underwent repair compared with meniscectomy; more than 90% of
repairs were done with an all-inside technique. 28
The type of tear, tear location, concomitant ACL injury, and
patient age all have been previously cited as possible factors
affecting healing in children. 27 Data on the success of meniscal
repair in children have been limited, but a 2019 systematic review
of eight studies found the failure rate to be 17.3% at an average of
16.6 months. Approximately half of these repairs had a concurrent
ACL reconstruction performed at that time. 29 Patient-reported
outcomes and activity scores were improved across all studies,
which support a decision for surgical intervention for pediatric
meniscus tears. Bucket-handle meniscus tears are associated with a
lower rate of concurrent ACL repair (37%) and have been found to
have slightly higher reoperation rates, 32%. 30 Despite these failure
rates, return to sports is above 90% in pediatric patients. 30

Meniscal Allograft: Indication and

Techniques
Meniscal allograft transplantation (MAT) is an option for patients
younger than 50 years with meniscal deficiency and lack of chondral
injury. A 2019 systematic review of long-term survival of MAT
reported mean survivorship of 73.5% at 10 years and 60.3% at 15
years. Patients reported improved outcomes postoperatively. 31
Comparing survivorship of medial and lateral MAT, a 2020 study
demonstrated that 4% of medial and 7.2% of lateral MAT clinical
failures were identified at a mean of 63.1 months. Using MRI,
failures were identified for 4% of medial and 8.8% of lateral MAT at
a mean of 62.6 months. Failure differences were not statistically
different, and patient-reported outcomes were also similar. 32
Return to play has been a more recent area of focus for these
patients. In a 2020 review, 77.4% of patients reported return to play,
with 68.4% returning at the same or higher level. 33 The timeline for
rehabilitation and return to play varies depending on the study;
13.3% were allowed return to play at 3 months, 15.5% at 4 months,
and 27.9% at 6 months. 33
Comparing techniques of medial meniscal allograft, bone plug
fixation resulted in similar mean contact pressures and mean
contact area compared with a native meniscus. Soft-tissue fixation
resulted in higher contact pressures and lower contact area. 34 More
research is needed in this area as well as return to play in high-level
athletes.

Summary
In the absence of significant osteoarthritis, meniscus repair should
be performed whenever possible, including in the se ing of simple
longitudinal tears, bucket-handle tears, radial tears, root tears, and
symptomatic horizontal cleavage tears that involve the vascular
zones of the meniscus. Repair of unstable medial meniscus ramp
lesions is indicated, but benefits of stable ramp lesion repair have
not been demonstrated. Allograft transplantation is a reasonable
salvage option with 60% survival at 15 years. Partial meniscectomy
for degenerative meniscus tears in knees with osteoarthritis should
be considered a second-line treatment only after failure of
conservative care.

Key Study Points

Bucket-handle meniscus repairs have a failure rate of approximately 15%, and
association with ACL reconstruction seems to be protective against failure.
Root repairs demonstrate lesser progression of osteoarthritis and conversion to TKA
compared with both nonsurgical treatment and partial meniscectomy, with partial
meniscectomy having the 60% conversion to TKA at about 6 years.
The rate of partial or complete healing noted for radial tear repairs is greater than
90%, with significant improvements in patient-reported outcome measures.
Ramp lesions are present in approximately 10% of ACL-torn knees, can be identified
via trans-notch view or a posteromedial portal, and should be repaired if unstable.
Meniscal allograft provides approximately 68% return to same-level play, and mean
survivorship of 74% at 10 years.

Annotated References
1. DePhillipo NN, Moatshe G, Chahla J, et al: Quantitative and
qualitative assessment of the posterior medial meniscus
anatomy: Defining meniscal ramp lesions. Am J Sports Med
2019;47(2):372-378. In this cadaver descriptive study, the
meniscocapsular and meniscotibial ligament a achments
merged as a common a achment on the posterior horn of the
medial meniscus, acting as a unit to stabilize the periphery.
2. Aman ZS, DePhillipo NN, Storaci HW, et al: Quantitative and
qualitative assessment of posterolateral meniscal anatomy:
Defining the popliteal hiatus, popliteomeniscal fascicles, and the
lateral meniscotibial ligament. Am J Sports Med 2019;47(8):1797-
 1803. In this cadaver descriptive study, the a achments of the
meniscotibial ligament and popliteomeniscal fascicles were
defined.
3. Wang W, Li Z, Peng H, et al: Accuracy of MRI diagnosis of
meniscal tears of the knee: A meta-analysis and systematic
review. J Knee Surg 2021;34(2):121-129. MRI is highly accurate in
the detection of medial and lateral meniscal tears, although
sensitivity for detection of lateral tears is lower, possibly because
of complex anatomy and concomitant injuries seen in lateral
meniscal tears.
4. Misir A, Kizkapan T, Yildiz K, et al: Using MRI only in the
prediction of meniscus tear repairability. Knee Surg Sports
Traumatol Arthrosc 2019;27(3):898-904. MRI is highly accurate in
the prediction of repairability of vertical and bucket-handle tears,
and moderately accurate in all tear types. Level of evidence: III.
5. Aprato A, Sordo L, Constantino A, et al: Outcomes at 20 years
after menisectomy in patients aged 50 to 70 years. Arthroscopy
2021;37(5):1547-1553. Twenty years after arthroscopic partial
meniscectomy in patients age 50 to 70 years, 15.7% converted to
TKA, with risk for conversion being osteoarthritis at time of
arthroscopy, age, malalignment, and lateral meniscectomy. Level
of evidence: IV.
6. Beaufils P, Becker R, Kopf S, et al: The surgical management of
degenerative meniscus lesions: The 2016 ESSKA meniscus
consensus. Knee Surg Sports Trauamatol Arthrosc 2017;25(2):335-
346.
7. Wasserburger JN, Shul CL, Hankins DA, et al: Long-term
national trends of arthroscopic meniscal repair and debridement.
Am J Sports Med 2021;49(6):1530-1537. Practice trends among
American Board of Orthopaedic Surgery Part II examinees from
2001 to 2017 suggest decreased numbers of meniscal
débridement and increased rates of repairs in the younger than
30 years and 30- to 50-year age groups.
 8. Kopf S, Beaufile P, Hirschmann MT, et al: Management of
traumatic meniscus tears: The 2019 ESSKA meniscus consensus.
Knee Surg Sports Traumatol Arthrosc 2020;28(4):1177-1194. Twenty-
seven questions regarding care of traumatic meniscus tears were
addressed using current literature. The meniscus should be
repaired whenever possible because of superior outcomes with
preservation. Indications for meniscus repair have expanded to
include tear types previously not repaired. Level of evidence: II.
9. Costa GG, Grassi A, Zocco G, et al: What is the failure rate after
arthroscopic repair of bucket-handle meniscal tears? A
systematic review and meta-analysis. Am J Sports Med
2022;50(6):1742-1752. Failure of repair is more common in bucket-
handle meniscus repairs than simple longitudinal tears, when
bucket-handle tears are medial, and when bucket-handle repairs
are performed in isolation of ACL reconstruction. Overall failure
rate is approximately 15%. Level of evidence: IV.
10. Ardizzone CA, Houck DA, McCartney DW, et al: All-inside
repair of bucket-handle meniscal tears: Clinical outcomes and
prognostic factors. Am J Sports Med 2020;48(13):3386-3393. A
clinical failure rate of 29% was reported for all-inside repairs of
bucket-handle meniscus tears, but failure rates were associated
with the RapidLoc and Biofix Arrow implants. Failure was also
associated with male sex and longer follow-up. Level of evidence:
IV.
11. Yeo DYT, Suhaimi F, Parker DA: Factors predicting failure rates
and patient-reported outcome measures after arthroscopic
meniscus repair. Arthroscopy 2019;35(11):3146-3164. This
systematic review noted concomitant ACL reconstruction and
reduced tear complexity were associated with reduced failure
rate. Time from injury to surgery less than 3 months, lesser
degrees of degenerative joint disease, and lesser varus alignment
were associated with be er patient-reported outcome measures.
Level of evidence: IV.
12. Fillingham YA, Riboh JC, Erickson BJ, et al: Inside-out versus
all-inside repair of isolated meniscus tears: An updated
 systematic review. Am J Sports Med 2017;45(1):234-242.
13. Goh JKM, Tan TJ, Kon CKK, et al: All-inside repair of bucket
handle meniscus tears-Mid-term outcomes with postoperative
magnetic resonance imaging. Knee 2021;30:195-204. All-inside
repair in a series of 21 bucket-handle menisci yielded 90%
integrity of repair on postoperative MRI at minimum 24 months
follow-up, with 10% with recurrent bucket-handle tearing. Level
of evidence: IV.
14. Krych AJ, Bernard CD, Kennedy NI, et al: Medial versus lateral
meniscus root tears: Is there a difference in injury presentation,
treatment decisions, and surgical repair outcomes? Arthroscopy
2020;36(4):1135-1141. A retrospective study of 137 patients is
presented. Patients with lateral tears had an average age of 24.6
years, body mass index of 25.8, and Kellgren-Lawrence grade of
0.6. Patients with medial meniscus tears were an average of 51.4
years, body mass index of 32.1, and Kellgren-Lawrence grade of
1.3. Level of evidence: II.
15. Bernard CD, Kennedy NI, Tagliero AJ, et al: Medial meniscus
posterior root tear treatment: A matched cohort comparison of
nonoperative management, partial meniscectomy, and repair. Am
J Sports Med 2020;48(1):128-132. The study provides a matched
comparison of root repair versus meniscectomy versus
nonsurgical treatment. Sixty percent of patients with
meniscectomy, 26.7% treated nonsurgically, and zero patients
treated surgically progressed to TKA within 74 months. Repair
was associated with less progression on Kellgren-Lawrence score.
Level of evidence: III.
16. Chang PS, Radtke L, Ward P, et al: Midterm outcomes of
posterior medial meniscus root tear repair: A systematic review.
Am J Sports Med 2022;50(2):545-553. A systematic review of 28
studies including 994 patients is presented. Clinical outcome
scores, change in Kellgren-Lawrence grade on radiographs, and
progression to TKA were collected. At midterm follow-up,
posterior medial meniscus root repair provides improvements in
 clinical outcomes scores and delays progression of radiographic
arthritis. Level of evidence: III.
17. Fauce SC, Geisler BP, Chahla J, et al: Meniscus root repair vs
meniscectomy or nonoperative management to prevent knee
osteoarthritis after medial meniscus root tears: Clinical and
economic effectiveness. Am J Sports Med 2019;47(3):762-769. In a
meta-analysis and cost-effectiveness analysis from nine studies,
osteoarthritis developed in 53% of repairs and 99.3% of
débridements. A total of 33.5% of repairs and 51.5% of
débridements went on to TKA. For nonsurgical treatment, 95.1%
patients progressed to osteoarthritis, and 45.5% to TKA. Level of
evidence: III.
18. Samuelsen BT, Aman ZS, Kennedy MI, et al: Posterior medial
meniscus root tears potentiate the effect of increased tibial slope
on anterior cruciate ligament graft forces. Am J Sports Med
2020;48(2):334-340. The authors present a cadaver study of 10
human knees where an osteotomy was made to adjust tibial
slope. Posterior medial root tear was made and repaired.
Increased tibial slope resulted in increased ACL forces, and was
potentiated by a posterior medial root tear.
19. Milliron EM, Magnussen RA, Cavendish PA, Quinn JP,
DiBartola AC, Flanigan DC: Repair of radial meniscus tears
results in improved patient-reported outcome scores: A
systematic review. Arthrosc Sports Med Rehabil 2021;3(3):e967-e980.
In a systematic review of 12 studies, 243 radial tears were
followed an average of 35 months. Complete healing was noted in
62% of tears and partial healing in 30% as measured by second-
look arthroscopy or MRI in six studies. Level of evidence: IV.
20. Tsujii A, Yonetani Y, Kinugasa K, et al: Outcomes more than 2
years after meniscal repair for radial/flap tears of the posterior
lateral meniscus combined with anterior cruciate ligament
reconstruction. Am J Sports Med 2019;47(12):2888-2894. A total of
41 consecutive ACL repairs with concomitant radial tears of the
posterior horn of the lateral meniscus were followed for at least 2
years. There were no significant differences between groups at
 follow-up. Eighteen of 30 exhibited complete healing, 9 of 30
partial healing, and 3 repairs failed. Level of evidence: IV.
21. Doig T, Fagan P, Frush T, Lovse L, Chen C, Lemos S: The all-
inside all-suture technique demonstrated be er biomechanical
behaviors in meniscus radial tear repair. Knee Surg Sports
Traumatol Arthrosc 2020;28(11):3606-3612. Thirty porcine cadavers
were repaired by three techniques and cyclic loading and
maximum load were tested. Inside-out repair had the highest
maximum load to failure, similar stiffness, and displacement
after load to failure compared with all-inside, all-suture
techniques.
22. Billeires J, Pujol N, U45 Commi ee of ESSKA: Meniscal repair
associated with a partial meniscectomy for treating complex
horizontal cleavage tears in young patients may lead to excellent
long-term outcomes. Knee Surg Sports Traumatol Arthrosc
2019;27(2):343-348. A case series of partial meniscectomy with
repair of horizontal cleavage component with mean follow-up of
8.5 years yielded good subjective outcomes with a 15%
reoperation rate. Level of evidence: IV.
23. Nakayama H, Kanto R, Kambara S, et al: Successful treatment of
degenerative medial mensiscus tears in well-aligned knees with
fibrin clot implantation. Knee Surg Sports Traumatol Arthrosc
2020;28(11):3466-3473. A series of complex meniscal tears, mostly
complex horizontal tears, repaired with fibrin clot and repair of
cleavage and radial components, resulted in 25% clinical failure
rate, with failure highly associated with varus malalignment.
Level of evidence: IV.
24. Naendrup J, Pfeiffer TR, Chan C, et al: Effect of meniscal ramp
lesion repair on knee kinematics, bony contact forces, and in situ
forces in the anterior cruciate ligament. Am J Sports Med
2019;47(13):3195-3202. Cadaver knees were loaded in various
conditions of anterior translation, rotation, and axial load from 0°
to 90° of flexion intact versus with ramp lesions. A ramp lesion
did not alter kinematics, forces in ACL, or bony contact forces
compared with the intact state.
25. Tashiro Y, Mori T, Oniduka T, et al: Meniscal ramp lesions
should be considered in anterior cruciate ligament-injured knees,
especially with larger instability or longer delay before surgery.
Knee Surg Sports Traumatol Arthrosc 2020;28(11):3569-3575. A
consecutive series of ACL-reconstructed knees underwent
preoperative bilateral KT-2000 testing. Knees with more chronic
injury had ramp lesions. Knees with ramp lesions had greater
side-to-side difference in preoperative anterior translation. Repair
was indicated in unstable ramp lesions. Level of evidence: II.
26. Balazs GC, Gredi er HG, Wang D, et al: Non-treatment of
stable ramp lesions does not degrade clinical outcomes in the
se ing of primary ACL reconstruction. Knee Surg Sports
Traumatol Arthrosc 2020;28(11):3576-3586. Stable ramp lesions
were not repaired, and subjective outcome scores as well as
reoperation rates were similar to those of ACL-reconstructed
knees without ramp lesions. Repair of unstable ramp lesions
resulted in similar subjective outcome scores, but higher
meniscal reoperation rate. Level of evidence: III.
27. Yang BW, Lio a ES, Paschos N: Outcomes of meniscus repair in
children and adolescents. Curr Rev Musculoskelet Med
2019;12(2):233-238. The authors review current literature on the
clinical and functional outcomes of meniscus repair in children.
28. Jackson T, Fabricant PD, Beck N, Storey E, Patel NM, Ganley TJ:
Epidemiology, injury pa erns, and treatment of meniscal tears in
pediatric patients: A 16-year experience of a single center. Orthop
J Sports Med 2019;7(12):2325967119890325. A total of 880
adolescents underwent meniscus repair. Males were more likely
to have posterior horn tears, lateral meniscus tears, and
concomitant ACL tears. Females were more likely to have medial
meniscus tears. They were also more likely to have isolated
meniscal tears. Level of evidence: IV.
29. Liechti DJ, Constantinescu DS, Ridley TJ, Chahla J, Mitchell JJ,
Vap AR: Meniscal repair in pediatric populations: A systematic
review of outcomes. Orthop J Sports Med
2019;7(5):2325967119843355. A systematic review of eight studies
 is presented. Concomitant ACL reconstruction was performed in
52% of meniscus repairs. A total of 287 patients had 301 meniscus
tears, including 134 medial meniscus tears, 127 lateral meniscus
tears, and 32 combined medial and lateral meniscus tears. The
failure rate averaged 17.3% at a mean time of 16.6 months. Level
of evidence: IV.
30. Kramer DE, Kalish LA, Martin DJ, et al: Outcomes after the
operative treatment of bucket-handle meniscal tears in children
and adolescents. Orthop J Sports Med 2019;7(1):2325967118820305.
A retrospective review of 280 adolescents with bucket-handle
meniscus tears is presented; 63% of tears occurred in males, 11%
were discoid, and 43% of patients had a concomitant ACL tear. A
total of 32% of patients underwent reoperation (only 21% of those
with ACL repair) and 99% of patients returned to sport. Level of
evidence: IV.
31. Novare i JV, Patel NK, Lian J, Vaswani R, Getgood A, Musahl V:
Long-term survival analysis and outcomes of meniscal allograft
transplantation with minimum 10-year follow-up: A systematic
review. Arthroscopy 2019;35(2):659-667. The authors present a
systematic review of 11 studies. At 10 years the mean
survivorship was 73.5% and at 15 years it was 60.3%; 9.4% of cases
required a realignment procedure. Level of evidence: IV.
32. Kim C, Bin SI, Kim JM, et al: Medial and lateral meniscus
allograft transplantation showed no difference with respect to
graft survivorship and clinical outcomes: A comparative analysis
with a minimum 2-year follow-up. Arthroscopy 2020;36(12):3061-
3068. A retrospective study of 299 knees followed for a minimum
of 2 years is presented. No significant differences between
patient-reported outcomes were found. There were no
statistically significant differences between clinical and MRI
failures between medial and lateral MAT. Level of evidence: III.
33. Hurley ET, Davey MS, Jamal MS, et al: High rate of return-to-
play following meniscal allograft transplantation. Knee Surg
Sports Traumatol Arthrosc 2020;28(11):3561-3568. A review of 67
studies reported on return to play following MAT. Rate of return
 to play was 77.4% in 11 studies. The average time to return to play
was 9 months in six of the studies. Level of evidence: IV.
34. Ambra L, Mestriner A, Ackermann J, Phan A, Farr J, Gomoll A:
Bone-plug versus soft tissue fixation of medial meniscal allograft
transplants: A biomechanical study. Am J Sports Med
2019;47(12):2960-2965. Nine human cadavers underwent total
meniscectomy, bone plug, and all soft-tissue allograft. Mean
contact pressure, mean contact area, and peak contact pressure
were measured. Soft-tissue fixation had increased mean contact
pressure and lower mean contact area than native meniscus.
C H AP T E R 4 6

Knee Arthritis and Reconstruction

Vonda J. Wright MD, MS, FAAOS, Elizabeth B. Gausden MD, MPH, FAAOS

Dr. Gausden or an immediate family member serves as a paid consultant to or is an employee of DePuy, a Johnson & Johnson Company.
Neither Dr. Wright nor any immediate family member has received anything of value from or has stock or stock options held in a
commercial company or institution related directly or indirectly to the subject of this chapter.

ABSTRACT
Knee osteoarthritis is a common, multifactorial, slowly progressive disease often associated with
aging or trauma. The global prevalence of knee osteoarthritis is estimated at 22% in people older
than 40 years, with the condition being diagnosed in more than 654 million individuals
worldwide. This makes the knee the most common location for osteoarthritis, with high
personal and socioeconomic costs. Historically, treatments have focused on relief from pain and
accompanying osteoarthritis-related disability until terminal treatment with arthroplasty is
indicated. Currently, no available therapy is capable of arresting or reversing cartilage
degradation or structural changes, thus more focus is being placed on detailing the etiologic
mechanisms of osteoarthritis, describing precise osteoarthritis phenotypes as targets for drug
therapy, evaluating the role of age-related hormone changes and cell senescence in disease
progression, and prevention of onset and advancement of disease. Technical developments in
arthroplasty are moving toward advanced forms of robotic assistance, precision implants, and
standardization of techniques to improve outcomes. There have been advances in the
nonsurgical and surgical care of knee arthritis and treatment over the past 2 to 3 years.
Keywords: arthroplasty; orthobiologics; osteoarthritis; osteoarthritis phenotype;
unicompartment

Introduction
Worldwide, knee osteoarthritis represents the most common musculoskeletal disease with
significant personal and societal health and financial effects, 1 with disability rates, morbidity,
financial costs, and mortality rates rivaling those of rheumatoid arthritis. 2 The lifetime risk of
the development of osteoarthritis is estimated to be greater than 45%, with the knee
representing four-fifths of the total osteoarthritis burden. 3 The age wave coupled with a rising
incidence of obesity is making osteoarthritis a leading cause of disability with profound
individual and societal effects. 4 The etiology of knee osteoarthritis is a ributed to many factors
including age-related wear; cartilage and subchondral bone overload; joint overuse; acute
trauma; congenital and acquired malalignment; metabolic factors such as obesity, chronic
inflammation, and diabetes mellitus type 2; and genetic predisposition. Although diagnosis of
osteoarthritis can be made via radiographs documenting joint-space narrowing, subchondral
sclerosis, bone cysts, or deformity, knee osteoarthritis may present with significant signs and
symptoms without substantial radiographic changes. Therefore, diagnosis should include
consideration of underlying pathology as well as the clinical picture. 5 , 6 Surgical intervention
with knee arthroplasty is an effective treatment for advanced knee osteoarthritis but is not
without financial and personal costs. Nonsurgical pain management uses a spectrum of
pharmacologic and lifestyle approaches, but few current therapies address prevention of knee
osteoarthritis or halt progression of the disease. Given the high variability of osteoarthritis, new
research is focusing on describing osteoarthritis subtypes and designing treatments to prevent
onset and progression of specific phenotypes. It is important to be aware of updates in the
understanding of knee osteoarthritis pathology, nonsurgical intervention, and technical
advances in surgical approaches.

Anatomy, Risk Factors for Osteoarthritis, and Pathophysiology

of the Knee
As a pivotal connector of the lower-extremity kinetic chain, the knee serves a central role in
overall locomotion and experiences mechanical stressors from functional abnormalities above
and below the joint. The most significant synovial joint in the body, the knee complex consists
of four unique bony joints connected and covered by multiple tissue types with diverse
functions including bone, cartilage, ligament, tendon, synovium, fat, and skin. Degradation of
the joint cartilage, the definition of arthritis, may be caused by a variety of stimuli over time and
is generally slowly progressive with increasing symptoms and severity over time. 7
At a basic level, a diarthrodial joint is composed of two bones, the cartilage layer bone endcap
and the layer of synovium serving to seal, feed, and lubricate the joint. Chondrocytes, enveloped
in extracellular matrix, are exquisitely sensitive to changes in mechanical microenvironment
load and inflammatory state, causing them to upregulate production of matrix
metalloproteinase (MMP) including MMP-1 and MMP-13 (important in type II collagen) and
MMP-3 (a potent aggrecanase). Production of these cytokines leads to increased proteoglycan
degradation and collagen breakdown. 8 As cartilage degradation progresses with accompanying
phenotypic changes to the chondrocytes themselves, subchondral bone remodeling commences
leading to a cycle of overload and responsive cytokine production all acting in a paracrine
manner furthering cartilage breakdown and the inflammatory processes. In addition,
inflammation of the infrapatellar fat pad in an environment of osteoarthritis may contribute to
pain in osteoarthritis by secreting increased adipocytokines and inflaming the adjacent
synovium. 9
Multiple risk factors contribute to the onset and progression of knee osteoarthritis. Age and
trauma are significant contributors, with traumatic cartilage damage at any age increasing the
risk of future knee osteoarthritis nearly fourfold. 7 Female genetics, weight/joint overload,
repetitive overuse, low bone density, and lean muscle mass also contribute to osteoarthritis
development and progression. The utilization of total knee arthroplasty (TKA) has increased
faster than the utilization of total hip arthroplasty, which is singularly a ributed to the
increasing obesity rates in the United States. 10 Recently, new research as described in a 2021
study illuminates the importance of estrogen in maintenance of cartilage integrity and points to
the loss of estrogen in perimenopause and menopause as a cause of joint pain and progression
of frank osteoarthritis. 11 Another area of increased exploration into the pathophysiology of
osteoarthritis is the rise of senescent cells seen with chronologic aging.
Loss of cartilage, changes in chondrocyte morphology, vascular channel changes in the
subchondral bone, and fat pad fibrosis as well as loss of sex hormones and the rise of senescent
cells with aging are thought to contribute to the pain pa ern associated with osteoarthritis.
These heterogeneous pathways to disease progression necessitate reframing knee osteoarthritis
from a single entity into a multitude of unique osteoarthritis phenotypes requiring and allowing
exploration of each as an opportunity for precision medicine. Osteoarthritis phenotypes may
include the synovial inflammatory phenotype, pain-driven phenotypes, cartilage degradation
phenotype, systemic metabolic pathway, or osteoporotic overload phenotype, for example. 12
Diagnosis and Imaging of Osteoarthritis
In patients presenting with pain, stiffness, and swelling, the first step in diagnosis of knee
osteoarthritis is often radiographs. Multiple grading scales for diagnosis exist, including the
American College of Rheumatology criteria, 13 the common Kellgren-Lawrence scale, 14 the
Ahlbäck classification, 15 or the knee osteoarthritis grading system. 16 Progressive joint-space
narrowing, subchondral sclerosis, osteophyte formation, and subchondral cysts are the hallmark
radiographic features. Knee osteoarthritis is, however, multifactorial and may exist without
significant radiographic evidence. Conversely, significant radiographic findings may exist
without pain.

Knee Osteoarthritis—Continuum of Care

Multiple etiologies are responsible for the development and progression of knee osteoarthritis.
This poses a challenge for a one-size-fits-all approach to treatment and mandates consideration
of the heterogeneous pathways leading to the disease in designing care. The variety of potential
osteoarthritis phenotypes will allow for more precise treatment designs targeting each
individual patient’s osteoarthritis profile such as predominant inflammation, cell senescence,
cartilage metabolism, and subchondral vascularity. Exponential technology such as artificial
intelligence and machine learning and metabolomics may allow expedited understanding of the
key differentiators of unique osteoarthritis phenotypes. Current care pathways include lifestyle
modification and augmentation, systemic pharmacologics, intra-articular injections including
orthobiologics, and surgical realignment or replacement of one or more compartments.

Nonsurgical Modalities
The American Academy of Orthopaedic Surgeons, American College of Rheumatology, and the
Osteoarthritis Research Society International have independently evaluated nonsurgical
approaches to knee osteoarthritis. Table 1 summarizes their recommendations. 17 - 19

Table 1
Nonsurgical Treatment Recommendations of the American Academy of Orthopaedic
Surgeons (AAOS), American College of Rheumatology (ACR), and Osteoarthritis Research
Society International (OARSI)

Oral Topical IA IA
Exercise TENS Cane Weight Chondroitin Acetaminophen Opioids
NSAIDs NSAIDs Steroids HA
AAOS ++ +/− NA + − +/− ++ ++ + +/− —
(tramadol)
ACR ++ − ++ ++ − + ++ − 0 ++ —
OARSI + +/− + + − + + + +/− + +/
−
(++) strong recommendation, (+) recommended, (−) recommend against, (+/−) inconclusive, (0) no recommendation.
HA = hyaluronic acid, IA = intra-articular, TENS = transcutaneous electrical nerve stimulation

Given the complexities of osteoarthritis etiology, any single intervention, whether lifestyle,
systemic, or intra-articular, is unlikely to address all facets of osteoarthritis presentation or
progression. It is now recommended that a multimodal intra-articular approach be undertaken,
combining several effective treatments. 20 Current approaches focus on pain relief and are
unable to modify or prevent the disability of long-term osteoarthritis. The FDA has called for a
focus on drug development that actually modifies the disease process and underlying
pathophysiology to prevent structural damage and disability. 21 Although there is no currently
approved drug in this category, the goal is true disease remission and early intervention before
joint-space narrowing, angular deformities, and major structural damage.
Novel investigational drugs targeting inflammatory mediators work to counteract the low-
grade chronic sterile inflammation that arises secondary to the immune system dysregulation of
aging. 22 These may include interleukin 1 inhibitors that prevent the proinflammatory cytokine
from mediating the pain response, bone resorption, and ultimate cartilage destruction. Another
approach targets tumor necrosis factor alpha production. Tumor necrosis factor alpha functions
as a proinflammatory cytokine produced by synoviocytes and chondrocytes in the knee causing
pain and structural damage. It also plays a paracrine role in the production of interleukins,
MMP, and a variety of other destructive molecules. 11
An important category in antiaging research focuses on reducing the number of circulating
and intra-articular senescent cells known to secrete proinflammatory and catabolic factors
leading to joint destruction. Senescence is one of four known cell fates; however, these cells,
neither fully healthy and functioning nor undergoing apoptosis, exist in a state of cellular limbo
and secrete multiple factors in response to oxidative stress that act negatively on the joint. 23
Secretory senescent cells cause cell cycle arrest via increased production of p16, which have a
detrimental effect on multiple organs and overall longevity. Murine studies in which these p16-
expressing cells were killed with known senolytics prevented development of pos raumatic
osteoarthritis, reduced pain, and improved chondrocyte function in vitro. 12
Cartilage destruction is the hallmark of osteoarthritis; thus this category of new drug therapy
is focusing on stimulation of cartilage repair and delaying destruction. One such approach
prevents the Wnt signaling-mediated phenotypic conversion of chondrocytes into osteoblasts
and the resultant secretion of catabolic enzymes. 24 Another promising approach protects the
two main components of articular cartilage, aggrecan and type II collagen by preventing the
proteolytic effects of MMP and aggrecanase. Although still in laboratory trials, this approach
demonstrates cartilage protection in culture. 25
In addition to prevention of cartilage destruction, several approaches emphasize stimulating
the growth of cartilage. Fibroblast growth factor appears to promote chondrogenesis and
stimulate matrix formation and repair in animal models. 26 The first-line diabetes drug,
metformin, was also found to prevent cartilage degeneration and decrease pain in a murine
osteoarthritis model. 27 In a 2020 retrospective study, patients with diabetes mellitus and
osteoarthritis on metformin were found to have significantly fewer total joint arthroplasties
than those patients not on metformin. 27
Finally, subchondral bone is also subject to resorption and remodeling, leading to
progression of osteoarthritis. Multiple drug therapies are under evaluation for supporting this
osteoarthritis phenotype including diphosphonates, calcitonin, strontium ranelate, teriparatide
(recombinant human parathyroid hormone), and vitamin D. 11
Harnessing the potential of the body to heal itself via orthobiologics/regenerative techniques
is a significant topic in the nonsurgical approaches to knee arthritis. Unfortunately, the
marketing of products has often outpaced the evidence-based approach to this treatment
modality and currently much additional research is required to fully elucidate the dose,
composition, and cellular components necessary to achieve optimal relief.
Platelet-rich plasma (PRP) leads the field of potential autologous biologic approaches to knee
osteoarthritis. A 2021 meta-analysis of 18 level I studies consisting of more than 800 patients
was performed to compare the efficacy of PRP with that of hyaluronic acid. This analysis found
PRP to improve pain and function significantly more than in the hyaluronic acid group (44%
versus 12.6%). In this evaluation, leukocyte-poor PRP was found to be superior to a leukocyte-
rich approach. 28
In the orthobiologic approach, defining the specific phenotypic subtype for optimal response
may increase overall efficacy. Although subgroup analysis is in its beginning stages, identifying
soluble biomarkers in blood and joint fluid would allow the management of knee osteoarthritis
to progress from one-size-fits-all to a more personalized approach. This is particularly true in
the use of PRP because the concentrated blood component is effective in modulating the
inflammatory process via releasing chemokine and cytokines, which act on intra-articular
fibroblasts and macrophages to decrease synovial inflammation 29 and may ameliorate
subchondral bone lesions when used with bone graft. Much more detailed research is still
required to fully understand the role of PRP in the management of knee osteoarthritis.
Although promising, the use of mesenchymal stem cells for the management of knee
osteoarthritis and chondral defects has not been proven to be definitively effective. Recently, an
analysis of 25 studies of 439 patients found pain relief was not significantly different when
comparing patients receiving mesenchymal stem cells versus the control group. In contrast,
functional capacity in those patients undergoing mesenchymal stem cell treatment and
concomitant surgery and cartilage volume but not quality were found to have significant
improvement when compared with control patients, although the effect size was small. 30 Again,
the small number of studies and heterogeneity in study design and reporting limits definitive
application of this treatment in current care.

Surgical Approach
Osteotomy to correct angular deformities in early stage to midstage of arthritis is still used, but
its popularity is decreasing. The declining use of corrective osteotomies has coincided with the
increasing utilization of unicondylar knee arthroplasty (UKA). The use of UKA, including
medial or lateral unicondylar arthroplasty or patellofemoral arthroplasty, has increased and has
historically been reserved for cases of unicompartmental joint-space narrowing. Although the
indications for UKA are constantly evolving, patients with flexion contractures greater than 10°,
uncorrectable varus or valgus deformities, and anterior cruciate ligament deficiency are still
be er candidates for TKA. The advantage of UKA over TKA includes bone preservation, faster
recovery, and lower risk of medical complications. 31 However, revision rate following UKA
remains higher compared with that of TKA, particularly in younger patients. 32
For more than 30 years, TKA has been an effective modality for restoring mobility and
structural alignment in knees with end-stage destruction from osteoarthritis. Advances have
focused on implant design, wear characteristics, and optimizing postoperative function. Despite
improved implant survivorship, decreasing overall all-cause revision rates, and improved
postoperative function, a significant percentage of patients undergoing knee arthroplasty
remain unsatisfied. 33 New technologies in knee arthroplasty focus on increased functional
outcomes and survival via improvements in precision instrumentation and individualized
implants (patient-specific instrumentation [PSI]), the implementation of robotic assistance
(computer-assisted surgery), and standardization of preoperative, intraoperative, and
postoperative surgical protocols to decrease variability and costs while increasing outcomes and
quality.
Several advances in perioperative patient management have been introduced in the past
decade. Multidisciplinary efforts have led to significant improvements in perioperative pain
management via multimodal analgesia, which has facilitated shorter hospital stays and even
same-day discharge following TKA. 32 Regional anesthesia in combination with intra-articular
injections has been effective in lowering opioid consumption post-TKA. The use of tranexamic
acid is now a mainstay in TKA, resulting in lower blood loss and diminishing the need for blood
transfusion. 32
Cemented fixation of the tibial, femoral, and patellar components has been the gold standard
for TKA, especially after early versions of noncemented TKAs demonstrated high failure rates. 34
, 35 , 36
However, in recent years, modern advances in component design have led many surgeons
to revisit noncemented TKA. 37 , 38 Highly porous metals that promote bone ingrowth,
commonly used in cones and sleeves in revision TKA, are now being incorporated into primary
TKA design. Early failure, especially on the tibial side, has been reported to be more common in
larger male patients with noncemented implants. 39 However, there was no increase in failure
rates in obese patients with an alternative noncemented TKA design with a larger keel and four-
peg design when compared with the cemented version of the same implant. 40 Noncemented
TKA fixation remains an area of active research and interest. Long-term results of comparative
studies are needed to determine the optimal fixation method for specific patient populations.
Computerized navigation and robotic surgery are increasingly prevalent in UKA and TKA.
Computerized navigation, such as OrthAlign and Intellijoint, generally uses accelerometers to
help surgeons align cu ing guides according to their pretemplated goals. Robotic technology,
such as Mako, Rosa, and Velys, uses preoperative two-dimensional or three-dimensional
imaging in combination with intraoperative stressing of the knee to evaluate soft-tissue tension
and guide both orientation and amount of bony resection. Both techniques improve precision of
implant positioning relative to manual techniques with intramedullary and extramedullary
guides. However, this has yet to translate into improved patient outcomes for TKA. An
additional benefit of this technology includes eliminating the need for intramedullary canal
entry and thus decreasing the risk of emboli.
Significant improvement in placement of UKA is described with robotic assistance 33 with
more accurate tibia resection and minimization of alignment outliers. Some evidence points to
robotic UKA outperforming manual insertion. 41 Robot augmentation has also contributed to
improved ligament balancing, return to work and sport, and decreased postoperative pain.
Precise component positioning is crucial for UKA compared with TKA.
PSI and customized implants are evolving fields with multiple manufacturers offering
preoperative three-dimensional guided synthesis of patient-specific cu ing gigs and implants
for both TKA and unicompartmental arthroplasty. The goal of these systems is to personalize
bone resection and implant placement to reproduce the patients’ native anatomy. To date,
multiple meta-analyses of primary PSI studies have failed to clearly delineate a significant
reduction of outliers in mechanical axis or three-plane rotational alignment. 42 Furthermore,
more research is warranted to show clear improvements in clinical and functional outcomes
following PSI.
Multiple products have been developed that use intraoperative sensors during trialing of TKA
to gather data on ligament function in real time and facilitate implant positioning and soft-
tissue releases. This theoretically allows more objective data independent of surgeon capacity,
patient habitus, or depth of anesthesia. Few data exist at this time documenting improvements
in functional outcomes in sensor-assisted surgery versus conventionally balanced knees. One of
the issues appears to be the very definition of what specifically defines a well-balanced knee
other than the feel of the knee in the experienced surgeons’ hands. Further studies are required
to quantify mechanical values for measuring and defining exactly what balance is. These studies
are worth undertaking as soft-tissue imbalance remains a major cause of dissatisfaction
following knee arthroplasty. 43
Recently, Persona IQ received FDA approval for insertion in vivo. This device provides long-
term data on the knee function during real-time activity. The first of these devices was
implanted and significant data are forthcoming. Perhaps these long-term data will elucidate
reasons for dissatisfaction in the subset of patients experiencing it. 44

Summary
Knee osteoarthritis is a common cause of personal and societal disability, with numbers of
affected individuals increasing with the aging population and individuals with obesity.
Historically addressed by managing pain and symptoms until arthroplasty was indicated,
current nonsurgical advances focus on characterizing osteoarthritis phenotypes and developing
new drugs to prevent development of osteoarthritis or halt progression of structural damage
and harness the potential of autologous orthobiologic solutions to provide precision treatment.
Surgical innovations seek to use exponential technology such as advanced imaging, artificial
intelligence, or robotically augmented procedures to improve long-term functional outcomes
and improve quality.

Key Study Points

Knee osteoarthritis is a common, multifactorial, slowly progressive disease often associated with aging or trauma.
The etiology of knee osteoarthritis is attributed to many factors including age-related wear, cartilage and subchondral bone
overload, joint overuse, acute trauma, congenital and acquired malalignment, metabolic factors such as obesity, chronic
inflammation, diabetes mellitus type 2, and genetic predisposition.
The variety of potential osteoarthritis phenotypes will allow for more specific treatment designs targeting each individual
patient’s osteoarthritis profile such as predominant inflammation, cell senescence, cartilage metabolism, and subchondral
vascularity.
Nonsurgical advances focus on characterizing osteoarthritis phenotypes and developing new drugs to prevent development
of osteoarthritis or halt progression of structural damage and harness the potential of autologous orthobiologic solutions to
provide precision treatment. These approaches are in development.
New technologies in knee arthroplasty focus on increased functional outcomes and survival via improvements in precision
instrumentation and individualized implants (PSI), the implementation of robotic assistance (computer-assisted surgery),
and standardization of preoperative, intraoperative, and postoperative surgical protocols to decrease variability and costs
while increasing outcomes and quality.

Annotated References
1. Rodríguez-Merchán EC, Gómez-Cardero P: Unicompartmental knee arthroplasty: Current
indications, technical issues and results. EFORT Open Rev 2018;3(6):363-373.
2. Pincus T, Castrejon I, Yazici Y, Gibson KA, Bergman MJ, Block JA: Osteoarthritis is as severe
as rheumatoid arthritis: evidence over 40 years according to the same measure in each
disease. Clin Exp Rheumatol 2019;37 suppl 120(5):7-17. In the past 40 years, osteoarthritis has
been assumed to be less severe and debilitating than rheumatoid arthritis. This article
reviews the data produced over the past 4 decades and summarized why this assumption is
false and how the clinical tools used for rheumatoid arthritis can accurately be applied to
osteoarthritis. Level of evidence: V.
3. Murphy L, Schwar TA, Helmick CG, et al: Lifetime risk of symptomatic knee osteoarthritis.
Arthritis Rheum 2008;59(9):1207-1213.
4. Peat G, Thomas MJ: Osteoarthritis year in review 2020: Epidemiology & therapy.
Osteoarthritis Cartilage 2021;29(2):180-189. This systematic review of new concepts in knee
osteoarthritis covers a variety of new research including osteoarthritis and COVID-19, novel
pharmacotherapy trials, osteoarthritis phenotype research, osteoarthritis comorbidities, and
inequalities in osteoarthritis. Level of evidence: V.
5. Zhang Y, Jordan JM: Epidemiology of osteoarthritis. Clin Geriatr Med 2010;26(3):355-369.
 6. Hannan MT, Felson DT, Pincus T: Analysis of the discordance between radiographic changes
and knee pain in osteoarthritis of the knee. J Rheumatol 2000;27(6): 1513-1517.
7. Jang S, Lee K, Ju JH: Recent updates of diagnosis, pathophysiology, and treatment on
osteoarthritis of the knee. Int J Mol Sci 2021;22(5):2619. The authors describe noncellular and
cellular therapies for osteoarthritis and summarize clinical trials for cell-based osteoarthritis
research. Level of evidence: V.
8. Houard X, Goldring MB, Berenbaum F: Homeostatic mechanisms in articular cartilage and
role of inflammation in osteoarthritis. Curr Rheumatol Rep 2013;15(11):375.
9. Belluzzi E, Macchi V, Fontanella CG, et al: Infrapatellar fat pad gene expression and protein
production in patients with and without osteoarthritis. Int J Mol Sci 2020;21(17):6016. Fifty-
three patients were enrolled during anterior cruciate ligament surgery to characterize the role
of the infrapatellar fat pad in osteoarthritis pathogenesis by measuring the levels of
adipocytes inflammation, adipocytokines, interleukin 6, and vascular endothelial growth
factor. Infrapatellar fat pad inflammation and markers were higher in osteoarthritis than in
anterior cruciate ligament alone, indicating that the infrapatellar fat pad may contribute to
osteoarthritis development. Level of evidence: I.
10. Derman PB, Fabricant PD, David G: The role of overweight and obesity in relation to the
more rapid growth of total knee arthroplasty volume compared with total hip arthroplasty
volume. J Bone Joint Surg Am 2014;96(11):922-928.
11. Cai X, Yuan S, Zeng Y, Wang C, Yu N, Ding C: New trends in pharmacological treatments for
osteoarthritis. Front Pharmacol 2021;12:645842. The push to phenotype subsets of
osteoarthritis may lead to opportunities for novel drug development to address specific
contributing factors for osteoarthritis development and treatment. This study details specific
potential phenotypes and the pharmacotherapeutics that could be developed to target them.
Level of evidence: V.
12. Grässel S, Muschter D: Recent advances in the treatment of osteoarthritis. F1000Res
2020;9:325. This study details the potential osteoarthritis phenotypes that may be used to
target novel treatments to arrest structural deterioration of cartilage and bone. Possible
subtypes include the cartilage and bone degenerative subtype, the inflammatory and pain
phenotypes, and the potential that a single patient may have several interacting phenotypes
of varying expression. Level of evidence: V.
13. Wu CW, Morrell MR, Heinze E, et al: Validation of American College of Rheumatology
classification criteria for knee osteoarthritis using arthroscopically defined cartilage damage
scores. Semin Arthritis Rheum 2005;35(3):197-201.
14. Kohn MB, Sassoon AA, Fernando ND: Classifications in Brief: Kellgren-Lawrence
Classification of Osteoarthritis. Clinical Orthopaedics and Related Research, 2016, p 474.
15. Hernández-Vaquero D, Fernández-Carreira JM: Relationship between radiological grading
and clinical status in knee osteoarthritis. A multicentric study. BMC Muscoskelet Disord
2012;13(1):194.
16. Oosthuizen CR, Takahashi T, Rogan M, Porteous A, Maposa I, et al: The knee osteoarthritis
grading system for arthroplasty. J Arthroplasty 2019;34(3):450-455. This study evaluated the
knee osteoarthritis grading system in 330 patients and found this measure to accurately and
reliably assess the need for TKA. Level of evidence: III.
17. McAlindon TE, Bannuru RR, Sullivan MC, et al: OARSI guidelines for the non-surgical
management of knee osteoarthritis. Osteoarthritis Cartilage 2014;22(3):363-388.
18. Kolasinski SL, Neogi T, Hochberg MC, et al: 2019 American College of
Rheumatology/Arthritis foundation guideline for the management of osteoarthritis of the
hand, hip, and knee. Arthritis Rheumatol 2020;72(2):220-233. Nonsurgical management of the
 symptoms of knee osteoarthritis continues to be multifactorial and not entirely uniform
among clinicians. This consensus outlines recommendations from the American College of
Rheumatology/Arthritis Foundation. Level of evidence: I.
19. Jevsevar DS, Brown GA, Jones DL, et al: The American Academy of Orthopaedic Surgeons
evidence-based guideline on: Treatment of osteoarthritis of the knee, 2nd edition. J Bone Joint
Surg Am 2013;95(20):1885-1886.
20. Georgiev T: Multimodal approach to intraarticular drug delivery in knee osteoarthritis.
Rheumatol Int 2020;40(11):1763-1769. These authors evaluated a multimodal approach to knee
osteoarthritis and concluded that current approaches require a combination of currently
available injectables such as steroid, hyaluronic acid, and biologics to achieve maximum
symptom relief. Level of evidence: V.
21. Latourte A, Kloppenburg M, Riche e P: Emerging pharmaceutical therapies for
osteoarthritis. Nat Rev Rheumatol 2020;16(12):673-688. This article describes the
pathophysiologic processes targeted by emerging therapies for osteoarthritis, along with
relevant clinical data and discussion of the main challenges for the further development of
these therapies, to provide context for the latest advances in the field of pharmaceutical
therapies for osteoarthritis. Level of evidence: V.
22. Millerand M, Berenbaum F, Jacques C: Danger signals and inflammation in osteoarthritis.
Clin Exp Rheumatol 2019;37(suppl 120):48-56. This article examines the concept of
inflammaging, which is the sterile chronic inflammation in association with aging and the
cytokines the process produces in the joint microenvironment, which are thought to lead to
development and progression of osteoarthritis. The authors detail how this understanding
may be used to develop new pharmacologic treatments for osteoarthritis. Level of evidence: V.
23. Coryell PR, Diekman BO, Loeser RF: Mechanisms and therapeutic implications of cellular
senescence in osteoarthritis. Nat Rev Rheumatol 2021;17(1):47-57. Cellular senescence is one of
several naturally occurring cell destinies. Changes in age-related mitochondria function may
lead to increased expression of the senescence-associated secretory phenotype and increased
degradation of cartilage. New research is needed to develop interventions targeted at
senescent cells to stop disease progression. Level of evidence: V.
24. Deshmukh V, O’Green AL, Bossard C, et al: Modulation of the Wnt pathway through
inhibition of CLK2 and DYRK1A by lorecivivint as a novel, potentially disease-modifying
approach for knee osteoarthritis treatment. Osteoarthritis Cartilage 2019;27(9):1347-1360.
Authors detail the Wnt pathway of disease progression in osteoarthritis, the specific receptors
for focused intervention and development of lorecivivint as a drug for a new approach to
osteoarthritis. Level of evidence: I.
25. Siebuhr AS, Werkmann D, Bay-Jensen A-C, et al: The Anti-ADAMTS-5 Nanobody® M6495
protects cartilage degradation Ex Vivo. Int J Mol Sci 2020;21(17):5992. Novel pathways for
ameliorating the chronic sterile inflammatory state of osteoarthritis are under evaluation. The
authors describe one such pathway and advances in cartilage protection based on it. Level of
evidence: I.
26. Senne ML, Meloni GR, Farran AJE, Guehring H, Mauck RL, Dodge GR: Sprifermin
treatment enhances cartilage integration in an in vitro repair model. J Orthop Res
2018;36(10):2648-2656.
27. Li H, Ding X, Terkeltaub R, et al: Exploration of metformin as novel therapy for
osteoarthritis: Preventing cartilage degeneration and reducing pain behavior. Arthritis Res
Ther 2020;22(1):34. This study of a murine knee osteoarthritis model details the potential
efficacy of metformin in a enuating the structural degradation and pain symptom. Mice
treated with metformin demonstrated less cartilage degradation via scanning electron
 microscopy and increased functional capacity. Metformin acts by decreasing MMP-13 and
elevating collagen production. Level of evidence: I.
28. Belk JW, Kraeutler MJ, Houck DA, Goodrich JA, Dragoo JL, McCarty EC: Platelet-rich plasma
versus hyaluronic acid for knee osteoarthritis: A systematic review and meta-analysis of
randomized controlled trials. Am J Sports Med 2021;49(1):249-260. This meta-analysis of 18 level
I studies found PRP to improve clinical outcomes when compared with hyaluronic acid alone.
Leucocyte-poor PRP may be the superior concentrate for this purpose. Level of evidence: V.
29. Andia I, Atilano L, Maffulli N: Moving toward targeting the right phenotype with the right
platelet-rich plasma (PRP) formulation for knee osteoarthritis. Ther Adv Musculoskelet Dis
2021;13:1759720X211004336. This meta-analysis reviews the efficacy of PRP versus other intra-
articular injections for pain relieve and function in osteoarthritis. PRP appears to have
superiority in this analysis, however studies are small as are the effect size. Level of evidence:
V.
30. Maheshwer B, Polce EM, Paul K, Verma NN, Cole BJ, et al: Regenerative potential fo
mesenchymal stem cells for the treatment of knee osteoarthritis and chondral defects: A
systematic review and meta-analysis. Arthroscopy 2020;37(1):362-378. A meta-analysis of 25
studies involving 439 individuals found no significant difference in pain or cartilage quality
with administration of mesenchymal stem cells versus placebo; however, functional
improvement and cartilage volume increased. Level of evidence: I.
31. Crawford DA, Berend KR, Thienpont E: Unicompartmental knee arthroplasty: US and global
perspectives. Orthop Clin North Am 2020;51(2):147-159. Authors provide a step-by-step
evidence-based method for unicompartmental knee arthroplasty with the purpose of
decreasing the higher failure rates seen with this procedure compared with TKA. Level of
evidence: V.
32. Kleeblad LJ, van der List JP, Zuiderbaan HA, Pearle AD: Larger range of motion and
increased return to activity, but higher revision rates following unicompartmental versus total
knee arthroplasty in patients under 65: A systematic review. Knee Surg Sports Traumatol
Arthrosc 2018;26(6):1811-1822.
33. Batailler C, White N, Ranaldi FM, Neyret P, Servien E, Lustig S: Improved implant position
and lower revision rate with robotic-assisted unicompartmental knee arthroplasty. Knee Surg
Sports Traumatol Arthrosc 2019;27(4):1232-1240. The aim of this case-control study was to
compare implant position and revision rate for UKA, performed with either a robotic-assisted
system or with conventional technique. Robotic-assisted UKA has a lower rate of
postoperative limb alignment outliers, as well as a lower revision rate, compared with
conventional technique. The accuracy of implant positioning is improved by this robotic-
assisted system. Level of evidence: III.
34. Campbell MD, Duffy GP, Trousdale RT: Femoral component failure in hybrid total knee
arthroplasty. Clin Orthop Relat Res 1998;356:58-65.
35. Berger RA, Lyon JH, Jacobs JJ, et al: Problems with cementless total knee arthroplasty at 11
years followup. Clin Orthop Relat Res 2001;392:196-207.
36. Peters PCJr, Engh GA, Dwyer KA, Vinh TN: Osteolysis after total knee arthroplasty without
cement. J Bone Joint Surg Am 1992;74(6):864-876.
37. Dalury DF: Cementless total knee arthroplasty: Current concepts review. Bone Joint J 2016;98-
B(7):867-873.
38. DeFrancesco CJ, Canseco JA, Nelson CL, Israelite CL, Kamath AF: Uncemented tantalum
monoblock tibial fixation for total knee arthroplasty in patients less than 60 years of age:
Mean 10-year follow-up. J Bone Joint Surg Am 2018;100(10):865-870.
39. Meneghini RM, de Beaubien BC: Early failure of cementless porous tantalum monoblock
tibial components. J Arthroplasty 2013;28(9):1505-1508.
40. Goh GS, Fillingham YA, Su on RM, Small I, Courtney PM, Hozack WJ: Cemented versus
cementless total knee arthroplasty in obese patients with body mass index ≥35 kg/m2: A
contemporary analysis of 812 patients. J Arthroplasty 2022;37(4):688-693.e1. The case-control
study evaluated the role of cemented versus cementless TKA in obese patient implant
survivorship. Obese patients with BMI ≥35 kg/m2 undergoing cementless and cemented TKA
of the same modern design had similar outcomes and survivorship at early to mid-term
follow-up. Level of evidence: III.
41. Banger M, Doonan J, Rowe P, Jones B, MacLean A, Blyth MJB: Robotic arm-assisted versus
conventional medial unicompartmental knee arthroplasty: Five-year clinical outcomes of a
randomized controlled trial. Bone Joint J 2021;103-b(6):1088-1095. UKAs have higher rates of
failure than TKA and are sensitive to patient selection and precision alignment. Robots are
thought to increase alignment accuracy and ligament balancing. This article presents the 5-
year outcomes of a comparison between manual and robotically assisted UKAs. This study
has shown excellent clinical outcomes in both groups with no statistical or clinical differences
in the patient-reported outcome measures. The notable difference was the lower
reintervention rate at 5 years for robotic arm-assisted UKA when compared with a manual
approach. Level of evidence: I.
42. Batailler C, Swan J, Sappey Marinier E, Servien E, Lustig S: New technologies in knee
arthroplasty: Current concepts. J Clin Med 2021;10(1):47. This article reviews the benefits and
limitations of new UKA techniques including patient-specific planning, robotic assistance,
and 3D printing of implants all designed with the intention of decreasing the up to 20% of
patients who remain dissatisfied with UKA.
43. Joseph J, Simpson PM, Whitehouse SL, English HW, Donnelly WJ: The use of navigation to
achieve soft tissue balance in total knee arthroplasty – A randomized clinical study. Knee
2013;20(6):401-406.
44. Iyengar KP, Gowers BTV, Jain VK, Ahluwalia RS, Botchu R, Vaishya R: Smart sensor implant
technology in total knee arthroplasty. J Clin Orthop Trauma 2021;22:101605. This narrative
review evaluated smart sensor technology for gathering real-tie kinematic, wear, and patient
function data via implantable sensors during TKA. Level of evidence: V.
S E CT I ON 9

Foot and Ankle

SECTION EDITOR
David Joseph Ciufo, MD

Kenneth J. Hunt, MD, FAAOS

C H AP T E R 4 7

Foot and Ankle Anatomy and

Biomechanics
Marissa D. Jamieson MD, T. Jay Kleeman MD, FAAOS

Neither of the following authors nor any immediate family member has received anything of value
from or has stock or stock options held in a commercial company or institution related directly or
indirectly to the subject of this chapter: Dr. Jamieson and Dr. Kleeman.

ABSTRACT
It is important to review some of the recent advances in anatomy,
imaging, and biomechanics of the foot and ankle as well as the
utility of gait analysis in diagnosing complex foot and ankle
conditions. Restoration of anatomy and kinematics in hallux valgus
deformity, syndesmotic disruption, and lateral ankle ligament
injuries continues to be a subject of debate, as does the ideal
surgical treatment. Total ankle arthroplasty continues to be an
important topic for foot and ankle surgeons, with evolving
technology aiding in the diagnosis and treatment of the painful
ankle replacement.
Keywords: anatomy; biomechanics; imaging; syndesmosis; total
ankle arthroplasty

Introduction
It is essential to have a thorough understanding of normal anatomy
and biomechanics of the foot and ankle to effectively diagnose and
treat pathologic conditions. Whether correcting deformity,
reconstructing the foot or ankle after trauma, or properly aligning a
total ankle arthroplasty (TAA), an orthopaedic surgeon must
understand the interaction of static and dynamic structures in
maintaining stability and function. Weight-bearing CT is advancing
the understanding of complex three-dimensional conditions
including hallux valgus, cavovarus deformity, and progressive
collapsing foot deformity. With increasing interest in minimally
invasive surgery, comprehensive knowledge of structures at risk
with percutaneous approaches is imperative for successful
outcomes. An awareness of recent developments in applied
anatomy and biomechanics as well as imaging of the foot and ankle
is important.

Anatomy

Osseous
There are 28 bones that make up the foot, as well as a variable
number of common ossicles. The ankle is a mortise joint with
inherent bony stability. It is composed of the distal tibial plafond,
including the medial and posterior malleoli, as well as the lateral
malleolus of the fibula, which houses the body of the talus. The foot
can be visualized as a tripod composed of the calcaneus, first
metatarsal head, and lesser metatarsals, with deviation from this
structural base causing biomechanical issues. The foot can be
divided into three main regions from proximal to distal: the
hindfoot (talus and calcaneus), the midfoot (navicular, cuboid, and
three cuneiforms), and the forefoot (metatarsals, phalanges, and
sesamoids).
The foot’s unique anatomy and biomechanics allow it to
transition from rigid to flexible throughout the gait cycle. During
push-off, the foot inverts, causing the Chopart joints
(calcaneocuboid and talonavicular) to lock and form a stable
platform. During stance, the foot everts, unlocking the Chopart
joints to allow for accommodation to the ground. Furthermore, the
medial column, consisting of the talus, navicular, medial
cuneiform, and first metatarsal, is stiff and creates the longitudinal
arch of the foot, whereas the lateral column, consisting of the
calcaneus, cuboid, and fourth and fifth metatarsals, is more flexible,
allowing for accommodation on uneven terrain.
Proper alignment of the medial column continues to be a subject
of debate in the treatment of hallux valgus. A be er three-
dimensional understanding of hallux valgus, through the increased
use of weight-bearing CT, has shown that medial rotation or
pronation of the first metatarsal plays an important role in the
pathomechanics of the deformity by altering the directional pull of
the dynamic structures of the great toe. A recent review
summarizes the current understanding of axial first metatarsal
rotation and the modifications to previous corrective osteotomies
and fusions now designed to correct this rotational deformity 1
(Figure 1).
 Figure 1 Anatomic and biomechanical changes of hallux valgus.Illustration of
the various steps implicated in the pathogenesis of first metatarsal and hallucal
rotation and translation (left; A through C) in hallux valgus deformity, along with
their anatomic manifestations (right; D through F). A, Pronation of the first
metatarsal; B, varus translation and accentuated rotation of the first metatarsal
head; C, rotation and valgus translation of the hallux; D, rotation of the abductor
hallucis tendon plantarly, functionally inactivating it; E, flexor and extensor
hallucis tendon insertions are rotated and pull the proximal end of the distal
phalanx into valgus; F, adductor hallucis longus tendon insertion is rotated,
adding pronation-promoting force to the base of the hallux.(Redrawn with
permission from Steadman J, Barg A, Saltzman CL: First metatarsal rotation in
hallux valgus deformity. Foot Ankle Int 2021;42[4]:510-522, Figure 1.)

Neurovascular
With growing interest in minimally invasive surgical procedures for
deformity correction, fracture fixation, and soft-tissue
reconstruction, a comprehensive understanding of neurovascular
anatomy is important to avoid iatrogenic injury to these structures.
Minimally invasive Achilles tendon repair can place the sural nerve
at risk laterally during blind passage of sutures and needles. Two
recent cadaver studies using a popular device for minimally
invasive Achilles repair evaluated the incidence of sural nerve
puncture during needle passage. One study showed zero nerve
penetrations, one needle touching the nerve, and no nerve
entrapment after jig removal. 2 The other study showed 9 sural
nerve penetrations in 4 of 10 specimens or 18% of the passes;
however, removal of the device led to zero incidence of nerve
entrapment. 3
Percutaneous posterior-to-anterior fixation for posterior malleolar
fractures can also place the sural nerve at risk, but a recent
anatomic study found a safe zone for screw placement immediately
lateral to the Achilles tendon and 1 cm proximal to the tip of the
medial malleolus. This avoided injury to the sural nerve and short
saphenous vein in all specimens. 4 Similarly, anterior-to-posterior
percutaneous fixation of posterior malleolar fractures can place the
anterior neurovascular structures at risk. A 2021 anatomic study
showed no damage to neurovascular structures when screws were
placed medial to the tibialis anterior, but damage or close proximity
to neurovascular structures when placed lateral to the tibialis
anterior or extensor digitorum longus. 5
Most TAA implants require an anterior approach to the ankle,
involving anterior-to-posterior blind placement of pins, chisels, and
saws to secure resection guides and resect the distal tibia. This
places the posterior tibial tendon, posterior tibialis artery/vein, and
tibial nerve at risk. An additional posteromedial incision just
proximal to the tip of the medial malleolus, with placement of a
blunt retractor between the posterior tibial tendon and the
posterior cortex of the distal tibia, has been proposed as a way to
prevent iatrogenic neurovascular injury during anterior approach
TAA. 6
Blood supply to the talus is known to be tenuous because of the
bone’s high surface area covered with articular cartilage (Figure 2).
This limited blood supply is thought to contribute to the frequent
occurrences of osteochondral lesions of the talus and necrosis. A
common procedure used to fill subchondral bone defects
associated with osteochondral lesions of the talus involves injecting
a highly porous synthetic calcium phosphate bone graft substitute
into the talus. However, two recent case series have shown a high
rate of osteonecrosis of the talus after this procedure, which can
lead to devastating articular collapse and arthritis of the ankle 7 , 8
(Figure 3). It has been suggested that this technique may damage
the extraosseous blood supply of the talus and the delicate
intraosseous network, thereby preventing revascularization. 6

Figure 2 Artist’s rendering of talar blood supply.A, Sagittal section through the
midtalus demonstrating the distribution of the three major arteries supplying the
talus. B, Coronal section through the posterior midtalus demonstrating the
distribution of the deltoid and tarsal canal branches.(Reproduced with
permission from Foran IM, Bohl DD, Vora AM, Mehraban N, Hamid KS, Lee S:
Talar osteonecrosis after subchondroplasty for acute lateral ligament injuries:
case series. Foot Ankle Orthop 2020;5[1]:2473011420907072, Figure 3.)
 Figure 3 Coronal CT scan from a 31-year-old woman 3 months after
subchondroplasty of the talus.The area of increased density makes it difficult to
distinguish between osteonecrosis and the calcium phosphate bone graft
substitute. The arrow shows the area of talar surface fragmentation.

Tendons and Ligaments

The ankle joint is stabilized by three ligamentous complexes that
give it stability throughout the range of motion: laterally the
anterior talofibular ligament, calcaneofibular ligament, and
posterior talofibular ligament; the deltoid ligament complex
medially; and the syndesmotic ligaments and interosseus
membrane, which stabilize the distal tibiofibular joint.
 One of the syndesmotic ligaments, the posterior inferior
tibiofibular ligament, extends from the fibula to the posterior
malleolus. Previous understanding was that a posterior malleolus
fracture gave rise to syndesmotic instability because of insertion of
the deep posterior inferior tibiofibular ligament on the posterior
malleolus. However, a 2019 anatomic study showed that the
superficial posterior inferior tibiofibular ligament has a very broad
insertion on the posterior tibia that is larger than the average size
of the posterior malleolar fragment. Therefore, the presence of
syndesmotic instability in the se ing of a posterior malleolar
fracture requires that a ligamentous injury must also occur. 9
The foot’s architecture and bony tripod is stabilized by several
critical ligamentous structures, with plantar ligaments on the
tension side being stronger and more robust than dorsal ligaments.
The Lisfranc ligament is a short, thick, interosseous ligament that
runs from the medial cuneiform to the base of the second
metatarsal and is critical for stabilization of the midfoot and medial
longitudinal arch. A recently described lateral Lisfranc ligament
spans between the bases of the second through fifth metatarsals
and blends with the long plantar ligament, creating a transverse
suspensory metatarsal ligament. 10 This ligamentous complex
provides a connection of both the transverse and longitudinal
arches of the foot, which may explain why lateral column instability
can sometimes be overcome with medial column stabilization in
complex tarsometatarsal joint injuries.
Ligaments provide static stability and structure to the foot and
ankle, and multiple opposing tendon groups contribute to the
dynamic stability of the foot and ankle and allow for the complex
motion required for gait and activity. Any imbalance in these
tendon forces can cause imbalance and deformity.

Imaging

Plain Radiography
Plain radiography is the preferred initial study in the evaluation of a
patient with foot and ankle complaints. Standard views include AP,
oblique, and lateral weight-bearing views of the foot and AP,
mortise, and lateral weight-bearing views of the ankle. It may be
helpful to include both extremities in the AP views for comparison.
Weight-bearing views have become the standard of care (when
tolerated by the patient) as they provide be er dynamic evaluation
of foot and ankle deformity, malalignment, arthritic collapse,
instability, and impingement under physiologic loading. 11
Ankle stress radiographs are used to determine stability of
isolated lateral malleolar ankle fractures, syndesmotic injuries, and
in the se ing of chronic ankle ligamentous instability. Manual foot
stress radiographs may be helpful in the evaluation of Lisfranc
injuries and turf toe injuries.
Additional views can be helpful when evaluating certain
pathologies. An axial Harris view helps define calcaneus fractures, a
Broden view is used to view the posterior facet of the subtalar joint,
and the Canale view gives the best image of the talar neck. An
internal oblique AP foot view helps evaluate an accessory navicular,
and a sesamoid view is useful for the evaluation of sesamoid
pathology and their alignment relative to the cristae of the first
metatarsal (Figure 4). The Sal man view is used for evaluation of
hindfoot alignment in relationship to the ankle and can be
particularly useful for surgical planning of deformities. It is
important to be familiar with these special views for clinical
evaluation in the office and for intraoperative use.
 Figure 4 A, AP internal oblique radiograph of the foot showing a type II
accessory navicular. B, Sesamoid view of the foot showing a bipartite tibial
sesamoid.

There has been some interest in the intraoperative use of three-

dimensional fluoroscopy, which involves a modified mobile C-arm
unit, instead of standard two-dimensional fluoroscopy for complex
anatomy or fracture pa erns. However, a 2020 study suggests
longer surgical time without any improvement in clinical outcomes
or quality of calcaneal fracture reduction. 12 This technology may
provide new benefits as it evolves.

CT/Weight-Bearing CT
Standard multidetector CT scans are beneficial for three-
dimensional evaluation in certain clinical se ings including
preoperative planning and understanding of deformity or intra-
articular fractures, definition of arthritic changes, osteochondral
fractures, coalitions, and evaluation of postoperative fusion or
osteotomy/fracture healing. They are readily available and can be
done quickly in most clinic and hospital se ings but do require
radiation.
The recent development of weight-bearing CT scans with the use
of cone beam technology has expanded some of the indications for
CT. 11 There is a growing body of literature supporting the use of
weight-bearing CT in specific clinical scenarios. They have
demonstrated value for evaluation of progressive collapsing foot
deformity with regard to subtalar and talonavicular alignment,
subtalar or subfibular impingement, and forefoot position. 13
Similarly, weight-bearing CT is useful in hallux valgus deformity to
assess first ray pronation, sesamoid alignment, and midfoot
instability. Weight-bearing CT can also be used in the se ing of
acute injuries to detect subtle instability, such as in Lisfranc or
syndesmotic injuries that can be missed on plain radiographs 14 , 15
(Figure 5). Additionally, it has been shown that time spent on
image acquisition is lower for weight-bearing CT alone compared
with radiographs with conventional CT scan, as is standard for
many injuries. 16 Many current software programs can create
radiographs from CT images, which would allow for a single
imaging modality with greater reproducibility. Furthermore, the
radiation dose from a weight-bearing CT has been shown to be
lower than a conventional CT scan. 16 Accessibility to weight-
bearing CT is a barrier for many surgeons at this time, but as
indications evolve and expand this will likely become a more widely
used imaging modality for many foot and ankle conditions.
 Figure 5 A, Weight-bearing CT axial image showing subtle widening of the
Lisfranc articulation between the medial cuneiform and base of the second
metatarsal (arrow) when compared with the contralateral side. B, Sagittal
weight-bearing CT image showing dorsal subluxation of the second metatarsal
base on the middle cuneiform, which was difficult to appreciate on plain
radiographs.

Magnetic Resonance Imaging

MRI is often indicated to evaluate soft-tissue injuries including
ligament and tendon tears or degeneration, nerve entrapment or
neuromas, and bony injuries including stress fractures,
osteonecrosis, early arthritis, and osteochondral lesions. MRI (with
gadolinium contrast) is important in the workup of soft tissue or
bony masses/tumors as well as infection including osteomyelitis.
In general, 3T MRI is preferred over 1.5T MRI because it provides
a higher resolution image and greater anatomic detail for the small
structures in the foot and ankle. T2-weighted fat suppression 3T
images are especially useful for the diagnosis of nerve pathology
and Morton neuroma. 17
Parametric mapping techniques or quantitative MRI, specifically
T2, T2*, and T1 Rho, are capable of detecting early cartilage
degeneration and tissue breakdown before it is apparent on
standard MRI. They are also helpful in assessing the quality of
cartilage after a microfracture or cartilage restoration procedure
and may help guide treatment and rehabilitation plans 17 (Figure 6).

Figure 6 T2 mapping magnetic resonance image demonstrating hyaline

cartilage distribution following an osteochondral autograft transfer procedure.
(Reproduced from Chou L, ed: Orthopaedic Knowledge Update: Foot and Ankle,
ed 6. American Academy of Orthopaedic Surgeons, 2020.)

Ultrasonography
Ultrasonography is a useful and low-cost tool for the quick
evaluation and diagnosis of tendon ruptures or tears, soft-tissue
masses, joint effusions, nerve pathology, foreign bodies, and
abscesses or hematomas. It is particularly helpful in evaluating
dynamic tendon issues such as peroneal tendon intrasheath or
fibular subluxation and trigger toe. Ultrasonography can be used to
accurately guide intra-articular, nerve, or tendon/ligament
injections. Minimally invasive ultrasound-guided techniques for
recalcitrant plantar fasciitis or Achilles tendinitis have become a
popular and widely used form of treatment.
However, the use of ultrasonography is operator dependent, and
many orthopaedic surgeons are not trained extensively. In the
appropriate se ing, it can be an affordable and accessible tool that
can add to diagnostic and therapeutic treatment of patients.

Nuclear Imaging
Although nuclear imaging has been largely replaced with MRI, it is
still valuable in the diagnosis of foot and ankle pathology and can
be used as an alternative in patients who are unable to undergo
MRI because of implanted devices. Nuclear medicine provides both
anatomic and physiologic information through the injection of a
radiotracer (most commonly technetium-99 or gallium-67) into the
patient that accumulates in specific locations depending on the
underlying pathology.
A three-phase bone scan detects areas of high osteoblastic
activity such as in stress fractures, complex regional pain syndrome
(which shows diffuse increased uptake in all three phases), bone
and soft-tissue tumors (particularly osteoid osteoma), and
osteomyelitis. A leukocyte or tagged white blood cell scan is the
gold standard to differentiate neuropathic arthropathy from
osteomyelitis.
Poor imaging quality has always been a concern with nuclear
imaging, but single-photon emission CT is able to combine
physiologic information with the anatomic detail of a CT scan. This
technology provides early detection and accurate sizing of
osteochondral lesions and is becoming helpful in the assessment of
a painful TAA. 18 Single-photon emission CT is able to distinguish
between gu er impingement, periarticular hindfoot arthritis,
periprosthetic stress fracture, and aseptic loosening, which will
show as diffuse increased tracer uptake along the prosthetic-bone
interface (Figure 7). It has shown to be more reliable than MRI in
diagnosing the cause of pain after TAA. 18 , 19
Figure 7 AP and lateral radiographs (A and B) and single-photon emission CT
coronal and sagittal images (C and D) from a patient with a painful total ankle
arthroplasty demonstrating osteolysis and increased uptake beneath both tibial
and talar implants. The patient was found to have loosening of both components
 at the time of revision surgery and underwent revision to a stemmed implant.
(Reproduced with permission from Gurbani A, Demetracopoulos C, O’Malley
M, et al: Correlation of single-photon emission computed tomography results
with clinical and intraoperative findings in painful total ankle replacement. Foot
Ankle Int 2020;41[6]:639-646, Figure 3.)

Another emerging imaging modality that can be used to evaluate

talar perfusion after TAA is 18F-fluoride positron emission
tomography/CT. 20

Biomechanics
Understanding the complex biomechanics, or interaction of the
structure and function of the foot and ankle, in response to loading
is essential for the appropriate diagnosis and treatment of foot and
ankle pathology. Research in functional anatomy and biomechanics
continues to advance the understanding of clinical disease, improve
surgical techniques, and develop improved implants, orthotics, and
bracing. Surgical and nonsurgical treatment aim to alter or restore
the anatomic and structural components of the foot and ankle with
a goal of improving function and decreasing pain. To achieve the
desired surgical result, it is important to understand the
interactions of these alterations on other components of the body
as well. It is important to highlight recent advances in
biomechanics as it applies to specific foot and ankle conditions.
The diagnostic criteria and management of chronic lateral ankle
instability continue to evolve over time as the anatomic and
biomechanical understanding of ankle ligamentous structures
evolves. There has been a recent emphasis on the anterolateral
drawer test, as opposed to the traditional anterior drawer test, in
making an accurate diagnosis of chronic lateral ankle instability.
This test involves translating the foot anteriorly while allowing the
foot to internally rotate, which accommodates for the potential
constraint of an intact deltoid ligament. 21 A 2019 study showed the
importance of repairing the calcaneofibular ligament in addition to
the anterior talofibular ligament to restore native ankle joint
kinematics and increase stability. 22 No surgical option has been
found to be superior biomechanically between Broström, Broström
with Gould modification, repair with suture tape augmentation,
allograft or autograft reconstruction, and all-arthroscopic repair;
however, there is concern about possibly overtightening constructs
with suture tape augments that lack viscoelastic creep. 21
Restoration of anatomy and kinematics in syndesmotic injuries
has remained elusive in biomechanical and clinical studies. There
has been growing interest in the direct anatomic repair of
syndesmotic ligaments, sagi al plane and rotational instability, and
the contribution of the deltoid ligament. Recent arthroscopic
cadaver studies have shown that diagnosis of syndesmotic injuries
was more accurate when based on sagi al plane motion of the
fibula as opposed to coronal plane diastasis, with the optimal cutoff
point to arthroscopically identify unstable injuries being 2 mm of
total fibular translation. 23 , 24 Sagi al and axial instability can also
be tested in open fracture repair. Additionally, three-dimensional
volumetric measurements of the syndesmotic space using weight-
bearing CT has been shown to be the most effective way to
distinguish stable from unstable syndesmosis injuries and is more
sensitive that traditional coronal or sagi al two-dimensional
measurements. 15
A 2020 biomechanical cadaver study found that adding suture
anchor augmentation of the anterior-inferior tibiofibular ligament
to suture bu on fixation increased the external rotation constraint
of the fibula; however, none of the tested constructs reproduced
intact-state kinematics. 25 In the se ing of syndesmotic and deltoid
ligament injury, another study showed that repair of the deltoid
ligament in addition to syndesmosis fixation restored internal
rotation and anterior and lateral translation of the talus back to
intact state levels; however, none of the repair states restored
external rotation back to the intact state. 26 There may be an
opportunity for improvement in current surgical technique for
repair of the syndesmosis, particularly related to restoration of
external rotation stability.
 Surgical treatment of insertional Achilles tendinitis typically
involves excision of the diseased tendon, resection of an associated
Haglund deformity, and repair of the tendon back to the calcaneus
via suture anchor. A cadaver study found that a double-row
synthetic suture anchor construct had a 50-N increase in clinical
load to failure compared with a single-row all-suture anchor repair
construct; however, neither construct had sufficiently high load to
failure to allow for immediate weight bearing. 27
Compared with ankle fusion, TAA is be er at maintaining
normal ankle kinematics and motion, thereby minimizing or
accommodating for degenerative changes in adjacent joints.
Establishing neutral alignment after a TAA is essential for implant
longevity and function. Often, end-stage varus ankle arthritis has
concomitant varus hindfoot pathology that may need to be
managed at the time of surgery to restore coronal plane alignment.
A recent clinical study found that after correction of varus ankle
alignment with TAA, varus hindfoot alignment self-corrected
without any additional surgical intervention. The study authors
presented a means to predict the amount of hindfoot correction
possible based on the amount of ankle correction, which may help
with surgical decision-making regarding the need to include
hindfoot osteotomies or additional fusions during TAA. 28
Progressive collapsing flatfoot deformity, formerly known as
adult acquired flatfoot deformity or posterior tibial tendon
dysfunction, is a complex three-dimensional deformity of the foot
that involves varying degrees of hindfoot valgus, forefoot
abduction, and midfoot varus with or without posterior tibial
tendon pathology. Recent studies using weight-bearing CT are
helping to reclassify the staging of progressive collapsing foot
deformity. This newer classification distinguishes flexible (stage I)
deformities from rigid (stage II) deformities and further delineates
based on a key deformity feature: class A involves hindfoot valgus,
class B midfoot or forefoot abduction, class C forefoot varus or
medial column instability, class D peritalar subluxation, and class E
ankle instability. Each class has characteristic clinical and
radiographic findings as detailed by the consensus group
classification. 29 These deformities have significant interactions,
with subtalar or hindfoot valgus leading to peritalar subluxation
and eventual sinus tarsi or subfibular impingement. Increased
tension medially can lead to deltoid failure with progressive valgus
tilt of the tibiotalar joint. 30 , 31 In severe cases, this can lead to
syndesmotic widening also from chronic lateral ankle overload. 31
Optimal surgical correction of progressive collapsing foot
deformity is still highly debated, with interest in addressing
individual components of the deformity. Lateral column
lengthening corrects forefoot abduction, but there have been
concerns for resultant subtalar stiffness. However, a 2021
biomechanical cadaver study found no decrease in subtalar motion
after lateral column lengthening, suggesting that soft-tissue
scarring rather than bony constraint may be responsible for clinical
stiffness. 32 Repair or reconstruction of the spring ligament has
become a topic of interest; although, there is concern that spring
ligament repair may not provide durable long-term support and
maintenance of correction. Recent studies have evaluated the use of
augmentation techniques with allograft or suture tape to improve
the success of the procedure. 33 A cadaver study found a significant
increase in load to failure after cyclical loading when the spring
ligament was augmented with suture tape versus suture repair
alone. 34

Gait
Any alteration in the biomechanics of the foot and ankle, whether
from disease, acute injury, external braces/immobilization, or
surgical manipulation, will affect gait. Clinical recognition of
various gait pa erns can aid in the diagnosis and management of
foot and ankle problems. Formal gait analysis in a lab with video,
electromyography, and pressure mapping can provide detailed
insight into complex foot and ankle deformities and gait
abnormalities, but these systems have limited availability.
 One of the benefits of TAA over ankle fusion is restoration of a
more normal gait. A recent prospective gait analysis study of
patients who underwent TAA showed improvements in multiple
objective parameters of gait compared with preoperative function,
including increased cadence, walking speed, step length, and peak
ankle power, that was sustained 7 years after the original surgery. 35
Despite many recent advances in implant design and surgical
techniques, hindfoot and ankle kinematics following TAA are
poorly understood. Malalignment of TAA has been associated with
poorer patient outcomes and earlier failure rates, and recent gait
analysis studies may help explain why this occurs and guide new
implant designs.
Recent cadaver gait analysis studies have shown that both
coronal and sagi al plane malalignment of the TAA components
caused altered range of motion (ROM), rotation, and contact
pressures of the tibiotalar joint, plantar pressures during stance,
and periarticular foot kinematics. 36 One study evaluating the effect
of coronal plane malalignment of the tibial component in TAA
showed that varus malalignment led to varus shift and internal
rotation of the tibiotalar joint, a slight increase in the tibiotalar
ROM, and a decrease in the first metatarsophalangeal ROM;
whereas valgus malalignment resulted in increased hallux pressure
with a slight off-loading of the third and fourth metatarsals. 37
Another similar study found that sagi al plane malalignment of
the talar component caused changes in plantar pressures and the
kinematics of periarticular foot joints, and also shifted the center of
pressure laterally during stance. Posterior translation of the talus
caused more differences compared with anterior translation,
including decreased ankle ROM and increased transverse plane
motion. 38 These studies underscore the importance of achieving
appropriate alignment intraoperatively to restore normal gait and
to help prevent unfavorable clinical outcomes associated with
implant loosening, impingement, and early failure.

Summary
Recent advances in applied anatomy and biomechanics have
focused on safe approaches for minimally invasive surgery,
syndesmotic and lateral ankle ligament surgical repair, hallux
valgus deformity, progressive collapsing foot deformity, and
understanding TAA longevity. Exciting new imaging technology,
including weight-bearing CT, single-photon emission CT, and
quantitative MRI, will continue to evolve and become valuable tools
in the diagnosis and treatment of various foot and ankle conditions.

Key Study Points

Hallux valgus and progressive collapsing foot deformity are complex three-
dimensional deformities now better understood because of weight-bearing CT.
Anatomic reduction of the syndesmosis and restoration of uninjured kinematics
continues to be elusive, and currently there is no agreement on the best surgical
fixation technique.
Restoration of coronal and sagittal plane alignment in TAA is critical for restoration of
foot and ankle kinematics and biomechanics.
Single-photon emission CT is helpful in the evaluation of the painful TAA.
Advanced MRI sequencing may allow for improved functional visualization of
articular cartilage and associated pathology.

Annotated References
1. Steadman J, Barg A, Sal man CL: First metatarsal rotation in
hallux valgus deformity. Foot Ankle Int 2021;42(4):510-522.
Traditionally, standard radiographs are used in hallux valgus
evaluation. Newer imaging techniques increase the
understanding of the three-dimensional aspects of hallux valgus
including rotation of the first metatarsal and may lead to
improved reconstruction techniques. Level of evidence: III.
2. McGee R, Watson T, Eudy A, et al: Anatomic relationship of the
sural nerve when performing Achilles tendon repair using the
percutaneous Achilles repair system, a cadaveric study. Foot
Ankle Surg 2021;27(4):427-431. This cadaver study examines the
use of a popular device for minimally invasive Achilles tendon
repair and the risk to the sural nerve with blind passage of
 needles and sutures. The study shows relative safety to the sural
nerve.
3. Krautmann KM, Stewart GW: Evaluation of anatomic
relationship between sural nerve and instrumentation during
mini-open achilles tendon repair: A cadaveric study. Foot Ankle
Orthop 2019;4(4). This cadaver study examines a popular device
for minimally invasive Achilles tendon repair and risk to the
sural nerve. There is a significant risk of puncture but a low rate
of nerve entrapment when the device is removed. Level of
evidence: IV.
4. Clarke T, Whitworth N, Pla S: Defining a safe zone for
percutaneous screw fixation of posterior malleolar fractures. J
Foot Ankle Surg 2021;60(5):929-934. Some posterior malleolus
fractures are amenable to percutaneous screw fixation. This
cadaver study defines a safe zone just lateral to the Achilles
tendon and 1 cm proximal to the tip of the medial malleolus that
avoids damage to neurovascular structures. Level of evidence: V.
5. Peng J, McKissack H, Yu J, et al: Anatomic structures at risk in
anteroposterior screw fixation of posterior malleolar fractures: a
cadaver study. Foot Ankle Surg 2021;27(2):162-167. Anterior
anatomic structures are at risk with anterior-to-posterior
percutaneous placement of screws for posterior malleolus
fractures. This cadaver study showed that risk is minimized when
placed medial to the tibialis anterior tendon. Level of evidence:
IV.
6. Tejero S, Chans-Veres J, Prada-Chamorro E, DeOrio JK:
Protective approach for anatomical structures at risk in total
ankle replacement. J Foot Ankle Surg 2021;60(2):417-420. The
anterior approach to ankle arthroplasty can place the posterior
structures at risk during the use of saws and chisels in distal tibia
resection. An additional posterior medial approach can reduce
the risk of iatrogenic injury to these structures.
7. Hanselman AE, Cody EA, Easley ME, Adams SB, Parekh SG:
Avascular necrosis of the talus after subchondroplasty. Foot Ankle
 Int 2021:42(9):1138-1143. This retrospective case series shows a
concerning rate of avascular necrosis of the talus after a
procedure in which a calcium phosphate bone graft substitute is
injected into the talus to treat symptomatic bone marrow lesions.
Level of evidence: IV.
8. Foran IM, Bohl DD, Vora AM, Mehraban N, Hamid KS, Lee S:
Talar osteonecrosis after subchondroplasty for acute lateral
ligament injuries: case series. Foot Ankle Orthop
2020;5(1):2473011420907072. This retrospective case series shows
a risk of osteonecrosis of the talus after a procedure in which a
calcium phosphate bone graft substitute is injected into the talus
to treat symptomatic bone marrow lesions. Level of evidence: V.
9. Jayatilaka MLT, Philpo MDG, Fisher A, Fisher L, Molloy A,
Mason L: Anatomy of the insertion of the posterior inferior
tibiofibular ligament and the posterior malleolar fracture. Foot
Ankle Int 2019;40(11):1319-1324. This study refutes the importance
of the posterior malleolar fragment in certain ankle fractures.
There is a larger bony insertion of the posterior inferior
tibiofibular ligament onto the posterior tibia than the average
posterior malleolar fragment, suggesting that instability requires
ligamentous injury as well.
10. Mason L, Jayatilaka MLT, Fisher A, Fisher L, Swanton E, Molloy
A: Anatomy of the lateral plantar ligaments of the transverse
metatarsal arch. Foot Ankle Int 2020;41(1):109-114. This cadaver
study describes a lateral plantar ligament that a aches to the
bases of second through fifth metatarsals and blends with the
long planar ligament effectively connecting the transverse and
longitudinal arches of the foot.
11. Conti MS, Ellis SJ: Weight-bearing CT scans in foot and ankle
surgery. J Am Acad Orthop Surg 2020;28(14):e595-e603. Weight-
bearing CT scans are improving understanding of complex foot
and ankle deformities including flatfoot deformity, hallux valgus,
cavovarus, lateral ankle instability, and ankle fractures.
12. Halm JA, Beerekamp MSH, de Muinck-Keijzer RJ, et al:
Intraoperative effect of 2D vs 3D fluoroscopy on quality of
reduction and patient-related outcome in calcaneal fracture
surgery. Foot Ankle Int 2020;41(8):954-963. In this prospective
randomized controlled study, patients were randomized to
conventional two-dimensional or three-dimensional fluoroscopy
during surgical fixation of calcaneus fractures. Three-dimensional
fluoroscopy prolonged surgery time without improving fracture
reduction or function. Level of evidence: I.
13. Jeng CL, Rutherford T, Hull MG, Cerrato RA, Campbell JT:
Assessment of bony subfibular impingement in flatfoot patients
using weight-bearing CT scans. Foot Ankle Int 2019;40(2):152-158.
This study found that 35% of patients with posterior tibial
tendinitis and flatfoot deformity had subfibular impingement on
a coronal weight-bearing CT image and 38% had impingement
between the talus and calcaneus on a sagi al weight-bearing CT
scan. Level of evidence: III.
14. Hagemeijer NC, Chang SH, Abdelaziz ME, et al: Range of
normal and abnormal syndesmotic measurements using
weightbearing CT. Foot Ankle Int 2019;40(12):1430-1437. This study
found significant side-to-side differences in measurements of
syndesmotic area and sagi al translation on weight-bearing CT
in patients with syndesmotic instability. The contralateral side
should be included to detect subtle instability. Level of evidence:
III.
15. Bhimani R, Ashkani-Esfahani S, Lubberts B, et al: Utility of
volumetric measurement via weight-bearing computed
tomography scan to diagnose syndesmotic instability. Foot Ankle
Int 2020;41(7):859-865. The most sensitive measurement on
weight-bearing CT to detect syndesmotic instability is three-
dimensional volumetric measurement spanning from the distal
tibial plafond to 5 cm proximally. This measurement was more
sensitive than two-dimensional measurements. Level of evidence:
III.
16. Richter M, Lin F, de Cesar Ne o C, Barg A, Burssens A:
Results of more than 11,000 scans with weightbearing CT - impact
on costs, radiation exposure, and procedure time. Foot Ankle Surg
2020;26(5):518-522. This study evaluated the use of weight-bearing
CT scans in replacement of radiographs and conventional CT in
4,987 patients and found a 10% decrease in radiation dose per
patient, 77% decreased time spent on imaging acquisition, and
increased financial profit for the institution.
17. Argentieri EC, Sneag DB, Nwawka OK, Po er HG: Updates in
musculoskeletal imaging. Sports Health 2018;10(4):296-302.
18. Gurbani A, Demetracopoulos C, O’Malley M, et al: Correlation
of single-photon emission computed tomography results with
clinical and intraoperative findings in painful total ankle
replacement. Foot Ankle Int 2020;41(6):639-646. In this
retrospective review of patients with a painful TAA, 89.2% of
patients had findings on single-photon emission CT that matched
intraoperative diagnosis. Single-photon emission CT was more
accurate than MRI in diagnosing the cause of a painful TAA.
Level of evidence: III.
19. Serino J, Kunze KN, Jacobsen SK, et al: Nuclear medicine for
the orthopedic foot and ankle surgeon. Foot Ankle Int
2020;41(5):612-623. There is still a role for nuclear imaging in foot
and ankle pathology including bone scans, gallium scans,
leukocyte scans, and single-photon emission CT. Level of
evidence: V.
20. Dyke JP, Garfinkel JH, Volpert L, et al: Imaging of bone
perfusion and metabolism in subjects undergoing total ankle
arthroplasty using. Foot Ankle Int 2019;40(12):1351-1357. There is
concern about disrupting blood supply to the talus during TAA.
This study showed that 18F-fluoride positron emission
tomography/CT scan can quantify perfusion of the talus after
TAA and that perfusion remained intact. Level of evidence: II.
21. Chang SH, Morris BL, Saengsin J, et al: Diagnosis and treatment
of chronic lateral ankle instability: review of our biomechanical
 evidence. J Am Acad Orthop Surg 2021;29(1):3-16. There is no
biomechanically superior surgical technique for chronic lateral
ankle instability. Arthroscopic repair appears to be
biomechanically equivalent to open repairs. Anatomic repair has
sufficient strength to allow immediate weight bearing in a
protective boot.
22. Hunt KJ, Pereira H, Kelley J, et al: The role of calcaneofibular
ligament injury in ankle instability: implications for surgical
management. Am J Sports Med 2019;47(2):431-437. In this cadaver
study, sectioning of the calcaneofibular ligament caused
significant instability of the ankle joint, increased inversion of the
talus and calcaneus, and medial displacement of the calcaneus.
Surgical repair of the calcaneofibular ligament should be
considered.
23. Lubberts B, Massri-Pugin J, Guss D, et al: Arthroscopic
assessment of syndesmotic instability in the sagi al plane in a
cadaveric model. Foot Ankle Int 2020;41(2):237-243. In this cadaver
arthroscopic study, sagi al plane instability occurred after
transection of all three syndesmotic ligaments or partial
syndesmotic transection with deltoid ligament transection. The
optimal cutoff to determine instability was 2 mm of the total
fibular translation.
24. Bhimani R, Lubberts B, Sornsakrin P, et al: Do coronal or
sagi al plane measurements have the highest accuracy to
arthroscopically diagnose syndesmotic instability? Foot Ankle Int
2021;42(6):805-809. This arthroscopic cadaver study showed that
measurement of sagi al plane fibular translation had more
accuracy, sensitivity, and specificity than coronal plane diastasis
for evaluating syndesmotic instability.
25. Wood AR, Arshad SA, Kim H, Stewart D: Kinematic analysis of
combined suture-bu on and suture anchor augment constructs
for ankle syndesmosis injuries. Foot Ankle Int 2020;41(4):463-472.
This cadaver biomechanical study evaluated the effect of suture
bu on and suture anchor augmentation of the anterior inferior
tibiofibular ligament in syndesmotic injuries. Only the constructs
 with suture anchor augmentation of the anterior inferior
tibiofibular ligament increased external rotation constraint of the
fibula.
26. Mococain P, Bejarano-Pineda L, Glisson R, et al: Biomechanical
effect on joint stability of including deltoid ligament repair in an
ankle fracture soft tissue injury model with deltoid and
syndesmotic disruption. Foot Ankle Int 2020;41(9):1158-1164. This
cadaver biomechanical study evaluated injury to both the deltoid
ligament and syndesmosis. This study showed that repair of both
structures reduced internal rotation and lateral translation back
to intact levels but neither repair alone nor in combination
restored external rotation.
27. Lakey E, Kumparatana P, Moon DK, et al: Biomechanical
comparison of all-soft suture anchor single-row vs double-row
bridging construct for insertional achilles tendinopathy. Foot
Ankle Int 2021;42(2):215-223. This biomechanical cadaver study
showed that double-row suture bridge constructs had a 50-N
increase in load to clinical failure compared with single-row all-
suture anchor constructs for insertional Achilles tendon repairs,
but neither was strong enough to allow for immediate weight
bearing.
28. Son HS, Choi JG, Ahn J, Jeong BO: Hindfoot alignment change
after total ankle arthroplasty for varus osteoarthritis. Foot Ankle
Int 2021;42(4):431-439. This clinical case series quantified the
amount of hindfoot varus alignment correction possible with
correction of varus alignment at the tibiotalar joint with TAA.
Level of evidence: IV.
29. Myerson MS, Thordarson DB, Johnson JE, et al: Classification
and nomenclature: progressive collapsing foot deformity. Foot
Ankle Int 2020;41(10):1271-1276. This consensus group statement
renames adult acquired flatfoot deformity to the more descriptive
progressive collapsing flatfoot deformity and presents a new
classification system. The use of MRI and weight-bearing CT is
recommended in this classification system. Level of evidence: V.
30. Dibbern KN, Li S, Vivtcharenko V, et al: Three-dimensional
distance and coverage maps in the assessment of peritalar
subluxation in progressive collapsing foot deformity. Foot Ankle
Int 2021;42(6):757-767. This case-control study used three-
dimensional distance mapping through weight-bearing CT to
evaluate progressive collapsing foot deformity and associated
peritalar subluxation. Revealing of the middle facet provided a
more robust and consistent measure of peritalar subluxation
compared with the posterior facet. Level of evidence: III.
31. Auch E, Barbachan Mansur NS, Alexandre Alves T, et al: Distal
tibiofibular syndesmotic widening in progressive collapsing foot
deformity. Foot Ankle Int 2021;42(6):768-775. This retrospective
study used weight-bearing CT to evaluate patients with
progressive collapsing foot deformity. The study authors found
distal tibiofibular syndesmotic widening suggesting that chronic
lateral impingement results in change in syndesmotic alignment.
Level of evidence: III.
32. Harris MC, Hedrick BN, Zide JR, et al: Effect of lateral column
lengthening on subtalar motion in a cadaveric model. Foot Ankle
Int 2021;42(4):488-494. This cadaver study found no significant
decrease in subtalar motion after lateral column lengthening. It
suggests that clinical decreased motion after this procedure
could be due to soft-tissue constraint rather than bony anatomy.
33. Heyes G, Swanton E, Vosoughi AR, Mason LW, Molloy AP:
Comparative study of spring ligament reconstructions using
either hamstring allograft or synthetic ligament augmentation.
Foot Ankle Int 2020;41(7):803-810. This retrospective cohort study
examined augmented spring ligament repair using a synthetic
fiber tape device or hamstring allograft in flatfoot reconstruction.
Both showed improved radiological alignment; however, the
synthetic augmentation group showed superior patient-reported
outcomes. Level of evidence: III.
34. Aynardi MC, Saloky K, Roush EP, Juliano P, Lewis GS:
Biomechanical evaluation of spring ligament augmentation with
the FiberTape device in a cadaveric flatfoot model. Foot Ankle Int
 2019;40(5):596-602. In this cadaver study, specimens with
simulated flatfoot deformities underwent spring ligament repair
or repair augmented with suture tape. In cyclical loading, the
augmented specimens showed significantly lower rates of failure.
35. Brodsky JW, Sco DJ, Ford S, Coleman S, Daoud Y: Functional
outcomes of total ankle arthroplasty at a mean follow-up of 7.6
years: a prospective, 3-dimensional gait analysis. J Bone Joint Surg
Am 2021;103(6):477-482. This prospective study compared
preoperative gait analysis with postoperative analysis performed
a mean of 7.6 years after TAA. The study authors showed
sustained improvements in multiple parameters. Level of
evidence: IV.
36. Saito GH, Sturnick DR, Ellis SJ, Deland JT, Demetracopoulos
CA: Influence of tibial component position on altered kinematics
following total ankle arthroplasty during simulated gait. Foot
Ankle Int 2019;40(8):873-879. This cadaver study evaluated ankle
kinematics before and after TAA based on tibial component
position. The study authors found significantly increased internal
talar rotation following TAA compared with the native condition,
which correlated with the medial to lateral position of the tibial
implant.
37. Buckner BC, Stender CJ, Baron MD, Hornbuckle JHT, Ledoux
WR, Sangeorzan BJ: Does coronal plane malalignment of the
tibial insert in total ankle arthroplasty alter distal foot bone
mechanics? A cadaveric gait study. Clin Orthop Relat Res
2020;478(7):1683-1695. This cadaver gait study showed that
coronal plane malalignment in TAA altered foot kinematics and
plantar pressure. Varus malalignment caused varus shift and
internal rotation of the tibiotalar joint and valgus malalignment
caused increased hallux pressure.
38. McKearney DA, Stender CJ, Cook BK, et al: Altered range of
motion and plantar pressure in anterior and posterior malaligned
total ankle arthroplasty: a cadaveric gait study. J Bone Joint Surg
Am 2019;101(18):e93. This cadaver gait study showed that anterior
and posterior malalignments of the talar component altered foot
bone kinematics and plantar pressures. More significant
differences were found for posterior malalignments than for
anterior ones.
C H AP T E R 4 8

Degenerative Conditions and

Osteonecrosis of the Foot and
Ankle
Jensen K. Henry MD, Constantine A. Demetracopoulos MD,
FAAOS

Dr. Demetracopoulos or an immediate family member has received royalties from Exactech, Inc.;
is a member of a speakers’ bureau or has made paid presentations on behalf of Exactech, Inc.;
and serves as a paid consultant to or is an employee of Exactech, Inc., In2Bones, MedShape,
and RTI Surgical. Neither Dr. Henry nor any immediate family member has received anything of
value from or has stock or stock options held in a commercial company or institution related
directly or indirectly to the subject of this chapter.

ABSTRACT
Degenerative conditions and osteonecrosis of the foot and ankle
can be debilitatingly painful and functionally limiting for patients.
Unlike other anatomic sites, arthritis of the foot and ankle is often
pos raumatic in etiology. Initial evaluation includes a careful
history, physical examination, and weight-bearing radiographs.
Nonsurgical modalities are routinely a empted first, and include
anti-inflammatory medications, activity modification, shoe wear
modifications, and orthotics. Surgical treatments vary based on the
anatomic location and pathology; however, in the foot and ankle,
arthrodesis is a commonly utilized and reliable technique. Yet,
despite the ubiquity of fusion as a treatment option, concerns
regarding related complications—including loss of motion,
adjacent joint arthritis, and nonunion—have led surgeons to use
additional procedures, including arthroscopy, decompression, and
arthroplasty.
Keywords: ankle arthritis; foot arthritis; hallux rigidus; hindfoot
arthritis; midfoot arthritis

Introduction
Pain in the foot and ankle is incredibly common, affecting 1 in 5
adults older than 45 years. 1 Degenerative conditions represent a
substantial portion of these complaints, and can be a significant
cause of pain, disability, and loss of function. Conversely,
osteonecrosis of the foot and ankle is relatively less common, but
prompt recognition and initiation of treatment will not only
provide symptomatic improvement by lessening pain, but also
prevent progression that can lead to arthritis and deformity. It is
important to highlight the most common degenerative and
osteonecrotic pathologies of the foot and ankle, with a ention
directed to initial nonsurgical treatments, orthotic/shoe wear
recommendations, and surgical treatment strategies.

Ankle Arthritis
Ankle arthritis is a common painful and disabling condition of the
ankle, affecting appropriately 6% of the population. 2 Unlike the
other major joints of the body, where primary osteoarthritis is the
most common etiology, ankle arthritis is most commonly due to
pos raumatic causes. More than 70% of patients with ankle
arthritis report a history of trauma (fracture or chronic instability);
less common causes include primary osteoarthritis, osteonecrosis,
inflammatory arthritis, crystalline arthropathy, infection,
neuroarthropathy, hemophilia, and hemochromatosis. 3 - 5
In these
patients, pos raumatic arthritis may result from the initial cartilage
damage at the time of injury, or from residual malalignment of the
ankle that leads to often rapidly progressive wear of the joint. 3 , 5
 Patients with ankle arthritis can experience debilitating pain and
loss of function. Studies of patient-reported outcomes have shown
that patients with ankle arthritis have Short Form-36 Physical
Component Summary scores that are almost two standard
deviations below the mean of the normal US population. 6
Moreover, physical function scores in these patients are either
similar to or worse than those of individuals with chronic kidney
disease on dialysis, congestive heart failure, and Parkinson disease.
6
Mechanical activity-related pain is a hallmark of ankle arthritis.
Swelling and decreased range of motion are also common.
However, patients classically lose key elements of function as well:
patients with end-stage arthritis have significantly shorter step
length, decreased peak ankle flexion moment, decreased ankle
power, slower walking speed, and decreased ambulation tolerance. 3
All patients should undergo a thorough history and physical
examination, including a ention to prior injuries, extent of
symptoms, and assessment of motion and alignment, as well as a
neurovascular examination. Imaging work-up typically includes
weight-bearing radiographs of the ankle, but may also include
specialized views such as the hindfoot alignment view to assess for
hindfoot malalignment. The traditional radiographic findings of
osteoarthritis (joint space narrowing, subchondral sclerosis,
osteophytic changes, and subchondral cysts) should be noted, but
a ention should also be paid to the alignment of the tibiotalar joint
and lower extremity, coronal and sagi al plane deformities at the
ankle joint, and alignment of the foot. Advanced imaging with CT
and MRI is not required for diagnosis but can be utilized according
to the surgeon’s discretion. CT of the ankle may be used to
determine the bone quality of the ankle and assess for the presence
of subchondral cysts. MRI may be used to assess for concomitant
ligamentous insufficiency and degenerative tendinopathies, as well
as avascular changes within the talus or distal tibial plafond. If the
patient ultimately elects to undergo surgical intervention, weight-
bearing CT may be useful to assess the three-dimensional standing
alignment and bone quality, whereas MRI may identify focal
cartilage defects.
Nonsurgical treatment modalities can be beneficial for symptom
management in ankle arthritis patients. Like all arthritic conditions,
activity modification, NSAIDs, and weight management can be
useful. 4 , 5 Shoe wear modifications, such as a supportive sneaker
with a heel-to-toe rocker-bo om sole, may be beneficial. 7 A more
aggressive orthotic option is an ankle–foot orthosis, which provides
excellent support with the caveat that it may be cumbersome or
irritating with daily use. 4 , 5 Corticosteroid injections may be both
diagnostic and therapeutic in these patients, but should be used
selectively, as the soft tissues of the foot and ankle are vulnerable to
a enuation and destruction with multiple steroid injections. 5
Surgical treatment of ankle arthritis continues to evolve. Multiple
joint-preserving options have emerged, although their effects are
still debated in the literature. Nevertheless, options such as ankle
débridement with anterior tibial/dorsal talar exostectomy,
supramalleolar tibial osteotomy, and ankle distraction arthroplasty
with an external frame and tensioned wires have been pursued. 4 , 5
Further study of the benefits of these surgical strategies, and the
ultimate effects on their ability to delay or prevent joint-sacrificing
surgery, is warranted.
For decades, ankle arthrodesis was the most accepted surgical
option for tibiotalar arthritis. Fusion of the tibiotalar joint results in
reliable pain relief, good patient satisfaction, and improvements in
overall function. 8 Arthrodesis can be performed with a variety of
techniques and approaches, including open or arthroscopic, and
can be stabilized with screws, plates, external fixation, or a
combination of the above. 4 Moreover, it allows for correction of
severe malalignment and multiplanar deformities. However, ankle
arthrodesis is not without complications and long-term concerns,
and there are several valid criticisms. Complication rates are high,
ranging from 9% to as high as 40% in some studies, and nonunion
continues to be a major concern despite advances in surgical
technique, fixation strategy, and the use of biologic adjuvants. 9 In
addition, ankle arthrodesis places aberrant stress on the adjacent
joints and can accelerate arthritic changes in the hindfoot and
midfoot joints. 9 , 10
Total ankle arthroplasty has dramatically improved over the past
2 decades. Advancements in implant design and surgical technique
have led to expanded indications and patient candidacy. Implant
survival rates now reach 80% to 90% or higher at 5 to 10 years, 9 , 11
and newer implants that were introduced to the market in the late
2010s have shown promising early results 12 - 15 (Figure 1).
Furthermore, in direct head-to-head studies of ankle arthrodesis
and total ankle arthroplasty, total ankle arthroplasty more closely
restores gait mechanics to normal, and has improved patient-
reported outcome scores, foot mobility, and ability to navigate
stairs and inclines. 9 , 16

Figure 1 A, Preoperative and B, postoperative AP and lateral weight-bearing

radiographs showing posttraumatic ankle arthritis in a patient with chronic ankle
instability. The patient underwent total ankle arthroplasty with a modern, low-
profile implant.

Hindfoot Arthritis (Subtalar, Talonavicular,

and Calcaneocuboid)
The hindfoot includes the subtalar, talonavicular, and
calcaneocuboid joints, which function as a complex to provide
stability and shock-absorption throughout gait. 5 Accordingly, when
these joints are arthritic, patients routinely complain of pain with
ambulation, and particularly when walking on uneven ground. Pain
is usually localized to the specific areas of the affected joints; for
example, patients with subtalar arthritis will have pain with
palpation at the sinus tarsi. Arthritis in the hindfoot often results
from trauma, such as a history of talar fracture (especially talar
neck). 5 Similarly, calcaneocuboid arthritis often develops after
calcaneal fractures with extension through the anterior process of
the calcaneus. 5 Isolated talonavicular joint is less common, and
often results from inflammatory disease, but also may be due to
trauma, degeneration, or deformity. 5
Nonsurgical treatment measures include NSAIDs, activity
modification, bracing, orthotics, and injections. The mainstay of
surgical treatment for persistently symptomatic hindfoot arthritis is
arthrodesis of the affected joint(s), via a single, double, or triple
arthrodesis.
At the subtalar joint, arthrodesis has a good to excellent success
rate, with union rates reaching 90% or higher 5 , 17 , 18 (Figure 2).
Outcomes are notably worse with a history of tobacco use, revision
arthrodesis, or trauma with loss of calcaneal height. 5 , 17 , 18
Although the rate of calcaneocuboid joint arthritis after trauma is
high, it is often well tolerated by patients. Given the importance of
maintaining motion within the lateral column of the foot,
particularly for walking on uneven ground, many surgeons use a
higher threshold to perform an arthrodesis of the calcaneocuboid
joint. 5 , 17 Arthrodesis at the talonavicular joint is more challenging.
The unique spherical shape of the joint, as well as the challenges in
exposing the entire joint surface, make arthrodesis at this region
highly susceptible to nonunion. 5 , 19 Moreover, fusion of the
talonavicular joint has a tremendously limiting effect on the motion
of the adjacent joints of the hindfoot, reducing motion at the
subtalar joint to less than 10% of its native motion and leading to
arthritic changes in one-third of patients. 5 , 19

Figure 2 A, Preoperative and B, postoperative mortise and lateral radiographs

from a patient with subtalar arthritis who underwent subtalar arthrodesis.

Midfoot Arthritis
Arthritis of the midfoot, which consists of the tarsometatarsal
joints and naviculocuneiform joints, is a common but challenging
problem. Similar to other areas of the foot, arthritis in this region is
most commonly due to pos raumatic etiology, but may also be due
to primary osteoarthritis, inflammatory arthritis, or gout. 20
Although the range of motion of the midfoot is relatively minimal
(4° to 7°) at baseline, degenerative changes and further loss of
motion have disabling and painful effects for patients. 20 , 21 Patients
will present with pain in the midfoot with ambulation that is
exacerbated by activities that require rising off their heels. 20 They
often have dorsal bossing with painful osteophytes over the foot
that preclude many types of shoe wear. 5 , 20 In severe cases, patients
go on to experience not just arthritic changes but deformity in the
region, leading to abduction and dorsiflexion at the midfoot, a
rocker-bo om foot, and pes planus. 5 , 21
Like all areas of the foot, initial nonsurgical treatment of patients
with midfoot arthritis consists of activity modification, NSAIDs,
orthotics, shoe wear modification, and selective injections. The use
of either a stiff-soled shoe or a rigid full-length carbon fiber insert
will reduce the plantar pressure and contact time experienced by
the midfoot during gait. 20 The addition of a rocker-bo om sole
(double rocker bo om) aids in propulsion during gait. 7 , 20
Injections in the midfoot, like all injections in the foot and ankle,
should be used sparingly given the concerns for deleterious effects
of cortisone on the soft tissues, but with limited use can be
uniquely valuable in this region: in addition to providing
therapeutic value, they can also be diagnostic in their ability to
identify which midfoot joints are most symptomatic. It is highly
encouraged that these injections be performed under image
guidance to ensure appropriate placement and to minimize the risk
to the soft tissues. 22
Surgical treatment of midfoot arthritis depends foremost on the
location of the pathology. In the medial and middle columns of the
foot, arthrodesis is the standard of care surgically (Figure 3). The
challenges of surgical intervention in this region include the
frequent need for multiple incisions, risk of nonunion (3% to 7%),
and the need to correct associated deformities such as abduction
and loss of arch height. 20 , 23 Even in the best cases, many patients
may still have residual pain from arthritis in adjacent joints, and
many will require orthotics postoperatively or additional surgery
over time. 23
 Figure 3 A, Preoperative and B, postoperative AP and lateral radiographs from
a patient with midfoot arthritis who underwent arthrodesis of the
naviculocuneiform and second and third tarsometatarsal joints.

Surgical treatment of the lateral column in the midfoot presents

unique treatment challenges. Arthrodesis of the lateral column
results in poor outcomes because of the inherent need for mobility
in this region, the extent of postfusion complications, the risk of
lateral column pain, and stress fractures. 20 As an alternative to
fusion, techniques such as soft-tissue interpositional arthroplasty
or ceramic arthroplasty have been proposed. 24 However, the
optimal treatment continues to be debated, and is often
nonsurgical.

First Metatarsophalangeal Joint Arthritis

(Hallux Rigidus)
Arthritis of the first metatarsophalangeal (MTP) joint, or hallux
rigidus, is the most common form of osteoarthritis in the foot. 25
Hallux rigidus is characterized by pain, swelling, and stiffness at
the first MTP joint. Most commonly, the initial presentation is loss
of great toe dorsiflexion. 5 Patients can also have a dorsal osteophyte
of the first metatarsal head which leads to pain with shoe wear. 25
During the physical examination, it is important to discern whether
the patient has pain only at the extremes of toe dorsiflexion and
plantar flexion, or if there is pain throughout the midrange of
motion. It is also important to assess the relative flexibility of the
great toe. Finally, the surgeon should assess whether the patient
has pain exclusively over the dorsal osteophyte with shoe wear,
pain with motion of the great toe, or both. 26
Weight-bearing radiographs of the foot should be obtained. In
early stages of hallux rigidus, the dorsal osteophyte may be the
primary finding. As the disease progresses, there will be joint space
narrowing, periarticular sclerosis, and apparent fla ening of the
metatarsal head due to osteophyte formation. 26 In late stages of
hallux rigidus, arthritis may progress to the sesamoids as well, and
periarticular cystic changes will occur. Weight-bearing CT and MRI
are less frequently used but may be performed at the surgeon’s
discretion. There are more than 10 classification systems for hallux
rigidus, the most common of which is the Coughlin and Shurnas
classification, which incorporates clinical and radiographic
parameters. 26 However, the limiting nature of all the hallux rigidus
classification systems is that they do not correlate closely with the
severity of symptoms as reported on patient-reported outcome
measures. 27 Further research in this area is warranted.
Nonsurgical modalities for hallux rigidus include NSAIDs,
activity modification, shoe wear modifications, and orthotics.
Patients with pain due to the dorsal osteophytes should be advised
to seek out shoes with a taller toe box or flexible/accommodative
fabric that does not put additional pressure on the spur. A carbon
fiber footplate with a Morton extension provides a rigid support
under the MTP joint to minimize motion and pain while leaving the
lesser toes free. 28 A rocker-bo om sole (toe only) may also decrease
dorsiflexion motion of the first MTP joint. 7 , 28 Corticosteroid
injections should be used sparingly but may provide diagnostic and
therapeutic value.
Surgical treatments for hallux rigidus are varied and frequently
debated. Cheilectomy, which involves resection of the dorsal third
of the metatarsal head and removal of osteophytes around the MTP
joint, is a commonly utilized joint-preserving option. 28 , 29
Cheilectomy may be performed via an open approach or through a
minimally invasive approach using percutaneous incisions and
burrs, as discussed in a 2020 study. 30 Because it only addresses the
bony osteophytes rather than intra-articular pathology, cheilectomy
is best suited for patients with pain primarily due to dorsal spur
impingement. However, one study reported excellent results of
cheilectomy for late-stage hallux rigidus when combined with
dorsal closing-wedge extension (Moberg) osteotomy of the proximal
phalanx, effectively increasing the dorsiflexion ability of the MTP
joint. 29 Arthroscopy of the first MTP joint has also been proposed
as a minimally invasive treatment of hallux rigidus with the added
ability to address intra-articular and sesamoid pathologies. 31
Additional studies of these minimally invasive techniques will be
valuable in assessing their efficacy long term. Regardless, patients
should be cautioned that these joint-preserving treatments may not
completely improve their pain from intra-articular causes, and
additional surgery may be needed as the arthritis progresses.
For more severe stages of hallux rigidus, MTP arthrodesis is the
gold standard and results in excellent and reliable pain reduction
(Figure 4). Satisfaction rates after MTP fusion are consistently 90%
to 100%, with high (>90%) union rates and low rates of
revision/complications. 26 , 28 The primary limitation of MTP
arthrodesis is loss of motion of the first MTP, which may deter
some patients because of concerns about activity participation or
shoe wear. Unfortunately, nonarthrodesis options that a empt to
address intra-articular pathology have been limited. Arthroplasty
and hemiarthroplasty implants have largely been abandoned
because of their unacceptably high rates of complications,
including bone loss, subsidence, and loosening. 28 , 32 There has
been recent interest in a novel synthetic cartilage implant made of
polyvinyl alcohol, which was shown in early studies to preserve
motion at the first MTP and improve pain. 33 However, when
compared to arthrodesis, the synthetic cartilage implant results in
significantly less improvement in pain and symptoms, and
reoperation rates for failure range from 15% to 20%. 33 , 34
 Figure 4 A, Preoperative and B, postoperative AP and lateral radiographs of a
patient with hallux rigidus who was treated with metatarsophalangeal joint
arthrodesis.

Osteonecrosis

Osteonecrosis of the Talus

Osteonecrosis of the talus typically results from trauma: according
to a 2021 study, history of fracture is reported in three-fourths of
cases, and of those patients, most sustained talar neck fractures. 35
The talus is especially susceptible to osteonecrosis due to its
vulnerable blood supply: because it has no tendon a achments or
muscular origins, all of the blood supply of the talus is
extraosseous. 35 , 36 Moreover, because more than 60% of the talar
surface is articular cartilage, there is li le vascular redundancy and
few areas for blood vessel infiltration. 35 - 37 Nontraumatic etiologies
of osteonecrosis include thrombophilic disease, inflammatory
disease (lupus), sickle cell disease, excessive alcohol or steroid use,
or idiopathic causes. The history of presentation is notable for
chronic progressive anterior ankle pain that worsens with
ambulation and activity.
Any work-up begins with weight-bearing radiographs of the foot
and ankle to assess the status of the bone, alignment, and arthritis.
Although early osteonecrosis may present with normal
radiographs, the hallmark of later stages is dense sclerosis (because
the necrotic bone cannot be resorbed), collapse, and ultimately,
arthritic changes at the tibiotalar joint and/or subtalar joint (Figure
5). MRI is typically obtained to assess the extent of the pathology
and bone viability. Early in the process, MRI may only show bony
edema, but later will reveal necrosis of the bone with surrounding
edema and cartilage loss at the level of the joint. 35 The Ficat
classification, which originally used radiographic and MRI findings
to categorize osteonecrosis of the femoral head, has been applied to
the talus as well. 35
 Figure 5 A and B, AP and lateral radiographs, and C and D, MRI sagittal and
coronal views from a patient with osteonecrosis of the talus.

Initial treatment with activity modification, bracing, NSAIDs,

and judicious use of injections can provide some symptomatic
relief in patients. A patellar tendon-bearing brace can be used to
offload the ankle and hindfoot. 35 , 37 Joint-preserving options may
be useful in early stages (necrosis without secondary arthritic
changes in the joint) and include core decompression and
vascularized or nonvascularized bone grafting. 37 Small series have
shown that these treatments can be beneficial in alleviating
symptoms, although more than 10% may eventually require joint-
sacrificing surgeries. 35 , 37
Talar osteonecrosis refractory to the aforementioned measures, or
end-stage talar osteonecrosis with secondary arthritic changes, is
typically managed with joint-sacrificing options. If part of the talus
is viable and unaffected, isolated tibiotalar or subtalar fusion can be
considered. 35 Alternatively, in cases that are associated with ankle
arthritis, if there is sufficient bone stock within the talar body, a
total ankle arthroplasty can be performed with a revision-type talar
implant. In cases of extensive involvement of the talus, treatment
with tibiotalocalcaneal arthrodesis with bulk allograft is indicated
due to the extent of disease throughout the talus and the presence
of arthritis and both the tibiotalar and subtalar joints. 35
Alternatively, surgeons have described performing
tibiotalocalcaneal arthrodesis using external frames, or custom
three-dimensional printed titanium cages filled with bone graft. 35
However, the risk of complications and nonunions is still high; 1 in
5 patients go on to nonunion and 15% require some type of revision
surgery. 35 A novel option described in a 2021 study is a total or
partial talus replacement, in which the talus is removed and
replaced with a custom three-dimensional printed implant based
on the patient’s healthy contralateral side. 35 However, further
investigation is needed to understand the optimal indications and
outcomes of this technique.

Osteonecrosis of the Navicular, Kohler

Disease, and Mueller-Weiss Syndrome
Osteonecrosis of the navicular can broadly be categorized by age
groups in a bimodal distribution—in young children ages 2 to 9
years (Kohler disease; Figure 6) and in middle-aged adults,
commonly women (alternatively named Mueller-Weiss syndrome or
Brailsford disease). In either case, the etiology is unknown; as
described in a 2019 study, theories include primary osteonecrosis,
pos raumatic osteonecrosis, osteochondritis, congenital
abnormality, or undiagnosed stress fracture. 38
Patients typically
present with insidious onset of pain over the dorsum of the midfoot
and ultimately stiff deformity develops in the region. Navicular
osteonecrosis has been associated with multiple foot deformity
pa erns, including cavovarus, planovalgus, or even paradoxical pes
planovarus, but also may occur in a normally aligned foot. 38
Because of the vague symptoms and rarity of the disease, diagnosis
is often delayed in these patients.

Figure 6 A, AP and B, lateral radiographs from a 5-year-old child with Kohler

disease of the navicular.

Weight-bearing radiographs of the foot are the key to diagnosis,

although they may not show abnormality in early stages of the
disease. As the disease progresses, radiographs typically show a
comma-shaped dense navicular on the AP view, with narrowing
and sclerosis on the lateral view. 38 As the lateral portion of the
navicular continues to collapse, the talar head moves laterally and
appears to touch the cuneiforms. 36 In severe stages, imaging may
reveal subtalar varus malalignment, navicular collapse, and
ultimately, complete extrusion of the navicular. 36
Initial nonsurgical treatment with NSAIDs, activity modification,
shoe modification with a stiff sole, midfoot double rocker-bo om
sole, or casting/bracing should be a empted. Any orthotic or brace
should a empt to offload the talonavicular joint during heel rise
and reduce midfoot motion. 38 Patients in whom nonsurgical
treatment fails can be considered for surgery based on the severity
of symptoms, rather than the severity of radiologic findings. There
is no literature consensus on optimal surgical treatment, but the
ultimate goal is a plantigrade, well-aligned foot with restoration of
the medial column. 38 Proposed surgical strategies include joint-
sparing techniques such as decompression, débridement, or
excision, but most typically include isolated talonavicular
arthrodesis versus double or triple hindfoot arthrodesis, typically
accompanied by excision of the lateral portion of the navicular. 38
Again, because the data are limited, optimal treatment may vary
widely based on the individual patient characteristics and surgeon
experience.

Osteonecrosis of the Lesser

Metatarsals/Freiberg Infraction
As described in a 2019 study, osteonecrosis of the metatarsals may
occur secondary to multiple etiologies, including trauma, aberrant
vascular supply, foot biomechanics, and systemic diseases
including hypercoagulability and lupus. 39 Freiberg infraction
specifically refers to osteonecrosis at the second metatarsal head,
after it was identified in the early 20th century in young adult
female patients. The second metatarsal is the most commonly
affected, but osteonecrosis may also occur in the third (27%), fourth
(3%), and fifth (<2%) metatarsals. 39 Patients classically present with
pain on the plantar or dorsal surface of the forefoot that is
exacerbated by walking barefoot, or in shoes with poor support. The
diagnosis presents similarly to stress fractures of the metatarsals
and metatarsalgia, which should be ruled out based on the history,
physical examination, and imaging.
On physical examination, patients will often have swelling or an
effusion at the affected MTP joint in addition to focal tenderness.
Loose bodies or crepitus may be palpated. The surgeon should also
assess for Achilles tendon and/or gastrocnemius-soleus complex
tightness, which may contribute to excessive pressure on the
forefoot.
Radiologic evaluation consists of weight-bearing foot radiographs
and typically MRI (Figure 7). Freiberg infraction is categorized into
five stages: (1) fissuring in the ischemic epiphysis; (2) central
resorption of bone with subchondral subsidence and articular
surface defect (manifesting as fla ening of the metatarsal head); (3)
continued resorption and irregularities of the intact joint surface;
(4) fracture of the peripheral projections and osteochondral loose
bodies at the joint; and (5) fla ening deformity and arthrosis. 40

Figure 7 AP radiograph (A, left) and representative magnetic resonance

images (A, right and B) from a 73-year-old woman with Freiberg infraction.

Initial management, especially for early stages of the disease,

should focus on symptom management and prevention of
worsening deformity. Management typically consists of activity
modification, NSAIDs, and protected weight-bearing using either a
cast, boot, or orthotic/shoe with a rigid sole and/or a metatarsal
pad. 41 These measures are effective for symptom resolution in most
patients.
In severe cases that are refractory to nonsurgical management,
multiple surgical strategies have been described, although the
overall data are limited secondary to the relative rarity of this
pathology. Open or arthroscopic joint débridement allows the
surgeon to remove synovitis, any delaminated cartilage, loose
bodies, and peripheral osteophytes. 41 Core decompression is
theorized to decrease the intraosseous pressure and allow
revascularization in the affected area. 41 Grafting with cancellous
bone graft into the metatarsal shaft, or osteochondral plug
transplant into the joint, have also been described. 41 Osteotomy
(either shortening of the shaft or closing wedge of the head/neck)
can offload the metatarsal and reposition the articular surface.
Finally, excisional arthroplasty or interpositional arthroplasty (with
interposed extensor digitorum brevis tendon) may be performed. 41
Again, in general, there have been positive reports on all of these
techniques, but the data are sparse.

Summary
Degenerative conditions are common in the foot, and broadly can
be categorized into ankle arthritis, subtalar and/or talonavicular
arthritis, midfoot arthritis, and first MTP arthritis. However,
osteonecrosis of the foot is relatively rare, but can occur in almost
any bone of the foot or ankle. In all cases, initial treatment with
activity modification, NSAIDs, shoe wear modification, and
orthotics/bracing is appropriate. For patients in whom nonsurgical
treatment fails, surgical options are vast and include arthroplasty,
decompression, débridement, and arthrodesis.

Key Study Points

 Degenerative conditions of the foot and ankle are common, and initial treatment
consists of activity modification, NSAIDs, shoe wear modification, bracing, and
orthotics.
Arthrodesis is a commonly used surgical option for many degenerative conditions of
the foot and ankle.
At the tibiotalar joint, arthritis can be managed with arthrodesis or arthroplasty in the
well-indicated patient.
Osteonecrosis is relatively rare but can occur in any bone in the foot, and surgeons
should maintain a high index of suspicion when evaluating patients with insidious
chronic foot pain.

Annotated References
1. Thomas MJ, Roddy E, Zhang W, et al: The population prevalence
of foot and ankle pain in middle and old age: A systematic
review. Pain 2011;152:2870-2880.
2. Desai SJ, Glazebrook M, Penner MJ, et al: Quality of life in
bilateral vs. unilateral end-stage ankle arthritis and outcomes of
bilateral vs. unilateral total ankle replacement. J Bone Joint Surg
Am 2017;99:133-140.
3. Segal AD, Shofer J, Hahn ME, et al: Functional limitations
associated with end-stage ankle arthritis. J Bone Joint Surg Am
2012;94:777-783.
4. Thomas RH, Daniels TR: Ankle arthritis. J Bone Joint Surg Am
2003;85-A:923-936.
5. Coughlin MJ, Sal man CL, Anderson RB: Mann’s Surgery of the
Foot and Ankle. Saunders/Elsevier, 2014.
6. Sal man CL, Zimmerman MB, O’Rourke M, et al: Impact of
comorbidities on the measurement of health in patients with
ankle osteoarthritis. J Bone Joint Surg Am 2006;88:2366-2372.
7. Janisse DJ, Janisse E: Shoe modification and the use of orthoses
in the treatment of foot and ankle pathology. J Am Acad Orthop
Surg 2008;16:152-158.
8. Thomas R, Daniels TR, Parker K: Gait analysis and functional
outcomes following ankle arthrodesis for isolated ankle arthritis.
J Bone Joint Surg Am 2006;88: 526-535.
 9. Lawton CD, Butler BA, Dekker RG, et al: Total ankle arthroplasty
versus ankle arthrodesis – A comparison of outcomes over the
last decade. J Orthop Surg Res 2017;12:76.
10. Coester LM, Sal man CL, Leupold J, Pontarelli W: Long- term
results following ankle arthrodesis for post-traumatic arthritis. J
Bone Joint Surg Am 2001;83:219-228.
11. Stewart MG, Green CL, Adams SB, et al: Midterm results of the
Salto Talaris total ankle arthroplasty. Foot Ankle Int
2017;38(11):1215-1221.
12. Penner M, Davis WH, Wing K, et al: The infinity total ankle
system: Early clinical results with 2- to 4-year follow-up. Foot
Ankle Spec 2018;11:159-166.
13. Cody EA, Taylor MA, Nunley JA, et al: Increased early revision
rate with the INFINITY total ankle prosthesis. Foot Ankle Int
2019;40(1):9-17. This level IV retrospective study reviewed the
clinical and radiographic outcomes of a cohort of patients
undergoing total ankle replacement with the INFINITY
prosthesis. Despite having improvements in clinical outcomes,
the authors noted a high incidence of early failure of the tibial
component. Level of evidence: IV.
14. Saito GH, Sanders AE, de Cesar Ne o C, et al: Short-term
complications, reoperations, and radiographic outcomes of a new
fixed-bearing total ankle arthroplasty. Foot Ankle Int 2018;39:787-
794.
15. Rushing CJ, Law R, Hyer CF: Early experience with the
CADENCE total ankle prosthesis. J Foot Ankle Surg 2021;60:67-73.
This level IV retrospective study reported the early outcomes of a
cohort of patients who underwent total ankle replacement with
the CADENCE prosthesis. This was a small cohort of patients (34
ankles) with short follow up (minimum 1 year and average of 24
months). They noted a 94% survivorship in their cohort, and 28%
of patients had a postoperative complication. Level of evidence:
IV.
16. Jastifer J, Coughlin MJ, Hirose C: Performance of total ankle
arthroplasty and ankle arthrodesis on uneven surfaces, stairs,
and inclines: A prospective study. Foot Ankle Int 2015;36:11-17.
17. Easley ME, Trnka HJ, Schon LC, Myerson MS: Isolated subtalar
arthrodesis. J Bone Joint Surg Am 2000;82:613-624.
18. Hollman EJ, van der Vliet QMJ, Alexandridis G, et al: Functional
outcomes and quality of life in patients with subtalar arthrodesis
for pos raumatic arthritis. Injury 2017;48: 1696-1700.
19. Chen CH, Huang PJ, Chen TB, et al: Isolated talonavicular
arthrodesis for talonavicular arthritis. Foot Ankle Int 2001;22:633-
636.
20. Williams KL: Midfoot arthritis, in Chou LB, ed: Orthopaedic
Knowledge Update: Foot and Ankle 5. American Academy of
Orthopaedic Surgeons, 2014, pp 159-166.
21. Jung HG, Myerson MS, Schon LC: Spectrum of operative
treatments and clinical outcomes for atraumatic osteoarthritis of
the tarsometatarsal joints. Foot Ankle Int 2007;28:482-489.
22. Protheroe D, Gadgil A: Guided intra-articular corticosteroid
injections in the midfoot. Foot Ankle Int 2018;39: 1001-1004.
23. Gougoulias N, Lampridis V: Midfoot arthrodesis. Foot Ankle
Surg 2016;22:17-25.
24. Patel A, Rao S, Nawoczenski D, et al: Midfoot arthritis. J Am
Acad Orthop Surg 2010;18:417-425.
25. Coughlin MJ, Shurnas PS: Hallux rigidus: Demographics,
etiology, and radiographic assessment. Foot Ankle Int 2003;24:731-
743.
26. Coughlin MJ, Shurnas PS: Hallux rigidus. Grading and long-
term results of operative treatment. J Bone Joint Surg Am 2003;85-
A:2072-2088.
27. Nixon DC, Lorbeer KF, McCormick JJ, et al: Hallux rigidus grade
does not correlate with foot and ankle ability measure score. J Am
Acad Orthop Surg 2017;25:648-653.
28. Ho B, Baumhauer J: Hallux rigidus. EFORT Open Rev 2017;2:13-
20.
29. O’Malley MJ, Basran HS, Gu Y, et al: Treatment of advanced
stages of hallux rigidus with cheilectomy and phalangeal
osteotomy. J Bone Joint Surg Am 2013;95:606-610.
30. Stevens R, Bursnall M, Chadwick C, et al: Comparison of
complication and reoperation rates for minimally invasive versus
open cheilectomy of the first metatarsophalangeal joint. Foot
Ankle Int 2020;41:31-36. This level III retrospective study
compares reoperations and complications in open and minimally
invasive surgery cheilectomies. The authors describe their
technique for minimally invasive surgery cheilectomy in hallux
rigidus. At mean 3-year follow-up, reoperations and
complications were higher in the minimally invasive surgery
group. Level of evidence: III.
31. Hunt KJ: Hallux metatarsophalangeal (MTP) joint arthroscopy
for hallux rigidus. Foot Ankle Int 2015;36:113-119.
32. Myerson MS, Schon LC, McGuigan FX, Oznur A: Result of
arthrodesis of the hallux metatarsophalangeal joint using bone
graft for restoration of length. Foot Ankle Int 2000;21:297-306.
33. Baumhauer JF, Singh D, Glazebrook M, et al: Prospective,
randomized, multi-centered clinical trial assessing safety and
efficacy of a synthetic cartilage implant versus first
metatarsophalangeal arthrodesis in advanced hallux rigidus. Foot
Ankle Int 2016;37:457-469.
34. Cassinelli SJ, Chen S, Charlton TP, Thordarson DB: Early
outcomes and complications of synthetic cartilage implant for
treatment of hallux rigidus in the United States. Foot Ankle Int
2019;40(10):1140-1148. This level IV case series was one of the first
American studies (and one of the first studies from surgeons
outside the initial randomized controlled trials) of the synthetic
cartilage implant. The authors noted worse outcomes in their
series compared to the initial RCTs, including a 20% reoperation
rate and 38% dissatisfaction. Level of evidence: IV.
35. Parekh SG, Kadakia RJ: Avascular necrosis of the talus. J Am
Acad Orthop Surg 2021;29:e267-e278. This is a level V review article
on the pathogenesis, nonsurgical, and surgical treatment options
for avascular necrosis of the talus. The authors highlight the
challenges presented by this condition, and offer their insights
on the current management of this condition, highlighting their
use of total talus replacement. Level of evidence: V.
36. DiGiovanni CW, Patel A, Calfee R, Nickisch F: Osteonecrosis in
the foot. J Am Acad Orthop Surg 2007;15:208-217.
37. Gross CE, Sershon RA, Frank JM, et al: Treatment of
osteonecrosis of the talus. JBJS Rev 2016;4:1-9.
38. Ahmed ASAA, Kandil MI, Tabl EA, Elgazzar AS: Müller-Weiss
disease: A topical review. Foot Ankle Int 2019;40:1447-1457.
Mueller-Weiss disease is an uncommon condition of the foot and
ankle. This level 5 study, published in the leading foot and ankle
journal, provides a modern update of the presentation, imaging
findings, and treatment options. Level of evidence: V.
39. Wax A, Leland R: Freiberg disease and avascular necrosis of the
metatarsal heads. Foot Ankle Clin 2019;24:69-82. Freiberg disease
is relatively uncommon, and there are few peer-reviewed studies
in the modern era available. This comprehensive review
summarizes this rare condition with modern surgical and
nonsurgical treatment options. Level of evidence: V.
40. Smillie IS: Treatment of Freiberg’s infraction. Proc R Soc Med
1967;60:29-31.
41. Carmont MR, Rees RJ, Blundell CM: Current concepts review:
Freiberg’s disease. Foot Ankle Int 2009;30:167-176.
C H AP T E R 4 9

The Diabetic Foot

Bonnie Y. Chien MD, Lew C. Schon MD, FAAOS, Eric W.
Tan MD, FAAOS

Dr. Schon or an immediate family member has received royalties from Arthrex, Inc., Darco, DJ
Orthopaedics, Stryker, and Zimmer; is a member of a speakers’ bureau or has made paid
presentations on behalf of Avitus, Paragon 28, and Zimmer; serves as a paid consultant to or is
an employee of CurveBeam, Gerson Lehrman Group, Guidepoint Global, MiRus, Paragon 28,
and Zimmer; has stock or stock options held in CurveBeam and Parvizi Surgical Innovation; has
received research or institutional support from Bioventus and Zimmer; has received nonincome
support (such as equipment or services), commercially derived honoraria, or other non–research-
related funding (such as paid travel) from Concepts in Medicine LLC, OMEGA, and Smith &
Nephew; and serves as a board member, owner, officer, or committee member of the American
Academy of Orthopaedic Surgeons. Dr. Tan or an immediate family member is a member of a
speakers’ bureau or has made paid presentations on behalf of Arthrex, Inc.; serves as a paid
consultant to or is an employee of Arthrex, Inc. and Orbis Medical Devices, Inc.; and serves as a
board member, owner, officer, or committee member of the American Academy of Orthopaedic
Surgeons and the American Orthopaedic Foot and Ankle Society. Neither Dr. Chien nor any
immediate family member has received anything of value from or has stock or stock options held
in a commercial company or institution related directly or indirectly to the subject of this chapter.

ABSTRACT
As the incidence and prevalence of diabetes continues to rise, the
burden of orthopaedic issues, particularly of the foot, remains a
major cause of hospitalizations and morbidity. To effectively
manage these issues, a thorough understanding of the systemic
effects and consequences of diabetes is imperative. It is important
to review the pathophysiology and diagnosis of diabetic foot issues,
as well as nonsurgical and surgical treatment options and
considerations for this challenging patient population.
Keywords: Charcot arthropathy; diabetic foot; peripheral
neuropathy

Introduction
There are an estimated 34.2 million people, or 10.5% of the
population in the United States, with diabetes, 1 whereas the
worldwide burden reaches 463 million adults. 2 Direct costs for
diabetes care amounted to approximately $237 billion in 2017. 3 , 4
Approximately one-third of individuals with diabetes will
experience a foot ulcer at some point in their lives, with nearly 20%
requiring an amputation. 5 Diabetic foot ulcers precede more than
80% of all nontraumatic amputations. In the United States, there
are 108,000 lower extremity amputations performed per year in
patients with diabetes. 3 The 5-year mortality for Charcot
arthropathy and diabetic foot ulcers is estimated to approach
approximately 30%, whereas that for minor and major amputations
reaches 46.2% and 56.6%, respectively. The diabetic foot is the
result of multiple diabetes-related systemic diseases including
peripheral sensory neuropathy, peripheral arterial disease (PAD),
skin disorders, renal disease, and osteopenia/osteoporosis. Given
the scope of the diabetes epidemic, orthopaedic surgeons must not
only be able to readily diagnose diabetic foot issues, but perhaps
more importantly, to manage the associated complications, ranging
from ulceration to infection to Charcot arthropathy.

Peripheral Neuropathy and Vasculopathy

Diabetes is a systemic disease stemming from accumulation of and
damage to vasculature by advanced glycation end products, which
instigate an inflammatory cascade leading to impaired perfusion
and global organ dysfunction. 6 Hyperglycemia, insulin resistance,
and dysregulation of lipid metabolism induce multiple downstream
inflammatory kinases and transcription factors such as nuclear
factor kappa B, resulting in proinflammatory cytokine production,
including interleukin (IL)-1 B, IL-2, IL-6, and tumor necrosis factor
alpha. These cytokines activate cellular oxidative stress that leads to
neuronal damage. 7 In addition, excess glucose and fa y acids
overload energy metabolism processes in peripheral nerve cells,
and toxic substrates accumulate in Schwann cells and dorsal root
ganglion neurons, inducing axonal degeneration. It is this
peripheral neuropathy that results in the loss of protective
sensation; its severity is directly correlated with increased risk of
ulceration, amputation, and death. The occurrence rate of distal to
proximal, symmetric polyneuropathy in individuals with diabetes is
approaching 75%. 8 Clinically, the most obvious sign is loss of
sensitivity to the Semmes-Weinstein 5.07/10 g monofilament test.
Multiple points in the foot can be tested and a global extent of
neuropathy can be determined (Figure 1). It is important to note
that motor and autonomic nerves can be affected as well. This can
cause progressive deformity because of muscle imbalance, altered
loading, and trophic and apocrine changes in the skin. Each of
these plays an important role in diabetic foot complications.
Figure 1 Photograph shows the Semmes-Weinstein monofilament test.The
5.07 value indicates the stiffness of the single-fiber nylon threads that make up
the monofilament while 10 g is the force needed to bend it. The 5.07/10 g
combination is thought to be the best indicator to determine loss of protective
sensation.
 In addition, a common misconception is that patients with
neuropathy do not experience pain. The pathogenesis of
neuropathic pain is not fully understood. It likely is related to
chronic hyperglycemic damage to nerves that can cause an increase
in voltage-gated channels that activate nerve potentials and
regeneration of nerve sprouts creating neuromas. The expansion of
new nerves can damage surrounding nerves and expand the
sensitized area via ectopic impulses, leading to a hyperexcited
response, both on a peripheral and central nervous system level. 9
Neuropathic pain is often bilateral and symmetric, characterized as
electric shock–like, burning, and radiating, without necessarily
having a trigger. The typical treatment for neuropathic pain is
pharmacologic, including selective serotonin reuptake inhibitors
and gabapentin or pregabalin.
Furthermore, according to a 2021 study, diabetes is associated
with a twofold to sevenfold increase in PAD. 10 It can increase the
incidence, accelerate the progression, and worsen the severity of
PAD. The amputation rate is four times higher than the national
average in patients with concomitant diabetes mellitus and PAD. 11
With the loss of normal sensory input, motor feedback, vascularity,
and autonomic function, the skin can become dry, easily crack,
ulcerate, and become infected. Therefore, glycemic level checks
establishing proper control of diabetes, foot care, and vascular
assessment should be routinely performed.

Diabetic Foot Ulcers and Infection

Risk Factors and Clinical Evaluation

Neuropathy, vasculopathy, and repetitive trauma create a vicious
cycle for initial and recurrent ulceration. The highest risk factor for
ulceration and infection is history of a previous ulcer. 12 Physical
examination should include assessment of foot deformity and
alignment, areas of contracture or bony prominence that increase
plantar pressure, callus or ulceration presence and depth, and the
Semmes-Weinstein 5.07 (10 g) monofilament test. Poorly fi ing
shoes exerting excessive pressure should be noted. An ulcer that
can be probed to bone has high sensitivity, specificity, and negative
predictive value for osteomyelitis. 13
The presence of the dorsalis pedis and posterior tibialis pulses
should be clearly documented. If absent, arterial Doppler
ultrasonography should be pursued, particularly in the se ing of a
nonhealing ulcer or if surgical intervention is contemplated. An
absolute toe pressure greater than 30 mm Hg has been shown to be
more predictive of healing than the ankle-brachial index, which can
be falsely increased by vessel calcification. 14 , 15 In addition,
transcutaneous oxygen pressure measurements greater than 40 mm
Hg indicate acceptable wound-healing potential. 16 If severe
vascular compromise is present, a vascular surgeon should be
consulted for potential revascularization procedures.

Grading
The Meggi -Wagner classification is commonly used for grading
ulcers. Stages 0 through 2 are based on increasing ulcer depth
without abscess or osteomyelitis, stage 3 represents deep ulcer with
abscess or osteomyelitis, whereas stages 4 and 5 denote localized
and extensive foot gangrene, respectively. This system is simple to
use, has high interrater agreement, and has been validated for
healing and need for lower extremity amputation; however, it does
not account for PAD or infection, nor provide sufficient prognostic
information. 17
More recently, the International Working Group on the Diabetic
Foot has strongly recommended the SINBAD system for
communication about ulcer characteristics. SINBAD is an acronym
for site, ischemia, neuropathy, bacterial infection, and depth, and is
a reproducible, easy scoring system that is not reliant on any
special tests (Table 1). Furthermore, the classification has been
validated for ulcer healing and amputation prediction. 18
Table 1
SINBAD Classification Creates an Easy Acronym and Scoring
System With a Maximum of Six Points for Communication About
Diabetic Ulcers

Category Definition Score

Site Forefoot 0
Midfoot and hindfoot 1
Ischemia At least 1 pedal pulse intact 0
Nonintact pedal pulses 1
Neuropathy Protective sensation intact 0
Protective sensation lost 1
Bacterial infection None 0
Present 1
Area Ulcer <1 cm 2 0
Ulcer ≥1 cm 2 1
Depth Confined to skin and subcutaneous tissue 0
Extending to muscle, tendon or deeper 1
Total possible score 6

Multidisciplinary Care
Given the systemic effects of diabetes, successful ulcer prevention
and treatment involves a multidisciplinary team, including the
orthopaedic surgeon, vascular surgeon, plastic surgeon,
endocrinologist, infectious disease specialist, nutritionist, as well as
the orthotist. Other comorbidities such as hypertension,
hyperlipidemia, renal failure, smoking, nutritional status, and
glucose control based on hemoglobin A1c should be optimized and
rectified to reduce the risks of diabetes-related complications.
Hemoglobin A1c reflects glycemic levels over 2 to 3 months and is
the standard measure to monitor glycemia, with values ≥6.5%
defining diabetes. According to a 2020 systematic review,
hemoglobin A1c greater than or equal to 8% and fasting glucose
levels greater than or equal to 126 mg/dL have been associated with
increased probability of lower extremity amputation in patients
with diabetic foot ulcers. 19
Nonsurgical Management
Treatment of diabetic ulcers must address abnormal mechanical
pressure over the affected area, vascular status, and eradicate
infection. The goal is to achieve an ulcer-free and infection-free
state as well as enable a shoeable foot in therapeutic footwear with
custom inserts and orthotics, as needed.

Wound Care
Without frank abscess or osteomyelitis, most superficial ulcers with
necrotic tissue and callus should be sharply débrided to remove
any potential nidus for infection and to stimulate the healing
response with new granulation tissue. This can be done in the office
or clinic se ing. This is generally well tolerated because of the
patient’s neuropathy. Wet to dry dressings can débride and absorb
exudate from draining wounds, whereas moisturizing agents can be
added to dried lesions. In addition, a negative-pressure dressing
may be needed for persistent ulcers to facilitate healing. Multiple
adjuvant treatments are available, including alginates, colloids, and
silver-impregnated or iodine-impregnated dressings. Additionally,
hyperbaric oxygen therapy is an FDA-approved treatment for
nonhealing ulcers.
After débridement, the vulnerable ulcer or callus area should
then be appropriately offloaded. Regular evaluation with education
on daily skin checks, appropriate shoe wear, and warning signs
indicative of local or systemic deterioration should be emphasized.

Orthoses/Shoe Wear
Offloading distributes the mechanical stress across a larger surface
area over the foot and prevents shear stresses across vulnerable
areas. Total contact casting has been the gold standard with
improved healing rates and faster healing time compared with
removable walking devices. 20 Once the ulcer has reepithelialized
using wound care treatments as described previously, long-term
appropriate shoe wear is necessary to prevent reulceration and
infection. Systematic reviews of footwear and insole designs have
demonstrated stronger evidence for rocker soles and moderate
evidence for custom insoles to reduce peak plantar pressure. 21
Medicare-eligible patients can receive one pair of extra-depth, extra-
wide custom shoes and three pairs of custom insoles per year. 22
Figure 2 shows different orthoses and supportive shoe wear to
protect the diabetic foot in both situations of ulceration as well as
deformity.
Figure 2 Photographs show various orthoses, shoe wear, braces, and boots
to offload and protect the diabetic feet.A, Custom diabetic shoes. These shoes
are usually extra deep and wide. B, Plastazote-based custom inserts.
Plastazote is a manufactured polyethylene foam that is both tough and flexible,
lightweight, does not absorb water, and rebounds to its original shape with
pressure. These properties make it a suitable material for inserts. C, Arizona
brace. This brace is a type of ankle-foot orthosis that was originally designed for
flatfeet but can also be worn inside shoes to support the hindfoot in more neutral
alignment, as patients with diabetes often have similar flatfeet deformities. D,
Charcot restraint orthotic walker boot. This is another ankle-foot orthosis for
 Charcot arthropathy involving the hindfoot and ankle that comes prefabricated
and allows customization with inserts and liners inside the boot.

Nutrition
Patients with diabetes who have foot ulcers are often malnourished.
23
Albumin levels should be routinely checked as part of the
broader infection workup, in addition to white blood cell count,
erythrocyte sedimentation rate, and C-reactive protein level. An
albumin level >3.0 g/dL has been found to be necessary for more
predictable healing, increasing the chance of limb salvage. 24 , 25

Antibiotic Therapy
Most infected diabetic ulcers are polymicrobial, with Staphylococcus
aureus the most common pathogen in non–limb-threatening
infections and gram-negative bacteria and anaerobes dominant in
limb-threatening and life-threatening infections. 26 The role of oral
antibiotic therapy is limited to milder infections and chronic
suppression. If there is inadequate response by 24 to 48 hours,
osteomyelitis, clinical sepsis, or a threatened limb, broad-spectrum
empiric intravenous antibiotics should be initiated. For patients
with possible methicillin-resistant S aureus or Pseudomonas,
empirical antibiotics for these pathogens should be selected. These
antibiotics can be tailored once surgical culture data are obtained.
Consultation with an infectious disease provider should be sought
for patient-specific antibiotic selection.

Vascular Intervention
Revascularization procedures have drastically changed the clinical
course of diabetic foot ulcerations and infections that
conventionally would have necessitated an amputation. This has
resulted in a nearly 30% reduction of major amputation for critical
limb ischemia in patients with diabetes. 27 Once PAD is confirmed
with duplex arterial ultrasonography, a decision on
revascularization is made based on CT angiography and a vascular
surgery consultation. The two main revascularization approaches
are endovascular and open, with both having similar wound-
healing and amputation rates. 28 Revascularization should therefore
be strongly considered before both elective and urgent surgeries. 29

Surgical Management: Débridement With or

Without Primary Versus Secondary Closure
When an ulcer is associated with an abscess or osteomyelitis,
surgical irrigation and débridement is necessary. Sterile deep tissue
and bone culture not exposed to the environment should be
obtained to minimize contamination and provide more accurate
microbiologic information to guide antibiotic therapy. Each
infected compartment must be thoroughly débrided and irrigated
with all necrotic tissue and infected bone removed to prevent the
spread of infection more proximally. Often, multiple débridements
are necessary and wounds may be left open with negative-pressure
dressing application between each débridement. Local delivery of
antibiotics in the form of cement beads or powder can be packed
into the wound to enhance local infection clearance. 30 , 31
Furthermore, plastic surgery may be needed for complex wound
management and soft-tissue coverage.

Amputation
Although amputation is associated with high morbidity in patients
with diabetes, it may be necessary in the se ing of nonhealing foot
wounds, unrelenting infection, and ischemia. The amputation level
is dictated by the extent of infection, vascular supply, soft-tissue
integrity, and functional status. Regardless of the type of incision
that is used, all necrotic and infected tissue must be adequately
excised. In addition, long, full-thickness, plantar soft-tissue flaps
should be maintained to the extent possible after débridement and
bony amputation for wound closure. Depending on the amputation
level, custom extra-depth shoes with molded insoles, ankle-foot
orthoses, or toe fillers are often needed to facilitate mobility.

1. Greater toe
Preservation of the flexor hallucis brevis a achment at the proximal phalanx is
critical to maintaining stability and avoiding sesamoid retraction, which can expose
the first metatarsal head to increased pressures and ulceration. 32 The flexor hallucis
brevis should undergo tenodesis if the proximal phalanx is removed. Postoperatively,
a rigid orthotic, such as a Morton extension, can be used to support the medial
column.

2. Lesser toes
Lesser toe amputations do not produce much deformity or dysfunction except if
the second toe is amputated proximal to or at the metatarsophalangeal joint level. If
some of the proximal phalanx base can be retained, it may prevent the hallux from
shifting into the residual space, creating hallux valgus.
3. Ray
Ray-level amputations most often occur at the bordering first and fifth metatarsals.
The first ray should be preserved whenever possible as it bears most of the weight
through the foot. If the first ray is resected, the loss of the tibialis anterior tendon will
result in a foot drop. Rea aching the tendon to the remaining bone, if possible, may
improve patient function. Similarly, if bony resection of the fifth metatarsal base is
performed, the peroneus brevis a achment should be rea ached to soft tissue or bone
to preserve eversion. This helps to ensure that inversion forces are balanced by
eversion forces, preventing supination deformity and lateral column overload with
subsequently increased risk of recurrent ulceration and infection.

4. Midfoot
When more than two metatarsals need to be amputated, transmetatarsal
amputation is preferable. The metatarsals are cut in a parabola shape following the
normal relative cascade length. To preserve Lisfranc joint stability, about 3 cm of the
proximal second metatarsal base should be maintained. 32 Bone cuts should be
beveled plantarly to offload the typically compromised plantar soft tissue. With
amputations at the Lisfranc joint and proximally, the tibialis anterior and peroneus
brevis a achments should be transferred to maintain dynamic balance. The Achilles
tendon often must be lengthened to offset the loss of dorsiflexion strength and to
prevent an equinus deformity.
5. Hindfoot
Hindfoot amputations at the Chopart joint level, which retain the talus and
calcaneus, usually result in equinus posturing even with Achilles tendon lengthening.
As such, a Syme or Boyd amputation is often performed instead. A Syme amputation
is an ankle disarticulation that creates a weight-bearing surface at the tibial plafond
with the heel pad. Its success depends on the posterior tibialis arterial supply as well
as securing the heel pad to the distal tibia to prevent heel pad migration. The Boyd
 amputation preserves the calcaneus, providing longer stump length and a sturdier
weight-bearing surface. However, it is technically more challenging than the Syme
amputation and relies on tibia-calcaneus arthrodesis.

6. Transtibial amputation
Given the challenges with hindfoot, Syme, and Boyd amputations, it is reasonable
to consider a below-knee or transtibial amputation in severe infection, heel ulcers,
peripheral vascular disease, or nonsalvageable limbs. Although there is higher
mortality and energy expenditure than with more distal amputations, a transtibial
amputation typically provides a more reliable and definitive procedure for patients.

Charcot Arthropathy

Staging/Diagnosis
Although Charcot arthropathy develops in a much smaller
proportion of patients with diabetes (0.56%), it is a devastating
consequence from combined external microtrauma and internal
microvascular effects of poorly controlled diabetes that
progressively destroys the foot and ankle joints. 33 Because of this,
early diagnosis and aggressive care are necessary steps to reduce
the risk of infection and amputation.
Although the exact pathogenesis of Charcot arthropathy remains
unclear, both neuropathy and inflammation appear to be important
contributing factors. Two predominant theories regarding the
etiology include (1) neurovascular—central nervous system damage
directly affects bone nourishment, autonomic reflexes that
stimulate hyperemia, and inflammation resulting in bone
resorption and osteopenia, and (2) neurotraumatic—subclinical
trauma triggers an inflammatory response leading to microfracture,
subluxation, and dislocation. There is likely some element of both.
The pathway to bony resorption and subsequent fracture,
fragmentation, and dislocation stems from increased
proinflammatory cytokines such as tumor necrosis factor alpha and
IL-1B. These factors activate receptor activator of nuclear factor
kappa B ligand binding to receptor activator of nuclear factor kappa
B, upregulating osteoclastic activity that mediates osteolysis. 34
Furthermore, secondary to baseline, coexisting peripheral
neuropathy, the patient often is not aware of any specific trauma,
further exacerbating the bony damage and deformity.
Examination of the foot demonstrates edema, erythema, and
warmth, which is notably different compared with the contralateral,
unaffected side. Frequently, these symptoms of Charcot
arthropathy are misdiagnosed as infection, thrombosis, or gout.
Erythema that subsides after 5 minutes of elevation can help
differentiate Charcot from cellulitis. Weight-bearing radiographs of
the foot and ankle should be obtained to evaluate for any initial
bony deformity and destruction evident in Charcot arthropathy. On
MRI, both acute Charcot arthropathy and infection demonstrate
low signal on T1-weighted images and hyperintensity on T2-
weighted images with contrast enhancement. However, MRI can
show certain pa erns that are more consistent with each etiology;
for instance, bony edema with contiguous spread from a sinus tract,
ulceration, or abscess would more likely suggest osteomyelitis.
Changes associated with Charcot arthropathy include periarticular
and subchondral changes such as fractures and dislocations that
may involve multiple areas. Alternatively, a tagged white blood cell
scan may be er differentiate Charcot arthropathy from
osteomyelitis, especially in the se ing of metal implants. 35
Laboratory infection workup including white blood cell count, C-
reactive protein level, and erythrocyte sedimentation rate can all be
elevated in both Charcot and infection; however, an erythrocyte
sedimentation rate >70 mm/hr has been shown to be strongly
associated with osteomyelitis. 36
Charcot arthropathy was first characterized by Eichenhol . 37
Stage 1 is the fragmentation phase characterized by warmth,
erythema, and edema, which is often confused with infection. On
plain radiographs, the bones are fragmented and associated with
fracture and joint subluxation/dislocation. Stage 2 is the
coalescence phase in which inflammation subsides, and
radiographs show less active bony collapse with replacement by
new bone. Stage 3 is the consolidation phase where the bone and
joint architecture is stabilized, albeit with residual deformity. These
stages can occur in any part of the foot and ankle. The four
commonly affected anatomic areas have been categorized by
Brodsky 38 as type 1, midfoot (tarsometatarsal and
naviculocuneiform joints), most common; type 2, hindfoot
(subtalar, talonavicular, and calcaneocuboid joints), second most
common; type 3A, ankle joint, rare, most unstable; type 3B,
calcaneal tuberosity fracture. 38
Charcot neuroarthropathy most visibly manifests as pes
planovalgus with a plantarmedial bony exostosis in a rocker-
bo om–like deformity with equinus deformity of the ankle from
contracture of the Achilles tendon. This deformity likely stems
from variable denervation of intrinsic and extrinsic musculature,
leading to imbalance in the foot and ankle dorsiflexors and
plantarflexors. During weight bearing, this deformity creates a
pathologic bending moment through the midfoot, which
exacerbates the midfoot arch collapse and rocker-bo om deformity.
39
Combined with absent protective sensation, concurrent obesity,
and osteoporosis that accompany diabetes, the foot will continue to
deform.
The main goal for Charcot arthropathy treatment, whether
surgical or not, is to prevent and cure ulceration and infection by
maintaining a plantigrade foot that can fit into accommodative shoe
wear. Clinically, a plantigrade foot allows the first and fifth
metatarsal heads as well as the heel to evenly contact the ground.
Radiographically, the longitudinal axis through the talar neck
should align with that of the first metatarsal on both the lateral and
AP foot radiographs. If a stable plantigrade foot is achieved
without progressive destructive bony and joint changes, patients
often can function and recover without pain or surgery, even if
radiographically, there is evidence of some residual deformity or
malunion.

Nonsurgical Management
Stage 1 is often managed with non–weight bearing and offloading
in a total contact cast. In the initial hyperemic and edematous
phase, the cast may need to be changed weekly with repeat skin
checks and radiographs. Once swelling and bony consolidation
have stabilized in stage 2, the patient can be transitioned to a
removable ankle-foot orthosis such as a Charcot Restraint Orthotic
Walker or double upright ankle-foot orthosis to accommodate the
deformity and provide stability during weight bearing. Finally,
when the Charcot has se led to stage 3 and the foot size is stable,
the patient can return to accommodative shoes with custom
orthotics.

Surgical Correction of Nonplantigrade Foot

Surgical intervention is usually not recommended during stage 1
when bony fragility can prohibit adequate internal fixation. Ideally,
surgical reconstruction is performed at stage 3 after the acute
inflammatory phase has consolidated. The goal of surgery is to
prevent ulceration and infection, reduce pain, and produce a stable,
shoeable foot. A 2020 study suggests that surgical reconstruction of
Charcot-associated deformities can improve patient outcomes and
prevent further infection and deformity progression. 40 Prior to
elective reconstruction surgery, it is imperative that the global
medical backdrop of diabetes be addressed: glycemic control as
measured by hemoglobin A1c, vascular and nutritional status, and
smoking cessation. Plastic surgery expertise may need to be
solicited in anticipation of complex wounds and ulceration that may
preclude primary closure or negative-pressure therapy and
subsequently require soft-tissue rearrangement or a free flap.
Surgical planning focuses on addressing soft-tissue contractures
and imbalances as well as bony deformity. Techniques include soft-
tissue release, débridement, exostectomy, osteotomy, fusion, and
amputation. The ankle plantarflexors typically are lengthened.
Surgical reconstruction of the common rocker-bo om deformity
with forefoot abduction/adduction typically involves a biplanar
osteotomy with wedge resection at the apex of deformity (Figure 3).
The foot is then aggressively stabilized with internal, external, or
combination rigid fixation to achieve a fusion (Figures 4 and 5).
With infection, fixation can be performed primarily with external
fixation with supplemental percutaneous wire fixation or staged
with temporary external fixation and then transition to internal
fixation once the infection has cleared. The recovery from these
surgical reconstructions is extensive and prolonged non–weight
bearing is necessary, often at least 12 to 16 weeks. Meticulous
a ention to both soft-tissue and bony healing is paramount
throughout the postoperative period to avoid complications.
Figure 3 Intraoperative photographs showing a biplanar wedge osteotomy to
correct abduction and rocker-bottom deformities in the midfoot.A, Biplanar
osteotomy with the wedge resection wider medially and plantarly. B, This
purposeful widening of the wedge medially and plantarly then allows correction
of the abduction and rocker-bottom midfoot deformity in Charcot arthropathy.
Figure 4 A, Photograph shows rocker-bottom deformity associated with
Charcot arthropathy. B, AP, oblique, and lateral radiographs of the foot
demonstrate fragmentation and subluxation at both the tarsometatarsal and
naviculocuneiform joints. The cuboid has become more plantar in position, thus
creating a prominent bony exostosis. C, AP, oblique, and lateral radiographs of
the foot after fixation with screws, including extra-long and wide-caliber screws
that traverse from the hindfoot across the midfoot. Antibiotic beads have also
been packed into the plantar wound.
 Figure 5 A, Lateral foot radiograph from a patient with plantar plate fixation on
the tension side of the deformity to create more stability after fixation and fusion.
B, A hybrid static frame can be used in the setting of infection as well as
tenuous internal fixation to supplement stability.

Amputation
Amputation is typically considered the last resort in the treatment
of recalcitrant infection and deformity in patients with Charcot
arthropathy, but remains an important part of the reconstructive
ladder. However, amputation may be a primary surgical
consideration for patients with extensive soft-tissue compromise,
vascular insufficiency, or limited bone stock available for
reconstruction. The level of amputation should be made based on
the factors highlighted in the previous section.

Summary
The diabetic foot is associated with ulceration, infection,
vasculopathy, neuropathy, and Charcot arthropathy as well as loss
of limb and even life. Diabetes is a multiorgan disease with
tremendous risk of musculoskeletal morbidity and complications,
requiring invested treatment from a multidisciplinary team,
including the orthopaedic surgeon.
Key Study Points
The diabetic foot is affected by vascular, neurologic, musculoskeletal, nutritional, and
bony and soft-tissue factors, all of which must be addressed for optimal outcomes.
Charcot neuroarthropathy is a severe, challenging complication of diabetes. Careful
attention to clinical and radiographic factors is necessary to avoid a delay in
diagnosis.
Treatment of the diabetic foot is involved. Nonsurgical treatment such as total
contact casting and custom shoes offload vulnerable areas. Surgical management
involves soft-tissue balancing, osteotomy, and fusion to create a relatively painless,
ulcer-free and infection-free, plantigrade foot that can fit into custom shoes or
braces. Adjunct revascularization has decreased amputation rates. Nevertheless,
the diabetic foot is always at risk for amputation.

Annotated References
1. Centers for Disease Control and Prevention: National Diabetes
Statistics Report. 2020. Available at:
h ps://www.cdc.gov/diabetes/data/statistics-report/index.html.
Accessed July 2, 2021. This is a report from the Centers for
Disease Control and Prevention in 2020 on the most recent
estimates of diabetes and the burden in the United States,
updated from 2017.
2. International Diabetes Federation: Diabetes facts & figures.
Available at: h ps://idf.org/aboutdiabetes/what-is-diabetes/facts-
figures.html. Accessed July 2, 2021.
3. Armstrong DG, Boulton AJM, Bus SA: Diabetic foot ulcers and
their recurrence. N Engl J Med 2017;376(24):2367-2375.
4. American Diabetes Association: Economic costs of diabetes in
the U.S. in 2017. Diabetes Care 2018;41(5):917-928.
5. Cascini S, Agabiti N, Davoli M, et al: Survival and factors
predicting mortality after major and minor lower-extremity
amputations among patients with diabetes: A population-based
study using health information systems. BMJ Open Diabetes Res
Care 2020;8(1):e001355. This cohort study was performed on
patients with diabetes undergoing amputation to identify risk
 factors for mortality, including older age, cardiovascular
complications, and chronic renal disease. It also discusses the
association of lower extremity amputation with high rates of
diabetic ulcers. Level of evidence: III.
6. Cooper ME, Bonnet F, Oldfield M, Jandeleit-Dahm K:
Mechanisms of diabetic vasculopathy: An overview. Am J
Hypertens 2001;14(5 pt 1):475-486.
7. Pop-Busui R, Ang L, Holmes C, Gallagher K, Feldman EL:
Inflammation as a therapeutic target for diabetic neuropathies.
Curr Diab Rep 2016;16(3):29.
8. Albers JW, Pop-Busui R: Diabetic neuropathy: Mechanisms,
emerging treatments, and subtypes. Curr Neurol Neurosci Rep
2014;14(8):473.
9. Tesfaye S, Boulton AJ, Dickenson AH: Mechanisms and
management of diabetic painful distal symmetrical
polyneuropathy. Diabetes Care 2013;36(9):2456-2465.
10. Soyoye DO, Abiodun OO, Ikem RT, Kolawole BA, Akintomide
AO: Diabetes and peripheral artery disease: A review. World J
Diabetes 2021;12(6):827-838. This is a review article that discusses
the relationship between diabetes and PAD, with patients with
diabetes having more than twofold increase in PAD, with
resulting complications such as nonhealing ulcers and
amputation. Level of evidence: III.
11. Barnes JA, Eid MA, Creager MA, Goodney PP: Epidemiology
and risk of amputation in patients with diabetes mellitus and
peripheral artery disease. Arterioscler Thromb Vasc Biol
2020;40(8):1808-1817. This review article discusses the added
combined burden of diabetes and PAD, with diabetes
exacerbating the progression and severity of PAD. With
concomitant diabetes and PAD, the amputation rate is even
higher. Level of evidence: III.
12. Monteiro-Soares M, Boyko EJ, Ribeiro J, Ribeiro I, Dinis-Ribeiro
M: Predictive factors for diabetic foot ulceration: A systematic
review. Diabetes Metab Res Rev 2012;28(7):574-600.
13. Lavery LA, Armstrong DG, Peters EJ, Lipsky BA: Probe-to-bone
test for diagnosing diabetic foot osteomyelitis: Reliable or relic?
Diabetes Care 2007;30(2):270-274.
14. Herraiz-Adillo A, Cavero-Redondo I, Alvarez-Bueno C, Pozuelo-
Carrascosa DP, Solera-Martinez M: The accuracy of toe brachial
index and ankle brachial index in the diagnosis of lower limb
peripheral arterial disease: A systematic review and meta-
analysis. Atherosclerosis 2020;315:81-92. This systematic review
article compares the diagnostic accuracy of ankle brachial versus
toe brachial indices for PAD. Overall, despite significant
heterogeneity and selection bias, the toe brachial index appeared
to show be er accuracy and sensitivity. Level of evidence: III.
15. Brownrigg JR, Hinchliffe RJ, Apelqvist J, et al: Performance of
prognostic markers in the prediction of wound healing or
amputation among patients with foot ulcers in diabetes: A
systematic review. Diabetes Metab Res Rev 2016;32(suppl 1):128-
135.
16. Leenstra B, Wijnand J, Verhoeven B, et al: Applicability of
transcutaneous oxygen tension measurement in the assessment
of chronic limb-threatening ischemia. Angiology 2020;71(3):208-
216. This review examines variables affecting transcutaneous
oxygen measurements. It does identify that in its systematic
review of other studies, TcPO2 greater than 40 mm Hg in general
is a positive predictor for good ulcer healing and limb prognosis.
Level of evidence: III.
17. Camilleri A, Ga A, Formosa C: Inter-rater reliability of four
validated diabetic foot ulcer classification systems. J Tissue
Viability 2020;29(4):284-290. The authors performed a prospective
comparative study with 40 patients, grading each ulcer using four
different classification systems. All classifications had high
interrater reliability, with the Meggi -Wagner system having the
strongest. Level of evidence: III.
18. Monteiro-Soares M, Russell D, Boyko EJ, et al: Guidelines on the
classification of diabetic foot ulcers (IWGDF 2019). Diabetes Metab
 Res Rev 2020;36(suppl 1):e3273. The International Working Group
on the Diabetic Foot published this new guideline on the use of
active diabetic foot ulcer classifications. Taking into account
communicability, predictability and prognostication, the authors
recommended the SINBAD system as easy to use among
providers. Level of evidence: III.
19. Lane KL, Abusamaan MS, Voss BF, et al: Glycemic control and
diabetic foot ulcer outcomes: A systematic review and meta-
analysis of observational studies. J Diabetes Complications
2020;34(10):107638. This meta-analysis examined the association
between glycemic control and wound healing and amputation
rates in patients with diabetic foot ulcers. Hemoglobin A1c
greater than or equal to 8% and fasting glucose levels ≥126 mg/dL
were determined to increase the likelihood of lower extremity
amputation. Level of evidence: III.
20. Armstrong DG, Nguyen HC, Lavery LA, van Schie CH, Boulton
AJ, Harkless LB: Off-loading the diabetic foot wound: A
randomized clinical trial. Diabetes Care 2001;24(6):1019-1022.
21. Ahmed S, Barwick A, Bu erworth P, Nancarrow S: Footwear
and insole design features that reduce neuropathic plantar
forefoot ulcer risk in people with diabetes: A systematic
literature review. J Foot Ankle Res 2020;13(1):30. This systematic
review found strong evidence for rocker soles to reduce peak
plantar pressure and moderate evidence for custom insoles to
offload forefoot plantar pressure. However, no direct conclusion
could be drawn regarding footwear and insole effects on ulcer
occurrence. Level of evidence: III.
22. Therapeutic shoes & inserts. 2021. Available at:
h ps://www.medicare.gov/coverage/therapeutic-shoes-inserts.
Accessed July 2, 2021. Medicare Part B covers one pair of custom
shoes and inserts (+2 additional inserts) and one pair of extra-
depth shoes (+3 pairs of inserts) each year. Medicare covers these
shoes only if the prescriber and supplier are enrolled in
Medicare.
23. Lauwers P, Dirinck E, Van Bouwel S, et al: Malnutrition and its
relation with diabetic foot ulcer severity and outcome: A review.
Acta Clin Belg 2022;77(1):79-85. This review article identified that
malnutrition is highly prevalent in patients with diabetic foot
ulcer. All studies examined indicated that malnutrition likely has
a negative effect on ulcer outcome. Level of evidence: III.
24. Pinzur MS, Stuck RM, Sage R, Hunt N, Rabinovich Z: Syme
ankle disarticulation in patients with diabetes. J Bone Joint Surg
Am 2003;85(9):1667-1672.
25. Wukich DK, Hobizal KB, Brooks MM: Severity of diabetic foot
infection and rate of limb salvage. Foot Ankle Int 2013;34(3):351-
358.
26. Pitocco D, Spanu T, Di Leo M, et al: Diabetic foot infections: A
comprehensive overview. Eur Rev Med Pharmacol Sci 2019;23(2
suppl):26-37. This comprehensive review focuses specifically on
diabetic foot ulcers and infection as a common sequelae. It
discusses the polymicrobial flora and provides preliminary
guidance on appropriate empiric antibiotic therapy to cover the
most common microorganisms. Level of evidence: III.
27. Egorova NN, Guillerme S, Gelijns A, et al: An analysis of the
outcomes of a decade of experience with lower extremity
revascularization including limb salvage, lengths of stay, and
safety. J Vasc Surg 2010;51(4):878-885.e1.
28. Forsythe RO, Apelqvist J, Boyko EJ, et al: Effectiveness of
revascularisation of the ulcerated foot in patients with diabetes
and peripheral artery disease: A systematic review. Diabetes
Metab Res Rev 2020;36(suppl 1):e3279. This is another systematic
review from the International Working Group of the Diabetic
Foot. Outcomes appeared to be generally similar in patients
treated with open versus endovascular revascularization.
Although revascularization can be successful, mortality was
almost 50% at 5 years. Level of evidence: III.
29. Heidari N, Charalambous A, Kwok I, Vris A, Li Y: Does
revascularization prior to foot and ankle surgery reduce the
 incidence of surgical site infection (SSI)? Foot Ankle Int 2019;40(1
suppl):15S-16S. The authors released a consensus statement
recommending vascular optimization prior to elective foot and
ankle surgery if there is presence of inadequate circulation. They
recognize that there are no studies demonstrating any specific
benefit. Level of evidence: V.
30. Doorgakant A, Davies MB: An approach to managing midfoot
Charcot deformities. Foot Ankle Clin 2020;25(2):319-335. A
systematic approach to managing complex Charcot midfoot
deformities is presented in this article, with a ention to surgical
techniques. It discusses the trend toward earlier surgical
intervention in these patients for improved outcomes. Level of
evidence: III.
31. Krause FG, deVries G, Meakin C, Kalla TP, Younger AS:
Outcome of transmetatarsal amputations in diabetics using
antibiotic beads. Foot Ankle Int 2009;30(6):486-493.
32. Philbin TM, Berlet GC, Lee TH: Lower-extremity amputations in
association with diabetes mellitus. Foot Ankle Clin 2006;11(4):791-
804.
33. Svendsen OL, Rabe OC, Winther-Jensen M, Allin KH: How
common is the rare Charcot foot in patients with diabetes?
Diabetes Care 2021;44(4):e62-e63. This Danish registry–based
study is one of the largest to assess the incidence and prevalence
of Charcot foot in patients with diabetes. They found a
prevalence of 0.56% and incidence of 7.4 per 10,000 person-years.
Level of evidence: III.
34. Kavitha KV, Patil VS, Sanjeevi CB, Unnikrishnan AG: New
concepts in the management of Charcot neuroarthropathy in
diabetes. Adv Exp Med Biol 2021;1307:391-415. This online book
chapter examines the etiology of Charcot neuroarthropathy to
shed light on treatment options. Although the exact etiology of
Charcot neuroarthropathy remains unknown, stimulation of
osteoclast activity is thought to play an important role. Level of
evidence: III.
35. Ertugrul BM, Lipsky BA, Savk O: Osteomyelitis or Charcot
neuro-osteoarthropathy? Differentiating these disorders in
diabetic patients with a foot problem. Diabet Foot Ankle 2013;4.
36. Heidari N, Oh I, Li Y, et al: What is the best method to
differentiate acute Charcot foot from acute infection? Foot Ankle
Int 2019;40(1 suppl):39S-42S. This is a consensus statement with
moderate evidence discussing diagnostic modalities to
differentiate Charcot neuroarthropathy from acute
infection/osteomyelitis. Absence of ulcers and erythema/edema
resolution with elevation make infection less likely. Laboratory
testing, MRI, and culture may benefit in unclear situations. Level
of evidence: V.
37. Eichenhol SN: Charcot Joints. Thomas, 1966.
38. Brodsky J: The diabetic foot, in Coughlin MJ, Mann RA,
Sal man CL, eds: Surgery of the Foot and Ankle. ed 8. Mosby, 2007,
pp 1281-1368.
39. Pinzur MS: Current concepts review: Charcot arthropathy of the
foot and ankle. Foot Ankle Int 2007;28(8):952-959.
40. Pinzur MS: Treatment of ankle and hindfoot Charcot
arthropathy. Foot Ankle Clin 2020;25(2):293-303. The author
discusses his extensive experience with ankle and hindfoot
Charcot arthropathy, which is more challenging than midfoot
deformities. The importance of establishing a normal
relationship of the talus with the calcaneus and the midfoot is
emphasized in surgical reconstruction. Level of evidence: V.
C H AP T E R 5 0

Foot and Ankle Reconstruction

Meghan Kelly MD, PhD

Dr. Kelly or an immediate family member serves as a board member, owner, officer, or committee
member of the American Academy of Orthopaedic Surgeons and the American Orthopaedic Foot
and Ankle Society.

ABSTRACT
Chronic conditions, injuries, and deformities of the foot and ankle
can lead to considerable pain and disability in patients. An
overview of management of foot and ankle injuries and the chronic
conditions that are most commonly encountered by orthopaedic
surgeons should include hallux valgus, the most common deformity
of the metatarsophalangeal joint. This condition can be managed
with a number of surgical procedures depending on the severity of
the deformity and physical examination findings. Other forefoot
disorders include hammer toe, Morton neuroma, turf toe, plantar
plate injuries, and bunione e deformity. These conditions can be
managed without surgery; however, surgical options are available if
nonsurgical measures fail. In the midfoot, deformities such as
progressive collapsing flatfoot or cavovarus also can be initially
managed with bracing and physical therapy, but, if unsuccessful,
joint-sparing bone and soft-tissue balancing procedures can correct
deformity to lessen pain and improve function. Fracture or
disruption of the Lisfranc joint complex is included in the
discussion because it may represent a serious injury that results in
midfoot instability. Severe injury requires surgery to restore
alignment and strength and to maintain stability of the midfoot.
With conditions about the ankle, such as chronic ankle instability,
syndesmotic injury, and acute and chronic Achilles tendon
ruptures, if nonsurgical treatment fails surgery becomes necessary.
Keywords: Achilles tendon; cavovarus; hallux valgus; Lisfranc;
progressive collapsing foot deformity

Introduction
The biomechanical interactions between the foot and ankle joints
are fundamental to maintaining normal function and preventing
degeneration and pain. These interactions can be influenced by the
presence of both congenital and pos raumatic conditions and
deformity. Nonsurgical treatments are typically a empted initially;
however, if these fail, there are surgical options to allow patients to
return to higher activity levels.

Hallux Valgus
Hallux valgus is the most common deformity of the
metatarsophalangeal (MTP) joint and can result from both intrinsic
and extrinsic factors. These include genetic predisposition,
ligamentous laxity, and systemic diseases such as cerebral palsy,
rheumatoid arthritis, or inflammatory arthritis. 1 Hallux valgus also
can result from extrinsic factors such as wearing high-heeled shoes
and shoes with a narrow, pointed toe box. The progression of hallux
valgus deformity is a gradual failure of the medial capsule of the
MTP joint, leading to varus of the metatarsal. 2 As a result, the
flexor hallucis longus and extensor hallucis longus are laterally
deviated relative to the MTP joint axis, and the pull of the adductor
hallucis provides a valgus and pronating force on the proximal
phalanx. Ultimately the crista of the sesamoids erodes, resulting in
lateral subluxation of the sesamoids and further progression of the
deformity.
Patients often report pain over the medial eminence (the
prominent medial portion of the metatarsal head) and numbness
extending into the hallux caused by the stretch of the dorsal medial
cutaneous nerve (a branch of the superficial peroneal nerve). Other
conditions, including metatarsalgia, hammer toes, and claw toes,
may accompany these changes. Patients should be carefully
examined for the underlying ligamentous laxity and evidence of
MTP joint arthritis because this can influence surgical
management. Weight-bearing foot radiographs should be evaluated
for the hallux valgus angle (HVA, normal > 15°), intermetatarsal
angle (IMA, normal < 9°), and distal metatarsal articular angle
(normal < 10°; Figure 1). Plantar gapping of the first tarsometatarsal
(TMT) joint can indicate hypermobility. 3 Initial treatment for hallux
valgus includes footwear modification, bunion pads, night splints,
or special orthotics; however, these have not been shown to be
effective for preventing progression of the deformity.
 Figure 1 AP radiograph of a hallux valgus deformity demonstrating
measurements of hallux valgus angle (HVA) and intermetatarsal angle (IMA).

Surgical correction is considered when nonsurgical methods have

failed to relieve pain and function. An MTP fusion should be
considered in severe bunions or if there is evidence of MTP joint
arthritis because deformity correction will not improve arthritic
pain. Bunions can be managed surgically by a number of different
methods, and the decision is primarily based on characteristics
observed on radiographs. 1 , 4 In general, mild bunions (defined as
IMA < 12° and HVA < 20°) are often managed with a distal
metatarsal osteotomy, whereas moderate bunions (IMA < 15° and
HVA < 40°) are best managed with a proximal metatarsal
osteotomy. Severe bunions (IMA < 15° and HVA < 40°) may require
proximal and distal osteotomies. In addition, if there is evidence of
TMT instability, a Lapidus (TMT joint fusion with distal soft-tissue
correction) should be performed. 3 All osteotomies should be
accompanied by a medial eminence resection and a modified
McBride procedure (a distal soft-tissue rebalancing procedure
involving a lateral capsular release, medial capsule imbrication, and
an adductor hallucis release). In addition, if there is evidence of an
angular deformity of the proximal phalanx (hallux valgus
interphalangeus), a medial-wedge closing osteotomy (Akin) can be
performed. 1 Figure 2 provides a surgical treatment algorithm for
hallux valgus correction. Radiographic evaluation of the sesamoids
can assist with determining the degree of correction. 5

Figure 2 Surgical treatment algorithm for hallux valgus deformity.HVA = hallux

valgus angle, IMA = intermetatarsal angle, MTP = metatarsophalangeal, TMT =
tarsometatarsal
Morton Neuroma
Morton neuroma is an entrapment neuropathy involving the
transverse metatarsal ligament that most often occurs in the third
web space at the location of the confluence of the medial and lateral
plantar nerves. 6 Patients often present with burning plantar foot
pain radiating to the toes that worsens with activity, and may note
sensation alterations in the toes. Imaging is not required; however,
as described in a 2019 study, ultrasonography can be used to
visualize a neuroma, whereas MRI and radiographs are best used to
rule out other pathologies. 7 Ethanol or lidocaine injections can be
performed for diagnostic or therapeutic purposes. 6 Nonsurgical
treatment for Morton neuroma involves wearing shoes with a wide
toe box, metatarsal bars, NSAIDs, and calf stretches. If nonsurgical
methods fail, surgical excision can improve symptoms. The most
common postoperative complication is either inadequate resection
or a stump neuroma.

Lesser Toe Conditions

Lesser toes function with a delicate balance of intrinsic muscles and
extensor and flexor tendons. When this balance is disrupted, lesser
toe deformities can occur. 8 Hammer toes (either flexible or fixed)
occur when there is a contracture of the proximal interphalangeal
joint with extension of the MTP and distal interphalangeal joints.
Claw toes occur when the intrinsic muscles overpower the flexor
and extensor tendons in the toe, resulting in a flexed deformity of
the proximal interphalangeal and distal interphalangeal joints.
Because this process is driven by the foot intrinsic muscles, it is
often seen with traumatic and neurologic etiologies. Finally, mallet
toes are fixed at the distal interphalangeal joint. Treatments include
silicone sleeves or Budin splints. For flexible deformities, surgical
management involves the tendons (eg, flexor digitorum longus
tenotomy with or without extensor digitorum longus repair at the
distal interphalangeal joint), whereas fixed deformities involve
interphalangeal joint resection or arthrodesis 9 (Table 1).
Table 1
Lesser Toe Deformity Characterizations and Surgical
Management

Treatment
Deformity Treatment (Fixed)
(Flexible)
Hammer MTP joint FDL-to-EDL PIP resection, EDL lengthening, MTP joint
toe extension transfer capsulotomy, and collateral ligament release
PIP joint (Girdlestone-Taylor)
flexion
DIP joint
extension
Claw toe MTP joint FDL tenotomy PIP joint resection, DIP joint resection, FDL
extension tenotomy
PIP joint
flexion
DIP joint
flexion
Mallet DIP joint FDL tenotomy DIP resection
toe flexion
DIP = distal interphalangeal, EDL = extensor digitorum longus, FDL = flexor digitorum longus,
MTP = metatarsophalangeal, PIP = proximal interphalangeal

Bunionette Deformity
A bunione e is the deviation of the fifth metatarsal, causing pain
on the lateral aspect of the foot. 10 A type I bunione e is an
overgrowth of the lateral condyle of the metatarsal head, whereas a
type II presents as a curved metatarsal. A type III bunione e
presents as a widened IMA of the fourth and fifth metatarsals.
Treatment of bunione es is primarily nonsurgical, including shoe
modifications and orthotics. Surgical treatment of a type I
bunione e includes ostectomy of the metatarsal head; types II and
III require metatarsal osteotomies to correct alignment. 10 , 11

Turf Toe
Turf toe is a disruption of the plantar capsuloligamentous complex
of the great toe caused by an axial load with the foot in equinus.
This results in hyperextension of the first MTP joint. 12 The injuries
range from a stretching of the capsuloligamentous complex (grade
1) to a complete tear of the capsuloligamentous complex (grade 3).
Patients often present with pain and swelling at the MTP joint and
pain with extension of the great toe. Weight-bearing radiographs of
both feet can be used to evaluate for proximal migration of the
sesamoids, which suggests a tear of the capsuloligamentous
complex. If there is clinical suspicion of this injury, MRI can be
used to determine the degree of ligamentous and articular injury.
Treatment of grade 1 and 2 turf toe includes symptomatic
management with stiff insoles or a Morton extension foot plate or a
short period of immobilization in a controlled ankle movement
boot or a toe spica in mild plantar flexion. Cortisone should not be
used because it can weaken the capsule. Surgical intervention can
be considered in the se ing of a traumatic bunion, a loose body, or
grade 3 injury with significant sesamoid retraction or a large
capsular tear. 13 Surgical intervention involves repair of the plantar
capsuloligamentous complex and can result in good outcomes in
cases of a grade 3 turf toe injury. 12 , 14

Lesser Toe Plantar Plate Injuries

Plantar plate injuries to the lesser toes can be a result of acute or
chronic trauma and can occur with inflammatory arthritis,
neuromuscular disease, or from multiple steroid injections. The
plantar plate stabilizes the MTP joint; therefore, when disrupted
the toe dorsiflexes at the MTP joint because the extensor digitorum
longus tendon overpowers the intrinsic muscles. 15 Plantar plate
injuries often are associated with hammer toes. 16 Nonsurgical
treatment options include orthotics with a metatarsal bar, crossover
toe taping, a gel toe sleeve, or a Budin splint. Surgical treatment
involves a release of the MTP joint and capsule and repair. 17 This
procedure often is done in conjunction with a distal metatarsal
osteotomy to allow for proper reduction of the joint and to
maintain forefoot balance. 16
Progressive Collapsing Foot Deformity
Progressive collapsing foot deformity (PCFD), previously termed
adult acquired flatfoot deformity or posterior tibial tendon
dysfunction, is a syndrome resulting from a series of alterations in
the architecture of the foot. 18 It often begins as dysfunction of the
posterior tibial tendon and the thinning and stretching of the
calcaneonavicular (spring) ligament. 19 , 20 This results in the
collapse of the midfoot and valgus tilt of the calcaneus. The rotation
of the calcaneus results in uncoverage of the talar head and lateral
translation of the navicular on the talus. Although previous
classifications were based on deformity and physical examination,
there has been recent emphasis on development of a new
classification system that be er encompasses this pathology
associated with PCFD. 18 The new classification is split into flexible
(stage I) and rigid (stage II) deformities and is separated into five
anatomic locations of deformity labeled A through E (Table 2). For
each deformity location, an indication of whether it is flexible or
fixed is indicated as well. For example, a patient with a flexible
hindfoot valgus and forefoot varus without additional deformity
would be classified as 1AC, whereas a patient with a fixed hindfoot
valgus with a flexible forefoot varus would be classified as 2A1C.
This be er represents the spectrum of disease and be er classifies
the range of deformities in the syndrome. Often initially, patients
present with medial pain from posterior tibial tendinitis, and as the
deformity worsens the pain shifts to the lateral ankle as a result of
subfibular impingement on the calcaneus. Physical examination
demonstrates hindfoot valgus and loss of medial arch. When
viewed from behind, the “too many toes” sign is evident on the
affected foot, and there is failure of inversion when performing a
heel raise.

Table 2
New Classification of Progressive Collapsing Foot Deformity

Stage
 Stage
I—Flexible II—Rigid
Class Location
I—Flexible Clinical Findings
II—Rigid Radiographic Findings
Class Location Clinical Findings Radiographic Findings
A Hindfoot Hindfoot valgus (“too Hindfoot valgus
many toes” sign)
B Midfoot Forefoot abduction Decreased talar head coverage
Increased talonavicular coverage angle
C Forefoot Forefoot varus medial Plantar gapping at first
column instability tarsometatarsal/naviculocuneiform joints
Increased talus, first tarsometataral angle
D Peritalar Subfibular impingement Significant subtalar joint subluxation
region
E Ankle Ankle instability Valgus tilt of ankle
Modified with permission from Myerson MS, Thordarson DB, Johnson JE, et al: Classification
and nomenclature: progressive collapsing foot deformity. Foot Ankle Int 2020;41(10):1271-
1276.

Imaging in patients undergoing evaluation for PCFD should

include weight-bearing foot and ankle radiographs to evaluate for
the lateral talar/first TMT angle and uncovering of the talar head.
Hindfoot alignment views can be helpful as well for surgical
planning. Although not required for diagnosis, advanced imaging
modalities such as CT or MRI can be performed to identify the
presence of subtalar osteoarthritis and to evaluate the posterior
tibial tendon integrity. Initial treatments for PCFD include
NSAIDs, ice, medial heel post orthotics, and physical therapy
focusing on posterior tibial tendon strengthening. If the deformity
changes extend into the ankle, an Arizona brace can be prescribed.
If nonsurgical measures have failed, surgical treatment is based on
the degree and locations of deformity.
Surgical treatment of patients with PCFD is based on the location
and flexibility of deformities. In most cases if a deformity is flexible,
osteotomies are performed to improve alignment, whereas fusions
are performed in the se ing of a rigid deformity. For example, a
patient with an isolated hindfoot valgus with adequate
talonavicular coverage and without forefoot varus can be treated
with an isolated bony procedure such as medializing calcaneal
osteotomy. This is often performed in the se ing of additional soft-
tissue procedures such as a spring ligament reconstruction and/or
flexor digitorum longus transfer that often occurs with a
gastrocnemius recession. 21 If there is evidence of talar head
uncoverage greater than 50%, a lateral column lengthening is
considered and there does not appear to be a difference in
outcomes in patients older than 65 years compared with younger
patients who undergo the same procedures. 22 , 23 For patients with
fixed deformities, a double or triple arthrodesis is performed (the
subtalar, talonavicular, and calcaneocuboid joints). Once the
hindfoot and midfoot procedures are completed, the forefoot
should be evaluated for a residual varus deformity, which can
develop over time as compensation for the hindfoot valgus. If
present, a dorsal opening wedge osteotomy of the medial
cuneiform (Co on) should be performed to prevent lateral foot
overload. 24 However, if there is evidence of TMT joint arthritis, a
first TMT joint plantar flexion fusion should be performed instead
of a Co on osteotomy. Finally, if the deformity extends to the ankle,
treatment is based on whether there is evidence of ankle arthritis. 19
, 20
If cartilage loss is less than 50% on the lateral aspect of the joint
and the deformity is flexible, ligament rebalancing through
procedures such as a deltoid reconstruction can be performed to
restore talar tilt. However, if ankle arthritis is evident, either an
ankle fusion or ankle arthroplasty can be considered in conjunction
with the foot procedures.

Cavovarus Foot Deformity

Cavus foot is defined as a plantarflexed first ray, which results in a
high medial longitudinal arch. This often occurs in conjunction
with a varus deformity of the heel. 25 Cavovarus is often bilateral
and, for many patients, asymptomatic. Often the development of
cavovarus disorder is related to neurologic conditions including
cerebrovascular accident, traumatic nerve injuries, or cerebral palsy
or can be a result of a pos raumatic deformity from a talar or
calcaneal fracture. 26 , 27 One of the most common neurologic
conditions resulting in a cavovarus foot deformity is Charcot-Marie-
Tooth disease, an autosomal dominant motor sensory neuropathy
that presents in two types: type 1, which has an underlying myelin
disorder; and type 2, which demonstrates abnormal axonal
function, resulting in a later presentation than type 1. 25 The
neuropathy progresses from distal to proximal, resulting in early
dysfunction of the intrinsic muscles in the feet and progressing to
the anterior tibialis muscle and then the peroneus brevis. As a
result, there is an overpowering by the posterior tibialis muscle and
the peroneus longus muscle, pulling the hindfoot into varus and
ultimately resulting in plantar flexion of the first ray and a cavus-
appearing arch.
These patients can also present with claw toes, metatarsalgia, and
subtle foot drop and will describe a history of recurrent ankle
sprains or a history of fifth metatarsal fractures in conjunction with
ankle sprains, and peroneal tendinopathy. 28 Physical examination
will reveal an Achilles tendon or gastrocnemius muscle contracture
and lateral callosities and a varus hindfoot (peek-a-boo heel sign in
which the medial heel pad is visible from the front); however, it is
important to evaluate the etiology of the hindfoot varus by the use
of the Coleman block test. 25 - 27 A block is placed under the heel
and the lateral half of the foot, and if the hindfoot varus is
corrected, then the varus is considered flexible, or forefoot driven.
Weight-bearing radiographs performed of the foot and ankle will
reveal an increased Meary angle, metatarsal stacking, and increased
calcaneal pitch (Figure 3). The varus heel produces the drive-
through sign, a visible space in the subtalar joint. Hindfoot
radiographs can be obtained to evaluate the degree of varus.
Additional imaging modalities, such as weight-bearing CT and
MRI, can be used to evaluate for evidence of arthritis or tendon
dysfunction, respectively, but they are not required for diagnosis. If
there is no known neurologic diagnosis, then electromyography or
a nerve conduction study, genetic evaluation, or a muscle biopsy
can be used to determine the underlying etiology.
 Figure 3 Weight-bearing lateral (A) and AP (B) radiographs of a cavovarus
foot demonstrating increased calcaneal pitch, increased Meary angle, and
metatarsal stacking.

Initial management of cavovarus deformity is with lateral heel

posting orthotics with medial arch support and a recessed first ray
and physical therapy focused on peroneal tendon strengthening. 25
If the deformity is more severe, an ankle-foot orthosis or an
Arizona brace can be considered to allow for concomitant
stabilization of the ankle joint. Once nonsurgical measures have
failed, surgery can be considered. As with PCFD, joint-sparing
procedures are considered initially for flexible deformities. 27 Initial
management of a flexible hindfoot deformity is focused on the rigid
forefoot, including a dorsiflexion osteotomy of the first metatarsal
or dorsiflexion TMT arthrodesis to correct the forefoot-driven varus.
To decrease the pull of the first metatarsal head, the osteotomy is
often done in conjunction with a peroneus longus brevis transfer.
In addition a plantar fascia release can be performed because these
procedures can increase the pull on the plantar aponeurosis.
Finally, if a clawed hallux is present, a release of the extensor
hallucis longus and transfer to the metatarsal neck (Jones
procedure) and an interphalangeal fusion can be performed.
If the deformity is fixed or hindfoot driven, the hindfoot varus is
corrected using either a lateralizing or closing wedge osteotomy of
the calcaneus. 25 In addition, patients with dorsiflexion weakness
(eg, CMT) may benefit from transfer of the posterior tibial tendon
to the lateral cuneiform through the interosseus membrane of the
tibia to use the overpowering posterior tibialis muscle as a
dorsiflexor and everter of the foot. If the deformity is fixed or
arthritis is present, as in the se ing of PCFD, subtalar joint or triple
arthrodesis is considered.
It is important to evaluate for the presence of a subtle cavus
deformity in all patients presenting with recurrent ankle instability
or fifth metatarsal fractures because management of these
conditions may be less successful as a result of the influence of the
underlying foot deformity. 28

Chronic Ankle Instability

Ankle sprains are one of the most common injuries encountered by
health care professionals. According to a 2021 study, it is estimated
that up to 23,000 inversion injuries occur daily in the United States.
29
An inversion force results in an injury to the lateral ligamentous
structures of the ankle joint (the anterior tibiofibular ligament
[ATFL], the calcaneofibular ligament [CFL], [PTFL] and the
posterior talofibular ligament). Approximately 90% of the time,
there is an injury to the ATFL, whereas the CFL is injured
approximately 20% to 40% of the time. 30 Ankle sprains are initially
managed with rest, ice, compression, and elevation, with early
involvement of physical therapy focused on proprioception and
neuromuscular training. Although most patients improve with
physical therapy, up to 20% of patients can progress to chronic
ankle instability. 31
 Several factors predispose a patient to the development of
chronic ankle instability, including connective tissue disorders,
generalized ligamentous laxity, cavus foot alignment, or tarsal
coalitions. 29 - 31 Patients often describe a sense of giving way and a
history of recurrent sprains with intermi ent pain and swelling of
the affected ankle. Evaluation of a patient may reveal joint effusion
and pain with palpation over the lateral ligamentous complex.
Patients also may describe pain posterior to the fibula because the
peroneal tendons are the secondary stabilizers of the ankle joint.
Integrity of the ATFL and CFL can be evaluated with an anterior
drawer test and a talar tilt test, which should be compared with the
contralateral limb. The patient’s underlying tissue laxity should be
taken into consideration. Weight-bearing ankle radiographs (AP,
mortise, and lateral) should be performed and can be
supplemented with a stress test while performing an anterior
drawer or talar tilt test. MRI is not required to establish a diagnosis
of instability but can be useful to evaluate for associated pathology
such as peroneal tendon tears or osteochondral lesions of the talus,
which may have implications for surgical management.
Most ankle sprains do not develop into chronic instability. Thus,
acute repair of lateral ligaments after a first-time injury is rarely
indicated. Nonsurgical measures should be a empted, including
physical therapy, bracing, and orthotics if a hindfoot deformity is
present. However, if these measures fail, and chronic instability
develops, surgery can be considered. Surgery for chronic ankle
instability can be classified as either anatomic or nonanatomic
repair and can be performed with or without augmentation. 29 , 32
Anatomic measures involve repair or reconstruction of the ATFL
and CFL into their insertion sites in the fibula. The Broström repair
with the Gould modification is the most common and effective
method involving imbrication of the lateral ligamentous complex
with a reinforcing extensor retinacular repair (the Gould
modification). 32 , 33 This method has excellent long-term outcomes:
one study revealed 91% satisfaction at 26-year follow-up of a series
of 22 patients, whereas another study demonstrated 93% patient
satisfaction in a mean follow-up of 11 years of 150 patients. 34 , 35
More recent methods have been developed, including arthroscopic
repair and augmentation with suture tape, to allow for an
accelerated rehabilitation protocol, but long-term studies are not
available to date. Nonanatomic methods of lateral ligament
stabilization generally use the peroneal brevis tendon to stabilize
the ankle joint. 32 This can be an a ractive option in the se ing of
poor ligament quality, revision se ings, or ligamentous laxity,
factors that predispose a patient to failure of an anatomic repair or
reconstruction.

Syndesmosis Injury
The syndesmosis is a complex of structures including the anterior
inferior tibiofibular ligament, the posterior inferior tibiofibular
ligament, the interosseus membrane, the interosseus ligament, and
the inferior transverse ligament with the purpose to resist
rotational, axial, and translational forces between the tibia and the
fibula. 36 The syndesmosis often is injured in the se ing of an
external rotation injury and occurs in approximately 13% of ankle
fractures; however, it can also be injured in the se ing of an ankle
sprain without associated fracture. Patients with concern for a
syndesmotic injury without evidence of an ankle fracture have pain
over the syndesmosis, which is anterior and proximal to the ATFL.
Weight-bearing radiographs may reveal decreased tibiofibular
overlap and increased medial clear space. Contralateral weight-
bearing ankle radiographs are helpful for comparison. MRI may be
used if there is clinical suspicion for injury in the se ing of normal
radiographs 37 (Figure 4).
 Figure 4 Coronal (A) and axial (B) magnetic resonance images of a chronic
syndesmosis injury.

A syndesmotic sprain without diastasis noted on radiographs can

be managed nonsurgically with a period of immobilization
followed by physical therapy. Outcomes for nonsurgical treatment
are highly variable, and healing can take longer than for a typical
ankle sprain. Surgical intervention involves reduction of the
syndesmosis and stabilization with either screws or a flexible
suture bu on construct. In addition, a hybrid construct of both a
syndesmotic screw and a suture bu on can be performed. The use
of screw fixation relies on an accurate reduction of the syndesmosis;
however, studies have suggested that malreduction can occur up to
40% of the time, and often screws require surgical removal. 38 More
recent studies suggest that flexible fixation may result in a quicker
return to activity compared with screw construct and have
improved rates of reduction. 39 , 40

Peroneal Tendinopathy
The peroneal tendons are the secondary stabilizers of the ankle
joint, and patients with a history of ankle instability may present
with pain along the tendon sheath. 41 A thorough history and
physical examination should be performed to evaluate for extrinsic
factors that may predispose a patient to continued pain and
inflammation including chronic ankle instability, a cavus foot,
ligamentous laxity, prominent peroneal tubercle, a low-lying
peroneal brevis muscle belly, or an accessory peroneus muscle.
Evaluation often demonstrates pain distal to the fibula and along
the peroneal tendon sheath and pain with resisted ankle eversion.
Weight-bearing radiographs of the ankle can be performed to
assess for evidence of chronic ankle instability or for hindfoot
deformities. MRI can be useful to evaluate for a peroneal tendon
tear or other associated pathologies such as a low-lying muscle
belly or an accessory tendon.
Initial treatment for peroneal tendinitis is physical therapy and
anti-inflammatory medications. If pain is a limiting factor, an
ultrasound-guided tendon sheath injection of an anti-inflammatory
medication such as ketorolac can be used to provide relief and
allow strength improvement with physical therapy. 41 , 42 Other
nonsurgical modalities include a brief period of immobilization,
bracing, or orthotics, especially in the presence of the varus
hindfoot. If nonsurgical measures fail, surgical intervention can be
considered. This often involves evaluation of both the peroneal
longus and brevis tendons and tenolysis of any inflammatory tissue
or adhesions. If a tear is present and comprises less than 50% of the
tendon, it can be débrided; however, if more than 50% of the
tendon is degenerative, either a tendon tubularization or a
tenodesis can be considered. It is important to note that if there is
an underlying foot deformity, the deformity should be corrected at
the time of surgery to prevent recurrence.

Achilles Tendon Disorders

Achilles Tendon Rupture

The Achilles tendon is the largest and thickest tendon in the body,
withstanding forces up to 12 times body weight. 43 The Achilles
tendon is round in cross-section to an area about 4 cm proximal to
the insertion into the calcaneus where it begins to fla en. This
location also represents a watershed region of vascularity, leaving it
prone to injury. Seventy-five percent of ruptures occur between 2
and 6 cm proximal to the Achilles insertion into the calcaneus and
are often a result of an eccentric loading event. Patients are
primarily between the ages of 30 and 40 years and describe a sense
of ge ing kicked from behind with subsequent pain and swelling.
Up to 30% of patients may reveal prodromal symptoms of Achilles
tendinosis before rupture.
The diagnosis of an Achilles rupture is primarily a clinical
diagnosis, often including pain, swelling, and ecchymosis in the
affected side. A palpable defect along the Achilles tendon may be
present as well as an increase in resting dorsiflexion compared with
the contralateral limb when the patient is lying prone with the
knees bent. Furthermore, a positive Thompson test (lack of plantar
flexion with calf squeeze) is highly sensitive and specific for
rupture. Although not necessary for diagnosis, ultrasonography or
MRI can be used to further evaluate the level of rupture, associated
pathology, or for preoperative planning purposes (Figure 5).
 Figure 5 Sagittal view of an acute Achilles rupture on T1-weighted MRI.

Acute ruptures can be successfully managed surgically or

nonsurgically using an accelerated rehabilitation protocol. 44 - 47
Traditionally, nonsurgical management involved casting or
splinting and immobilization of a patient for 6 to 8 weeks, which
demonstrated a higher rate of re-rupture compared with surgically
treated patients. 43 , 48 However, recent studies using an accelerated
rehabilitation protocol, which allows for protected weight bearing
starting at 2 weeks and activity advancement with the assistance of
physical therapy, demonstrated similar re-rupture rates to those
treated surgically and most patients returning to their prior level of
sports and activity. 45 , 46 , 49 It should be noted that inclusion criteria
for the accelerated rehabilitation protocol include placement into a
plantarflexed splint or cast within 48 hours and a midsubstance
rupture, whereas exclusion criteria include patients with a history
of diabetes or use of steroids. 46 Surgical management has been
demonstrated to have a shorter return to work and sport; therefore,
further studies are needed to determine the optimal management
of these injuries. 45 , 50
Surgical management of Achilles ruptures can be performed by
open, mini-open, or percutaneous techniques. 43 The open approach
involves an end-to-end repair of the tendon using either a Krakow
or locking Bunnell-style repair and can be reinforced with the
insertion of the suture from the proximal stump into the calcaneus.
The mini-open or percutaneous approaches are a ractive options
because they have been shown to have a lower risk of wound
complications or scarring and quicker surgical time, and although
they have a higher risk of sural nerve injury and incidence of a
palpable suture knot in some studies, this has not been a universal
finding. 51 , 52 The percutaneous method involves using a specialized
jig inserted into the paratenon of the Achilles tendon where
nonabsorbable sutures are placed in a locking manner. This
method can be used for a direct repair or with augmentation of
suture anchors into the calcaneus as described in a 2019 study. 53
Chronic Achilles tendon ruptures (those present for longer than
8 weeks) are often repaired surgically and are frequently the result
of a missed initial diagnosis. 54 Without repair this can lead to
chronic weakness in the affected leg or loss of push-off strength,
resulting in the need of an ankle-foot orthosis for ambulation. In a
chronic se ing, these may also require augmentation for repair
based on the size of the defect. For defects smaller than 2 cm, a
direct repair can be performed; however, a defect between 2 and 5
cm may require a concomitant gastrocnemius fascia lengthening, a
V-Y tendon advancement, and/or a flexor hallucis longus transfer.
For those larger than 5 cm, an allograft with or without a
gastrocnemius turndown, V-Y advancement, or tendon transfer will
be required. Studies surrounding these treatments are generally
limited to small case studies.
Achilles Tendinosis
Achilles tendinopathy can be categorized into insertional and
noninsertional based on the location of pain. 55 This is generally
accompanied with swelling and prominence. Evaluation of the
tendon reveals a degenerative process termed angiofibroplastic
hyperplasia: the presence of dense populations of fibroblasts,
vascular hyperplasia, and disorganized collagen resulting in
decreased strength and elasticity. Noninsertional Achilles-
tendinosis often presents with pain and swelling 4 to 6 cm from the
insertion of the Achilles tendon into the calcaneus. Insertional
Achilles tendinopathy presents as pain at the insertion and is often
seen in patients with a history of obesity, hypertension, diabetes,
inflammatory arthropathies, and in those with increased age.
Evaluation of these patients should focus on assessment for
equinus contracture, and weight-bearing ankle radiographs should
be obtained to determine whether a Haglund deformity
(prominence of the superior posterolateral calcaneus) or
intratendinous calcification is present. Advanced imaging
modalities, such as ultrasonography or MRI, are not required for
diagnosis but can be used to evaluate tendon quality for
preoperative planning.
Nonsurgical management of Achilles tendinopathy starts with a
brief period of rest, immobilization, silicone heel cups, and calf
stretching focused on the equinus contracture. Physical therapy
also has demonstrated high levels of success with insertional, and
to a lesser degree noninsertional, Achilles tendinopathy focusing
on eccentric strengthening. The addition of extracorporeal shock
wave therapy to an eccentric physical therapy program has
demonstrated improved patient outcomes compared with physical
therapy alone. 56 However, the use of platelet-rich plasma has not
shown a clear benefit in several studies. 57 , 58
Surgical management of Achilles tendinopathy can be
considered after a 6-month trial of nonsurgical therapy. 55
Insertional Achilles tendinopathy is managed with débridement of
the tendon and resection of the Haglund deformity. If tendon
débridement is more than 50% of the cross-sectional area, the
repair should be augmented with a flexor hallucis longus tendon
transfer. 59 Furthermore, if the tendon is entirely taken off the
calcaneus, a double-row repair with suture anchors can be
performed to ensure adequate healing to the posterior aspect of the
calcaneus. More recently an endoscopic resection of the Haglund
deformity, tendon débridement, and rea achment with suture
augmentation has been described with excellent results. However
additional larger and comparative studies are needed to determine
whether this method has superior outcomes compared with an
open approach. 60 Posteromedial and posterolateral portals are used
for access to the calcaneus, but there is a risk of injury to the sural
nerve.
There are a number of treatments proposed for the surgical
management of noninsertional tendinosis. Percutaneous
tenotomies, tendon stripping, and endoscopic tendon débridement
can be performed. 61 , 62 However in the se ing of severe
degeneration, an open repair may be required and may require
augmentation if more than 50% of the tendon is involved. 62

Plantar Fasciitis
Plantar fasciitis is common among athletes and nonathletes and is a
chronic overuse condition resulting in microtears in the origin of
the plantar fascia on the medial aspect of the calcaneal tubercle. 63
Persistent and repetitive trauma to the plantar fascia causes
recurrent inflammation that can also involve other structures
including the abductor hallucis, flexor digitorum brevis, and
quadratus plantae that share the same insertion location on the
calcaneus. Patients often note start-up pain (pain with first step in
the morning or after a period of rest) that improves with
ambulation and then worsens throughout the day. Physical
examination reveals tenderness at the medial insertion of the
plantar fascia, and often this is accompanied by a tight Achilles
tendon. Weight-bearing radiographs often are normal, but there
may be evidence of a plantar heel spur in chronic se ings.
Additional imaging is not required unless there is concern for other
accompanying conditions. Initial management consists of
stretching of the plantar fascia and calf stretching along with
NSAIDs for pain control. Night splints and shoe inserts can be
considered; however, their effectiveness is not universal. In severe
cases, a brief period of immobilization may improve symptoms but
should be done in conjunction with diligent stretching exercises.
Injections with NSAIDs also can be considered, but corticosteroid
injections are not recommended because they can lead to plantar
fat pad atrophy or plantar fascia rupture. For patients in whom
nonsurgical management for 6 months has failed, extracorporeal
shock wave therapy can be effective. If, despite all nonsurgical
treatments, there are continued symptoms, a surgical release of the
plantar fascia can be considered, which should be performed in
conjunction with release of the abductor hallucis.

Lisfranc Injuries
The Lisfranc complex is made up of three articulations: the
tarsometatarsal (second metatarsal and medial cuneiform), the
intermetatarsal (first and second metatarsal), and the intertarsal
(medial and middle cuneiform) joints. 64 The metatarsal bases form
an arch in the coronal plane with the second metatarsal base
serving as a keystone, and it is proximally recessed; therefore, it is
an important osseous structure contributing to the overall stability
of the midfoot. Ligaments that run from the medial cuneiform and
the second metatarsal base include the dorsal and plantar oblique
ligaments and the Lisfranc ligament, the strongest in the complex.
Lisfranc injuries tend to fall into two categories: a direct injury
that is often high energy (crush injury, motor vehicle collision) and
is associated with soft-tissue trauma and potential for vascular
compromise, and indirect injuries from athletic injuries or a fall
from height resulting in an axial load or rotational forces through a
hyperplantarflexed foot. 65 Patients with difficulty bearing weight,
significant midfoot swelling, and plantar arch ecchymosis should
be approached with a high degree of suspicion because up to 40%
of injuries are missed on initial radiographs. 64 , 65 Patients often
present with significant tenderness to palpation at the first and
second TMT joint and pain with passive pronation and abduction.
High-energy etiologies can present with deep peroneal nerve or
artery injuries and should be evaluated for the development of
compartment syndrome.
Initial imaging should include bilateral weight-bearing AP views
of the feet. The AP view should be evaluated for alignment of the
medial second metatarsal with the medial border of the middle
cuneiform with less than 2 mm of diastasis between the first and
second metatarsal bases compared with the contralateral foot. On
the oblique view the medial border of the fourth metatarsal should
align with the medial edge of the cuboid. Finally on the lateral view,
the dorsal cortices of the first metatarsal and medial cuneiform
should align. A fleck sign (an avulsion fracture of the second
metatarsal base) may also be observed. CT can be used to evaluate
high-energy injuries if there are concerns for additional fractures
(Figure 6). MRI can be a useful adjunct if there is concern for a
ligamentous injury because radiographic findings may be
equivocal. Lisfranc injuries are classified into three categories: type
A is total incongruity (homolateral) in which all TMT joints are
incongruent; type B is partial incongruity in which one or more
articulations remain intact; and type C is divergent in which the
medial TMT joints displace medially, whereas lateral TMTs displace
laterally.
 Figure 6 Weight-bearing AP radiograph (A) demonstrating a subtle Lisfranc
injury and second metatarsal fracture (fleck sign, arrow) better appreciated on
coronal CT (B).

Lisfranc injuries can be managed nonsurgically if the patient is a

poor surgical candidate or there is no evidence of instability on
examination or imaging. This treatment involves limited weight
bearing for 6 weeks with gradual return to weight bearing.
However, surgical treatment is used for most Lisfranc injuries
because nonsurgical management in the se ing of instability can
result in significant pain and pos raumatic arthritis rates of up to
30%. Surgical management of a Lisfranc injury can be either a
primary arthrodesis or open reduction and internal fixation (ORIF),
with the most important clinical factor being an accurate reduction.
66
It is debatable whether ORIF versus primary arthrodesis results
in superior outcomes. However, primary arthrodesis is generally
advocated in the se ing of a delayed presentation or ligamentous
injury, or in patients who may present with conditions, such as
obesity or diabetes, that may affect successful healing. If primary
arthrodesis is to be performed, the fourth and fifth TMT joints
should only undergo temporary fixation. ORIF can allow for
preservation of the joints but requires a second surgery for removal
of hardware. More recently, as described in a 2020 study, the
development of flexible fixation techniques allows for ORIF to occur
without the need for a second surgery; however, additional studies
are needed to determine whether this method results in superior
outcomes in comparison to either screw and plate ORIF or
arthrodesis. 67

Summary
A number of conditions can arise with alterations in foot structure
and biomechanics resulting in pain and loss of function. An
understanding of the role of these deformities and how to approach
reconstruction is important to ensure a successful recovery.
Ligamentous and tendon injuries also can result in severe loss of
function and chronic pain; therefore, an understanding of soft-
tissue balancing and appropriate diagnosis is important to ensure a
return to a normal level of function.

Key Study Points

Surgical management of hallux valgus is based on the degree of deformity and
aspects of the physical examination. Often this involves a lateral MTP joint capsular
release, imbrication of the medial joint capsule, and a metatarsal osteotomy in the
absence of MTP joint arthritis or TMT joint instability.
PCFD often occurs in the setting of posterior tibial tendon dysfunction, whereas
cavovarus deformity often has a neurologic etiology. If initial management with
physical therapy and bracing fails, surgical management involves a combination of
tendon transfers and osteotomies to improve alignment.
Ankle instability is the sense of giving way and recurrent sprains and is initially
managed with physical therapy with a focus on proprioception and neuromuscular
training. Surgical intervention for ankle instability is either an anatomic or
nonanatomic repair or reconstruction of the lateral ligament complex to restore
function.
Lisfranc injuries are often missed on initial examination but can lead to midfoot
collapse and instability. Surgical options include primary fusion or ORIF of the
Lisfranc joint depending on imaging findings and injury pattern.
Annotated References
1. Shi GG, Whalen JL, Turner NSIII, Kitaoka HB: Operative
approach to adult hallux valgus deformity: Principles and
techniques. J Am Acad Orthop Surg 2020;28(10): 410-418. This
review article discusses hallux valgus deformity, etiology,
diagnosis, and surgical correction options.
2. Easley ME, Trnka HJ: Current concepts review: hallux valgus part
1 – Pathomechanics, clinical assessment, and nonoperative
management. Foot Ankle Int 2007;28(5): 654-659.
3. Doty JF, Harris WT: Hallux valgus deformity and treatment: A
three-dimensional approach. Foot Ankle Clin 2018;23(2):271-280.
4. Easley ME, Trnka HJ: Current concepts review: Hallux valgus
part II – Operative treatment. Foot Ankle Int 2007;28(6):748-758.
5. Chen JY, Rikhraj K, Gatot C, Lee JY, Singh Rikhraj I: Tibial
sesamoid position influence on functional outcome and
satisfaction after hallux valgus surgery. Foot Ankle Int
2016;37(11):1178-1182.
6. Di Caprio F, Meringolo R, Shehab Eddine M, Ponziani L:
Morton’s interdigital neuroma of the foot: A literature review.
Foot Ankle Surg 2018;24(2):92-98.
7. Raouf T, Rogero R, McDonald E, et al: Value of preoperative
imaging and intraoperative histopathology in Morton’s neuroma.
Foot Ankle Int 2019;40(9):1032-1036. The authors present a
retrospective review of 313 suspected neuromas to evaluate the
utility of preoperative imaging and histopathology to determine
whether these factors guide treatment decisions. More than 98%
of suspected Morton neuromas were confirmed on pathology
demonstrating the accuracy of a clinical evaluation. Level of
evidence: IV.
8. Coughlin MJ: Lesser-toe abnormalities. J Bone Joint Surg Am
2002;84(8):1446-1469.
 9. Coughlin MJ, Dorris J, Polk E: Operative repair of the fixed
hammertoe deformity. Foot Ankle Int 2000;21(2):94-104.
10. Shi GG, Humayun A, Whalen JL, Kitaoka HB: Management of
bunione e deformity. J Am Acad Orthop Surg 2018;26(19):e396-
e404.
11. Moran MM, Claridge RJ: Chevron osteotomy for bunione e.
Foot Ankle Int 1994;15(12):684-688.
12. Anderson RB, Hunt KJ, McCormick JJ: Management of common
sports-related injuries about the foot and ankle. J Am Acad Orthop
Surg 2010;18(9):546-556.
13. Covell DJ, Lareau CR, Anderson RB: Operative treatment of
traumatic hallux valgus in elite athletes. Foot Ankle Int
2017;38(6):590-595.
14. Smith K, Waldrop N: Operative outcomes of grade 3 turf toe
injuries in competitive football players. Foot Ankle Int
2018;39(9):1076-1081.
15. Deland JT, Lee KT, Sobel M, DiCarlo EF: Anatomy of the plantar
plate and its a achments in the lesser metatarsal phalangeal
joint. Foot Ankle Int 1995;16(8):480-486.
16. Doty JF, Coughlin MJ: Metatarsophalangeal joint instability of
the lesser toes and plantar plate deficiency. J Am Acad Orthop
Surg 2014;22(4):235-245.
17. Flint WW, Macias DM, Jastifer JR, Doty JF, Hirose CB, Coughlin
MJ: Plantar plate repair for lesser metatarsophalangeal joint
instability. Foot Ankle Int 2017;38(3):234-242.
18. Myerson MS, Thordarson DB, Johnson JE, et al: Classification
and nomenclature: Progressive collapsing foot deformity. Foot
Ankle Int. 2020;41(10):1271-1276. This article presents a consensus
statement regarding the nomenclature for progressive collapsing
flatfoot deformity. Level of evidence: V.
19. Deland JT: Adult-acquired flatfoot deformity. J Am Acad Orthop
Surg 2008;16(7):399-406.
20. Pinney SJ, Lin SS: Current concept review: Acquired adult
flatfoot deformity. Foot Ankle Int 2006;27(1):66-75.
21. Schon LC, de Cesar Ne o C, Day J, et al: Consensus for the
indication of a medializing displacement calcaneal osteotomy in
the treatment of progressive collapsing foot deformity. Foot Ankle
Int 2020;41(10):1282-1285. The authors present a consensus
statement regarding the use of a calcaneal osteotomy for
treatment of progressive collapsing foot deformity. Level of
evidence: V.
22. Thordarson DB, Schon LC, de Cesar Ne o C, et al: Consensus
for the indication of lateral column lengthening in the treatment
of progressive collapsing foot deformity. Foot Ankle Int
2020;41(10):1286-1288. The authors present a consensus statement
regarding the use of lateral column lengthening in patients with
progressive collapsing foot deformity. Level of evidence: V.
23. Conti MS, Jones MT, Savenkov O, Deland JT, Ellis SJ: Outcomes
of reconstruction of the stage II adult-acquired flatfoot deformity
in older patients. Foot Ankle Int 2018;39(9):1019-1027.
24. Johnson JE, Sangeorzan BJ, de Cesar Ne o C, et al: Consensus
on indications for medial cuneiform opening wedge (co on)
osteotomy in the treatment of progressive collapsing foot
deformity. Foot Ankle Int 2020;41(10):1289-1291. The authors
present a consensus statement regarding the use of midfoot
osteotomies to correct residual hindfoot varus in surgical fixation
of collapsing progressive foot deformity. Level of evidence: V.
25. Kaplan JRM, Aiyer A, Cerrato RA, Jeng CL, Campbell JT:
Operative treatment of the cavovarus foot. Foot Ankle Int
2018;39(11):1370-1382.
26. Neumann JA, Nickisch F: Neurologic disorders and cavovarus
deformity. Foot Ankle Clin 2019;24(2):195-203. This review article
discusses the etiology, progression, and treatments of cavovarus
foot deformity.
27. Deben SE, Pomeroy GC: Subtle cavus foot: Diagnosis and
management. J Am Acad Orthop Surg 2014;22(8):512-520.
28. Fortin PT, Gue ler J, Manoli AII: Idiopathic cavovarus and
lateral ankle instability: Recognition and treatment implications
relating to ankle arthritis. Foot Ankle Int 2002;23(11):1031-1037.
29. Allen T, Kelly M: Modern open and minimally invasive
stabilization of chronic lateral ankle instability. Foot Ankle Clin
2021;26(1):87-101. The authors review the etiology and surgical
and nonsurgical management of chronic lateral ankle stability.
30. Stephens MM, Sammarco GJ: The stabilizing role of the lateral
ligament complex around the ankle and subtalar joints. Foot
Ankle 1992;13(3):130-136.
31. Petersen W, Rembi ki IV, Koppenburg AG, et al: Treatment of
acute ankle ligament injuries: A systematic review. Arch Orthop
Trauma Surg 2013;133(8):1129-1141.
32. Yasui Y, Shimozono Y, Kennedy JG: Surgical procedures for
chronic lateral ankle instability. J Am Acad Orthop Surg
2018;26(7):223-230.
33. Broström L: Sprained ankles. VI. Surgical treatment of
“chronic” ligament ruptures. Acta Chir Scand 1966;132(5):551-565.
34. Bell SJ, Mologne TS, Sitler DF, Cox JS: Twenty-six-year results
after Broström procedure for chronic lateral ankle instability. Am
J Sports Med 2006;34(6):975-978.
35. Tourné Y, Mabit C, Moroney PJ, Chaussard C, Saragaglia D:
Long-term follow-up of lateral reconstruction with extensor
retinaculum flap for chronic ankle instability. Foot Ankle Int
2012;33(12):1079-1086.
36. Wake J, Martin KD: Syndesmosis injury from diagnosis to
repair: Physical examination, diagnosis, and arthroscopic-assisted
reduction. J Am Acad Orthop Surg 2020;28(13):517-527. This review
article discusses treatment of acute and chronic syndesmotic
injury.
37. Beumer A, van Hemert WL, Niesing R, et al: Radiographic
measurement of the distal tibiofibular syndesmosis has limited
use. Clin Orthop Relat Res 2004;2004(423): 227-234.
38. Sagi HC, Shah AR, Sanders RW: The functional consequence of
syndesmotic joint malreduction at a minimum 2-year follow-up. J
Orthop Trauma 2012;26(7):439-443.
39. Sanders D, Schneider P, Taylor M, Tieszer C, Lawendy AR,
Canadian Orthopaedic Trauma Society: Improved reduction of
the tibiofibular syndesmosis with tightrope compared with screw
fixation: Results of a randomized controlled study. J Orthop
Trauma 2019;33(11):531-537. This randomized controlled trial
assessed 103 patients who underwent surgical reduction of the
syndesmosis demonstrating malreduction of the syndesmosis
39% of the time with screw fixation and 15% of the time with
flexible fixation. Level of evidence: I.
40. Zhang P, Liang Y, He J, Fang Y, Chen P, Wang J. A systematic
review of suture-bu on versus syndesmotic screw in the
treatment of distal tibiofibular syndesmosis injury. BMC
Musculoskelet Disord 2017;18(1):286.
41. van Dijk PAD, Kerkhoffs GMMJ, Chiodo C, DiGiovanni CW:
Chronic disorders of the peroneal tendons: Current concepts
review of the literature. J Am Acad Orthop Surg. 2019;27(16):590-
598. This review article discusses pathologies related to peroneal
tendons.
42. Clarke HD, Kitaoka HB, Ehman RL: Peroneal tendon injuries.
Foot Ankle Int 1998;19(5):280-288.
43. Kadakia AR, Dekker RGII, Ho BS: Acute Achilles tendon
ruptures: An update on treatment. J Am Acad Orthop Surg
2017;25(1):23-31.
44. Willits K, Amendola A, Bryant D, et al: Operative versus
nonoperative treatment of acute Achilles tendon ruptures: A
multicenter randomized trial using accelerated functional
rehabilitation. J Bone Joint Surg Am 2010;92(17):2767-2775.
45. Soroceanu A, Sidhwa F, Aarabi S, Kaufman A, Glazebrook M:
Surgical versus nonsurgical treatment of acute Achilles tendon
rupture: a meta-analysis of randomized trials. J Bone Joint Surg
Am 2012;94(23):2136-2143.
46. Glazebrook M, Rubinger D: Functional rehabilitation for
nonsurgical treatment of acute Achilles tendon rupture. Foot
Ankle Clin 2019;24(3):387-398. This review article discusses the
accelerated rehabilitation protocol used in the study discussed in
reference 41.
47. Lan o I, Heikkinen J, Flinkkila T, et al: A prospective
randomized trial comparing surgical and nonsurgical treatments
of acute Achilles tendon ruptures. Am J Sports Med
2016;44(9):2406-2414.
48. Khan RJ, Fick D, Keogh A, Crawford J, Brammar T, Parker M:
Treatment of acute Achilles tendon ruptures. A meta-analysis of
randomized, controlled trials. J Bone Joint Surg Am
2005;87(10):2202-2210.
49. Lerch TD, Schwinghammer A, Schmaranzer F, et al: Return to
sport and patient satisfaction at 5-year follow-up after
nonoperative treatment for acute Achilles tendon rupture. Foot
Ankle Int 2020;41(7):784-792. This retrospective observational
study examines functional outcomes at 1 year and 5 years
following nonsurgical management of Achilles tendon rupture.
Level of evidence: III.
50. Renninger CH: Operative and nonoperative management of
Achilles tendon ruptures in active duty military population. Foot
Ankle Int 2016;37(3):269-273.
51. Ga M, Driessen A, Eschweiler J, Tingart M, Migliorini F: Open
versus minimally-invasive surgery for Achilles tendon rupture: A
meta-analysis study. Arch Orthop Trauma Surg 2021;141(3):383-
401. This is a meta-analysis of 25 studies (levels I-III) examining
complications related to 2,223 patients undergoing surgical
treatment for Achilles tendon ruptures by either open or
minimally invasive techniques. Level of evidence: III.
52. Grassi A, Amendola A, Samuelsson K, et al: Minimally invasive
versus open repair for acute Achilles tendon rupture: Meta-
analysis showing reduced complications, with similar outcomes,
 after minimally invasive surgery. J Bone Joint Surg Am
2018;100(22):1969-1981.
53. Patel MS, Kadakia AR: Minimally invasive treatments of acute
Achilles tendon ruptures. Foot Ankle Clin 2019;24(3):399-424. This
is a review article regarding outcomes of minimally invasive
treatment for Achilles tendon ruptures and surgical techniques.
54. Hahn F, Meyer P, Maiwald C, Zane i M, Vienne P: Treatment of
chronic Achilles tendinopathy and ruptures with flexor hallucis
tendon transfer: Clinical outcome and MRI findings. Foot Ankle
Int 2008;29(8):794-802.
55. Kearney R, Costa ML: Insertional Achilles tendinopathy
management: A systematic review. Foot Ankle Int 2010;31(8):689-
694.
56. Vahdatpour B, Forouzan H, Momeni F, Ahmadi M, Taheri P:
Effectiveness of extracorporeal shockwave therapy for chronic
Achilles tendinopathy: A randomized clinical trial. J Res Med Sci
2018;23:37.
57. Madhi MI, Yausep OE, Khamdan K, Trigkilidas D: The use of
PRP in treatment of Achilles tendinopathy: A systematic review
of literature. Study design – systematic review of literature. Ann
Med Surg (Lond) 2020;55:320-326. This systematic review of 11
studies evaluates the effect of platelet-rich plasma on Achilles
tendinosis, which demonstrate possible improvement in
symptoms in smaller studies but no improvement in higher
powered studies.
58. Zhang YJ, Xu SZ, Gu PC, et al: Is platelet-rich plasma injection
effective for chronic Achilles tendinopathy? A meta-analysis. Clin
Orthop Relat Res 2018;476(8):1633-1641.
59. Hunt KJ, Cohen BE, Davis WH, Anderson RB, Jones CP: Surgical
treatment of insertional Achilles tendinopathy with or without
flexor hallucis longus tendon transfer: A prospective, randomized
study. Foot Ankle Int 2015;36(9):998-1005.
60. Vega J, Baduell A, Malagelada F, Allmendinger J, Dalmau-
Pastor M: Endoscopic Achilles tendon augmentation with suture
 anchors after calcaneal exostectomy in haglund syndrome. Foot
Ankle Int 2018;39(5):551-559.
61. Wagner P, Wagner E, Ortiz C, Zanolli D, Keller A, Maffulli N:
Achilles tendoscopy for non insertional Achilles tendinopathy. A
case series study. Foot Ankle Surg 2020;26(4):421-424. This study is
a consecutive case series with midterm (medial follow-up 87
months) functional results, satisfaction rates, and complications
of 11 patients who underwent Achilles tendoscopy for
noninsertional Achilles tendinitis. Level of evidence: IV.
62. Murphy GA: Surgical treatment of non-insertional Achilles
tendinitis. Foot Ankle Clin 2009;14(4):651-661.
63. Neufeld SK, Cerrato R: Plantar fasciitis: Evaluation and
treatment. J Am Acad Orthop Surg 2008;16(6):338-346.
64. Watson TS, Shurnas PS, Denker J: Treatment of Lisfranc joint
injury: Current concepts. J Am Acad Orthop Surg 2010;18(12):718-
728.
65. Lewis JSJr, Anderson RB: Lisfranc injuries in the athlete. Foot
Ankle Int 2016;37(12):1374-1380.
66. Ly TV, Coe ee JC: Treatment of primarily ligamentous Lisfranc
joint injuries: Primary arthrodesis compared with open reduction
and internal fixation. A prospective, randomized study. J Bone
Joint Surg Am 2006;88(3):514-520.
67. Nery C, Baumfeld D, Baumfeld T, et al: Comparison of suture-
augmented ligamentplasty to transarticular screws in a Lisfranc
cadaveric model. Foot Ankle Int 2020;41(6):735-743. This is a
biomechanical cadaver study comparing fixation of a ligamentous
Lisfranc injury using transarticular screws versus an augmented
suture construct.
S E CT I ON 1 0

Spine
SECTION EDITOR
Wesley H. Bronson, MD, MS
C H AP T E R 5 1

Spine Anatomy
Samuel K. Cho MD, FAAOS, David A. Weiner MD, Jonathan
Lee MD

Dr. Cho or an immediate family member has received royalties from Globus Medical; serves as a
paid consultant to or is an employee of Stryker; has received nonincome support (such as
equipment or services), commercially derived honoraria, or other non–research-related funding
(such as paid travel) from Globus Medical; and serves as a board member, owner, officer, or
committee member of American Academy of Orthopaedic Surgeons, American Orthopaedic
Association, AOSpine North America, Cervical Spine Research Society, North American Spine
Society, and Scoliosis Research Society. Neither of the following authors nor any immediate
family member has received anything of value from or has stock or stock options held in a
commercial company or institution related directly or indirectly to the subject of this chapter: Dr.
Weiner and Dr. Lee.

ABSTRACT
The vertebral column is composed of 7 cervical, 12 thoracic, 5
lumbar, and 4 to 5 coccygeal segments. Stability is conferred
through a combination of osseous articulations, strong ligamentous
a achments, and dynamic muscular control. The weight and
stability of the cranium is managed through a special upper cervical
articulation that allows for great flexibility and a complex range of
motion. The entire weight of the upper body and trunk is
transferred to the lower body via the sacrum and spinopelvic
ligaments. The spinal cord and nerves lie within this osseous and
ligamentous construct, giving rise to 31 spinal nerves. The blood
supply to the spine is primarily based on segmental arteries that
coalesce to form the anterior spinal artery. This construct normally
works harmoniously to allow for human biomechanics and
neurologic function. In the disease state, the fine balance is
disturbed, resulting in dysfunctional mobility, neurology, or both.
An appropriate knowledge of spinal anatomy can help the
orthopaedic surgeon with diagnosis and intervention in a safe and
effective manner.
Keywords: intervertebral disk; spinal anatomy; spinal cord; spine
biomechanics; vertebrae

Introduction
The human spine is a complicated anatomic unit, consisting of
osseous, ligamentous, muscular, intervertebral, vascular, and
neural elements. The interaction of these individual elements
allows for motion, protection of the spinal cord, and the
distribution of forces throughout the body.

Embryology and Development

The spinal cord is derived from the neural crest and neural plate
early in embryologic development. Beginning at week 3, the embryo
becomes planar before the development of the neural crest. A
temporary structure known as the primitive groove appears around
this time. This primitive groove will deepen and begin to fold on
itself within the ectodermal layer of the embryo. When the cleft has
completely closed, it becomes the neural tube. During the closing
of the neural tube, the neural crest will form dorsally as the
notochord remains ventral (Figure 1).
 Figure 1 Illustration shows early embryonic development of the spine.The
midsagittal groove deepens within the ectoderm and begins to fold onto itself,
creating the neural tube.(Reproduced from Rinella A: Human embryology
emphasizing spinal and neural development, in Spivak JM, Connolly PJ, eds:
Orthopaedic Knowledge Update Spine 3. American Academy of Orthopaedic
Surgeons, 2006, pp 3-13.)

The neural crest will eventually form the peripheral nervous

system, whereas the neural tube is the primitive form of the central
nervous system/spinal cord. The notochord will form the structural
elements of the spine, including the anterior vertebral bodies and
intervertebral disks.
The failure of complete neural tube closure results in a variety of
clinical pathology. Failure of cranial closure can result in
anencephaly. Failure of caudal closure can result in spina bifida
occulta, meningocele, myelomeningocele, or myeloschisis.
Conversely, diastematomyelia is thought to be due to a remnant
neuroenteric canal during the third and fourth weeks of gestation.
The development of individual vertebra occurs from the somites.
These surround the notochord and neural tube. There are 4
occipital, 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 8 to 10
coccygeal somites. Of these, 31 somites persist. Each vertebra has
three primary ossification centers—the centrum and one in each
half of the vertebral arch. The centrum gives rise to the vertebral
body anteriorly. The neural arch gives rise to the posterior
elements, as well as the pedicles and a small portion of the anterior
vertebral body. The costal ossification center gives rise to the
anterior portion of the lateral mass, transverse process, or rib
depending on the region of the spine. In the intervertebral disk, the
notochord gives rise to the nucleus pulposus, whereas the
sclerotome gives rise to the anulus fibrosus. The development and
segmentation of these structures happens simultaneously in the
embryo, with failure of formation or segmentation leading to a
variety of clinical pathologies (Figure 2).
Figure 2 Illustrations demonstrating vertebral development.A, Somite
differentiation: the somites differentiate into sclerotomes overlying the notochord
and dermal myoblasts. B, Metameric shift: the sclerotomes begin to divide into
two components. C, Each sclerotome divides, forming an intervertebral disk
between the two segments. D, Formation of vertebral bodies and innervation of
the dermatomes and myotomes.(Reproduced from Rinella A: Human
embryology emphasizing spinal and neural development, in Spivak JM, Connolly
 PJ, eds: Orthopaedic Knowledge Update Spine 3. American Academy of
Orthopaedic Surgeons, 2006, pp 3-13.)

The spinal cord is derived from the neural tube. The dorsally
located cells become primarily afferent sensory pathways, whereas
ventrally they become primarily efferent motor control pathways. 1 ,
2

Spinal Cord and Nerve Roots

The spinal cord is the central neurologic element that provides a
connection between the brain and the body. It is composed of
highly organized pathways divided between efferent (outgoing) and
afferent (incoming) signals.
The spinal cord changes position throughout development. At
birth, the conus medullaris lies at the L3 level and migrates to the
L1-L2 level by adulthood. As a result, the neurologic level of the
spinal cord does not always correlate to the vertebral level, as
described in a 2019 study. 3 There are 31 pairs of spinal nerves that
correspond to the level at which they exit the spinal
canal/neuroforamen. In the cervical spine, the roots exit above the
same numbered pedicle, transitioning after C7 to exiting below the
same numbered pedicle (ie, C4 root exits superior to the C4 pedicle,
whereas the T2 root exits below the T2 pedicle).
As in the brain, the spinal cord is covered in three layers of
meninges. The innermost layer is the pia mater, which is adherent
to the underlying neural tissue. The next layer is the arachnoid
mater, followed by the dura mater. Within the subarachnoid space
there is a protective buffer of cerebrospinal fluid that surrounds the
spinal cord. This fluid communicates with the cerebrospinal fluid
produced in the cerebral ventricles (Figure 3).
 Figure 3 Diagram showing the layers of the spinal cord.(Reproduced with
permission from Agur A, Dalley A: Moore’s Essential Clinical Anatomy, ed 6.
Wolters Kluwer, 2019.)

On a microscopic level, the spinal cord is composed of two

distinct types of tissues—gray and white ma er. The gray ma er
corresponds to the neuronal cell bodies, whereas the white ma er
represents the myelinated axons. As the cord progresses from
cranial to caudal, the proportion of gray ma er decreases relative to
white ma er.
Dorsal cells are primarily sensory in nature whereas ventral cells
are primarily motor (Figure 4). Vibration, deep pressure, and
proprioception are transmi ed via the dorsal columns. The lateral
spinothalamic tract is responsible for pain and temperature
sensations, whereas anterolaterally, the ventral spinothalamic tract
is responsible for light touch sensation. Efferent motor function
runs along the lateral corticospinal tract. The arrangement of
myelinated fibers within these tracts is such that the upper
extremities are deeper, with more distal targets such as the trunk
and legs becoming progressively superficial. 4

Figure 4 Drawings of the cross-sectional anatomy of the cervical spinal cord.1

= fasciculus gracilis, 2 = fasciculus cuneatus, 3 = dorsal spinocerebellar tract, 4
= ventral spinocerebellar tract, 5 = lateral spinothalamic tract, 6 = spino-olivary
tract, 7 = ventral corticospinal tract, 8 = tectospinal tract, 9 = vestibulospinal
tract, 10 = olivospinal tract, 11 = propriospinal tract, 12 = lateral corticospinal
tract, C = cervical, L = lumbar, S = sacral, T = thoracic.(Redrawn with
permission from Louis-UgboPedlowHeller JFXJGJr: Anatomy of the cervical
spine, in Benzel EC, ed: The Cervical Spine, ed 5. Wolters Kluwer Health, 2012,
pp 1-33. © Cervical Spine Research Society.)

At each spinal level there are anterior and posterior rootlets.

These consolidate to form anterior and posterior roots, ultimately
combining to form a common segmental nerve root with both
motor and sensory components. The dorsal root ganglion lies on
the posterior root and is the location of peripheral sensory nerve
synapse with afferent signals.
The constellation of symptoms that occur in the pathologic state
can often be traced to the disruption of the blood supply to
grouped white ma er tracts.

Osseous Anatomy
The human spine exhibits four distinct regions (cervical, thoracic,
lumbar, and sacral), each associated with a different sagi al
curvature (Figure 5). When summed, this curvature maintains the
calvarium centered over the pelvis. In general, each vertebra
consists of the same basic structure. Anteriorly there is the
vertebral body, which consists of dense superior and inferior end
plates filled with cancellous bone. Connecting the vertebral body to
the posterior elements are the pedicles. The pedicle is a dense
cortical strut that is filled with cancellous bone. The pedicle is also
the superior border of the neuroforamen and connects to the
superior articular process (SAP). The SAP is the posterior border of
the neuroforamen and articulates with the inferior articular process
(IAP) of the cranial level (ie, L4 IAP articulates with the L5 SAP).
The SAP is confluent with the lamina. This is the dorsal shell that
provides bony protection to the spinal cord and nerves. The IAP is
an extension of the caudal aspect of the lamina. There is a dense
region of laminar bone between the SAP and IAP that is
responsible for weight transfer known as the pars interarticularis.
Finally, there are the spinous process and transverse processes that
serve as a achment points for various interspinous ligaments and
muscular units.
 Figure 5 Illustrations show sagittal (A) and coronal (B) views of the spine.

Cervical Anatomy
The cervical region consists of seven vertebrae. Special
consideration is given to the first two and last of these vertebrae.
Because the cervical vertebrae require the least amount of weight
bearing, their bodies are relatively small and thin with respect to
the size of their posterior elements. Furthermore, they have greater
medial-lateral dimension than anterior-posterior dimension. The
first two cervical vertebrae are unique in their development and
structure. This special articulation accounts for approximately 50%
of the rotational, flexion, and extension capabilities of the cervical
spine. The first cervical vertebra is known as the atlas, whereas the
second cervical vertebra is known as the axis. Because of the
articulation of the atlas with the skull, the superior articular facet
joints of this vertebral body are unique in that they have very li le
slope, thus enabling articulation with the caudally directed occipital
condyle. The atlas is also unique in that it does not have a true
vertebral body or spinous process. The anterior arch of the atlas
serves as an articulation point to the odontoid process that stems
from the axis (dens). This articulation allows for stable rotation as
well as resistance to horizontal translation and displacement. The
transverse ligament runs across the anterior arch of C1, lying
posteriorly to the tip of the dens. This maintains the pivotal
relationship between the atlas and dens. This is supplemented by
the apical ligament and paired alar ligaments that confer stability
to the occipitocervical junction (Figure 5).
In the cervical spine, the articular unit of SAP and IAP is referred
to as the lateral mass. Additionally, there is a foramen that exists
from C2 to C6 that houses the vertebral artery and its related
venous plexus.
The lower cervical vertebra, C7, is notable for its elongated
spinous process and trapezoidal shape. Because it is a transitional
segment between cervical and thoracic regions, its superior end
plate is smaller in the anterior-posterior dimension when compared
with the inferior end plate. 5

Thoracic Anatomy
There are 12 thoracic vertebrae that are roughly sized between that
of the cervical and lumbar vertebrae. The general shape of the
thoracic vertebra is more heart-like when compared with the
cervical or lumbar vertebra and tends to be elongated in anterior-
posterior dimension. The unique and obvious characteristic of the
thoracic vertebra is the addition of the costovertebral joint and
support of the rib corresponding to the same vertebral level. This
costovertebral articulation is located ventral to the SAP of the
corresponding level and adjacent to the transverse process. Their
physical relationship is such that multiple connecting ligamentous
structures and a synovial cavity exist between the neck of the rib
and the transverse process. There is no costovertebral articulation
at T11 and 12 as these are transitional levels.
Lumbar Anatomy
The lowest five vertebrae in the presacral spine make up the lumbar
region. These vertebrae tend to be larger in all dimensions as they
are responsible for supporting the most weight. They are larger in
the medial-lateral dimension than anterior-posterior and are
recognizable from their cervical and thoracic counterparts because
of the lack of a transverse foramen or costovertebral articulation.
The lumbar vertebrae also have a pronounced mammillary process,
which serves as the origin and insertion point of deep paraspinal
musculature (Figure 6).
 Figure 6 Illustration demonstrates the anatomic structures comprising the
three longitudinal columns of stability in the thoracolumbar spine: the anterior
column (anterior two-thirds of the vertebral body, anterior part of the anulus
fibrosus, and anterior longitudinal ligament), the middle column (posterior third of
the vertebral body, posterior part of the anulus fibrosus, and posterior longitudinal
ligament), and the posterior column (facet joint capsules, ligamentum flavum,
bony neural arch, supraspinous ligament, interspinous ligament, and articular
processes).(Adapted with permission from McAfee P, Yuan H, Fredrickson BE,
Lubicky JP: The value of CT in thoracolumbar fractures: An analysis of one
hundred consecutive cases and a new classification. J Bone Joint Surg Am
1983;65[4]:461-473.)

Sacral Anatomy
The sacrum is composed of five fused vertebrae forming a single
triangular unit. This functions as the lumbopelvic connection point
and keystone of the trunk and lower extremities. The orientation of
the sacrum is in significant flexion such that there is a steep angle
created between the lowest lumbar vertebra and the highest sacral
element. This angle is very variable. The cranialmost aspect of the
sacrum consists of a region known as the sacral ala. These are
laterally based wings that connect to the upper region of the
sacroiliac joint and provide a surgical utility as an area of dense
bone that can be used in posteriorly based fusion procedures.
Although fused, the first three sacral levels consist of all the basic
elements of a normal vertebral body including neuroforamen and
rudimentary disks; however, because of the sacral ala and sacroiliac
joint, there is both a dorsal and ventral foramen that allows for the
egress of a dorsal and ventral sacral nerve root.

Ligamentous Anatomy
Ligaments of the spine act as tensioners that achieve force
transmission through the spine. The ligaments that compose the
spinopelvic complex are the strongest in the human body. The
ligaments that exist within each vertebral level add to the partial
stability conferred by the osseous and muscular spinal elements.
The anterior longitudinal ligament is a broad-based, strong
ligament that runs on the anterior surface of the entire vertebral
column. It is composed of three distinct layers. The most superficial
layer extends three to four vertebral levels. The middle layer spans
two to three levels, whereas the deep layer extends only one
vertebral level. The a achment point is at the anulus fibrosus with
looser a achments to the vertebral body where it blends into the
periosteum.
The posterior longitudinal ligament runs the length of the
vertebral column and is continuous with the tectorial membrane.
Similar to the anterior longitudinal ligament, the a achment point
is the anulus fibrosus.
The supraspinous ligament is a well-developed and thick
a achment between the tips of the spinous processes. It runs the
length of the spine starting at the ligamentum nuchae and
terminates on the sacrum (Figure 7).
 Figure 7 A, Illustration demonstrating sagittal view of the occipitocervical
articulation. Posterior (B) and anterior (C) illustrations of the atlantoaxial
articulation. AC = accessory ligament, AL = alar ligament, AP = apical ligament,
TR = transverse atlantal ligament.(Reproduced with permission from Bransford ,
RJ, Alton , TB, Patel , AR, Bellabarba , C. Upper Cervical Spine Trauma. Journal
of the American Academy of Orthopaedic Surgeons: November 2014 - Volume
22 - Issue 11 - p 718-729. https://journals.lww.com/jaaos/pages/default.aspx.)

The interspinous ligament is prominent in the lumbar spine and

poorly developed elsewhere. It runs obliquely between spinous
processes in the interval between the supraspinous ligament in the
ligamentum flavum.
The ligamentum flavum is a subarticular ligament that runs from
the medial aspect of the lamina and extends laterally to blend with
the facet joint capsule. Superiorly it originates from the anterior
surface of the cephalad lamina at approximately the middle region
of the lamina. The inferior border creates a “shingles on a roof”
structure with termination on the posterior border of the caudal
vertebra. The ligamentum flavum has a high elastin content, which
gives it a yellow color with elastic properties. It is sometimes
referred to as the yellow ligament.
The intertransverse ligament spans the length of the transverse
processes. In the lumbar region this is a relatively thin and
membranous type a achment, which divides the retroperitoneum
from the deep musculature of the back.
The articular facet capsule is a sheet of connective tissue that
surrounds the facet joints. It a aches to the articular region of the
SAP and IAP. Medially it blends with the ligamentum flavum.
The spinopelvic ligamentous complex consists of the iliolumbar
ligament, sacroiliac ligament, sacrotuberous ligament, and
sacrospinous ligament. The iliolumbar ligament connects the fifth
lumbar vertebra to the ilium. It originates on the transverse process
of the fifth lumbar vertebra and inserts immediately ventral to the
sacroiliac joint on the crest of the ilium.
The sacroiliac ligament spreads across the sacroiliac joint. It
consists of three distinct regions. The ventral ligament consists of
multiple thin bands that span the ventral surface of the sacrum and
articular surface of the ilium. The dorsal ligament lies deep in the
valley between the sacrum and the ilium. It is very strong and
provides the primary tensile force between the sacrum and ileum.
There is an interosseous ligament that lies deep to the dorsal
ligament.
 The sacrotuberous ligament is a broad, flat complex of fibers
connecting the posterior inferior ilium with portions of the sacrum,
coccyx, and tuberosity of the ischium (Figure 8).

Figure 8 Illustration shows the spinopelvic ligaments as seen from the AP

view.(Reproduced with permission from Dalley AF, Agur MR: Grant’s Atlas of
Anatomy. ed 14. LWW, 2016, Figure 1.20A.)

The sacrospinous ligament is a thin triangular sheet a ached via

a broad base to the lateral margins of the sacrum and coccyx. Its
apex is connected to the spine of the ischium. 1

Muscular Control of the Spine

As described previously, the vertebral column with its intricate
osseous anatomy serves as the origin and insertion site for many
muscles. The intrinsic muscles of the spine stabilize and move the
axial skeleton itself, whereas the extrinsic muscles help to support
and move the appendicular skeleton.
Intrinsic Muscles
The intrinsic muscles connect the vertebra with each other and the
skull, and work in concert to provide stability. The muscles are
innervated by the dorsal rami of the exiting spinal roots. The
intrinsic muscles primarily consist of the erector spinae and
multifidus muscles, but also include more specialized muscles
spanning the occiput to upper thoracic region that help control the
skull.
Between C2 and the skull, the posterior suboccipital muscles
include the rectus capitis posterior major and minor, obliquus
capitis superior, and obliquus capitis inferior, which contribute to
extension of the head. Anteriorly, from C1 to the skull, the rectus
capitis allows flexion and the rectus capitis lateralis permits lateral
bending.
Much of the cervical spine muscular anatomy (Figure 9) has been
described in a classic study. 6 The posterior musculature, often
compared with a suspension bridge, includes the splenius capitis
and cervicis, and deeper semispinalis capitis and cervicis. The
splenius capitis originates at the spinous process of the lower
cervical and upper thoracic vertebrae and inserts on the skull near
the mastoid process. The splenius cervicis is slightly deeper and
originates on thoracic spinous processes and inserts on cervical
transverse processes. Both function in extension, lateral bending,
and axial rotation, whereas the cervicis adds axial rotation for the
skull. The semispinalis capitis originates on the articular processes
of the lower cervical vertebrae and transverse processes of the
upper thoracic vertebrae, and it inserts medially on the skull
between the inferior and superior nuchal line. The deeper
semispinalis cervicis originates on thoracic transverse processes
and inserts on cervical spinous processes from mostly C2 and
extends to C5. Anteriorly, the longus capitis runs with a
superomedial orientation along the anterior surface of transverse
processes to the basiocciput, creating a small flexion moment arm
as it lies close to the vertebral bodies. The longus colli has fibers
that run vertically along the anterior vertebral bodies with a small
flexion moment arm. Some fibers run superolaterally from the
thoracic vertebral bodies to lower cervical transverse processes for
contralateral rotation, and others run superomedially from
transverse processes to the anterior vertebral bodies for ipsilateral
rotation. The cross-sectional area of the longus colli is inversely
correlated to cervical lordosis. 7
 Figure 9 A, Illustrations show the cross section through the cervical spine
showing complex musculature. B, The trapezius forms the most superficial
layer of posterior cervical muscles. Deep to the trapezius are the splenius
capitis, splenius cervicis, and more laterally the sternocleidomastoid. C, The
superficial layer of deep cervical muscles; splenium cervicis and splenium
capitis. D, The lateral muscles include the superficial layer of deep cervical
muscles; longissimus cervicis and iliocostalis cervicis. E, Deep layer of cervical
muscles.(Reproduced from Clark CR: The Cervical Spine, ed 4. Lippincott
Williams & Wilkins, 2005, pp 23, 26-28.)

Although the intrinsic muscles grossly have similarities in their

connections, their slight differences in orientation, a achments,
and muscle length depending on the body’s position allow for
differences in moment arm, magnitude, and total magnitude of
force to help maintain posture. Injury to the intrinsic muscles may
occur from whiplash or motor vehicle accidents, when there are
eccentric contractions and resultant compressive loads across the
disks and facet joints. 8 Other reasons for the accumulation of
inflammatory and pain metabolites include mechanisms resulting
in unbalanced load sharing to other structures such as muscle
atrophy and decreased spinal stability. 9
The erector spinae and multifidus represent the bulk of the
spinal musculature, spanning mostly the thoracolumbar spine and
providing spinal extension. Studies have described these muscle
groups. 10 , 11 The erector spinae is a group of muscles that include,
from medial to lateral: the spinalis, longissimus, and iliocostalis
(Figure 10). The spinalis is generally absent in the cervical region,
and aponeurotic in the lumbar region. The longissimus is further
categorized from caudal to cranial into the longissimus thoracis,
cervicis, and capitis. The longissimus thoracis has lumbar fascicles
that arise from the lumbar transverse processes and a ach in a
caudal fashion onto the iliac crest as the lumbar intermuscular
aponeurosis. The thoracic fascicles arise from all thoracic transverse
processes and most ribs, and a ach to the lumbar spinous process,
the sacrum, or the ilium. As opposed to the lumbar fascicles, which
are small fusiform muscles, the thoracic fascicles are long, slender
muscles that form the strong erector spinae aponeurosis. The
cervicis runs between the transverse processes of thoracic and
cervical vertebrae, and capitis from the transverse processes to the
mastoid process of the skull. The iliocostalis lumborum has lumbar
fascicles that arise from the tip of the transverse process of L1-L4
and a ach to the thoracolumbar fascia and iliac crest, and thoracic
fascicles arise from the ribs and a ach to the iliac spine and crest
forming the lateral erector spinae aponeurosis. The iliocostalis
cervicis connects the ribs to the transverse processes of the cervical
vertebra. The multifidus arises from the spinous processes and
lamina and a ach to two to four adjacent segments caudal,
continuing all the way down to the sacrum, providing small
segments of vertebral stabilizations during extension. Unique
features of the multifidus muscles include their high density of
muscle fibers, high passive elastic capacity, and short sarcomere
length, which can generate greater force as it stretches in flexion.
 Figure 10 Illustration shows the deep muscles of the back.(Reproduced from
Donnelly J, Simons D, Travell J, Fernández-de-las-peñas C, Finnegan M:
Travell, Simons and Simons’ – Myofascial Pain and Dysfunction: The Trigger
Point Manual, ed 3. Lippincott Williams & Wilkins, 2018.)

Extrinsic Muscles
The extrinsic muscles, innervated by the ventral rami of the spinal
nerves, are involved in control of the skull, shoulder girdle, rib
cage, and pelvis. Regarding the pelvis, the quadratus lumborum
spans from the iliolumbar ligament and iliac crest onto the 12th rib
and transverse processes of L1-L4, providing stability in lateral
flexion. The psoas major, which a aches to the anterior transverse
processes, sides of the vertebral bodies, and vertebral disks, joins
the iliacus to form the iliopsoas inserting on the lesser trochanter of
the femur to flex the thigh and trunk.
The sternocleidomastoid originates from the sternum and medial
clavicle to a ach on the skull at the mastoid process and superior
nuchal line of the occiput. It consists of superficial fascicles,
sternomastoid and cleido-occipital, and deep fascicles of the
cleidomastoid for flexion, contralateral rotation, and lateral bending
all working in harmony. The strap muscles include the infrahyoid
muscles and suprahyoid muscles that manipulate the hyoid bone
for swallowing and maintaining an open airway. The scalene
muscles, spanning from the ribs to the transverse processes of the
cervical vertebrae, as well as serratus posterior, a aching to the
thoracolumbar vertebrae, help with respiration. The trapezius,
rhomboid major and minor, and levator scapulae connect via the
thoracic and cervical spine to move the scapula. The latissimus
dorsi, which are a ached to the thoracolumbar vertebrae and fascia,
iliac crest, and lower ribs, inserts into the humerus.
Collectively, the intrinsic and extrinsic muscles stabilize the
spine itself and its proximal limb a achments.
Vascular Anatomy

Arterial Blood Supply

The arterial blood supply of the spinal cord consists of the anterior
spinal artery and two dorsolateral posterior spinal arteries (Figure
11). These three longitudinal vessels receive blood from the
medullary branches of the segmental spinal arteries. There is an
additional pair of vertebral arteries in the cervical region and a
sacroiliolumbar system. An intricate venous plexus helps to drain
the blood supply.

Figure 11 Illustration shows the origin and general location of principal arteries
supplying the spinal cord.(Reproduced from Haines D: Neuroanatomy Atlas in
Clinical Context, ed 10. Lippincott Williams & Wilkins, 2018.)

The anterior spinal artery supplies 80% of the intrinsic spinal

cord vasculature and largely affects the cortical spinal tracts. It is
largest in the lumbosacral region where it supplies the proximal
cauda equina and lumbosacral cord intumescence. From a
developmental standpoint, the anterior spinal artery is derived
from the fusion of bilateral pairs of ascending and descending
anastomotic branches of the original segmental arteries of the
developing spinal cord. 12 The longitudinal series of three major
regions, the cervicothoracic (C1-T3), midthoracic (T3-T8), and
 g
thoracolumbar region (T8-conus), are functionally independent
vessels that may show wide luminal variations and anatomic
discontinuities. 13 The artery of Adamkiewicz is the largest anterior
segmental medullary artery, arising from the left posterior
intercostal artery at the 9th and 12th intercostal artery and supplies
the lower two-thirds of the anterior spinal artery. There are also
three preferential anterior medullary arteries for the cervical region
and one or two for the midthoracic region. The tunica media and
intimal muscular layers of the arteries autoregulate intrinsic spinal
cord blood flow from the anterior spinal artery to its central artery
branches. Compression by dorsal osteophytes and cartilaginous
protrusions against the ventral surface of the anterior spinal artery
and its nutritional importance may have consequences in spinal
stenosis.
The paired dorsolateral or posterior spinal arteries arise from the
posterior inferior cerebellar vessels and are of lesser caliber and
nutritional significance. They represent more of a plexiform
distribution over the dorsum of the cord, with a greater frequency
of smaller medullary sources.
The vertebral arteries arise from the subclavian arteries and enter
deep to the transverse process of C6 (or C7 7.5% of the time),
ascend through the transverse foramen before exiting posteriorly
across the arch of C1, and through the foramen magnum. They also
provide a ventrally coursing anterior central artery and a medially
directed posterior central artery to each subaxial vertebral element.
The odontoid process is also supplied by pairs of anterior and
posterior central branches that course upward from the surfaces of
the body of C2. The upper cervical spinal cord also receives blood
from the lateral spinal arteries, which arise from the intradural
parts of the vertebral arteries near the origins of the posterior
inferior cerebellar arteries.
The sacroiliolumbar arterial system begins below L4 after the
bifurcation of the aorta. The sacroiliolumbar system consists of
primarily the internal iliac (hypogastric) arteries, and includes the
fourth lumbar artery, iliolumbar artery, and the middle and lateral
sacral arteries. These supply the lower lumbosacral elements of the
spine, cauda equina, and back musculature inferior to the L4 level,
and the vasa nervorum of the lumbosacral plexus.

Venous Blood Supply

The venous supply of the vertebral column relies on an external and
internal venous plexus (Figure 12). The anterior external plexus
coincides with anterior central arteries and receives tributaries that
perforate the anterior and lateral sides of the vertebral body. The
posterior external plexus drains from the segmental artery branches
that supply the muscular and postlaminar regions. The posterior
external plexus is a paired system that lies in the two vertebrocostal
grooves, with cross-anastomoses between the spinous processes. It
is a valveless venous complex that communicates with the lumbar
and intercostal tributaries of the caval and azygos system. In the
posterior nuchal region, the plexus is more extensive with
intraspinous tributaries from the vertebral veins, which drain into
the deep cervical and jugular veins. The internal venous plexus, also
known as Batson plexus, is a series of irregular, valveless epidural
sinuses that extend from the coccyx to the foramen magnum. The
plexus is arranged in a series of cross-connected expansions
embedded in the epidural fat that produce anterior and posterior
ladderlike configurations up the vertebral canal, supported by a
network of collagenous fibers.
 Figure 12 Illustration shows the spinal vein anatomy.(Modified from Moore KL,
Dalley AF, Agur AMR: Clinically Oriented Anatomy, ed 8. Wolters Kluwer, 2018.)

The major external connections of the epidural plexus consist of

veins that pass through the intervertebral foramen and empty into
the segmentally available intercostal or lumbar veins.
These are valveless, so blood can pass in any direction in
accordance to shifting intra-abdominal and intrathoracic pressures
without developing varices. The epidural plexus serves in a
mechanical capacity as a hydraulic shock-absorbing sheath that
helps buffer the spinal cord during movement. Retrograde flow
from venous connections to the lower pelvic organs to the spine
allows a pathway for metastasis and infections. 14 Similarly, the
pharyngovertebal veins that drain the nasopharynx may also result
in the spread of metastatic disease and infection to the cervical
spine. 15

Intervertebral Disk

Structure
The intervertebral disks separate the vertebral bodies and serve as
a shock absorber for the spine. The intervertebral disk consists of
three main parts: the cartilaginous end plate, the inner nucleus
pulposus, and the outer anulus fibrosus. The cartilaginous end
plates are in direct contact with the vertebral bodies. The end plates
are cranial and caudal to the thick anulus fibrosus, which encloses
the gel-like nucleus pulposus (Figure 13).

Figure 13 Illustration shows the orientation of fibers along the vertebral body.
(Reproduced from Nordin M, Frankel V: Basic Biomechanics of the
Musculoskeletal System, ed 5. Lippincott Williams & Wilkins, 2021.)

The central nucleus pulposus is responsible for the ability of the

disk to cushion against compressive loads via its proteoglycan
matrix held together by an irregular network of collagen type II and
elastin fibers. In childhood, the cells notochordal in origin are
progressively replaced by round cells resembling chondrocytes. 16
The cells maintain the nucleus pulposus’ hypoxic environment via
hypoxia-inducible factor-1-alpha–mediated pathways and
synthesize the proteoglycans and collagen type II in response to
hydrostatic pressure, as discussed in a 2021 study. 17 The
proteoglycans have highly anionic glycosaminoglycan side chains
that a ract water. Aggrecan, the most commonly found
proteoglycan, has hundreds of anionic side chains, which creates a
hydrophilic environment and allows the extracellular matrix to
absorb and release water. On a daily basis, 25% of the water can be
lost and regained in young lumbar disks. The change in
proteoglycan and glycosaminoglycan concentration affects the
osmotic pressure and ability to cushion against compressive loads.
The concentration of water varies with age, location within the disk,
and body position. The resultant hydrostatic pressure pushes
outwardly against the anulus fibrosus.
Although the nucleus pulposus’ proteoglycan and collagen type
II network is irregular, the anulus fibrosus is made up of 10 to 20
concentric sheets of highly organized collagen type I surrounding
the periphery. The cellular makeup is thin, elongated fibroblastlike
cells on the outside, and spheroid, articular chondrocyte-like cells
on the inside. 18 Radially oriented elastin fibers connect the collagen
sheets. Within each sheet, the collagen type I fibers run parallel to
each and are oriented 30° to the vertebral body, but are 120° to each
other between adjoining sheets (Figure 13). The outer fibers of the
anulus fibrosus a ach to the periphery of the vertebral bodies, and
the inner fibers pass directly into the end plate. As a result of the
highly organized architecture, the anulus fibrosus exhibits high
tensile strength in maintaining its original shape and resisting the
hydrostatic pressure of the nucleus pulposus. The anulus fibrosus
has sympathetic perivascular nerves in the outer 1 to 2 mm and a
small number of mechanoreceptors that provide proprioceptive
feedback in the anterior longitudinal and posterior longitudinal
ligaments. Ingrowth of capillaries and sensory nerves may
contribute to discogenic pain via neuropeptide Y, substance P, and
acetylcholinesterase. 19
The cartilaginous end plate resembles the epiphyseal plates and
serves as the growth centers of the vertebral bodies. Over time, the
hyaline cartilage thins and by adulthood is replaced by a 1-mm
layer of avascular tissue composed of rounded chondrocytes and
type II collagen. The end plates are semipermeable and allow for
nutrient and waste exchange. They have a smaller contribution to
the shock-absorptive properties of the spine, transmi ing most of
the force to the disks.
The intervertebral disks are one of the most avascular structures
in the body. In the first 5 years of life, there are vascular channels
that traverse the end plates. By adulthood, the blood supply of the
disk relies on two capillary plexuses, the first supplies the
peripheral 1 to 2 mm of the outer anulus fibrosus and the other is
more centrally located starting in the vertebral bodies and ending
at the bone-cartilage junction. Nutrition is completely dependent
on diffusion as glucose and oxygen readily leave the vertebral
capillaries and diffuse into the nucleus pulposus extracellular
matrix. As a result of the low oxygen tension, there is significant
anaerobic metabolism and low pH within the disk.

Disk Degeneration
Risk for disk degeneration is multifactorial and includes genetics,
aging, and repetitive biomechanical trauma. There is structural
failure and disorganization of the anulus fibrosus, hardening of the
nucleus, and thinning and calcification of the cartilaginous end
plates. Other signs notable on radiographs and advanced imaging
studies include osteophyte formation, end plate irregularities, disk
space narrowing, disk bulging, and annular tears. The progressive
structural damage and aging process alters the extracellular matrix
via a cell-mediated response. There is increased proteolytic
degradation of aggrecan and change of proportion of
glycosaminoglycans to heparan sulfate and keratan sulfate. This
results in decreased water absorption and decreased hydrostatic
pressure. There is an increase in collagen type I content with
replacement of collagen type II in the nucleus, and more
disorganization of the collagen type I in the anulus fibrosus.
Altered enzyme activity, decreased end plate permeability,
impaired metabolite transport with an increase in proinflammatory
cytokines, nitric oxide, and prostaglandin E2 drive the cells toward
senescence and apoptosis. A 2021 study reported on methods of
regenerating the intervertebral disk at the tissue, cell, and
molecular levels. 20

Biomechanics
The basic three functions of the spine are to transmit force, allow
motion, and protect the spinal cord and nerves running through it.

Functional Unit
The spine as a functional unit includes an intervertebral disk
sandwiched between a cranial and caudal vertebra, with
intervening facet joints and supporting ligaments. As previously
discussed, the disk serves as a shock absorber, transmits
mechanical load, and permits motion between the vertebral bodies.
The functional units are stacked on top of each other; the cervical
and lumbar regions are lordotic and the thoracic and sacral regions
are kyphotic. The joints are more coronally oriented in the cervical
spine and become more sagi ally oriented toward the lumbar
spine. The posterior element of the spine provides important
a achment points for the muscles to stabilize the spine and serve
as lever arms for the extremities. The ligaments help orient the
vertebrae independent of the muscles, and they help to protect the
spinal cord by restricting spinal motion. Collectively with the
pelvis, the alternating curves and supporting structures of the spine
help to maintain the center of gravity. Failure of any of these
components can result in biomechanical alteration, injury, and
failure.

Planes of Motion
Most studies on spinal motion are based on cadaver models.
Motions include flexion, extension, lateral bending, twisting, and
are usually coupled. Flexion affects the interspinous and
supraspinous ligaments first, and the posterior anulus fibrosus last.
21
Resistance to extension occurs though the disk and anterior
longitudinal ligament, with 60% to 70% of the applied load going
through the posterior arch. 22 In the sagi al plane, the cervical spine
followed by the lumbar spine have the greatest range of motion. In
the coronal plane, there is overall less range of motion in
magnitude, and primarily occurs in the cervical spine. Axial
rotation occurs in the thoracic spine and the atlantoaxial joint. 23

Forces
Forces include bending, shear, tension, compression, and torsion.
In compression, the end plate is the weakest point, failing at 2,000
to 14,000 N. The nucleus pulposus bulges and compromises the
vertebral body, usually at the superior end plate of the caudal level.
24
Strength increases by 0.3 kN per caudal lumbar level in the
lumbar spine. 25 Shear forces impact the disk fibers and
intervertebral ligaments, and the facet joints can resist 0.6 to 2.8
kN. 26 Torsion is first resisted by the anulus fibrosus, followed by
the facet joints limiting motion to 1° to 2°. 27 Lateral bending affects
the disks first.
Supraphysiologic forces to the spine are responsible for trauma
to the tissue. Acute trauma is a single force that exceeds the
tolerance level of the tissue, such as in a disk rupture. Cumulative
trauma is due to repetitive loads and microtrauma without proper
rest, which permanently weakens the tissue structure and results in
degeneration. The last type of trauma to tissue involves instability.
Normal motion is restricted to a set neutral zone limit, which
changes with age and injury. Instability is the abnormal
displacement of the spine or joints past the neutral zone limit
under physiologic loading, because of the loss of alignment and the
musculoskeletal system’s resultant a empts to overcompensate.
 As it relates to potential injury risk or damage, there is a need for
in vivo studies to fully characterize pain-modulated kinematics,
estimate pain, and determine the effect of altered kinematics
because of pain avoidance on the overall mechanical response of
the spine. Spine kinematic profiles of asymptomatic individuals
and those with low back pain demonstrate no difference in range of
motion. However, trunk velocity and acceleration are strongly
diminished as patients move slower to minimize the stimulation of
the pain-producing nociceptors. 28

Summary
The vertebral column is composed of 7 cervical, 12 thoracic, 5
lumbar, and 4 to 5 coccygeal segments. The spine as a functional
unit includes an intervertebral disk sandwiched between a cranial
and caudal vertebra, with their intervening facet joints and
supporting ligaments. In addition to the vertebrae, intervertebral
disks, and ligaments, the vasculature and muscular anatomy all
serve to support the spinal cord and nerve roots. The three basic
functions of the spine are to transmit force, allow motion, and
protect the spinal cord and nerves running through it. A thorough
understanding of spine anatomy provides the foundation for how
to diagnose and manage spine pathologies.

Key Study Points

The peripheral nervous system is derived from the neural crest. The spinal cord
develops from the neural tube, and the spinal column originates as the notochord.
The unique osseous structure of the vertebrae confers stability and function that is
unique to the type of motions of each spinal region.
The arterial blood supply of the spinal cord consists of the anterior spinal artery and
two posterior spinal arteries that receive blood from the medullary branches of the
segmental spinal arteries. The epidural venous plexus serves as a potential pathway
for metastasis and infections.
The intervertebral disk, which serves as a shock absorber of the spine, consists of
the cartilaginous end plates, anulus fibrosus, and the nucleus pulposus.
The spine planes of motion include flexion, extension, lateral bending, and twisting.
Forces include bending, shear forces, tension, compression, and torsion.
Annotated References
1. Parke WW, Bono CM, Garfin SR: Applied anatomy of the spine,
in Herkowi HN, Grafin SR, Eismont FJ, Bell GR, Balderston RA,
eds: Rothman-Simeone: The Spine. ed 6. Elsevier Saunders, 2011,
pp 15-53.
2. Muller F, O’ Rahilly R: The human chondrocranium at the end of
the embryonic period proper with particular reference to the
nervous system. Am J Anat 1980;159:33-58.
3. McAnany SJ, Rhee JM, Baird EO, et al: Observed pa erns of
cervical radiculopathy: How often do they differ from a standard,
“Ne er diagram” distribution? Spine J 2019;19(7):1137-1142. The
authors retrospectively reviewed patients undergoing single
level, anterior cervical diskectomy and fusion to determine the
observed pa ern of radiculopathy and dermatomal paresthesias
and compared it against the standard “Ne er diagram”. They
found that only 54% of patients follow the classically taught
dermatomal distributions. Level of evidence: III.
4. Wardak Z, Lavelle ED, Kistler BJ, Lavelle WF: Functional
anatomy of the spine, in Benzel EC, ed: Spine Surgery Techniques,
Complication Avoidance, and Management. ed 3. Elsevier Saunders,
2012, pp 55-62.
5. Crain CMJ: Anatomy, in Patel VV, Patel A, Harrop JS, Burger E,
eds: Spine Surgery Basics. Springer, 2014, pp 3-12.
6. Kamibayashi LK, Richmond FJ: Morphometry of human neck
muscles. Spine 1998;23(12):1314-1323.
7. Mayoux-Benhamou MA, Revel M, Vallee C, et al: Longus colli has
a postural function on cervical curvature. Surg Radiol Anat
1994;16(4):367-371.
8. Vasavada AN, Brault JR, Siegmund GP. Musculotendon and
fascicle strains in anterior and posterior neck muscles during
whiplash injury. Spine 2007;32(7):756-765.
 9. Hamberg-van Reenen HH, Ariens GA, Bla er BM, et al: Physical
capacity in relation to low back, neck, or shoulder pain in a
working population. Occup Environ Med 2006;63(6):371-377.
10. Macintosh JE, Bogduk N: 1987 Volvo award in basic science. The
morphology of the lumbar erector spinae. Spine 1987;12(7):658-
668.
11. Delp SL, Suryanarayanan S, Murray WM, Uhlir J, Triolo RJ:
Architecture of the rectus abdominis, quadratus lumborum, and
erector spinae. J Biomech 2001;34(3):371-375.
12. Corbib JL: Anatomie et Pathologie Arterielles de la Moelle. Masson
et Cie Paris, 1961, pp 787-796.
13. Lazorthes G, Gouaze A, Zadeh JO, et al: Arterial vascularization
of the spinal cord. J Neurosurg 1971;35: 253-262.
14. Batson OV: The function of the vertebral veins and their role in
the spread of metastases. Am Surg 1940;112: 138-145.
15. Parke WW, Rizzoli HZ, Brown MD: The pharyngovertebral
veins: An anatomic rationale for Grisel’s syndrome. J Bone Joint
Surg Am 1984;66:568-574.
16. Sive JI, Baird P, Jeziorsk M, et al: Expression of chondrocyte
markers by cells of normal and degenerate intervertebral discs.
Mol Pathol 2002;55:91-97.
17. Kim JW, Jeon N, Shin DE, et al: Regeneration in spinal disease:
Therapeutic role of hypoxia-inducible factor-1 alpha in
regeneration of degenerative intervertebral disc. Int J Mol Sci
2021;22(10):5281. The authors reviewed the role of hypoxia-
inducible factor-1-alpha in the development and homeostasis of
the nucleus pulposus, including the metabolic activity,
extracellular matrix composition, and eventual angiogenesis,
autophagy, and apoptosis during intervertebral disk
degeneration. Level of evidence: III.
18. Inoue H: Three-dimensional architecture of lumbar
intervertebral discs. Spine 1981;6:139-146.
19. Palmgren T, Grönblad M, Virri J, Seitsalo S, Ruuskanen M,
Karaharju E: Immunohistochemical demonstration of sensory
and autonomic nerve terminals in herniated lumbar disc tissue.
Spine (Phila Pa 1976) 1996;21(11): 1301-1306.
20. Baumgartner L, Wuer -Kozak K, Le Maitre CL, et al: Multiscale
regulation of the intervertebral disc: Achievements in
experimental, in silico, and regenerative research. Int J Mol Sci
2021;22:703. This is a review of the key cell regulatory signaling
pathways and their effect on extracellular matrix turnover in
initiation and progression of the intervertebral disk
degeneration. Regenerative strategies target the cell, tissue, and
organ levels. Level of evidence: V.
21. Adams MA, Hu on WC, Sto JR: The resistance to flexion of
the lumbar intervertebral joint. Spine 1980;5:245-253.
22. Adams MA, Dolan P, Hu on WC: The lumbar spine in
backward bending. Spine 1988;13:1019-1026.
23. White AA, Panjabi MM: Clinical Biomechanics of the Spine.
Lippinco -Raven, 1990.
24. Adams MA, Bogduk N, Burton AK, et al: The Biomechanics of
Back Pain. Churchill Livingstone Edinburgh, 2013.
25. Gallagher S, Marras WS, Litsky AS, et al: Torso flexion loads and
the fatigue failure of human lumbosacral motion segments. Spine
2005;30:2265-2273.
26. Cyron BM, Hu on WC, Troup JD: Spondylolytic fractures. J Bone
Joint Surg Br 1976;58:462-466.
27. Adams MA, Hu on WC: The relevance of torsion to the
mechanical derangement of the lumbar spine. Spine 1981;6:241-
248.
28. Marras WS, Ferguson SA, Gupta P, et al: The quantification of
low back disorder using motion measures: Methodology and
validation. Spine 1999;24:2091-2100.
C H AP T E R 5 2

Spine Evaluation, Clinical

Examination, and Imaging
Themistocles S. Protopsaltis MD, FAAOS, Karan S. Patel
MD

Dr. Protopsaltis or an immediate family member has received royalties from Altus; serves as a
paid consultant to or is an employee of Globus Medica, Medicrea, Medtronic, Nuvasive, and
Stryker; and has stock or stock options held in Spine Align and Torus Medical. Neither Dr. Patel
nor any immediate family member has received anything of value from or has stock or stock
options held in a commercial company or institution related directly or indirectly to the subject of
this chapter.

ABSTRACT
The complex anatomic and pathophysiologic nature of the spine
makes evaluating and caring for patients with spine pathology and
pain a challenge. Obtaining a thorough history and performing a
complete physical examination can aid in appropriately diagnosing
and treating spine pathology. A detailed neurologic examination of
the spine requires an understanding of cervical and lumbar spine
anatomy. An examination includes the use of special tests, and
provocative maneuvers can help narrow a differential diagnosis and
guide the use of imaging and diagnostic modalities. Orthopaedic
surgeons should be knowledgeable about the aspects of a spine
evaluation, including the history, physical examination, and
imaging, that are necessary to accurately diagnose spine pathology
and care for patients.
Keywords: cervical spine provocative tests; lumbar spine
provocative tests; myelopathic signs; neurologic examination; spine
history and physical examination

Introduction
Evaluating patients with complaints of back and neck pain is
challenging because of the complex nature of spine anatomy and
pathophysiology. Despite advancements in imaging technology, key
aspects of a spine evaluation involve obtaining a thorough history
and performing a detailed physical examination. A complete
history and neurologic physical examination can help identify
causative factors of a patient’s complaint and guide appropriate
treatment.

History
The patient history is an important component of patient
evaluation. A thorough history can aid in developing a differential
diagnosis, identifying the cause of a patient’s symptoms, and
determining an appropriate treatment plan. 1 When evaluating a
patient, it is important to identify the nature of the complaint; the
onset and duration of symptoms; the intensity, location, and
radiation of any pain, numbness, or paresthesia; and any alleviating
and aggravating factors. 2 Patients may present after receiving prior
testing and treatments, so obtaining such information is key to
avoid repeating unnecessary diagnostic and treatment modalities.
Finally, understanding the degree of pain and disability
experienced by patients and learning the circumstances
surrounding their symptoms (eg, work-related injury) can identify
potential psychosocial factors that may affect their recovery. 1
A thorough history can be used to describe back and neck pain in
a number of different ways. It can be described as mechanical pain
if it is associated with activity, progressively worsens over the
course of a day, and improves with rest. Pain that occurs
independent of activity, is constant, worsens at night, and is not
relieved with rest is nonmechanical pain and may indicate the
presence of infection or malignancy. 3 Pain can also be described as
axial pain if it is diffuse and referred to the cervical, thoracic, or
lumbar region of the back. Axial pain can be caused by pathology of
musculotendinous structures, facet joints, anulus fibrosus, and
abdominal visceral structures that refer pain to the back. 1
Radicular pain is radiating pain that occurs in a typical dermatomal
distribution and may be associated with numbness, paresthesia,
and weakness in a myotomal distribution and tension signs on
physical examination. Such symptoms indicate nerve root
compression, which may occur because of pathologies such as disk
herniation or spinal canal and foraminal stenosis. 3 Patients who
present with vague pain that does not follow a specific pa ern and
complain of progressive motor and sensory deficits, such as hand
paresthesia, a slow broad-based gait, and difficulty with upper
extremity fine motor tasks (eg, fastening bu ons, handwriting),
may have myelopathy due to spinal cord compression. 4
For patients who present with complaints of low back and leg
pain, it is important to use the history to differentiate between hip
and lumbar spine pathology. Hip pain is generally localized to the
groin, occurs immediately with walking, and is aggravated by
dressing the symptomatic leg or ge ing in and out of a car. 5 Lower
extremity pain originating in the lumbar spine often radiates below
the knee, can be bilateral, and can be associated with tingling or
numbness. 5
The location of a patient’s pain or radiating symptoms can be
used to determine the affected spinal level. Symptoms that follow a
specific dermatomal or myotomal pa ern may indicate involvement
of the corresponding nerve root. The dermatome pa erns currently
considered standard were first described in a 1948 study 6 (Figure
1). Clinically, however, patients may present with symptoms that
vary from these standards. A 2019 study of cervical radiculopathy
compared patient-reported pa erns of radicular symptoms with a
standard textbook dermatomal map and found only 54% correlation
between the two. 7 This finding can be a ributed to anatomic
variations among patients, variations in the severity of a patient’s
disease and symptoms, and to the fact that the standard
dermatome and myotome maps may not fully account for
overlapping innervations. 8

Figure 1 Diagram of the dermatomal distributions of the upper and lower

extremities.(Reproduced with permission from Standaert CJ, Herring SA,
Sinclair JD: Patient history and physical examination: Cervical, thoracic, and
lumbar, in Garfin SR, Bell GR, Fischgrund JS, Bono CM, eds: Rothman-
Simeone and Herkowitz’s The Spine, ed 7. Elsevier, 2018. with permission from
Elsevier. Also special credit to American Spinal Injury Association: International
Standards for Neurological Classification of Spinal Cord Injury, revised 2019;
Richmond, VA.)
 A comprehensive history should identify the presence of red
flags. These are symptoms and findings that can be used to
recognize serious conditions such as infection, tumor, cauda equina
syndrome, and fractures 1 (Table 1). Although many red flags, such
as unintentional weight loss, night pain, and age older than 50
years, have been reported to suggest a diagnosis of malignancy, a
systematic review identified a history of malignancy as the red flag
finding with the highest pos est probability for detecting spinal
malignancy. 9 Similarly, the presence of multiple red flags, such as
older age, prolonged use of corticosteroids, and history of trauma,
had the highest pos est probability for detecting spinal fractures. 9
Spinal infections often occur because of hematogenous spread from
other regions and should be considered when a history of a recent
infection is identified. 1 , 10 Cauda equina syndrome should be
considered when a history of progressive bilateral lower extremity
weakness, saddle anesthesia, and bowel or bladder dysfunction,
particularly urinary retention, is revealed in the patient history. 1 , 10
A detailed history can help formulate a focused differential
diagnosis and guide the physical examination.

Table 1
Key Red Flag Symptoms and Findings for Potential Medical
Conditions

Malignancy
History of malignancy
Unintentional weight loss
Age older than 50 yr
Infection
Fever
Recent infection
Immunosuppressive illnesses/medications
Fracture
History of osteoporosis, ankylosing spondylitis, or trauma
Corticosteroid use
Older age (men older than 65 yr, women older than 75 yr)
Cauda Equina Syndrome
Bowel or bladder dysfunction
Urinary retention
Progressive lower extremity weakness
Saddle anesthesia, perineal numbness, or paresthesia

Physical Examination
A well-performed physical examination can help narrow the
differential diagnosis and identify findings that can further clarify
the cause of a patient’s symptoms. A spine physical examination
should follow the usual pa ern and include inspection, which
includes gait assessment, palpation, and a neurologic examination
that includes provocative maneuvers. 1

Inspection
The physical examination begins with inspection from the moment
a physician first sees a patient. Simply observing a patient and
paying careful a ention to their si ing and standing posture and
head position can offer information about their overall spinal
alignment. 11 Typical spine sagi al alignment includes cervical
lordosis, thoracic kyphosis, lumbar lordosis, and sacrococcygeal
kyphosis. 1 These can be altered in patients with spinal deformity
and sagi al malalignment. Asymmetry in bony structures such as
the rib cage and scapula, obliquity of the pelvis, and a limb-length
discrepancy can also indicate underlying deformity. Skin findings
such as café au lait spots and midline dimples and tufts of hair may
indicate underlying neurofibromatosis or occult spinal dysraphism.
3
Furthermore, muscle atrophy and asymmetry may be noticeable in
patients with nerve root pathology and underlying neurologic
impairment.

Gait
Gait assessment can offer insight into a patient’s underlying
pathology. Observing a patient ambulate on their heels and then on
their toes can help assess for pathology involving the L4/L5 (tibialis
anterior muscles) and S1 (gastrocnemius-soleus complex) nerve
roots, respectively. Tandem gait testing (heel-to-toe walking) can
assess for coordination, balance, and myelopathy. Similarly,
observing a slow, wide-based gait may indicate myelopathy or
cerebellar involvement, whereas a high steppage gait may indicate
a foot drop or L4/L5 pathology. The slow gait often observed in
patients with myelopathy occurs because it takes these patients
more time to fully recruit muscles and achieve peak
electromyography during the gait cycle than in healthy control
patients. 12 An antalgic gait may indicate underlying hip
osteoarthritis and can be used to help differentiate between hip and
lumbar spine pathology.

Range of Motion
Given the complexity in movement of the spine, as opposed to
movement of peripheral joints such as the knee, numerous
measurement techniques have been developed to assess range of
motion. This has resulted in the reporting of a wide range of
normal values for cervical and lumbar range of motion 13 - 15 (Table
2). Despite the variability in normal values, assessing motion can be
useful. It can be expected to decrease with age and degenerative
disease. Pain with certain movements such as lateral bending and
extension may indicate foraminal and facet joint pathology,
respectively. In addition to measuring spine range of motion, hip
range of motion should also be evaluated because a painful and
restricted hip range of motion is a major indicator of underlying
hip pathology. 5

Table 2
Average Range of Motion

Cervical Spine
Flexion: 50°-60°
Extension: 60°-70°
Lateral bending: 40°-45°
Rotation: 70°-75°
Lumbar Spine
Flexion: 50°-80°
Extension: 20°-40°
Lateral bending: 30°-40°
Rotation: 35°-45°

Palpation
Palpation of spinous processes should start at the base of the
occiput and continue down to the sacrum. Midline tenderness
should be differentiated from tenderness in the surrounding soft-
tissue structures. A palpable step-off of the spinous process in the
lumbar spine may indicate underlying spondylolisthesis. Palpation
of the sacroiliac joints and greater trochanters may help identify
pathology that may also be a source of back pain. 11

Neurologic Examination
A thorough neurologic examination makes up the core of a spine
physical examination. Nerve root and spinal cord pathologies such
as radiculopathy and myelopathy are often the most common
neurologic manifestations of spine pathology, so identifying them
with a neurologic examination is important. A neurologic
examination should begin with a quick examination of cranial
nerves II through XII because this can offer insight into any
preexisting brain stem or upper motor neuron pathology.
The sensory examination is a key component of the neurologic
examination, and it requires a thorough understanding of the
sensory dermatomes (Figure 1). Because four distinct sensations
have defined anatomic pathways in the spinal cord, a thorough
examination should assess all four. Sensation should be assessed in
dermatomal pa erns to light touch with co on wool, pinprick with
the sharp end of co on swab, proprioception with a low-frequency
tuning fork, and temperature with a metal reflex hammer. Sensory
deficits in a dermatomal distribution could indicate nerve root
pathology, whereas deficits in multiple dermatomes could suggest
a peripheral neuropathy. 1 , 16 A 2021 study evaluating the efficacy of
sensory tests reported that the combination of light touch and
pinprick testing was adequate to identify abnormal sensory
findings in 88% of patients with known lumbar radiculopathy and
disk herniations. 17
Similar to the sensory examination, the motor examination
consists of several parts. In addition to assessing muscle strength,
muscle tone, muscle bulk, coordination and involuntary
movements, and reflexes should also be assessed. Muscle tone can
be assessed with resistance to passive range of motion. Reduced
tone may suggest a lower motor neuron pathology, whereas
increased tone may suggest an upper motor neuron pathology.
Similarly, asymmetric muscle bulk and atrophy can also imply a
neurologic injury. Coordination and involuntary movements can be
assessed during the inspection and gait portion of the physical
examination and with finger-to-nose and rapid alternating hand
movements. 1
Muscle strength testing can be performed isometrically or with
repetitive movements such as multiple single-leg toe raises. Muscle
strength is graded on a scale from 0 to 5 1 , 3 (Table 3). An
understanding of myotomes and muscle groups innervated by the
cervical and lumbar nerve roots is key to performing a thorough
muscle strength and reflex examination (Table 4 and Figure 2).
Weakness of muscles in a specific myotome may indicate pathology
affecting that nerve root.

Table 3
Muscle Strength Grading Scale

Grade Clinical Sign

5 Normal strength, active motion against full resistance
4 Active motion against gravity and partial resistance
3 Active motion against gravity only
2 Active motion only with gravity eliminated
1 Little motion or slight contraction
0 No observed muscle contraction
Table 4
Cervical and Lumbar Neurologic Examination Guide

Nerve
Motor Testing Sensation Testing Reflex
Root
C5 Shoulder abduction, elbow flexion Lateral upper arm Biceps
C6 Wrist flexion, elbow flexion Lateral forearm, thumb Brachioradialis
C7 Elbow extension, wrist flexion, Long finger Triceps
finger extension
C8 Finger flexion, hand grip Little finger —
T1 Finger abduction Medial forearm and —
elbow
T4 — Nipple —
T10 — Umbilicus —
L1 — Groin —
L2 Hip flexion, hip adduction Anterior thigh —
L3 Knee extension, hip flexion Knee, medial thigh —
L4 Ankle dorsiflexion, knee extension Medial leg, medial Patellar
malleolus
L5 Toe dorsiflexion, hip abduction, Lateral leg, dorsal foot, —
ankle dorsiflexion great toe
S1 Ankle plantar flexion, toe flexion, foot Lateral foot, small toe Achilles
eversion
S2 Toe flexion Posterior thigh —
 Figure 2 Illustration shows motor examination for cervical (A) and lumbar (B)
nerve roots.(Reproduced with permission from An H, Singh K: History and
physical examination, in Synopsis of Spine Surgery, ed 3 Georg Thieme Verlag,
2016, p 1, online resource [324 pages], chap 2.)

Testing deep tendon reflexes can also help localize pathology and
distinguish between upper and lower motor neuron injury.
Diminished deep tendon reflexes can be found in lower motor
neuron diseases, and brisk reflexes can be seen in upper motor
neuron diseases. Reflexes are graded on a scale from 0+ to 4+, where
2+ reflexes are normal.

Cervical Spine Special Tests and Provocative

Maneuvers
Various special tests and provocative maneuvers have been
developed to aid in diagnosing spine pathology. Although these
tests alone cannot make a diagnosis of cervical pathology, they can
aid in narrowing a differential diagnosis and guiding imaging and
diagnostic modalities.
The Spurling test is performed with the patient si ing with the
neck extended, laterally flexed, and rotated toward the affected side
while axial compression is applied to the patient’s head. 2
Reproduction of radicular symptoms including pain, numbness,
and paresthesias in a dermatomal distribution is considered a
positive test. This test is useful in confirming a diagnosis of cervical
radiculopathy because it has good specificity (74% to 96%) but
cannot be used as a screening test because it has a poor sensitivity
(approximately 30%) for cervical radiculopathy. 2 , 18 - 20
The Valsalva maneuver is performed with the patient si ing as
they hold their breath and bear down. Reproduction of radicular
symptoms and pain is considered positive and indicates the
presence of space-occupying pathology in the spinal canal such as a
disk herniation. 1 , 16 Similar to the Spurling test, this maneuver has
high specificity (94%) and low sensitivity (22%) for cervical spine
pathology. 21
The compression test is performed with the patient si ing with
the head in neutral position as axial compression is applied to the
head for a few seconds. The axial load compresses the spine and
decreases the cross-sectional area of the neural foramen.
Reproduction of radicular pain and symptoms is considered a
positive test. 16 This test can also be performed with the neck in
extension to load the facet joints and with the neck in flexion to
offload the facet joints and load the intervertebral disk. 22
The upper limb tension test is performed with the patient supine
while the examiner holds the affected arm and depresses the
patient’s scapula, abducts the shoulder, supinates the forearm,
extends the wrist and fingers, externally rotates the shoulder,
extends the elbow, and laterally flexes the neck away from the
affected side in sequential order. 2 , 21 This maneuver places the
nerves in the affected arm on stretch and is considered positive
when radicular symptoms are reproduced or if elbow extension is
limited by more than 10° because of pain when compared with the
contralateral side. This test has high sensitivity (97%) and can be
used as a screening test to rule out cervical radiculopathy. 20 , 21
The distraction test or axial manual traction test can be
performed with the patient si ing or supine while the examiner
applies axial traction on the patient’s head to distract the cervical
spine. The test is considered positive if radicular symptoms
improve. This test decreases pressure from the intervertebral disks
and opens the foramen to reduce nerve compression. It has high
specificity (90% to 100%) and low sensitivity (44%) for cervical
radiculopathy. 2 , 21
The shoulder abduction test, or Bakody sign, is a relief test
performed with the patient si ing with their affected arm abducted
and hand resting on their head. This test decreases stretch on nerve
roots, and an improvement in radicular symptoms is considered a
positive test. Similar to the Spurling and distraction tests, this
maneuver has high specificity (85% to 92%) and low sensitivity (17%
to 47%) for cervical radiculopathy. 2 , 20 , 21

Lumbar Spine Special Tests and Provocative

Maneuvers
Multiple provocative tests and maneuvers exist to assess lumbar
spine pathology. The straight leg raise test or Lasègue test is
performed with the patient supine as the examiner passively
elevates the patient’s leg with the knee extended. 23 Reproduction of
radicular pain down the posterior thigh past the knee with the leg
raised between 30° and 70° is considered a positive test. 1 Within
this range, this test places the lower lumbar nerve roots on stretch.
A variation of this test is the Bragard test, which involves passive
dorsiflexion of the foot on the raised leg. Reproduction of radiating
pain and symptoms down the leg is considered a positive test. 1 , 11
The crossed straight leg raise test is another variation that is
considered positive if radicular symptoms are reproduced in the
symptomatic leg when the supine straight leg raise test is
performed on the contralateral leg. 11 The straight leg raise test can
also be performed with the patient si ing. The bowstring test is a
variation of the straight leg raise where the knee is flexed slightly in
the raised leg and symptoms are reproduced by pressing on the
popliteal fossa. 1
The femoral stretch test is performed with the patient lying
prone with the knee passively flexed as the examiner lifts the leg to
extend the hips. This maneuver places the femoral nerve and upper
lumbar nerve roots on tension, and reproduction of radicular pain
down the anterior thigh is considered positive. 1 The straight leg
raise and its variations test the L4-S1 nerve roots, whereas the
femoral stretch test tests L2-L4 nerve roots.
The sensitivity and specificity of these tests have been studied. A
Cochrane review evaluating the accuracy of these tests to identify
lumbar radiculopathy reported a high sensitivity (92%) and low
specificity (28%) for the straight leg raise test, whereas the crossed
straight leg raise test had a high specificity (90%) and low
sensitivity (28%). 24 High sensitivity (100%) and specificity (83%)
have been reported for the femoral nerve stretch test. 25

Myelopathic and Long Tract Signs

Numerous special tests exist to identify patients with cervical
myelopathy and diseases affecting upper motor neurons. In
patients with upper motor neuron injury, deep tendon reflexes may
be brisk and hyperactive. Another long tract sign is the Babinski
sign. Plantar stimulation for this maneuver is performed by
stroking the lateral aspect of the plantar foot from the heel toward
the metatarsal heads. A normal response is downward movement
and flexion of the toes. An abnormal response indicative of upper
motor neuron injury is extension of the toes and ankle. This sign
has a high specificity (100%) and low sensitivity (13%). 26
The Hoffman sign is performed by keeping the patient’s wrist in
a relaxed extended position and stabilizing the extended middle
finger. Flicking the distal interphalangeal joint of the middle finger
produces flexion and adduction of the thumb in a patient with
myelopathy and upper motor neuron disease. 3 This sign has been
reported to have a high specificity (84%) and sensitivity (59%) for
cervical myelopathy. 26
The inverted brachioradialis reflex is another long tract sign. It is
considered positive if tapping the brachioradialis muscle results in
contraction of finger flexors instead of the expected wrist extension.
3 , 26
This reflex has been reported to have high specificity (81%) and
low sensitivity (51%) for myelopathy. 26
The finger escape sign is performed by asking patients to hold
their fingers in full extension and adduction for a few seconds.
Escape of the li le finger into adduction and flexion is considered a
positive finding. 3
 Clonus or rhythmic nonvoluntary beats of muscle contraction
with forced dorsiflexion of the ankle is considered a positive finding
for upper motor neuron disease if the clonus is sustained for more
than two to five beats. It has been reported to have high specificity
(100%) and low sensitivity (13%) for myelopathy. 26

Sacroiliac Joint and Nonorganic Pain

Sacroiliac joint pathology can be a source of low back pain and
should be evaluated to differentiate it from lumbar pathology.
Common provocative tests for sacroiliac joint pathology include
distraction, compression, sacral thrust, thigh thrust, Gaenslen test,
and Patrick test. The Patrick test is performed during flexion,
abduction, and external rotation of the hip. It is positive for
sacroiliac joint pathology if pain is referred to the sacroiliac joint
with this maneuver.
An important aspect of the spine physical examination is to
identify nonorganic sources of pain that may confound the
evaluation. The presence of three or more of the Waddell signs
indicates symptom magnification and nonorganic sources of pain.
These signs include superficial and diffuse tenderness to palpation,
simulation of pain (eg, back pain caused by axial loading of the
head), distraction (eg, failure to elicit positive straight leg tests
when the patient is distracted), overreaction, and regional
disturbances in nonanatomic distributions. 27

Imaging Modalities
Multiple imaging modalities are used to image the spine.
Radiography, CT, and MRI are the three most commonly used
imaging techniques. Digital orthogonal radiographs are
inexpensive and readily available and are typically the first-line
imaging modality obtained for spine patients. They allow osseous
structures of the spine and surrounding soft tissues to be imaged.
In addition to AP and lateral views, special views such as oblique,
flexion and extension, and open-mouth views allow specific osseous
and ligamentous anatomic structures to be evaluated. 28 , 29 Recent
advancements in low-dose biplanar digital radiographic imaging
systems such as EOS imaging allow for low-dose whole body
alignment radiographs to be obtained. These images are
particularly useful in evaluating spinal alignment, and excellent
intrarater and interrater reliability has been reported when using
EOS imaging to measure sagi al spine and pelvic alignment
parameters. 30
CT, particularly modern multidetector-row spiral CT, has greatly
improved the detailed evaluation of the osseous structures of the
spine. CT scans are routinely used in the trauma se ing and help to
identify fractures that may be missed with radiographs alone. 28
They are also useful in the perioperative se ing for evaluating
pathologically calcified soft tissues and identifying hardware
location. 28 With the addition of angiography and three-dimensional
reconstructions, CT scans allow vascular and soft-tissue structures
to be identified. Furthermore, navigation and robot-assisted
technologies often rely on CT to identify intraoperative bony
landmarks. Recent advancements in CT technology have shown that
sub-millisievert CT of the cervical and lumbar spine is capable of
providing diagnostically acceptable images while greatly reducing
radiation exposure. 31 , 32
MRI is used to produce multiplanar images with excellent spatial
and anatomic resolution. 28 It allows for evaluation of bone and soft-
tissue structures including the spinal cord and nerves and is the
most commonly used modality to identify spinal pathology such as
degenerative changes, disk herniations, stenosis, infection, and
malignancy. Despite its advantages, MRI should be used
appropriately in patients who present for spine evaluations.
Unfortunately, it is often obtained early in patients who present
with a complaint of low back pain and is associated with greater
health care costs, more surgery, and higher use of prescription
opioids. 33
Diagnostic Procedures
In addition to physical examination and imaging modalities,
numerous diagnostic procedures exist to identify spinal pathology.
Electrodiagnostic studies, such as nerve conduction studies and
needle electrode examinations, are capable of determining the
location and degree of nerve dysfunction. These studies can
identify peripheral versus central causes of radiculopathy and can
also be used to differentiate between motor neuron diseases that
may produce a clinical picture similar to radiculopathy. 28
Spinal injections are often used for diagnostic and therapeutic
purposes in patients with spine pathology. Selective nerve root
injections, which involve the injection of a small amount of local
anesthetic around a nerve root in cervical or lumbar foramen, can
be used to identify spinal levels with pathology. In one study,
patients who experienced more than 90% reduction in pain and
symptoms after a selective nerve root injection had a 91% rate of
successful postoperative result, whereas patients who experienced
less than 90% reduction after selective nerve root injection had only
a 60% rate of successful postoperative results. 34 Similar injections
can be given around facet joints and the sacroiliac joints to identify
them as sources of pain. Like selective nerve root injections,
epidural steroid injections can also be used to diagnose and treat
radicular pain due to disk herniations and stenosis. Although these
are typically low-risk procedures, a 2021 study reported an
increased risk of infection in patients who received a lumbar
epidural steroid injection before lumbar fusion surgery. 35 This risk
was highest at 5.74% if the epidural steroid injection was given
within 30 days of surgery. 35

Summary
Evaluating a patient with spine pathology is a challenging task that
requires obtaining a detailed history and performing a thorough
physical examination. The nature of a patient’s complaint, aspects
of the history, and findings on examination can guide the diagnosis.
Although technologic advancements in imaging and diagnostic
modalities have made identifying pathology easier, speaking with
patients and examining them remains the best way to understand
and treat the true nature of their problem.

Key Study Points

Obtaining a complete history and performing a thorough physical examination are
fundamental in assessing patients and identifying spinal pathology.
Physical examination findings in combination with patient-reported history and
imaging and diagnostic studies can determine a diagnosis.
Although numerous special tests and provocative maneuvers exist for specific spinal
pathologies, one positive finding is not enough to obtain a diagnosis.

Annotated References
1. Standaert CJ, Herring SA, Sinclair JD: Patient history and
physical examination: Cervical, thoracic, and lumbar, in Garfin
SR, Bell GR, Fischgrund JS, Bono CM, eds: Rothman-Simeone and
Herkowi ’s The Spine, ed 7. Elsevier, 2018, pp 183-200.
2. Hippensteel KJ, Brophy R, Smith MV, Wright RW: A
comprehensive review of physical examination tests of the
cervical spine, scapula, and rotator cuff. J Am Acad Orthop Surg
2019;27(11):385-394. This literature review article describes
cervical spine physical examination tests and compares them
with shoulder-specific physical examination tests. Level of
evidence: III.
3. An H, Singh K: History and physical examination, in Lamsback
W, ed: Synopsis of Spine Surgery. ed 3. Georg Thieme Verlag, 2016,
p 1. online resource (324 pages). chap 2.
4. Kane SF, Abadie KV, Willson A: Degenerative cervical
myelopathy: Recognition and management. Am Fam Physician
2020;102(12):740-750. This literature review article describes the
pathophysiology and examination findings of degenerative
cervical myelopathy. Level of evidence: V.
 5. Rainville J, Bono JV, Laxer EB, et al: Comparison of the history
and physical examination for hip osteoarthritis and lumbar
spinal stenosis. Spine J 2019;19(6):1009-1018. This study compared
physical examination tests used to diagnose and differentiate
between lumbar spine pathology and hip osteoarthritis. Level of
evidence: III.
6. Keegan JJ, Garre FD: The segmental distribution of the
cutaneous nerves in the limbs of man. Anat Rec 1948;102(4):409-
437.
7. McAnany SJ, Rhee JM, Baird EO, et al: Observed pa erns of
cervical radiculopathy: How often do they differ from a standard,
“Ne er diagram” distribution? Spine J 2019;19(7):1137-1142. The
authors present a retrospective study comparing observed
dermatomal pa erns of cervical radiculopathy with textbook
dermatome maps in patients with single-level cervical spine
disease. A total of 54% of patients reported symptoms that
followed a standard dermatome pa ern. Level of evidence: III.
8. Riew KD: Variations in cervical myotomes and dermatomes.
Spine J 2019;19(7):1143-1145. This commentary provides several
reasons why few patients conform to textbook descriptions of
radiculopathy including flawed dermatome maps, variability in
symptoms and disease, and anatomic variations. Level of
evidence: V.
9. Downie A, Williams CM, Henschke N, et al: Red flags to screen
for malignancy and fracture in patients with low back pain:
Systematic review. Br Med J 2013;347:f7095.
10. Deyo RA, Rainville J, Kent DL: What can the history and
physical examination tell us about low back pain? J Am Med Assoc
1992;268(6):760-765.
11. Hoppenfeld SS: Physical examination of the lumbar spine, in
Physical Examination of the Spine and Extremities. Appleton-
Century-Crofts, 1976, pp 237-265.
12. Haddas R, Cox J, Belanger T, Ju KL, Derman PB: Characterizing
gait abnormalities in patients with cervical spondylotic
 myelopathy: A neuromuscular analysis. Spine J 2019;19(11):1803-
1808. This nonrandomized prospective controlled cohort study
compared neuromuscular activity in patients with cervical
spondylotic myelopathy with that of healthy control patients. The
authors identified that onset of muscle activity in patients with
cervical spondylotic myelopathy is not delayed; rather, many
muscles take longer to fully contract. Level of evidence: II.
13. Lan CA, Klein G, Chen J, Mannion A, Solinger AB, Dvorak J: A
reassessment of normal cervical range of motion. Spine (Phila Pa
1976) 2003;28(12):1249-1257.
14. Ng JK, Kippers V, Richardson CA, Parnianpour M: Range of
motion and lordosis of the lumbar spine: Reliability of
measurement and normative values. Spine (Phila Pa 1976)
2001;26(1):53-60.
15. Mannion AF, Klein GN, Dvorak J, Lanz C: Range of global
motion of the cervical spine: Intraindividual reliability and the
influence of measurement device. Eur Spine J 2000;9(5):379-385.
16. Hoppenfeld SS: Physical examination of the cervical spine and
temporomandibular joint, in Physical Examination of the Spine and
Extremities. Appleton-Century-Crofts, 1976, pp 105-132.
17. Hasvik E, Haugen AJ, Grøvle L: Pinprick and light touch are
adequate to establish sensory dysfunction in patients with
lumbar radicular pain and disc herniation. Clin Orthop Relat Res
2021;479(4):651-663. This study determined the frequency with
which abnormal sensory findings occur in patients with lumbar
disk herniations. A standard sensory examination of pinprick and
light touch identified 88% of patients with abnormal baseline
findings. Level of evidence: I.
18. Tong HC, Haig AJ, Yamakawa K: The Spurling test and cervical
radiculopathy. Spine (Phila Pa 1976) 2002;27(2):156-159.
19. Viikari-Juntura E, Porras M, Laasonen EM: Validity of clinical
tests in the diagnosis of root compression in cervical disc disease.
Spine (Phila Pa 1976) 1989;14(3):253-257.
20. Thoomes EJ, van Geest S, van der Windt DA, et al: Value of
physical tests in diagnosing cervical radiculopathy: A systematic
review. Spine J 2018;18(1):179-189.
21. Wainner RS, Fri JM, Irrgang JJ, Boninger ML, Deli o A,
Allison S: Reliability and diagnostic accuracy of the clinical
examination and patient self-report measures for cervical
radiculopathy. Spine (Phila Pa 1976) 2003;28(1):52-62.
22. Matheus V, Benzel EC: Physical examination of the cervical
spine, in Patel VV, Patel A, Harrop JS, Burger E, eds: Spine Surgery
Basics. Springer Berlin Heidelberg, 2014, pp 13-21.
23. Kamath SU, Kamath SS: Lasègue’s sign. J Clin Diagn Res
2017;11(5):RG01-RG02.
24. van der Windt DA, Simons E, Riphagen II, et al: Physical
examination for lumbar radiculopathy due to disc herniation in
patients with low-back pain. Cochrane Database Syst Rev
2010(2):CD007431.
25. Tawa N, Rhoda A, Diener I: Accuracy of clinical neurological
examination in diagnosing lumbo-sacral radiculopathy: A
systematic literature review. BMC Musculoskelet Disord
2017;18(1):93.
26. Rhee JM, Heflin JA, Hamasaki T, Freedman B: Prevalence of
physical signs in cervical myelopathy: A prospective, controlled
study. Spine (Phila Pa 1976) 2009;34(9):890-895.
27. Waddell G, McCulloch JA, Kummel E, Venner RM: Nonorganic
physical signs in low-back pain. Spine (Phila Pa 1976)
1980;5(2):117-125.
28. Kim GU, Chang MC, Kim TU, Lee GW: Diagnostic modality in
spine disease: A review. Asian Spine J 2020;14(6):910-920. This
literature review article describes diagnostic modalities in spine
disease. Level of evidence: V.
29. Eismont FJ, Bell GR: Spine imaging, in Garfin SR, Bell GR,
Fischgrund JS, Bono CM, eds: Rothman-Simeone and Herkowi ’s
The Spine, ed 7. Elsevier, 2018, pp 201-240.
30. Kim SB, Heo YM, Hwang CM, et al: Reliability of the EOS
imaging system for assessment of the spinal and pelvic
alignment in the sagi al plane. Clin Orthop Surg 2018;10(4):500-
507.
31. Warncke ML, Wiese NJ, Tahir E, et al: Highly reduced-dose CT
of the lumbar spine in a human cadaver model. PLoS One
2020;15(10):e0240199. This lumbar spine cadaver study
determined that a sub-millisievert, low-dose cervical spine CT
protocol can provide diagnostically acceptable images
comparable to standard-dose CT. Level of evidence: III.
32. Weinrich JM, Regier M, Well L, et al: Feasibility of sub-
milliSievert CT of the cervical spine: Initial results in fresh
human cadavers. Eur J Radiol 2019;120:108697. This cervical spine
cadaver study determined that a highly reduced dose lumbar
spine CT protocol can provide diagnostically acceptable images
comparable to standard-dose CT. Level of evidence: III.
33. Jacobs JC, Jarvik JG, Chou R, et al: Observational study of the
downstream consequences of inappropriate MRI of the lumbar
spine. J Gen Intern Med 2020;35(12):3605-3612. This study
determined that the downstream consequences of early MRI in
patients with back pain include increased rates of surgery,
prescription opioid use, higher pain scores, and higher cost of
care. Level of evidence: III.
34. Sasso RC, Macadaeg K, Nordmann D, Smith M: Selective nerve
root injections can predict surgical outcome for lumbar and
cervical radiculopathy: Comparison to magnetic resonance
imaging. J Spinal Disord Tech 2005;18(6):471-478.
35. Krei TM, Mangan J, Schroeder GD, et al: Do preoperative
epidural steroid injections increase the risk of infection after
lumbar spine surgery? Spine (Phila Pa 1976) 2021;46(3):E197-E202.
This study determined the association between preoperative
epidural corticosteroid injection and infection rate after lumbar
spine decompression and lumbar spine fusion surgery.
Preoperative epidural steroid injections increase infection rates
after fusion surgeries. Level of evidence: III.
C H AP T E R 5 3

Cervical Degenerative
Conditions
Jose A. Canseco MD, PhD, Brian A. Karamian MD, Gregory
R. Toci MD, Alan S. Hilibrand MD, MBA, FAAOS

Dr. Hilibrand or an immediate family member has received royalties from Biomet and CTL
Amedica; has stock or stock options held in Paradigm spine; and serves as a board member,
owner, officer, or committee member of American Academy of Orthopaedic Surgeons. Neither of
the following authors nor any immediate family member has received anything of value from or
has stock or stock options held in a commercial company or institution related directly or
indirectly to the subject of this chapter: Dr. Canseco and Dr. Karamian.

ABSTRACT
Degeneration of the cervical spine leads to changes that may result
in axial neck pain, radiculopathy, myelopathy, and/or deformity. An
updated overview of cervical degenerative conditions and treatment
options is important to help guide physicians and surgeons in the
treatment of patients with cervical spine pathology.
Keywords: cervical spine; degenerative spine disease; myelopathy;
spinal stenosis

Introduction
Cervical spondylosis refers to the age-related degeneration of the
cervical spine, primarily involving the intervertebral disks, facet
joints, and uncovertebral joints. Disk degeneration occurs as a
result of aging and repetitive loading, as hydrostatic pressures and
disk heights are reduced over time (Figure 1). Cervical
intervertebral disks support load distribution and proper head
motion, and the degeneration of these disks redistributes
physiologic loads, resulting in structural degeneration of the disk
(tearing, bulging, or herniation), ligament hypertrophy and
calcification, and the formation of osteophytes. 1 This process may
result in chronic neck pain and disability, although many patients
are asymptomatic. 2 Loss of intervertebral disk height along with
bony and ligamentous hypertrophy may cause foraminal stenosis
compressing the exiting spinal nerve roots leading to symptoms of
radiculopathy. Central stenosis also results from degenerative
changes typically located within the subaxial spine, which may lead
to symptoms of myelopathy. Progressive degeneration of the spinal
column, including atrophy of the surrounding musculature and
a enuation of spinal ligaments, may also lead to structural
deformity.

Figure 1 Magnetic resonance images of disk degeneration grades.

Axial Neck Pain

Axial neck pain may result from a simple cervical sprain or strain,
or from cervical disk degeneration in the absence of radiculopathy
or myelopathy. History and physical exam for patients with axial
neck pain is difficult, as pain is often chronic, nonspecific, and
insidious in nature. 3 In patients presenting with radiculopathy or
myelopathy and concomitant axial neck pain, cervical disk disease
may be a large contributor to their pain. 3
 Atlantoaxial osteoarthritis has a prevalence of 4% and may be a
contributor to axial neck pain, especially in spondylotic elderly
patients. 4 Atlantoaxial osteoarthritis is frequently unrecognized, as
its presentation varies with symptoms including radiating and
nonradiating pain in the posterior neck and occiput, pain with axial
rotation and lateral bending, and pain with palpation of the C1-C2
facet joints. Because the differential diagnosis for posterior neck
pain is wide ranging, atlantoaxial osteoarthritis is sometimes
misdiagnosed as migraines, cluster headaches, or occipital
neuralgia. 4

Cervical Radiculopathy
Cervical radiculopathy occurs from compression or irritation of
spinal nerve roots. Patients with radiculopathy present with
radiating pain as the prominent feature; however, they may also
present with concomitant ipsilateral neck and shoulder pain. 5
Traditionally, radiculopathy was thought to follow a dermatomal
distribution based on the cervical levels involved. However,
nonstandard localization of symptoms is common at all cervical
levels, affecting up to 46% of patients with single-level disease. 5
This may be due to variations in brachial plexus anatomy or
intradural connections of spinal roots. Accordingly, advanced
imaging is required to confirm the level of disease. Given the
possibility of peripheral nerve compression and shoulder pathology
resembling symptoms of cervical radiculopathy, a careful history
and physical examination must be performed to determine if a
patient’s pain is cervical in origin. The Spurling test, in conjunction
with other nerve tension tests such as the Phalen test for median
nerve compression, can help differentiate between central and
peripheral etiologies of radicular-type pain. Cervical radiculopathy
may also occur because of a tortuous vertebral artery, a rare type of
vascular anomaly in which the artery loops around the exiting nerve
root, and it is important for spine surgeons to be aware of this
possibility when reviewing preoperative imaging. 6
 Nonsurgical treatment should be a empted prior to surgical
intervention. Three major surgical treatment options for cervical
radiculopathy include anterior cervical diskectomy and fusion
(ACDF), cervical disk arthroplasty, and posterior cervical
foraminotomy. Based on a 2020 meta-analysis of 21 randomized
controlled trials, there is no superior surgical treatment option. 7
ACDF continues to be the most common treatment option for
single-level radiculopathy, whereas posterior cervical foraminotomy
has been decreasing in prevalence with the advent of cervical disk
arthroplasty. 8 Further discussion of surgical and nonsurgical
management for cervical radiculopathy is presented later in the
chapter.

Cervical Myelopathy
Cervical myelopathy, which occurs from compression of the spinal
cord, is the most common cause of spinal cord dysfunction, and
commonly presents with symptoms in the upper extremity
including weakness, numbness, and loss of dexterity. 9 However, 1%
of patients may report no upper extremity symptoms at all. 10
Clinical diagnosis is frequently supported by MRI, which may aid in
determining the nature and severity of cervical degeneration and
spinal cord involvement. 1 The severity of spinal cord damage
(myelomalacia) can be determined from hyperintensity on T2-
weighted sequences and hypointensity on T1-weighted sequences 11
(Figure 2). Changes in the spinal cord can be categorized as
indistinct, which typically indicates reversible edema and/or
Wallerian degeneration (Figure 2, B), or sharp with clear borders
that typically indicates irreversible tissue loss and necrosis (Figure
2, A and C). 11 The amplitude of low-frequency fluctuations on
functional MRI may be a predictive biomarker for postoperative
improvement in cervical myelopathy following surgery. 12 CT may
be used to evaluate bone quality, and to identify ossification of the
posterior longitudinal ligament and/or ligamentum flavum. 11
Although the incidence of ossification of the posterior longitudinal
ligament is approximately 2% in the general population, it is of
particular interest in cervical myelopathy patients, with a reported
incidence as high as 11%. 11 Standard radiographs, including
flexion-extension films, are also useful for surgical planning and the
assessment of global alignment, balance, and stability. 11

Figure 2 A through C, Sagittal magnetic resonance images show cord signal

change in cervical myelopathy. Arrows indicate level of involvement.

Other symptoms of cervical myelopathy include gait disturbance,

imbalance, and weakness. Patients with cervical myelopathy have
increased center of mass sway and head sway to maintain standing
posture, requiring greater muscle activity and energy expenditure
in the trunk and lower extremities. 13 Physical examination may
demonstrate hyperreflexia, positive Hoffman sign, difficulty with
rapid alternating movements, positive Babinski sign, and clonus.
Many symptoms of cervical myelopathy are nonspecific, and a
differential diagnosis should include multiple sclerosis, transverse
myelitis, normal-pressure hydrocephalus, and stroke, in addition to
spinal cord compression from other etiologies such as trauma,
tumor, and infection. Normal-pressure hydrocephalus may be
especially difficult to differentiate as asymptomatic spinal cord
compression is also common within this patient population. 14
Although the pathophysiology of cervical myelopathy is presumed
to be from spinal cord compression, the severity of cervical
myelopathy and level of functional impairment, as measured by the
Japanese Orthopaedic Association score, may be further
exacerbated by arteriosclerosis of the carotid and vertebral arteries
suggesting a vascular contribution to symptomatology. 15
Somatosensory-evoked potentials, a type of neurophysiologic
monitoring, may be used to predict the progression of disease
severity in cases of mild cervical myelopathy. 16 Somatosensory-
evoked potentials used in conjunction with motor-evoked
potentials (MEP) are able to identify patients with subtle
presentations, differentiate between spinal cord compression and
neurodegenerative disorders, and assist in determining
postoperative recovery. 11 Transcranial electrical motor-evoked
potentials have been shown to have superior sensitivity compared
to somatosensory-evoked potentials for detecting cervical
myelopathy in the early stages of the disease. 11
Cervical myelopathy sometimes is associated with fa y
infiltration and atrophy of deep paraspinal muscles, particularly the
longus capitis, longus colli, and multifidus at the level of spinal
cord compression and caudally, which play a role in cervical
alignment. 17 The degree of change in sagi al alignment parameters
on dynamic radiographs has been noted to be related to the
severity of symptoms in patients with cervical myelopathy. For
example, in a 2020 study, patients with C2-C7 lordosis in flexion
greater than 29° demonstrated be er outcomes than patients with
lordosis in flexion of up to 29°, regardless of surgical or nonsurgical
treatment. 18 Along with muscle atrophy, fragility fractures are a
significant contributor to morbidity and mortality in patients with
cervical myelopathy, with the incidence decreasing after surgical
intervention. 19
Nonsurgical treatment may be initiated for mild myelopathy,
although surgical intervention is recommended to prevent
progression of myelopathy and the resultant denervation and
atrophy of musculature. Although all patients stand to improve
following surgery, patients with increased age, symptom duration
longer than 1 year, increased baseline symptom severity, history of
diabetes and smoking, and psychiatric comorbidities may
experience inferior outcomes. 11 , 20 Surgery is recommended for
patients with moderate or severe cervical myelopathy as measured
by the modified Japanese Orthopaedic Association score. 1

Cervical Kyphosis/Deformity
Deformity of the cervical spine may be associated with axial neck
pain, radiculopathy, and myelopathy, resulting in significant
functional impairment and a reduction in patient quality of life.
Cervical deformity may result from the progression of spondylosis.
21
However, iatrogenic deformity following prior cervical spine
surgery remains the most common cause. Denervation and
subsequent atrophy of the posterior cervical musculature
a enuates the posterior cervical tension band, increasing the
compressive forces experienced by the anterior column and
resulting in cervical kyphosis. The incidence of postsurgical
kyphosis following laminoplasty or laminectomy ranges from 11%
to 21%. 21 Physical findings may include a chin-on-chest deformity,
which can be assessed by a head suspension test, in which a patient
with a rigid deformity who lays supine maintains his/her head
suspended in the air. However, presentation is variable and upper
cervical deformity may not be visually apparent in some patients.
Sagi al and coronal alignment is assessed on PA and lateral
radiographs, whereas stability and flexibility are assessed on
flexion-extension radiographs. 21 Important sagi al radiographic
parameters include C2-C7 lordosis, sagi al vertical axis, T1 slope,
and chin-brow vertebral axis for horizonal gaze. Surgeons must
consider that cervical alignment is highly dependent on
thoracolumbar alignment, and 53% of adults with thoracolumbar
deformity may have concomitant cervical deformity. 21

Nonsurgical Management
There is a wide variety of nonsurgical management options for
disorders of cervical degeneration, including activity modification,
NSAIDs, muscle relaxants, analgesics, physical therapy, cervical
traction, injections, acupuncture, bracing, cervical manipulation,
and manual treatments. 1 , 4 According to a 2019 study, nonsurgical
management is relatively inexpensive when compared to surgical
management (1-year cost per patient: $1,143 versus $22,559 for
ACDF). 22 However, there remains significant variability in
preoperative management likely because of a lack of evidence-
based guidelines for both nonoperative treatment and diagnostic
modalities. Comparing nonsurgical and surgical management is
challenging beacause of the disparity in preoperative diagnoses,
severity of disease, and indications for treatment. Furthermore,
there is a considerable amount of crossover between groups as
patients progress toward surgery. However, theoretical models
suggest that ACDF may be more cost effective than cervical
epidural injections for radiculopathy if patients undergoing
epidural injection are only able to avoid surgery less than 50% of
the time. 23
It is important to remember that cervical myelopathy patients do
not benefit from cervical epidural injections, as it has not been
shown to prevent nor delay surgical treatment. 24 In fact, patients
who underwent cervical epidural injections had higher odds of
having surgery between 1 and 5 years after injection, with no
difference in surgery rates at 1 month. 24

Surgical Management
Surgery is commonly used in the management of cervical
myelopathy, deformity, and cervical radiculopathy refractory to
nonsurgical management. The evidence supporting surgery for
patients with axial neck pain without radicular or myelopathic
symptoms is poor. As with any surgical intervention, a discussion
of postoperative expectations is essential for shared decision-
making between surgeon and patient. Predictors of poor clinical
outcomes following surgery include advanced patient age,
nonambulatory status, longer symptom duration, smoking status,
workers’ compensation status, and disability. 25 Poor baseline
patient-reported outcome measures, particularly neck disability
index for patients with cervical radiculopathy and modified
Japanese Orthopaedic Association score for patients with cervical
myelopathy, are the strongest predictors of poor postoperative
outcomes. 25

Anterior and Posterior Options

The cervical spine is most commonly approached anteriorly
through a muscle-sparing dissection and can be used to address
single-level and multilevel pathology via ACDF with or without
corpectomy. Distraction of the intervertebral disk space during
ACDF results in indirect decompression by increasing foraminal
space and maximizing cervical canal diameter, with evidence to
suggest that increased distraction does not lead to adverse
outcomes. 26 Although commonly used, anterior procedures may be
complicated by postoperative dysphagia, hoarseness from injury or
manipulation to the recurrent laryngeal nerve, vertebral artery
injury, or esophageal perforation. A more recent investigation has
suggested that patients undergoing multilevel ACDF can also
expect significant improvements in postoperative symptoms, with
no differences in clinical outcomes between patients undergoing
three-level and four-level ACDF. 27 For multilevel disease (three or
more), posterior approaches have historically been preferred for
patients with normal alignment as they allow for wider
laminectomy-type decompressions as well as motion-sparing
laminoplasties. However, the posterior approach to the cervical
spine is associated with increased postoperative pain and increased
frequency of complications, including persistent sagi al
malalignment, progressive kyphosis, and wound complications. 27 -
32

Combined approaches (anterior and posterior) allow for

exposure of both the anterior and posterior columns of the cervical
spine combining techniques such as diskectomy and corpectomy of
the anterior spine with laminectomy and instrumentation of the
posterior spine. Circumferential instrumentation allows for
improved stability, mitigating the chance of pseudarthrosis.

Fusion and Motion-Sparing Procedures

Fusion procedures restrict motion by bridging vertebral segments.
Fusion carries the risk of adjacent segment disease by translating
forces created by a fused lever arm to the adjacent disk. ACDF is
the most common spine surgery and is frequently used to address
single-level or multilevel cervical degenerative disease (Figure 3).
Posterior cervical fusion is more often reserved for older patients
with myelopathy and multilevel disease. 33 However, it has become
an increasingly prevalent procedure because of an aging US
population, as well as a shift away from isolated posterior cervical
laminectomy because of the risk of postoperative kyphosis. 34

Figure 3 Lateral preoperative (A) and postoperative (B) radiographs of an

anterior cervical diskectomy and fusion.(Courtesy of Alan S. Hilibrand, MD,
2021.)
 Motion-sparing procedures include foraminotomy, laminectomy,
laminoplasty, and cervical disk arthroplasty. Foraminotomy is a
decompression procedure to enlarge the opening through which
the spinal nerve travels to relieve pain in patients with isolated
cervical radiculopathy. Most surgeons prefer a posterior over an
anterior approach to foraminotomy when treating patients with
cervical radiculopathy. 35
Laminoplasty involves decompressing the spinal cord by
increasing the space available within the spinal canal by hinging
open the lamina. There are several techniques, including the open-
door and double-door (or French door) techniques. Patients
undergoing laminoplasty have similar outcomes compared with
those undergoing posterior cervical fusion, but have decreased
lengths of hospital stay, readmissions, and complications compared
with posterior cervical fusion. 36 , 37 A preoperative C2-C7 lordosis
angle of less than 7° may predict postoperative kyphosis in patients
undergoing laminoplasty. 38 However, patients who are viable
candidates for cervical laminoplasty still more commonly undergo
laminectomy and fusion, despite having similar outcomes with
increased complications. 39
Cervical disk arthroplasty is an anterior surgical procedure
approved for one-level or two-level cervical degenerative disk
disease 40 (Figure 4). Cervical disk replacement, as opposed to
fusion, preserves the index-level facet joints and likely reduces the
risk of development of adjacent segment changes by preserving
physiologic motion at the surgical level(s). 41 Considerations for
successful cervical disk replacement include the degree of motion
and the intrinsic stability of the implant. 40 Prostheses that allow
translation independent of rotation are more likely to restore the
physiologic range of motion and load-sharing from adjacent levels.
However, according to a 2020 study, excessive amounts of motion
may be related to the development of heterotopic ossification,
which can decrease range of motion over time. 41 Prostheses with
resistance to angular and translational motion may confer more
stability to the spinal construct at the expense of decreased motion
and increased risk of adjacent segment disease. Other factors,
including prosthesis height, prosthesis placement, and the integrity
of the soft-tissue envelope following the surgical procedure, also
play a significant role in the stabilization of the disk replacement
construct. 42 Patient selection is also critical when considering
cervical disk replacement. Ideal patients include those with good
bone quality without instability or kyphosis. Patients with
ossification of the posterior longitudinal ligament or ankylosing
spondylitis are often excluded, as the increased motion may lead to
progression of their condition. 40

Figure 4 Lateral preoperative (A) and postoperative (B) radiographs of a

cervical disk arthroplasty.(Courtesy of Alan S. Hilibrand, MD, 2021.)

ACDF versus cervical disk replacement is a topic of frequent

debate, and adoption of cervical disk arthroplasty has been slow.
Many surgeons consider cervical disk arthroplasty to be expensive,
but recent studies have suggested that it is comparably cost-
effective to ACDF. 43 In addition, cervical disk replacement has
been shown to have similar outcomes at 2 years compared to ACDF
in a double-blind randomized controlled trial, including Neck
Disability Index, visual analog scale, arm and neck pain scores,
Short Form 36 Health Survey Questionnaire, and EuroQol
questionnaire, among other outcome measures. 44 Cervical disk
replacement also has been associated with lower rates of adjacent
segment disease and reoperation compared with ACDF. 40 Other
reported benefits include a decreased rate of postoperative
dysphagia and improved clinical outcomes in two-level disease. 40

Summary
Cervical degeneration may cause a spectrum of disorders, including
radiculopathy, myelopathy, and deformity, that lead to pain and
disability. Both nonsurgical and surgical treatments exist, and it is
reasonable to pursue nonsurgical options in patients with mild
conditions. Surgery is effective in improving outcomes, and the
approach and procedure type must be individualized to the patient
with the goal of reducing pain, restoring function, and fixing
deformity.

Key Study Points

Degenerative cervical spine disease can range from spondylosis and radiculopathy
to deformity and myelopathy.
Nonsurgical treatment options for disorders of cervical degeneration include activity
modification, NSAIDs, muscle relaxants, analgesics, physical therapy, cervical
traction, injections, acupuncture, bracing, cervical manipulation, and manual
treatments.
Surgical management, when indicated, can include anterior, posterior, and combined
approaches to the cervical spine with motion-sparing or fusion procedures as viable
options.

Annotated References
1. Badhiwala JH, Ahuja CS, Akbar MA, et al: Degenerative cervical
myelopathy – Update and future directions. Nat Rev Neurol
2020;16(2):108-124. The authors review degenerative cervical
myelopathy, describing the literature regarding epidemiology,
 pathophysiology, pathology, clinical assessment, imaging, and
management. Level of evidence: V.
2. Habibi H, Suzuki A, Tamai K, et al: The severity of cervical disc
degeneration does not impact 2-year postoperative outcomes in
patients with cervical spondylotic myelopathy who underwent
laminoplasty. Spine (Phila Pa 1976) 2020;45(18):E1142-E1149. A
retrospective comparative study of 144 patients undergoing
laminoplasty for cervical myelopathy is presented. The authors
found no differences in outcomes based on the severity of
preoperative disk degeneration. Level of evidence: III.
3. Oitment C, Watson T, Lam V, et al: The role of anterior cervical
discectomy and fusion on relieving axial neck pain in patients
with single-level disease: A systematic review and meta-analysis.
Global Spine J 2020;10(3):312-323. A systematic review and meta-
analysis is presented of 37 studies on the effects of single-level
anterior cervical decompression and fusion on axial neck pain.
Significant improvements in pain and function were observed
following surgery. Level of evidence: III.
4. Adogwa O, Buchowski JM, Sielatycki JA, et al: Improvements in
neck pain and disability following C1-C2 posterior cervical
instrumentation and fusion for atlanto-axial osteoarthritis. World
Neurosurg 2020;139:e496-e500. This is a retrospective
observational study of 42 patients who underwent posterior
atlantoaxial fusion for atlantoaxial osteoarthritis. Significant
improvements in pain and function were observed following
surgery. Level of evidence: IV.
5. McAnany SJ, Rhee JM, Baird EO, et al: Observed pa erns of
cervical radiculopathy: How often do they differ from a standard,
“Ne er diagram” distribution? Spine J 2019;19(7):1137-1142. This
is a retrospective cohort study of 239 patients with single-level
cervical spine disease to determine if localization of symptoms
follows dermatomal distributions. Up to 46% of patients had
nonstandard localization of symptoms based on the spinal level
involved. Level of evidence: III.
 6. Tonsbeek AM, Groen JL, Vleggeert-Lankamp CLAM: Surgical
interventions for cervical radiculopathy caused by a vertebral
artery loop. World Neurosurg 2019;135:28-34. A review of 12
articles is presented, consisting of 14 patients with cervical
radiculopathy due to a tortuous vertebral artery. Multiple
successful surgical interventions were described and
summarized. Level of evidence: IV.
7. Broekema AEH, Groen RJM, de Souza NFS, et al: Surgical
interventions for cervical radiculopathy without myelopathy: A
systematic review and meta-analysis. J Bone Joint Surg
2020;102(24):2182-2196. The authors present a systematic review
and meta-analysis of 21 randomized controlled trials of surgical
treatment for cervical radiculopathy, which was unable to identify
a superior surgical intervention. Level of evidence: I.
8. Mok JK, Sheha ED, Samuel AM, et al: Evaluation of current
trends in treatment of single-level cervical radiculopathy. Clin
Spine Surg 2019;32(5):E241-E245. This is a retrospective database
review to determine the prevalence of anterior cervical
diskectomy and fusion, cervical disk arthroplasty, and posterior
cervical foraminotomy for the treatment of single-level cervical
radiculopathy from 2010 to 2016. Level of evidence: III.
9. Brain WR, Northfield D, Wilkinson M: The neurological
manifestations of cervical spondylosis. Brain 1952;75(2):187-225.
10. Houten JK, Pasternack J, Norton RP: Cervical myelopathy
without symptoms in the upper extremities: Incidence and
presenting characteristics. World Neurosurg 2019;132:e162-e168.
This is a retrospective case series of 12 patients with a diagnosis
of cervical myelopathy requiring surgery who experienced no
symptoms in the upper extremity. A lack of upper extremity
symptoms was found in 1.2% of patients reviewed. Level of
evidence: IV.
11. Jannelli G, Nouri A, Molliqaj G, Grasso G, Tessitore E:
Degenerative cervical myelopathy: Review of surgical outcome
predictors and need for multimodal approach. World Neurosurg
 2020;140:541-547. This is a review of degenerative cervical
myelopathy, particularly concerning surgical outcome predictors,
as well as preoperative diagnosis and imaging. Level of evidence:
V.
12. Takenaka S, Kan S, Seymour B, et al: Resting-state amplitude of
low-frequency fluctuation is a potentially useful prognostic
functional biomarker in cervical myelopathy. Clin Orthop Relat
Res 2020;478(7):1667-1680. The authors present a prospective
study of 28 patients undergoing surgical treatment for cervical
myelopathy to assess the amplitude of low-frequency fluctuation
on functional MRI. The amplitude of low-frequency fluctuation
was found to be a predictive biomarker of improvement
following surgery. Level of evidence: II.
13. Haddas R, Lieberman I, Boah A, Arakal R, Belanger T, Ju KL:
Functional balance testing in cervical spondylotic myelopathy
patients. Spine (Phila Pa 1976) 2019;44(2):103-109. A prospective
study of 32 patients with myelopathy found increased sway and
muscle activity in maintaining balance compared with healthy
control patients. Level of evidence: III.
14. Naylor RM, Lenartowicz KA, Graff-Radford J, et al: High
prevalence of cervical myelopathy in patients with idiopathic
normal pressure hydrocephalus. Clin Neurol Neurosurg
2020;197:106099. A retrospective review of 52 patients with
normal-pressure hydrocephalus to determine the rate of
concomitant cervical myelopathy is presented. Up to 75% of
patients had cervical stenosis, with 17% undergoing surgical
treatment for cervical myelopathy. Level of evidence: IV.
15. Kumagai G, Wada K, Tanaka S, Asari T, Ishibashi Y: Cervical
arteriosclerosis is associated with preoperative clinical symptoms
in patients with cervical spondylotic myelopathy. Eur Spine J
2021;30(2):547-553. This is an evaluation of cervical
arteriosclerosis in 31 patients with cervical myelopathy to
determine the association between ultrasonographic findings of
the carotid and vertebral arteries and severity of symptoms.
 Patients with lumbar stenosis without cervical myelopathy served
as the control group. Level of evidence: IV.
16. Feng X, Hu Y, Ma X: Progression prediction of mild cervical
spondylotic myelopathy by somatosensory-evoked potentials.
Spine (Phila Pa 1976) 2019;45(10):E560-E567. A retrospective
cohort review of 200 patients with a clinical diagnosis of mild
cervical spondylotic myelopathy found that somatosensory-
evoked potentials were able to predict the progression of disease
severity. Level of evidence: IV.
17. Hou X, Lu S, Wang B, Kong C, Hu H: Morphologic
characteristics of the deep cervical paraspinal muscles in patients
with single-level cervical spondylotic myelopathy. World
Neurosurg 2020;134:e166-e171. This is a retrospective case-control
study of 15 patients with cervical myelopathy, who were age and
sex-matched to healthy subjects for the comparison of
morphology of deep paraspinal muscles. Patients with
myelopathy had significantly more fa y infiltration and atrophy.
Level of evidence: III.
18. Lin T, Wang Z, Chen G, Liu W: Is cervical sagi al balance
related to the progression of patients with cervical spondylotic
myelopathy? World Neurosurg 2020;137:e52-e67. A retrospective
study of 126 patients with myelopathy found preoperative
cervical curvature index change constant to be an independent
risk factor for increased neck disability index. Level of evidence:
III.
19. Horowi JA, Puvanesarajah V, Jain A, et al: Fragility fracture
risk in elderly patients with cervical myelopathy. Spine (Phila Pa
1976) 2019;44(2):96-102. A Medicare database study of 60,332
patients with myelopathy found fragility fractures to be a
significant source of morbidity and mortality in elderly patients.
Level of evidence: III.
20. Shenoy K, Patel PD, Henstenburg JM, et al: Impact of
preoperative weakness and duration of symptoms on health-
related quality-of-life outcomes following anterior cervical
 discectomy and fusion. Spine J 2020;20(11):1744-1751. A
retrospective study of 45 patients with weakness prior to ACDF
found preoperative weakness to be a predictor of worse pain and
quality-of-life measures but more potential for improvement
following surgery. Level of evidence: III.
21. Cho SK, Safir S, Lombardi JM, Kim JS: Cervical spine deformity:
Indications, considerations, and surgical outcomes. J Am Acad
Orthop Surg 2019;27(12):e555-e567. A review of cervical spine
deformity etiologies, presentations, and surgical treatment
considerations is presented. Level of evidence: V.
22. Barton C, Kalakoti P, Bedard NA, Hendrickson NR, Saifi C,
Pugely AJ: What are the costs of cervical radiculopathy prior to
surgical treatment? Spine (Phila Pa 1976) 2019;44(13):937-942. A
cost analysis of 1 year of preoperative care of 12,514 patients
undergoing anterior cervical decompression and fusion for
cervical radiculopathy. Per-capita nonsurgical costs were $1,143,
compared with per-capita costs of $22,559 for surgery. Level of
evidence: III.
23. Rihn JA, Bhat S, Grauer J, et al: Economic and outcomes
analysis of recalcitrant cervical radiculopathy: Is nonsurgical
management or surgery more cost-effective? J Am Acad Orthop
Surg 2019;27(14):533-540. The authors present a study of a
theoretical cohort of patients with cervical radiculopathy
simulated to treatment with either anterior cervical
decompression and fusion or cervical epidural injections,
analyzed with Markov chain decision tree Monte Carlo
simulation. Level of evidence: III.
24. Manzur MK, Samuel AM, Vaishnav A, Gang CH, Sheha ED,
Qureshi SA: Cervical steroid injections are not effective for
prevention of surgical treatment of degenerative cervical
myelopathy. Global Spine J 2021; July 5 [Epub ahead of print]. This
is a retrospective comparative study of 686 patients with cervical
myelopathy to determine if cervical epidural injections either
prevent or prolong surgical treatment. Patients with injections
 were associated with higher odds of surgery within 1 year up to 5
years. Level of evidence: III.
25. Archer KR, Bydon M, Khan I, et al: Development and validation
of cervical prediction models for patient-reported outcomes at 1
year after cervical spine surgery for radiculopathy and
myelopathy. Spine (Phila Pa 1976) 2020;45(22):1541-1552. A
retrospective analysis of 4,988 patients with cervical
radiculopathy and 2,641 patients with cervical myelopathy was
performed to develop a predictive model of patient outcomes 1
year after surgery, which resulted in a discriminative
performance of 0.654 to 0.725. Level of evidence: II.
26. Karamian BA, Levy HA, Canseco JA, et al: Does facet distraction
affect patient outcomes after ACDF? Global Spine J 2021; March 24
[Epub ahead of print]. A retrospective study of 229 patients
undergoing ACDF found increased interfacet distance did not
correlate with increased neck pain or disability following surgery.
Level of evidence: III.
27. Canseco JA, Minetos PD, Karamian BA, et al: Comparison
between three- and four-level anterior cervical discectomy and
fusion: Patient-reported and radiographic outcomes. World
Neurosurg 2021;151:e507-e516. A retrospective study of three-level
and four-level ACDFs found significant clinical improvement
following surgery and no difference between the two groups.
Level of evidence: III.
28. Wada E, Suzuki S, Kanazawa A, Matsuoka T, Miyamoto S,
Yonenobu K: Subtotal corpectomy versus laminoplasty for
multilevel cervical spondylotic myelopathy. Spine (Phila Pa 1976)
2001;26(13):1443-1447.
29. Guigui P, Benoist M, Deburge A: Spinal deformity and
instability after multilevel cervical laminectomy for spondylotic
myelopathy. Spine (Phila Pa 1976) 1998;23(4):440-447.
30. Hosono N, Yonenobu K, Ono K: Neck and shoulder pain after
laminoplasty. Spine (Phila Pa 1976) 1996;21(17):1969-1973.
31. Badiee RK, Mayer R, Pennicooke B, Chou D, Mummaneni PV,
Tan LA: Complications following posterior cervical
decompression and fusion: A review of incidence, risk factors,
and prevention strategies. J Spine Surg 2019;6(1):323-333. A review
of complication rates following posterior cervical decompression
and fusion is presented. Level of evidence: V.
32. Shamji MF, Cook C, Pietrobon R, Tacke S, Brown C, Isaacs RE:
Impact of surgical approach on complications and resource
utilization of cervical spine fusion: A nationwide perspective to
the surgical treatment of diffuse cervical spondylosis. Spine J
2009;9(1):31-38.
33. Youssef JA, Heiner AD, Montgomery JR, et al: Outcomes of
posterior cervical fusion and decompression: A systematic review
and meta-analysis. Spine J 2019;19(10):1714-1729. The authors
present a meta-analysis of 1,238 patients who underwent
posterior cervical fusion and decompression, which found
patients had significant clinical improvement with low rates of
revision and/or complications. Level of evidence: III.
34. Kim BS, Dhillon RS: Cervical laminectomy with or without
lateral mass instrumentation. Clin Spine Surg 2019;32(6): 226-
232. A narrative review of cervical laminectomy with or without
lateral mass instrumentation and fusion for the treatment of
cervical myelopathy is presented. Level of evidence: V.
35. Kim S-J, Seo J-S, Lee S-H, Bae J: Comparison of anterior cervical
foraminotomy and posterior cervical foraminotomy for treating
single level unilateral cervical radiculopathy. Spine (Phila Pa 1976)
2019;44(19):1339-1347. The authors present a retrospective case-
control study of 80 patients (40 in each group) who underwent
either anterior cervical foraminotomy or posterior cervical
foraminotomy for the treatment of single-level cervical
radiculopathy. Level of evidence: III.
36. Boniello A, Petrucelli P, Kerbel Y, et al: Short-term outcomes
following cervical laminoplasty and decompression and fusion
with instrumentation. Spine (Phila Pa 1976) 2019;44(17):E1018-
 E1023. This is a retrospective database study of cervical
laminoplasty or laminectomy compared with posterior
laminectomy and fusion. Patients who had undergone fusion
were found to have a higher rate of complications despite similar
preoperative demographics and comorbidities. Level of evidence:
III.
37. Mesregah MK, Buchanan IA, Formanek B, Wang JC, Buser Z:
Intra- and post-complications of cervical laminoplasty for the
treatment of cervical myelopathy: An analysis of a nationwide
database. Spine (Phila Pa 1976) 2020;45(20):E1302-E1311. The
authors present a retrospective database study of 490 patients
undergoing cervical laminoplasty for cervical myelopathy who
were then propensity-matched to patients who underwent
posterior laminectomy and fusion. There were decreased
complications in the laminoplasty group. Level of evidence: IV.
38. Machino M, Ando K, Kobayashi K, et al: Postoperative kyphosis
in cervical spondylotic myelopathy: Cut-off preoperative angle for
predicting the postlaminoplasty kyphosis. Spine (Phila Pa 1976)
2019;45(10):641-648. A prospective cohort study of 1,025 patients
with cervical myelopathy undergoing laminoplasty was
conducted to determine whether cervical sagi al alignment
predicted postoperative kyphosis. A preoperative C2-C7 lordosis
value of less than 7° predicted postoperative kyphosis. Level of
evidence: III.
39. Lopez WY, Goh BC, Upadhyaya S, et al: Laminoplasty – An
underutilized procedure for cervical spondylotic myelopathy.
Spine J 2021;21(4):571-577. A retrospective comparative cohort
study of 250 patients with cervical myelopathy who underwent
either laminoplasty or laminectomy was conducted. Despite
being candidates for laminoplasty, many patients were still
undergoing laminectomy and fusion despite the higher
complication rates. Level of evidence: III.
40. Joaquim AF, Makhni MC, Riew KD: Evidence-based use of
arthroplasty in cervical degenerative disc disease. Int Orthop
2019;43(4):767-775. A review of meta-analyses and clinical trials in
 cervical disk arthroplasty is presented, which concluded that
cervical disk arthroplasty was safe and effective in one- or two-
level disease. Level of evidence: I.
41. Zhao Y, Zhou F, Sun Y, Pan S: Single-level cervical arthroplasty
with ProDisc-C artificial disc: 10-year follow-up results in one
centre. Eur Spine J 2020;29(11):2670-2674. A retrospective
observational study is presented of 27 patients who underwent
ProDisc-C cervical disk arthroplasty with follow-up of 10 years.
Level of evidence: IV.
42. Patwardhan AG, Havey RM: Biomechanics of cervical disc
arthroplasty – A review of concepts and current technology. Int J
Spine Surg 2020;14(suppl 2):S14-S28. The authors present a
biomechanical review of cervical disk arthroplasty in regard to
implant design, healthy cervical spine kinematics, and the
cervical spine kinematics and load sharing following cervical disk
arthroplasty. Level of evidence: V.
43. Reyes AA, Canseco JA, Jeyamohan H, Grasso G, Vaccaro AR:
Financial aspects of cervical disc arthroplasty: A narrative review
of recent literature. World Neurosurg 2020;140:534-540. A review of
the financial literature regarding cervical disk arthroplasty and
anterior cervical decompression and fusion found cervical disk
arthroplasty to have similar cost-effectiveness. Level of evidence:
V.
44. Vleggeert-Lankamp CLA, Janssen TMH, van Zwet E, et al: The
NECK trial: Effectiveness of anterior cervical discectomy with or
without interbody fusion and arthroplasty in the treatment of
cervical disc herniation; a double-blinded randomized controlled
trial. Spine J 2019;19(6): 965-975. A double-blind randomized
controlled trial of 109 patients undergoing anterior cervical
diskectomy and fusion, anterior cervical diskectomy, and anterior
cervical disk arthroplasty found no differences in outcomes at 2-
year follow-up. Level of evidence: I.
C H AP T E R 5 4

Thoracolumbar Conditions
Srikanth N. Divi MD, Kamil T. Okroj MD, Alpesh A. Patel MD,
MBA, FAAOS

Dr. Patel or an immediate family member has received royalties from Alphatec Spine, Amedica,
and NuVasive; serves as a paid consultant to or is an employee of Alphatec Spine, Amedica,
DePuy, a Johnson & Johnson Company, Kuros Biosciences, NuVasive, and Zimmer; has stock or
stock options held in Amedica, Cytonics, EndoLuxe, NociMed, nView Medical Inc., Spine
BioPharma, and Tissue Differentiation Intelligence; and serves as a board member, owner,
officer, or committee member of American Orthopaedic Association, Cervical Spine Research
Society, and North American Spine Society. Neither of the following authors nor any immediate
family member has received anything of value from or has stock or stock options held in a
commercial company or institution related directly or indirectly to the subject of this chapter: Dr.
Divi and Dr. Okroj.

ABSTRACT
Degenerative thoracolumbar conditions are among the most
common presenting musculoskeletal complaints. Low back pain
affects many people with pain and disability. The structural causes
of low back pain can be varied but are generally managed without
surgery because surgical treatment for isolated low back pain has
limited high-quality data. Common degenerative conditions of the
thoracolumbar spine include disk herniations, spinal stenosis,
spondylolisthesis, and scoliosis. Each of these conditions can result
in back pain, radiating lower extremity pain, or neurologic
symptoms including a loss of motor strength or sensation.
Evaluation includes a consistent and complete neurologic
examination paired with appropriate diagnostic imaging
(radiographs, MRI, etc). Nonsurgical management including
medications, physical therapy, and injections often leads to
successful relief of symptoms. Surgery is reserved for patients with
persisting or progressive symptoms. Surgical treatment focuses on
decompression of areas of neurologic compression concordant with
patient symptoms. Open and minimally invasive techniques have
demonstrated successful relief of pain and improvement in
physical function. Conditions with spinal instability
(spondylolisthesis, scoliosis) often necessitate surgical arthrodesis
to stabilize or improve spinal alignment with successful pain relief
and functional improvement demonstrated in high-quality
comparative studies. The optimal surgical arthrodesis technique is
controversial and requires matching patient needs and risk/benefit
analysis and also considers surgeon experience.
Keywords: degenerative scoliosis; disk herniation; spinal stenosis;
spondylolisthesis

Introduction
Degenerative thoracolumbar conditions are among the most
common spine disorders encountered in the clinical se ing. They
encompass a wide range of disease, from disk herniations, subtle
instability between vertebral segments causing nerve root
compression to severe spinal stenosis, high-grade instability, and
thoracolumbar spinal deformity. Low back pain is a highly
prevalent condition and is among the most common causes of
presentation to the doctor’s office. A recent systematic analysis of
the Global Burden of Disease showed that low back pain is the
fourth leading cause of disability among those aged 25 to 49 years. 1
Over the past 30 years, low back pain increased from the 13th
highest percentage of disability-adjusted life-years to the ninth
highest, irrespective of age. 1 Although most cases of back pain are
self-resolving, underlying degenerative disease can cause persistent
symptoms. The prevalence of lumbar spondylosis is approximately
3.6% globally and up to 4.5% in North America. 2
This shift in global prevalence has put increased strain on health
care systems with ever-increasing costs. In a 2021 study, the authors
noted that only 1.2% of patients with back pain undergo a surgical
intervention, but patients with persistent back pain account for
approximately 30% of total US health care cost. 3 One potential
avenue for mitigating the economic effect of degenerative spine
conditions is through increased scrutiny on timely and effective
treatment and a shift toward value-based care. Accurate diagnosis
and treatment can rely on many technologic modalities including
CT, MRI, and electromyography. However, practice heterogeneity
exists with the use of these modalities between primary care
physicians, pain management physicians, and spine specialists,
further contributing to increased costs and inconsistent outcomes.

Common Clinical Presentations

Patients with thoracolumbar disease generally present with a
combination of axial back pain and radicular symptoms. Axial back
pain can have multiple etiologies including muscular, discogenic,
and mechanical. Muscular back pain is the most common cause of
back pain and commonly presents as stiffness and difficulty with
bending. Discogenic back pain is directly related to intervertebral
disk degeneration and tears within the anulus fibrosus. Mechanical
pain is related to instability within a vertebral segment, which
includes micromotion within the facet joints and can eventually
lead to macroinstability in the form of a spondylolisthesis. Patients
commonly complain of pain with lifting and prolonged standing.
Although thoracolumbar decompressions and fusions have been
shown to improve back pain in some patients, the results of surgery
on axial low back pain are less reliable than surgery for radicular
symptoms. These symptoms are therefore generally managed with
nonsurgical measures. 4
Radicular symptoms are caused by nerve root compression and
include a combination of neurogenic pain, numbness/paresthesias,
and weakness. These symptoms are localized within a dermatomal
distribution correlating with the nerve roots being compressed. In
patients with severe central canal stenosis, they can present with
neurogenic claudication, which includes heaviness and cramping in
the bu ock and thighs, general fatigue in the lower extremities, and
bilateral radicular pain in the legs that is worse with prolonged
standing and improved with si ing or forward flexion. The etiology
of radicular symptoms is easier to discern given their dermatomal
distributions, which allows surgeons to correlate findings on
advanced imaging with the patient’s symptoms.
In more severe thoracolumbar disease, patients can present with
myelopathy or cauda equina syndrome. Myelopathy is caused by
direct compression of the spinal cord and presents with gait
instability as well as lower extremity pain, numbness, or weakness.
Cauda equina syndrome is caused by severe compression of the
nerve roots and presents as a combination of severe low back pain,
lower extremity radiculopathy, weakness, bowel and/or bladder
incontinence, loss of rectal tone, and saddle anesthesia.

Lumbar Disk Herniation

Lumbar disk herniations occur when there is a weakening or
disruption in the outer anulus fibrosus, allowing the inner nucleus
pulposus to herniate. Disk herniations are more common in men
than women, with the peak incidence of lumbar disk herniations
around the fourth and fifth decades of life, with a lifetime
prevalence of 10%. 5 The most common location of herniation is
paracentral because of the absence of the posterior longitudinal
ligament in that area. Paracentral disk herniations tend to compress
the traversing nerve root in the lateral recess. Less common
locations for herniation are central and lateral herniations. Central
herniations do not always affect exiting nerve roots but may cause
cauda equina syndrome when they are very large. Lateral
herniations exit directly into the foramen or just lateral to it and
affect the exiting nerve root at that level. The most common level
for herniations to occur is at L5-S1, followed by L4-5, because of the
high biomechanical strain at those levels.
Clinical Presentation and Workup
Lumbar disk herniations present with acute back pain and
unilateral radicular symptoms, often after some strenuous activity
or heavy lifting. In more severe, central herniations, patients can
also present with cauda equina syndrome.
Initial workup of patients presenting with lumbar disk
herniations is an accurate history and physical examination,
carefully assessing for radicular symptoms. If there is concern for
cauda equina syndrome, a rectal examination should be performed
to assess for rectal tone and sensation. Patients with lumbar disk
herniations may exhibit a positive straight-leg raise test and their
radicular symptoms can be made worse with a Valsalva maneuver.
Radiographic evaluation begins with a standard set of weight-
bearing lumbar spine radiographs. In the absence of red flags or
significant neurologic deficit, further advanced imaging can be
delayed to permit a trial of nonsurgical treatment. Further
advanced imaging should be obtained if symptoms persist despite
nonsurgical treatment or if a substantial neurologic deficit is
present. The gold standard for diagnosing disk herniations is MRI
without contrast. This will show a disk fragment (hypointense on
T2-weighted imaging) extruded into the spinal canal, foramen, or
less frequently, lateral to the foramen (Figure 1). In cases where a
patient is unable to undergo MRI, a CT myelogram should be
obtained. In the scenario where there is concern for a recurrent disk
herniation after a prior diskectomy, MRI with and without contrast
should be ordered to help differentiate between a recurrent disk
herniation versus postoperative scarring. Postoperative scar will fill
with contrast, whereas disk material will not.
 Figure 1 Sagittal and axial T2-weighted magnetic resonance images showing
a large left-side lumbar disk herniation causing severe compression of the
traversing left S1 nerve root.The patient presented with left-side posterior
buttock, thigh, and calf pain with calf atrophy and weakness.

Nonsurgical Management
An overwhelming majority of disk herniations (approximately 90%)
will resolve spontaneously and do not require surgical intervention.
6
The mainstay of treatment is management of symptoms with
medications and physical therapy. The primary medications used
are NSAIDs, muscle relaxants, and steroids. Physical therapy
focuses primarily on lumbar extension exercises. Epidural
corticosteroid injections can be considered as well. A systematic
review showed that epidural injections are efficacious in treating
patient pain and improving function in the se ing of a lumbar disk
herniation. 7

Surgical Management
Indications for surgery in the se ing of a lumbar disk herniation
are persistent symptoms for greater than 6 weeks despite
nonsurgical treatment or a severe or progressively worsening
neurologic deficits. Acute cauda equina syndrome or signs and
symptoms of myelopathy from conus medullaris compression also
indicate surgical treatment. The primary surgical intervention for
lumbar disk herniations is a diskectomy. These can be performed
through either an open or minimally invasive approach.
The landmark Spine Patient Outcomes Research Trial (SPORT)
compared patient-reported outcomes between nonsurgical and
surgical management of patients with lumbar disk herniations.
Overall, 1,244 patients were enrolled in the trial, which included
both randomized and observational cohorts. Primary outcomes
included the Oswestry Disability Index (ODI) and Medical
Outcomes Study 36-Item Short Form (SF-36) bodily pain and
physical function scores. Because of significant crossover between
groups in the randomized cohort, the intent-to-treat analysis did
not demonstrate any statistically significant differences between
groups when looking at the primary outcome measures. However,
an as-treated analysis combining both cohorts demonstrated
significant improvement in pain, function, satisfaction, and self-
rated progress in the patients who underwent surgery compared
with the nonsurgical group. Although both groups showed overall
improvement, the surgical group had a larger treatment effect early
on, which narrowed by 2 years. In subsequent as-treated analyses at
4 and 8 years, both groups maintained their improvement, but the
surgical group still demonstrated a slightly superior treatment
effect over the nonsurgical group. 8 - 10
In regard to outcomes between minimally invasive and open
approaches for lumbar diskectomies, a systematic review and meta-
analysis reported similar outcomes between both groups. However,
patients undergoing minimally invasive diskectomies had an
overall shorter length of hospital stay and earlier return to work
than the open diskectomy cohorts. 11
Thoracic Disk Herniation
Symptomatic thoracic disk herniations are much less common than
lumbar disk herniations, with a reported incidence of
approximately 0.5%. 12 Thoracic disk herniations most commonly
occur in the lower thoracic spine given the increased mobility and
mechanical stresses in that area. Patients generally present with
back pain and/or radicular symptoms localized to the chest
wall/flank. In cases that involve spinal cord compression, patients
can present with myelopathy.
Similar to lumbar disk herniation, a set of weight-bearing
radiographs and MRI are the primary imaging modalities of choice.
CT scans have greater utility in thoracic disk herniations to identify
calcifications within the disk, which might alter the approach if
surgery is required.
Surgical intervention is indicated in patients experiencing
refractory pain despite at least 6 weeks of nonsurgical management
or in the se ing of severe or progressively worsening neurologic
deficits or myelopathy. Given the presence of the spinal cord within
the thoracic spine, a standard posterior approach for diskectomy as
seen in the lumbar spine is not feasible because of the high risk of
neurologic complications. Therefore, thoracic diskectomies are
performed either through a posterolateral (transpedicular), lateral
(costotransversectomy), or anterior (transthoracic) approach. An
anterior approach is recommended for central calcified herniated
disks but can introduce significant pulmonary morbidity. A
posterolateral approach is often suitable for noncalcified lateralized
thoracic disk herniations. Because of the high morbidity associated
with transthoracic approaches, minimally invasive thoracoscopic
techniques have gained popularity. However, there is currently no
high-level comparative evidence to establish a clear benefit of
minimally invasive techniques over open techniques for the
management of thoracic disk herniations.
Lumbar Spinal Stenosis
Lumbar stenosis is a degenerative condition characterized by
narrowing of the spinal canal. Given it is a degenerative disease, its
incidence increases with age. It is estimated that approximately
20% of the population demonstrates radiographic findings of
stenosis by the age of 40 years, which jumps to almost 50% by the
age of 60 years. 13 The narrowing is caused by a combination of
multiple factors, most notably facet hypertrophy, hypertrophic
ligamentum flavum, and bulging intervertebral disks, which are
accelerated in areas of higher biomechanical stress such as the
lower lumbar spine. The location of stenosis within the vertebral
segment (central, lateral recess, foraminal) can vary based on each
patient’s pathology. Eventually, as the spinal canal continues to
narrow, it can cause compression of nerve roots, resulting in
radiculopathy, neurogenic claudication, or rarely cauda equina
syndrome. 14

Clinical Presentation and Workup

Patients with symptomatic lumbar stenosis generally present with a
combination of radiculopathy and/or neurogenic claudication.
Patients should also be evaluated for claudication originating from
vascular disease.
Workup should consist of weight-bearing lumbar spine
radiographs, as well as flexion-extension views. These will generally
show degenerative changes including decreased intervertebral disk
heights and spurring of the end plates. It is important to evaluate
for the presence of instability. In the presence of neurologic
symptoms, MRI without contrast should be obtained. This will
often show evidence of ligamentum flavum hypertrophy, bulging
disks, and facet hypertrophy leading to central canal, lateral recess,
and/or foraminal stenosis. 14

Nonsurgical Management
The first line of treatment for spinal stenosis is a combination of
medications, physical therapy, and corticosteroid injections.
Medications primarily include NSAIDs and neuromodulators (eg,
gabapentin, pregabalin). When patients have significant nerve root
irritation, an oral steroid taper can be used. Narcotics should be
avoided given their depressive and addictive qualities. Although
corticosteroid injections can provide temporary symptomatic relief,
one study found in a subgroup analysis of the SPORT trial that
patients who received injections before surgery showed less
improvement in patient-reported outcomes postoperatively (SF-36).
15
A Cochrane systematic review from 2016 investigated surgical
versus nonsurgical treatment for spinal stenosis and did not find
strong evidence to support one over the other. However, as
expected, complications were significantly higher in the surgical
groups (ranging from 10% to 24%) and no complications were
reported in the nonsurgical groups. 16

Surgical Management
Surgical management for lumbar stenosis is indicated in patients
with lumbar spinal stenosis who have persistent neurologic
symptoms despite nonsurgical treatment efforts. The primary
surgical intervention for lumbar stenosis is a facet-sparing
laminectomy. These can be performed through either an open or
minimally invasive approach. In instances where iatrogenic
instability has been introduced, either through a pars fracture or
disruption of the facet joint at a given level, patients should
undergo an arthrodesis at that level. Certain pa erns of foraminal
lumbar stenosis might necessite a fusion despite no evidence of
instability. In the case of front-back foraminal stenosis due to facet
hypertrophy, direct decompression with a Kerrison rongeur might
be difficult and/or innefective. Therefore, a facetectomy with
subsequent instrumented fusion will decompress the foramen
more reliably. Additionally, in patients with significant top-down
stenosis due to disk degeneration, some type of interbody fusion
that helps restore foraminal height is the most appropriate
treatment option.
The SPORT trial also compared patient-reported outcomes
between nonsurgical and surgical management of patients with
lumbar stenosis. The study enrolled 654 patients in total and
included both randomized and observational cohorts. By 8 years,
52% of patients were randomized to nonsurgical care and
underwent surgery. Again, an intent-to-treat analysis found no
difference in primary outcomes between these patients. The as-
treated analysis of the randomized cohort found that the treatment
effect of surgery diminished after the fourth year and became
insignificant after the fifth year. 17 , 18 In contrast, the as-treated
analysis of the observational cohort found that the treatment effect
remained statistically significant for all three primary outcomes at 8
years. 19 A combined as-treated analysis also demonstrated
continued benefit from surgery.
Regarding open versus minimally invasive techniques, a 2019
prospective randomized controlled trial (RCT) demonstrated
similar outcomes between open and minimally invasive techniques
for improvements in pain, function, and disability at 3 years.
However, the minimally invasive group had, on average, shorter
length of hospital stay and a lower complication rate. 20 When
looking at different minimally invasive techniques, another recent
RCT showed that the use of a biportal technique/endoscopy had
favorable clinical outcomes, less pain, and shorter length of
hospital stay compared with microscopic surgery with tubular
retractors for the treatment of lumbar stenosis. 21

Lumbar Spondylolisthesis
Spondylolisthesis is defined as the anterior translation of one
vertebral segment relative to an adjacent vertebral segment.
Although it can be seen in the cervical spine and more rarely in the
thoracic spine, it is most commonly encountered in the lumbar
spine. Several different etiologies have been identified and were
initially organized into the following broad categories according to
the Wiltse classification: type I, congenital dysplasia with sacral
doming; type II, isthmic; type III, degenerative; type IV, traumatic;
and type V, pathologic. 22 An additional sixth subtype, postsurgical,
can be added to the original five to describe instability in or
adjacent to the prior surgical bed. Degenerative spondylolisthesis is
the most common subtype and differs from the other conditions in
that the neural arch is still intact, whereas in the other conditions,
the bony architecture connecting adjacent vertebral segments is
disrupted. This can be a result of fracture or a disrupted pars
interarticularis because of chronic stress fracture, tumor, or a
developmental defect. The pathophysiology and management of
degenerative spondylolisthesis and isthmic spondylolisthesis are
covered as these are the most commonly encountered pathologies
in the general population.

Degenerative Spondylolisthesis
The reported prevalence of degenerative spondylolisthesis ranges
from 19.1% to 43.1% with an average age of 71.5 to 75.7 years and
L4-5 being the most commonly involved level, followed by L5-S1. 23
In addition, there is a significantly higher prevalence in females,
with an up to 6:1 female:male ratio. 23 Vertebral subluxation
secondary to degenerative spondylolisthesis is thought to develop
secondary to degenerative changes, leading to incompetence of the
facet joints. The initial event in this degradation pathway is thought
to be degenerative disk disease resulting in se ling of the anterior
column. Next, ligamentum flavum and facet hypertrophy may
develop in the posterior column as an a empt to stabilize the
degenerated vertebral segment. When the integrity of the facet
joint complex is compromised, microinstability develops, resulting
in either anterolisthesis (forward slippage) or retrolisthesis
(backward slippage). In the lumbar spine, retrolisthesis is typically
stable and rarely contributes to dynamic nerve compression.
However, depending on the degree of dynamic instability,
anterolisthesis can result in significant nerve compression in the
intervertebral foramen or in the lateral recess (subarticular zone),
causing radicular symptoms along the dermatome or myotome of
the affected nerve root. In addition, degenerative spondylolisthesis
can also result in severe central canal stenosis causing neurogenic
claudication symptoms. As such, there is an overlap between
patients with lumbar spinal stenosis as discussed earlier.
The natural history of degenerative spondylolisthesis has not
been well characterized in the literature but is generally described
to be favorable. A long-term follow-up case series in a Japanese
population of 145 nonsurgically managed patients with
degenerative spondylolisthesis found progression in 34% of
patients. Neurologic deficits developed in 24% after a minimum of
10 years of follow-up. 24 The authors also noted that low back pain
improved with stabilization and nonsurgical management.

Isthmic Spondylolisthesis
Isthmic spondylolisthesis refers to vertebral translation secondary
to bilateral pars defects or spondylolysis. This defect in the neural
arch essentially disconnects the anterior and posterior columns of
the cranial vertebral segment, causing anterior translation of the
cranial vertebral body. Spondylolysis is defined by chronic
unhealed stress fractures to the pars interarticularis and exists on a
spectrum, from unilateral to bilateral defects, to varying stages of
healing and pseudarthrosis. These stress fractures are thought to
develop with chronic repetitive axial loading, as evidenced by a
complete absence of spondylolysis in newborns and
nonambulatory patients. 25 , 26 The combination of more coronally
oriented facet joints and relatively thin pars in the lower lumbar
spine compared with the upper lumbar spine predisposes this area
to stress fractures, especially with repetitive activities that involve
hyperextension such as gymnastics or football. The pars
interarticularis is generally a weak point in the spinal column and
bears high stress, especially with lumbar flexion or extension. In
patients with bilateral defects, spondylolisthesis eventually
develops in up to 40% to 66%; therefore, not all patients with
defects in the posterior neural arch have vertebral translation. 27
The prevalence of isthmic spondylolisthesis in children is
approximately 2.6% and can increase to 4% or more in adulthood.
In asymptomatic adults, the prevalence is estimated to be 3.7% to
11.5%. 27
Isthmic spondylolisthesis is commonly asymptomatic and is
often diagnosed incidentally. The rate of progression can depend
on many factors, but local anatomy can play a large role. Because of
the incompetence of the posterior bony neural arch in patients with
isthmic spondylolisthesis, axial load is transmi ed through the
spine disproportionately through the anterior column. This places
increased stress and shear force on the intervertebral disk. Patients
with increased pelvic incidence and sacral slope also have a higher
level of shear force in the anterior column, further contributing to
instability. The combination of decreased disk height (resulting in
decreased up-down neuroforaminal height) and increased anterior
translation (resulting in decreased anterior-posterior foraminal
distance) contributes to the progression of neurologic symptoms
via foraminal stenosis in isthmic spondylolisthesis. In contrast to
degenerative spondylolisthesis, central canal stenosis is rare in
isthmic spondylolisthesis because the disconnected lamina and
inferior articular process remain in place with the caudal vertebral
segment. As the cranial vertebra translates forward, this actually
increases space in the central spinal canal.

Classification of Spondylolisthesis
Several classification systems exist for quantification of the degree
of slip seen between vertebral segments, but the Meyerding
grading system is the most widely accepted. This classification
describes the relative subluxation or slippage of the cranial
vertebral segment on the caudal segment. It is measured using
standing, neutral lateral radiographs of the lumbar spine. The
grade percentage of the slip is determined by drawing a line along
the posterior vertebral body wall of the cranial and caudal vertebral
segments and measuring the amount of translation of the cranial
vertebral body wall. This distance is then measured as a percentage
of the length of the caudal vertebral body (measured at the superior
end plate). 28 The degree of slip is classified as follows: grade 1 (zero
to 25%), grade 2 (25% to 50%), grade 3 (50% to 75%), grade 4 (75% to
100%), and grade 5 (>100%, spondyloptosis). Dynamic films (flexion
and extension standing lateral radiographs) are helpful for the
assessment of mobility and slip severity. A difference in more than
4 mm of translation or 10° of rotation between flexion and extension
films is considered dynamic instability. 28 The Meyerding grading
system is an excellent communication tool because it is easy to use
and has high interrater and intrarater reliability.

Clinical Presentation and Workup

Patients may present with symptoms similar to several other
lumbar pathologies. Common presenting complaints include low
back pain with or without the presence of leg pain. Back pain in
patients with degenerative spondylolisthesis is mechanical and is
exacerbated by lumbar extension, arising from a bent forward
posture, or prolonged standing. This can be differentiated from
discogenic pain, which is worsened in positions that load the
anterior column such as bending forward or prolonged si ing. For
both types of spondylolisthesis, the most common presentation is a
combination of back and leg pain.
Lower extremity pain can present in a radicular (dermatomal)
pa ern or a claudicatory pa ern. Radicular pa erns typically cause
pain along the specific dermatome of the involved nerve root and
can be unilateral or bilateral. However, neurogenic claudication
refers to a pa ern of diffuse posterior bu ock, thigh, and leg pain
that is associated with an upright posture and walking and is more
frequently bilateral. As with lumbar spinal stenosis, because a
claudicatory pa ern of leg pain can also be seen in patients with
circulatory disorders, key questions should be asked when
obtaining patient history to differentiate both conditions. In
vascular claudication, lower extremity pain is worsened with
walking for a fixed distance, walking uphill, or even using a bicycle
while pain is relieved with standing (without si ing). In neurogenic
claudication, lower extremity pain is improved with forward
bending or si ing, but not when remaining standing. Patients tend
to walk in a stooped forward posture to relieve pain (ie, shopping
cart sign). In addition, walking uphill and using a bicycle are
typically painless.
Initial workup of patients presenting with spondylolisthesis
includes a history and physical examination, carefully assessing for
any weakness or sensory deficits that should be correlated with
radicular pa erns of pain. A palpable step-off may not be easily
appreciated in patients with spondylolisthesis and therefore should
not be relied on. In addition, tenderness to palpation in the midline
or the paraspinal musculature is nonspecific. Patients may exhibit a
positive straight leg raise test if there is a significant radicular
component to their pain.
Standing AP, lateral, and flexion/extension radiographs should be
obtained to assess overall coronal and sagi al alignment (Figure 2,
A). In addition, any areas with concern for spondylolisthesis should
be carefully assessed. Measurement of anterior translation on
flexion and extension radiographs can highlight subtle instability
that may not be apparent on lateral radiographs. Oblique
radiographs can also be obtained to assess for the presence of pars
defects. These radiographs are taken at 45º oblique to the sagi al
plane and show the area of the ipsilateral pars interarticularis. CT,
however, is the superior imaging modality for the detection of
spondylolysis and appears as a clear discontinuity. Therefore, CT
can be considered when there is a clinical suspicion of pars defects
but equivocal radiographic findings. MRI is perhaps the most
useful imaging modality in combination with plain radiographs.
MRI highlights areas of neuroforaminal, lateral recess, and central
canal stenosis that should be correlated closely with patient history
and physical examination to identify the pathologic levels (Figure 2,
B). It is important to consider that standing lateral radiographs
should always be obtained at the very minimum because supine
MRI or CT scans may show a completely reduced level with
spondylolisthesis. Increased facet fluid signal (>1.5 mm) has been
found to be highly predictive for the presence of degenerative
spondylolisthesis at L4-5 in the absence of measurable
anterolisthesis on supine MRI; however, the authors of one study
suggest that any sizeable facet effusion (≥1 mm) should be
evaluated with standing flexion and extension films. 29
 Figure 2 A, Standing AP and lateral lumbar radiographs demonstrating a grade
I L4-5 spondylolisthesis. B, Sagittal and axial T2-weighted MRI sequences
redemonstrate the grade I L4-5 spondylolisthesis with central canal stenosis.

The aforementioned Meyerding classification quantifies slip

severity, but other measurement techniques can be used to assess
the degree of angular deformity that develops in spondylolisthesis,
especially in isthmic spondylolisthesis. The slip angle measures the
amount of kyphosis and rotation that develops between the two
displaced vertebral segments. It is measured as the angle
subtended between a line across the inferior end plate of the
cranial vertebra and another line across the superior end plate of
the caudal vertebra. In isthmic spondylolisthesis, the inferior end
plate can be dysplastic, making this measurement difficult. In these
cases, the lumbosacral slip angle can be calculated by drawing a
line across the superior end plate of L5 and another line
perpendicular to the posterior aspect of the S1 body. Higher slip
angles have been associated with increased mechanical instability,
greater risk of slip progression, and postoperative pseudarthrosis
in isthmic spondylolisthesis. 27 Therefore, close a ention should be
paid to the correction of this angle, which improves segmental
kyphosis and reduces shear stress. Disk height can also be
calculated as the average height between the anterior and posterior
disk height.

Nonsurgical Management
Nonsurgical treatment modalities for patients presenting with
spondylolisthesis and back pain with or without leg pain are similar
to other lumbar pathologies. Initial treatment options include
targeted physical therapy and pain management with anti-
inflammatory medications and neuromodulatory agents (ie,
gabapentin, pregabalin, etc). Physical therapy treatment should be
aimed toward core strengthening and stabilization exercises, with
specific targeting of the abdominal musculature and lumbar
multifidus muscles. A brace is not recommended because this can
further weaken core musculature and theoretically lead to a higher
degree of instability. Secondary options for nonsurgical
management include epidural steroid injections, which may
include targeted transforaminal injections or interlaminar
injections.

Surgical Management
Surgical management options for patients with spondylolisthesis
can range from decompression alone to decompression and fusion.
Approaches to fusion can include posterolateral fusion with or
without instrumentation, in combination with interbody fusion.
Common approaches to the disk space for interbody fusion include
anterior retroperitoneal, lateral antepsoas, lateral transpsoas,
posterior midline, and posterior transforaminal. Controversy exists
as to the optimal treatment option for each pathology. Several
patient-specific factors must be considered even before surgical
intervention, including the degree of instability, degree of stenosis
(foraminal, lateral recess, and/or central), patient comorbidities,
history of prior lumbar surgery, and invasiveness of the approach.
In a 2019 systematic literature review of the best available clinical
guidelines for surgical management of spondylolisthesis, the
authors highlight optimal treatment based on current literature. 30
Overall, the body of literature currently supports surgical
intervention over nonsurgical management for patients with
symptomatic degenerative spondylolisthesis. Perhaps the most
well-known study is the SPORT trial that followed up 324 patients
who underwent surgical intervention with decompression, fusion
without instrumentation, or fusion with instrumentation and 187
patients who were treated nonsurgically. In the as-treated post hoc
analysis, patients who underwent surgery reported greater
improvements in ODI and SF-36 bodily pain and physical function
scores at 2 years as well as 4 years. 31 More recently, the 8-year
results were also reported with similar findings of durable
improvements in the surgical group in both the ODI and SF-36
scores. 32 Of note, most of these patients had a grade I
spondylolisthesis, with the remainder of patients being grade II. In
addition, patients undergoing decompression alone were not
compared with those who also underwent concomitant fusion.
Those who underwent nonsurgical management also demonstrated
modest improvement in patient-reported outcomes in pain and
function, with no notable cases of cauda equina, demonstrating
clinical stability for patients with this condition.
In 2016, the New England Journal of Medicine published two RCTs
analyzing decompression alone versus decompression with fusion
for patients with grade I spondylolisthesis that demonstrated
conflicting results. 33 , 34 In one RCT, 247 patients with or without
spondylolisthesis at 1 or 2 levels were randomized to either group,
with no demonstrable differences in ODI or 6-minute walk test at 2
and 5 years. 33 However, in the other RCT, 66 patients were
randomized to either group, with the fusion group demonstrating a
greater SF-36 physical component summary score at 2, 3, and 4
years with no differences noted in ODI. The authors purport that
the strengths of their study include that only patients with single-
level disease were included and also they characterized the degree
of dynamic spondylolisthesis with flexion and extension films. 34
With regard to retrospective studies, there are similar differences in
the literature. In one large retrospective study analyzing patient
outcomes at 2 years, the authors found that patients undergoing
decompression and those with decompression and fusion achieved
minimal clinically important difference and a ained substantial
clinical benefit at similar rates. 35 In the end, more high-quality
prospective evidence is needed to determine the recommendation
of fusion in addition to decompression.
When analyzing different techniques for fusion, the current body
of literature shows equivocal findings mainly because of a lack of
adequately powered, high-quality studies. However, the use of
pedicle screw instrumentation to obtain rigid spinal fixation has
become commonplace in patients with degenerative
spondylolisthesis. One prospective study randomized patients
undergoing posterior decompression and fusion to those with and
those without transpedicular instrumentation. 36 At 2 years,
patients with pedicle screw instrumentation had a significantly
higher fusion rate compared with uninstrumented patients (82%
versus 45%, P = 0.0015). Minimally invasive surgery techniques have
also been applied to decompression and fusion in the se ing of
degenerative spondylolisthesis, with most studies showing
equivocal patient-reported outcomes. However, patients who
underwent minimally invasive surgical fusion had less
intraoperative blood loss and shorter length of hospital stay. 30
 An expanding area of controversy currently is the use of anterior
column support with an interbody device. Arguments for the use of
interbody devices include restoration of disk and foraminal height,
restoration of lordosis, as well as increased fusion area. When
compared with posterolateral fusion alone, the use of an interbody
device has not been shown to definitively improve patient-reported
outcomes or fusion rates in either degenerative spondylolisthesis or
isthmic spondylolisthesis and may be associated with increased
surgical time and cost. 37 , 38 The surgical approach as well as the
need for an interbody fusion should be evaluated on a case-by-case
basis.

Principles of Adult Degenerative Scoliosis

Adult degenerative scoliosis is a heterogeneous condition that
results in a three-dimensional deformity of the spinal column in the
coronal, sagi al, and axial planes (Figure 3). Although patients can
have adult spinal deformity secondary to progression of adolescent
idiopathic scoliosis, most cases of degenerative scoliosis arise de
novo in adulthood. In addition, degenerative scoliotic changes can
be seen secondary to other spinal conditions, such as bone
metabolism disorders (osteoporosis, etc), rheumatologic
conditions, or after prior spine surgery. Similar to other
degenerative spine conditions, the prevalence of adult degenerative
scoliosis is thought to be increasing, with current global estimates
reported to be around 37.6%, with a higher prevalence in females
and patients older than 60 years. 39 De novo degenerative scoliosis
is more likely to be localized to the lumbar spine, with less
magnitude, but with a faster rate of progression than idiopathic
scoliosis.
 Figure 3 AP (A) and lateral (B) lumbar plain radiographs demonstrate a left-
side lumbar degenerative scoliotic curve from L2-5 with right-side asymmetric
disk collapse and rotatory subluxation at L3-4.

Symptoms can range from being asymptomatic to severe

disability. The primary patient complaint is back pain that limits
ambulatory capacity and patient functionality. Many patients may
also complain of radicular pain if they have nerve root
impingement. The presence of concomitant lumbar spinal stenosis
can cause significant neurogenic claudication symptoms, further
limiting functionality. Patients may notice a mild deformity, but
significant sagi al imbalance may also result in an inability to
maintain an upright posture.
There are important differences in the physical examination of a
patient with deformity that should be noted. A thorough evaluation
should include careful observation of the patient’s standing posture
in the coronal and sagi al plane, with note of any pelvic
asymmetry, rib prominence, or shoulder asymmetry. Supine
examination is critical in the assessment of patients with deformity
with a ention to the hip and knee joint range of motion. Flexion
contractures of the hips and knees may be present in patients with
severe positive sagi al imbalance. The patient’s gait should be
evaluated for any disturbances because chronic hip and knee
flexion contractures contribute to a crouch knee gait.
Thorough radiographic evaluation of patients with degenerative
scoliosis and patients with spinal deformity is critical for
determining the appropriate management options. Thirty-six-inch
full-length scoliosis films with PA and lateral views are obtained to
assess spinal alignment in the coronal and sagi al planes and
should at least visualize the spinal column from the external
auditory meatus through the hip joints. When possible, inclusion of
the entire body allows evaluation for lower extremity compensation,
including pelvic retroversion, knee flexion, and ankle dorsiflexion.
Pelvic obliquity may signify leg-length discrepancy, and any leg-
length differences should be equalized with standing blocks to gain
a true understanding of spinal alignment. Side-bending films can
help identify rigid, structural curves versus mobile, compensatory
curves. Measurements of spinopelvic parameters and global
parameters are used to quantify a patient’s alignment. Common
parameters are listed in Table 1, with example measurements
shown in Figures 4 and 5.

Table 1
Definition and Explanation of Regional Spinopelvic Parameters
and Global Parameters

Global and Spinopelvic

Name Measurements Explanation
Definition
 Global and Spinopelvic
Name Measurements Explanation
Definition
Pelvic tilt Angle subtended by a line from the Indicates rotation of pelvis about
(PT) midpoint of the sacral end plate to the hip joints. PT > 20° indicates
center of the femoral heads and a pelvic retroversion and patient
vertical reference line attempt at compensation for
sagittal imbalance
Sacral Angle subtended by a line through the —
slope (SS) sacral end plate and a horizontal
reference line
Pelvic Angle subtended by a line perpendicular Orientation of the sacrum in the
incidence to the sacral end plate and a line from pelvis. PI can also be described
(PI) the center of the femoral heads to the as the sum of PT and SS (PI = PT
center of the sacral end plate + SS)
Lumbar Angle subtended by a line through the —
lordosis superior end plate of L1 and a line
(LL) through the superior end plate of S1
PI-LL Difference between PI and LL A high degree of mismatch (PI-LL
(mismatch) > 10°) has been implicated in
worse patient outcomes
L4-S1 Angle subtended by a line through the Two-thirds of overall lumbar
lordosis superior end plate of L4 and a line lordosis originates from L4-S1
through the superior end plate of S1
Sagittal Distance between a plumb line from the Indicates SVA > 5 cm is
vertical C7 centroid and the posterior-superior associated with poor patient
axis (SVA) corner of S1 outcomes
Thoracic Angle subtended by a line through the —
kyphosis superior end plate of T1 and a line
through the inferior end plate of T12
T1 pelvic Angle subtended by a line from the T1 Aggregates information provided
angle centroid to the center of the femoral by PT and SVA to give a global
(TPA) heads and a line from the center of the measurement of sagittal
sacral end plate to the center of the imbalance
femoral heads
Figure 4 Radiographs showing example measurements of spinopelvic
parameters.From left to right: pelvic tilt—the angle between the sacral end plate
and a vertical reference line; pelvic incidence—the angle between a line
perpendicular to the sacral end plate and a line to femoral heads; and sacral
slope—the angle between a horizontal reference line and a line through the
sacral end plate.
 Figure 5 Radiographs showing example measurements of global alignment
parameters.A, T1 pelvic angle (TPA) depicts the angle between a line from the
sacral end plate to the femoral heads, and a line from the T1 centroid to the
femoral heads. B, The C7 sagittal vertical axis (SVA) depicts the distance from a
plumb line from the C7 centroid to the posterior-superior corner of S1.

Goals of surgical management in patients with degenerative

scoliosis should be extensively discussed with the patient. The
range of surgical treatment includes decompression only to address
neurologic compression, to local or regional decompression and
fusion, to decompression and global correction of alignment. In
addition, the approach for surgery can range from anterior, lateral,
posterior, or combined approaches. A careful understanding
regarding the goals of surgery between the surgeon and the patient
should be discussed, including decompression for radicular or
claudicatory symptoms and deformity correction for alignment and
the reduction of axial pain. To date, many studies have assessed the
correlation between ideal radiographic parameters and improved
health-related quality of life outcomes. Specifically, three scores
have been identified that correlated with severe disability as
measured by an ODI greater than 40: (1) pelvic tilt greater than 22°,
(2) sagi al vertical axis (SVA) greater than 47 mm, and (3) pelvic
incidence–lumbar lordosis (PI-LL) mismatch greater than or equal
to 11°. 40
Over the past decade, correction of spinal deformity has focused
on the optimization of these key parameters to obtain optimal
alignment. Pelvic incidence refers to the orientation of the sacrum
in the pelvis and is a morphologic parameter that is set by the end
of adolescence. Lumbar lordosis is the lordotic curvature present in
the lumbar spine. To obtain spinal harmony, patients with a high
pelvic incidence tend to have a high lumbar lordosis and vice versa.
With progressive degenerative changes, lumbar lordosis decreases
with age, whereas pelvic incidence remains the same, resulting in
positive sagi al balance and a high PI-LL mismatch. Pelvic tilt
describes the orientation of the pelvis around the hip joints and is
increased in cases of positive sagi al balance (high PI-LL
mismatch) where the patient a empts to compensate by
retroverting their pelvis to obtain a more upright posture.
Although these parameters describe the relationship of the
thoracolumbar spine and the pelvis, other parameters be er
describe global alignment. SVA refers to the distance on a standing
radiograph between a plumb line from the C7 centroid to the
posterior-superior corner of S1 and quantifies the degree to which a
patient is pitched forward. TPA refers to the T1 pelvic angle that
incorporates pelvic tilt and SVA to describe the sagi al orientation
of the spine.
Despite progress in optimizing patient outcomes, surgery to
correct deformity in adults is still fraught with many postsurgical
complications. These may include perioperative medical
complications such as pneumonia, myocardial infarction, stroke,
deep venous thrombosis, and pulmonary embolism or surgical
complications such as proximal junctional failure, pseudarthrosis,
or wound dehiscence. Recently, the degree of surgical correction
required to optimize health-related quality of life has come into
question. Prior studies suggested that undercorrection of sagi al
deformity correlated with worse health-related quality of life
outcomes; however, overcorrection has also been shown to be
associated with an increased risk of proximal junctional kyphosis
and other adverse outcomes. 41 Determining the appropriate
amount of correction needed for each patient may depend on
identifying the specific drivers of deformity in each patient: age,
comorbidities, etc. More recently, an adult spinal deformity
comorbidity score developed by the International Spine Study
Group incorporated pertinent preoperative variables including age,
comorbidities, Charlson Comorbidity Index, American Society of
Anesthesiologists functional classification, and the ODI to
accurately identify patients with major postoperative surgical and
medical complications. 42 Although this study and others have
identified several key elements critical to successful management of
patients with degenerative scoliosis, additional high-quality
prospective studies are needed.
Summary
Degenerative thoracolumbar conditions are highly prevalent and
disabling conditions. Patients with isolated low back pain
secondary to degenerative conditions are typically treated with
nonsurgical management. Other common conditions including disk
herniations, spinal stenosis, spondylolisthesis, and degenerative
scoliosis typically result in back pain, radicular symptoms, or
neurogenic claudication. Careful evaluation of motor and sensory
function may reveal deficits along affected myotomes and
dermatomes. Evaluation with imaging is done initially with plain
radiographs, and with CT and MRI as indicated. Nonsurgical
management with medications, physical therapy, and epidural
injections can be effective in alleviating pain. Surgical management
ranges from decompression to fusion procedures. The optimal
approach for each patient requires careful individual evaluation.

Key Study Points

Low back pain is weakly associated with any single condition of the thoracolumbar
spine and rarely benefits from surgical intervention.
Most conditions identified on advanced diagnostic imaging are age related, normal,
and asymptomatic.
Nonsurgical treatment is generally successful and surgical treatment should be the
exception, not the rule, in medical decision making.
Among patients with confirmed, symptomatic neurologic compression, surgical
decompression yields successful relief of pain and improvement in physical
function.
Surgical arthrodesis is indicated for spinal instability; however, the literature has not
demonstrated any single technique as better than another.

Annotated References
1. Abbafati C, Abbas KM, Abbasi-Kangevari M, et al: Global
burden of 369 diseases and injuries in 204 countries and
territories, 1990-2019: A systematic analysis for the Global Burden
of Disease Study 2019. Lancet 2020;396(10258):1204-1222. This is a
 2019 update on the Global Burden of Disease for 369 diseases.
Compared with prior studies on the Global Burden of Disease,
musculoskeletal disease and in particular back pain have steadily
risen, especially in the age group of 25 to 49 years. Level of
evidence: V.
2. Reid PC, Morr S, Kaiser MG: State of the union: A review of
lumbar fusion indications and techniques for degenerative spine
disease. J Neurosurg Spine 2019;31(1):1-14. This is a review article
describing lumbar fusion techniques and indications. Level of
evidence: V.
3. Philipp LR, Leibold A, Mahtabfar A, Montenegro TS, Gonzalez
GA, Harrop JS: Achieving value in spine surgery: 10 major cost
contributors. Global Spine J 2021;11(1 suppl):14S-22S. This invited
review article describes the top 10 current cost contributors in
spine surgery. An initial poll was undertaken and items that were
mentioned with greater frequency were considered for further
discussion. Level of evidence: V.
4. Förster M, Mahn F, Gockel U, et al: Axial low back pain: One
painful area – Many perceptions and mechanisms. PLoS One
2013;8(7):e68273.
5. Kim Y-K, Kang D, Lee I, Kim S-Y: Differences in the incidence of
symptomatic cervical and lumbar disc herniation according to
age, sex and national health insurance eligibility: A pilot study on
the disease’s association with work. Int J Environ Res Public Health
2018;15(10):2094.
6. Saal JA, Saal JS: Nonoperative treatment of herniated lumbar
intervertebral disc with radiculopathy: An outcome study. Spine
1989;14(4):431-437.
7. Manchikanti L, Benyamin RM, Falco FJE, Kaye AD, Hirsch JA:
Do epidural injections provide short- and long-term relief for
lumbar disc herniation? A systematic review. Clin Orthop Relat
Res 2015;473(6):1940-1956.
8. Lurie JD, Tosteson TD, Tosteson ANA, et al: Surgical versus
non-operative treatment for lumbar disc herniation: Eight-year
 results for the spine patient outcomes research trial (SPORT).
Spine 2014;39(1):3-16.
9. Weinstein JN, Tosteson TD, Lurie JD, et al: Surgical vs
nonoperative treatment for lumbar disk herniation: The spine
patient outcomes research trial (SPORT) – A randomized trial. J
Am Med Assoc 2006;296(20):2441-2450.
10. Weinstein JN, Lurie JD, Tosteson TD, et al: Surgical versus
nonoperative treatment for lumbar disc herniation. Spine
2008;33(25):2789-2800.
11. Qin R, Liu B, Hao J, et al: Percutaneous endoscopic lumbar
discectomy versus posterior open lumbar microdiscectomy for
the treatment of symptomatic lumbar disc herniation: A systemic
review and meta-analysis. World Neurosurg 2018;120:352-362.
12. Greenberg JO: Thoracic disc herniations; incidence and
characteristics in an outpatient magnetic resonance imaging
center. J Neuroimaging 1992;2(3):125-130.
13. Kalichman L, Cole R, Kim DH, et al: Spinal stenosis prevalence
and association with symptoms: The Framingham study. Spine J
2009;9(7):545-550.
14. Hilibrand A, Rand N: Degenerative lumbar stenosis: Diagnosis
and management. J Am Acad Orthop Surg 1999;7(4):239-249.
15. Kepler C, Radcliff K, Hilibrand A, et al: Do epidural steroid
injections affect the outcome of patients treated for lumbar
stenosis? A subgroup analysis of the SPORT. Spine J
2011;11(10):S24.
16. Zaina F, Tomkins-Lane C, Carragee E, Negrini S: Surgical versus
non-surgical treatment for lumbar spinal stenosis. Cochrane
Database Syst Rev 2016; 2016(1):CD010264.
17. Weinstein JN, Tosteson TD, Tosteson AN, et al: Surgical versus
nonsurgical therapy for lumbar spinal stenosis. N Engl J Med
2008;358(8):794-810.
18. Weinstein JN, Tosteson TD, Lurie JD, et al: Surgical versus non-
operative treatment for lumbar spinal stenosis four-year results
 of the spine patient outcomes research trial (SPORT). Spine
2010;35(14):1329-1338.
19. Lurie JD, Tosteson TD, Tosteson A, et al: Long-term outcomes
of lumbar spinal stenosis: Eight-year results of the spine patient
outcomes research trial (SPORT). Spine 2015;40(2):63-76.
20. Horan J, Husein M, Bolger C: WP1-4 Bilateral laminotomy
through a unilateral approach (minimally invasive) vs open
laminectomy for lumbar spinal stenosis. J Neurol Neurosurg
Psychiatry 2019;90(3):e2.4-e3. This study compared 62 patients
with lumbar spinal stenosis randomized to a minimally invasive
unilateral approach versus a traditional open approach and
found that both approaches were equivalent in improving pain,
ODI, and walking distance. Level of evidence: III.
21. Kang T, Park SY, Kang CH, Lee SH, Park JH, Suh SW: Is biportal
technique/endoscopic spinal surgery satisfactory for lumbar
spinal stenosis patients? A prospective randomized comparative
study. Medicine 2019;98(18):e15451. This study prospectively
analyzed patients with lumbar spinal stenosis undergoing either
bilateral endoscopic approach or minimally invasive surgical
approach with a tubular retractor and found that the bilateral
endoscopic approach had lower surgery time, less drain output,
lower opioid usage, and shorter length of hospital stay with
equivalent outcomes at 6 months. Level of evidence: III.
22. Wiltse LL, Newman PH, Macnab I: Classification of
spondylolisis and spondylolisthesis. Clin Orthop Relat Res
1976;117:23-29.
23. Bydon M, Alvi MA, Goyal A: Degenerative lumbar
spondylolisthesis: Definition, natural history, conservative
management, and surgical treatment. Neurosurg Clin N Am
2019;30(3):299-304. This review article describes the natural
history and management of degenerative spondylolisthesis with
consideration and update of literature regarding decompression
alone or decompression and fusion. Level of evidence: V.
24. Matsunaga S, Ijiri K, Hayashi K: Nonsurgically managed
patients with degenerative spondylolisthesis: A 10- to 18-year
follow-up study. J Neurosurg 2000;93(2 suppl):194-198.
25. Rosenberg N, Bargar W, Friedman B: The incidence of
spondylolysis and spondylolisthesis in nonambulatory patients.
Spine 1981;6(1):35-38.
26. Frederickson B, Baker D, McHolick W, Yuan H, Lubicky J: The
natural history of spondylolysis and spondylolisthesis. J Bone
Joint Surg Am 1984;66(5):699-707.
27. Bhalla A, Bono CM: Isthmic lumbar spondylolisthesis.
Neurosurg Clin N Am 2019;30(3):283-290. This review article
considered the natural history, pathophysiology, and updated
treatment strategies for isthmic spondylolisthesis. Level of
evidence: V.
28. Koslosky E, Gendelberg D: Classification in brief: The
Meyerding classification system of spondylolisthesis. Clin Orthop
Relat Res 2020;478(5):1125-1130. This narrative review article
describes the classification system for spondylolisthesis with
consideration of prior studies that assessed both interobserver
and intraobserver reliability for the different classification
techniques. Level of evidence: V.
29. Chaput C, Padon D, Rush J, Lenehan E, Rahm M: The
significance of facet joint cross-sectional area on magnetic
resonance imaging in relationship to cervical degenerative
spondylolisthesis. Spine 2007;32(17):1883-1887.
30. Chan AK, Sharma V, Robinson LC, Mummaneni PV: Summary
of guidelines for the treatment of lumbar spondylolisthesis.
Neurosurg Clin N Am 2019;30(3):353-364. This systematic review
article summarized treatment guidelines for management of
degenerative lumbar spondylolisthesis. A total of 46 studies were
included and 37 were used for evidence-based recommendations.
Level of evidence: III.
31. Weinstein JN, Lurie JD, Tosteson TD, et al: Surgical compared
with nonoperative treatment for lumbar degenerative
 spondylolisthesis: Four-year results in the spine patient
outcomes research trial (SPORT) randomized and observational
cohorts. J Bone Joint Surg Am 2009;91(6):1295-1304.
32. Abdu WA, Sacks OA, Tosteson ANA, et al: Long-term results of
surgery compared with nonoperative treatment for lumbar
degenerative spondylolisthesis in the spine patient outcomes
research trial (SPORT). Spine 2018;43(23):1619-1630.
33. Försth P, Ólafsson G, Carlsson T, et al: A randomized,
controlled trial of fusion surgery for lumbar spinal stenosis. N
Engl J Med 2016;374(15):1413-1423.
34. Ghogawala Z, Dziura J, Butler WE, et al: Laminectomy plus
fusion versus laminectomy alone for lumbar spondylolisthesis. N
Engl J Med 2016;374(15):1424-1434.
35. Rampersaud YR, Fisher C, Yee A, et al: Health-related quality of
life following decompression compared to decompression and
fusion for degenerative lumbar spondylolisthesis: A Canadian
multicentre study. Can J Surg 2014;57(4):126-133.
36. Fischgrund JS, Mackay M, Herkowi HN, Brower R,
Montgomery DM, Kurz LT: Degenerative lumbar
spondylolisthesis with spinal stenosis: A prospective,
randomized study comparing decompressive laminectomy and
arthrodesis with and without spinal instrumentation. Spine
1997;22(24):2807-2812.
37. Alhammoud A, Schroeder G, Aldahamsheh O, et al: Functional
and radiological outcomes of combined anterior-posterior
approach versus posterior alone in management of isthmic
spondylolisthesis. A systematic review and meta-analysis. Int J
Spine Surg 2019;13(3):230-238. This systematic review and meta-
analysis of six articles compared outcomes of anterior-posterior
versus posterior-only approaches for isthmic spondylolisthesis
and found that overall there were no significant differences in
fusion rate or clinical outcomes, despite a higher rate of
complications with the anterior approach. Level of evidence: III.
38. Kelly JP, Alcala-Marquez C, Dawson JM, Mehbod AA, Pinto MR:
Treatment of degenerative spondylolisthesis by instrumented
posterolateral versus instrumented posterolateral with
transforaminal lumbar interbody single-level fusion. J Spine Surg
2019;5(3):351-357. This retrospective cohort study compared
patients undergoing a single-level posterolateral fusion alone
versus those undergoing a posterolateral fusion with a
transforaminal lumbar interbody fusion. Two-year follow-up data
showed no difference in ODI improvement between the groups,
whereas implant cost and surgical time were higher in the
transforaminal lumbar interbody fusion group. Level of evidence:
III.
39. McAviney J, Roberts C, Sullivan B, Alevras AJ, Graham PL,
Brown BT: The prevalence of adult de novo scoliosis: A systematic
review and meta-analysis. Eur Spine J 2020;29(12):2960-2969. This
systematic review article of five studies involving more than 4,000
patients assessed the prevalence of adult de novo scoliosis and
found that the pooled prevalence estimate was 37.6%, with
females more likely to experience scoliosis compared with males
and substantially increased rates in patients older than 60 years.
Level of evidence: IV.
40. Schwab FJ, Blondel B, Bess S, et al: Radiographical spinopelvic
parameters and disability in the se ing of adult spinal deformity:
A prospective multicenter analysis. Spine 2013;38(13):803-812.
41. Diebo BG, Shah NV, Boachie-Adjei O, et al: Adult spinal
deformity. Lancet 2019;394(10193):160-172. This narrative review
article outlined contemporary management strategies for adult
spinal deformity including consideration of global disparities in
treatment, surgical planning and risk stratification, and
treatment outcomes. Level of evidence: V.
42. Sciubba D, Jain A, Kebaish KM, et al: Development of a
preoperative adult spinal deformity comorbidity score that
correlates with common quality and value metrics: Length of stay,
major complications, and patient-reported outcomes. Global Spine
J 2021;11(2):146-153. This retrospective study identified 273
patients with adult spinal deformity with 2-year follow-up to
create a novel comorbidity score that incorporated major
complications, length of hospital stay, and patient-reported
outcomes. Level of evidence: III.
C H AP T E R 5 5

Thoracolumbar Minimally
Invasive Surgical Techniques
Jason M. Cuéllar MD, PhD, FAAOS, Neel Anand MD,
FAAOS

Dr. Cuéllar or an immediate family member serves as a paid consultant to or is an employee of

Axiom, Carestream, and Centinel Spine; serves as an unpaid consultant to Cytonics Corporation;
and has stock or stock options held in Cytonics Corporation. Dr. Anand or an immediate family
member has received royalties from Elsevier, Globus Medical, and Medtronic; is a member of a
speakers’ bureau or has made paid presentations on behalf of DePuy, a Johnson & Johnson
Company, and Medtronic; serves as a paid consultant to or is an employee of Medtronic, Spinal
Simplicity, and Viseon; has stock or stock options held in Atlas Spine, Globus Medical,
Medtronics, On-Point, Paradigm Spine, Spinal Balance, Spinal Simplicity, Theracell, and Viseon;
has received research or institutional support from Kuros Biosciences, National Institutes of
Health (NIAMS & NICHD), and Premia Spine; and serves as a board member, owner, officer, or
committee member of American Academy of Orthopaedic Surgeons, Educational Committee of
ISASS, Publication Committee of ISASS, Educational Committee of SMISS, Scoliosis Research
Society, and Society for Minimally Invasive Spine Surgery (SMISS).

ABSTRACT
It is important to review the history and current use of image
guidance navigation and robotic-assisted spinal surgery. As this
technology develops, it offers spine surgeons another surgical tool
to reduce intraoperative radiation while possibly improving the
accuracy of pedicle screw placement. This technology can be used
to assist in the incorporation of minimally invasive surgical
techniques for the correction of idiopathic and degenerative
scoliosis deformity correction surgery.
Keywords: deformity correction surgery; image-guidance
navigation; minimally invasive spine surgery; robotic-assisted spine
surgery; scoliosis correction

Introduction
Over the past 20 years, the field of spine surgery has changed
dramatically, mostly because of the development and adoption of
revolutionary technologies such as spine arthroplasty, direct lateral
interbody fusion via transpsoas and antepsoas approaches,
minimally invasive transforaminal interbody fusion techniques,
expandable cage technology, and computer-assisted navigation
with or without robotic assistance. The adoption of these
techniques has enabled surgeons to correct degenerative and
deformity disorders with the inclusion of fewer levels fused, less
muscle damage, and shorter recovery times with improved short-
and long-term outcomes.

Minimally Invasive Transforaminal Lumbar

Interbody Fusion
Transforaminal lumbar interbody fusion (TLIF) is a long-
established and well-accepted surgical approach to lumbar spinal
fusion. Since its inception in 1982, the TLIF procedure has evolved
greatly, 1 overcoming several limitations posed by other posterior
fusion techniques including risk of dural tears, nerve root injury,
and epidural fibrosis. 1 Still, open TLIF procedures are highly
invasive, and although fusion is achieved in most cases,
complication risk, blood loss, and muscle injury remain subjects of
concern. 2 - 5 The advent of minimally invasive spinal surgery
techniques brought about a new wave of TLIF approaches, leading
to the introduction of the minimally invasive surgery (MIS) TLIF
procedure in 2003. 6 MIS TLIF, similar to open TLIF, aims to provide
anterior column support, restoring sagi al alignment and
increasing disk space height through decompression and fusion.
Indications and Relative Contraindications
Indications for MIS TLIF match those for open TLIF. Grade I or II
spondylolisthesis (with or without radiculopathy), and mechanical
back pain caused by these presentations, are indications for the
procedure. Degenerative disk disease with diskogenic low back
pain, postlaminectomy instability, recurrent disk herniation,
lumbar spinal stenosis, spine trauma, and pseudoarthrosis may be
additional indications depending on other clinical factors. 7 , 8
Contraindications are less precise and are highly dependent on the
individual patient and the surgeon’s experience. High-grade
spondylolisthesis (>grade II), more than two-level fusion, severe
osteoporosis, and presence of conjoined roots may contraindicate
the use of MIS TLIF. 7 , 8

Advantages and Disadvantages

Traditional open TLIF can result in unnecessary damage to the
paraspinal musculature and other muscular structures during
dissection. 9 , 10 MIS TLIF emerged as a way to achieve the goals of
traditional open TLIF while avoiding damage to local musculature.
The MIS procedure is less invasive and has comparable outcomes
relative to open TLIF. According to numerous comparative studies,
MIS TLIF results in shorter length of hospital stay, fewer
complications postsurgery, and decreased blood loss. 11 - 13

Lordosis
A primary goal in fusion surgery is the achievement of acceptable
sagi al alignment. The difficulty of achieving this aim is well
documented with traditional TLIF. The restoration of lordosis is
particularly difficult with MIS TLIF given the reduced surgical
window, which decreases the ease of insertion of interbody devices.
Novel technologic developments, such as expandable interbody
cages, have emerged in recent years in an effort to improve
lordosis-associated outcomes postsurgery.
Learning Curve
A significant learning curve exists for surgeons inexperienced in
MIS. Because MIS lacks the three-dimensional spatial orientation
and tactile environment of open surgery, MIS can be especially
challenging for new surgeons. Increased familiarity with the
anatomy is necessary given the reduced visualization and narrow
surgical field of MIS. This is especially true for the MIS TLIF
procedure given the vast heterogeneity that exists between
approaches. For MIS TLIF specifically, it has been found that
surgeon experience is directly correlated with length of
postoperative stay and increased probability of fusion. 14 It is
therefore critical for new surgeons to be aware of this learning
curve.

Surgical Technique
Patients undergoing a TLIF procedure are typically positioned
prone on a Jackson table and are usually placed under general
anesthesia. Intraoperative imaging can be used to localize the
incision; at minimum, one facet should be exposed at the level of
interest. Incisions should be placed approximately 5 cm from the
patient’s midline to allow for easy placement of pedicle screws. A
tubular retractor can be inserted as the soft tissue is bluntly
dissected; this, along with intraoperative microscopy, provides
sufficient visualization. At this point, a partial or total facetectomy
is performed, as well as an ipsilateral laminotomy. When
visualization of the disk is achieved, a diskectomy can be
performed. The posterior longitudinal ligament and the anterior
longitudinal ligament are preserved. A bony fusion can be
facilitated by rasping the cartilaginous end plates of the superior
and inferior vertebrae. Bone graft and structural implants should
be inserted into the diskectomy space. Further decompression and
removal of the lamina can be performed as necessary before
closure. These steps are largely consistent among MIS TLIF
procedures; yet, there exists significant diversity in the specific
technique.

Navigation
There exist a wide variety of navigation techniques for surgeons
performing MIS TLIF. Broadly, these can be categorized into robot-
assisted and fluoroscopy-based techniques. Traditional fluoroscopy
and fluoroscopy-based instrumentation are generally preferred
given that they pose lower risk of complications and a less
significant learning curve relative to robot-assisted techniques. 15
Robotic navigation is growing in popularity as technology advances.

Expandable Versus Nonexpandable Cages

As already mentioned, achieving desired lumbar lordosis is difficult
using MIS TLIF. Lengthening the anterior column or shortening the
posterior column can help to restore lordosis. In MIS TLIF
procedures, this may be accomplished through the use of
expandable intervertebral cages. These fit within the narrow access
corridor exposed in MIS TLIF and expand in situ. When positioned
asymmetrically, these can correct coronal alignment. Despite the
increasing popularity of expandable cages, their utility in
improving lordosis is disputed—a meta-analysis of several studies
monitoring clinical and radiographic outcomes conducted in 2019
suggests that although expandable cages can result in a larger
change in segmental lordosis than standard nonexpandable cages,
they are not associated with higher fusion rate or lumbar lordosis. 16
Some direct comparison studies included in this meta-analysis,
however, associate the use of expandable cages with improved
fusion rate and lordosis correction. This contributes to the notion
that there indeed exists vast individuality in the MIS TLIF
approach. Variation in outcomes could be a ributed to the use of
expandable or nonexpandable cages or to cage placement and other
surgeon-specific parameters.
MIS Applications in Spinal Deformity
Adult spinal deformity (ASD) is a complex condition characterized
by vast heterogeneity in clinical presentation; it is estimated that
more than 60% of elderly patients are affected by ASD. Conditions
that can be defined under the category of ASD include degenerative
de novo scoliosis, adult idiopathic scoliosis, and iatrogenic
scoliosis. As a result, there are a variety of strategies for surgical
correction of ASD. It is generally characterized by a coronal Cobb
angle greater than 20°, a sagi al vertebral axis greater than 5 cm, or
a pelvic tilt greater than 20°. Primary goals of spinal deformity
surgery include neural element decompression, promotion of
sagi al and coronal balance, and achievement of an arthrodesis.
MIS has become increasingly popular in recent years as an avenue
by which these goals can be accomplished. There exist several MIS
techniques for ASD surgery; the choice of technique, as well as the
larger choice of whether to opt for MIS, is largely dependent on
patient and surgeon.

History and Usage

Over the past 2 decades, MIS has evolved rapidly. Although during
its inception MIS was mostly used for simple cases, as its
advantages become clear and techniques improve, MIS is
increasingly used in the management of complex cases. One
emerging field is MIS correction of ASD. Multiple MIS approaches
are used in ASD correction; these will be described further. Among
Scoliosis Research Society members, 43.1% of surgeons use MIS as
part of their surgical management of ASD. 17 However, 43.5% of this
cohort uses MIS in less than 20% of their cases, and only 7.2%
exclusively use MIS. 17 These discrepancies can be a ributed to the
steep learning curve associated with MIS and the perceived need
for increased comparative studies between MIS and traditional
open techniques in ASD correction to ascertain the advantages of
MIS.
Approaches
Three primary categories of MIS approaches for ASD surgery exist:
MIS decompression, circumferential MIS (cMIS), and MIS + open
(hybrid) surgery. 18 All of these techniques have demonstrated
comparable efficacy in terms of primary surgical goals relative to
traditional open techniques. 19 , 20 In addition, all have
demonstrated advantages over open techniques, including shorter
length of postoperative hospital stay, reduced complications, and
lower blood loss. 20 - 22 However, as with MIS in general, technical
difficulty poses a limitation—limited surgical access and reduced
visualization are disincentives for the use of MIS approaches in
ASD correction.

MIS Decompression
Used primarily for patients exhibiting symptoms of neural element
compression, MIS decompression approaches to ASD correction
involve decompression and sometimes single-level fusion. MIS
decompression is typically only used in mild cases of ASD; the
primary benefit of an MIS approach, as opposed to typical open
decompression, is in the decreased damage to posterior
ligamentous structures.

Circumferential MIS
cMIS aims to achieve 360° deformity correction. Often used for
patients who require multilevel fusion, cMIS uses multilevel
interbody cages and posterior instrumentation introduced through
MIS techniques. cMIS can be performed as either a one-staged or
two-staged procedure. cMIS and traditional open surgery have been
demonstrated to have comparable radiographic outcomes.

Hybrid Surgery
Hybrid surgery, as the name suggests, incorporates both MIS and
traditional open techniques. This approach benefits from the ease
of achievement of sagi al balance given by open surgery and from
the demonstrated postoperative advantages of MIS. Consequently,
hybrid approaches are typically used for cases in which other MIS
approaches may be insufficient to achieve sagi al balance
correction.

Techniques
Common techniques observed in MIS correction of ASD include
lateral lumbar interbody fusion, TLIF, anterior lumbar interbody
fusion, percutaneous segmental fixation, rod rotation and
reduction, and retractor-mediated decompression. This list is not
comprehensive because nearly all techniques can be performed
using an MIS approach. The prevalence of interbody fusion
techniques among this list can be a ributed to the ease of achieving
arthrodesis given by disk removal and interbody cage placement.
Figure 1 is an example of a difficult deformity case for which
computer-aided guidance and robotic assistance were used
together with MIS techniques for corrective surgery.
 Figure 1 A, Preoperative AP and lateral radiographs and coronal and sagittal
CT cuts from a patient with severe degeneration below an old hook and rod
construct fusion from T10 to L2, 30 years previously. B, Intraoperative
fluoroscopic images showing from left to right direct lateral interbody cages at
L2-3, L3-4, and L4-5 followed by an anterior lumbar interbody fusion (ALIF) at L5-
S1. On the far right are two images from the preoperative planning for the
posterior pedicle screw procedure. There provided a great benefit in the ability to
plan around the prior hardware. C, Preoperative planning for the Mazor X robotic
screw insertion system on the left compared with the postoperative result on the
right in the coronal plane/AP view. D, Preoperative planning for the Mazor X
robotic screw insertion system on the left compared with the postoperative
result on the right in the sagittal plane/lateral view. E, Preoperative standing AP
and lateral radiographs of scoliosis on the left compared with postoperative AP
and lateral radiographs after deformity correction using minimally invasive
surgery techniques including MIS direct lateral interbody fusion, ALIF, and
posterior robotically guided pedicle screws. The ability to use the computer-
aided planning to avoid the prior hardware and navigate this complex deformity
highlights a great benefit of this technique.

Surgical Decision Making

Because ASD presentation is so varied, patient concerns regarding
ASD are diverse, and desired outcomes are patient-dependent. As a
result, surgical decision making in the management of ASD is a
major subject of discussion. Distinguishing factors between
surgical and nonsurgical patients include quality-of-life measures,
symptom severity, and severity of malalignment. 23 Scoring systems
such as the Schwab classification and the Global Alignment and
Proportion score a empt to classify ASD and recommend
treatment based on quality-of-life measures and mechanical
complication rate, but these measures are of less use in the case of
MIS, as validation of these systems has not yet been performed on
an MIS cohort. In 2019, an updated decision-making framework for
MIS approaches to ASD correction was published. 24 The minimally
invasive spinal deformity algorithm uses preoperative predictors of
suboptimal deformity correction to assess whether patients are
candidates for low-level decompression or fusion or muscle-sparing
interbody fusion and pedicle screw fixation. A 2019 study provides
a detailed protocol for cMIS correction of ASD specifically, taking
into account clinical, functional, and radiographic parameters. 17
These frameworks can serve as useful guides to the use of MIS in
ASD correction.

Robotic Spine Surgery With Computer-

Assisted Navigation
The first spine robot for pedicle screw guidance system,
SpineAssist, was developed by Mazor Robotics Ltd. and was
approved by the FDA in 2004. The SpineAssist was replaced by the
Mazor Renaissance in 2011 and the Mazor X in 2016. Several
improvements in technique with enhanced capabilities and
problem elimination have been accomplished with each generation.
Systems have also been developed by Zimmer Biomet (ROSA
Spine, 2016) and Globus Medical (ExcelsiusGPS, 2017). Because of
the longer duration of use, the Mazor SpineAssist and Mazor
Renaissance have been the most widely studied to date. 25 , 26

Main Goals of Navigation and Robotics

Increase Precision and Accuracy

There is mounting evidence that despite the added cost of image-
guided navigation (IGN) and robotic assistance, the improved
accuracy of screw placement leads to fewer revision surgeries, thus
making it more cost effective overall compared with free-hand
screw placement. 27 , 28 There have been studies demonstrating that
robotic-assisted pedicle screw placement accuracy is as good or
be er 29 than conventional open or computer-aided navigation
techniques. Several studies have demonstrated a high rate of
accuracy, in the range of 96% to 98% for the ROSA Spine robot and
ExcelsiusGPS 30 - 32 and lower intraoperative complications than
fluoroscopy-guided free-hand insertion. 33 - 35 A meta-analysis of 750
spine patients reported no significant differences in the accuracy,
complication rate, or radiation exposure between robotic-assisted
and open free-hand pedicle screw insertion. 36 However, a
significant decrease in radiation exposure time with percutaneous
or MIS robotic-assisted surgery compared with free-hand technique
was reported.
There is evidence that the surgeon learning curve sharply drops
after 6 months and reaches a plateau at 12 months of robotic
assistance with computer-aided navigation for the placement of
lumbar pedicle screws, 37 with a large decrease in the total
fluoroscopy time after the first eight cases. 38

Reduction of Radiation Exposure to the

Patient
In one recent study, it was observed that on a per-level basis that
fluoroscopic-guided MIS leads to nearly twice as much radiation to
the patient when compared with IGN and robotic assistance, even
with the intraoperative CT. The open pedicle screw technique
demonstrated the lowest amount of intraoperative radiation use
compared with all other techniques. 39 In another recent
multicenter study comparing IGN with fluoroscopic-guided MIS
screw insertion, there was a 78% reduction in fluoroscopy time in
the robotic-assisted group using IGN. 40

Reduction of Radiation Exposure to the

Surgeon
Although IGN and robotic-assisted pedicle screw techniques may
require more radiation exposure to the patient when compared with
open and MIS fluoroscopic-guided techniques, most of the
radiation used can be avoided by the surgeon and other operating
room staff because they can leave the room during localization and
CT image capture. This has been observed in multiple studies.
When multiplied over many procedures per year during a
surgeon’s and staff member’s career, these radiation dose savings
will be substantial.

Minimize Incision Size and/or Reduced

Muscle Damage
Robotic-assisted pedicle screw insertion has been increasingly used
for percutaneous applications, enabling screw insertion with less
muscle retraction and thus reduced postoperative pain and muscle
damage. This may be most apparent when an open decompression
and posterolateral fusion is less important, such as following an
anterior lumbar interbody fusion. Some surgeons are using similar
approaches to fluoroscopic-guided MIS TLIF without the need for
fluoroscopic guidance, therefore substantially reducing surgeon
radiation exposure.

Reduce Surgical Time

Overall surgical time for one-level and two-level TLIF has been
shown to be longer or similar for CT IGN and robotic-assisted cases
when compared with open and MIS fluoroscopic-guided cases
because although screw insertion was faster with IGN and robotics,
the added time of equipment setup eliminated the time savings. 39

Surgical Planning and Intraoperative

Technique
Although the details will vary between robotic systems, surgical
planning for robotic-assisted pedicle screw insertion generally falls
into two categories. A preoperative CT scan is performed and then
uploaded into surgical planning software that can be used to plan
screw placement including trajectory, diameter, length, rod length,
and even skin incision distance from the midline. The second
technique involves intraoperative anatomic acquisition, such as
intraoperative radiography using an O-arm scan or three-
dimensional fluoroscopic image acquisition. The acquired images
are then uploaded into the robotic and navigation system for screw
placement planning.
Once the surgical plan has been performed, the IGN system
must be somehow linked to the patient in space. For the Mazor X
system, this process involves the placement of a pin into the
posterior superior iliac spine or a clamp on a spinous process. The
robotic arm is then a ached to this pin or clamp. A visualization
reference system is then placed at the foot or head of the surgical
table and is used to detect surgical instruments that have reference
frame markers on them which are detected in three-dimensional
space by the visualization system (navigation cameras). The IGN
system then knows exactly where the tip of each surgical
instrument (ie, pedicle probe, tap, screwdriver, etc) is in reference
to the patient’s bony anatomy, which is a ached to the pin and
robotic arm.
Once the surgical planning steps are complete, the spine is
exposed in either an open manner or if the MIS technique is
feasible and preferred, stab incisions can be used. The robotic arm,
which has been previously draped within the sterile field, is
brought into the surgical field and the IGN system sends the arm to
the exact location required to enable the dilation system, pedicle
screw cannulation instrument, tap, and screw to be placed through
the canula at the end of the robotic arm into the pedicle (Figure 2,
A). Figure 2, B shows the operating room setup. After all screws
have been inserted, the robotic arm is removed and rods can be
placed, either through the percutaneous towers in an MIS manner
or open standard technique.

Figure 2 A, Photograph of intraoperative use of the Mazor X robotic arm with

image-guided navigation for lumbar pedicle screw insertion. Shown is the
image-guided cannula placed through a percutaneous stab incision, at the
pedicle screw start point. B, Operating room setup with the patient placed prone
on a Jackson table with the Mazor X robotic arm mounted to the right side of the
Jackson table and the image guidance camera apparatus above the head of the
bed and the image guidance screen at the foot of the bed.

Summary
With the recent development of MIS techniques such as MIS
decompression/diskectomy, direct lateral interbody fusion, oblique
lateral interbody fusion, and MIS TLIF, spine surgeons have greatly
expanded the options by which spinal pathologies can be managed
with greatly reduced blood loss, shorter length of hospital stay, and
reduced recovery times. The recent development of computer-
assisted navigation and robotics coupled with these new techniques
further enhances precision and accuracy while reducing
occupational radiation exposure. The clinical scientific literature
that confirms improved outcomes and safety will greatly lag behind
the constant improvements being made, highlighting the
importance of ongoing continual high-quality studies.

Key Study Points

Robotic-assisted pedicle screw insertion is at least as accurate as traditional
fluoroscopic-guided technique, but with reduced radiation exposure to the surgeon
and operating room staff, and some studies have reported few intraoperative
complications with robotic assistance.
There is a steep learning curve for robotic-assisted pedicle screw placement, which
may last 6 months or 8 to 10 cases.
Fluoroscopic-guided MIS TLIF has shorter length of hospital stay and more rapid
recovery but greater surgeon radiation exposure than traditional open or robotic-
assisted.
Direct lateral interbody fusion/oblique lateral interbody fusion can be used in
conjunction with percutaneous posterior pedicle screw insertion for MIS deformity
correction (aka cMIS deformity correction) while reducing blood loss, reducing length
of hospital stay, and reducing the number of levels fused.

Annotated References
1. Harms J, Rolinger H: A one-stager procedure in operative
treatment of spondylolistheses: Dorsal traction-reposition and
anterior fusion (author’s transl). Article in German. Z Orthop Ihre
Grenzgeb 1982;120:343-347.
2. Cho K-J, Suk S-I, Park S-R, et al: Complications in posterior
fusion and instrumentation for degenerative lumbar scoliosis.
Spine (Phila Pa 1976) 2007;32:2232-2237.
3. Carreon LY, Puno RM, Dimar JR II, et al: Perioperative
complications of posterior lumbar decompression and
arthrodesis in older adults. J Bone Joint Surg Am 2003;85:2089-
2092.
4. Kawaguchi Y, Matsui H, Tsuji H: Back muscle injury after
posterior lumbar spine surgery. Part 1: histologic and
histochemical analyses in rats. Spine (Phila Pa 1976) 1994;19:2590-
2597.
 5. Kawaguchi Y, Matsui H, Tsuji H: Back muscle injury after
posterior lumbar spine surgery. Part 2: Histologic and
histochemical analyses in humans. Spine (Phila Pa 1976)
1994;19:2598-2602.
6. Foley KT, Holly LT, Schwender JD: Minimally invasive lumbar
fusion. Spine (Phila Pa 1976) 2003;28:S26-S35.
7. Pelton MA, Nandyala SV, Marquez-Lara A, et al: Minimally
invasive transforaminal lumbar interbody fusion, in Minimally
Invasive Spine Surgery. Springer, 2014, pp 151-158.
8. Chaudhary KS, Groff MW: Minimally invasive transforaminal
lumbar interbody fusion for degenerative spine. Tech Orthop
2011;26:146-155.
9. Gejo R, Matsui H, Kawaguchi Y, et al: Serial changes in trunk
muscle performance after posterior lumbar surgery. Spine (Phila
Pa 1976) 1999;24:1023-1028.
10. Rantanen J, Hurme M, Falck B, et al: The lumbar multifidus
muscle five years after surgery for a lumbar intervertebral disc
herniation. Spine (Phila Pa 1976) 1993;18:568-574.
11. Goldstein CL, Macwan K, Sundararajan K, et al: Comparative
outcomes of minimally invasive surgery for posterior lumbar
fusion: A systematic review. Clin Orthop Relat Res 2014;472:1727-
1737.
12. Khan NR, Clark AJ, Lee SL, et al: Surgical outcomes for
minimally invasive vs open transforaminal lumbar interbody
fusion: An updated systematic review and meta-analysis.
Neurosurgery 2015;77:847-874.
13. Tian N-F, Wu Y-S, Zhang X-L, et al: Minimally invasive versus
open transforaminal lumbar interbody fusion: A meta-analysis
based on the current evidence. Eur Spine J 2013;22:1741-1749.
14. Chan FJ, Stelma S, Cho W, et al: Analysis of surgeon experience
and impact of comorbidities on early discharge after mini-open
transforaminal lumbar interbody fusion. Curr Orthop Pract
2016;27:382-387.
15. Wang TY, Mehta VA, Sankey EW, et al: Operative time and
learning curve between fluoroscopy-based instrument tracking
and robot-assisted instrumentation for patients undergoing
minimally invasive transforaminal lumbar interbody fusion (MIS-
TLIF). Clin Neurol Neurosurg 2021;206:106698. In a study of 119
cases, the authors observed that compared with MIS TLIF using
fluoroscopy, robotic assistance consistently increased
intraoperative time. Conversely, instrument-tracking image
guidance saved time with a minimal learning curve. Level of
evidence: II.
16. Alvi MA, Kurian SJ, Wahood W, et al: Assessing the difference
in clinical and radiologic outcomes between expandable cage and
nonexpandable cage among patients undergoing minimally
invasive transforaminal interbody fusion: A systematic review
and meta-analysis. World Neurosurg 2019;127:596-606.e1. This is a
meta-analysis of 12 studies including 706 patients comparing
expandable with nonexpandable cages in MIS TLIF. At the last
follow-up, there was no significant difference in clinical outcome,
fusion rate, subsidence rate, or reoperation rate, although the
segmental lordosis was significantly greater for the expandable
cage group. Level of evidence: I.
17. Anand N, Agrawal A, Burger EL, et al: The prevalence of the use
of MIS techniques in the treatment of adult spinal deformity
(ASD) amongst members of the Scoliosis Research Society (SRS)
in 2016. Spine Deform 2019;7:319-324. A total of 357 Scoliosis
Research Society surgeons were surveyed about their adoption of
MIS techniques for the management of ASD. A total of 154
surgeons (43%) stated they use MIS as part of their surgical
treatment protocol. Level of evidence: IV.
18. Kanter AS, Tempel ZJ, Ozpinar A, et al: A review of minimally
invasive procedures for the treatment of adult spinal deformity.
Spine (Phila Pa 1976) 2016;41:S59-S65.
19. Uribe JS, Deukmedjian AR, Mummaneni PV, et al:
Complications in adult spinal deformity surgery: An analysis of
 minimally invasive, hybrid, and open surgical techniques.
Neurosurg Focus 2014;36:E15.
20. Wang MY, Mummaneni PV: Minimally invasive surgery for
thoracolumbar spinal deformity: Initial clinical experience with
clinical and radiographic outcomes. Neurosurg Focus 2010;28:E9.
21. Anand N, Baron EM, Khandehroo B: Is circumferential
minimally invasive surgery effective in the treatment of moderate
adult idiopathic scoliosis? Clin Orthop Relat Res 2014;472:1762-
1768.
22. Anand N, Baron EM, Khandehroo B, et al: Long-term 2-to 5-year
clinical and functional outcomes of minimally invasive surgery
for adult scoliosis. Spine (Phila Pa 1976) 2013;38:1566-1575.
23. Fujishiro T, Boissière L, Cawley DT, et al: Decision-making
factors in the treatment of adult spinal deformity. Eur Spine J
2018;27:2312-2321.
24. Mummaneni PV, Park P, Shaffrey CI, et al: The MISDEF2
algorithm: An updated algorithm for patient selection in
minimally invasive deformity surgery. J Neurosurg Spine
2019;32:221-228. The minimally invasive spinal deformity surgery
algorithm was created to provide an updated framework for
decision making in MIS techniques for ASD treatment
techniques. Level of evidence: V.
25. D’Souza M, Gendreau J, Feng A, et al: Robotic-assisted spine
surgery: History, efficacy, cost, and future trends. Robot Surg
2019;6:9-23. This is a comprehensive review article regarding
robotic-assisted spinal surgery including the development of
early designs and their progression through the advancement of
the technology. Level of evidence: V.
26. Huang M, Tetreault TA, Vaishnav A, et al: The current state of
navigation in robotic spine surgery. Ann Transl Med 2021;9:86.
This study reviews the current state of robotic spine surgery and
includes a discussion of each system currently in use. Level of
evidence: V.
27. Dea N, Fisher CG, Batke J, et al: Economic evaluation comparing
intraoperative cone beam CT-based navigation and conventional
fluoroscopy for the placement of spinal pedicle screws: A patient-
level data cost-effectiveness analysis. Spine J 2016;16:23-31.
28. D’Souza M, Macdonald NA, Gendreau JL, et al: Graft materials
and biologics for spinal interbody fusion. Biomedicines 2019;7:75.
This review provides an overview of the advantages and
disadvantages of currently available graft materials for spinal
fusion surgery. Level of evidence: V.
29. Han X, Tian W, Liu Y, et al: Safety and accuracy of robot-assisted
versus fluoroscopy-assisted pedicle screw insertion in
thoracolumbar spinal surgery: A prospective randomized
controlled trial. J Neurosurg Spine 2019;30:615-622. This is a
randomized study of 234 patients receiving 1,116 pedicle screws
in total, comparing the accuracy of robotic-assisted with
fluoroscopically inserted pedicle screws. There was a 2.1% breach
rate in the fluoroscopy-assisted group compared with zero in the
robotic-assisted group. Level of evidence: I.
30. Jain D, Manning J, Lord E, et al: Initial single-institution
experience with a novel robotic-navigation system for
thoracolumbar pedicle screw and pelvic screw placement with
643 screws. Int J Spine Surg 2019;13:459-463. This was a feasibility
study demonstrating the safety of placing pedicle screws and
pelvic bolts using the combination of robotics and an IGN
system. Level of evidence: IV.
31. Wallace DJ, Vardiman AB, Booher GA, et al: Navigated robotic
assistance improves pedicle screw accuracy in minimally invasive
surgery of the lumbosacral spine: 600 pedicle screws in a single
institution. Int J Med Robot 2020;16:e2054. This is a study of the
first 101 cases using robotic-assisted pedicle screws performed by
this group. The authors reported an accuracy rate of 98% in 630
lumbosacral pedicle screws. Level of evidence: II.
32. Elswick CM, Strong MJ, Joseph JR, et al: Robotic-assisted spinal
surgery: Current generation instrumentation and new
 applications. Neurosurg Clin N Am 2020;31:103-110. The authors
report on their experience using the ExcelsiusGPS system and
report accurate placement of pedicle screws when used in both
an open or minimally invasive manner. Level of evidence: III.
33. Kantelhardt SR, Martinez R, Baerwinkel S, et al: Perioperative
course and accuracy of screw positioning in conventional, open
robotic-guided and percutaneous robotic-guided, pedicle screw
placement. Eur Spine J 2011;20:860-868.
34. Liounakos JI, Kumar V, Jamshidi A, et al: Reduction in
complication and revision rates for robotic-guided short-segment
lumbar fusion surgery: Results of a prospective, multi-center
study. J Robot Surg 2021;15:793-802. This is a multicenter study
comparing complication and revision rates between fluoroscopic-
guided and robotic-guided pedicle screw surgery in 585 patients.
The authors reported a significant reduction in postoperative
complication rates at 90 days and 1 year in the robotic guidance
group. Level of evidence: II.
35. Good CR, Orosz L, Schroerlucke SR, et al: Complications and
revision rates in minimally invasive robotic-guided versus
fluoroscopic-guided spinal fusions: The MIS ReFRESH
prospective comparative study. Spine (Phila Pa 1976) 2021;46:1661-
1668. This is a multicenter study comparing complication and
revision rates in 485 patients undergoing lumbar fusions using
either robotic or fluoroscopic guidance. The authors report a
significant reduction in the complication (5.8 times lower) and
revision rates (11 times lower) in the robotic guidance group.
Level of evidence: II.
36. Yu L, Chen X, Margalit A, et al: Robot-assisted vs freehand
pedicle screw fixation in spine surgery – A systematic review and
a meta-analysis of comparative studies. Int J Med Robot
2018;14:e1892.
37. Hu X, Lieberman IH: What is the learning curve for robotic-
assisted pedicle screw placement in spine surgery? Clin Orthop
Relat Res 2014;472:1839-1844.
38. Kim HJ, Jung WI, Chang BS, et al: A prospective, randomized,
controlled trial of robot-assisted vs freehand pedicle screw
fixation in spine surgery. Int J Med Robot 2017;13:e1779.
39. Wang E, Manning J, Varlo a CG, et al: Radiation exposure in
posterior lumbar fusion: A comparison of CT image-guided
navigation, robotic assistance, and intraoperative fluoroscopy.
Global Spine J 2021;11:450-457. This is a retrospective study that
evaluated the amount of radiation exposure that occurred during
one-level or two-level TLIF fluoro when performed with IGN,
open without image guidance, or MIS without image guidance.
Level of evidence: II.
40. Jamshidi AM, Massel DH, Liounakos JI, et al: Fluoroscopy time
analysis of a prospective, multi-centre study comparing robotic-
and fluoroscopic-guided placement of percutaneous pedicle
screw instrumentation for short segment minimally invasive
lumbar fusion surgery. Int J Med Robot 2021;17:e2188. This is a
prospective multicenter study comparing robotic guidance with
fluoroscopic guidance for lumbar MIS fusions. The authors
report a reduction in total fluoroscopy time of 78% compared
with the fluoroscopic-guided technique. Level of evidence: II.
C H AP T E R 5 6

Spinal Column Infections

Barrett Boody MD, Cristian A. Balcescu MD

Dr. Boody or an immediate family member serves as a paid consultant to or is an employee of

Medtronic and Relievant Medsystems and has received research or institutional support from
Biom’edUp. Neither Dr. Balcescu nor any immediate family member has received anything of
value from or has stock or stock options held in a commercial company or institution related
directly or indirectly to the subject of this chapter.

ABSTRACT
Infections involving the spinal column and neural elements can
lead to serious illness or death. Chronic or untreated infections can
lead to deformity and instability as well as neurologic deficits. It is
important for the orthopaedic surgeon to understand the etiology
of various infection types, including osteomyelitis and diskitis,
spinal epidural abscesses, and postoperative spinal infections, and
be aware of prevention strategies for postoperative spinal
infections.
Keywords: diskitis; osteomyelitis; postoperative spinal infection;
spinal epidural abscess

Introduction
Spinal column infections are associated with a substantial risk of
morbidity and mortality. Gaining an understanding of the different
types of infections that can occur in the spinal column as well as
obtaining prompt diagnosis and treatment are crucial to
minimizing the risk of significant long-term consequences.
Osteomyelitis/Osteodiskitis

Epidemiology
Osteomyelitis refers to an infection of the osseous aspects of the
spinal column, whereas osteodiskitis refers to an infection of the
intervertebral disk space. Because the vascular supply of the disk
space is relatively limited with most of its blood supply originating
from the vertebral body and occurring via diffusion across the end
plate, infection of the disk space usually originates from the
vertebral body. Osteomyelitis typically involves the anterior column
and is rarely seen in the posterior column. 1 Significant morbidity
and mortality can occur if this condition is left untreated. The
incidence of osteomyelitis has been reported at 2.2 per 100,000
people per year and appears to be increasing to 5.8 per 100,000
people per year. 2
The risk factors for osteomyelitis of the spine are similar to those
found for osteomyelitis of the appendicular skeleton. Conditions
that affect the immune system such as diabetes, smoking, HIV, and
hepatitis C are among the more common risk factors associated
with osteomyelitis. Other factors include the presence of another
infection, previous spine surgery, and skin compromise. A
systematic review of 14 studies with a total of 1,008 patients who
had pyogenic vertebral osteomyelitis (PVO) was conducted. The
authors found that the median age of the patients was 59 years, and
62% of affected individuals were male. 3 Comorbidities in this study
included diabetes mellitus in 24% and intravenous drug use in 11%.
3
The lumbar spine was affected in 59% of patients followed by the
thoracic spine in 30% and cervical spine in 11% 3 (Figure 1).
 Figure 1 Magnetic resonance images from a 54-year-old man with insidious
onset of worsening thoracic back pain.After inflammatory markers were noted to
be elevated, the patient underwent total spine MRI with and without contrast
enhancement. This study demonstrates T11–12 diskitis/osteomyelitis with
ventral epidural phlegmon. The patient was successfully treated with intravenous
antibiotics and brace treatment.

Pathogenesis
Osteomyelitis and diskitis typically occur either from direct
inoculation or hematogenous spread from another site. 4
Hematogenous spread accounts for most cases as the multiple
vascular supplies to the spine provide an avenue for bacteria to
readily seed the vertebrae. 1 , 4 Direct inoculation typically requires
skin compromise, such as following spinal surgery or in the se ing
of chronic ulcers. 5 After bacteria have been introduced to the
vertebral body, they may spread through diffusion and lead to
diskitis of the adjacent disk spaces.
Staphylococcus aureus is the most common bacterial cause of
osteomyelitis/osteodiskitis. The second most common pathogen
isolated in cases of PVO is another gram-positive bacteria,
Streptococcus. Gram-negative bacteria are also a frequent cause of
spinal infections, with the most common species including
Escherichia coli and Klebsiella pneumoniae. 6 In patients with a history
of intravenous drug abuse, Pseudomonas aeruginosa also has been
described as a common bacterial cause. 7 , 8
In a 2020 study of 586 patients with PVO over a 12-year period, S
aureus was found to be the most common pathogen at 43.5%,
followed by gram-negative infection at 22.2% and Streptococcus at
20.1%. 9 A total of 64% of patients underwent echocardiography and
11.2% of these patients had infective endocarditis. Gram-negative
infections were found more commonly in older patients, females,
and those with cirrhosis or a solid tumor. S aureus was more
common in males and younger patients. MRSA was more common
in those with chronic renal disease. 9

Diagnosis
Patients with osteomyelitis/osteodiskitis most frequently present
with back pain that worsens over the course of weeks to months,
followed by fevers. 3 , 10 As the infection progresses, bony
retropulsion or abscess formation in the epidural space can occur
and lead to neurologic deficits. 3 A systematic review found that
34% of patients presented with some form of neurologic deficit,
including symptoms ranging from radiculopathy to urinary
incontinence. 3
Initial laboratory workup may show either an elevated or normal
white blood cell (WBC) count. The erythrocyte sedimentation rate
(ESR) and the C-reactive protein (CRP) levels are typically elevated
and reflect the body’s inflammatory response to the infection. On
diagnosis, blood cultures should be obtained to help identify the
offending pathogen and guide antibiotic management. 1
Radiographic changes associated with osteomyelitis/osteodiskitis
typically are seen in the vertebral body and rarely involve the
posterior elements. Changes to the architecture of the vertebral
body including sclerosis of the subchondral bone and scalloping of
the end plates may be found. 1 In acute cases, these radiographic
changes may not be observed as they take several weeks to develop.
In chronic cases, deformity and focal kyphosis caused by the bony
erosion may be present. Standing full-length radiographs can help
assess for changes in alignment. 1
These bony changes can further be assessed using noncontrast
CT, which can more clearly delineate the extent of vertebral end-
plate erosion and other bony changes. 1
MRI with and without contrast enhancement most clearly
evaluates the soft-tissue structures and should be performed in all
patients in whom osteomyelitis/osteodiskitis is suspected to
evaluate for associated epidural abscess, to evaluate local spread of
the infection, and to determine the chronicity of the infectious
process. In patients with vertebral osteomyelitis/osteodiskitis, T1-
weighted imaging will reveal a hypointense signal at the affected
end plate and disk, whereas T2-weighted imaging will show a
corresponding hyperintense signal in the vertebral body and disk. 1
Contrast-enhanced studies provide improved visualization of these
processes and more clearly delineate the affected areas where the
contrast is taken up at the site of the infection. 1

Treatment
In the absence of neurologic deficits, vertebral
osteomyelitis/osteodiskitis can be managed without surgery. This
typically consists of culture-directed intravenous antibiotics. Blood
cultures obtained before the initiation of antibiotics can help
identify the organism. CT-guided bone biopsies are often obtained,
although the efficacy of this treatment modality has been called
into question. In one study, 323 patients with possible PVO
underwent image-guided biopsies. Of the 92 patients highly
suspected to have infection before the biopsy, the biopsy was only
positive for a bacterial pathogen 30.4% of the time. 11 Intermediate
and low prebiopsy probability groups had positive biopsies in
16.1% and 5%, respectively. 11
 When a high suspicion for PVO exists despite a negative CT-
guided biopsy, the biopsy may be repeated. One study of 136
patients with suspected PVO found that 44.1% of patients had
initial biopsy results that identified the pathogen, whereas
pathology was identified in 79.6% of patients who had an additional
biopsy when biopsy findings were negative the first time. 12
Infectious disease specialists should be consulted to help guide
the antibiotic treatment course for these patients. Intravenous
antibiotics are typically continued for 6 weeks and then
transitioned to oral antibiotics if necessary. 1 Serial laboratory
evaluation (WBC count, ESR, CRP level) should be conducted
during this treatment to monitor for improvement. Intravenous
cefazolin is the most commonly used antibiotic in the se ing of
gram-positive non–methicillin-resistant S aureus (MRSA) infections,
whereas intravenous vancomycin is the treatment of choice in most
cases of MRSA osteomyelitis. 10
Brace treatment can also be implemented in the management of
vertebral osteomyelitis. 1 A lumbosacral orthosis is used in cases of
lumbar osteomyelitis, whereas a thoracolumbar orthosis or Jewe
extension is used for thoracic infections. Although there are no
long-term studies on the benefits of brace treatment, braces help
support the spinal column when it has been weakened by the
infectious process. 1
Indications for surgical management of vertebral osteomyelitis
include failure of nonsurgical treatment, development of an
associated epidural abscess with neurologic deficit, and
development of bony instability or significant kyphotic deformity.
Surgical management of osteodiskitis with a small epidural abscess
without neurologic deficit is controversial. The primary goals of
surgical management are débridement of the infection,
stabilization of the spine, and preservation of neurologic function.
Coronal or sagi al plane deformities that occur following infection
can also be corrected with surgery. 1
 When a significant portion of the vertebral body is involved
results in deformity or failure of medical management, surgical
management often consists of a subtotal or total corpectomy
depending on the amount of the vertebral body affected.
Reconstruction is subsequently performed with autograft, allograft,
or cage placement. 1 Although iliac crest autograft is preferred
when feasible, allograft or cages can be used with similar efficacy
and have been demonstrated to be safe despite local infection. The
approach used is dictated by the level affected and surgeon
preference and can include anterior, lateral, or posterior
approaches. 1 Pedicle screws are typically used to help stabilize the
affected levels. In cases where an associated epidural abscess has
formed, a laminectomy may also be performed for evacuation. 1
Even with appropriate management, there is significant
morbidity associated with PVO. In a retrospective review of 65
patients with osteomyelitis/osteodiskitis related to recent spinal
surgery, the overall 1-year mortality rate was 6%. At final follow-up,
these patients were noted to have significantly lower Oswestry
Disability Index and lower quality of life scores measured by the
EuroQol five-dimension questionnaire compared with unaffected
individuals. 13 A retrospective cohort analysis of 1,505 patients with
osteomyelitis/osteodiskitis found that these patients had a 1.47
mortality rate ratio relative to unaffected individuals. 14

Spinal Epidural Abscess

Epidemiology
Spinal epidural abscess (SEA) is an infection of the epidural space
in the spinal canal. If left untreated, this infection is associated with
high morbidity and mortality, and it can have devastating
neurologic complications due to the proximity of the infection to
the neural elements. 1 , 15 SEA is most common in males ages 50 to
70 years and rarely is seen in the pediatric population. The
incidence of SEA has been reported to range from 2 to 5 cases per
10,000 hospital admissions. 15 - 17
Risk factors for SEA include intravenous drug use, recent trauma,
and alcohol use. 18 Procedures involving direct inoculation such as
spinal epidural or facet injections also increase the risk of SEA.
Patients with medical comorbidities including diabetes and
immunocompromising conditions are also at increased risk. 18 In a
review of 128 patients with SEA, the most common risk factor was
intravenous drug use (39.1%) followed by diabetes (21.9%). 19
S aureus is the most common bacterial cause of SEA; methicillin-
susceptible S aureus is more common than MRSA. Other pathogens
that have been reported include coagulase-negative Staphylococcus
species, Streptococcus species, and gram-negative bacteria. 18 The
lumbar spine has been found to be the most frequent location for
SEA in multiple studies. One study reported that 54.7% of cases
were in the lumbar spine, with 39.1% in the thoracic spine. 19

Pathogenesis
SEA can result from either direct inoculation or hematogenous
spread. 1 In a review of all SEA cases at one tertiary care hospital
over 10 years, hematogenous spread was the most common source,
with recent surgeries/procedures being the second most common. 17
Neurologic dysfunction in the se ing of SEA can occur due to
either direct compression or secondary to spinal cord ischemia. 15
This ischemia may be caused by mass effect of the abscess on the
cord or through bacterial occlusion of the vasculature. 15 The
abscess may be located either ventrally or dorsally. Ventral SEA
most commonly occurs in the se ing of vertebral
osteomyelitis/osteodiskitis, whereas dorsal SEA more commonly
can be from a de novo process. 1

Diagnosis
The classic presentation of SEA involves four stages of increasing
disability. 16 , 20 Initially the patient experiences focal back pain,
followed by the development of radicular pain. This subsequently
evolves into motor and sensory deficits with possible bowel and
bladder incontinence. In the last stage, patients may present with
paralysis. A systematic review of 1,099 patients found that 66.8% of
patients initially presented with back pain, 52% with motor
weakness, 40% with sensory abnormalities, 27.1% with
bowel/bladder incontinence, and 43.7% with fever. 18
Initially, laboratory workup for patients with SEA includes WBC
count, ESR, CRP level, and blood cultures. One or more of these
inflammatory markers is typically significantly elevated; however,
lack of elevated inflammatory markers does not rule out SEA. This
initial laboratory workup can also help predict the success of
nonsurgical treatment. A retrospective study of 128 patients found
that diabetes mellitus, CRP level greater than 115, WBC count
greater than 12.5, and positive blood cultures predicted failure of
medical treatment. 19
Initial imaging workup for patients with suspected SEA should
include AP and lateral radiographs of the suspected area to assess
for bony changes. CT scan may also be performed to assess for this
in greater detail. 1 The imaging modality of choice is MRI with and
without contrast enhancement. T1-weighted imaging will
demonstrate a hypointense signal in the abscess, and T2-weighted
images will be hyperintense in the abscess. An abscess will
demonstrate rim enhancement with contrast enhancement 1 (Figure
2). In a 2019 retrospective review, the authors suggested that
patients with a confirmed spinal infection should undergo MRI of
the entire spine given the high rate of multifocal involvement. 20
 Figure 2 Magnetic resonance images from a 62-year-old man with methicillin-
susceptible Staphylococcus aureus bacteremia treated with intravenous
antibiotics.The patient began experiencing significant axial low back pain
associated with lower extremity radiculopathy. He underwent laminectomy of L3
to L5 and evacuation of epidural collection and had significant clinical
improvement.

Treatment
Treatment of patients with SEA has typically been surgical given
the concern over neurologic deterioration with nonsurgical care.
However, nonsurgical management is becoming more commonly
used as the first-line treatment of patients with SEA in the absence
of neurologic deficits. 1 Nonsurgical treatment includes culture-
directed intravenous antibiotics for at least 6 weeks with careful
monitoring for neurologic deterioration and serial inflammatory
markers. 1
Surgical management involves laminectomy to provide the thecal
sac with more space as well as evacuation of the abscess and other
infectious material. Benefits of surgery include removal of the
inflammatory cascade around the thecal sac and decreased mass
effect. 1
Mixed outcomes have been reported for nonsurgical
management of patients with SEA. In a systematic review, 1,099
patients with SEA were assessed, with 59.7% initially undergoing
surgery and 40.3% receiving nonsurgical care. 18 No difference was
found in outcomes between the two groups. In a separate study,
128 patients with SEA were evaluated. Fifty-one of these patients
were initially treated with IV antibiotics, although 41% of these
patients eventually underwent surgery. Patients who underwent
intravenous antibiotics with immediate surgery demonstrated the
most improvement in their motor function as measured by the
American Spinal Cord Injury Association score. 19
Surgical indications for SEA include neurologic deterioration,
systemic illness in the se ing of positive blood cultures despite
antibiotic therapy, substantial and ongoing pain despite medical
management, and progressive deformity at the involved level in the
se ing of associated osteodiskitis. 1 , 21 Surgical treatment consists
of a laminectomy with irrigation and débridement of the abscess.
Fusion may also be performed if instability is present; however, in a
retrospective study of 738 patients with SEA, patients who
underwent laminectomy and fusion have a significantly higher rate
of return to the operating room for recurrent infections and higher
rates of blood transfusions. 22

Postoperative Spinal Infections

Postoperative spinal infections can have devastating consequences,
and prevention of infection is critical to good patient outcomes.
However, determining infection prevention guidelines is
challenging given the paucity of high-quality evidence.

Prevention Strategies
In an investigation of best practice guidelines for infection
prevention in pediatric patients undergoing spine surgery, the
authors found greater than 90% consensus among pediatric spine
surgeons for 13 separate prevention strategies. 23 These strategies
included chlorhexidine skin washes the night before surgery,
preoperative urine cultures/treatment if positive, preoperative
patient education sheets, nutritional assessment, perioperative
cefazolin, perioperative intravenous prophylaxis for gram-negative
bacilli, limited operating room access, clipping instead of shaving
hair, intrawound vancomycin powder, impervious dressings
postoperatively, and minimization of dressing changes before
discharge. However, these recommendations were largely based on
expert opinion.
Patient selection and preoperative medical optimization are also
critical to minimizing postoperative infection. The incidence of
surgical site infection after adult spinal deformity surgery was
analyzed. Patient factors found to be associated with increased risk
of infection include prior history of surgical site infection, obesity,
diabetes, smoking, revision surgery, age, urinary incontinence,
tumor resection, and the presence of three or more comorbidities. 24
Increased risk of postoperative infection in patients with diabetes is
specifically related to the medical management of diabetes as
indicated by hemoglobin A1c level. The risk of infection was found
to increase proportionally to hemoglobin A1c level. 25 Although
there is debate regarding the exact cutoff for hemoglobin A1c
before elective spine surgery, studies have demonstrated that
hemoglobin A1c levels higher than 7.5% significantly increase the
patient’s risk for postoperative infections. Prior surgical site
infection has been reported to have an increased odds ratio for
postoperative infection of 3.2. 24 Posterior surgical approaches to
the lumbar spine have also been found to increase postoperative
infection risk compared with anterior lumbar surgery, with an odds
ratio for infection of 0.32.
Preoperative aseptic showers have previously been suggested to
eradicate colonization of the skin flora before surgery. However, a
Cochrane review including seven studies demonstrated that there
is no consistent effect or proven effectiveness for this practice. 26
Different skin preparation solutions have additionally been studied
through randomized controlled trials, and although they may
decrease the rate of positive cultures after skin preparation, a
decrease in the risk of postoperative infections has not been shown.
Screening for methicillin-susceptible S aureus/MRSA
preoperatively has been found to be an effective strategy for
decreasing postoperative infections in adult spine surgery. A 2020
meta-analysis demonstrated that there is an increased risk of
postoperative infection in positive carriers and that eradication in
carriers lowers the infection risk. The authors concluded that
preoperative screening and eradication are recommended. 27
Contamination in the operating room can also contribute to
postoperative infection risk. Multiple studies have been performed
investigating the sources of contamination. In one study, the
contamination rate from the microscope was assessed, and it was
noted that the eyepiece was contaminated 24% of the time and that
there was a 44% contamination rate of the microscope drape from
overhead structures. 28 , 29 Another group looked at C-arm
contamination and found that the top portion of the C-arm was
contaminated 56% of the time and that the upper front portion of
the C-arm was contaminated 28% of the time. 30 One study
demonstrated an 89% contamination rate from scrubs worn post
call and a 41% contamination rate from unworn scrubs. 31
Intraoperative factors for postoperative infection include surgical
time, estimated blood loss, and intravenous and intrawound
antibiotics. In one study, the odds ratio for deep postoperative
wound infection in patients with surgical times of 2 to 5 hours was
2.4 compared with those whose surgery lasted less than 2 hours.
The odds ratio for infection in patients whose surgical time was
greater than 5 hours compared with those whose surgical time was
less than 2 hours was 2.85. 24 An estimated blood loss of greater
than 1 L is an independent risk factor for postoperative wound
infection with an odds ratio of 2.2. Wound irrigation with dilute
betadine solution has been investigated in a randomized controlled
trial and found to decrease surgical site infections. 32 The use of
closed suction drains has not been found to affect the risk of
infection. 33 One randomized controlled trial did find that the use of
antibiotic sutures decreases the rate of surgical site infections. 34
Perioperative antibiotics should be administered within 60
minutes of incision and redosed throughout the surgery. The
preferred agents are typically cephalosporins unless a severe
allergy exists. The most commonly used antibiotic is cefazolin,
which must be redosed every 4 hours intraoperatively or after 1.5 L
of blood loss, so communication with anesthesia is critical. In the
se ing of severe cephalosporin allergy, vancomycin or clindamycin
may be used instead. The routine use of vancomycin perioperatively
for MRSA prophylaxis and gentamicin for gram-negative
prophylaxis remains controversial.
Intrawound vancomycin powder is commonly used to help
prevent postoperative infection, and multiple studies have
investigated its efficacy. One study analyzed patients undergoing
instrumented fusions and demonstrated a deep infection rate of
2.6% in the control group versus 0.2% in a vancomycin powder
group. 35 Another group looked at 1,001 patients undergoing
posterior cervical fusion who were separated into a control group
and a group that received intrawound vancomycin powder, a
superficial drain, and an alcohol foam prep. The control group was
found to have a 1.86% infection rate, whereas there were no
reported infections in the treatment group despite having a
significantly higher age and a greater percentage of more than four-
level surgeries. 36 Multiple other studies have been performed
supporting the use of intrawound vancomycin powder. An animal
study in rabbits found that the use of prophylactic cefazolin alone
led to persistent S aureus contamination compared with the
intrawound vancomycin powder group. 37 - 39 A separate study
demonstrated a clear decrease in infection with intrawound
vancomycin in adult spinal deformity surgery. 39 This study also
determined that the use of vancomycin powder would result in
$244,000 cost savings per 100 thoracolumbar deformity corrections
performed. 39
 However, a randomized controlled trial compared systemic
prophylaxis alone with the addition of intrawound vancomycin and
found that the infection rate was lower but not significant, leading
the authors to conclude that intrawound vancomycin may not be
effective when infection rates are low. 40
Intrawound tobramycin has more recently been investigated as a
method for preventing gram-negative infections. This is of
particular concern in patients with pediatric neuromuscular
scoliosis because they have a high rate of gram-negative infection.
The literature supporting intrawound tobramycin is largely from
the orthopaedic trauma literature. One group retrospectively
reviewed 1,085 patients with open fractures treated with either
intravenous antibiotics alone or in combination with intrawound
tobramycin. The treatment groups had an infection rate of 3.7%
compared with the control group of 12%. 41 In an animal study,
intrawound tobramycin eliminated E coli surgical site
contamination in all subjects, while 39 out of the 40 control rabbits
continued to have bacterial growth. 42
Negative-pressure wound therapy (NPWT) over a closed surgical
wound as a prevention measure is becoming an area of interest
clinically and in the literature. A 2020 study outlining a single
surgeon’s experience with using NPWT after instrumented spinal
fusion surgery examined the use of NPWT in both anterior wounds
after anterior instrumented interbody fusions as well as its use
after posterior instrument fusions. Of note, posterior fusions
received NPWT only if they were deemed high risk by the surgeon
and all anterior wounds received NPWT after a specific time point.
The authors concluded that NPWT reduced postoperative wound
complications after anterior lumbar fusions and when used
preferentially in posterior spine fusions for neoplastic, infectious
etiologies, after long fusions (>7 levels), intraoperative durotomies,
and those undergoing revision surgeries. 43
A 2021 prospective, nonrandomized trial investigated the use of
prophylactic NPWT in open posterior instrumented spinal fusion
as well as decompression-alone procedures. The authors found that
there was a nonstatistically significant reduction in infections after
decompression-alone procedures (4.2% versus 9.1%) and a
statistically significant decrease in infections after instrumented
cases, from 11.4% to 3.2%. A statistically significant decrease in
infections was noted in patients with body mass index >30 kg/m2 as
well as those ages 40 to 64 years. 44

Epidemiology
Postoperative spine infections are an important and costly
complication of spine surgery and increase the risk of chronic pain,
pseudarthrosis, and adverse neurologic sequelae. 45 Rates of
postoperative spine infection range from 0.6% to 18% depending on
several patient-related risk factors including obesity, smoking,
malnutrition, and immunosuppression. 46 - 50 Procedure-related risk
factors potentially include the duration of surgery, number of
people in the operating room, increased blood loss, and wound
drains. 47 , 48 In addition, instrumented fusion is associated with a
higher incidence of postoperative infection compared with
decompression alone. 49 Higher rates of infection have been
reported after posterior cervical surgery as well. 45 In one
retrospective study from 2021 that analyzed 15,000 patients
undergoing both decompression alone and fusion, it was found that
preoperative epidural steroid injections may increase the risk of
infection after lumbar fusion, but not when undergoing
decompression alone, especially if performed within 30 days of
surgery. 51
A 2021 study aimed to characterize the organisms involved in
postoperative spinal infections within 90 days of instrumented
fusion. 52 This group retrospectively analyzed all spinal fusion cases
in an 8.5-year period at their institution and found that out of 6,727
cases, there was a 5.2% incidence of infection. A total of 55.2% were
monomicrobial and 43.5% were polymicrobial, with 1.3% being
culture negative. In monomicrobial infections, 79.4% were caused
by cutaneous flora such as gram-positive Enterococcus, and 20.6%
were caused by enteric and gram-negative organisms. Gram-
negative infections were more likely to be polymicrobial and have
an earlier presentation. They observed an anatomic gradient to the
infections with gram-positive skin organisms in the cervical spine
transitioning to gram-negative enteric organisms in the
lumbosacral spine. 52

Diagnosis
The presentation of postoperative spine infection is variable but
commonly includes pain and tenderness to palpation near the
incision site. Wound drainage, swelling, and erythema may be
present. Deep wound infections may present up to 90 days
postoperatively. 42 Wound dehiscence and purulent drainage are
obvious signs of infection, but it is not uncommon for infected
wounds to appear relatively benign. 41 Tight fascial closures may
allow deeper infections to develop without any obvious superficial
manifestations. Fever and other signs and symptoms of sepsis are
less common but can occur with highly virulent organisms such as
MRSA. 46 Fatigue or malaise may be present in patients with
chronic infections.
In the absence of infection, ESR and CRP levels are elevated after
surgery and normalize within 3 months and 2 to 3 weeks,
respectively. 53 CRP level peaks at 2 to 3 days postoperatively and
normalizes in a faster and more predictable pa ern. 53
Postoperative infection should be considered if CRP does not
decline or if a second peak is observed. Although standard workup
includes a complete blood count, leukocytosis is present in fewer
than 50% of cases. 45 , 46 Similarly, blood cultures should be drawn
before initiating antibiotics but are often negative in patients with
postoperative infections. Superficial wound cultures are generally
not indicated because of a high likelihood of contamination.
Intraoperative cultures are considered the gold standard for
confirming the presence of infection and isolating the causative
pathogen. 45
Plain radiographs are often normal in postoperative infections
but are useful for ruling out alternative causes of a patient’s clinical
presentation, including hardware failure. Radiographs may show
radiolucencies around screws in latent infections. 51 In addition,
end plate erosion and loss of disk height can be observed in
patients with diskitis. CT and MRI may be useful for identifying
atypical fluid collections but often yield relatively nonspecific
results in the acute postoperative period that are difficult to
distinguish from normal postoperative changes and noninfectious
soft-tissue edema. 54

Treatment
Patients with postoperative spine infections are treated with
surgical irrigation and débridement, and long-term intravenous
antibiotics. Patients who present with a changing neurologic
examination or signs and symptoms of sepsis should be
immediately taken to the operating room for irrigation and
débridement, and surgical decompression. Tissue cultures are
obtained intraoperatively, and the wound is explored to determine
whether the infection is superficial or deep. Thorough débridement
of infected and necrotic tissue should be performed, and several
irrigation and débridement procedures are at times necessary. One
study of surgical site infections reported an average of four
irrigation and débridement procedures (range, 1 to 16) costing a
total of $250,000–$1,000,000 per patient. 55 Antibiotic-impregnated
beads can be used, especially when local soft-tissue vascularity and
perfusion have been compromised by multiple rounds of
débridement, thereby decreasing the delivery of intravenous
antibiotics to the infection site. 56 Primary closure over suction
drains can be performed if the underlying tissue and surgical site
appear healthy after débridement. Packing or vacuum-assisted
closure with repeat débridement in 2 to 5 days can otherwise be
implemented. 57
Long-term intravenous antibiotic therapy is critical in the
management of postoperative infection. Although there is no clear
consensus regarding antibiotic duration, cases of deep infection are
often treated with at least 4 to 6 weeks of intravenous antibiotics
when hardware is present. 45 A shorter course is sometimes chosen
in patients without hardware. Antibiotic choice and duration
should be tailored to culture results and inflammatory marker
response. Some authors have also advocated for the addition of
suppressive antibiotic therapy with oral sulfamethoxazole-
trimethoprim or doxycycline. 58
In cases of early postoperative infection (less than 3 months after
surgery), instrumentation is often retained to avoid destabilizing
the spine. 59 For late-onset infections, there is some controversy in
the literature on whether hardware retention or removal is
indicated. 58 Hardware removal has often been favored because
indolent organisms such as coagulase-negative staphylococci or
Cutibacterium acnes are likely to form biofilm. 55 Studies have found
that repeated irrigation and débridement could not eradicate
postoperative infection when implants were retained, and therefore
removal was eventually necessary in most patients. 60 - 62 However,
other authors have reported successful eradication of infection with
aggressive surgical débridement, microbial-guided antibiotic
therapy, and implant preservation. 63 In a retrospective case series
of MRSA surgical site infections, seven patients were treated with
surgical débridement, implant retention, and antibiotics without
the need for implant removal. 64 Implant removal or replacement
should be strongly considered if long-term antibiotics and surgical
débridement fail to eradicate late-onset deep surgical site
infections.

Summary
It is important for the orthopaedic surgeon to review the
epidemiology and diagnosis of spinal column infections including
osteomyelitis, diskitis, SEA, and postoperative spinal infection,
along with strategies for prevention of postoperative spinal
infections. MRI with and without contrast enhancement is the
study of choice to evaluate for spinal column infection. S aureus is
the most common pathogen encountered in spinal column
infections. The mainstay of treatment is typically surgical irrigation
and débridement along with antibiotics when neurologic deficits
are present. Nonsurgical management with intravenous antibiotics
and bracing treatment can be considered. Postoperative infections
can be managed with surgical irrigation and débridement or
antibiotics with/without hardware removal or replacement.

Key Study Points

MRI with and without gadolinium contrast material is the best imaging study for
assessment of intraspinal infections.
S aureus is the most common pathogen causing osteomyelitis/osteodiskitis and
SEA.
Nonsurgical management, including intravenous antibiotics and bracing treatment,
can be considered for neurologically intact patients with osteomyelitis/osteodiskitis.
Patients with neurologic deficits require surgical treatment as well as intravenous
antibiotics.
Intrawound vancomycin powder has been demonstrated to decrease the rate of
postoperative infections in elective spine surgery.
Patients with postoperative spine infections are typically treated with surgical
irrigation and débridement and long-term antibiotics, with or without hardware
exchange/removal.

Annotated References
1. Rothman RH, Simeone FA, Garfin SR: Rothman-Simeone and
Herkowi ’s the Spine. Elsevier, 2018.
2. Kehrer M, Pedersen C, Jensen TG, Lassen AT: Increasing
incidence of pyogenic spondylodiscitis: A 14-year population-
based study. J Infect 2014;68(4):313-320.
 3. Mylona E, Samarkos M, Kakalou E, Fanourgiakis P, Skoutelis A:
Pyogenic vertebral osteomyelitis: A systematic review of clinical
characteristics. Semin Arthritis Rheum 2009;39(1):10.
4. Sans N, Faruch M, Lapegue F, Ponsot A, Chiavassa H, Railhac JJ:
Infections of the spinal column–spondylodiscitis. Diagn Interv
Imaging 2012;93(6):520.
5. Larson DL, Gilstrap J, Simonelic K, Carrera GF: Is there a
simple, definitive, and cost-effective way to diagnose osteo-
myelitis in the pressure ulcer patient? Plast Reconstr Surg
2011;127(2):670.
6. Graham SM, Fishlock A, Millner P, Sandoe J: The management
gram-negative bacterial haematogenous vertebral osteomyelitis:
A case series of diagnosis, treatment and therapeutic outcomes.
Eur Spine J 2013;22(8):1845.
7. Wiesseman GJ, Wood VE, Kroll LL, Linda L: Pseudomonas
vertebral osteomyelitis in heroin addicts. Report of five cases. J
Bone Joint Surg Am 1973;55(7):1416.
8. Bryan V, Franks L, Torres H: Pseudomonas aeruginosa cervical
diskitis with chondro-osteomyelitis in an intravenous drug
abuser. Surg Neurol 1973;1(3):142.
9. Kim DY, Kim UJ, Yu Y, et al: Microbial etiology of pyogenic
vertebral osteomyelitis according to patient characteristics. Open
Forum Infect Dis 2020;7(6):ofaa176. This is a retrospective review
of all patients at one institution with culture-confirmed PVO over
a 12-year period analyzing patient characteristics as well as
microbiological etiology of the infections. They found that S
aureus was more common in younger patients, and gram-negative
infections were more common in females, older patients, and
those affected by cirrhosis or a tumor. MRSA was more common
in those with chronic renal disease. Level of evidence: IV.
10. Nickerson EK, Sinha R: Vertebral osteomyelitis in adults: An
update. Br Med Bull 2016;117(1):121.
11. Sehn JK, Gilula LA: Percutaneous needle biopsy in diagnosis
and identification of causative organisms in cases of suspected
 vertebral osteomyelitis. Eur J Radiol 2012;81(5):940.
12. Gras G, Buzele R, Parienti JJ, et al: Microbiological diagnosis of
vertebral osteomyelitis: Relevance of second percutaneous biopsy
following initial negative biopsy and limited yield of post-biopsy
blood cultures. Eur J Clin Microbiol Infect Dis 2014;33(3):371.
13. Dragsted C, Aagaard T, Ohrt-Nissen S, Gehrchen M, Dahl B:
Mortality and health-related quality of life in patients surgically
treated for spondylodiscitis. J Orthop Surg
2017;25(2):2309499017716068.
14. Aagaard T, Roed C, Dahl B, Obel N: Long-term prognosis and
causes of death after spondylodiscitis: A Danish nationwide
cohort study. Infect Dis (Lond) 2016;48(3):201.
15. Darouiche RO: Spinal epidural abscess. N Engl J Med
2006;355(19):2012.
16. Johnson KG: Spinal epidural abscess. Crit Care Nurs Clin North
Am 2013;25(3):389.
17. Vakili M, Crum-Cianflone NF: Spinal epidural abscess: A series
of 101 cases. Am J Med 2017;130(12):1458.
18. Arko L, Quach E, Nguyen V, Chang D, Sukul V, Kim BS: Medical
and surgical management of spinal epidural abscess: A
systematic review. Neurosurg Focus 2014;37(2):E4.
19. Patel AR, Alton TB, Bransford RJ, Lee MJ, Bellabarba CB,
Chapman JR: Spinal epidural abscesses: Risk factors, medical
versus surgical management, a retrospective review of 128 cases.
Spine J 2014;14(2):326.
20. Balcescu C, Odeh K, Rosinski A, et al: High prevalence of
multifocal spine infections involving the cervical and thoracic
regions: A case for imaging the entire spine. Neurospine
2019;16(4):756-763. A retrospective review of all surgically treated
nontuberculous spinal infections at one tertiary referral center is
presented. The authors found that patients with a cervical or
thoracic spinal infection had a high rate of multifocal spinal
infections. It was suggested that in patients with spinal infections
requiring surgical intervention, whole-spine MRI should be
 performed before surgery to evaluate for multifocal involvement.
Level of evidence: IV.
21. Shah AA, Ogink PT, Nelson SB, Harris MB, Schwab JH:
Nonoperative management of spinal epidural abscess:
Development of a predictive algorithm for failure. J Bone Joint
Surg Am 2018;100(7):546.
22. Chaker AN, Bhimani AD, Esfahani DR, et al: Epidural abscess:
A propensity analysis of surgical treatment strategies. Spine
(Phila Pa 1976) 2018;43(24):E1479-E1485.
23. Vitale MG, Riedel MD, Glo becker MP, et al: Building
consensus: Development of a best practice guideline (BPG) for
surgical site infection (SSI) prevention in high-risk pediatric
spine surgery. J Pediatr Orthop 2013;33(5):471.
24. Pullter Gunne AF, van Laarhoven CJ, Cohen DB: Incidence of
surgical site infection following adult spinal deformity surgery:
An analysis of patient risk. Eur Spine J 2010;19(6):982.
25. Cancienne JM, Werner BC, Chen DQ, Hassanzadeh H, Shimer
AL: Perioperative hemoglobin A1c as a predictor of deep
infection following single-level lumbar decompression in
patients with diabetes. Spine J 2017;17(8):1100.
26. Webster J, Osborne S: Preoperative bathing or showering with
skin antiseptics to prevent surgical site infection. Cochrane
Database Syst Rev 2015;(2):CD004985.
27. Ning J, Wang J, Zhang S, Sha X: Nasal colonization of
Staphylococcus aureus and the risk of surgical site infection after
spine surgery: A meta-analysis. Spine J 2020;20(3):448-456. The
authors present a systematic review and meta-analysis
investigating an association between nasal colonization of
MRSA/methicillin-susceptible S aureus and surgical site infection
after spinal surgery. They found that nasal MRSA colonization is
associated with increased risk of surgical site infection and that
decolonization may be associated with a decrease in surgical site
infection. Level of evidence: III.
28. Bible JE, Biswas D, Whang PG, Simpson AK, Grauer JN: Which
regions of the operating gown should be considered most sterile?
Clin Orthop Relat Res 2009;467 (3):825.
29. Bible JE, O’Neill KR, Crosby CG, Schoenecker JG, McGirt MJ,
Devin CJ: Microscope sterility during spine surgery. Spine (Phila
Pa 1976) 2012;37(7):623.
30. Biswas D, Bible JE, Whang PG, Simpson AK, Grauer JN: Sterility
of C-arm fluoroscopy during spinal surgery. Spine (Phila Pa 1976)
2008;33(17):1913.
31. Krueger CA, Murray CK, Mende K, Guymon CH, Gerlinger TL:
The bacterial contamination of surgical scrubs. Am J Orthop (Belle
Mead NJ) 2012;41(5):E69.
32. Cheng MT, Chang MC, Wang ST, Yu WK, Liu CL, Chen TH:
Efficacy of dilute betadine solution irrigation in the prevention of
postoperative infection of spinal surgery. Spine (Phila Pa 1976)
2005;30(15):1689.
33. Parker MJ, Livingstone V, Clifton R, McKee A: Closed suction
surgical wound drainage after orthopaedic surgery. Cochrane
Database Syst Rev 2007;(3):CD001825.
34. Rozzelle CJ, Leonardo J, Li V: Antimicrobial suture wound
closure for cerebrospinal fluid shunt surgery: A prospective,
double-blinded, randomized controlled trial. J Neurosurg Pediatr
2008;2(2):111.
35. Sweet FA, Roh M, Sliva C: Intrawound application of
vancomycin for prophylaxis in instrumented thoracolumbar
fusions: Efficacy, drug levels, and patient outcomes. Spine (Phila
Pa 1976) 2011;36(24):2084.
36. Pahys JM, Pahys JR, Cho SK, et al: Methods to decrease
postoperative infections following posterior cervical spine
surgery. J Bone Joint Surg Am 2013;95(6):549.
37. Zebala LP, Chuntarapas T, Kelly MP, Talco M, Greco S, Riew
KD: Intrawound vancomycin powder eradicates surgical wound
contamination: An in vivo rabbit study. J Bone Joint Surg Am
2014;96(1):46.
38. Rahman RKK, Lenke LG, Bridwell KH, et al: Intrawound
vancomycin powder lowers the acute deep wound infection rate
in adult spinal deformity patients: PAPER #36. Spine (Phila Pa
1976) 2011;73.
39. Theologis AA, Demirkiran G, Callahan M, Pekmezci M, Ames C,
Deviren V: Local intrawound vancomycin powder decreases the
risk of surgical site infections in complex adult deformity
reconstruction: A cost analysis. Spine (Phila Pa 1976)
2014;39(22):1875.
40. Tubaki VR, Rajasekaran S, She y AP: Effects of using
intravenous antibiotic only versus local intrawound vancomycin
antibiotic powder application in addition to intravenous
antibiotics on postoperative infection in spine surgery in 907
patients. Spine (Phila Pa 1976) 2013;38(25):2149.
41. Ostermann PA, Seligson D, Henry SL: Local antibiotic therapy
for severe open fractures. A review of 1085 consecutive cases. J
Bone Joint Surg Br 1995;77(1):93.
42. Lara a JL, Shillingford JN, Hardy N, et al: Intrawound
tobramycin powder eradicates surgical wound contamination: An
in vivo rabbit study. Spine (Phila Pa 1976) 2017;42(24):E1393.
43. Naylor RM, Gilder HE, Gupta N, et al: Effects of negative
pressure wound therapy on wound dehiscence and surgical site
infection following instrumented spinal fusion surgery-a single
surgeon’s experience. World Neurosurgery 2020;137:e257-e262.
This single-surgeon retrospective review concluded that
prophylactic NPWT use after anterior lumbar interbody fusion
and in high-risk patients undergoing posterior instrumented
fusion led to a decrease in wound complications. Level of
evidence: IV.
44. Mueller KB, D’Antuono M, Patel N, et al: Effect of incisional
negative pressure wound therapy vs standard wound dressing on
the development of surgical site infection after spinal surgery: A
prospective observational study. Neurosurgery 2021;88(5):E445-
E451. This prospective, nonrandomized trial showed that the use
 of prophylactic NPWT significantly reduced infections after
posterior instrumented spinal fusion. There was a reduction in
infections after decompression-alone procedures; however, this
was not statistically significant. Level of evidence: II.
45. Dowdell J, Brochin R, Kim J, et al: Postoperative spine infection:
Diagnosis and management. Global Spine J 2018;8(4 suppl):37S-
43S.
46. Weinstein MA, McCabe JP, Cammisa FPJr: Postoperative spinal
wound infection: A review of 2,391 consecutive index procedures.
J Spinal Disord 2000;13(5):422-426.
47. Pullter Gunne AF, Cohen DB: Incidence, prevalence, and
analysis of risk factors for surgical site infection following adult
spinal surgery. Spine (Phila Pa 1976) 2009;34(13):1422-1428.
48. Fang A, Hu SS, Endres N, Bradford DS: Risk factors for infection
after spinal surgery. Spine (Phila Pa 1976) 2005;30(12):1460-1465.
49. Veeravagu A, Patil CG, Lad SP, Boakye M: Risk factors for
postoperative spinal wound infections after spinal
decompression and fusion surgeries. Spine (Phila Pa 1976)
2009;34(17):1869-1872.
50. Smith JS, Shaffrey CI, Sansur CA, et al: Rates of infection after
spine surgery based on 108,419 procedures: A report from the
Scoliosis Research Society morbidity and mortality commi ee.
Spine (Phila Pa 1976) 2011;36(7):556-563.
51. Krei TM, Mangan J, Schroeder GD, et al: Do preoperative
epidural steroid injections increase the risk of infection after
lumbar spine surgery? Spine (Phila Pa 1976) 2021;46(3):197-202. A
retrospective study of 5,108 fusion and 9,903 decompression-only
patients was performed. No association was found between
infection and preoperative epidural steroid infections at any time
for decompression alone. There was an increased risk of infection
with preoperative epidural steroid injections and fusion and
epidural steroid injections within 30 days when compared with
more than 90 days before surgery. Level of evidence: III.
52. Long DR, Bryson-Cahn C, Pergamit R, et al: 2021 Young
Investigator Award winner: Anatomic gradients in the
microbiology of spinal fusion surgical site infection and
resistance to surgical antimicrobial prophylaxis. Spine (Phila Pa
1976) 2021;46(3):143-151. This retrospective review of surgical site
infection occurring within 90 days postoperatively at a single
facility found that there was a gradient to infection type from
gram-positive cutaneous-type flora predominance in the cervical
spine to gram-negative/anaerobic enteric-type flora in the
lumbosacral region. More than half (57.5%) of the organisms
detected in infections were resistant to the prophylactic antibiotic
given at the time of surgery. Level of evidence: III.
53. Mok JM, Pekmezci M, Piper SL, et al: Use of C-reactive protein
after spinal surgery: Comparison with erythrocyte sedimentation
rate as predictor of early postoperative infectious complications.
Spine (Phila Pa 1976) 2008;33(4):415-421.
54. Herrera IH, de la Presa RM, Gutierrez RG, Ruiz EB, Benassi
JMG: Evaluation of the postoperative lumbar spine. Radiologia
2013;55(1):12-23.
55. Hedequist D, Haugen A, Hresko T, Emans J: Failure of
a empted implant retention in spinal deformity delayed surgical
site infections. Spine (Phila Pa 1976) 2009;34(1):60-64.
56. Lall RR, Wong AP, Lall RR, Lawton CD, Smith ZA, Dahdaleh
NS: Evidence-based management of deep wound infection after
spinal instrumentation. J Clin Neurosci 2015;22(2):238-242.
57. Canavese F, Gupta S, Krajbich JI, Emara KM: Vacuum-assisted
closure for deep infection after spinal instrumentation for
scoliosis. J Bone Joint Surg Br 2008;90(3):377-381.
58. Kowalski TJ, Berbari EF, Huddleston PM, Steckelberg JM,
Mandrekar JN, Osmon DR: The management and outcome of
spinal implant infections: Contemporary retrospective cohort
study. Clin Infect Dis 2007;44(7):913-920.
59. Nunez-Pereira S, Pellise F, Rodriguez-Pardo D, et al: Implant
survival after deep infection of an instrumented spinal fusion.
 Bone Joint J 2013;95-B(8):1121-1126.
60. Agarwal A, Kelkar A, Agarwal AG, et al: Implant retention or
removal for management of surgical site infection after spinal
surgery. Global Spine J 2020;10(5):640-646. In a literature review of
49 articles, it was concluded that long-term antibiotics and
irrigation and débridement were common methods used to
address postoperative infection. Most authors implied or
suggested removal/replacement of implants for late surgical site
infections. Level of evidence: III.
61. Di Silvestre M, Bakaloudis G, Lolli F, Giacomini S: Late-
developing infection following posterior fusion for adolescent
idiopathic scoliosis. Eur Spine J 2011;20(suppl 1):S121-S127.
62. Ha KY, Kim YH: Postoperative spondylitis after posterior
lumbar interbody fusion using cages. Eur Spine J 2004;13(5):419-
424.
63. Ahmed R, Greenlee JD, Traynelis VC: Preservation of spinal
instrumentation after development of postoperative bacterial
infections in patients undergoing spinal arthrodesis. J Spinal
Disord Tech 2012;25(6):299-302.
64. Takizawa T, Tsutsumimoto T, Yui M, Misawa H: Surgical site
infections caused by methicillin-resistant Staphylococcus
epidermidis after spinal instrumentation surgery. Spine (Phila Pa
1976) 2017;42(7):525-530.
C H AP T E R 5 7

Current Concepts in Primary

Benign, Primary Malignant, and
Metastatic Tumors of the Spine
Gideon Blumstein MD, MS, Matthew W. Colman MD,
FAAOS, FAOA

Dr. Colman or an immediate family member has received royalties from Alphatec Spine and Spinal
Elements; is a member of a speakers’ bureau or has made paid presentations on behalf of DePuy,
a Johnson & Johnson Company, K2M, and Orthofix, Inc.; serves as a paid consultant to or is an
employee of Alphatec Spine, K2M/Stryker Spine, Orthofix, Spinal Elements, and Xenix Medical;
has received research or institutional support from AO Spine North America and CSRS; and
serves as a board member, owner, officer, or committee member of AO Spine North America,
Cervical Spine Research Society, LSRS, Musculoskeletal Tumor Society, and North American
Spine Society. Neither Dr. Blumstein nor any immediate family member has received anything of
value from or has stock or stock options held in a commercial company or institution related
directly or indirectly to the subject of this chapter.

ABSTRACT
The evaluation, diagnosis, and treatment of spinal tumors remains
a challenging issue in orthopaedic surgery. Although ultimate
management is typically carried out by highly specialized
practitioners in the fields of orthopaedic spine surgery and
orthopaedic oncology, a foundational understanding of the topic is
required for all practitioners who may encounter and evaluate
patients with suspected spinal tumors to avoid delays in treatment
or inappropriate management that can lead to deleterious results.
Most spinal column tumors are metastatic, and a thorough
oncologic history is required of all patients who present with back
pain, radicular symptoms, or myelopathy. Prior history of cancer
must prompt early workup and imaging. Primary tumors of the
spine are rare and often insidious in nature and present challenges
to early diagnosis. Careful evaluation and early referral to
specialized care improve treatment options and outcomes.
Treatment of spinal tumors varies greatly depending on the
biology, location, and extent of disease and may include surgical,
pharmaceutical, or radiotherapeutic approaches. Surgical treatment
may be curative in some cases but is also extensively used for
palliation in tumors that are resistant to radiation or chemotherapy.
Treatment of benign spinal tumors is at times equally challenging
because of tumor location and potential compression of neural
elements. Although appropriate evaluation, imaging, and referral
must not be delayed, tissue biopsy should not be performed before
discussion with the physician ultimately treating spinal tumors, as
inappropriate biopsy may significantly limit treatment options.
Keywords: malignant; metastatic; multidisciplinary; reconstruction;
spondylectomy

Introduction
Spinal tumors encompass a broad spectrum of benign and
malignant processes, both primary and metastatic, with varying
degrees of biologic activity. Because of the broad spectrum of
biology and tissue origin of spinal tumors, treatment algorithms
are varied and complex, and many do not currently have
established evidence-based guidelines. Therefore, accurate, timely
diagnosis and thoughtful, patient-specific, multidisciplinary
evaluation, and treatment planning are paramount.

Current Staging of Spinal Tumors

Benign and malignant tumors of the spine continue to be staged in
a manner similar to that of their appendicular counterparts via the
Enneking benign and Enneking malignant staging systems (Table
1). The key determinants of stage for benign tumors include
rapidity of growth, lytic component, bone destruction, and
expansion beyond cortical boundaries. For malignant bone tumors,
key determinants of stage include presence of metastasis, size,
depth, and histologic grade. The American Joint Commission on
Cancer staging system for malignant bone tumors uses tumor
grade (high or low), tumor size (larger or smaller than 8 cm), the
presence of regional lymph node metastasis, and the presence and
location of metastasis, with staging distinction between skip
metastasis (separate lesions within the same bone), pulmonary
metastasis, and nonpulmonary metastasis. 1 A spine-specific
staging system (Weinstein-Boriani-Biagini; Figure 1) for benign or
malignant tumors continues to be the standard by which
practitioners describe the anatomic distribution of spinal tumors.
This system is based on a clock-face division of the vertebral axial
view, with a radial depth modifier. This system is not only
descriptive, but it also guides treatment, because it implies
resection extent, surgical approach, feasibility of obtaining a wide
margin, and other treatment-related factors. Also, a staging system
originally described in 2010 describes the anatomic extent of cord-
level tumor compression. Not only is this system descriptive, but it
also helps guide treatment based on MRI, which can help predict
which patients are candidates for stereotactic radiosurgery 2 (Table
2).

Table 1
Summary of Current Staging in Musculoskeletal Oncology,
Depicting Enneking Benign and Enneking Malignant Systems

Stage T N M Description
Enneking Benign
1 0 0 0 Latent
2 0 0 0 Active
3 1 0 0 Aggressive
Enneking Malignant
IA 0 0 0 Low grade, intracompartmental
IB 1 0 0 Low grade, extracompartmental
 Stage T N M Description
IIA 0 0 0 High grade, intracompartmental
IIB 1 0 0 High grade, extracompartmental
III Any Any 1 Metastasis of any kind
Modified with permission of Springer Nature BV from W.F. Enneking . Staging of
musculoskeletal neoplasms. Musculoskeletal Tumor Society. Skeletal Radiol 1985;13(3):183-
94. Permission conveyed through Copyright Clearance Center.

Figure 1 Illustration shows the Weinstein, Boriani, and Biagini classification of

spinal tumors, adapted to a thoracic vertebra from Boriani.Radial clock-face
numerals describe anatomic distribution, whereas depth modifiers describe
extraosseous (A), intraosseous superficial (B), intraosseous deep (C),
intraspinal extradural (D), and intradural (E) extension.(Adapted with permission
from Boriani S, Weinstein JN, Biagini R: Primary bone tumors of the spine.
Terminology and surgical staging. Spine 1997;22:1036-1044.)

Table 2
Bilsky Grade Scoring System With Treatment Algorithm for
Metastatic Spinal Tumors

Bilsky
Definition Treatment
Score
0 Disease confined to bone Radiosensitive based on levels involved (<3 levels =
1a Epidural impingement SRS, >3 levels = 3D-CRT/IMRT) Radioresistant:
without thecal sac separation surgery, then radiation based on number
deformation of levels involved
1b Epidural impingement with If no neurologic deficits, same algorithm as for grade
thecal sac deformation, 0, 1a; if any neurologic deficits = dexamethasone 4
not abutting cord mg TID, separation surgery and radiation based on
1c Epidural impingement with number of levels involved
thecal sac deformation,
spinal cord abutment, no
cord compression
2 Cord compression with
visible CSF
3 Cord compression without Dexamethasone 4 mg TID, separation surgery and
visible CSF radiation based on number of levels involved
Data from Bilsky M, Laufer I, Fourney D, et al: Reliability analysis of the epidural spinal cord
compression scale. J Neurosurg Spine 2010;13(3):324-328.
3D-CRT = three-dimensional conformal radiotherapy, CSF = cerebrospinal fluid, IMRT =
intensity-modulated radiation therapy, TID = three times a day

Imaging
The initial standard of care in imaging spinal tumors is a plain
radiograph series. Although abnormalities may be subtle or
obscured by overlying visceral anatomy, plain radiographs are an
excellent initial screening tool to diagnose lytic or blastic lesions
and to determine the lesion aggressiveness by demonstrating bone
destruction or periosteal reaction. The so-called winking owl sign of
an obliterated en face pedicular cortical density is a late but
important finding. When not otherwise contraindicated, standing
weight-bearing radiographs should be obtained because they give
an indication of mechanical deformity, instability, or fracture.
Contrast-enhanced MRI of the entire spinal column is an
appropriate study when managing most tumors because multifocal
disease is common in metastatic carcinoma and possible in primary
bone tumors such as chordoma. This modality allows concurrent
visualization of neoplastic tissue, neural structures, and other soft-
tissues. CT allows excellent visualization of bony detail, which, in
addition to demonstrating the pa ern of bone destruction, may
reveal characteristic findings that facilitate a diagnosis, such as the
calcification pa erns unique to chondrosarcoma and chordoma, the
trabecular appearance of hemangioma, or the sclerotic bony
reaction of osteoid osteoma or osteoblastoma. Aside from imaging
of the spinal axis itself, it may be important to use systemic
imaging such as technetium Tc-99 bone scintigraphy, body MRI, or
positron emission tomography in circumstances such as staging or
metastatic surveillance for spinal tumors. The role of these systemic
modalities is not well defined for most histologies, and their use is
currently center and physician specific.
One emerging imaging modality that deserves mention is
intraoperative computerized navigation. Based on either scanning
fluoroscopy, CT, or MRI, this modality allows for the linking of two-
dimensional and three-dimensional patient images with real-time
intraoperative instrumentation and maneuvers such as bony cuts or
instrumentation insertion. As in the extremities and pelvis, early
experience with this modality seems to indicate improved accuracy
of instrumentation and tumor resection along with lower levels of
surgeon ionizing radiation exposure, as discussed in a 2019 study. 3
However, no data exist regarding benefit in terms of local
recurrence or other patient-related outcomes (Figure 2).
 Figure 2 A and B, Preoperative bone scan and axial CT from a 20-year-old
man with C4 osteoid osteoma causing severe intractable neck pain not relieved
with acetylsalicylic acid or NSAIDs. C and D, Intraoperative CT images of lesion
excision using intraoperative CT-based navigation. E, Postexcision axial CT.

Anatomic Considerations in Spinal Tumor

Management
Structural mobility and rigidity are key in evaluating spinal tumors.
Junctional (occipitocervical, cervicothoracic, thoracolumbar, and
lumbosacral) and mobile zones (cervical, lumbar) are areas of high
stress that do not tolerate structural bone loss as well as the
thoracic spine, which is protected by sternocostal architecture. 4
Likewise, spinal cord–bearing levels (occiput-L1) are less tolerant to
deformity or epidural encroachment than the spinal nerve root
containing levels of the lumbosacral spine. The occipitocervical
articulation is particularly unique and relies heavily on occipital-C1-
C2 ligamentous support from the transverse and alar ligaments.
Bony destruction from tumor or after resection of the dens, C2
lateral masses, C1 ring, or C1 lateral masses can result in the
functional equivalent of a traumatic occipitocervical dissociation
and requires careful reconstructive consideration. Likewise,
resections of the sacrum that involve more than half of the L5-S1
articulation may create sacropelvic discontinuity in this high-stress
zone.
Vascular anatomy in the spine has important considerations in
spinal tumors. The spinal cord is nourished primarily by the
anterior spinal artery via sporadic radiculomedullary vessels,
including the thoracolumbar artery of Adamkiewicz, which do not
occur at every spinal level. Although compensatory mechanisms
exist and the authors of a 2020 study have described safe resection
of up to three spinal levels, 5 reports of paraparesis after key
radiculomedullary vessel sacrifice have been described. 6
Preoperative angiogram, risk discussions, and intraoperative
maneuvers such as temporary clamping before definitive vessel
sacrifice are important. The cervical spine tends to have more
vascular redundancy than the poorly collateralized thoracic spine, 7
whereas vascular-related neurologic events are extremely rare in the
lumbosacral region.

Primary Malignant Tumors

Primary malignant tumors of the spinal axis represent a
challenging clinical problem. Aggressiveness and fastidiousness of
disease, anatomic constraints, technical nature of surgery, and
significant complication profiles are obstacles that can stand in the
way of successful tumor eradication. The modern standard of care
is adherence to Enneking-appropriate surgical oncology principles
in the management of bone sarcoma. This encompasses
multidisciplinary evaluation, appropriate use of adjuvants,
meticulously planned biopsy technique, and margin-negative en
bloc resection of tumors.

En Bloc Spondylectomy
Advances in surgical technique and a detailed understanding of
spinal anatomy have allowed Enneking’s principles to be applied to
tumors of the mobile spine. Tumor distribution according to the
Weinstein-Boriani-Biagini classification dictates the extent of
resection. For example, malignant tumors in the posterior elements
may require a fairly straightforward en bloc removal of the lamina
alone, whereas tumors that occupy the entire anterior body may
require deletion of the entire spinal segment, termed total en bloc
spondylectomy.
The technique of total en bloc spondylectomy began in the 1970s
and is currently being used. 8 - 10 There are many different
approaches to performing en bloc spinal tumor resections, and the
surgical strategy relies on recognition that the spinal canal is a bony
ring that must be osteotomized before rotating the vertebral body
away from the neural elements. This can be done with posterior,
anterior, or combined approaches. 11 For staged anterior/posterior
procedures, the posterior ring is usually osteotomized in the first
stage, with placement of stabilizing segmental instrumentation
above and below the tumor segment. In the second stage, the
tumor is accessed via retroperitoneal or thoracotomy approach,
great vessels are mobilized, transdiskal or transosseous cuts are
made, and the specimen is delivered via rotation away from the
neural elements. Cuts are facilitated via the use of thread wire saws
that may be passed ventral to the thecal sac, around the vertebral
bodies, and dorsal to the great vessels. In all posterior technique,
the same basic steps are accomplished, but the procedure is more
technical, given blind passage of thread wire saws and vertebral
body cuts made ventral to dorsal, toward the thecal sac.
The most likely location for a marginal or contaminated margin is
the dural margin. This may be managed by dural resection en bloc
with the specimen, but persistent cerebrospinal fluid leakage may
be an issue, especially in radiated beds. Thus, intraoperative
brachytherapy may be used to maintain and treat the dural layer
where margins are anticipated to be close. 12
 If wide margins can be achieved via en bloc spondylectomy, the
oncologic benefit in terms of local recurrence and overall survival
has been demonstrated. Key factors in addition to margin status for
the risk of local recurrence include the absence of adjuvant
radiation therapy, large tumor size, and high tumor grade. Overall
survival is dependent on a wider array of variables, but most
authors have reported overall survival rates after wide margin en
bloc spondylectomy for spine sarcoma that are similar to those for
extremity sarcoma. There are, however, exceptions to this in higher
grade diseases where spinal involvement itself is still a poor
prognosticator. For example, spinal osteosarcoma carries a dismal
prognosis even with successful wide margin resection and adjuvant
chemotherapy. 13 - 15
Complication rates following total en bloc spondylectomy are
high. One study reported an overall perioperative complication rate
of 42%, with potential risk factors being prior intralesional surgery,
staged anterior-posterior surgery, higher number of total spon-
dylectomy segments, and exposure to radiation therapy. 16
Instrumentation failure because of cage subsidence and/or
pseudarthrosis is the most common major complication event,
reported in 3% to 40% of patients. Other significant issues include
wound infections, neurologic decline, deep vein
thrombosis/pulmonary embolism, massive blood loss, and
pneumothorax.
Recently, patient-reported quality-of-life outcomes following en
bloc spondylectomy have been studied. Despite the reasonable
hypothesis that such an extended surgical procedure done for
malignant tumors would lead to poor postoperative quality of life,
disease-specific and general health metrics are comparable to those
in other spine-related conditions such as postpseudoarthrosis
repair and are not statistically different from those in patients
treated for the same conditions with definitive radiation therapy
and no surgery according to a 2019 study. 17 Mental health scores
may approach normal population means if patients are considered
to be free of disease; conversely, local recurrence or metastasis
affects both mental and physical summary scores, suggesting an
interplay between psychological and physical factors. 17

Reconstructive Issues Following Spondylectomy

The occipitocervical region of the spine has an especially unique
articulation. Key ligamentous stabilizing structures include the
transverse and alar ligaments, but in clinical situations where
spinal tumors are involved, it is more frequently the bony columnar
support that is compromised. Following C2 spondylectomy,
posterior reconstruction alone appears to be insufficient, and
central or lateral columnar reconstruction from the clivus or occiput
to C3 provide equivalent stability. 18 , 19
Reconstruction of the mobile spine following partial or total
spondylectomy uses techniques borrowed from other clinical
se ings. Key concepts include the use of load-sharing rigid
posterior segmental instrumentation and load-bearing anterior
column reconstruction. Recent advances include recognition of the
importance of biologic fusion, leading to use of microvascularized
autograft, especially in se ings where adjuvant radiation has been
used. Cage subsidence, which leads to cyclical micromotion,
appears to be the root cause of most episodes of implant failure, 20
and advances to increase end plate surface area and structural
rigidity of reconstruction cages may lead to improved outcomes.
The sacrospinal articulation provides further challenge in
reconstruction following tumors. After partial or total sacrectomy,
posterior spinopelvic instrumentation, even with multiple rod
constructs, appears inferior to constructs that reconstruct the
anterior spinopelvic columns via cathedral-type vascularized or
nonvascularized supports. 21

Chordoma
Chordoma is a rare (annual incidence of one per one million
persons) slow-growing, low-grade neoplasm of the axial skeletal
system with a prevalence in the sacrococcygeal area (50%), skull
 y p yg
base (35%), and mobile spine (15%). Within the mobile spine, the
cervical segments are the most common site. The cell of origin is
thought to be a remnant of the primitive notochord, which becomes
the nucleus pulposus for the intervertebral disk in developed
humans. This explains the almost exclusively axial location, as well
as possibly the rarely reported cases of multicentric chordoma. In
addition, the notochordal cell of origin is thought to possibly
implicate benign notochordal cell tissue as a precursor lesion,
although according to a 2021 study, subsequent investigations have
not definitively demonstrated progression to classic chordoma. 22
The rate of metastasis is 30% to 40% and typically occurs late in the
disease course, consistent with the low-grade nature of the lesion.
The imaging hallmark of a hyperintense, lobular, T2 bright axial
lesion (Figure 3) with occasional calcifications on CT scan
sometimes obviates the need for formal biopsy, especially in
difficult-to-access areas and considering chordoma’s fastidious
tendency to seed biopsy or needle tracts. When in doubt, histologic
diagnosis via core needle biopsy placed in a resectable location
along a proposed incision line is always preferable. Conventional
chordoma displays the classic physaliferous cell, a foamy,
vacuolated cell distributed in myxoid stroma. The hallmark of
chordoma staining is brachyury positivity, a transcription factor for
notochordal differentiation, but keratin positivity is an important
factor that distinguishes chordoma from chondrosarcoma. This is
especially relevant given the variants of chordoma that may include
chondroid or even dedifferentiated histologic subtypes.
 Figure 3 Sagittal T2-weighted magnetic resonance image of a late
presentation of massive sacral chordoma, demonstrating lobular, hyperintense
appearance.The tumor appears to originate from the S5 segment, with anterior
extension displacing the rectum and other abdominal contents, and posterior
extension into the subcutaneous fat.

Given that chordoma is a low-grade lesion, the treatment of

choice is wide en bloc excision, and the tumor is classically
radioinsensitive and chemoinsensitive. However, modern treatment
of chordoma usually involves an element of neoadjuvant and
adjuvant radiation therapy, which allows for local control of
macroscopic and microscopic satellite lesions to which chordoma is
prone. This adjuvant also helps marginate the tumor in cases where
anything be er than a marginal margin may not be possible. In
addition, for sacral locations, the recognition that both radiation
therapy and surgery should potentially involve the gluteus and
piriformis musculature has enhanced successful local control.
Using this methodology, one study reported only one local
recurrence over 23 cases of primary chordoma, 11 a rate much lower
than that previously reported for this tumor. 23 , 24 Prognostic factors
for local recurrence are consistently large tumor size, previous
tumor contamination, and intralesional resection, whereas
predictors of poor survival include preoperative motor deficit and
older age. 25

Chondrosarcoma
Chondrosarcoma, like chordoma, is a fastidious, rare,
predominantly low-grade, slow-growing neoplasm of cartilage cell
lineage. It is even more rare in the spine, with only 10% to 12% of
chondrosarcomas presenting in the axial skeleton, most commonly
in the thoracic region. 26 Most arise as spontaneous primary
neoplasms, but secondary chondrosarcomas arising in the se ing
of multiple hereditary exostosis or one of several multiple
enchondroma syndromes do occur. 27 The lesion typically appears
as an aggressive, T2 bright tumor with extraosseous component and
intralesional calcifications. Survival mirrors that for other sarcomas,
with most series reporting in the 60% to 70% survival range at 5
years, with an approximately 40% overall metastatic rate. 28
Being low grade, chondrosarcoma is classically treated with
surgery alone, ideally wide margin, en bloc technique. One series of
22 mobile spine chondrosarcomas featured a local recurrence rate
of 7.5% with en bloc marginal or wide surgery, but 100% local
recurrence with intralesional cure age and an 80% mortality from
disease in the intralesional group. 25 A series of 98 spinal
chondrosarcomas reinforced the dramatic importance of wide en
bloc surgery on local recurrence and overall survival; the en bloc
group had only 3% local recurrence and nearly 90% 10-year overall
survival, and an intralesional group, even after gross total resection,
had local recurrence of 21% and approximately 60% 10-year overall
survival. Despite a classic insensitivity to radiation therapy, some
authors do report excellent results with a combined
surgery/radiation therapy approach. 11 , 28 In addition,
chemotherapy is a standard of care in most institutions for the
dedifferentiated variant of chondrosarcoma.

Osteogenic Sarcoma
Osteogenic sarcoma, unlike chondrosarcoma and chordoma, is a
high-grade malignancy predominantly in children in whom
pulmonary micrometastasis or macrometastasis is the rule, not the
exception. With an overall annual incidence of nearly 5 per million,
axial presentation is even more rare, and it occurs in only 3% to 5%
of cases of osteogenic sarcoma. 29 Radiographs, MRI, and CT
typically demonstrate a destructive lesion with extraosseous
extension, so a high proportion of patients present with neurologic
symptoms, which may hasten multidisciplinary treatment
planning. Histology demonstrates pleomorphic spindle cells that
produce disorganized osteoid, which is the defining and unifying
characteristic even for histologic variants such as chondroid or
telangiectatic osteosarcoma. Osteogenic histology is the most
common histology in secondary sarcomas such as postradiation or
Paget disease–related sarcoma, which account for a second spike in
incidence of osteogenic sarcoma in older adults. Classically, this
disease has a dismal prognosis, with some series finding a zero
survival rate despite aggressive treatment. 28 The historical reason
for this is likely a combination of high-grade biologic behavior with
high macrometastatic rate, inconsistent chemotherapy regimen use,
and technical difficulty with wide en bloc resection. Recent
Surveillance, Epidemiology, and End Results data list the 5-year
survival rate for all patients with spinal osteogenic sarcoma at only
18%. 30
Modern treatment of osteogenic sarcoma of the spine
incorporates surgery plus neoadjuvant or adjuvant chemotherapy
using methotrexate, adriamycin, platinum compounds, and
ifosfamide. Radiation therapy may be used for contaminated
margins or recurrent disease but is not first-line treatment. Several
recent studies have reinforced the poor prognosis of this disease,
with only approximately 30% to 50% of patients successfully
achieving a margin-negative resection, with correspondingly high
local recurrence rates of 30% to 40%, high metastatic rate of 60% to
65%, and low overall survival (50% to 90% mortality, median
survival 23 to 38 months). 14 , 31 , 32 Despite the rarity of this disease
and correspondingly small study numbers, there is some indication
that wide or marginal en bloc surgery does enhance survival, and
this treatment should be sought if anatomic and patient factors
allow. 14 Risk factors for poor survival include sacral tumor location,
tumors larger than 10 cm, and patients presenting with primary
metastases.

Ewing Sarcoma
Like osteogenic sarcoma, the family of Ewing sarcoma (EWS)
tumors of the spine (including primitive neuroectodermal tumor)
are high-grade malignancies in children. Although the annual
incidence is slightly less than that for osteogenic sarcoma, the spine
is more commonly affected in EWS, in up to 10% of cases, with a
particular propensity for the sacral and lumbar spine. 29 Given the
high-grade nature, patients with EWS of the spine may present with
neurologic compromise, and microscopic systemic involvement is
assumed even in the absence of macrometastases. Additional
clinical factors include the common occurrence of elevated
inflammatory markers and constitutional symptoms that mimic
infection or hematologic malignancies.
 Radiographs and axial imaging typically demonstrate an
aggressive, destructive lesion with soft-tissue extension, and
histology demonstrates malignant small round blue cells that stain
positively for the EWS-FLI1 protein product from translocation
t(11;22). It is important to distinguish primary isolated spinal EWS
from metastatic EWS, and positron emission tomography has
emerged in EWS family tumors as more sensitive than bone
scintigraphy. 33 Survival is reported via Surveillance, Epidemiology,
and End Results data to be be er than that for osteogenic sarcoma
of the spine, with 5-year overall survival of 41%. 30
Unlike any other spine sarcoma, this neoplasm is exquisitely
sensitive to radiation therapy, 34 so the classic therapeutic approach
has consisted of combination chemotherapy for systemic and local
control with or without radiation therapy and no surgery. This is in
contradistinction to modern protocols for extremity EWS, which
usually involve surgery for local control. Recently published
longitudinal experiences with this rare tumor have not clarified the
issue of whether to add wide en bloc resection to other adjuvants in
spinal EWS. In one report of 43 patients with EWS of the sacrum or
mobile spine, there was no difference in event-free survival or
overall survival in a surgery plus radiation and chemotherapy group
when compared with a group receiving radiation therapy and
chemotherapy alone. 35 Another dynamic that further complicates
the picture is that radiation therapy dosing may be eliminated or
reduced in cases where wide resection is possible, which provides a
theoretical downstream benefit by reducing the risk of secondary
malignancy. Thus, decisions regarding the care of spinal EWS
should be made in a multidisciplinary se ing with careful
consideration of the issues on a case-by-case basis.

Benign Primary Spinal Tumors

The most common benign tumor of the spine is hemangioma,
estimated to occur in approximately 10% of the population. This
ubiquitous tumor typically demonstrates bright T1 and bright T2
MRI signaling because of the interposed normal marrow elements
with a typical zebrafish pa ern. CT demonstrates coarsened
trabeculae. In most cases these tumors are latent and found
incidentally. Although typically indolent, they may cause
pathologic fracture or compression because of hemodynamic
change (frequently during pregnancy) and in rare cases behave in a
more aggressive way, causing neurologic deficit. A series of 68
patients undergoing surgical treatment for symptomatic
hemangioma, the largest study to date, found a strikingly low rate
of recurrence with intralesional treatment. 36 This is likely because
of the underlying benign nature of this lesion, with aggressive local
behavior resulting from instability or mass effect rather than any
feature inherent to the lesion. Preoperative embolization has
proven to be of limited utility in aggressive lesions. Histologic
confirmation for patients with aggressive or recurrent disease is
necessary to rule out diagnostic entities such as epithelioid
hemangioendothelioma, which may have cellular atypia, visceral
involvement, and up to a 20% mortality rate.
The most common benign tumors that present with Enneking
stage 2 or 3 biologic activity are osteoblastoma, aneurysmal bone
cyst (ABC), and giant cell tumor (GCT) of bone. Osteoblastoma and
ABC, along with osteoid osteoma, typically present in young
patients in the posterior elements of the spine. Osteoblastoma,
although indistinguishable histologically from osteoid osteoma,
classically presents as a larger lesion (>2 cm) with duller and more
unremi ing pain pa ern and has the potential for malignant
degeneration. 37 Aggressive-appearing variants should be carefully
distinguished from osteogenic sarcoma. Recent evidence has
indicated that for stage 2 lesions, intralesional treatment provides
an excellent method of local control, but that for stage 3 lesions, it
leads to high rates of local recurrence. Current preferred treatment
for stage 3 osteoblastoma is en bloc excision, but a report of good
local control with gross total excision via intralesional
vertebrectomy was published in a 2020 study. 38 Where total
excision is not possible or when prior contamination has occurred,
radiation therapy is an option for adjuvant treatment, but caution
regarding downstream complications such as neuritis or secondary
sarcoma should be considered, and the benefit is controversial. 39
Predictors of local recurrence in stage 3 osteoblastoma of the spine
may include preoperative alkaline phosphatase level, intralesional
surgery, and size greater than 3 cm. 40 Figure 4 demonstrates the
aggressiveness of spinal osteoblastoma.

Figure 4 A and B, Preoperative magnetic resonance and axial CT images of

aggressive vertebral osteoblastoma. C, Postoperative magnetic resonance
image showing recurrence of lesion. D and E, AP and lateral radiographs after
hemivertebrectomy and reconstruction.

The concept of using margin-negative, en bloc surgery for benign

disease extends to other stage 3 lesions, including ABC and GCT of
bone. ABCs, however, are typically difficult to remove in one piece.
39
Figure 5 demonstrates a typical case of an ABC. They present as
thin-walled expansile blood-filled cavities, and, as such, the most
common surgical treatment is intralesional total excision, which has
been performed with low rates of local recurrence. 41 Recently
investigators have reported alternative treatments for ABCs, such
as selective arterial embolization. Although embolization may need
to be repeated, one retrospective multicenter comparison did not
detect a benefit to adding surgery to selective arterial embolization.
42
The two modalities, of course, are frequently combined. Recently,
spinal ABCs have been shown to be successfully managed using
concentrated bone marrow injection in some small series. Although
this approach remains to be proven in a broader clinical se ing, it
may prove to be useful because of potentially lower risk of
complication than surgery or selective arterial embolization. 43
 Figure 5 A and B, Sagittal and axial T2-weighted magnetic resonance image
with classic appearance of the fluid-fluid levels of an aneurysmal bone cyst in
the posterior elements of T11. To obtain spinal cord decompression, the tumor
was removed en bloc, and it exhibited typical friable gross appearance (C) and
histology (D). Reconstruction with posterior segmental instrumentation and
structural allograft was used (E and F).

GCT of bone can also behave aggressively and may need to be

managed with en bloc margin-negative surgery when presenting
with stage 3 biologic behavior. 39 This tumor consists of neoplastic
stromal cells, which create a giant cell reactive background,
activating the bone lysis cascade. The tumor has a slight female
preponderance, occurs in middle-aged adults, and may rarely result
(2% to 5%) in benign metastases to the lungs. Up to 10% of these
tumors occur in the spine, and recurrence rates are considerably
higher in the spine than other locations. Marginal resection or
intralesional resection with adjuvant treatment has been the
treatment of choice; however, when not possible given anatomic
constraints, GCTs of the spine have been managed with
embolization or radiation therapy. This strategy has provided
mixed results with regard to local recurrence, with a lingering
concern of malignant transformation with radiation therapy.
According to a 2021 study, 44 the use of denosumab, a monoclonal
antibody receptor activator of nuclear factor kappa-B ligand
inhibitor, has proven to be of significant benefit in inoperable
spinal GCT, halting the progression of disease and in many cases
shrinking the tumor. Although these benefits appear to last only
while treatment is ongoing, early evidence suggests a role for
denosumab as a neoadjuvant treatment to aid in surgical resection,
and ongoing clinical trials are currently investigating this use. 44

Metastatic Spinal Disease

The most common primary histologies that metastasize to the
spine mirror those in the extremities and consist of lymphoma,
myeloma, and carcinoma of breast, lung, prostate, renal, and
thyroid origin. The axial skeleton is the most common skeletal site
of metastasis, and in patients with metastatic cancer, spinal
involvement approaches 90% based on postmortem studies. 45 The
valveless venous plexus, which runs in parallel to the caval system,
Batson plexus, may explain some of this propensity, but a complex
choreography of delamination, transit, and implantation must
occur for a metastatic focus to develop, and anatomic implantation
sites are not limited to venous distribution. 46 True intradural
metastases are quite rare (<5%), and most present as intraosseous
lesions with or without epidural extension.
Symptomatic spinal metastases will develop in as many as 20% of
patients with cancer. Unlike most primary tumors that remain
localized and can therefore be eradicated, metastatic disease in the
spine is typically treated using a palliative algorithm. That being
said, a spectrum of disease exists depending on tumor, neurologic,
and patient factors, and in some rare cases the treatment approach
for a metastasis may resemble the curative algorithm of a primary
malignancy. The key factors to consider in treatment of metastatic
disease of the spine include neurologic grading, analysis of spinal
mechanical stability, tumor histology, and patient
comorbidities/performance status. These were well delineated as
part of the NOMS (neurologic, oncologic, mechanical, and
systemic) framework, which is a valuable systematic method of
approaching and treating spinal metastases. 47 Figure 6 describes
this thought process and the resulting wide array of treatment
options, underscoring the importance of patient-centered
multidisciplinary cooperative decision making.

Figure 6 Illustration depicts the NOMS (neurologic, oncologic, mechanical,

systemic) framework for systematically approaching treatment of spinal
metastases.EBR = external beam radiation, IMRT = intensity-modulated
radiation therapy, SINS = spinal neoplastic instability score.

Diagnostics in Metastatic Spinal Disease

Even when metastatic disease is suspected based on cancer history,
great caution should be taken to obtain an accurate diagnosis
before initiating treatment. This is especially true when a solitary
lesion is encountered. As many as 80% of cases may be correctly
diagnosed before biopsy based on a thorough history and physical
examination; CT of the chest, abdomen, and pelvis; systemic
imaging such as technetium Tc-99 scintigraphy, positron emission
tomography-CT; and appropriate laboratory studies such as
complete blood count, protein electrophoresis, erythrocyte
sedimentation rate, and tumor-specific serum markers. Biopsy at
the treating center via a resectable needle approach is the standard
of care when the diagnosis is uncertain.

Radiosensitivity
The responsiveness of a spinal neoplasm to radiation therapy is of
key importance in metastatic spine disease. Whereas some
extremely sensitive tumors may be managed with radiation alone,
most tumors are managed with a combination of medical,
radiotherapeutic, and surgical modalities. Very sensitive tumors
may be more appropriate for more extensive surgical a empts at
local control, whereas exquisitely sensitive tumors are frequently
managed without surgery, even when locally advanced.
Additionally, given advances in the accuracy of radiation therapy
modalities, most neoplasms can be effectively targeted and dosed
while minimizing toxicity to normal tissues and improving the
durability of surgical local control after intralesional resection.
Exquisitely radiosensitive histologies include myeloma, lymphoma,
and germ cell tumors such as seminoma. Moderately sensitive
tumors include breast, small cell lung, prostate, ovarian, and
neuroendocrine tumors. Poor responders include renal, thyroid,
and tumors of gastrointestinal origin, with very poor responses
observed in non–small cell lung cancer and melanoma. 48

Predicting Mechanical Instability

Treatment of spinal metastases in patients who are neurologically
intact remains a challenge. The potential complications of surgical
treatment should be weighed against the possibility of future
pathologic fracture, deformity, and instability leading to
catastrophic neurologic injury. The spine instability neoplastic
score has been widely adopted to guide treatment for stabilization.
The scoring system, which has been widely reproduced and
validated, is based on mobility and junctional location of the
involved spinal segment, baseline alignment, pain, amount of
vertebral collapse, lytic character, and status of the posterior
tension band 4 (Table 3). Scores of 0 to 6 indicate stability, scores of
13 to 18 indicate instability, and scores of 7 to 12 are indeterminate.
Criticisms of this scoring system are that it does not take into
account the tumor histology, which may be rapidly healable with
bracing and proper adjuvant treatments such as radiation therapy.
In addition, most tumors will fall into the indeterminate category,
for which the score does not suggest treatment strongly toward or
away from surgical stabilization.

Table 3
The Spinal Instability Neoplastic Score

Factor Subcategory Score

Tumor location Junctional Occiput-C2 3
C7-T2 3
T11-L1 3
L5-S1 3
Mobile C3-C6 2
L2-L4 2
Semirigid T3-T10 1
Rigid S2-S5 0
Alignment Subluxation 4
Baseline sagittal/coronal imbalance 2
No deformity 0
Pain Mechanical 3
Occasional nonmechanical 1
None 0
Vertebral collapse >50% 3
<50% 2
Precollapse (>50% of body 1
involved)
None of the above 0
Tumor type Lytic 2
Mixed 1
Blastic 0
 Factor Subcategory Score
Posterior element Bilateral 3
involvement
Unilateral 1
None 0
Adapted from Fisher CG, DiPaola CP, Ryken TC, et al: A novel classification system for
spinal instability in neoplastic disease: an evidence-based approach and expert consensus
from the Spine Oncology Study Group. Spine 2010;35:E1221-E1229.

Prognosis
Spinal metastases generally portend poor outcomes, with a typical
life expectancy of less than 12 months. When considering the
underlying frailty of many in this patient population, the increased
risk of surgical complications means that for some patients, the
expected time to recovery and discharge home may be longer than
their predicted life expectancy. Since the 1990s many classification
systems have been developed to help predict prognosis and guide
treatment, including Tomita, Sioutos, Van der Linden, Tokuhashi,
and Bauer. The variables in these prediction models include
neurologic grade, number of metastatic sites, presence of visceral
sites, histology, and patient performance status. The modified
Bauer scoring system was found to be the most accurate in
predicting short-term, medium-term, and long-term survival. This
system gives favorable credit for no visceral metastases, no lung
primary histology, presence of favorable histology (breast, renal,
myeloma, lymphoma), and one or fewer skeletal sites. Another
classically used system, the modified Tokuhashi, similarly places
favorable emphasis on low numbers of spinal/extraspinal/visceral
sites and favorable histologies (breast, thyroid, prostate, carcinoid)
but adds the intuitively important patient performance status and
neurologic status.
More recently, several modern and sophisticated prognostication
systems have emerged to more accurately assess prognosis for
patients with metastatic spinal disease. The New England Spinal
Metastasis Score incorporated serum albumin as a proxy for health
reserve, which increased accuracy at 1 year. This score was
subsequently externally validated through the National Surgical
Quality Improvement Program database. More recently, the
Skeletal Oncology Research Group developed a series of predictive
algorithms, since published as a nomogram (Figure 7) and available
as online calculators, which incorporate laboratory data, markers of
disease extent, physiologic reserve, and pathology to predict
survival at 30 days, 90 days, and 1 year. 49 Different inputs are
proportionally weighted, increasing overall accuracy. Newer models
are currently being developed using machine learning and other
artificial intelligence algorithms to account for a larger number of
variables, including more laboratory values and tumor genomic
markers of sensitivity to various therapies. More accurate models
predicting patient frailty have also been published recently, which
may help guide decision making about the extent of surgical
treatment for specific patients. 50 Although accuracy of scoring
systems continues to improve, any scoring system should be used
as a population-based tool to advise and guide treatment, and they
are not intended to accurately predict the survival of any individual
patient.
 Figure 7 Skeletal oncology research group nomogram with weighted scale of
different variables used in online prognosis calculators.(Reproduced with
permission from Paulino P, Janssen S, Van Dijk E, et al: Development of a
prognostic survival algorithm for patients with metastatic spine disease. J Bone
Joint Surg Am 2016;98[21]:1767-1776.)

Metastatic Epidural Cord Compression

Although most metastases present initially with back or neck pain
as the main complaint, progression to a neurologic deficit is not
uncommon. The Sco ish Cord Compression Group estimated the
average duration between back pain and neurologic deficit is 66
days. 51 The cause of neurologic deficit can be from direct tumor
compression, tumor-related bone reaction, or pathologic fracture
creating deformity around the neural elements. The Spine
Oncology Study Group described a grading system based on tumor
extension into the spinal canal and degree of thecal sac effacement,
suggesting that cord deformity and complete spinal fluid
effacement with or without neurologic deficit be strongly
considered for surgical neurologic decompression. Although the
best predictor of postoperative neurologic recovery is preoperative
neurologic status, timing of decompression is also important.
Incomplete or evolving spinal cord injuries from tumor-related
mechanical compression are surgical emergencies. The best data
would suggest that decompression within 48 hours of symptom
onset leads to the best prognosis for recovery, 52 but practically
speaking, these difficult clinical situations should be managed as
soon as possible. Unfortunately, the treating surgeon is
occasionally not able to establish a diagnosis before planning
decompression. In this situation, the tumor should be handled
carefully at a tertiary center, with open biopsy, intraoperative
histologic analysis, and decompression in the least contaminating
way possible if a diagnosis cannot be established. A landmark
prospective study confirmed a benefit to surgical decompression
plus conventional radiation therapy compared with conventional
radiation therapy alone with regard to maintenance and
reestablishment of ambulatory status and opioid use. 53

Approaches in Metastatic Spinal Tumor

Surgery
The standard open surgical approaches used in the management of
spinal tumors including metastatic disease are similar to those
used in other clinical se ings. Throughout the spine, posterior
laminectomy is useful for dorsal element tumors and direct dorsal
decompression. Transpedicular decompression allows an element
of lateral decompression at cord level in the thoracolumbar spine,
but in the cervical spine the vertebral arteries and exiting nerve
roots must be carefully handled with any posterolateral surgery.
The only approaches that provide any significant anterior column
access for excision and reconstruction of tumors in the
thoracolumbar spine include direct anterior access via
retroperitoneal or transthoracic approaches, or posteriorly based
anterior column approaches (lateral extracavitary,
costotransversectomy). The experience with direct anterior (usually
in combination with a staged posterior approach) versus all-
posterior-based anterior column exposures has been mixed, with
some authors identifying no difference in complication rates, 54 and
others claiming a significant reduction in perioperative
complications and recovery time with all-posterior-based
approaches. 55 The all-posterior approaches are especially useful in
the upper thoracic spine where nerve roots may be sacrificed easily
for exposure and where great vessel anatomy makes direct anterior
approaches more difficult.
Recently, several surgical technique–related advances have
emerged. The first involves so-called separation surgery, a
multidisciplinary treatment approach in which local control is
mostly achieved via high-dose stereotactic radiosurgery, facilitated
by limited surgery to separate the tumor from the neural elements
and provide dorsal stabilization. 56 In addition, intralesional care of
metastatic spine disease may be successfully accomplished with
minimally invasive surgery (MIS). This broad term has many
different meanings and applications, but recent experience with
either MIS dorsal laminectomy and percutaneous instrumentation,
or even MIS lateral corpectomy and stabilization, 57 has been
positive. Principal outcome measures that are improved via MIS
surgery such as intraoperative blood loss and shorter hospital stay
mirror the experience with MIS surgery in nonneoplastic
conditions.

Other Modalities
Patients with relatively poor prognoses and limited lifespan may
benefit from nonsurgical means of stabilization or tumor control.
Kyphoplasty and vertebroplasty are percutaneous methods of
restoring anterior and middle column height following pathologic
vertebral fracture and are reported to achieve modest amounts of
kyphotic correction (4° to 6°) and height restoration (4 to 5 mm). A
2021 randomized trial demonstrated this treatment’s superiority
over conservative management for vertebral column fractures in
cancer patients with acute fractures. 58 However, vertebral
augmentation procedures have a narrow indication in this se ing.
Epidural cord compression or an insufficient posterior wall or
pedicle are relative contraindications for these procedures because
of concern for worsening of cord compromise or cement
extravasation. Other percutaneous interventions such as
radiofrequency or cryoablation may be combined with kyphoplasty.
58

Radiosurgery is an emerging modality that takes advantage of

technologic advances in radiation dose shaping, body
immobilization, and computer-driven treatment planning. Unlike
conventional external beam radiation therapy, high doses are given
over one or few fractions, and because of the accuracy of dose
delivery, healthy tissues are largely spared, especially when
techniques such as separation surgery are also used. This modality
has allowed the treatment of typically radioresistant histologies, the
re-irradiation of recurrent tumors, and the definitive local control
and pain palliation for patients who have short life expectancies or
who are unfit for surgery. 59

Rationale for Metastasectomy via Wide

Margin, En Bloc Surgery
Occasionally, patients with oligometastatic disease may be
considered for more aggressive surgery with wide margins via en
bloc total or partial spondylectomy. Patients with metastases are by
definition stage IV and may not be technically cured. However,
some investigators have observed a survival benefit, even for long
periods, using a metastasectomy protocol in carefully selected
patients with histologies such as breast, renal, melanoma, and
thyroid. 60 - 62 Some factors that support the use of wide resection
margins in the se ing of metastatic disease include excellent
patient performance status, radiosensitive histology, histology
associated with long survival such as renal cell carcinoma, solitary
or oligometastases, lack of visceral metastasis, long latency period
between metastasis and primary tumor management, and anatomic
resectability of the tumor. One explanation for the observations
that have been made in the literature for a survival benefit to
metastasectomy is that of selection bias: the most appropriate
patients for aggressive surgery are also those who are likely to
survive the longest. However, the effect has been observed in many
different independent studies and may have a reasonable
explanation. For example, if tumor burden can be reduced to
microscopic or no detectable levels, it is possible that the host
immune system can keep the tumor in check for long periods of
time or eradicate it altogether. In any case, there is no doubt that
spondylectomy carries higher risks, complication profiles, and
recovery duration than other methods of surgical treatment, and, as
such, its use should be weighed carefully with a multidisciplinary
team that closely involves the patient.

Summary
Spine neoplasms present as a diverse array of benign, malignant,
and metastatic processes. Obtaining an accurate diagnosis, using a
multidisciplinary approach, and simultaneously optimizing
oncologic, neurologic, and structural care of the spine lead to the
best outcomes.

Key Study Points

The most common tumors of the spine are metastatic, of which the most common
are lymphoma, myeloma, and carcinoma of breast, lung, prostate, renal, and thyroid
origin. Spine lesions develop in up to 90% of patients with metastatic cancer.
Treatment depends on location, specific biology, and ultimate goals of care and may
include radiation, chemotherapy, and surgical resection.
The most common primary tumors of the spine are chordoma, chondrosarcoma,
osteogenic sarcoma, and Ewing sarcoma. Chordoma and chondrosarcoma are
low-grade tumors and do not respond well to radiation or chemotherapy. Negative-
margin surgical resection and reconstruction are the first-line treatment of choice.
Osteogenic sarcoma is treated with a combination of surgical resection,
neoadjuvant and adjuvant chemotherapy, and, in some cases, radiation therapy.
Treatment options for Ewing sarcoma are varied and include surgical resection,
chemotherapy, and radiation therapy depending on patient-specific factors.
The most common benign primary spinal tumors are hemangiomas, osteoblastoma,
ABC, and GCT of bone. Despite being benign, these tumors may cause significant
 morbidity because of compression of neural elements and present treatment
challenges because of location and proximity to vital structures.
A multidisciplinary approach is required for biopsy planning, chemotherapy, radiation
therapy, and surgical planning for successful treatment of spinal tumors. However,
early evaluation and imaging should not be delayed.

Annotated References
1. Amin MB, Edge SB, Greene FL, et al, eds: AJCC Cancer Staging
Manual, ed 8. Springer, 2017.
2. Bilsky M, Laufer I, Fourney D, et al: Reliability analysis of the
epidural spinal cord compression scale. J Neurosurg Spine
2010;13(3):324-328.
3. Ando K, Kobayashi K, Machino M, et al: Computed tomography-
based navigation system-assisted surgery for primary spine
tumor. J Clin Neurosci 2019;63:22-26. In this prospective study of
O-arm assisted navigation in 18 patients undergoing resection of
primary spinal tumors, there was no evidence of screw
misplacement, mechanical implant failure, or recurrence in the
study group. Level of evidence: IV.
4. Fisher C, DiPaola C, Ryken T, et al: A novel classification system
for spinal instability in neoplastic disease: An evidence-based
approach and expert consensus from the Spine Oncology Study
Group. Spine 2010;35(22):E1221-E1229.
5. Tan T, Rutges J, Marion T, Fisher C, Tee J: The safety profile of
intentional or iatrogenic sacrifice of the artery of Adamkiewciz
and its vacinity’s spinal segmental arteries: A systematic review.
Global Spine J 2020;10(4):464-475. This is a systematic review of
spinal and vascular surgery literature of neurologic injury after
iatrogenic or intentional sacrifice of the artery of Adamkiewciz or
contiguous segmental spinal arteries. Ten articles were included.
Risk of neurologic or motor deficits was found to be 4% with
occlusion of the artery of Adamkiewciz and 5.4% with occlusion
of more than six bilateral contiguous segmental spinal arteries.
Level of evidence: III.
 6. Apel DM, Marrero G, King J, Tolo VT, Basse GS: Avoiding
paraplegia during anterior spinal surgery. The role of
somatosensory evoked potential monitoring with temporary
occlusion of segmental spinal arteries. Spine (Phila Pa 1976)
1991;16(8 suppl):S365-S370.
7. Dommisse GF: The blood supply of the spinal cord. A critical
vascular zone in spinal surgery. J Bone Joint Surg Br 1974;56(2):225-
235.
8. Boriani S, Biagini R, De Iure F, et al: En bloc resections of bone
tumors of the thoracolumbar spine. A preliminary report on 29
patients. Spine 1996;21(16):1927-1931.
9. Stener B: Total spondylectomy in chondrosarcoma arising from
the seventh thoracic vertebra. J Bone Joint Surg Br 1971;53(2):288-
295.
10. Boriani S: En bloc resection in the spine: A procedure of surgical
oncology. J Spine Surg 2018;4(3):668-676.
11. DeLaney TF, Liebsch NJ, Pedlow FX, et al: Long-term results of
Phase II study of high dose photon/proton radiotherapy in the
management of spine chordomas, chondrosarcomas, and other
sarcomas. J Surg Oncol 2014;110(2):115-122.
12. Zuckerman S, Lim J, Yamada Y, Bilsky M, Laufer I:
Brachytherapy in spinal tumors: A systematic review. World
Neurosurg 2018;118:3235-3244.
13. Shimizu T, Murakami H, Demura S, et al: Total en bloc
spondylectomy for primary tumors of the lumbar spine. Medicine
2018;97(37):312366.
14. Dekutoski M, Clarke M, Rose P, et al: Osteosarcoma of the
spine: prognostic variables for local recurrence and overall
survival, a multicenter ambispective study. J Neurosurg Spine
2016;25(1):59-68.
15. Colman MW, Karim SM, Lozano-Calderon S, et al: Quality of life
after en-bloc resection of tumors in the mobile spine. Spine J
2015;15(8):1728-1737.
16. Amendola L, Cappuccio M, De Iure F, et al: En bloc resections
for primary spinal tumors in 20 years of experience: effectiveness
and safety. Spine J. 2014;14(11):2608-2617.
17. Periera N, Janssen S, Stoop N, et al: Physical function and
quality of life after resection of mobile spine chondrosarcoma.
Global Spine J 2019;9(7):743-753. This study evaluated patient-
reported outcomes in patients who underwent resection of spinal
chondrosarcoma in a single institution over a 30-year period.
Outcomes demonstrated worst patient-reported physical
function, quality of life, and comparable pain to the general US
population, as well as mild to moderate disability scores.
However, these scores were comparable to those of patients
undergoing surgery for other nonmalignant spine pathology or
patients undergoing definitive radiation therapy for similar
pathology. Patients who experienced complications requiring
revision surgery scored significantly worse in all patient-reported
outcome measures than those who did not experience
complications requiring revision surgery. Level of evidence: III.
18. Koller H, Hartmann S, Raphael G, Schmölz W, Orban C, Thome
C: Surgical nuances and construct pa erns influence construct
stiffness in C1-2 stabilization: a biomechanical study of C1-2
gapping and advanced C1-2 fixation. Eur Spine J 2021;30(6):1596-
1606. This biomechanical study evaluated C1-2 gapping on
construct stiffness using a spine tester with six degrees of
freedom. Rod diameter, material, and use of cross-link were
evaluated. Use of cross-link significantly improved construct
stability.
19. Park S, Lee C, Chang B, et al: Rod fracture and related factors
after total en bloc spondylectomy. Spine J 2019;19(10):1613-1619.
This retrospective multicenter study investigated rod fracture
following total en bloc spondylectomy in patients with primary
malignant or oligometastatic spine tumors. Twelve of 32 patients
experienced rod fracture at an average of 29.2 months. History of
radiation therapy and total en bloc spondylectomy at lumbar
 level were significant risk factors for rod fracture. Level of
evidence: III.
20. Wei R, Guo W, Yang R, et al: Reconstruction of the pelvic ring
after total en bloc sacrectomy using a 3D-printed sacral
endoprosthesis with re-establishment of spinopelvic stability: A
retrospective comparative study. Bone Joint J 2019;101-B(7):880-
888. This is a retrospective review of 32 patients undergoing
pelvic reconstruction using three-dimensionally printed
endoprosthesis compared with spinopelvic fixation alone or
anterior spinal column fixation and spinopelvic fixation. Patients
undergoing three-dimensional endoprosthesis reconstruction
had improved spinopelvic stability and implant survival
compared with the other two groups. Level of evidence: III.
21. Deshpande V, Nielsen GP, Rosenthal DI, Rosenberg AE:
Intraosseous benign notochord cell tumors (BNCT): Further
evidence supporting a relationship to chordoma. Am J Surg Pathol
2007;31(10):1573-1577.
22. Zuckerman S, Lee S, Chang G, et al: Outcomes of surgery for
sacral chordoma and impact of complications: A report of 50
consecutive patients with long-term follow-up. Global Spine J
2021;11(5):740-750. This retrospective database study of patients
undergoing en bloc resection of sacral chordoma demonstrated
that negative-margin resection was associated with decreased
local recurrence. Major complications and revision surgery did
not significantly affect overall survival or local recurrence. Level
of evidence: IV.
23. Palthe O, Tromp I, Ferriera A, et al: Sacral chordoma: A clinical
review of 101 cases with 30-year experience in a single institution.
Spine J 2019;19(5):869-879. This retrospective case series of 101
cases of sacral chordoma in a single institution (73 primary
tumors and 28 first-time recurrence) found that increased tumor
size was an independent risk factor for worse overall survival and
shorter relapse-free interval. Primary tumors not receiving
adjuvant radiation therapy had shorter time to local recurrence.
Level of evidence: IV.
24. Barber S, Sadrameli S, Lee J, et al: Chordoma-current
understanding and modern treatment paradigms. J Clin Med
2021;10(5):1054. This review article describes the current state of
understanding of the diagnosis, molecular and genetic
pathophysiology, and treatment algorithms of chordoma.
25. Boriani S, De Iure F, Bandiera S, et al: Chondrosarcoma of the
mobile spine: Report on 22 cases. Spine 2000;25(7):804-812.
26. Mesfin A, Ghermandi R, Castiello E, Donati DM, Boriani S:
Secondary chondrosarcoma of the lumbar spine in hereditary
multiple exostoses. Spine J 2013;13(9):1158-1159.
27. Arshi A, Sharim J, Park D, et al: Chondrosarcoma of the osseus
spine. Spine 2017;42(9):644-652.
28. Chang UK, Lee DH, Kim MS: Stereotactic radiosurgery for
primary malignant spinal tumors. Neurol Res 2014;36(6):597-606.
29. Kim HJ, McLawhorn AS, Goldstein MJ, Boland PJ: Malignant
osseous tumors of the pediatric spine. J Am Acad Orthop Surg
2012;20(10):646-656.
30. Mukherjee D, Chaichana KL, Gokaslan ZL, Aaronson O, Cheng
JS, McGirt MJ: Survival of patients with malignant primary
osseous spinal neoplasms: Results from the Surveillance,
Epidemiology, and End Results (SEER) database from 1973 to
2003. J Neurosurg Spine 2011;14(2):143-215.
31. Pombo B, Ferreira A, Cardoso P, Oliveira A: Clinical
effectiveness of Enneking appropriate versus Enneking
inappropriate procedure in patients with primary osteosarcoma
of the spine: A systematic review with meta-analysis. Eur Spine J
2020;29(2):238-247. This is a systematic review with meta-analysis
of patients undergoing treatment for primary osteosarcoma of
the spine, evaluating metastasis, local recurrence, and overall
survival in patients undergoing Enneking-appropriate or
Enneking-inappropriate procedures. Five studies were included
with 108 patients. At 24 months, patients receiving Enneking-
appropriate procedures had a lower recurrence and metastasis
rate and higher survival; however, there was no significant
 survival, recurrence, or metastasis rate at 12 months. Level of
evidence: III.
32. Schoenfeld AJ, Hornicek FJ, Pedlow FX, et al: Osteosarcoma of
the spine: Experience in 26 patients treated at the Massachuse s
General Hospital. Spine J 2010;10(8):708-714.
33. Volker T, Denecke T, Steffen I, et al: Positron emission
tomography for staging of pediatric sarcoma patients: Results of
a prospective multicenter trial. J Clin Oncol 2007;25:5435-5441.
34. Mirzaei L, Kaal SE, Schreuder HW, Bartels RH: The neurological
compromised spine due to Ewing sarcoma. what first: surgery or
chemotherapy? Therapy, survival, and neurological outcome of 15
cases with primary Ewing sarcoma of the vertebral column.
Neurosurgery 2015; November [Epub ahead of print].
35. Bacci G, Boriani S, Balladelli A, et al: Treatment of
nonmetastatic Ewing’s sarcoma family tumors of the spine and
sacrum: The experience from a single institution. Eur Spine J
2009;18(8):1091-1095.
36. Goldstein C, Varga P, Gokaslan Z, Boriani S: Spinal
hemangiomas: Results of surgical management for local
recurrence and mortality in a multicenter study. Spine
2015;40(9):656-664.
37. Mesfin A, Boriani S, Gambaro i M, Bandiera S, Gasbarrini A:
Can osteoblastoma evolve to malignanancy? A challenge in the
decision-making process for a benign spine tumor. World
Neurosurg 2020;136:150-156. Two cases of rare spinal
osteoblastoma recurring and transforming into osteosarcoma are
reported. Enneking-appropriate procedures should be
undertaken for benign, locally aggressive pathology. Repeat
biopsy at time of recurrence of known tumor should be
undertaken if imaging is not pathognomonic for benign process
or if significant changes are noted. Level of evidence: IV.
38. Jia Q, Liu C, Yang J, et al: Factors affecting prognosis of patients
with osteoblastoma of the mobile spine: A long-term follow-up
study of 70 patients in a single center. Neurosurgery 2020;86(1):71-
 79. This is a retrospective series of 70 patients with osteoblastoma
of the mobile spine in a single center. Epithelioid osteoblastoma
and Enneking stage 3 tumors were found to be more aggressive
and associated with lower recurrence-free survival than
conventional osteoblastoma or Enneking stage 2 lesions.
Recurrence rates were lower in patients receiving total en bloc
spondylectomy. Level of evidence: III.
39. Harrop JS, Schmidt MH, Boriani S, Shaffrey CI: Aggressive
“benign” primary spine neoplasms: Osteoblastoma, aneurysmal
bone cyst, and giant cell tumor. Spine 2009;34(22 suppl):S39-S47.
40. Yin H, Zhou W, Yu H, et al: Clinical characteristics and
treatment options for two types of osteoblastoma in the mobile
spine: A retrospective study of 32 cases and outcomes. Eur Spine J
2014;23(2):411-416.
41. Papagelopoulos PJ, Currier BL, Shaughnessy WJ, et al:
Aneurysmal bone cyst of the spine. Management and outcome.
Spine (Phila Pa 1976) 1998;23(5):621-628.
42. Terzi S, Gasbarrini A, Fuiano M, et al: Efficacy and safety of
selective arterial embolization in the treatment of aneurysmal
bone cyst of the mobile spine: A retrospective observational
study. Spine 2017;42(15):1130-1138.
43. Barbanti-Brodano G, Girolami M, Ghermandi R, et al:
Aneurysmal bone cyst of the spine treated by concentrated bone
marrow: Clinical cases and review of the literature. Eur Spine J
2017;26(suppl 1):158-166.
44. Bukata S, Blay J, Rutkowski P, et al: Denosumab treatment for
giant cell tumor of the spine including the sacrum. Spine
2021;46(5):277-284. In an international, open label, single-arm
phase 2 study of safety and efficacy of denosumab in patients
with GCT of the spine, including the sacrum, clinical benefit was
reported in 83% of patients. Denosumab is a potentially effective
treatment for GCT of the spine and may be of significant clinical
value, particularly in patients in whom surgical resection is not
safely feasible. Level of evidence: II.
45. Wong DA, Fornasier VL, MacNab I: Spinal metastases: the
obvious, the occult, and the impostors. Spine 1990;15:1-4.
46. Yuh WT, Quets JP, Lee HJ, et al: Anatomic distribution of
metastases in the vertebral body and modes of hematogenous
spread. Spine 1996;21(19):2243-2250.
47. Barzilai O, Fisher C, Bilsky M: State of the art treatment of
spinal metastatic disease. Neurosurgery 2018;82(6):757-769.
48. Zeng K, Sahgal A, Husain Z, et al: Local control and pa erns of
failure for “radioresistant” spinal metastases following
stereotactic body radiotherapy compared to a “radiosensitive”
reference. J Neuro Oncol 2021;152(1):173-182. A prospectively
maintained database of 1394 spinal segments in 605 patients
treated with stereotactic body radiation therapy for metastatic
spinal tumors classified as radioresistant (renal cell, melanoma,
sarcoma, gastrointestinal, and thyroid cancers) was compared
with a cohort treated for radiosensitive prostate cancer
metastasis. Local failure (disease progression) was higher in
patients with radioresistant tumors than in prostate cancer
cohort. The presence of epidural disease as well as lung and liver
metastasis were independent poor prognostic factors for local
failure and overall survival. Level of evidence: II.
49. Paulino P, Janssen S, Van Dijk E, et al: Development of a
prognostic survival algorithm for patients with metastatic spine
disease. J Bone Joint Surg Am 2016;98(21):1767-1776.
50. Shah A, Karhade A, Park H, et al: Updated external validation of
the SORG machine learning algorithms for prediction of ninety-
day and one-year mortality after surgery for spinal metastasis.
Spine J 2021;21(10):1679-1686. A retrospective cohort study to
externally validate the Skeletal Oncology Research Group (SORG)
machine learning algorithm for prediction of 90-day and 1-year
survival in patients with spinal metastatic disease was performed.
Included were 298 patients treated surgically for spinal
metastasis at a single center. Results for 90-day and 1-year
survival were compared with the SORG calibration cohort and
 were found to be well calibrated. This study demonstrated a
successful independent, external validation of the SORG
algorithm for prediction of 90-day and 1-year survival in patients
with spinal metastatic disease. Level of evidence: III.
51. Levack P, Graham J, Collie D, et al: Don’t wait for a sensory
level–listen to the symptoms: a prospective audit of the delays in
diagnosis of malignant cord compression. Clin Oncol
2002;14(6):472-480.
52. Quraishi NA, Rajagopal TS, Manoharan SR, Elsayed S, Edwards
KL, Boszczyk BM: Effect of timing of surgery on neurological
outcome and survival in metastatic spinal cord compression. Eur
Spine J 2013;22(6):1383-1388.
53. Patchell RA, Tibbs PA, Regine WF, et al: Direct decompressive
surgical resection in the treatment of spinal cord compression
caused by metastatic cancer: a randomised trial. Lancet
2005;366(9486):643-648.
54. Wiggins GC, Mirza S, Bellabarba C, West GA, Chapman JR,
Shaffrey CI: Perioperative complications with
costotransversectomy and anterior approaches to thoracic and
thoracolumbar tumors. Neurosurg Focus 2001;11(6):e4.
55. Lubelski D, Abdullah KG, Steinme MP, et al: Lateral
extracavitary, costotransversectomy, and transthoracic
thoracotomy approaches to the thoracic spine: Review of
techniques and complications. J Spinal Disord Tech 2013;26(4):222-
232.
56. Laufer I, Iorgulescu JB, Chapman T, et al: Local disease control
for spinal metastases following “separation surgery” and
adjuvant hypofractionated or high-dose single-fraction
stereotactic radiosurgery: Outcome analysis in 186 patients. J
Neurosurg Spine 2013;18(3):207-214.
57. Lau D, Chou D: Posterior thoracic corpectomy with cage
reconstruction for metastatic spinal tumors: Comparing the mini-
open approach to the open approach. J Neurosurg Spine
2015;23(2):217-227.
58. Abdelgawaad A, Ezzati A, Krajnovic B, Seyed-Emadaldin S,
Abdelrahman H: Radiofrequency ablation and balloon
kyphoplasty for palliation of painful spinal metastases. Eur Spine
J 2021;30(10):2874-2880. In this prospective study of palliative
efficacy of radiofrequency ablation and balloon kyphoplasty in
patients with painful spinal metastasis, 75 painful lesions in 60
patients were managed. Visual analog scale pain score was
improved in a statistically significant manner before and after
procedure (7.2 of 10 to 2.7 of 10). No neurologic complications
were noted. Radiofrequency ablation and balloon kyphoplasty
may be an effective palliative treatment for patients with painful
spinal metastasis without significant morbidity and
complications associated with traditional surgical treatment.
Level of evidence: IV.
59. Sharan AD, Szulc A, Krystal J, Yassari R, Laufer I, Bilsky MH:
The integration of radiosurgery for the treatment of patients with
metastatic spine diseases. Am Acad Orthop Surg 2014;22(7):447-
454.
60. Colman MW, Kirkwood JM, Scho T, Goodman MA, McGough
RL III: Does metastasectomy improve survival in skeletal
melanoma? Melanoma Res 2014;24(4):354-359.
61. Meyer T, Merkel S, Goehl J, Hohenberger W: Surgical therapy
for distant metastases of malignant melanoma. Cancer
2000;89(9):1983-1991.
62. Kato S, Murakami H, Takeuchi A, et al: Fifteen-year survivor of
renal cell carcinoma after metastasectomies for multiple bone
metastases. Orthopedics 2013;36(11):e1454-1457.
S E C T I O N 11

Pediatrics
SECTION EDITOR
Jonathan G. Schoenecker, MD, PhD, FAAOS
C H AP T E R 5 8

Pediatric Shoulder, Upper Arm,

and Elbow Trauma
Jessica H. Heyer MD, Alexandre Arkader MD, FAAOS

Dr. Arkader or an immediate family member has received royalties from OrthoPediatrics; serves
as a paid consultant to or is an employee of OrthoPediatrics; and serves as a board member,
owner, officer, or committee member of the Pediatric Orthopaedic Society of North America.
Neither Dr. Heyer nor any immediate family member has received anything of value from or has
stock or stock options held in a commercial company or institution related directly or indirectly to
the subject of this chapter.

ABSTRACT
Shoulder, upper arm, and elbow injuries are common reasons for
pediatric patients to seek medical treatment. Diagnosing and
treating these injuries requires knowledge of the ossification
pa erns of the elbow and shoulder. Providers must be aware of
treatment options that are available to the pediatric population,
which often differ from those for the adult population. It is
important to review the presentation, diagnosis, and treatment
options for various injuries of the clavicle, shoulder, humerus, and
elbow.
Keywords: clavicle fracture; humeral shaft fracture; lateral condyle
fracture; medial epicondyle fracture; pediatric upper extremity
trauma; supracondylar humerus fracture

Introduction
Pediatric upper extremity trauma is common, with treatments
including both surgical and nonsurgical management. The
evaluation should begin with a thorough history and physical
examination. As the only indications for emergent care for these
fractures are neurovascular or open injuries, the physical
examination should specifically identify if these injuries are or are
not present. When assessing a long bone, radiographs of the bone
and the adjacent joints should be obtained; similarly, when
assessing a joint, the long bone or bones proximally and distally
should be imaged as well. Interpretation of radiographs requires
knowledge of the age-dependent ossification pa erns of the
developing upper extremity and the relative contributions of the
most proximate physis (Figure 1).

Figure 1 Illustration showing anterior (A) and lateral (B) views of secondary
ossification centers of the elbow, with ages of appearance.(Reproduced from
Skaggs DL: Elbow fractures in children: Diagnosis and management. J Am
Acad Orthop Surg 1997;5[6]:303-312.)

Sternoclavicular Joint Injuries

The sternoclavicular joint connects the upper extremity to the axial
skeleton. The medial clavicle is the last bone to ossify and last
physis to close, at approximately age 18 to 20 years and 23 to 25
years, respectively. 1 Therefore, an injury that may initially appear
to be a sternoclavicular dislocation may instead be a physeal injury.
The sternoclavicular joint is a diarthrodial joint that is stabilized by
the costoclavicular ligament and sternoclavicular capsule.
Sternoclavicular dislocations/physeal injuries often occur because
of indirect trauma to the shoulder joint and present with swelling
and pain localized to the joint. 1 Less commonly, a high-energy
direct blow to the sternoclavicular joint can result in injury. When a
sternoclavicular injury is suspected on radiographs, serendipity
radiographic views and advanced imaging are recommended.
The joint can dislocate both anteriorly and posteriorly. Anterior
dislocations represent between 95% and 97% of dislocations and
are managed with a sling. 2 Acute anterior dislocations can be
managed with sedation and reduction within 7 to 10 days of injury,
but redislocation occurs in 50% of patients. 3 Although there are
limited cohorts of patients with anterior sternoclavicular
dislocations and long-term follow-ups, a small study of five patients
demonstrated four patients with good/excellent outcomes and only
one with fair/poor outcomes. 4 As discussed in a 2020 study,
posterior dislocations or posteriorly displaced fractures can lead to
impingement of the clavicle on mediastinal structures (the trachea,
esophagus, brachial plexus, and vascular structures), so they often
require surgical management. 5 These posterior dislocations are
reduced in an operating room with a cardiothoracic or vascular
surgeon on standby. Closed reduction is often unsuccessful or
unstable and can potentially lead to impingement of mediastinal
structures or chronic instability, so fixation is advocated. 5 Fixation
methods include all-suture fixation, wire cerclage fixation, and plate
fixation; Kirschner wire fixation is not recommended given
migration potential. Postoperatively, patients are non–weight
bearing in a sling for 4 to 6 weeks, followed by weight bearing as
tolerated and progressive motion, with return to all activities by 3
months. 6 , 7 A 2021 study of 37 patients who underwent open
reduction and suture fixation of acute posterior sternoclavicular
fracture-dislocations with 5-year follow-up demonstrated good
functional outcomes, with most patients returning to full activity
with no pain. Despite this, 29% of the patients reported that their
injury affected their ability to participate in sports, citing difficulty
with recreational activities that involve impact to the involved
upper extremity. 6

Clavicle Fractures
Clavicle fractures make up 8% to 15% of all pediatric fractures, with
up to 85% occurring in the middle third, and are seen in all age
ranges. 8 Newborns may sustain birth-related fractures and present
with pseudoparalysis of the arm because of pain. Birth-related
fractures may also have concomitant brachial plexus injuries, so the
patient should be evaluated with a thorough neurologic
examination of the extremity. Infants with a clavicle fracture can be
treated with pinning of the sleeve of the injured arm to the chest or
with a swaddle. In an infant with an incidental finding of a clavicle
fracture on radiographs with no tenderness, pseudarthrosis of the
clavicle should be considered. Congenital pseudarthrosis presents
with diaphyseal disruption, rounded-off edges of the clavicle on
radiographs, is nontender, and usually on the right side because of
the subclavian arch position. 9
Children and adolescents with clavicle fractures are generally
treated nonsurgically, although this continues to be a source of
debate (Figure 2). Absolute surgical indications include vascular
injury, threatening of the skin, and open fractures; relative surgical
indications include significant shortening (2 cm) of the shoulder
girdle, particularly on the dominant side in high-level athletes. 10
 Figure 2 A, Radiograph of an acute left clavicle fracture with 100%
displacement. B, Radiograph of the same left clavicle fracture after 3 months of
nonsurgical management, showing interval healing.(Reproduced with
permission from Children’s Hospital of Philadelphia, Division of Orthopaedic
Surgery, Philadelphia, PA.)

A 2019 systematic review demonstrated that surgical fixation of

displaced midshaft clavicle fractures resulted in faster return to
activity and improved Constant scores, but it came at the cost of
higher complications and frequent secondary surgical procedures
to remove implants. 11 From 1999 to 2011, an increase in surgical
fixation of clavicle fractures in adolescents was observed, despite a
lack of evidence-based support. 8 Adolescent patients who are
treated for clavicle fractures in adult hospitals are five times more
likely to undergo surgical fixation, compared with those treated in
pediatric hospitals. 12
However, more recent studies have found that there is no
difference in outcomes in managing midshaft clavicle fractures
surgically versus nonsurgically. In multiple studies, both groups
have good functional outcomes and equivalent functional scores,
and nonsurgical patients were found to have equal or be er
cosmetic satisfaction. 13 - 15

Shoulder Dislocation
Shoulder dislocations are less common in the pediatric population
as the proximal humeral physis usually fails before the soft tissues
of the joint. Most shoulder dislocations in the pediatric population
occur in male adolescents during contact sports. 16 Diagnostic
radiographs should include an AP, scapular Y, and axillary views.
Most commonly, the dislocation is anterior.
Patients undergo closed reduction, and the arm is placed into a
sling. A postreduction neurologic examination should be
documented; the axillary nerve is the most injured nerve. For first-
time dislocators, patients can participate in physical therapy after a
1- to 2-week period of immobilization. 17 Males and younger
patients are more likely to sustain a second dislocation, with more
than 70% sustaining a repeat dislocation. 18 , 19 Given this statistic,
and the damage that each dislocation has been found to cause to
the glenoid, there has been a recent push for surgical management
after first-time dislocations in high-risk patients. 16 , 20 In patients
with recurrent dislocations, surgery may be indicated to prevent
recurrence. Surgery, whether arthroscopic or open, is dictated by
concurrent pathology in the shoulder, including Hill-Sachs lesions,
labral tears, or bony Bankart lesions.

Proximal Humerus Fractures

Proximal humerus fractures account for 2% of all pediatric
fractures. 21 The proximal humerus physis provides 80% of the
growth of the bone, providing ample remodeling potential. Thus,
most proximal humerus fractures can be managed nonsurgically. In
patients older than 5 years, most fractures are Salter-Harris type II
extending into metaphysis (Figure 3).

Figure 3 A, Two radiographic views of an acute left proximal humerus fracture.

B, Left shoulder radiograph demonstrating the healed proximal humerus fracture
6 months after injury.(Reproduced with permission from Children’s Hospital of
Philadelphia, Division of Orthopaedic Surgery, Philadelphia, PA.)

Nondisplaced fractures, or fractures that are sustained

perinatally, can be managed with a sling, shoulder immobilizer, or
a hanging arm cast in the older patient for 3 to 4 weeks duration. 21
The only absolute surgical indications are open fractures and
fractures associated with vascular injury. 22 There is controversy
surrounding what angulation or displacement necessitates surgical
fixation; surgery may be beneficial if patients are older than 13
years, with angulation of over 40°, or with more than two-thirds
displacement of the shaft width (Neer IV). 21 , 22 Of note, an absolute
number for angulation has not been defined by the literature.
Patients with a block to internal/external rotation motion due to
impingement of the shortened shaft on the glenoid or who have a
block to reduction due to interposition of the biceps tendon will
benefit from reduction and surgical fixation. Younger patients with
more growth left tolerate more angulation and displacement than
older patients. Surgical fixation options include closed or open
reduction and fixation with percutaneous wires, cannulated screws,
plates, or retrograde elastic intramedullary nails, all of which have
been shown to have excellent outcomes. 22 Depending on the
fracture severity and specific sport, most patients return to full
activities by 3 to 4 months after surgical fixation. 21

Humeral Shaft Fractures

Humeral shaft fractures account for 5% of all pediatric fractures,
and they most commonly occur in patients younger than 3 years or
older than 10 years. 23 When associated with birth injury, infants
require reassessment to evaluate for possible concomitant brachial
plexus palsy, which occurs in nearly one-fourth of birth-related
humeral shaft fractures. 24 Patients may also present with initial
pseudoparalysis because of pain of the fracture. Humeral shaft
fractures in infants are managed with a swathe or pinning of a
sleeve to the chest.
Older children and adolescents with humeral shaft fractures are
most often treated nonsurgically with a coaptation splint,
Sarmiento brace, or hanging arm cast for approximately 6 weeks. 23
Surgical fixation is indicated for open fractures and may be
indicated for greater than 15° to 30° angulation, particularly those
with varus angulation, with less angulation tolerated with more
distal fractures. 25 Flexible elastic intramedullary nails, plating, and
external fixation techniques have all been described. 23 After flexible
nailing, patients are immobilized for 1 to 2 weeks, and radiographic
union is achieved between 7 and 10 weeks postoperatively. 23 , 25
When compared with nonsurgical management, surgical
management was found to have shorter immobilization time and
improved radiographic appearance but showed no difference in
functional long-term outcomes or pos reatment pain. 23

Supracondylar Humerus Fractures

Supracondylar humerus fractures are the most common elbow
fractures in the pediatric population and commonly occur in
patients between age 5 and 8 years. They are classified based on the
direction of displacement, either into extension or flexion. More
than 90% of the fractures are extension type, which is further
classified by the Gartland classification system. 26 The Gartland
classification system is based on posterior displacement of the
distal fragment (Figure 4). On the lateral elbow radiograph, the
anterior humeral line should intersect the middle third of the
capitellum, unless a patient is younger than 5 years, in which case
the anterior humeral line should touch the capitellum. 26 Type I
fractures are nondisplaced or minimally angulated, and on a lateral
elbow radiograph, they may only be evident based on a posterior
fat pad sign. Type II fractures have an intact posterior hinge,
whereas type III fractures are completely displaced posteriorly
because of complete disruption of the posterior cortex. A
modification to the Gartland classification added a type IV, which
can only be diagnosed intraoperatively. In type IV fractures, there
is circumferential disruption of both the anterior and posterior
periosteum, creating a fracture that is grossly unstable in both
flexion and extension.
 Figure 4 A, Lateral radiograph of a Gartland type I supracondylar humerus
fracture, demonstrating a posterior fat pad sign. B, Lateral radiograph of a
Gartland type II supracondylar humerus fracture. C, Lateral radiograph of a
Gartland type III supracondylar humerus fracture.(Reproduced with permission
from Children’s Hospital of Philadelphia, Division of Orthopaedic Surgery,
Philadelphia, PA.)

Patients with type I fractures are treated with a long arm cast for
3 to 4 weeks. Type III and many type II fractures are managed
surgically because of poor remodeling potential of the distal
humerus and to minimize the risk of malunion in extension,
disturbance of the normal arc of motion, and cubitus valgus. 27
Flexion-type supracondylar humerus fractures are also managed
surgically because these are unstable injuries similar to Gartland
III extension-type injuries.
A thorough preoperative neurologic examination is important
because it may reveal a nerve palsy in the upper extremity, which
has been found to occur in 11% of patients with supracondylar
humerus fracture. 28 Extension types are most commonly associated
with anterior interosseous nerve (AIN) palsies (5.3%), followed by
radial (4.5%), median (3.3%), and ulnar nerve palsies (2.3%),
whereas flexion types are most commonly associated with ulnar
nerve palsies (16%). 28 Patients with AIN or median nerve palsies
may lose their ability to detect worsening pain that can be a sign of
early compartment syndrome, so preoperatively they should
undergo frequent examinations for impending compartment
syndrome (pain with passive stretch, increasing pain, or increased
need for pain medication). Patients with isolated AIN palsies often
regain function without further intervention within 2 to 3 months
of injury. 29 It is important to also evaluate these patients for
ipsilateral upper extremity concomitant injuries, including of the
distal radius and diaphyseal forearm fractures, which increase their
risk of forearm compartment syndrome. 26
Surgical fixation involves closed reduction and percutaneous pin
fixation of the distal humerus, with the goal of restoring the
position of the anterior humeral line on lateral radiographs and
restoring coronal alignment; an open reduction may be required in
patients with unstable fractures or with periosteum,
brachioradialis, or neurovascular structures interposed in the
fracture site. Extension-type fractures are reduced with milking of
the arm to release the brachialis from the fracture site, and then
with traction and flexion of the elbow, followed by either pronation
of the wrist to close the lateral border or supination to close the
medial border. Pin configuration may vary because of the fracture
pa ern, but often two to three divergent lateral pins are used to
achieve maximal spread. Construct stability is enhanced by using
larger diameter pins, increased number of pins, and use of a medial
pin. 30 A medial pin can be placed in patients with persistent
rotational instability following appropriately placed lateral pins,
but the surgeon must be cognizant about the location of the ulnar
nerve during medial pin placement. Postoperatively, pins are
removed at 3 to 4 weeks, and the patient is allowed to move the
elbow. Studies have shown that normal range of motion usually
returns by 2 months and that a referral to physical therapy to
restore motion is often unnecessary. 31 , 32
Dysvascular extremities in the se ing of supracondylar humerus
fractures can be classified as pulseless but perfused, where the
capillary refill is less than 2 seconds and the hand is of skin color
that is normal for the patient, or pulseless and not perfused, when
the hand is absent of color. Dysvascular extremities should be taken
to the operating room emergently, aiming to restore blood flow to
the distal extremity. The brachial artery and/or median nerve may
be draped over the fracture fragment or may be entrapped in the
fracture site; up to 14% of patients with absent pulses have a true
vascular injury. 33 In a patient with a pulseless hand and AIN or
median nerve palsy, there should be a high suspicion for a
concurrent injury to the brachial artery or need for open reduction.
In a study of pulseless supracondylar humerus fractures with AIN
or median nerve palsy, 27% required open reduction and 8%
developed compartment syndrome. 34
Closed reduction is the first step in the management of these
extremities, and often it will restore the pulse (palpable or by
Doppler) to the radial artery or will at least improve perfusion to
the hand despite continued absence of the pulse as a result of
brachial artery vasospasm. To improve blood flow, the room can be
warmed, and warm towels can be placed onto the extremity. A hand
that remains nonperfused (pulseless and without color) after closed
reduction and pinning requires removal of pins and likely vascular
exploration. A hand that is perfused (of normal color) but pulseless
is a source of management controversy but can often be managed
with close observation postoperatively. The American Academy of
Orthopaedic Surgeons recommendations are inconclusive
regarding open exploration of patients with absent pulses and well-
perfused hands. 35
T-type distal humerus fractures represent a unique subtype of
supracondylar humerus fractures because they have intra-articular
extension. These injuries tend to occur in adolescents (older than 10
years) and are sustained after a fall onto a flexed elbow. 36 Because
of the intra-articular extension, these fractures generally require
open surgical fixation to maintain the lengths of the medial and
lateral columns, as well as to restore congruency of the articular
surface. 37

Lateral Condyle Fractures

Lateral condyle fractures (Figure 5) are the second most common
fracture of the elbow, comprising 10% to 20% of all pediatric elbow
fractures. 38 These fractures are intra-articular and therefore require
near-anatomic reduction; the articular surface can be difficult to
assess because of the largely cartilaginous portion of the lateral
condyle in younger patients. In addition to standard elbow
radiographs, an internal oblique view best demonstrates fracture
displacement of the lateral condyle. Fractures with more than 2 mm
of displacement, as measured on the internal oblique radiograph,
should undergo intervention, whereas those with less than 2 mm of
displacement can be managed with a long arm cast. 39 , 40 The
underlying stability of the fracture has been found to be conferred
by the integrity of the cartilaginous hinge. 41
 Figure 5 A, AP and lateral radiographs of an acute lateral condyle fracture. B,
AP and lateral radiographs obtained following open reduction and percutaneous
pinning.(Reproduced with permission from Children’s Hospital of Philadelphia,
Division of Orthopaedic Surgery, Philadelphia, PA.)

Nonsurgical management entails immobilization in a long arm

cast for 4 to 5 weeks. 40 Surgical fixation to restore articular
congruity can be performed with closed or open reduction and
percutaneous pin fixation or compression screws. Assessment of
the articular surface and the integrity of the lateral cartilaginous
hinge after a closed reduction can be aided by elbow arthrography.
When an open reduction is required, a lateral approach is used,
with care taken to avoid dissecting the soft tissues on the posterior
aspect of the lateral condyle to preserve the blood supply and
decrease risks of osteonecrosis. Fractures can be fixed with two to
three divergent smooth pins, which are removed at 4 to 6 weeks
postoperatively. Often more divergent pins are needed, especially
in very cartilaginous fragments in younger children. These fractures
may take a prolonged time to heal because of the synovial fluid that
bathes the fracture site; therefore, cast immobilization may need to
be extended after pin removal up to 8 weeks postoperatively. 38 , 40
The most common complication is lateral spur formation because
of bony overgrowth, which is correlated with the amount of initial
fracture displacement (periosteal lift), and it only has cosmetic
implications. 42
Nonsurgical management of displaced fractures, missed
fractures, or even appropriately managed lateral condyle fractures
can result in nonunion (1%), cubitus valgus (0.4%), malunion
(0.6%), osteonecrosis (1.4%), or tardy ulnar nerve palsy. 43

Medial Epicondyle Fractures

Medial epicondyle fractures can occur in isolation or concomitantly
with elbow dislocations (Figure 6). The medial epicondyle is the
a achment point for the ulnar collateral ligament and flexor
pronator mass, and it can be avulsed with a large valgus force (ie,
during overhead throwing) or after a fall. Displacement of medial
epicondyle fractures can be difficult to assess on a standard AP or
lateral radiograph because the piece usually displaces anteriorly;
the distal humeral axial view has been described to be er assess
the displacement of the fracture. 44 Historically, medial epicondyle
fractures were mostly managed without surgery in a long arm cast
for 3 to 4 weeks with return to sport at 3 months. 45 Indications for
surgical fixation include fragments entrapped in the joint after
elbow dislocation reduction, presence of elbow instability, or
greater than 5 mm of displacement. Increasing arguments are
being made for fixation to allow early motion of the elbow and
improve elbow stability in the se ing of a concomitant dislocation.
The fracture can be stabilized with Kirschner wires in young
children or with cannulated screws in older children. Care must be
taken to avoid injury to the ulnar nerve at the time of fixation
regardless of implant. A 2019 study of surgeon variation in the
management of medial epicondyle fractures demonstrated that
concomitant elbow dislocation and increasing fracture
displacement were the two main factors that lead a surgeon to opt
for surgical management; at 8 mm, most surgeons opted for
surgical fixation, and all opted for fixation with 19 mm of
displacement or more. 46
Figure 6 A, AP and lateral radiographs demonstrating an elbow dislocation and
associated medial epicondyle fracture. B, AP and lateral intraoperative
radiographs obtained after open reduction and screw fixation of the medial
epicondyle fracture, with interval reduction of the elbow dislocation.(Reproduced
with permission from Children’s Hospital of Philadelphia, Division of Orthopaedic
Surgery, Philadelphia, PA.)
 A 2020 systematic review found higher union rates with surgical
management compared with nonsurgical management, as well as
earlier allowance of motion and return to sport. 44 Patients with
ulnar nerve symptoms following injury had improved resolution
following surgical management.

Elbow Dislocation
As discussed previously, elbow dislocations can occur with a
concomitant elbow fracture (most commonly medial epicondyle)
but can also occur in isolation. Ulnohumeral dislocations account
for approximately 3% of pediatric elbow injuries and are most
frequently posterior or posterolateral. 47 In very young patients,
radiographs must be scrutinized to differentiate an elbow
dislocation from a transphyseal separation, which can be associated
with child abuse and requires surgical fixation. 48
Elbow dislocations should be reduced closed, with close
assessment of postreduction radiographs for concentricity of the
reduction and possible entrapped fragments (most commonly the
medial epicondyle). If the reduction is acceptable, the patient is
immobilized for up to 2 weeks in a long arm cast before range of
motion is allowed; return to full sport usually occurs by 5 months
postoperatively. 45 Longer periods of immobilization are associated
with loss of terminal extension. 47 Surgical intervention is required
for entrapped fragments, as discussed previously, or may be
indicated based on concomitant injuries or persistent instability. 48

Olecranon Fractures
Olecranon fractures are less common in the pediatric population,
accounting for approximately 7% of all pediatric elbow fractures. 49
They are often due to avulsion of the proximal apophysis by the
triceps. They can also occur secondary to a dislocation or direct
trauma. Nonsurgical management in a cast for 4 weeks is
acceptable for patients with minimally displaced fractures and
those with maintained articular congruity. 50 Displaced fractures
require surgical fixation to restore normal triceps function (Figure
7). Options for fixation include using tension band technique with
wires or sutures, a single cannulated screw for transverse,
noncomminuted fractures, or open reduction with plating for
comminuted fractures. 49 Postoperatively, patients are immobilized
for up to 4 weeks and then allowed motion as tolerated. 50
Atraumatic, bilateral, or avulsion olecranon fractures should raise
concern for osteogenesis imperfecta. 48

Figure 7 A, Lateral radiograph of an olecranon fracture. Intraoperative lateral

(B) and AP (C) imaging obtained after open reduction and pinning of the
olecranon fracture.(Reproduced with permission from Children’s Hospital of
Philadelphia, Division of Orthopaedic Surgery, Philadelphia, PA.)

Radial Head and Radial Neck Fractures

Radial neck fractures are more common than radial head fractures
in the pediatric population and constitute 5% to 10% of all pediatric
elbow injuries 51 (Figure 8). Radial neck fractures are typically
sustained after a fall onto an outstretched arm with a valgus force
and can be sustained during an elbow dislocation. Radiographs
should include a Greenspan view, which helps assess the
radiocapitellar joint. A posterior fat pad sign on lateral radiograph
may be indicative of an occult elbow fracture, including a
nondisplaced fracture of the radial neck. In all radiographic views,
the radial neck and head should be pointing at the capitellum.

Figure 8 A, AP and lateral radiographs of an acute radial neck fracture. B, AP

and lateral arthrograms obtained following reduction of the radial neck. C,
Postoperative AP and lateral radiographs demonstrating the reduced radial neck
fracture.(Reproduced with permission from Children’s Hospital of Philadelphia,
Division of Orthopaedic Surgery, Philadelphia, PA.)

In patients younger than 10 years, angulation of up to 45° may be

acceptable; and if older than 10 years, angulation of up to 30° and 2
mm of translation can be acceptable. If outside these parameters,
closed reduction should be the first line of treatment. 51 Only a very
small amount of translation of the radial head is tolerated because
of the risk of creating a cam effect that will block motion. Various
closed reduction techniques have been described: these include the
Pa erson technique, which involves applying direct pressure to the
radial head with the elbow in extension and supination with a varus
force, the Israeli technique, or the Esmarch technique. 51 After
closed reduction, the elbow is immobilized in a long arm cast for 2
to 3 weeks. A 2021 study evaluated which radial neck fractures were
likely to have failed closed reduction in the emergency department;
they found that patients who had at least 60° of angulation or
presented more than 24 hours after injury were more likely to
require surgical intervention. 52
If closed reduction is unsuccessful, surgical fixation is warranted.
Percutaneous assisted reduction using the blunt side of a Steinman
pin or other blunt instrument may lever the head into reducible
position, as can a retrograde nail placed up the radius to capture
the head (ie, the Métaizeau technique). When open reduction is
required, care must be taken to avoid the posterior interosseous
nerve. When using a Kaplan or Kocher approach, the posterior
interosseous nerve can be brought out anteriorly from the surgical
field by pronating the forearm. Plate fixation is rarely needed but
must stay in the safe zone of the proximal radius, which is the 90°
arc between the radial styloid and Lister tubercle, to avoid
impingent during supination and pronation. 53 After open
treatment, the complication rate approaches 40%, with the most
common being stiffness in pronation and supination; physical
therapy is often required in this population. Other compilations
include heterotopic ossification, osteonecrosis, radioulnar
synostosis, and posterior interosseous nerve injury. 54

Volkmann Ischemia
Volkmann ischemia is a rare complication of upper extremity
injuries secondary to a missed compartment syndrome, occlusion
of the artery, or both. 55 Acute compartment syndrome occurs when
there is too much swelling and pressure within a fascial
compartment of a limb and leads to irreversible death of the
muscles and nerves within the compartment. Acute compartment
syndrome is difficult to diagnose in the pediatric population; in this
population, the three A’s—anxiety, agitation, and increasing
analgesic requirements—are important signs of impending
compartment syndrome. Pain with passive stretch of the muscles
within the implicated compartment is another early sign but
requires the patient to be able to communicate and cooperate with
an examination. Younger age is associated with a delay in diagnosis
because of difficulty with examination and communication. 56
Volkmann ischemia and the resulting Volkmann ischemic
contracture occurs after acute compartment syndrome in the volar
forearm compartment, which results in necrosis and scarring of the
flexor muscles. This leads to a flexion deformity of the wrist and
fingers, which can be functionally devastating. Patients with
displaced supracondylar fractures, particularly those with vascular
or median nerve injuries, are at highest risk of this complication. If
compartment syndrome is identified early, emergent fasciotomies
are recommended; similarly, if an arterial occlusion is identified
without collateral flow, the occlusion should be addressed
emergently.
A 2019 study evaluated 26 patients who had sustained a
supracondylar humerus fracture associated with ischemic injury
and subsequently developed ischemic contracture of the forearm
muscles. 55 This study suggested that in a patient with a pulseless
supracondylar humerus fracture with worsening pain and evolving
nerve injury, treatment of the fracture should include exploration of
the vessel and nerve to ensure adequate decompression and
decrease the risk of limb ischemia.

Summary
Fractures and dislocations of the pediatric upper extremity are
unique entities compared with adult fractures and are a common
reason for referral to a clinician. Correct diagnosis and
management of these injuries help restore function in a timely
manner.

Key Study Points

Most clavicle fractures in the pediatric population can be managed nonsurgically,
with surgical management reserved for patients with vascular injury, open fractures,
and severe skin tenting.
The high growth potential of the proximal humerus, as well as the motion of the
shoulder joint, enables displaced proximal humerus fractures to be managed
nonsurgically with good remodeling and excellent functional outcomes.
The emergent versus urgent timing of surgical fixation for perfused pulseless
supracondylar humerus fractures remains debated. However, patients with a
pulseless hand with increasing pain and a median nerve injury are at high risk of
having a concomitant brachial artery injury.
The integrity of the cartilaginous hinge in a lateral condyle confers stability of the
fracture and its ability to be managed nonsurgically or via percutaneous means.
 Indications for medial epicondyle fracture fixation remain contested, with more
surgeons opting for surgical fixation in the setting of elbow dislocations or with
greater displacement of the fracture fragment. However, an entrapped medial
epicondyle within the joint is an absolute indication for surgical management.

Annotated References
1. Groh GI, Wirth MA: Management of traumatic sternoclavicular
joint injuries. J Am Acad Orthop Surg 2011;19(1):1-7.
2. Camara EH, Bousso A, Tall M, Sy MH: Posterior sternoclavicular
dislocations. Eur J Orthop Surg Traumatol 2009;19(1):7-9.
3. Sewell MD, Al-Hadithy N, Le Leu A, Lambert SM: Instability of
the sternoclavicular joint: Current concepts in classification,
treatment and outcomes. Bone Joint J 2013;95-B(6):721-731.
4. Boesmueller S, Wech M, Tiefenboeck TM, et al: Incidence,
characteristics, and long-term follow-up of sternoclavicular
injuries: An epidemiologic analysis of 92 cases. J Trauma Acute
Care Surg 2016;80(2):289-295.
5. Fournier MN, Sinclair MR, Zheng ET, et al: The frequency of
mediastinal injury in acute posterior sternoclavicular
dislocations: A multicenter study. J Pediatr Orthop
2020;40(10):e927-e931. This multicenter study evaluates the
incidence of mediastinal injuries in the se ing of acute posterior
sternoclavicular dislocations, of which none was seen. However,
50% of patients demonstrated compression of the
brachiocephalic vein on imaging prereduction. Level of evidence:
III.
6. Swarup I, Cazzulino A, Williams BA, Defrancesco C, Spiegel D,
Shah AS: Outcomes after surgical fixation of posterior
sternoclavicular physeal fractures and dislocations in children. J
Pediatr Orthop 2021;41(1):11-16. This article assessed the long-
term functional outcomes after open reduction and fixation of
posterior sternoclavicular fractures and dislocations in the
pediatric population. Of the 14 patients with patient-reported
 outcomes, Quick Disabilities of the Arm, Shoulder and Hand and
Patient-Reported Outcomes Measurement Information System scores
were near normal. However, 29% of patients noted difficulty
participating in sports. Level of evidence: IV.
7. Waters PM, Bae DS, Kadiyala RK: Short-term outcomes after
surgical treatment of traumatic posterior sternoclavicular
fracture-dislocations in children and adults. J Pediatr Orthop
2003;23(4):464-469.
8. Suppan CA, Bae DS, Donohue KS, et al: Trends in the volume of
operative treatment of midshaft clavicle fractures in children and
adolescents: A retrospective, 12-year single-institution analysis. J
Pediatr Orthop B 2016;25(4):305-309.
9. Kim AE, Vuillermin CB, Bae DS, Samora JB, Waters PM, Bauer
AS: Congenital pseudarthrosis of the clavicle: Surgical decision
making and outcomes. J Shoulder Elbow Surg 2020;29(2):302-307.
This study is a retrospective review of 47 patients with congenital
pseudarthrosis of the clavicle, comparing the surgical and
nonsurgical cohorts and outcomes. Patients who were treated in
adolescence with plate fixation had higher union rates than those
treated as infants with suture fixation. All patients available for
follow-up surveys demonstrated normal function. Level of
evidence: IV.
10. Shields E, Behrend CC, Beiswenger T, et al: Scapular dyskinesis
following displaced fractures of the middle clavicle. J Shoulder
Elbow Surg 2015;24(1):e331-e336.
11. Gao B, Dwivedi S, Patel SA, Nwizu C, Cruz AI: Operative versus
non operative management of displaced midshaft clavicle
fractures in pediatric and adolescent patients: A systematic
review and meta-analysis. J Orthop Trauma 2019;33(11):e439-e446.
This study is a meta-analysis evaluating outcomes after surgical
and nonsurgical management of displaced midshaft clavicle
fractures. There were no differences in union rates or Quick
Disabilities of the Arm, Shoulder and Hand scores. Surgical
management leads to faster return to activity and be er Constant
 scores, but higher complications requiring secondary surgery.
Level of evidence: III.
12. Zhang D, Heyworth BE, Lio a ES, Hergo KA, Earp BE:
Variation in treatment approaches to adolescent midshaft clavicle
fractures in pediatric versus adult hospitals. J Orthop Trauma
2021;35(5):271-275. This article compared treatment approaches to
adolescent midshaft clavicle fractures between two adult
hospitals and one pediatric hospital. The study authors found
that patients being treated at an adult hospital had five times the
rate of surgical treatment. Level of evidence: III.
13. Riiser MO, Molund M: Long term functional outcomes and
complications in operative versus nonoperative treatment for
displaced midshaft clavicle fractures in adolescents: A
retrospective comparative study. J Pediatr Orthop 2021;41(5):279-
283. This study retrospectively evaluated 109 adolescent patients
with midshaft clavicle fractures to evaluate long-term outcomes.
There were no functional differences between the groups.
Patients treated nonsurgically had be er cosmetic satisfaction.
Level of evidence: III.
14. Heyworth BE, Pennock AT, Li GY, et al: Two-year functional
outcomes of operative versus non operative treatment of
completely displaced midshaft clavicle fractures in adolescents:
Results from a prospective, multicenter, level 2 study. Orthop J
Sports Med 2019;7(7 suppl 5):2325967119S00428. This is a
prospective multicenter study evaluating patient-reported
outcomes after surgical versus nonsurgical management of
adolescent midshaft clavicle fractures. There were no significant
differences in patient-reported outcomes or satisfaction between
groups. Complications, specifically sensory deficits, were higher
in the surgical group. Level of evidence: II.
15. Nawar K, Eliua Y, Burrow S, Peterson D, Ayeni O, de Sa D:
Operative versus non operative management of mid diaphyseal
clavicle fractures in the skeletally immature population: A
systematic review and meta-analysis. Curr Rev Musculokelet Med
2020;13(1):38-49. This meta-analysis on surgically treated versus
 nonsurgically treated skeletally immature patients with midshaft
clavicle fractures found that there were no significant differences
in time to union, time to return to sports, and complication rates
between the two groups. Level of evidence: IV.
16. Beck JJ, Richmond CG, Tompkins MA, Heyer A, Shea KG, Cruz
AIJr: What’s new in pediatric upper extremity sports injuries? J
Pediatr Orthop 2018;38(2):e73-e77.
17. Paterson WH, Throckmorton TW, Koester M, Azar FM, Kuhn JE:
Position and duration of immobilization after primary anterior
shoulder dislocation: A systematic review and meta-analysis of
the literature. J Bone Joint Surg Am 2010;92(18):2924-2933.
18. Franklin CC, Weiss JM: The natural history of pediatric and
adolescent shoulder dislocation. J Pediatr Orthop 2019;39(6 suppl
1):S50-S52. This study is a systematic review and meta-analysis of
studies evaluating recurrent instability after anterior shoulder
dislocation in the pediatric population. The recurrence rate for
younger patients can be more than 70%, which can cause
significant damage to the joint. Level of evidence: IV.
19. Leroux T, Ogilvie-Harris D, Veille e C, et al: The epidemiology
of primary anterior shoulder dislocations in patients aged 10 to
16 years. Am J Sports Med 2015;43(9):2111-2117.
20. Ellis HBJr, Seiter M, Wise K, et al: Glenoid bone loss in
traumatic glenohumeral instability in the adolescent population.
J Pediatr Orthop 2017;37(1):30-35.
21. Popkin CA, Levine WN, Ahmad CS: Evaluation and
management of pediatric proximal humerus fractures. J Am Acad
Orthop Surg 2015;23(2):77-86.
22. Pahlavan S, Baldwin KD, Pandya NK, Namdari S, Hosalkar H:
Proximal humerus fractures in the pediatric population: A
systematic review. J Child Orthop 2011;5(3):187-194.
23. Canavese F, Marengo L, Cravino M, et al: Outcome of
conservative versus surgical treatment of humerus shaft fracture
in children and adolescents: comparison between non operative
 treatment, external fixation, and elastic stable intramedullary
nailing. J Pediatr Orthop 2017;37(3):e156-e163.
24. von Heideken J, Thiblin I, Hogberg U: The epidemiology of
infant shaft fractures of femur or humerus by incidence, birth,
accidents, and other causes. BMC Musculoskelet Discord
2020;21(1):840. This study evaluated the incidence of birth-related
and non–birth-related infantile femur and humeral shaft
fractures and associated risk factors. Specific to birth-related
humeral trauma, the incidence of fracture was 0.101 per 1,000
children, and was associated with shoulder dystocia (37%),
maternal obesity (47%), vacuum-assisted delivery (25%), male sex
(66%), large for gestational age (44%), breech, multiple birth, and
injury to the brachial plexus (24%). Level of evidence: IV.
25. Kelly DM: Flexible intramedullary nailing of pediatric humeral
fractures: Indications, techniques, and tips. J Pediatr Orthop
2016;36(4 suppl 1):S49-S55.
26. Abzug JM, Herman MJ: Management of Supracondylar
humerus fractures in children: Current concepts. J Am Acad
Orthop Surg 2012;20(2):69-77.
27. Ojeaga P, Wya CW, Wilson P, Ho CA, Copley LAB, Ellis HB:
Pediatric type II supracondylar humerus fractures associated
with successful closed reduction and immobilization. J Pediatr
Orthop 2020;40(8):e690-e696. This study evaluated type IIa
supracondylar humerus fractures that were managed with closed
reduction and immobilization; 76.6% maintained reduction.
Failure to improve the distance from the anterior humeral line or
the hourglass angle was associated with loss of reduction and
subsequent requirement of pin fixation. Level of evidence: III.
28. Babal JC, Mehlman CT, Klein G: Nerve injuries associated with
pediatric supracondylar humerus fractures: A meta-analysis. J
Pediatr Orthop 2010;30(3):253-263.
29. Barre KK, Skaggs DL, Sawyer JR, et al: Supracondylar humeral
fractures with isolated anterior interosseous nerve injuries: Is
 urgent treatment necessary? J Bone Joint Surg Am
2014;96(21):1793-1797.
30. Wallace M, Johnson DB, Pierce W, Iobst C, Riccio A, Wimberly
RL: Biomechanical assessment of torsional stiffness in a
supracondylar humerus fracture model. J Pediatr Orthop
2019;39(3):e210-e215. This article evaluated different 2.0-mm and
2.4-mm pin configurations for torsional stiffness in a three-
dimensional model. The 2.4-mm pin configurations were stiffer in
every configuration. Divergent and parallel pins had equal
stiffness, whereas two lateral pins and one medial pin were
equivalent to three lateral pins and one medial pin. Constructs
with medial pins were stiffer than those with only lateral pins.
Level of evidence: V.
31. Spencer HT, Wong M, Fong YJ, Penman A, Silvia M: Prospective
longitudinal evaluation of elbow motion following pediatric
supracondylar humeral fractures. J Bone Joint Surg Am
2010;92(4):904-910.
32. Schmale GA, Mazor S, Mercer LD, Bompadre V: Lack of benefit
of physical therapy on function following supracondylar humeral
fracture: A randomized controlled trial. J Bone Joint Surg Am
2014;96(11):944-950.
33. Griffin KJ, Walsh SR, Markar S, et al: The pink pulseless hand: A
review of the literature regarding management of vascular
complications of supracondylar humeral fractures in children.
Eur J Vasc Endovasc Surg 2008;36(6):697-702.
34. Harris LR, Arkader A, Broom A, et al: Pulseless supracondylar
humerus fracture with anterior interosseous nerve or median
nerve injury- an absolute indication for open reduction? J Pediatr
Orthop 2019;39(1):e1-e7. This study is a multicenter retrospective
review of patients with pulseless supracondylar humerus
fractures and either an AIN or median nerve palsy. 70% of
patients were treated with closed reduction and pinning, not
necessitating open reduction or antecubital fossa exploration.
Level of evidence: IV.
35. Badkoobehi H, Choi PD, Bae DS, Skaggs DL: Management of
the pulseless pediatric supracondylar humeral fracture. J Bone
Joint Surg Am 2015;97(11):937-943.
36. Popkin CA, Rosenwasser KA, Ellis HB: Pediatric and adolescent
T-type distal humerus fractures. J Am Acad Orthop Surg Glob Res
Rev 2017;1(8):e040.
37. Anari JA, Neuwirth AL, Carducci NM, Donegan DJ, Baldwin
KD: Pediatric t-condylar humerus fractures: A systematic review.
J Pediatr Orthop 2017;37(1):36-40.
38. Salguiero L, Roocroft JH, Bastrom TP, et al: Rate and risk factors
for delayed healing following surgical treatment of lateral
condyle humerus fractures in children. J Pediatr Orhtop
2017;37(1):1-6.
39. Ramo BA, Funk SS, Elliot ME, Jo CH: The Song classification is
reliable and guides prognosis and treatment for pediatric lateral
condyle fractures: An independent validation study with
treatment algorithm. J Pediatr Orthop 2020;40(3):e203-e209. This
study evaluated the interrater and intrarater reliability of the
Song classification for lateral condyle fractures and found good to
excellent agreement. The study authors found that Song 1 and 2
fractures were managed nonsurgically most of the time, whereas
Song 3 and 4 fractures had high rates of failure of nonsurgical
management. Level of evidence: IV.
40. Nazareth A, VandeBerg CD, Sarkisova N, et al: Prospective
evaluation of a treatment protocol based on fracture
displacement for pediatric lateral condyle humerus fractures: A
prospective study. J Pediatr Orthop 2020;40(7):e540-e546. This is a
prospective study evaluating a treatment protocol for pediatric
lateral condyle fractures. Fractures with less than 2-mm
displacement were managed in a long arm cast, those with 2- to 4-
mm displacement were managed with closed reduction and
percutaneous pinning, and those with more than 4-mm
displacement were managed with open reduction and
percutaneous pinning. There were no differences among the
 groups in regard to delayed unions or pin site infections, and
functional outcomes at 1 year were comparable to normative
data. Level of evidence: II.
41. Horn BD, Herman MJ, Crissci K, Pizzutillo PD, MacEwen GD:
Fractures of the lateral humeral condyle: Role of the cartilage
hinge in fracture stability. J Pediatr Orthop 2002;22(1):8-11.
42. Pribaz JR, Bernthal NM, Wong TC, Silva M: Lateral spurring
(overgrowth) after pediatric lateral condyle fractures. J Pediatr
Orthop 2012;32(5):456-460.
43. Shabtai L, Lightdale-Miric N, Rounds A, Arkader A, Pace JL:
Incidence, risk factors, and outcomes of avascular necrosis
occurring after humeral lateral condyle fractures. J Pediatr Orthop
B 2020;29(2):145-148. This is a retrospective study on the
incidence, outcomes, and risk factors for osteonecrosis following
lateral humeral condyle fractures. The incidence of osteonecrosis
was 1.4% and is associated with type III fractures. Five of seven
patients with osteonecrosis had no pain, and six of seven
regained full notion; none had varus or valgus residual deformity.
Level of evidence: III.
44. Pezzu i D, Lin JS, Singh S, Rowan M, Samora JB: Pediatric
medial epicondyle fracture management: A systematic review. J
Pediatr Orthop 2020;40(8):e697-e702. This study is a systematic
review evaluating the management of medial epicondyle
fractures and outcomes. The most common complication was
some loss of elbow extension and flexion. Surgical management
was associated with higher union rates, and when patients had
ulnar nerve symptoms surgical management helped resolve the
symptoms. Ulnar nerve symptoms occasionally developed after
nonsurgical management. Level of evidence: IV.
45. Axibal DP, Ke erman B, Skelton A, et al: No difference in
outcomes in a matched cohort of operative versus nonoperatively
treated displaced medial epicondyle fractures. J Pediatr Orthop B
2019;28(6):520-525. This is a retrospective review of patients with
displaced medial epicondyle fractures, comparing surgical and
 nonsurgical outcomes of matched cohorts. There were no
differences in outcomes regarding length of immobilization,
mean time to full motion, complications, and the need for
physical therapy. Level of evidence: III.
46. Hughes M, Dua K, O’Hara NN, et al: Variation among pediatric
orthopaedic surgeons when treating medial epicondyle fractures.
J Pediatr Orthop 2019;39(8):e592-e596. This study evaluated how 13
different pediatric orthopaedic surgeons would treat 60 different
medial epicondyle fracture cases. Concurrent elbow dislocation
had the greatest influence on the decision for surgical treatment.
Increasing displacement also was correlated with surgical
management. Level of evidence: V.
47. Murphy RF, Vuillermin C, Naqvi M, Miller PE, Bae DS, Shore BJ:
Early outcomes of pediatric elbow dislocation- risk factors
associated with morbidity. J Pediatr Orthop 2017;37(7):440-446.
48. Li le KJ: Elbow Fractures and dislocations. Orthop Clin North
Am 2014;45(3):327-340.
49. Kalbi M, Weber B, Lacker I, Beer M, Pressmar J: Olecranon
fractures in children: Treatment of a rare entity. Eur J Trauma
Emerg Surg 2020; November 24 [Epub ahead of print]. This was a
retrospective chart review of pediatric patients with olecranon
fractures, evaluating treatment type by fracture type/location.
Most patients were treated without surgery, whereas surgical
management consisted of either plate fixation or tension band
wiring. Surgery is indicated for displacement of 5 mm or more
intra-articular fractures, apophyseal fractures, and open
fractures. Level of evidence: III.
50. Holme TJ, Karbowiak M, Arnander M, Gelfer Y: Paediatric
olecranon fractures: A systematic review. EFORT Open Rev
2020;5(5):280-288. This study is a systematic review of 299 patients
across 15 articles with olecranon fractures. Nonsurgical treatment
for nondisplaced olecranon fractures less than 4 mm yielded
good outcomes, as did surgical management of displaced
fractures. More solid fixation is recommended for patients
 weighing more than 50 kg, as suture techniques were at risk for
failure. Level of evidence: IV.
51. Gibley RF, Garg S, Mehlman CT: Community orthopaedic
surgeon taking trauma call: Radial neck fracture pearls and
pitfalls. J Orthop Trauma 2019;33(8 suppl 2):S17-S21. This article
elucidates tips for managing radial neck fractures for the
community orthopaedic surgeon. Poorer outcomes for patients
with radial neck fractures are associated with older patient age,
inadequate reduction, prolonged immobilization, and need for
open reduction. Level of evidence: V.
52. Kong J, Lewallen L, Elliot M, Jo CH, McIntosh AL, Ho CA:
Pediatric radial neck fractures: Which ones can be successfully
closed reduced in the emergency department? J Pediatr Orthop
2021;41(1):17-22. This study retrospectively evaluated 70 patients
with radial neck fractures to determine risk factors for failure of
closed reduction in the emergency department. Failure of closed
reduction was more common in patients who had Judet type IV
classification or higher, higher fracture angulation (specifically
over 60°), and more than 24 hours to a empted reduction from
injury. Level of evidence: III.
53. Nicholson LT, Skaggs DL: Proximal radius fractures in children.
J Am Acad Orthop Surg 2019;27(19):e876-e886. This article reviews
the diagnosis and treatment strategies for pediatric proximal
radius fractures. Most of these fractures can be managed
nonsurgically with good outcomes. Increasing fracture
angulation, older age, articular extension, and need for internal
fixation are associated with worse outcomes. Level of evidence: V.
54. Lior S, Arkader A: Percutaneous reduction of displaced radial
neck fractures achieves be er results compared with fractures
treated by open reduction. J Pediatr Orthop 2016;36(suppl 1):Ss63-
S66.
55. Blakey CM, Biant LC, Birch R: Ischaemia and the pink, pulseless
hand complicating supracondylar fractures of the humerus in
childhood. J Bone Joint Surg [Br] 2019;91B(11):1487-1492. This
 study evaluated patients who initially had supracondylar
humerus fractures and normal color-pulseless hands, who were
referred for postinjury care. Three of 26 had undergone
successful surgical exploration prior to referral, whereas 23 of 36
had ischemic contractures of the forearm and hand. This study
encouraged urgent exploration of the fracture site in patients
with supracondylar humerus fracture with normal color,
pulseless hands when reduction is followed by persistent and
increasing pain. Level of evidence: III.
56. Broom A, Schur MD, Arkader A, Flynn J, Gorni ky A, Choi PD:
Compartment syndrome in infants and toddlers. J Child Orthop
2016;10(5):453-360.
C H AP T E R 5 9

Pediatric Forearm, Wrist, and

Hand Trauma
Kathleen D. Rickert MD, FAAOS, Jessica Burns MD, MPH

Neither of the following authors nor any immediate family member has received anything of value
from or has stock or stock options held in a commercial company or institution related directly or
indirectly to the subject of this chapter: Dr. Rickert and Dr. Burns.

ABSTRACT
Pediatric fractures most often occur in the forearm, wrist, and hand.
Accurate diagnosis with understanding of appropriate
management in the context of the patient’s fracture type and age is
critical to providing the best care and outcomes for pediatric
patients. Most forearm fractures can be managed with closed
reduction and long arm casting within accepted parameters of
residual displacement dependent on fracture location and patient
age. Proximal fractures in older children have lower remodeling
potential. Pediatric acute compartment syndrome of the forearm
typically occurs secondary to trauma with associated fracture and
requires compartment release. Distal radius fractures have
significant remodeling potential in children but high risk of a loss
of reduction. Fractures that extend into the physis warrant long-
term follow-up with appropriate and timely management of growth
arrest. Orthogonal views of the elbow and wrist are critical for the
diagnosis and management of Monteggia or Galeazzi fracture-
dislocations, respectively. Galeazzi and Monteggia fractures are
more successfully managed with closed reduction than adults but
require surgical management if unstable. Scaphoid fractures can
present late with nonunion, but most acute fractures are visible on
initial radiographs. Hand and finger fractures can largely be
managed nonsurgically with a short period of immobilization,
including for phalangeal neck fractures.
Keywords: both-bone forearm fracture; Monteggia; pediatric;
phalangeal neck; Seymour fractures

Introduction
Fractures of the forearm, wrist, and hand are the most common
types of pediatric fractures that present to the emergency room. 1
Different from fractures around the elbow, fractures of the forearm
have great remodeling potential. Correct management of pediatric
forearm, wrist, and hand fractures requires appropriate initial
workup and diagnosis, with consideration for the location and type
of fracture in the context of the age and body habitus of the patient.
As with the evaluation of other fractures, it is important to obtain
orthogonal views of the elbow, wrist, and hand or finger. Missed or
delayed diagnosis can occur with Monteggia or Galeazzi fracture-
dislocations, scaphoid fractures as well as open fractures with small
puncture wounds. The treating orthopaedic surgeon should
complete a full, independent evaluation of each patient to ensure
the optimal treatment of the patient.

Monteggia Fracture-Dislocation
With ulnar fracture or deformity, there can be subluxation or
dislocation of the radiocapitellar joint, known as a Monteggia
fracture-dislocation. This fracture type was first described as an
ulnar fracture with anterior dislocation of the radial head before the
first radiograph and later was further classified by the direction of
the radial head dislocation/subluxation and associated fractures 2
(Table 1). This type of injury should be suspected in cases where
there is any shortening or deformity of the ulna, especially in cases
of isolated ulnar injury. The recognition of radial head dislocation
or subluxation is critical but can be missed or inadequately treated.
This clinical problem can lead to chronic elbow morbidity,
including pain, valgus elbow instability, loss of motion,
osteoarthritis, or even posterior interosseous nerve palsy. 3 - 6

Table 1
Bado Classification of Monteggia Fracture-Dislocation

Bado
Radial Head Dislocation Ulnar Fracture Incidence
Classification
I Anterior Apex anterior diaphyseal 60%
II Posterior Apex posterior 15%
diaphyseal
III Lateral or anterolateral Metaphyseal 20%
IV Anterior/any with radial Diaphyseal 5%
fracture

When this type of fracture is recognized acutely, closed

management is successful in more than 80% of cases. 4 , 7 - 9 A
treatment strategy was proposed based on the fracture pa ern of
the ulna, with closed treatment only for incomplete or length-stable
ulnar fractures. 10 Intramedullary fixation was recommended for all
complete but length-stable fractures, whereas plate fixation of the
ulna was recommended for complete length-unstable fractures
(long oblique, comminuted). 10 This treatment algorithm was
validated by a multicenter study group in 2015 in which there
would have been no recurrent instability in 112 Monteggia lesions if
the ulna-based strategy had been used. 11 It has subsequently been
shown, however, that the ulna-based strategy may indicate surgery
when a trial of nonsurgical management should be pursued. In a
study of 59 Monteggia lesions with complete ulnar fractures, 76%
were successfully managed with closed reduction and casting. 7 In a
2021 study, 86.1% of patients with complete ulnar fractures
maintained reduction without surgery. 11
 After successful closed reduction, close follow-up is
recommended with weekly radiographs for the first 3 weeks to
confirm maintenance of reduction. Cast removal at 4 to 6 weeks can
be performed once there is sufficient healing of the ulna. 7 , 11 If
further immobilization is needed, a short arm cast or a removable
forearm splint can be used, and elbow range of motion can begin. 7
Loss of reduction usually occurs after more than 1 week, but
within 15 days. 11 Risk factors for unsuccessful closed reduction
include Bado classification, with type I more likely to succeed with
closed reduction and casting and type III more likely to require
surgical management. 7 , 11 Residual angulation of the ulna (>36°) is
a risk factor independent of fracture type. 7
In cases of unsuccessful closed reduction or loss of reduction,
surgical management can include an intramedullary device or open
reduction and internal fixation (ORIF) with plate-and-screw
construct. The intramedullary device can be an elastic stable
intramedullary nail (ESIN) 12 or Steinmann pin, 13 which can be
buried or left out of the skin without significant differences in
maintenance of reduction or complications. 14 Buried pins
necessitate a subsequent procedure for removal, whereas those left
out of the skin can be removed in the clinic (Figure 1). ORIF may be
required if the length of the ulna cannot be maintained with an
intramedullary device. 5 , 9 , 10 , 15 , 16
 Figure 1 Lateral forearm radiographs of Bado type I Monteggia fracture-
dislocation that was missed initially (A), likely due to splint obscuring the
radiocapitellar joint. The patient underwent closed reduction and intramedullary
fixation with a Steinmann pin left out of the skin 10 days after the original injury
(B). The Steinmann pin was removed 4 weeks postoperatively (C) and was
recasted for 2 additional weeks due to incomplete fracture healing. Ten weeks
after surgery, the patient had no pain and had symmetric elbow range of motion
(D).

Chronic Monteggia lesions occur because of either an initial

failure of diagnosis or a loss of reduction following management,
which occurs in up to 50% and 20% of cases, respectively. 16 , 17
Approximately 85% of chronic Monteggia fracture-dislocations are
Bado type I. 18 Initially, there may not be significant symptoms,
which can further delay the diagnosis. The ulna usually heals in a
shortened and angulated position, which remodels over time, and
symptoms are related to the chronic radial head dislocation. With
prolonged dislocation, the radial head, capitellum, and radial notch
of the ulna undergo dysplastic changes. 3 , 5 , 6 , 16 , 18 , 19 Without the
radiocapitellar joint, the elbow loses approximately one-third of its
valgus stability, and an increased carrying angle subsequently
develops with possible associated tardy ulnar nerve palsy. Nerve
tenting over the dislocated radial head can also lead to tardy
median nerve and posterior interosseous nerve palsies. 18 The loss
of anatomic relationships reduces the range of motion, leading to
contractures that abnormally load the joints, later resulting in
osteoarthritis. 6 , 16 , 18 , 19
There is no consensus regarding the appropriate treatment of
chronic Monteggia lesions, although there is li le role for
nonsurgical management. Surgical considerations include ulnar
osteotomy, radiocapitellar pinning, open reduction of the
radiocapitellar joint, and annular ligament reconstruction. 18 Some
authors report that ulnar osteotomy is the only necessary
procedure, whereas others contend that interposed
capsuloligamentous tissue blocks concentric reduction of the
radiocapitellar joint. 18 Regardless, ulnar osteotomy should be
performed without excessive lengthening to decrease the risk of
nonunion. Assessment of radiocapitellar stability should then be
performed with consideration for annular ligament repair. 3 , 18
Outcomes for management of chronic Monteggia lesions are
improved with decreased time from injury and younger age. 3

Radial and Ulnar Diaphyseal Forearm

Fractures
Diaphyseal radial and ulnar shaft fractures are relatively common,
representing up to 30% of all pediatric fractures. 1 These fractures
are typically sustained with a fall onto an outstretched hand
commonly with rotation, in either supination or pronation. Closed
reduction and casting are the standard of care for pediatric patients
and are successful in most cases. The ulna is a relatively straight
bone, while the apex anterolateral radial bow allows for rotational
movement. The goal with closed reduction is anatomic alignment;
however, with remodeling potential, there are general guidelines
for what is considered acceptable reduction 20 (Table 2).

Table 2
Acceptable Reduction Variables

Patient Age (Years) Radius Angulation Rotation Shortening

Patient Age (Years) Radius Angulation Rotation Shortening
Girls younger than 8 <15° <45° <1 cm
Boys younger than 10
Girls older than 8 <15° (distal) <30° <1 cm
Boys older than 10
Girls older than 8 <10° (proximal) <30° <1 cm
Boys older than 10

Greenstick fractures can usually be managed successfully with

closed reduction, taking care to reduce the rotational component.
In one study, 94% of 109 greenstick fractures were successfully
managed with a single reduction. The study authors recommended
two clinical follow-up visits and three interval radiographs to
reduce overall costs and radiation exposure. 21
Complete fractures can still be successfully managed with closed
reduction and casting in most cases; however, malreduction can
lead to deformity and lack of rotation of the forearm. Functional
motion of the adult elbow has been reported to be 30° to 130° of
flexion/extension and 50° of both supination and pronation,
whereas children and adolescents have greater demands for flexion
and pronation, with the mean arc of motion for functional tasks
being 28° to 146° of flexion/extension and 54° of supination and 65°
of pronation for contemporary tasks of typing and use of a cellular
phone. 22
Reduction in the emergency department or operating room of
both-bone fractures can be performed with traction and
manipulation while a child is under regional block or conscious
sedation. The splint or cast should be applied with the elbow in 90°
of flexion with neutral forearm rotation or position of stability. An
interosseous mold of the splint or cast is critical for fracture
reduction maintenance with a relatively straight ulnar border and
mold over the distal humeral condyles to prevent cast slippage. The
cast index, or ratio of sagi al-to-coronal diameter of the cast, should
be below 0.80 to decrease the risk of loss of reduction. 20 , 23 , 24
Follow-up radiographic evaluation after closed reduction is
recommended at 1, 2, 4, and 6 weeks after reduction, with
consideration to exclude radiographs at 4 weeks after reduction
because most cases that need repeat intervention are noticed within
2 weeks. 25
Closed reduction and casting are more likely to fail in proximal
radius diaphyseal fractures, and displacement to an unacceptable
alignment occurs in 70% to 80% of cases, likely due to longer time
to callus formation, more significant soft-tissue envelope, and
greater demand for near-anatomic alignment (<10°). 26 , 27 There
should be a lower threshold for surgical intervention for this
particular fracture group (Figure 2).
 Figure 2 AP radiographs of a forearm diaphyseal both-bone radius and ulna
fractures in a 12-year-old girl (A) that displaced after closed reduction with
greater than 10° of angulation of the proximal radius (B). C, AP and lateral
radiographs after the patient underwent open reduction and internal fixation with
plate-and-screw construct of the radius only. D, Six weeks after long-arm cast
immobilization, the patient had stable alignment of the forearm, significant
fracture healing, and no pain.

There is special consideration for children with obesity because

they have different fracture characteristics than children of normal
weight. 28 It is estimated that one-third of children and adolescents
are overweight and one in five have obesity. In a study of 565
patients with pediatric forearm fracture (28.7% overweight or with
obesity), children of normal weight were 4.1 times more likely to
sustain open fractures. Children who are overweight or those with
obesity were more likely to have fractures of the distal forearm and
isolated radial shaft fractures. A 2020 study has shown that children
with obesity are more likely to lose reduction and require surgical
intervention. 28
Open fractures of the radius and ulna occur in up to 9% of cases,
representing up to 80% of all pediatric open fractures. 29
Historically, patients with open fractures are treated surgically with
irrigation and débridement (I&D) of the open fracture site and
either closed reduction or surgical fixation of the radius and ulna.
There has been an emerging trend toward nonsurgical management
of Gustilo-Anderson type I open fractures with bedside
débridement, closed stabilization of the fracture, and antibiotic
administration. A 2020 comparative analysis showed no infection in
fractures managed nonsurgically compared with 1.9% of those
managed surgically. There is consensus that all Gustilo-Anderson
type II and III fractures should be managed with surgical
débridement and irrigation and fracture stabilization. 29
In cases of unacceptable fracture alignment or loss of reduction
(>30% of cases), 25 surgical intervention should be considered. The
most common methods of fixation include ESINs and plate-and-
screw constructs. In a systematic review of these two methods for
midshaft radius and ulna fractures in children, there were no
differences between time to fracture union (3 to 6 months), forearm
rotation, fracture angulation, or complications rates. ESIN was
found to have be er cosmesis and shorter duration of surgery;
however there was significant aberration in the radial bow without
affecting forearm rotation. 30 As noted previously, a Steinmann pin
left out of the skin has a similar rate of infections, refractures, and-
overall complications. 14
ESIN for the radius can have a starting point between the first
and second dorsal compartments or more dorsal between the
second and third dorsal compartments at the Lister tubercle. In a
systematic review of the surgical approach, the dorsal approach was
found to be associated with rupture of the extensor pollicis longus
in 2.6% of cases, whereas the lateral approach has a 2.9% rate of
transient superficial radial nerve palsy. 31 There is consideration for
fixation of a single bone with ESIN, depending on the fracture
pa ern and relative stability, which was found in a systematic
review to have comparable results with fixation of both bones. 32
ORIF with plate-and-screw construct is the standard treatment
for adult both-bone forearm fractures and is a consideration in
adolescents, length-unstable fractures, or those in a location less
amendable to ESIN, such as the metadiaphyseal junction. There is
consideration for a hybrid construct with plate and screw fixation of
the radius with ESIN or Steinmann pin of the ulna. With plate
fixation of both bones, early motion should be considered, although
the morbidity associated with prolonged immobilization of the
elbow is rarely seen in adolescent patients. 23 , 30

Compartment Syndrome
Acute compartment syndrome of the forearm in pediatric patients
is an orthopaedic surgical emergency. This phenomenon was first
described by Volkmann as an ischemic contracture of the forearm
due to loss of arterial blood supply that can cause permanent
muscle and nerve damage, leading to significant morbidity and
even mortality. The pediatric form of acute compartment syndrome
is distinct from that in the adult population and should be
considered a unique clinical condition. 33 In a 2020 systematic
review and meta-analysis of 12 studies, the most common causes of
pediatric acute compartment syndrome in 233 children was trauma,
with pediatric acute compartment syndrome occurring in the leg in
60% of cases and in the forearm in 27% of cases. Most patients had
fractures near the area of the compartment syndrome (75%), and
compartments were released after an average of 25.4 hours. Pain
was the most common presenting symptom (88%) and 32%
experienced paresthesias. Good outcomes were achieved in 85% of
patients, with loss of motion (10%) as the most common
complication. Time to fasciotomy, presence of fracture, age, sex, or
anatomic location were not predictors of outcome. Children present
differently than adults and delayed diagnosis may occur.
Fasciotomy should be performed in pediatric acute compartment
syndrome, even if there is delayed presentation or diagnosis longer
than 24 hours, as pediatric patients have good tissue recovery
potential. 33

Galeazzi Fractures
The Galeazzi fracture was first described in 1822 and represents a
fracture of the radius at any level associated with disruption of the
distal radioulnar joint. The traumatic mechanism is usually a fall on
an outstretched hand in hyperpronation. 34 This fracture type is less
frequent in children than in adults and usually occurs in older
children. They tend to be underdiagnosed in the pediatric
population, rates of which are unknown. In children, the standard
and first line of treatment is closed reduction and long arm casting
with the forearm in supination. Nonsurgical treatment has good
results in children but fails frequently in adults. In a review of
pediatric Galeazzi fractures, most children had dorsal dislocation of
the ulna, and one-half of these had fractures of both the radius and
ulna compared with the seven children who had volar dislocation of
the ulna and isolated radius fractures. Most patients (85%) were
successfully treated with closed reduction and long arm casting. 34
Even though Galeazzi fractures can be missed or underdiagnosed
in the pediatric population, they are not associated with the same
morbidity as a missed Monteggia fracture. Nonsurgical
management is successful with closed reduction and a long arm
cast in most patients, but surgical consideration should be
evaluated in older children and adolescents. 34

Distal Radius and Ulnar Fractures

Fractures in the metaphysis and physis of the distal radius are
common in pediatric patients, whereas intra-articular distal radius
fractures are uncommon. Nonsurgical management with closed
reduction and casting is the standard treatment due to a high
ability for the distal radius to remodel in the sagi al plane, and to a
lesser degree, in the coronal plane 35 (Figure 3).

Figure 3 AP and lateral radiographs of a displaced distal radius fracture with

an unstable short oblique pattern (A) that underwent closed reduction (B) with
mild improvement in alignment. Six months after the injury, there has been
complete remodeling in both the coronal and sagittal planes (C).
 Torus or buckle fractures refer to fractures that are incomplete,
inherently stable, have li le risk of displacement, and often occur
in the distal radial metaphysis secondary to compressive loads. 36
Two randomized controlled 37 , 38 trials comparing plaster casts with
removable wrist splints for 3 weeks showed no difference in
complications, healing, or pain, and those with wrist braces had
earlier return to wrist function. This was further shown in a
randomized controlled trial comparing plaster casts to soft
bandages with no differences in pain or healing and earlier wrist
motion in the soft bandage group. 39 To further the extremely
favorable natural history of these fractures, two randomized trials
of patients compared hospital follow-up with home removal of the
splint or soft cast. There was no difference in clinical results, and
families preferred the home removal. 36
Complete fractures usually benefit from closed reduction and
casting. Two randomized controlled trials 40 , 41 comparing closed
reduction and casting with immediate pin fixation showed that loss
of reduction occurred in 20% to 39% of those treated with closed
reduction and casting but did not occur in those treated with
immediate pin fixation. 36 This has prompted many orthopaedic
surgeons to recommend immediate surgical intervention for
displaced distal radius fractures. Patients treated with pin fixation
had a 6% to 38% rate of pin-site complications. The clinical results
and cost of treatment were similar between both groups in both
studies and revealed no difference between short arm and long arm
casting after manipulation. 36 As discussed in a 2020 meta-analysis,
orthopaedic surgeons should consider the amount of initial
displacement, the patient’s age, and the risks and benefits
associated with closed reduction and casting compared with
immediate pin fixation. 42
Physeal fractures of the distal radius can lead to premature
physeal arrest and resultant ulnar positivity. The Salter-Harris
classification defines physeal injuries. Salter-Harris type I fractures
occur through the hypertrophic zone of the physis, type II fractures
additionally occur through the metaphysis, type III fractures occur
through the hypertrophic zone and the epiphysis, and type IV
fractures occur through the epiphysis, physis, and metaphysis. 43
Early, gentle closed reduction is recommended for displaced
fractures. Repeated a empts and reduction more than 10 days after
the injury may increase the risk of physeal arrest. 44 A systematic
review of Salter-Harris type II distal radius fractures showed that
younger patients have greater remodeling potential, with physeal
arrest occurring in up to 4.3% of type II distal radius fractures. If
physeal arrest occurs in younger patients, there is greater potential
for morbidity associated with ulnar positivity. 45 Growth
disturbance leading to more than 1 cm of shortening typically leads
to symptomatic wrists. These fractures benefit from long-term
follow-up with contralateral radiographs. 46

Scaphoid Fractures
Scaphoid fractures are rare fractures in the pediatric population but
are the most common fracture of the carpus. These injuries account
for 3% to 4% of injuries to the hand and carpals in children. 47
Scaphoid fractures most often occur from a fall or during sporting
activities. 48 , 49 The symptoms of a scaphoid fracture, including pain
and swelling in the anatomic snu ox, can be subtle and result in
delayed presentation. Evaluation for scaphoid fractures includes
physical examination palpating the anatomic snu ox and scaphoid
tubercle for pain and swelling along with PA, lateral, and scaphoid
radiographic views. In a 2020 study, 89% of scaphoid fractures that
presented within 30 days of injury were visible on the first
radiographic examination. 48 Additionally, 93% of acute scaphoid
fractures (within 7 days of injury) in children younger than 11 years
were visible on at least one of the available radiographic views with
21% visible on all views. No fracture was visible solely on the PA
scaphoid view. 50 The study authors also found that younger
children often presented with fractures of the distal scaphoid
(distal corner and distal body), which has been the traditional
thinking, whereas older children presented with fractures of the
mid and proximal body of the scaphoid. Younger children with
scaphoid fractures were more likely to be obese; however, the
number of scaphoid fractures was higher in older children. There
was no significant difference in fracture orientation, displacement,
gap, or concomitant fractures with respect to age. 48 Evaluation for
concomitant injuries such as distal radius fracture, transscaphoid
perilunate dislocation, ulnar styloid fracture, capitate fracture, and
bilateral injuries is important because they may be present in up to
10% of children. 51
If initial radiographs are equivocal, radiography can be repeated
after 2 weeks of immobilization to assess for evidence of fracture
healing because the healing response is best seen between 2 and 5
weeks following injury. 50 In the small percentage of patients in
whom the fracture is not visualized but pain persists after 2 weeks,
CT or MRI may be performed to evaluate for the presence of a
fracture rather than continuing immobilization. 49 Nondisplaced
acute fractures are immobilized in a short arm thumb spica cast for
6 to 12 weeks with a union rate of 90%. 51 Obtaining early advanced
imaging may decrease the overall cost and morbidity of prolonged
immobilization for radiographically occult fractures. 49
Surgical intervention is recommended for displaced or proximal
pole fractures and nonunion or fractures with osteonecrosis, with a
reported union rate of up to 96.5% following surgical fixation.
Nonunion is rare following appropriate treatment; however, close
to one-third of pediatric patients present with a chronic nonunion.
51
Many treatment options have been proposed for the management
of nonunion, including prolonged immobilization, bone grafting
with Kirschner wire fixation, bone grafting without osteosynthesis,
and headless compression screw fixation, with or without bone
grafting. 52 A 2019 study reported the results of 12 patients treated
with a vascularized thumb metacarpal periosteal flap for scaphoid
nonunion. 52 A periosteal flap was harvested from the dorsum of the
thumb metacarpal fed by the first dorsal metacarpal artery and
transferred with the vascular pedicle to the nonunion site. This
procedure was found to be less technically demanding and with
less donor site morbidity than harvesting bone graft. Complete
bone healing was observed in all patients, and 79% of patients had
cross-sectional trabecular bridging at 12 weeks. At final follow-up,
overall range of motion, strength, and mean radiolunate and
scapholunate angles were similar to those on the patient’s
nonsurgical side.

Hand and Finger Fractures

Hand and finger fractures are common in the pediatric population
and second only to forearm fractures. 53 These fractures occur most
commonly through crush injuries or sporting events. 54 The most
frequent location of injury is the proximal phalanx of the li le
finger. 53 , 54 Most of these fractures can be managed with closed
reduction, appropriate immobilization, and early motion.
Appropriate evaluation of hand and finger fractures includes
thorough clinical examination assessing for open injuries, angular
or rotational malalignment of the injured digit, and orthogonal
radiographs. Rotational alignment can be confirmed through
flexion of the digits and confirming that all fingers point to the
scaphoid tubercle 53 - 56 (Figure 4).

Figure 4 A and B, Clinical photographs of rotational malalignment displaying

overlap of the ring finger on the long finger, and the ring finger no longer pointing
to the scaphoid tubercle with full flexion.

Immobilization for hand and finger fractures consists of buddy

taping, splinting, or casting. A 2019 randomized controlled trial
compared buddy taping with interdigital padding with a volar-
based intrinsic plus splint for pediatric extra-articular finger
fractures (excluding phalangeal neck fractures) and included 99
patients who were randomized to buddy taping (52) versus
splinting (47). 55 Thirty-nine fractures were unstable, with 31
requiring a reduction before immobilization (18 taping and 13
splinting). Secondary displacement was discovered at the first
follow-up visit in one patient (2%) from the taping group and three
patients (6%) from the splinting group. All of these secondary
displacements occurred in the proximal phalanx of the small finger
that required an initial reduction but had no further displacement.
None of the nondisplaced fractures had secondary displacement.
Nonsurgical management failed in only one patient with a proximal
shaft fracture in the splinting group. Additionally, the time for
placement of immobilization was lower (5 minutes versus 15
minutes) with significantly lower cost and higher patient comfort.
Overall, buddy taping was found to be a safe alternative to splinting
or casting for finger fractures even if a reduction is required. A
study from 2019 55 evaluated the need for follow-up radiographs for
proximal and middle phalangeal fractures to reduce radiation
exposure if possible. The study authors reviewed 365 patients with
single, extra-articular physeal fractures excluding multiple,
phalangeal neck, open, or intra-articular fractures. A total of 122
patients (33.4%) required reduction before immobilization and all
fractures were immobilized with buddy taping or a volar-based
intrinsic plus splint for 3 weeks. Secondary angular deformity
occurred in 2.2% (8/365) of all finger fractures and 6.6% (8/365) of
the reduced fractures. All fractures with secondary displacement
presented with an angular deformity of greater than 10° with the
common adjunct of malrotation (87.5%) and all required internal
fixation. No secondary deformity occurred in the minimally or
nondisplaced fractures. Metaphyseal and diaphyseal fractures of
the proximal and middle phalanges of the index to small fingers
with initial angulation greater than 10° require close radiographic
follow-up at 1 week, whereas minimally or nondisplaced fractures
are stable and do not require subsequent imaging. 55
 q q g g
There are several finger fractures that do require special a ention
and often surgical intervention such as phalangeal neck, intra-
articular, and Seymour fractures. Surgical fixation has traditionally
been recommended for displaced phalangeal neck fractures
because they have been considered unstable with less remodeling
potential due to the fracture being located away from the physis. In
contrast, recent literature has suggested that nonsurgical treatment
for patients with displaced phalangeal neck fractures can be
performed without further displacement and improved alignment
at final follow-up. 54 , 56 A 2020 study reported on patients with
displaced (type II) phalangeal neck fractures of the proximal or
middle phalanx with no more than 30° of angulation or 25%
translation and no malrotation (Table 3). Twelve patients
underwent reduction before immobilization in a cast or orthosis. It
was found that displaced phalangeal neck fractures can be
successfully managed nonsurgically without increased
displacement and overall have improved angulation and translation
in both coronal and sagi al planes on final radiography with or
without a reduction. 54 Furthermore, a 2021 article compared plaster
casting versus removable splinting for the management of type I
and type II phalangeal neck fractures. 50 Nineteen patients were
treated with a forearm-based intrinsic plus cast and 28 patents were
treated with custom-made thermoplastic hand (small children, 2) or
finger-based (larger children, 26) splint. All patients were
immobilized for 3 to 4 weeks before beginning therapy and
progressive motion with buddy taping. Seventeen patients
underwent reduction before immobilization. At final follow-up, all
children could make a full fist with no pain and had returned to
preinjury activity levels. Overall, no clinical or radiographic
differences in outcomes were detected for type I or type II
phalangeal neck fractures managed in a cast or splint. This suggests
that these finger fractures can be safely immobilized in finger-
based splints even for type II fractures with the added benefit of
improved hygiene, comfort, and reduced skin issues. The study
authors recommend that treatment be individualized for patient
and family comfort and compliance. 56
 y p
Table 3
Phalangeal Neck Fracture Classification

Classification Description
Type I Nondisplaced fracture
Type II Displaced fracture with cortical contact
Type II subclassification IIA—transverse fracture line
IIB—oblique fracture line
IIC—distal fragment with dorsal bony lip
IID—small distal fragment
Type III Displaced fracture with loss of cortical contact

Seymour fractures are another unique finger fracture of the

pediatric population that requires specific a ention. These are open
Salter-Harris I/II or juxtaphyseal fractures of the distal phalanx
often with interposed nail bed at the fracture site; yet, these
fractures are often missed, leading to a high rate of complications,
including infection and nail or physeal growth disturbance. 57
Radiographs often reveal a displaced fracture of the distal phalanx,
though noting the disruption of the nail plate/cuticle is vital to
diagnosis (Figure 5). The disruption of the nail plate and cuticle
indicates these to be open fractures with interposed tissue (Figure
6). Treatment for these fractures involves removal of the nail plate
with débridement of the fracture site, extrication of the interposed
nail bed, and reduction of the fracture. If the fracture is unstable, it
may require Kirschner wire placement in addition to
immobilization in a splint/cast. A 2019 article reviewed the
treatment of acute (within 24 hours of injury) Seymour fractures to
define optimal management, surgical indications, antibiotic choice,
and outcomes. 57 Sixty-five fractures in patients younger than 18
years were reviewed, with 58 cases (89%) being initially managed in
the emergency department. Thirty-seven of these patients (64%)
received a thorough irrigation before reduction and splinting under
either local anesthesia or conscious sedation. Four of the patients
seen in the emergency department initially required an unplanned
surgical procedure; three were due to fracture displacement at first
follow-up, and one was for an I&D not performed in the emergency
department. Seven cases were managed primarily in the operating
room with an I&D, open reduction, and Kirschner wire fixation. Of
the seven patients treated surgically, six underwent surgery due to
unsuccessful or unstable reduction because of interposed tissue in
the fracture site (four) or severe crush injury (two), or concomitant
extensor tendon laceration (one). Complications included infection
(8%), physeal disturbance (4%), nail dystrophy (4%), and
unplanned procedure (6%). Infections were usually superficially
managed with oral antibiotics. A late abscess and osteomyelitis
developed in one patient who did not undergo an initial I&D. Forty-
six of 58 patients seen in the emergency department received oral
antibiotics, with the most frequent antibiotic choice being
cephalexin for a median course of 7 days. Augmentin was the
second most frequently chosen antibiotic for a median course of 10
days. Prompt identification and appropriate management of
Seymour fractures are critical to avoid complications. 57 Acute
Seymour fractures may be successfully managed in the emergency
department if stable reduction is achieved following a well-defined
treatment protocol (Table 4).
Figure 5 Lateral radiograph of a Seymour fracture of the long finger before (A)
and after (B) attempted closed reduction before surgical reduction and fixation.
 Figure 6 Clinical photograph of displaced Seymour fracture with extrusion of
the germinal matrix.

Table 4
Seymour Fracture Treatment Protocol

Protocol Steps

Intravenous antibiotics
Nail plate removal
Extrication of interposed tissue
Irrigation and débridement
Closed reduction (Kirschner wire fixation in operating room if unstable)
Nail bed repair with absorbable sutures
Nail replacement or foil for splinting of eponychial fold
Splinting versus casting
Oral antibiotics

Summary
Pediatric forearm, wrist, and hand fractures are common and can
usually be nonsurgically managed successfully. Many fractures
benefit from closed reduction and casting with excellent results.
Care should be taken when evaluating forearm fractures, with
special a ention paid to the alignment of the radiocapitellar joint to
evaluate for Monteggia fracture-dislocations. Close follow-up after
closed reduction of Monteggia, both-bone forearm fractures, and
Galeazzi fractures should occur with special consideration for
adolescents with less than 2 years of growth remaining and
children with obesity. Most acute scaphoid fractures are visible on
the presenting radiographs, even in younger children, and are
effectively managed nonsurgically. Phalangeal neck fractures have
traditionally been surgical fractures but may be transitioned to
nonsurgical treatment for type I and II fractures. Understanding of
methods to obtain the correct diagnosis and proper treatment leads
to optimal outcomes for patients with pediatric forearm, wrist, and
hand fracture.

Key Study Points

Monteggia fracture-dislocations can be successfully managed with closed reduction
and casting in most acute cases, but chronic Monteggia lesions benefit from
surgical intervention with ulnar osteotomy and annular ligament repair.
Both-bone forearm fractures can often be managed with closed reduction and
casting, with surgery considered for adolescents and those with proximal radius
fractures.
Most acute scaphoid fractures (within 7 days of injury) in children younger than 11
years are visible on at least one of the available radiographic views, with 21% visible
on all views.
Type I and type II phalangeal neck fractures may be managed nonsurgically in a
removable finger-based splint with no more than 30° of angulation or 25% translation
and no malrotation on presentation.
Acute Seymour fractures may be adequately managed in the emergency
department with I&D, reduction, splinting, and a course of antibiotics.

Annotated References
1. Naranje SM, Erali RA, Warner WC, Sawyer JR, Kelly DM:
Epidemiology of pediatric fractures presenting to emergency
departments in the United States. J Pediatr Orthop 2016;36(4):e45-
e48.
 2. Rehim SA, Maynard MA, Sebastin SJ, Chung KC: Monteggia
fracture dislocations: A historical review. J Hand Surg Am
2014;39(7):1384-1394.
3. Nakamura K, Hirachi K, Uchiyama S, et al: Long-term clinical
and radiographic outcomes after open reduction for missed
Monteggia fracture-dislocations in children. J Bone Joint Surg Am
2009;91(6):1394-1404.
4. Dormans JP, Rang M: The problem of Monteggia fracture-
dislocations in children. Orthop Clin North Am 1990;21(2):251-256.
5. Miller TC, Fishman FG: Management of Monteggia injuries in
the pediatric patient. Hand Clin 2020;36(4):469-478. A literature
review of Monteggia fracture-dislocations in pediatric patients is
presented. Correct radiographic assessment of the radiocapitellar
joint is essential for correct diagnosis. Stable reduction should be
performed in the acute period through closed reduction or
surgical intervention. Level of evidence: IV.
6. David-West KS, Wilson NIL, Sherlock DA, Bennet GC: Missed
Monteggia injuries. Injury 2005;36(10):1206-1209.
7. Foran I, Upasani VV, Wallace CD, et al: Acute pediatric
Monteggia fractures: A conservative approach to stabilization. J
Pediatr Orthop 2017;37(6):e335.
8. Fowles JV, Sliman N, Kassab MT: The Monteggia lesion in
children. Fracture of the ulna and dislocation of the radial head. J
Bone Joint Surg Am 1983;65(9):1276-1282.
9. Leonidou A, Pagkalos J, Lepetsos P, et al: Pediatric Monteggia
fractures: A single-center study of the management of 40
patients. J Pediatr Orthop 2012;32(4):352-356.
10. Ring D, Jupiter JB, Waters PM: Monteggia fractures in children
and adults. J Am Acad Orthop Surg 1998;6(4):215-224.
11. Hart CM, Alswang J, Bram J, et al: Operative versus
nonoperative management of acute pediatric Monteggia injuries
with complete ulna fractures. J Pediatr Orthop 2021; June 2 [Epub
ahead of print]. This is a retrospective analysis of 73 pediatric
Monteggia fractures with complete ulnar fractures of which 51%
 received immediate surgical intervention and 49% underwent a
trial of closed reduction and casting. Ultimately, 13.9% of closed
reduction cases underwent surgical treatment for loss of
reduction. Level of evidence: III.
12. Poutoglidou F, Metaxiotis D, Kazas C, Alvanos D, Mpeletsiotis
A: Flexible intramedullary nailing in the treatment of forearm
fractures in children and adolescents, a systematic review. J
Orthop 2020;20:125-130. This therapeutic case series compared
surgical and nonsurgical initial management of acute pediatric
Monteggia fracture-dislocations in 73 patients. The surgical
group was more likely to be proximal and Bado type III and IV
fractures. A trial of nonsurgical management should be
considered. Level of evidence: IV.
13. Pugh DM, Galpin RD, Carey TP: Intramedullary Steinmann pin
fixation of forearm fractures in children. Long-term results. Clin
Orthop Relat Res 2000;376:39-48.
14. Kelly BA, Miller P, Shore BJ, Waters PM, Bae DS: Exposed versus
buried intramedullary implants for pediatric forearm fractures: A
comparison of complications. J Pediatr Orthop 2014;34(8):749-755.
15. Ramski DE, Hennrikus WP, Bae DS, et al: Pediatric Monteggia
fractures: A multicenter examination of treatment strategy and
early clinical and radiographic results. J Pediatr Orthop
2015;35(2):115-120.
16. Bae DS: Successful strategies for managing Monteggia injuries. J
Pediatr Orthop 2016;36:S67.
17. Souder CD, Roocroft JH, Edmonds EW: Significance of the
lateral humeral line for evaluating radiocapitellar alignment in
children. J Pediatr Orthop 2017;37(3):e150-e155.
18. Hubbard J, Chauhan A, Fi gerald R, Abrams R, Mubarak S,
Sangimino M: Missed pediatric Monteggia fractures. JBJS Rev
2018;6(6):e2.
19. Delpont M, Louahem D, Co alorda J: Monteggia injuries.
Orthop Traumatol Surg Res 2018;104(1 suppl):S113-S120.
20. Noonan KJ, Price CT: Forearm and distal radius fractures in
children. J Am Acad Orthop Surg 1998;6(3):146-156.
21. Ting BL, Kalish LA, Waters PM, Bae DS: Reducing cost and
radiation exposure during the treatment of pediatric greenstick
fractures of the forearm. J Pediatr Orthop 2016;36(8):816-820.
22. Valone LC, Waites C, Tartarilla AB, et al: Functional elbow range
of motion in children and adolescents. J Pediatr Orthop
2020;40(6):304-309. Twenty-eight patients went through different
functional and contemporary tasks while capturing kinematic
data. Mean arc of motion for functional tasks was 28° to 146° of
elbow flexion/extension and 54° of supination to 65° of pronation.
Level of evidence: II.
23. Caruso G, Caldari E, Sturla FD, et al: Management of pediatric
forearm fractures: What is the best therapeutic choice? A
narrative review of the literature. Musculoskelet Surg
2021;105(3):225-234. A review of the literature regarding
treatment options for pediatric forearm fractures is presented.
Nonsurgical management with cast immobilization is successful
for many pediatric fractures. There is not a true consensus for
management of all forearm fractures in pediatric patients. Level
of evidence: IV.
24. Pretell Mazzini J, Rodriguez Martin J: Paediatric forearm and
distal radius fractures: Risk factors and re-displacement – Role of
casting indices. Int Orthop 2010;34(3):407-412.
25. Luther G, Miller P, Waters PM, Bae DS: Radiographic evaluation
during treatment of pediatric forearm fractures: Implications on
clinical care and cost. J Pediatr Orthop 2016;36(5):465-471.
26. Wacker EM, Denning JR, Mehlman CT: Pediatric proximal radial
shaft fractures treated nonoperatively fail to maintain acceptable
reduction up to 70% of the time. J Orthop Trauma
2019;33(10):e378. A retrospective review of 309 complete pediatric
radial shaft fractures managed with closed reduction is
presented. Proximal third radial shaft fractures displaced to
 unacceptable parameters in 70% of cases compared with 33% of
more distal fractures. Level of evidence: IV.
27. Bowman EN, Mehlman CT, Lindsell CJ, Tamai J: Nonoperative
treatment of both-bone forearm shaft fractures in children:
Predictors of early radiographic failure. J Pediatr Orthop
2011;31(1):23-32.
28. Li Y, James C, Byl N, et al: Obese children have different
forearm fracture characteristics compared with normal-weight
children. J Pediatr Orthop 2020;40(2):e127-e130. The authors
present a comparative retrospective study of 565 pediatric
patients of normal weight to overweight and children with
obesity (2 to 17 years) with forearm fracture. Children of normal
weight were 4.1 times as likely to sustain open fractures. Children
with overweight and obesity were more likely to sustain distal
forearm fractures or isolated radius fractures. Level of evidence:
III.
29. Elia G, Blood T, Got C: The management of pediatric open
forearm fractures. J Hand Surg Am 2020;45(6):523-527. Patients
with open forearm fractures have traditionally been treated with
formal surgical I&D. There is limited evidence to support early
antibiotic administration, bedside I&D, and fracture stabilization
in the emergency department with a low risk for subsequent
infection. Level of evidence: I.
30. Patel A, Li L, Anand A: Systematic review: Functional outcomes
and complications of intramedullary nailing versus plate fixation
for both-bone diaphyseal forearm fractures in children. Injury
2014;45(8):1135-1143.
31. Nørgaard SL, Riber SS, Danielsson FB, Pedersen NW, Viberg B:
Surgical approach for elastic stable intramedullary nail in
pediatric radius shaft fracture: A systematic review. J Pediatr
Orthop B 2018;27(4):309-314.
32. Kim CY, Gentry M, Sala D, Chu A: Single-bone intramedullary
nailing of pediatric both-bone forearm fractures a systematic
review. Bull Hosp Jt Dis 2017;75(4):227-233.
33. Lin JS, Samora JB: Pediatric acute compartment syndrome: A
systematic review and meta-analysis. J Pediatr Orthop B
2020;29(1):90-96. The authors present a systematic review of acute
compartment syndrome in 233 pediatric patients, showing that
the forearm is the second most common location. Fasciotomy was
performed an average of 25.4 hours after injury with no outcome
difference in time from injury to fasciotomy. Level of evidence:
IV.
34. Eberl R, Singer G, Schalamon J, Petnehazy T, Hoellwarth ME:
Galeazzi lesions in children and adolescents: Treatment and
outcome. Clin Orthop Relat Res 2008;466(7): 1705-1709.
35. Lynch KA, Wesolowski M, Cappello T: Coronal remodeling
potential of pediatric distal radius fractures. J Pediatr Orthop
2020;40(10):556-561. A retrospective chart review study of 36
pediatric forearm fractures is presented. The remodeling rates
ranged from 2° to 2.59° per month during the first 6 months after
injury, indicating that many fractures may still remodel in the
coronal plane. Level of evidence: III.
36. Bae DS, Howard AW: Distal radius fractures: What is the
evidence? J Pediatr Orthop 2012;32:S128.
37. Symons S, Rowsell M, Bhowal B, Dias JJ: Hospital versus home
management of children with buckle fractures of the distal
radius. A prospective, randomised trial. J Bone Joint Surg Br
2001;83(4):556-560.
38. Davidson JS, Brown DJ, Barnes SN, Bruce CE: Simple treatment
for torus fractures of the distal radius. J Bone Joint Surg Br
2001;83(8):1173-1175.
39. Khan KS, Grufferty A, Gallagher O, Moore DP, Fogarty E,
Dowling F: A randomized trial of “soft cast” for distal radius
buckle fractures in children. Acta Orthop Belg 2007;73(5):594-597.
40. Bohm ER, Bubbar V, Yong Hing K, Dzus A: Above and below-
the-elbow plaster casts for distal forearm fractures in children. A
randomized controlled trial. J Bone Joint Surg Am 2006;88(1):1-8.
41. Webb GR, Galpin RD, Armstrong DG: Comparison of short and
long arm plaster casts for displaced fractures in the distal third of
the forearm in children. J Bone Joint Surg Am 2006;88(1):9-17.
42. Sengab A, Krijnen P, Schipper IB: Risk factors for fracture
redisplacement after reduction and cast immobilization of
displaced distal radius fractures in children: A meta-analysis. Eur
J Trauma Emerg Surg 2020;46(4):789-800. A meta-analysis of risks
for fracture redisplacement after reduction and casting of
pediatric displaced distal radius fractures is presented. Initial
complete displacement and presence of both-bone fracture were
independent risk factors for redisplacement. Level of evidence: I.
43. Abzug JM, Li le K, Kozin SH: Physeal arrest of the distal radius.
J Am Acad Orthop Surg 2014;22(6):381-389.
44. Valverde JA, Albiñana J, Certucha JA: Early pos raumatic
physeal arrest in distal radius after a compression injury. J Pediatr
Orthop B 1996;5(1):57-60.
45. Larsen MC, Bohm KC, Rizkala AR, Ward CM: Outcomes of
nonoperative treatment of salter-harris ii distal radius fractures.
Hand (N Y) 2016;11(1):29-35.
46. Cannata G, De Maio F, Mancini F, Ippolito E: Physeal fractures
of the distal radius and ulna: Long-term prognosis. J Orthop
Trauma 2003;17(3):172-179.
47. Christodoulou AG, Colton CL: Scaphoid fractures in children. J
Pediatr Orthop 1986;6(1):37-39.
48. Nguyen JC, Nguyen MK, Arkader A, et al: Age-dependent
changes in pediatric scaphoid fracture pa ern on radiographs.
Skeletal Radiol 2020;49(12):2011-2018. In a retrospective review of
180 pediatric scaphoid fractures, it was demonstrated that
younger children were more likely to have distal corner or body
fractures. There were no age-related differences in fracture
visibility, orientation, gap, displacement, or other associated
fractures. Level of evidence: III.
49. Karir A, Huynh MNQ, Carsen S, Smit K, Cheung K:
Management and outcomes of clinical scaphoid fractures in
 children. Hand (N Y) 2020; July 1 [Epub ahead of print]. A
retrospective review of 91 pediatric scaphoid fractures showed
that advanced imaging was obtained in fewer than 20% of cases
and almost all patients were immobilized immediately. There
was a low incidence (5.5%) of occult fractures. Level of evidence:
III.
50. Nguyen MK, Arkader A, Kaplan SL, et al: Radiographic
characterization of acute scaphoid fractures in children under 11
years of age. Pediatr Radiol 2021;51(9):1690-1695. A retrospective
review of 28 pediatric scaphoid fractures (patients younger than
10 years) showed that 93% of fractures were visible on at least
one view and 21% were visible on all views. Level of evidence: III.
51. Gholson JJ, Bae DS, Zurakowski D, Waters PM: Scaphoid
fractures in children and adolescents: Contemporary injury
pa erns and factors influencing time to union. J Bone Joint Surg
Am 2011;93(13):1210-1219.
52. Barrera-Ochoa S, Mendez-Sanchez G, Mir-Bullo X, Knörr J,
Bertelli JA, Soldado F: Vascularized thumb metacarpal periosteal
flap for scaphoid nonunion in adolescents: A prospective cohort
study of 12 patients. J Hand Surg Am 2019;44(6):521.e1-521.e11. A
total of 12 pediatric scaphoid nonunions underwent a
vascularized thumb metacarpal periosteal pedicled flap. There
were no complications, and consolidation was achieved in all
cases. There was nearly 80% bridging at 12 weeks. Level of
evidence: IV.
53. Vonlanthen J, Weber DM, Seiler M: Nonarticular base and shaft
fractures of children’s fingers: Are follow-up x-rays needed?
retrospective study of conservatively treated proximal and middle
phalangeal fractures. J Pediatr Orthop 2019;39(9):e657-e660. A
retrospective analysis of 365 pediatric finger fractures managed
nonsurgically is presented. No angulation occurred in the
minimally or nondisplaced fractures, but 6.6% of those that
underwent reduction had a subsequent loss of reduction. Level of
evidence: III.
54. Tan RES, Lim JX, Chong AKS: Outcomes of phalangeal neck
fractures in a pediatric population. J Hand Surg Am
2020;45(9):880.e1-880.e6. The authors present a retrospective
review of 35 pediatric type II Al-Qa an phalangeal neck fractures
with at least 10° of angulation or 25% translation in either plane
without malrotation. There was no displacement with
nonsurgical management. Level of evidence: IV.
55. Weber DM, Seiler M, Subotic U, Kalisch M, Weil R: Buddy
taping versus splint immobilization for paediatric finger
fractures: A randomized controlled trial. J Hand Surg Eur Vol
2019;44(6):640-647. In a randomized controlled trial, 99 extra-
articular pediatric finger fractures were randomized to either
taping or splinting. Patient comfort was higher and cost was
lower in the taping group. Level of evidence: I.
56. Liao JCY, Huan SKW, Tan RES, Lim JX, Chong AKS, Das De S: A
comparison of casting versus splinting for nonoperative
treatment of pediatric phalangeal neck fractures. J Pediatr Orthop
2021;41(1):e30-e35. A retrospective study of 47 pediatric
phalangeal neck fracture managed nonsurgically is presented.
There was no significant difference in clinical or radiographic
outcomes between removable splints and cast immobilization.
Splinting increased comfort and hygiene for Al-Qataan type I and
II fractures. Level of evidence: III.
57. Lin JS, Popp JE, Balch Samora J: Treatment of acute seymour
fractures. J Pediatr Orthop 2019;39(1):e23-e27. In a retrospective
study of 65 pediatric Seymour fractures, 89% were initially
managed in the emergency department, with seven cases with
surgical intervention. Surgery was performed because of
unsuccessful closed reduction. Four fractures required surgery
later due to fracture redisplacement. Level of evidence: IV.
C H AP T E R 6 0

Pediatric Upper Extremity

Disorders
Andrea H.W. Chan MD, MA, FRCSC, Kevin J. Little MD,
FAAOS, FAOA

Dr. Little or an immediate family member serves as a board member, owner, officer, or committee
member of the American Association for Hand Surgery, the American Society for Surgery of the
Hand, and the Pediatric Orthopaedic Society of North America. Neither Dr. Chan nor any
immediate family member has received anything of value from or has stock or stock options held
in a commercial company or institution related directly or indirectly to the subject of this chapter.

ABSTRACT
Congenital malformations of the hand and arm are the second most
common congenital disorders behind cardiac malformations. The
classification and treatment strategies for these disorders have
improved significantly, coupled with an increased focus on patient-
reported outcomes to drive patient-centered and family-centered
care. A multidisciplinary team approach is helpful to evaluate the
risks and benefits of all treatment plans to optimize patient
outcomes.
Keywords: congenital hand malformations; hand differences;
pediatric acquired hand conditions; pediatric hand

Introduction
Congenital hand malformations will be seen by all practitioners
who take care of pediatric patients. Most patients can function well
and adapt to their differences, and the role of the pediatric hand
specialist is to help guide caregivers and patients toward
maximizing function while minimizing interventions that can
disrupt their lives. Different malformations or dysplasias can have
specific associations that should be assessed.

Embryology of the Upper Extremity

The upper limb structures appear at very precise embryonic stages,
and development is pa erned along three interrelated spatial axes
(proximodistal, anteroposterior, and dorsoventral) (Figure 1). The
upper limb bud, an outgrowth of two mesoderm layers (somitic and
lateral plate) and overlying ectoderm, appears 26 days after
fertilization following notochord expression of sonic hedgehog
(SHH). Following this, cartilage precursor cells localize centrally
within the bud, whereas other connective tissue precursor cells
(tendon and muscles) localize at the bud periphery. Differentiation
into bony or cartilaginous components occurs in a proximal to
distal direction beginning with the humerus at day 36 and ends
with the distal phalanges at day 50 to form the skeletal elements.
This process is mediated by the interplay among a number of
important transcription factors (eg, Hox, Sox), growth factors (eg,
transforming growth factor beta, bone morphogenetic protein,
fibroblast growth factor [FGF]), and other proteins (eg, Wnt). The
subclavian-axillary-brachial arteries appear at day 33, and nerve
trunks enter the arm shortly thereafter at day 36. At day 47, the
fingers begin to separate at the hand paddle and complete
separation of the fingers occurs by day 54. 1 - 3
 Figure 1 Illustration of the upper extremity limb bud demonstrating the three
spatial axes of development.The apical ectodermal ridge (AER), an epithelial
thickening at the distal tip of the limb bud, is responsible for proximodistal
growth, which is mediated by the fibroblast growth factor (FGF) family. The zone
of polarizing activity (ZPA), located in the posterior (ulnar) aspect of the limb bud,
is the signaling center for the anteroposterior axis, which is mediated by the
signaling molecule sonic hedgehog (SHH). The dorsoventral axis is mediated by
the Wingless/Integrated (WNT) signaling pathway.

There are three linked limb axes that are responsible for the
outgrowth and pa erning of the upper extremity. The apical
ectodermal ridge (AER) is the first signaling axis to appear, and it is
located on the tip of the limb bud. The AER is responsible for
proximodistal pa erning and is primarily mediated by the FGF
family. Transverse limb deficiencies can occur as a result of FGF
signaling disruption. The zone of polarizing activity is a signaling
axis located in the posterior (or ulnar) margin of the limb bud
mesoderm. The zone of polarizing activity is responsible for
anteroposterior (or radioulnar) limb pa erning and is mediated by
SHH. Disruption in signaling can result in mirror duplication and
polydactyly. The dorsoventral axis exists in the non-AER ectoderm
of the limb bud. WNT proteins are largely responsible for
pa erning and outgrowth in this axis, and disruptions can lead to
conditions such as nail-patella syndrome. 1 , 2
The current accepted classification system to describe congenital
hand differences is the Oberg-Manske-Tonkin classification, which
uses understanding of developmental and molecular biology, axis
involvement, and genetic etiology to classify congenital hand
differences. 4

Symbrachydactyly
Symbrachydactyly is a sporadic unilateral hand difference that
results in the failure of formation of fingers. The incidence is 0.6 per
10,000 live births and has a male and left-sided preponderance. 5
Although the etiology is unknown, subclavian artery insufficiency
occurring before 42 days’ gestational age is the leading hypothesis.
This vascular insult likely leads to a disruption of the AER and
results in an isolated transverse limb bud deficiency. 6
Symbrachydactyly is characterized by the presence of nubbins
with rudimentary ectodermal tissue (nail plates, bone, and
cartilage). In general, there is relative sparing of the border digits
with shortened or absent central digits. Its clinical presentation,
however, is highly variable regarding the extent of the central
digital hypoplasia, and function and size of the border digits and
hand. As such, the classification can be challenging and multiple
differential diagnoses should be considered including amniotic
band syndrome, ulnar longitudinal deficiency, hypodactyly, Apert
syndrome, and central deficiency. Furthermore, although
symbrachydactyly occurs sporadically, it can also be associated with
Poland syndrome (unilateral aplasia or hypoplasia of the chest wall
and pectoralis major). Syndactyly can also be associated with
symbrachydactyly (Figure 2). The Foucher classification (Table 1)
grades symbrachydactyly based on the presence of a thumb and
digits and joint stability and helps guide surgical management.
 Figure 2 Clinical photograph of an 18-month-old patient with symbrachydactyly
of the right hand and associated hypoplasia of the pectoralis major muscle.
(Courtesy of Kevin J. Little, MD.)

Table 1
Foucher Classification for Symbrachydactyly

I All bones and digits present (brachydactyly and syndactyly)

IIA 2+ fingers; normal thumb; hypoplastic fingers
IIB Functional border digits, variable central nubbins; normal thumb
IIC Spoon hand; thumb conjoined with hypoplastic ulnar digits; thumb present with
variable stability
IIIA Monodactyly; normal thumb
IIIB Monodactyly; hypoplastic thumb with variable stability
IVA Peromelic with wrist mobility; absent thumb
IVB Peromelic with no wrist mobility; absent thumb
Reproduced with permission from Goodell PB, Bauer AS, Sierra FJ, James MA:
Symbrachydactyly. Hand (N Y) 2016;11(3):262-270.
 Treatment focuses on maximizing realistic function and
cosmesis, but also guiding acceptance and se ing appropriate
expectations. Nonsurgical management includes occupational
therapy to optimize vocational and avocational skill sets, opposition
paddles for stable monodactyly to facilitate pinch, and also to
identify and aid those who may experience negative psychological
effects. Surgical management is patient specific and largely focuses
on optimizing pinch, opposition, grasp, and release as well as
cosmesis. This includes syndactyly release and first web space
deepening to provide length to the thumb. Additionally,
brachydactyly can be treated with a nonvascularized free toe
phalanx if adequate soft-tissue coverage is available, vascularized
free toe-to-hand transfers particularly for Foucher classification
IIIA/IIIB, or distraction lengthening. 5 , 7

Radial Longitudinal Deficiency

Radial longitudinal deficiency (RLD) is a spectrum of preaxial
(radial-sided) hypoplasia of the upper limb and presents with
variable involvement of the humerus, radius, carpus, and thumb.
This malformation occurs primarily as a result of a disruption of
the anteroposterior (radioulnar) axis and occasionally the
proximodistal axis as well. RLD is the most common congenital
longitudinal deficiency, occurring in between one in 30,000 and one
in 100,000 live births. 8 Although most cases are the result of
sporadic mutations, autosomal dominant and recessive types exist.
8
Additionally, 33% to 44% of RLD is associated with other
syndromes, such as Holt-Oram, Fanconi anemia, VACTERL
(vertebral defects, anal atresia, cardiac defects, tracheoesophageal
fistula, renal anomalies, and limb abnormalities) association, and
thrombocytopenia-absent radius. 9 , 10 The more severe the
presentation, the more likely there is an associated syndrome. 9 It is
imperative that patients who present with RLD are evaluated with a
thorough musculoskeletal and systemic examination, treated for
these syndromes, and referred for genetic counseling (Table 2).
Table 2
Syndromes Commonly Associated With Radial Longitudinal
Deficiency

Associated Inheritance
Clinical Manifestations Management
Syndrome Pattern
Holt-Oram AD Cardiac anomalies (ventricular Echocardiogram
septal defect)
Triphalangeal thumb
Humeral defects
Fanconi anemia AR Aplastic anemia Complete blood
Acute bone marrow failure count
Diepoxybutane
chromosomal
fragility test a
Bone marrow
transplantation b
VACTERL Sporadic Vertebral anomalies, anal atresia, Scoliosis
association cardiac anomalies, radiographs c
tracheoesophageal fistula, renal Echocardiogram
agenesis, limb deformities Abdominal
ultrasonography
Thrombocytopenia- AR Thrombocytopenia Complete blood
absent radius count
AD = autosomal dominant, AR = autosomal recessive, VACTERL = vertebral defects, anal
atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities
a
Reserved for patients who are small for their age or have classic Fanconi anemia facial
features.
Before age 10 years.
b

Performed at an older age.

c

Clinical presentation can range from mild hypoplasia of the

thumb to a complete absence of the radial-sided structures.
Absence of the radial support results in radial wrist deviation and
volar carpal subluxation with variable stiffness of the wrist and
digits. Muscles arising from the lateral epicondyle are often absent,
contributing to poor wrist extension and a flexed wrist posture. In
more severe forms, the ulna can also be shortened and curved,
leading to a J-shaped forearm. The elbow can become stiff in
extension and the severely radially deviated posture of the wrist
actually facilitates hand-to-mouth function. 11
The most comprehensive classification for RLD is the Bayne and
Klug classification 12 with the added type N James modification 13
for isolated thumb hypoplasia, and Goldfarb modification 14 with
the addition of type V for associated humeral involvement (Table 3).
The most common type of RLD when the radius is affected is type
IV at 27%. 13 Type 0 and I can be commonly associated with
proximal radioulnar synostosis and congenital radial head
dislocation. 15

Table 3
Bayne and Klug Classification for Radial Longitudinal Deficiency
With James Modification

Distal
Type Humerus Proximal Radius Carpus Thumb
Radius
N Normal Normal Normal Normal Hypoplastic
or absent
0 Normal Normal, radioulnar Normal Absent, Hypoplastic
synostosis, congenital hypoplasia or absent
radial head dislocation or coalition
I Normal Normal, radioulnar >2 mm Absent, Hypoplastic
synostosis, congenital shorter hypoplasia or absent
radial head dislocation than ulna or coalition
II Normal Hypoplasia Hypoplasia Absent, Hypoplastic
hypoplasia or absent
or coalition
III Normal Variable hypoplasia Physis Absent, Hypoplastic
absent hypoplasia or absent
or coalition
IV Normal Absent Absent Absent, Hypoplastic
hypoplasia or absent
or coalition
V Proximal Absent Absent Absent, Hypoplastic
humeral hypoplasia or absent
hypoplasia or coalition

Indications for surgical treatment are variable but typically focus

on improving both function and cosmesis, including improving
wrist and forearm alignment, wrist and thumb stability, and thumb
deficiency reconstruction. Pollicization of the index finger is the
gold standard for isolated thumb hypoplasia (type N) with either
an absent or rudimentary thumb and an unstable carpometacarpal
joint (Blauth grade IIIB-V) when ulnar-sided preference for grasp
has not developed. For RLD types 0-II, the first line of treatment
often entails stretching and serial splinting. Tendon transfers,
centralization, and distraction lengthening of the hypoplastic
radius are surgical options to correct wrist deviation and radial
height. 16 As discussed in a 2021 study, for RLD types III and IV,
soft-tissue release with a bilobed flap, centralization, and
radialization are the most commonly performed procedures, with
centralization generally being preceded by radial soft-tissue
distraction 17 (Figure 3). In general, active motion and strength as
opposed to persistent wrist radial angulation are most important
for improved long-term outcome. 18
Figure 3 Clinical photographs from a 3-year-old patient with right hand type IV
radial longitudinal deficiency and thumb hypoplasia (A), and after centralization
with an Evans bilobed flap (B).(Courtesy of Andrea H.W. Chan, MD.)
Thumb Hypoplasia
Thumb hypoplasia can occur in isolation, or within the spectrum of
RLD in which up to 44% of reported cases are syndromic. 9 , 10 , 19 As
such, a systemic evaluation is critical. As per the Oberg-Manske-
Tonkin classification, thumb hypoplasia falls under type I
malformation along the anteroposterior (radioulnar) axis in either
the entire upper limb or hand plate alone. Clinically, the thumb is
smaller, the interphalangeal joint can be stiff because of extrinsic
muscle deficiency, the metacarpophalangeal joint is unstable
because of ulnar collateral ligament insufficiency, thenar bulk is
diminished and thumb opposition is limited because of intrinsic
thenar muscular deficiency, and the first web space is narrowed.
The Blauth classification for thumb hypoplasia with the Manske
modification 20 of grade III is outlined in Table 4. The most common
type is complete thumb absence (type V). This grading system is
based on progressive anatomic deficiencies and guides surgical
management. Thumb reconstruction involves an opponensplasty,
thumb ulnar collateral ligament reconstruction, and first web space
deepening, and is considered for Blauth grades II and IIIA in the
se ing of thumb carpometacarpal joint stability. Pollicization of the
index finger is reserved for Blauth grades IIIB to V, in which there is
either a rudimentary thumb that has an unstable carpometacarpal
joint or an absent thumb (Figure 4).

Table 4
Blauth Classification for Thumb Hypoplasia With Added Manske
Modification of Grade III, and Associated Surgical Treatment
Options

Clinical
Grade Surgical Treatment Options
Manifestations
I Smaller thumb Usually requires no treatment
Complete and
functional parts
 Clinical
Grade Surgical Treatment Options
Manifestations
II Smaller thumb Thumb reconstruction: Opponensplasty (FDS III or FDS IV),
Narrowed first MCP joint UCL reconstruction, web space deepening (four-
web space flap Z-plasty)
Hypoplastic thenar
muscles
Thumb UCL
instability
III Smaller thumb IIIA: Thumb reconstruction (see type II)
Narrowed first IIIB: Pollicization
web space
Hypoplastic
intrinsic and
extrinsic muscles
Globally unstable
thumb MCP joint
A: Stable thumb
CMC joint
B: Unstable thumb
CMC joint
IV Floating thumb Pollicization
(pouce flotant)
V Completely absent +/− pollicization (if patient has not developed ulnar-sided
thumb (aplasia) preference for grasp)
CMC = carpometacarpal, FDS = flexor digitorum superficialis, MCP = metacarpophalangeal,
UCL = ulnar collateral ligament
 Figure 4 Clinical photographs from a 2-year-old patient with right thumb Blauth
type IIIB hypoplasia (A), and after thumb ablation and index finger pollicization
(B).(Courtesy of Kevin J. Little, MD.)

Ulnar Longitudinal Deficiency

Ulnar longitudinal deficiency represents a spectrum of postaxial
(ulnar-sided) hypoplasia of the upper limb resulting from
disruption of the SHH signaling pathway in the zone of polarizing
activity. 21 However, because a feedback loop exists between SHH
and FGF during upper limb development, thumb hypoplasia can
also occur in the se ing of ulnar longitudinal deficiency. 21 Ulnar
longitudinal deficiency is 4 to 10 times less common than RLD
occurring with a frequency of one to 7.4 per 100,000. 15 , 22 Most cases
are sporadic and unlike RLD, organ anomalies are not associated.
Congenital hand differences, scoliosis, phocomelia, fibular
deficiency, and proximal focal femoral deficiency, however, are
highly associated.
Clinical findings are highly variable and can range from
hypoplastic to absent ulna, ulnar-sided digits (up to 90%), carpal
bones, humerus, or shoulder girdle; presence or absence of thumb
abnormalities (up to 70%), carpal coalitions, syndactyly (up to 30%),
metacarpal synostoses, congenital radial head dislocation, and
radioulnar synostosis. 21 , 23 , 24 The degree of upper limb shortening,
forearm bowing, and wrist ulnar deviation is also variable. The
elbow is usually abnormal and can be fused.
The Bayne classification is most commonly used and is based on
the progressive degree of ulnar hypoplasia, ranging from type I
(short distal ulna), type II (hypoplastic ulna), type III (total absence
with straight radius), and type IV (usually complete absence of the
ulna with radiohumeral synostosis and a bowed radius). The
classification has been modified to include type 0 to describe
abnormalities of the hand and wrist in the absence of forearm
pathology. 24
Surgical management focuses primarily on optimizing hand
pinch and grasp function, including first web space deepening,
thumb syndactyly release, thumb metacarpal derotation osteotomy,
and syndactyly releases of other digits. Indications for more
proximal surgical interventions are less clear and include
progressive or fixed ulnar wrist deviation for which excision of the
ulnar anlage can be performed and extreme shoulder internal
rotation for which humeral derotation osteotomy can be performed.

Congenital Radioulnar Synostosis

Congenital radioulnar synostosis (CRUS) is an abnormal
connection between the proximal radius and ulna that usually fixes
the forearm in a pronated position. As reviewed in a 2020 study,
this is a result of signaling errors during embryonic development
that result in failure of longitudinal segmentation. 25 No clear
inheritance pa ern is responsible; however, CRUS can be
associated with other conditions such as Apert syndrome, Poland
syndrome, Holt-Oram syndrome, and Cornelia de Lange syndrome.
25
Bilateral involvement occurs in 60%. 26
In general, most children with CRUS have compensatory motion
through the shoulder and wrist that has developed to maintain
function. CRUS is classified into four types based on radiographic
findings: type I (nonbony synostosis), type II (osseous synostosis),
type III (osseous synostosis with hypoplastic and posteriorly
dislocated radial head), and type IV (osseous synostosis with
anteriorly dislocated mushroom-shaped radial head). 27
Surgery has generally been recommended for patients with
severe functional limitations, bilateral involvement, fixed pronation
over 60°, and lost elbow flexion due to radial head impingement in
type IV. 25 , 28 Procedures focus on mobilization, such as synostosis
resection and interposition, or repositioning, such as derotation
osteotomy, radial head excision, and Ilizarov method with gradual
derotation using a frame. Ideal position of the forearm remains
controversial, but general recommendations for positioning for
bilateral involvement range from neutral to 30° of supination for
the nondominant extremity and neutral to 30° of pronation for the
dominant extremity. 25 , 29 - 31

Preaxial Polydactyly
Polydactyly is the second most common congenital hand difference
following syndactyly, with preaxial (radial/thumb) polydactyly
being the second most common type after postaxial polydactyly.
Although most cases are sporadic and unilateral, autosomal
dominant inheritance can occur, particularly with triphalangeal
thumbs (Fla -Wassel VII) wherein there is also a higher association
with conditions such as Fanconi anemia, Holt-Oram syndrome, and
Rubinstein-Taybi syndrome. 32 - 34 Preaxial polydactyly is the most
common duplication seen in Caucasian and Asian populations.
Preaxial polydactyly is characterized by heterogenous
presentations of a duplicated thumb; however, because each thumb
generally is deficient in its structures, split or bifid thumb may
be er describe this congenital hand difference. 33 , 35 Furthermore,
more complex forms can occur, such as divergent or divergent-
convergent (zigzag) duplications that result from both bony
abnormalities as well as anomalous or eccentric tendon insertions.
A pollex abductus, an anomalous connection between the flexor
pollicis longus and extensor pollicis longus tendons, should be
considered if the thumb interphalangeal joint is stiff.
The Fla -Wassel classification (Figure 5) describes preaxial
polydactyly according to seven types based on the bony level of
duplication from distal to proximal, with odd numbers being bifid
duplications, even numbers being complete duplications, and type
VII being a triphalangeal thumb. Fla -Wassel type IV (duplicated
proximal phalanges) is the most frequent type (40% to 45%). 33
Figure 5 Illustration of the Wassel classification for preaxial polydactyly.
 The ultimate treatment goal is to create a functional and
cosmetically acceptable thumb. Timing of surgery should occur
before pinch and fine motor development at approximately 9 to 12
months. 33 Ligation should be limited to pedunculated thumbs.
Simple excision generally is insufficient and leads to poorer
outcomes than reconstruction. Most techniques focus on using
components of both thumbs to create one thumb (Bilhaut-Cloquet
procedure), or excision of the less dominant thumb and
reconstruction of the remaining thumb using spare parts. The main
components of thumb reconstruction are joint stabilization,
corrective osteotomy, and tendon realignment. The most common
reason for reoperation is thumb angulation.

Postaxial Polydactyly
Postaxial polydactyly, or ulnar-border digital duplication, is more
common in patients of African descent. Although nonsyndromic
types typically occur in isolation through an autosomal dominant
inheritance pa ern, a greater incidence of syndromic associations is
reported in Caucasian populations, and a genetic workup should be
considered. Postaxial polydactyly can be classified into type A and
type B. 36 Type A represents a well-formed digit with an articulation
and is far less common than type B, which is a poorly formed
rudimentary digit connected by a soft-tissue bridge and is more
prevalent in African populations. Treatment options for type B
include simple ligation or surgical excision. Simple ligation with a
vascular clip or suture avoids the need for general anesthesia;
however, potential risks include bleeding, neuroma formation, and
residual bump. 37 Similar to preaxial polydactyly, type A postaxial
polydactyly surgical treatment involves surgical reconstruction,
which may include skin and intrinsic musculature rearrangement,
tendon rebalancing, corrective osteotomies, and joint stabilization
procedures. 38 , 39

Syndactyly
Syndactyly, or webbed digits, is the most common congenital hand
difference occurring in 1:2000 live births. 40 It is twice as common in
males 41 and 10 times more frequent in Caucasians than African
Americans. 42 Although most cases are sporadic, cases can occur
through an autosomal dominant pa ern with 10% to 40% being
familial. Additionally, syndactyly can occur in association with
other upper extremity anomalies such as cleft hand,
symbrachydactyly, synpolydactyly, and syndromes such as amniotic
band, Cenani-Lenz, Apert, and Poland. Syndactyly results as a
failure of differentiation in the AER of the hand paddle wherein
there is a lack of apoptosis of the interdigital mesenchyme. The
third web space is the most commonly affected, with the mnemonic
“5-15-50-30” reflecting the frequency of web space occurrence from
radial to ulnar.
Syndactyly is commonly classified into simple or complex, and
complete or incomplete. Simple syndactyly involves only skin and
subcutaneous tissue, whereas complex syndactyly involves bony
fusion with possible involvement of tendon and neurovascular
structures. Complete syndactyly involves the entire length of the
digit and can include the nail plate (synonychia), whereas the
syndactyly is considered incomplete if the web does not extend the
entire length.
Surgical treatment is generally recommended for syndactyly. The
main principles of treatment are separation of the digital skin
(bone, tendon, nail, and neurovascular structures for complex
cases), web space/commissure reconstruction, and tendon or
ligament reconstruction as needed. 43 Although timing remains
controversial, surgery is usually considered after 6 months of age to
minimize anesthetic risk and allow time for growth of anatomic
structures to facilitate surgical dissection, and prior to age 2 years
before establishment of fine motor function. 44 Syndactylized
border digits should be released before 9 months of age to avoid
secondary camptodactyly and/or clinodactyly due to tethering of
digits of disparate lengths. 43 , 45 Syndactyly of the second or third
web space can be delayed safely until approximately 18 to 24
months of age. When multiple adjacent syndactylized digits are
present, a staged approach should be undertaken to avoid vascular
compromise to the digits.
Multiple zigzag interdigitating flaps are used to separate the
digits to avoid linear scar formation and mitigate contracture.
Careful defa ing of the flaps aids with coverage. If there is
insufficient soft-tissue coverage after flap inset, then full-thickness
skin grafts from the hypothenar eminence, antecubital fossa, or
volar wrist or groin can be used. Various advancement flaps have
been described for the reconstruction of the web commissure with
the most common being a dorsal rectangular advancement flap
(Figure 6). Postoperative web space creep (distal migration of the
reconstructed commissure) can be minimized by performing
tension-free repair, liberal use of full-thickness as opposed to split-
thickness skin grafts, and avoiding linear scars.

Figure 6 A, Clinical photograph from a 5-year-old patient with a complex

syndactyly. B, Radiograph showing the proximal phalanx. C, Clinical photograph
after syndactyly release with skin flaps and full-thickness skin grafts.(Courtesy of
Andrea H.W. Chan, MD.)

Clinodactyly
Clinodactyly is defined as an abnormal bending of a finger in the
coronal plane. Most commonly clinodactyly involves the li le finger
at the middle phalanx, but it can affect all digits. When affected, the
digits tend to curve toward the middle of the hand, such that the
ring and li le fingers have a curvature toward the index and middle
fingers, and vice versa. Clinodactyly of the thumb tends to involve
the proximal phalanx and typically causes curvature away from the
hand. Clinodactyly is frequently inherited in an autosomal
dominant fashion with variable penetrance and is commonly
bilateral in appearance. Patients with sex chromosome
abnormalities (Klinefelter, Turner syndromes), and other common
genetic syndromes (Down, Rubenstein-Taybi, and Fanconi) often
present with clinodactyly, but a presentation of isolated
clinodactyly is more common.
The inward bending of the finger is due to aberrant middle
phalanx, which is short (brachymesophalangia) and either
trapezoid or triangular shaped. For patients with a trapezoidal
shaped bone, the clinodactyly is relatively stable, but those with a
bracket epiphysis or delta phalanx may have progression over time
because of tethered growth. This can lead to functional deficits with
overlap of the fingertips with digital flexion and difficultly with
gripping. Most often, the best treatment is observation and
occasional episodes of occupational therapy to help with functional
difficulties. Splinting has not been shown to be effective. In patients
with greater than 30° of angulation, however, surgical treatment
may be indicated. Patients younger than 6 years with a bracket
epiphysis can improve deformity over time with physiolysis (Figure
7). This involves removing a small portion of the bracket epiphysis
cartilage while sparing the collateral ligaments of the proximal
interphalangeal (PIP) and distal interphalangeal joints. This allows
for remodeling and improved growth over time with longitudinal
growth of both the proximal and distal physes. In older patients
with insufficient growth remaining, an opening wedge or reverse
wedge osteotomy of the middle phalanx can be performed to
maintain length and correct deformity. However, distal
interphalangeal stiffness is a complication of this because of
postoperative immobilization of the distal interphalangeal joint,
and recurrent deformity can develop. 46

Figure 7 Images of the right little finger of a 5-year-old patient with clinodactyly
due to a bracket epiphysis.A, Radiograph showing angular deformity of 36°. B,
Intraoperative fluoroscopy shows management with physiolysis. C, Three years
after surgery, the deformity has remodeled to 14°.(Courtesy of Kevin J. Little,
MD.)

Camptodactyly
Camptodactyly is an atraumatic curvature of the finger PIP joint in
the sagi al plane, most commonly involving the li le finger. This
curvature is noticed either early after birth (type I) or around the
first decade of life (type II), related to rapid growth. The underlying
cause of camptodactyly is debated and may be related to abnormal
tendon structure, involving the intrinsic muscles, lumbricals, or
flexor digitorum superficialis (FDS) tendons. Cosmetic concerns
often outweigh functional deficits, although with significant
contractures, patients may have difficulty with typing, sports,
donning or removing gloves, or reaching into their pockets.
Radiographic changes including fla ening of the dorsal surface of
the proximal phalanx head and middle phalanx base are noted in
approximately 30% of patients. The clinical evaluation should
include the amount of contracture present, and the degree of
correction with metacarpophalangeal joint flexion, as well as
improvements in active flexion with the Bouvier maneuver. This can
help elucidate if skin contractures are present, as well as the
relative contribution of intrinsic muscle imbalance or
abnormalities. 47
The initial treatment for camptodactyly should include stretching
exercises and nigh ime extension splinting, and may include a
daytime relative motion orthosis to improve active flexion. Surgical
treatment is reserved for the most severe contractures, often
greater than 60° and with functional deficits. Surgical treatment can
involve contracture release with rotational skin flap or Z-plasty for
the skin deficit, with additional soft-tissue releases of the fascia,
lumbricals, interosseous muscles, FDS tendon, check-rein
ligaments of the volar plate, joint capsule, and extensor mechanism
(Figure 8). Surgical treatment is fraught with complications
including stiffness, weakness, and recurrent deformity, and thus
should only be undertaken after a thorough discussion with
patients and families about the potential risks and benefits. 48 , 49
 Figure 8 Clinical photograph of the left hand of a 9-year-old patient with
camptodactyly of the ring and middle fingers treated with a four-flap Z-plasty at
the proximal interphalangeal joint.The long finger demonstrates the flap design
and the ring finger demonstrates the extension gained after flap closure.
(Courtesy of Kevin J. Little, MD.)

Kirner Deformity
Kirner deformity is an atraumatic sagi al plane curvature of the
distal phalanx of the li le finger, most commonly seen bilaterally
and in females. The cause of the curvature is unknown, but it
manifests as a volar tethering or volar curvature of the distal
phalanx, leading to a curved appearance of the finger. This does not
commonly lead to functional difficulties, and surgery is seldom
performed because of the risks of disordered growth of the phalanx
and the overlying nail.

Metacarpal Synostosis/Carpal Coalition

Carpal coalitions and metacarpal synostoses are present because of
a failure of segmentation of the normal hand bones. Carpal
coalitions are most commonly noted as incidental findings on wrist
or hand radiographs taken for other reasons. Coalitions are
typically found within a carpal row, and do not limit mobility. The
most common presentation is a carpal coalition between the lunate
and triquetrum, which is seen most commonly in patients of
African descent and in females twice as often as in males. Pain
through a mobile synchondrosis, which can be confirmed with
edema in the lunate and triquetrum with MRI, is an indication for
surgical treatment that typically involves arthrodesis of the
symptomatic synchondrosis.
Metacarpal synostosis is an abnormal connection between two
adjacent metacarpals, most commonly between the ring and li le
fingers. Metacarpal synostosis is associated with other syndromes
of hand-plate malformations, such as cleft hand, radial and ulnar
longitudinal dysplasia, symbrachydactyly, clinodactyly and Apert
syndrome. The synostosis does not lead to functional deficits but is
often associated with an abduction deformity of the li le finger,
which can lead to difficulties with grasping and hand strength. In
these patients, a longitudinal osteotomy with interposition bone
grafting to widen the metacarpals will correct the abduction
deformity and can improve function. 50

Cleft Hand
Cleft hand, or ectrodactyly, is a central ray deficiency in the hand,
with a V-shaped hand, contrary to the typical U-shaped hand seen
in symbrachydactyly. This deformity is secondary to a central
longitudinal deficiency and can be sporadic or associated with
syndromes in 25% to 40% of patients. Patients with bilateral cleft
hands frequently have foot abnormalities, which may even progress
into the lower leg. Patients with cleft hand frequently function quite
well, but often use the cleft as their thenar space for grasping and
pinching objects. A 2019 case series discusses the two main
classification schemes used to describe cleft hand: the Manske and
Halikis classification describes the thumb/index syndactyly, and the
Oberg classification describes the severity of the missing central
rays of the hand 51 (Table 5).

Table 5
Manske and Halikis Classification (Assessing the Thumb/Index
Web Space) Compared With the Ogino Classification (Assessing
Central Ray Deficiency) for Cleft Hand

Type Manske and Halikis Ogino

I Normal thumb/index web space Cleft hand without missing ray
II IIA: mildly narrowed web space Bony deficiency of single finger ray
IIB: moderately narrowed web space
III Thumb/index syndactyly Bony deficiency of two finger rays
IV Thumb merged into the cleft Bony deficiency of three finger rays
V n/a Bony deficiency of four finger rays

Treatment of cleft hand is complicated by the fact that the

deformity often is quite functional, whereas the cosmesis of the
hand is lacking. Cleft hand has been described as a functional
triumph but a social disaster. However, both cosmesis and function
can be improved in patients where the cleft is limiting grip, but
multiple surgeries are frequently required. The cleft can be closed,
and the skin rotated into the thumb/index web space to restore the
normal alignment of the digital rays, and secondary surgeries for
ring/li le finger syndactyly or metacarpal synostosis may be
necessary (Figure 9). Patients with transverse bones in the cleft
should have them removed extraperiosteally during cleft
reconstruction to reduce the risk of regrowth. Significant
thumb/index web narrowing or coalitions can limit the ultimate
functional results for patients with cleft hands, but patients with a
transverse bone do not have any functional differences when
compared with those without one. 52
 Figure 9 Clinical photographs from an 18-month-old boy with cleft hand.A,
Cleft hand with a missing middle finger ray, associated with a hypoplastic little
finger and duplicated thumb. B, Three years following cleft hand reconstruction
by transposing the cleft flap into the thumb/index web space, the patient is doing
well.(Courtesy of Kevin J. Little, MD.)

Amniotic Band Syndrome

Amniotic band syndrome is a deformity resulting from extrinsic
compression on the developing fetus. This congenital anomaly, also
known as constriction band syndrome, constriction ring syndrome,
or Streeter dysplasia, can lead to multiple anomalies throughout
the body. Strings of detached amniotic membrane are thought to
wrap around the fetus, which then compress the developing limbs
during maturation. The remnant of the amniotic bands can be seen
in some children immediately after birth (Figure 10). The
constrictions can lead to a fenestrated acrosyndactyly, compressive
scar bands around the extremities, and congenital amputations of
digits or entire limbs. Amniotic band syndrome is also associated
with clubfoot, cleft palate, cleft lip, or compressive bands on the
torso. 53
 Figure 10 Clinical photograph of the left hand of a 3-day-old infant with
amniotic band syndrome and acrosyndactyly and a congested index
fingertip.Note the amniotic band remnant still present (black arrow).(Courtesy of
Kevin J. Little, MD.)

Patients with tight compression leading to altered perfusion

benefit from urgent removal of the bands and release of the scar
tissue. Tight constrictions around the extremities may be associated
with a compressive neuropathy, which is variably relieved with
band release, soft-tissue reconstruction with multiple Z-plasty or Y-
V plasty skin flaps, and neurolysis of the nerve. Patients with
acrosyndactyly often benefit from surgical syndactyly release
(described previously), or excision of compressive digital bands
with soft-tissue mobilization. Bony overgrowth of the congenitally
or surgically amputated digits is common in these patients, and
they should be monitored with serial clinical and radiographic
examinations.
Macrodactyly
Macrodactyly is an overgrowth phenomenon that leads to
significant enlargement of part or all of the hand or limb. The
overgrowth is often nerve mediated and occurs in a neurotomal
distribution. There are multiple syndromes identified that lead to
macrodactyly, including fibrolipomatous hamartoma of the median
nerve, neurofibromatosis I, as well as CLOVES (Congenital
Lipomatous Overgrowth, Vascular malformations, Epidermal nevi
and Skeletal/Spinal abnormalities), Proteus, Parkes Weber, and
Klippel-Trenaunay syndromes. According to a 2019 review, most of
these syndromes have been shown to have a final common pathway
for overgrowth involving the PIK3CA cell signaling pathway. 54
Macrodactyly can be associated with syndactyly, curvature of the
finger due to asymmetric growth, and fibrous overgrowth leading to
permanent digital stiffness.
The overgrowth noted in macrodactyly is variable, with some
patients having only minor overgrowth, whereas others can have
significantly debilitating overgrowth leading to loss of hand and
arm function. Thus, the treatment strategy depends on the physical
examination findings, as well as the rate of overgrowth. The
overarching goal is to maximize function of the limb, while
a empting to limit the size of the overgrown limb to that of the
same-sex parent. Epiphysiodesis of the digit when it reaches the
length of the same-sex parent will limit longitudinal overgrowth
but will not limit circumferential overgrowth. Debulking of the
overgrown tissues can help decrease the circumferential size of the
digit, but may lead to scarring (keloid formation is common in
many patients with macrodactyly) and limited motion. Corrective
osteotomy or even ray resection can be performed for enlarged and
angulated digits. 55

Trigger Digit
Trigger Thumb
Trigger thumb was initially thought to be a congenital condition,
but has since been noted to be developmental, occurring typically
by age 2 years. It is one of the most common developmental hand
conditions seen, with an equal predilection for males and females,
with bilateral asynchronous presentation in up to 25% of patients.
Overgrowth of the flexor pollicis longus tendon leads to a difficulty
or inability of the tendon to glide through the first annular pulley of
the thumb. This overgrowth is palpable through the skin and is
called a No a node. Ultrasonographic studies have shown that the
flexor pollicis longus tendon is up to 77% larger at No a node when
compared with the area beneath the pulley, and have also
demonstrated that trigger thumbs can resolve as the pulley
enlarges over time, while the tendon size remains similar over time.
Thus, resolution has been shown to occur spontaneously in 32% to
76% of patients treated with observation. As discussed in a 2021
study, patients with initial interphalangeal flexion contractures of
less than 30° were associated with spontaneous resolution by 3
years of age, and spontaneous resolution decreased by 3% for every
degree increase of flexion contracture. 56
Surgical treatment, involving release of the A1 pulley of the
thumb, can be performed at any time, but is generally done
between the ages of 3 and 6 years. This allows for spontaneous
resolution to occur without additional risks of persistent digital
stiffness or anesthesia. Complications are rare, but a recurrence
rate of up to 4% has been reported because of incomplete release of
the pulley. Release can be confirmed by performing tenodesis-
assisted flexion and extension of the thumb. Open release is
preferred to percutaneous release, as a more limited exposure has
been shown to increase recurrence rates and risks injury to the
flexor pollicis longus tendon. 57

Trigger Finger
Triggering of the fingers is approximately 10 times less likely than
in the thumb in children. Trigger finger can present as early as 6
months of age, but, on average, presents at a later age than does
trigger thumb. Trigger finger is associated with
mucopolysaccharidoses, juvenile idiopathic arthritis, Down
syndrome, and Ehlers-Danlos syndrome. The flexor anatomy of the
finger is more complicated than that of the thumb, with
abnormalities of the FDS decussation, A1 pulley, or flexor
digitorum profundus tendon leading to triggering. Triggering at
the A1 pulley typically involves the flexor digitorum profundus and
leads to a flexion position of the PIP joint, whereas triggering of the
flexor digitorum profundus through the FDS decussation at the
level of Camper chiasm will lead to additional contractures at the
flexor digitorum profundus joint. In some cases, unlocking of the
trigger can be noted clinically with a separate trigger over both the
A1 and A2 pulleys.
Treatment initially consists of splinting, occupational therapy,
and range of motion exercises. Corticosteroid injections are not
indicated unless an underlying inflammatory process such as
juvenile idiopathic arthritis or tenosynovitis is suspected.
Spontaneous resolution of trigger finger is slow and can take more
than 1 year, but nonsurgical treatment should be a empted in
patients without locked triggering or significant pain. If
nonsurgical treatments are unsuccessful, surgical release can be
performed, noting that triggering at the chiasm cannot be released
with a simple A1 pulley release. Thus, for surgical trigger finger
release, a Brunner incision over the proximal phalanx is used from
the palmar crease to the PIP crease. This allows for exposure of the
A1, A2, and A3 pulleys; release of A1 and A3; and excision of a slip
of the FDS tendon to resolve all points of triggering. Postoperative
splinting is useful to aid in rehabilitation following trigger release
until the wound is healed, and then full mobility is typically
regained. 58

Brachial Plexus Birth Injury

Brachial plexus birth injury (BPBI) results from a traction injury to
the brachial plexus during the birthing process. The incidence
varies across the world, from 0.4 to four per 1,000 live births,
although the incidence has been slowly decreasing over the past
several decades. 59 , 60 The risk factors for BPBI include shoulder
dystocia, gestational diabetes, fetal macrosomia (>3.5 kg), assisted
(vacuum or forceps) delivery, breech delivery, multiple births (both
via cesarean section and natural), oxytocin administration, and
uterine tachysystole. 60 , 61
Most commonly, the upper trunk (C5, C6) is affected (Erb palsy),
resulting in weakness in shoulder elevation and elbow flexion.
Progressive injury will involve the middle trunk (C7), additionally
affecting elbow, wrist and finger extension, and the lower trunk (C8,
T1), resulting in a flaccid arm. An isolated lower trunk injury
(Klumpke palsy) affecting finger and hand function has also been
reported, but is very rare in BPBI and may be associated with
breech delivery. Spontaneous recovery is possible in patients with
BPBI, with increasing severity of injury correlating with decreased
spontaneous recovery potential.
Overall, approximately 20% to 30% of patients with BPBI will
have permanent residual deficits and may require surgical
intervention. 62 Patients with a global injury without signs of
recovery will benefit from surgical exploration of the brachial
plexus at 3 months of age, to maximize the potential for recovery of
hand function. Patients with an upper (C5, C6) or extended upper
trunk (C5, C6, C7) injury can wait for biceps recovery by 6 months
of age. Lack of biceps recovery by 6 months is indicative of a
complete (neurotmesis) injury to the brachial plexus with
insufficient long-term recovery potential. 63 Patients who meet these
milestones but still have insufficient recovery of isolated muscles
may benefit from targeted nerve transfers up to 18 months of age.
Thus, as discussed in a 2021 study, patients should be referred to a
brachial plexus injury center early in life, such that their recovery
can be carefully monitored and surgical intervention indicated
when milestones have not been met. 64
 Nerve injury during the neonatal period leads to decreased
muscle growth over time, resulting in progressive contractures. 65
This is most commonly noted in the shoulder, specifically the upper
subscapularis muscle (via the upper subscapular nerve branch),
which can lead to progressive internal rotation contracture. This
places excess pressure on the posterior margin of the glenoid and,
according to the Heuter-Volkmann principle, leads to overgrowth of
the anterior glenoid and undergrowth of the posterior glenoid. If
left unchecked, this process will lead to progressive glenohumeral
dysplasia, pseudoglenoid formation, and posterior subluxation of
the glenohumeral joint. Additionally, contracture of the biceps and
brachialis muscles (via the musculocutaneous nerve) leads to elbow
flexion contractures. 66 These contractures can be noted as early as 3
months of age. 67 Early referral to a brachial plexus center and
occupational therapy will help with patient education about these
processes and the initiation of range of motion, passive stretching,
and active motion exercises, which should be initiated early after
delivery. In the shoulder, screening ultrasonography should be
performed as soon as passive external rotation of the shoulder is
noted to be less than 45°. Shoulder subluxation that is passively
reducible in external rotation can be managed with botulinum toxin
A injections and a shoulder spica cast. If the joint is not passively
reducible, then a partial subscapularis release and joint relocation
surgery should be performed, followed by external rotation tendon
transfer to maintain joint stability and congruity long term. Patients
older than 4 years with a late diagnosis of shoulder subluxation
may benefit from glenoid or humeral osteotomy to improve
shoulder position. Elbow flexion contractures are often treated with
stretching, static progressive nigh ime splinting, and serial casting.

Summary
A wide variety of malformations, dysplasias, and growth disorders
can affect pediatric hands in many complex ways. Thus, a good
history, careful physical examination, and discussion with the
patient, caregivers, physicians, occupational therapists, and other
involved parties are essential to provide the best recommendations
for the patient. Understanding the unique and various ways these
disorders can present and how surgical and nonsurgical
interventions can affect function will ultimately help the patient
maximize their outcomes.

Key Study Points

Congenital hand malformations can be associated with cardiac, renal, or
hematologic abnormalities, and appropriate guidance, testing, or genetics referral is
indicated for many patients.
There is no single perfect treatment for all patients with congenital hand
abnormalities, and, as such, a discussion with patients and family is essential to
help guide the best outcomes for each patient.
In addition to functional and cosmetic concerns, patients may have psychosocial
implications from their hand differences, and appropriate referral may be indicated
for some patients.

Annotated References
1. Al-Qa an MM, Yang Y, Kozin SH: Embryology of the upper
limb. J Hand Surg Am 2009;34(7):1340-1350.
2. Al-Qa an MM, Kozin SH: Update on embryology of the upper
limb. J Hand Surg Am 2013;38(9):1835-1844.
3. Dy CJ, Swarup I, Daluiski A: Embryology, diagnosis, and
evaluation of congenital hand anomalies. Curr Rev Musculoskelet
Med 2014;7(1):60-67.
4. Oberg KC, Feenstra JM, Manske PR, Tonkin MA: Developmental
biology and classification of congenital anomalies of the hand
and upper extremity. J Hand Surg Am 2010;35(12):2066-2076.
5. Woodside JC, Light TR: Symbrachydactyly – Diagnosis, function,
and treatment. J Hand Surg Am 2016;41(1):135-143, quiz 143.
6. Goodell PB, Bauer AS, Sierra FJ, James MA: Symbrachydactyly.
Hand (N Y) 2016;11(3):262-270.
 7. Bain GI, Wa s AC, McLean J, Lee YC, Eng K: Cable-augmented,
quad ligament tenodesis scapholunate reconstruction: Rationale,
surgical technique, and preliminary results. Tech Hand Up Extrem
Surg 2013;17(1):13-19.
8. Wall LB, Ezaki M, Oishi SN: Management of congenital radial
longitudinal deficiency: Controversies and current concepts. Plast
Reconstr Surg 2013;132(1):122-128.
9. Goldfarb CA, Wall L, Manske PR: Radial longitudinal deficiency:
The incidence of associated medical and musculoskeletal
conditions. J Hand Surg Am 2006;31(7):1176-1182.
10. James MA, McCarroll HRJr, Manske PR: Characteristics of patients with hypoplastic
thumbs. J Hand Surg Am 1996;21(1):104-113.
11. Waters PM, Bae DS: Radial longitudinal deficiency, in Waters PMB, Donald S, eds:
Pediatric Hand and Upper Limb Surgery: A Practical Guide. Lippincott, Williams & Wilkins,
2012, pp 121-131, chap 13.
12. Bayne LG, Klug MS: Long-term review of the surgical treatment of radial deficiencies. J
Hand Surg Am 1987;12(2):169-179.
13. James MA, McCarroll HRJr, Manske PR: The spectrum of radial longitudinal deficiency: A
modified classification. J Hand Surg Am 1999;24(6):1145-1155.
14. Goldfarb CA, Manske PR, Busa R, Mills J, Carter P, Ezaki M: Upper-extremity
phocomelia reexamined: A longitudinal dysplasia. J Bone Joint Surg Am 2005;87(12):2639-
2648.
15. Bednar MS, James MA, Light TR: Congenital longitudinal deficiency. J Hand Surg Am
2009;34(9):1739-1747.
16. van Alphen NA, Moran SL: Radial deficiency, in Abzug JM, Kozin SH, Zlotolow DA, eds:
The Pediatric Upper Extremity. Springer-Verlag, 2015, pp 237-264, chap 11.
17. Wall LB, Kim DJ, Cogsil T, Goldfarb CA: Treatment of radial longitudinal deficiency: An
international survey. J Hand Surg Am 2021;46(3):241.e1-241.e11. An international survey was
performed to assess the treatment patterns for patients with radial longitudinal deficiency.
They reported consensus opinion for the treatment of type I radial deficiency and Type 3B and
IV thumb hypoplasia, but variable surgical approaches including for pollicization positioning
and more severe types of radial deficiency.
18. Ekblom AG, Dahlin LB, Rosberg HE, Wiig M, Werner M, Arner M: Hand function in adults
with radial longitudinal deficiency. J Bone Joint Surg Am 2014;96(14):1178-1184.
19. Tay SC, Moran SL, Shin AY, Cooney WP: The hypoplastic thumb. J Am Acad Orthop
Surg 2006;14(6):354-366.
20. Manske PR, McCarroll HR, James M: Type III-A hypoplastic thumb. J Hand Surg Am
1995;20(2):246-253.
21. Bauer AS, Bednar MS, James MA: Disruption of the radial/ulnar axis: Congenital
longitudinal deficiencies. J Hand Surg Am 2013;38(11):2293-2302, quiz 2302.
22. Froster UG, Baird PA: Upper limb deficiencies and associated malformations: A
population-based study. Am J Med Genet 1992;44(6):767-781.
23. Elhassan BT, Biafora S, Light T: Clinical manifestations of type IV ulna longitudinal
dysplasia. J Hand Surg Am 2007;32(7):1024-1030.
24. Havenhill TG, Manske PR, Patel A, Goldfarb CA: Type 0 ulnar longitudinal deficiency. J
Hand Surg Am 2005;30(6):1288-1293.
25. Rutkowski PT, Samora JB: Congenital radioulnar synostosis. J Am Acad Orthop Surg
2021;29(13):563-570. This article reviews the embryology, anatomy, clinical features, and
management of CRUS. Limited high-level evidence exists to guide treatment; however,
surgery should generally be reserved for those with severe rotational deformities. Level of
evidence: V.
26. Ogino T, Hikino K: Congenital radio-ulnar synostosis: Compensatory rotation around the
wrist and rotation osteotomy. J Hand Surg Br 1987;12(2):173-178.
27. Cleary JE, Omer GEJr: Congenital proximal radio-ulnar synostosis. Natural history and
functional assessment. J Bone Joint Surg Am 1985;67(4):539-545.
28. VanHeest AE, Lin TE, Bohn D: Treatment of blocked elbow flexion in congenital radioulnar
synostosis with radial head excision: A case series. J Pediatr Orthop 2013;33(5):540-543.
29. Rubin G, Rozen N, Bor N: Gradual correction of congenital radioulnar synostosis by an
osteotomy and Ilizarov external fixation. J Hand Surg Am 2013;38(3):447-452.
30. Horii E, Koh S, Hattori T, Otsuka J: Single osteotomy at the radial diaphysis for congenital
radioulnar synostosis. J Hand Surg Am 2014;39(8):1553-1557.
31. Barik S, Farr S, Gallone G, Zarantonello P, Trisolino G, Di Gennaro GL: Results after
treatment of congenital radioulnar synostosis: A systematic review and pooled data analysis.
J Pediatr Orthop B 2020;30(6):593-600. This is a systematic review of 23 articles analyzing
outcomes following surgical management. Derotation surgeries were most commonly
performed. A pronation position of 0° to 30° for the dominant arm and supination position of 0°
to 35° for the nondominant arm are considered the most ideal. Complications are related to
corrections over 65°. Level of evidence: II.
32. Rogers BH, Schmieg SL, Pehnke ME, Shah AS: Evaluation and management of preaxial
polydactyly. Curr Rev Musculoskelet Med 2020;13(4):545-551. A review of the embryology,
classification, evaluation, surgical management, and clinical outcomes related to preaxial
polydactyly.
33. Waters PM, Bae DS: Preaxial polydactyly, in Waters PM, Bae DS, eds: Pediatric Hand
and Upper Limb Surgery. Lippincott, Williams & Wilkins, 2012, pp 32-42, chap 4.
34. Baek GH: Duplication, in Abzug JM, Kozin SH, Zlotolow DA, eds: The Pediatric Upper
Extremity. Springer Reference, 2015, pp 325-368, chap 15.
35. Bauer AS, Netto AP, James MA: Thumb hypoplasia occurring in patients with preaxial
polydactyly. J Hand Surg Am 2020;45(3):182-188. This is a retrospective chart review of 132
patients who underwent reconstruction for thumb polydactyly. Ipsilateral thumb hypoplasia was
found at an incidence of 8.2%. The authors recommend preoperative clinical evaluation for
hypoplastic thumb in patients who present with preaxial polydactyly. Level of evidence: IV.
36. Temtamy SA, McKusick VA: The genetics of hand malformations. Birth Defects Orig Artic
Ser 1978;14(3):i-xviii, 1-619.
37. Abzug JM, Kozin SH: Treatment of postaxial polydactyly type B. J Hand Surg Am
2013;38(6):1223-1225.
38. Waters PM, Bae DS: Postaxial polydactyly, in Lippincott WW, ed: Pediatric Hand and
Upper Limb Surgery. Philadelphia, PA, Lippincott Williams and Wilkins, 2012, pp 26-31, chap
3.
39. Rayan GM, Frey B: Ulnar polydactyly. Plast Reconstr Surg 2001;107(6):1449-1454.
40. Flatt AE: The Care of Congenital Hand Anomalies. Mosby, 1977.
41. Kay S, McCombe D, Kozin S: Deformities of the hand and fingers, in Green D, Hotchkiss
R, Pederson W, Wolfe S, eds: Green’s Operative Hand Surgery, ed 6. Elsevier, 2011.
42. Flatt AE: Webbed fingers. Proc (Bayl Univ Med Cent) 2005;18(1):26-37.
43. Manske CM, Goldfarb CA: Syndactyly, in Abzug JM, Kozin SH, Zlotolow DA, eds: The
Pediatric Upper Extremity. Springer, 2015, pp 277-296, chap 13.
44. Hutchinson DT, Frenzen SW: Digital syndactyly release. Tech Hand Up Extrem Surg
2010;14(1):33-37.
45. Waters PM, Bae DS: Syndactyly, in Waters PMB, Donald S, eds: Pediatric Hand and
Upper Limb Surgery. Lippincott, Williams & Wilkins, 2012, pp 12-25, chap 2.
46. Piper SL, Goldfarb CA, Wall LB: Outcomes of opening wedge osteotomy to correct
angular deformity in little finger clinodactyly. J Hand Surg Am 2015;40(5):908-913.e1.
47. Wall LB, Ezaki M, Goldfarb CA: Camptodactyly treatment for the lesser digits. J Hand
Surg Am 2018;43(9):874.e1-874.e4.
48. Wang AMQ, Kim M, Ho ES, Davidge KM: Surgery and conservative management of
camptodactyly in pediatric patients: A systematic review. Hand (N Y) 2020;15(6):761-770. A
systematic review of treatments for patients with camptodactyly incorporated 16 previous
publications, including 7 case series and 9 retrospective cohort studies, is presented. The
guidelines showed that surgical and nonsurgical treatments were effective at reducing the
contracture, and that surgical correction should not be attempted unless the contracture was
>30° or the nonsurgical treatment failed. Level of evidence: III.
49. Foucher G, Loréa P, Khouri RK, Medina J, Pivato G: Camptodactyly as a spectrum of
congenital deficiencies: A treatment algorithm based on clinical examination. Plast Reconstr
Surg 2006;117(6):1897-1905.
50. Gottschalk HP, Bednar MS, Moor M, Light TR: Metacarpal synostosis: Treatment with a
longitudinal osteotomy and bone graft substitute interposition. J Hand Surg Am
2012;37(10):2074-2081.
51. Falcochio DF, Da Costa AC, Durigan CPI, Nascimento VDG, Santili C, Chakkour I:
Epidemiological and clinical aspects of cleft hand: Case series from a tertiary public hospital in
São Paulo, Brazil. Hand (N Y) 2019;14(6):814-818. This is a case series of patients with cleft
hand, which demonstrated that most patients had a typical ectrodactyly pattern with positive
family history and many had thumb web space contractures. Level of evidence: IV.
52. Aleem AW, Wall LB, Manske MC, Calhoun V, Goldfarb CA: The transverse bone in cleft
hand: A case cohort analysis of outcome after surgical reconstruction. J Hand Surg Am
2014;39(2):226-236.
53. Foulkes GD, Reinker K: Congenital constriction band syndrome: A seventy-year
experience. J Pediatr Orthop 1994;14(2):242-248.
54. Ezaki M, Beckwith T, Oishi SN: Macrodactyly: Decision-making and surgery timing. J
Hand Surg Eur 2019;44(1):32-42. A comprehensive review article on contemporary diagnosis,
epidemiology, surgical indications, and timing of surgery is presented. This review helps clarify
decision making and timing for patients with macrodactyly. Level of evidence: V.
55. Waters PM, Gillespie BT: Ray resection for progressive macrodactyly of the hand:
Surgical technique and illustrative cases. J Hand Surg Am 2016;41(8):e251-e256.
56. Hutchinson DT, Rane AA, Montanez A: The natural history of pediatric trigger thumb in the
United States. J Hand Surg Am 2021;46(5):424.e1-424.e7. A prospective case cohort study
evaluating the efficacy of observation of the spontaneous resolution of pediatric trigger thumb.
Overall, approximately one-third of patients had spontaneous resolution and 43% underwent
surgical release. The degree of flexion contracture at presentation correlated with the need for
surgical intervention. Level of evidence: II.
57. Masquijo JJ, Ferreyra A, Lanfranchi L, Torres-Gomez A, Allende V: Percutaneous trigger
thumb release in children: Neither effective nor safe. J Pediatr Orthop 2014;34(5):534-536.
58. Bauer AS, Bae DS: Pediatric trigger digits. J Hand Surg Am 2015;40(11):2304-2309.
59. Foad SL, Mehlman CT, Ying J: The epidemiology of neonatal brachial plexus palsy in the
United States. J Bone Joint Surg Am 2008;90(6):1258-1264.
60. Lalka A, Gralla J, Sibbel SE: Brachial plexus birth injury: Epidemiology and birth weight
impact on risk factors. J Pediatr Orthop 2020;40(6):e460-e465. This study evaluated a state
database of all live births, and evaluated the incidence and risk factors for BPBI. Overall, the
incidence of BPBI decreased over the 14 years evaluated in the database, with shoulder
dystocia, instrumented delivery, multiple births, non-white parents, and Medicaid insurance
being risk factors for BPBI. Level of evidence: II.
61. Louden E, Marcotte M, Mehlman C, Lippert W, Huang B, Paulson A: Risk factors for
brachial plexus birth injury. Children 2018;5(4):46.
62. Pondaag W, Malessy MJ, van Dijk JG, Thomeer RT: Natural history of obstetric brachial
plexus palsy: A systematic review. Dev Med Child Neurol 2004;46(2):138-144.
63. Buterbaugh KL, Shah AS: The natural history and management of brachial plexus birth
palsy. Curr Rev Musculoskelet Med 2016;9(4):418-426.
64. Pondaag W, Malessy MJA: Evidence that nerve surgery improves functional outcome for
obstetric brachial plexus injury. J Hand Surg Eur 2021;46(3):229-236. This review article
assessed the quality and quantity of evidence for nerve surgery in patients with BPBI. The
evidence supports treatment with nerve surgery early in patients with global injuries, which can
be delayed in patients with less severe injuries. Level of evidence: V.
65. Nikolaou S, Peterson E, Kim A, Wylie C, Cornwall R: Impaired growth of denervated
muscle contributes to contracture formation following neonatal brachial plexus injury. J Bone
Joint Surg Am 2011;93(5):461-470.
66. Weekley H, Nikolaou S, Hu L, Eismann E, Wylie C, Cornwall R: The effects of
denervation, reinnervation, and muscle imbalance on functional muscle length and elbow
flexion contracture following neonatal brachial plexus injury. J Orthop Res 2012;30(8):1335-
1342.
67. Moukoko D, Ezaki M, Wilkes D, Carter P: Posterior shoulder dislocation in infants with
neonatal brachial plexus palsy. J Bone Joint Surg Am 2004;86(4):787-793.
C H AP T E R 6 1

Pediatric Pelvis, Hip, and Femur

Trauma
Stephanie L. Logterman MD, Keith D. Baldwin MD, MSPT,
MPH, FAAOS

Dr. Logterman or an immediate family member serves as a board member, owner, officer, or
committee member of the Pediatric Research in Sports Medicine. Dr. Baldwin or an immediate
family member has stock or stock options held in Pfizer.

ABSTRACT
Pediatric pelvic, hip, and femoral trauma represents a broad swath
of trauma etiologies and mechanisms. Younger children may have
lower energy mechanisms, whereas older children and adolescents
may sustain higher-energy trauma, motor vehicle collisions, or
sports-related injuries. Careful a ention to associated injuries may
prevent catastrophic outcomes in the cases of head injuries or
nonaccidental trauma. Treatment is based on age, expected
remodeling, and presumed fracture stability. It is important to
review injury pathomechanisms with a focus on recent updates
related to management of these entities in children.
Keywords: pediatric distal femoral physeal fracture; pediatric
femoral shaft fracture; pediatric hip fracture; pediatric pelvic
fracture; pediatric traumatic hip dislocation

Introduction
Pelvic, hip, and femoral fractures in pediatric patients, though
uncommon, can have potentially devastating complications. These
fractures can occur from either low-energy or high-energy
mechanisms. Fracture location, stability, and patient age help guide
treatment of these injuries. Common complications of pediatric
pelvic, hip, and femoral fractures include osteonecrosis and physeal
arrest. The most recent research related to pelvic, hip, and femoral
fractures in pediatric patients is explored.

Pediatric Pelvic Fractures

Pelvic fractures in pediatric patients are uncommon and comprise
fewer than 0.2% of all fractures in children, most of which are
apophyseal avulsions. 1 The incidence of pediatric pelvic fractures is
estimated at 1 in 100,000 children, with 40% to 80% as a result of
motor vehicle collisions. 1 In more of a general trauma se ing,
pelvic ring fractures can occur. Many adult pelvic ring fractures
cause pelvic instability; however, pediatric pelvic ring fractures can
remain stable with a complete fracture on one side of the ring and
an incomplete fracture on the other side. The classification
generally used in pediatric pelvic fractures is the Torode and Zieg
classification, which was derived from a retrospective series of 141
patients. 2 The classification describes four pa erns (later expanded
to five) of injury (Figure 1). The first was an apophyseal avulsion
injury, typically of the hamstrings (ischial tuberosity), sartorius
(anterior superior iliac spine), or rectus femoris (anterior inferior
iliac spine). The second was an isolated fracture of the iliac wing,
the third was a stable pelvic ring fracture, and the fourth an
unstable pelvic ring fracture.
 Figure 1 An illustration of the modified Torode and Zieg classification of pelvic
fractures into four different types.It further subdivides type III injuries into type IIIA,
which are fractures of either the anterior or posterior ring, and type IIIB, which
involves fractures of both the anterior and posterior ring.(Reproduced with
permission from Shore BJ, Palmer CS, Bevin C, Johnson MB, Torode IP:
Pediatric pelvic fracture: A modification of a preexisting classification. J Pediatr
Orthop 2012;32[2]:162-168.)

Apophyseal Avulsion Injuries

Apophyseal avulsion injuries are considered to be uncommon
injuries but can occur in up to 16% of athletic injuries in the at-risk
adolescent age group. 3 The injury occurs as a result of a rapid
change in direction with an unbalanced contraction of the involved
muscle, typically during soccer, gymnastics, or football. The
traction of the muscle through the apophyseal secondary
ossification center results in an avulsion injury of the apophysis.
The mean age of injury is 14.5 years, and the most common
avulsion is the anterior inferior iliac spine (46%) followed by the
anterior superior iliac spine (32%), the ischial tuberosity (12%), and
the iliac crest (11%). 4
In general, most apophyseal fractures should be managed
nonsurgically. Guidelines recommend a short period of limited
weight bearing of 3 to 4 weeks with ice and NSAIDs for the first
week, followed by increasing resistance training at 4 weeks and
stretching at 6 to 8 weeks. 5 Surgical treatment is controversial and
level of evidence guiding decision making is poor. Clear indications
for surgery are lacking, of which symptomatic nonunion is likely
the least controversial indication. A surgical indication of
displacement more than 15 mm in ischial tuberosity fractures and
anterior superior iliac spine fractures is supported by low-level
studies or expert opinion, as is 2 cm for fractures of the anterior
inferior iliac spine. 5 - 7 These indications are patient dependent,
however, and a larger case series showed approximately 86% of
patients were asymptomatic at 3 months independent of bony
union. 8

Iliac Wing Fractures

Torode and Zieg type II or isolated iliac wing fractures are almost
five times more common in skeletally immature patients than in
older patients (29% of all pelvic fractures versus 6%). 9 This
relationship is reversed in more unstable pa erns such as
acetabular fractures (more than seven times more common in
mature children), sacroiliac, or pubic symphysis diastasis (almost
four times as common in skeletally mature patients). 9
 Although iliac wing fractures account for approximately 25% of
nonavulsion pelvic fractures in children, there is a paucity of
primary research describing outcomes. 10 The fractures are almost
exclusively managed nonsurgically, with no clearly identifiable
surgical indications apart from expanding hematoma, symptomatic
nonunion, or an open injury that requires débridement. Generally,
a period of 4 to 6 weeks of limited weight bearing is likely to result
in bony union. Given the generally benign nature of this entity, the
goal of treatment is to limit symptoms while the patient recovers.
Because the abdominal wall musculature a aches to the iliac wing,
it stands to reason that protected weight bearing with crutches or
walker until union is likely to produce fewer symptoms than non–
weight bearing where the entire involved hemipelvis would be held
against gravity by muscles a ached to the cranial aspect of the iliac
wing.

Pelvic Ring Injuries

Torode and Zieg type III injuries describe a stable pelvic ring
injury, and Torode and Zieg type IV fractures are unstable pelvic
ring injuries, with stability referring to the bony stability of the
pelvic ring. Difficulty exists in determining stability for two key
reasons. First, because of the nature of children’s bone, fractures
may exist that are torus or incomplete fractures, which are
inherently stable. Second, the abundant and thick periosteum in
younger children can render unstable adult pa erns stable in a
child. One study described a group of patients characterized as
having type IIIB fractures in which fractures of the anterior and
posterior ring existed but the fracture itself was still stable.
Although no changes in orthopaedic management were made,
these children were more likely to receive blood transfusions and
have a longer length of stay in the hospital. 11 The Tile classification
is a clinically helpful way to consider stability in this se ing, where
Tile A fractures are vertically stable and rotationally stable, Tile B
fractures are partially stable, generally rotationally unstable but
vertically stable (in the case of lateral compression/anterior-
posterior compression). Finally, Tile C fractures are vertically and
rotationally unstable. 12 The challenge comes because unless the
child is at or close to skeletal maturity, static radiographic
indications either on plain radiograph, CT, or MRI are less reliable
than in adult patients because of the common presence of
incomplete fractures and a thick periosteum.
A series of maneuvers has been suggested that could be
performed under anesthesia to check stability under the three
fracture pa erns generally seen: lateral compression, anterior-
posterior compression, and vertical shear. 13 These maneuvers can
detect occult pelvic instability and help determine if surgical
intervention is warranted in borderline fractures, particularly when
a Tile type B fracture occurs in a skeletally immature child. Tile type
A pelvic ring fractures can almost universally be managed
nonsurgically and include minimally displaced symphyseal
disruptions, oblique rami fractures, and incomplete fractures of the
sacrum. These generally do not require examination under
anesthesia and can be managed with a period of protected weight
bearing. After the patient gets out of bed and mobilizes, AP, inlet,
and outlet radiographic views or a flamingo view can be obtained
(weight bearing on involved side) to rule out latent instability. Tile
type B fractures are more likely to be unstable in skeletally mature
or close to mature adolescents. These may present with the classic
crescent fracture with fractures of the pubic rami in the case of
lateral compression fractures or symphyseal diastasis with
concomitant disruption of the posterior sacroiliac ligaments or
bone in the case of an anterior-posterior compression injury. In
younger children the instability may not be so obvious, and a stress
examination under anesthesia can differentiate a stable versus
unstable pelvis. An examination under anesthesia should be
considered, particularly in cases where the child needs an
anesthetic for an unrelated reason if the diagnosis is in question. 13
Tile C injuries are typically more severe and often are unstable on
presentation. These types of ring injuries are also more common in
more skeletally mature patients. 9 Pediatric pelvic fractures found to
be unstable should be considered for surgical fixation. Remodeling
of the pelvic ring is lackluster, even in younger children, and the
degree of functional disability has been related to the amount of
pelvic asymmetry. 14 , 15
Unstable pelvic injuries may present with a cadre of other serious
issues ranging from closed head injury to hemodynamic instability
to urogenital injury. Lateral compression injuries are often bumper
injuries in a child, and when struck by a moving vehicle, the child’s
body hits the ground first, followed by a head strike. Dissimilar
from adults, mortality is more often caused by head injury than by
exsanguination, and this is theorized to be a result of the increased
capacity for vasoconstriction that occurs in the venous plexus
surrounding the anterior pelvic ring. 16 These vessels are commonly
disrupted by anterior-posterior compression-type injuries, and as
such, patients with this pa ern are most likely to present with
hemodynamic instability, and they are also most likely to benefit
from the volume reduction afforded by a pelvic binder. Although
urethral and bladder neck injury can occur with any pubic
symphysis disruption, they are most likely to occur with vertical
shear injuries because the bladder is tethered to the anterior pelvis
by suspensory ligaments. Urologic consultation and cystography
should be considered in these injury pa erns.

Acute Management
Acute management of pediatric pelvic fractures should be based on
hemodynamic and fracture stability. Torode and Zieg type I to III
injuries (Tile A) can be managed with limitations in weight bearing
alone. Torode and Zieg type IV or Shore modification IIIB (Tile B)
fractures should be assessed for hemodynamic stability and then
an assessment made of fracture stability either with a static study
such as a CT scan, or in a more skeletally immature patient, with an
examination under anesthesia. Torode and Zieg type IV fractures
should be assessed for hemodynamic instability, acute issues
addressed, and compressive binders placed in the case of anterior-
posterior injuries with ongoing blood loss. A femoral traction pin
should be placed on the high side of the hemipelvis in the case of
vertical shear fractures. Advanced Trauma Life Support protocols
should be carried out with primary and secondary surveys, followed
by a trauma assessment for ongoing sources of blood loss. Careful
neurologic workup and imaging are critical along with assessment
of the integrity of the urogenital system. 16 Although outcomes of
nonsurgical treatment are generally good, when instability exists,
percutaneous or open fixation as indicated also results in good
outcomes with a favorable complication profile. 17 , 18

Hip Dislocation
Traumatic hip dislocation is an uncommon occurrence in childhood
(Figure 2). The mechanism of injury is generally lower energy in
younger children (age 10 years and younger) or higher energy in
older children and adolescents. 19 Younger children generally have
more ligamentous laxity than older children, so the incidence of
bony injury is lower in younger children. Femoral head fractures,
epiphyseal separations, and posterior wall fractures can be seen in
older children and adolescents, and careful evaluation for these
injuries postreduction should be undertaken. 20
 Figure 2 AP (A) and lateral (B) radiographs from a 2-year-old girl with a left
traumatic hip dislocation sustained after crashing into a fence while sledding.
The hip was treated with closed reduction in the emergency department. On
postreduction radiograph, there was concern the hip was not concentrically
reduced. MRI revealed a concentric reduction. The patient was brought to the
operating room for hip arthrography, which also confirmed a concentric hip
reduction, and the patient was placed into a one and one half-leg spica cast. AP
pelvis (C) 2 years after injury, with the patient doing well with no radiographic
evidence of osteonecrosis or other complication.

After the dislocation has been identified, an urgent sedated

reduction should be undertaken, because osteonecrosis is more
common when reduction is delayed more than 6 hours. 21 Most
dislocations in children can be managed with sedation and closed
reduction using gentle traction. Postreduction imaging should be
performed either with CT or MRI. Although both are acceptable,
MRI may be superior to CT in that there is no radiation associated
with MRI, and MRI is superior for examining interposition of soft
tissue or assessing chondral injury postreduction. 19 If closed
reduction is unsuccessful or if reduction is nonconcentric because
of interposed soft tissue or fracture, open reduction should be
performed. In terms of surgical approach, when a posterior
dislocation is present, a posterior approach is recommended, and
when an anterior dislocation is present, an anterior approach is
recommended. This is thought to minimize surgical trauma to the
opposite side of the joint and allow for repair of the damaged
capsule and tissues. 22
 Complications include noncongruent joint reduction, femoral
head epiphysiolysis, missed fractures (including femoral head and
posterior wall fractures), osteonecrosis, hip instability,
osteoarthritis, and neurologic injury (specifically sciatic nerve
injury). The outcome of pediatric hip dislocation varies based on
the energy of injury, the promptness of identification and
reduction, the identification of other injuries, and reduction
congruency. Asymptomatic coxa magna is common. 19 The patient
should be observed for at least 6 months and preferably 1 year for
changes in the femoral head including osteonecrosis.

Pediatric Femoral Neck and Pertrochanteric

Fractures
Pediatric femoral neck fractures are rare injuries, accounting for
fewer than 1% of fractures in children. Although rare, these
fractures account for a disproportionate amount of disability, pain,
and loss of function because of potential complications that can
occur. The blood supply of the proximal femur is limited to
branches of the medial femoral circumflex because the proximal
physis blocks contributions of the lateral femoral circumflex. This
renders the blood supply to the capital epiphysis very tenuous and
at risk for osteonecrosis of the femoral head with displaced
proximal femoral fractures 23 (Figure 3).
 Figure 3 Illustration shows the proximal femur vascularization.The primary
blood supply to the femoral head and neck is the medial femoral circumflex
artery. Note that there is no arterial anastomosis between the femoral neck and
epiphysis because the physis acts as a mechanical barrier.(Reproduced with
permission from Barreto Rocha DF, Horwitz DS, Sintenie JB: Femoral neck
fractures in children: Issues, challenges, and solutions. J Orthop Trauma
2019;33[suppl 8]:S27-S32.)

The Delbet classification is commonly used to describe pediatric

proximal femoral fractures 24 (Figure 4). The risk of osteonecrosis is
inversely related to the Delbet type because osteonecrosis risk is
higher with lower number types and lower with higher number
types. 25 Type I fractures are epiphyseal separations, and risk of
osteonecrosis is 38% because no blood flow occurs past the physis.
These fractures place the greatest stress on the epiphyseal vessels
that arise from the medial femoral circumflex artery. Type II
fractures are transcervical and carry a 28% risk of osteonecrosis.
Type III fractures are basicervical and have an osteonecrosis risk of
18%. Type IV fractures are intertrochanteric and have an
osteonecrosis risk of 5%. Other complications include premature
physeal closure (22%), coxa vara (18.5%), nonunion (11%), and
chondrolysis (13.5%). 26 , 27
 Figure 4 Illustration of the Delbet classification of pediatric femoral neck
fractures with the Ju modification that subdivides type I fractures into type IA,
which is a transphyseal fracture where the femoral head stays within the
acetabulum, and type IB, where the femoral head dislocates from the
acetabulum.(Reproduced with permission from Ju L, Jiang B, Lou Y, Zheng P:
Delayed treatment of femoral neck fractures in 58 children: Open reduction
internal fixation versus closed reduction internal fixation. J Pediatric Orthop B
2016;25[5]:459-465.)

Because of the high complication rate of pediatric femoral neck

fractures, research in this area generally focuses on modifiable risk
factors for this outcome. An anatomic reduction has been shown to
be more important than performing surgery in an emergent fashion
in terms of preventing osteonecrosis and other complications. 28
Whether to perform open or closed reduction is a source of debate:
whereas the literature shows a significant improvement using open
reduction, other papers show no difference in outcomes. 28 , 29 The
quality of reduction may confound this relationship. Ongoing
debate exists about the value of other modalities such as capsular
decompression, with earlier clinical studies suggesting superior
outcomes, but later studies being equivocal or difficult to interpret.
28 , 30

Subtrochanteric Femoral Fractures

Subtrochanteric femoral fracture in adults is typically defined as a
fracture that occurs within 5 cm of the lesser trochanter. This
definition is less robust in children in whom the total length of the
femur is shorter. Clinically this entity differs from fractures further
distal in the femoral shaft by being heavily influenced by flexion,
external rotation, and abduction forces on the proximal fragment by
muscles around the hip. In children younger than 5 years, closed
reduction with spica casting is an acceptable treatment, although
these fractures can be associated with a greater risk for late
displacement in a cast. 31 Close follow-up with spica casting is
necessary, particularly in subtrochanteric transverse or short
oblique fractures or fractures with a large amount of coronal
angulation on presentation; when all three of these factors are
present, up to 99% of these patients will obtain unsatisfactory final
alignment after treatment with a cast. 31 Older children and
adolescents with this fracture pa ern may be candidates for flexible
nails, submuscular plating, or reamed nailing depending on the age
and specific fracture pa ern. Studies have demonstrated that elastic
nailing can be used successfully to treat subtrochanteric femoral
fractures 32 , 33 (Figure 5). Various tactics have been described to
enhance the stability of fixation with elastic intramedullary nailing,
with some authors advocating for penetrating the greater
trochanter apophysis or the posterior femoral neck cortex with the
nail for patients ages 5 to 10 years, whereas others have recently
described using either locking eyelets or endcaps to enhance
stability. 34 Other studies have demonstrated the efficacy of plating
subtrochanteric femoral fractures, but sample size and fracture
heterogeneity make firm conclusions difficult to draw from these
retrospective data. 35 Optimal implant selection is likely
multifactorial with skeletal maturity, fracture stability, surgeon
comfort level, and other fracture characteristics likely playing a
role.
 Figure 5 AP (A) and lateral (B) radiographs of the left femur of an 8-year-old
girl who sustained a subtrochanteric femoral fracture after a fall from a scooter.
She underwent closed reduction and retrograde elastic intramedullary nail
placement in the operating room. At 4 months postoperatively, AP (C) and lateral
(D) radiographs demonstrate a healing femoral fracture with intact elastic
intramedullary nails. The nails were removed at 4 months postoperatively.

Femoral Shaft Fractures

Femoral shaft fractures are among the most common reasons for
admission to the hospital in pediatric patients despite representing
only 1% to 2% of all pediatric fractures. 36 Approximately 70% of
pediatric femoral fractures are diaphyseal in location. 37 In a child
younger than 3 years with a femoral fracture, abuse should always
be considered and investigated, especially in infants and children
who have not yet begun to walk. Patient age is strongly linked to
fracture etiology. It is estimated that 42% of femoral fractures in
nonwalking patients can be a ributable to nonaccidental trauma,
whereas only 2.5% of femoral fractures in children who are able to
walk is a ributable to nonaccidental trauma. 38 Because fractures
are the second-most common presentation of child abuse, it is
imperative that orthopaedic surgeons are aware of these statistics
and report appropriately.
The treating surgeon should consider fracture location, patient
age, associated injuries, and social situation when considering how
to treat femoral shaft fractures in pediatric patients. To assist
surgeons, the American Academy of Orthopaedic Surgeons
released an updated version of clinical practice guidelines to treat
pediatric femoral fractures. These new guidelines, however,
revealed the paucity of high-quality literature in existence to help
guide the treatment of pediatric femoral fractures as the commi ee
was only able to recommend 1 of 14 proposals. 39 Given the paucity
of strong recommendations and myriad of considerations when
choosing a treatment option for pediatric femoral fractures, a
categorization/decision tool (Figure 6) was devised for choosing an
appropriate treatment strategy based on age, fracture stability, and
other patient characteristics, described in a 2020 study. 40 This tool
was then validated by 17 experts each with more than 20 years of
call experience in a pediatric practice.
 Figure 6 Schematic shows the principle-based classification system to help
guide treatment of pediatric diaphyseal femoral fractures.(Reproduced with
permission from Weltsch D, Baldwin KD, Talwar D, Flynn JM: Expert consensus
for a principle-based classification for treatment of diaphyseal pediatric femoral
fractures. J Pediatr Orthop 2020;40[8]:e669-e675.)

For infants ages 6 months and younger and patients who are
nonambulatory, a “do-no-harm” strategy is adopted. Infants are
successfully treated in a Pavlik harness, whereas nonambulatory
children who are older with severe neuromuscular or medical
considerations can be treated with a brace for comfort if their
medical condition does not allow for surgical intervention. Closed
reduction and spica casting is the most common treatment for
children ages 6 months to 4 to 5 years. Spica casts should be
molded into valgus and recurvatum, as one study found that
pediatric femoral fractures gained 5° of varus and 10° of
procurvatum between spica cast application and fracture union. 41
Furthermore, a 2020 study found that patients had a 99% chance of
unacceptable fracture alignment following spica cast treatment if
they had a high-energy injury, proximal fracture location, and
greater than 8° of initial coronal angulation. 31 This active casting
strategy often requires a follow-up visit at 7 to 10 days for cast-
wedging in the event that the fracture drifts into varus as the
swelling remits.
Controversy exists, however, in the treatment of children ages 4
to 5 years because many surgeons are now using elastic
intramedullary nails in this patient population. A 2020 study found
that when comparing spica casting versus elastic intramedullary
nailing in preschool-aged children, spica casting resulted in a 4.4-
fold higher odds of unplanned revision surgery and that each year
of increasing age resulted in a 1.3-fold higher odds of revision
surgery. 42 Spica casts offer excellent results with some
disadvantages: skin irritation, prolonged immobilization, and
familial burden. In contrast, elastic intramedullary nailing offers
earlier ambulation and shorter duration of hospital stay but comes
with an increased cost, risk of infection, and need for implant
removal. Furthermore, another 2020 study demonstrated that the
intraoperative burden of elastic intramedullary nailing was
substantially greater than spica cast treatment in terms of
anesthetic and radiation exposure but had a similar complication
rate. 43 In terms of cost, a 2019 study found a significant difference
in the total hospital charges between spica cast treatment and
elastic intramedullary nailing of femoral fractures in patients age 3
to 6 years: $19,200 versus $59,700, respectively. 44
Traditional treatment of children ages 5 to 11 years is with elastic
intramedullary nailing or plate fixation. Length-stable fractures
such as transverse or short oblique fractures may be ideally suited
to the relative stability that elastic nailing imparts. Interestingly,
recent literature has demonstrated that use of elastic nails for
length-unstable femoral shaft fractures was an effective treatment
option that did not result in an increase in complications. 45 A
similar study demonstrated safe and successful use of elastic nails
in unstable fracture pa erns including proximal third femoral
fractures, spiral fractures, and comminuted fractures. 46 In addition,
a 2020 study found that fractures resulting from high-energy
mechanisms, displacement in the coronal plane, and distal third
fracture location were predictors of failing a closed reduction
intraoperatively and requiring an open reduction. 47 A 2020
systematic review and meta-analysis showed that use of elastic
intramedullary nails in children weighing more than 40 kg resulted
in worse radiographic outcomes and higher complication rates. 48
For children older than 11 years or patients who weigh more than
100 lb, fracture fixation using a rigid intramedullary nail is the
preferred treatment method. Other indications to look for length
are fracture comminution or length instability, a heavier child, or a
less ideal location (metadiaphyseal or subtrochanteric region).
Finally, in some cases the fracture is of secondary concern. Some
fractures, particularly those that result from higher-energy trauma,
may require damage control strategies, although even with very
severe injuries this strategy has been called into question in
children and adolescents. 49 A more common reason in children
that a damage control strategy would be adopted is the se ing of
vascular injury, where the limb is threatened and a temporizing
strategy is desirable to protect the vascular repair. External fixation
is generally quick, easy to apply, and allows access to measure
pulses in the se ing of a vascular repair.

Distal Femur Physeal Fractures

Distal femur physeal fractures present a unique challenge to the
treating surgeon both in terms of acute fixation and late sequelae.
The incidence of physeal arrest reported in the literature is 40% to
52%, with displaced fractures having four times greater odds of
development of a growth disturbance than nondisplaced fractures.
 In a 2021 study with a cohort of 101 patients with distal femur
50 , 51

physeal fractures, it was shown that years of growth remaining until

skeletal maturity was predictive of the need for future
interventions, and patients required 1.67 additional surgeries to
correct a leg length or angular deformity. 52 Children who sustain
distal femur physeal fractures should be followed until skeletal
maturity, and families should be counseled about the risk of leg
length discrepancy or angular deformity. MRI can be used in the
subacute se ing to identify growth arrest if suspected. Fractures in
this location should raise suspicion for a neurovascular injury given
the proximity to the popliteal fossa. Furthermore, minimally
displaced intra-articular fractures (Salter-Harris III and IV) can be
difficult to detect on plain radiographs; thus, the treating physician
should have a low threshold for obtaining advanced imaging such
as MRI or CT. Intra-articular fractures are most commonly Salter-
Harris III involving the medial femoral condyle 88% of the time. 53
Triplane fractures of the distal femur have also been described in
the literature and are similarly difficult to detect with plain
radiographs. 54
Nondisplaced fractures, especially Salter-Harris I fractures in
young children, are managed nonsurgically with casting. Fixation of
these injuries with smooth wires is the most common strategy in
younger patients as the smooth wires minimize injury to the physis
(Figure 7). In older patients, however, use of threaded wires or
screws is the preferred fixation method with physeal sparing all-
metaphyseal or all-epiphyseal constructs frequently employed to
stabilize these injuries. Despite more aggressive surgical
indications (ie, any fracture displacement) than in the past, the
overall complication rate from distal femur physeal fractures
remains high, as a 2020 study found a 36% complication rate with
surgical management versus 40% (P = 0.75) with nonsurgical
management. 55
 Figure 7 AP (A) and lateral (B) radiographs of the left knee of a 6-year-old girl
who sustained a displaced Salter-Harris II distal femoral fracture after a fall from
a trampoline. She underwent closed reduction and percutaneous pinning in the
operating room. Two smooth Kirschner wires were used for fixation to minimize
additional trauma to the physis. Intraoperative AP (C) and lateral (D) fluoroscopic
images of the knee show a reduced distal femoral fracture with Kirschner wires
in place. The Kirschner wires were buried under the skin and removed 1 month
later in the operating room.

Summary
Pediatric pelvic, hip, and femoral fractures result from a wide array
of traumatic mechanisms. Injuries caused by high-energy trauma,
although more common in adolescents, may also occur in younger
patients, and these children require appropriate resuscitation and
stabilization. Given the skeletal immaturity of pediatric patients,
they have unique fracture pa erns that can occur with low-energy
mechanisms. Children with fractures of the pelvis, hip, and femur
require long-term follow-up to monitor for late sequelae such as
osteonecrosis, growth disturbance, and angular deformity.

Key Study Points

Pediatric pelvic fractures are most commonly avulsion injuries from sports-related
activities. Most pediatric pelvic fractures can be successfully managed
nonsurgically; however, unstable pelvic ring injuries require surgical fixation.
The most common and concerning complication after a hip dislocation or femoral
neck fracture in children is osteonecrosis. Reduction of these injuries should be
performed carefully and urgently to help avoid complications.
Treatment of pediatric femoral fractures depends on fracture type, fracture location,
patient age, and patient weight.
Distal femur physeal fractures have a high incidence of physeal arrest. Surgeons
should counsel patients appropriately regarding treatment and be prepared to
manage growth disturbance or angular deformity following this injury.

Annotated References
1. Guillaume JM, Pesenti S, Jouve JL, Launay F: Pelvic fractures in
children (pelvic ring and acetabulum). Orthop Traumatol Surg Res
2020;106(1 suppl):S125-S133. Pelvic and acetabular fractures in
children are often due to high-energy mechanisms. Assessment
of hemodynamic stability should be the first priority in treating
these patients. Once the patient is clinically stable, treatment of
pelvic fractures should be guided by fracture stability with
unstable fractures requiring surgical fixation. Acetabular
fractures with joint instability or intra-articular displacement
necessitate surgical treatment.
2. Torode I, Zieg D: Pelvic fractures in children. J Pediatr Orthop
1985;5(1):76-84.
3. Rossi F, Dragoni S: Acute avulsion fractures of the pelvis in
adolescent competitive athletes: Prevalence, location and sports
distribution of 203 cases collected. Skeletal Radiol 2001;30(3):127-
131.
4. Calderazzi F, Nosenzo A, Galavo i C, Menozzi M, Pogliacomi F,
Ceccarelli F: Apophyseal avulsion fractures of the pelvis. A
review. Acta Biomed 2018;89(4):470-476.
5. Schiller J, DeFroda S, Blood T: Lower extremity avulsion
fractures in the pediatric and adolescent athlete. J Am Acad
Orthop Surg 2017;25(4):251-259.
6. Ferlic PW, Sadoghi P, Singer G, Kraus T, Eberl R: Treatment for
ischial tuberosity avulsion fractures in adolescent athletes. Knee
Surg Sports Traumatol Arthrosc 2014;22(4):893-897.
7. Ghanem IB, Rizkallah M: Pediatric avulsion fractures of pelvis:
Current concepts. Curr Opin Pediatr 2018;30(1):78-83.
8. Schue DJ, Bomar JD, Pennock AT: Pelvic apophyseal avulsion
fractures: A retrospective review of 228 cases. J Pediatr Orthop
2015;35(6):617-623.
9. Silber JS, Flynn JM: Changing pa erns of pediatric pelvic
fractures with skeletal maturation: Implications for classification
and management. J Pediatr Orthop 2002;22(1):22-26.
10. Junkins EPJr, Nelson DS, Carroll KL, Hansen K, Furnival RA: A prospective evaluation of
the clinical presentation of pediatric pelvic fractures. J Trauma 2001;51(1):64-68.
11. Shore BJ, Palmer CS, Bevin C, Johnson MB, Torode IP: Pediatric pelvic fracture: A
modification of a preexisting classification. J Pediatr Orthop 2012;32(2):162-168.
12. Tile M, Kellam J, Helfet D: Fractures of the Pelvis and Acetabulum. Lippincott Williams &
Wilkins, 2003.
13. Sagi HC, Coniglione FM, Stanford JH: Examination under anesthetic for occult pelvic ring
instability. J Orthop Trauma 2011;25(9):529-536.
14. Matta JM, Saucedo T: Internal fixation of pelvic ring fractures. Clin Orthop Relat Res
1989;242:83-97.
15. Smith WR, Oakley M, Morgan SJ: Pediatric pelvic fractures. J Pediatr Orthop
2004;24(1):130-135.
16. Swaid F, Peleg K, Alfici R, et al: A comparison study of pelvic fractures and associated
abdominal injuries between pediatric and adult blunt trauma patients. J Pediatr Surg
2017;52(3):386-389.
17. Scolaro JA, Firoozabadi R, Routt MLC: Treatment of pediatric and adolescent pelvic ring
injuries with percutaneous screw placement. J Pediatr Orthop 2018;38(3):133-137.
18. Sridharan SS, You D, Ponich B, Parsons D, Schneider P: Outcomes following pelvic ring
fractures in the paediatric population: A systematic review. J Clin Orthop Trauma
2020;11(6):963-969. A systematic review of 23 studies assessed outcomes following pediatric
pelvic ring injuries. Motor vehicle collision was the most common etiology of injury. Of these
fractures, 8.8% required surgical treatment. The most common complications were limb
length discrepancy and a limp. Level of evidence: V.
19. Vialle R, Odent T, Pannier S, Pauthier F, Laumonier F, Glorion C: Traumatic hip dislocation
in childhood. J Pediatr Orthop 2005;25(2):138-144.
20. Herrera-Soto JA, Price CT, Reuss BL, Riley P, Kasser JR, Beaty JH: Proximal femoral
epiphysiolysis during reduction of hip dislocation in adolescents. J Pediatr Orthop
2006;26(3):371-374.
21. Mehlman CT, Hubbard GW, Crawford AH, Roy DR, Wall EJ: Traumatic hip dislocation in
children. Long-term follow up of 42 patients. Clin Orthop Relat Res 2000;376:68-79.
22. Herrera-Soto JA, Price CT: Traumatic hip dislocations in children and adolescents: Pitfalls
and complications. J Am Acad Orthop Surg 2009;17(1):15-21.
23. Barreto Rocha DF, Horwitz DS, Sintenie JB: Femoral neck fractures in children: Issues,
challenges, and solutions. J Orthop Trauma 2019;33(suppl 8):S27-S32. Femoral neck
fractures are rare injuries in children and frequently occur from a high-energy mechanism.
These fractures require urgent reduction and surgical fixation. Femoral neck fractures are
associated with a high rate of complications with osteonecrosis being the most common and
the most devastating.
24. Ju L, Jiang B, Lou Y, Zheng P: Delayed treatment of femoral neck fractures in 58 children:
Open reduction internal fixation versus closed reduction internal fixation. J Pediatr Orthop B
2016;25(5):459-465.
25. Moon ES, Mehlman CT: Risk factors for avascular necrosis after femoral neck fractures
in children: 25 Cincinnati cases and meta-analysis of 360 cases. J Orthop Trauma
2006;20(5):323-329.
26. Morsy HA: Complications of fracture of the neck of the femur in children. A long-term
follow-up study. Injury 2001;32(1):45-51.
27. Li H, Zhao L, Huang L, Kuo KN: Delayed slipped capital femoral epiphysis after treatment
of femoral neck fracture in children. Clin Orthop Relat Res 2015;473(8):2712-2717.
28. Yeranosian M, Horneff JG, Baldwin K, Hosalkar HS: Factors affecting the outcome of
fractures of the femoral neck in children and adolescents: A systematic review. Bone Joint J
2013;95-B(1):135-142.
29. Song KS: Displaced fracture of the femoral neck in children: Open versus closed
reduction. J Bone Joint Surg Br 2010;92(8):1148-1151.
30. Ng GP, Cole WG: Effect of early hip decompression on the frequency of avascular
necrosis in children with fractures of the neck of the femur. Injury 1996;27(6):419-421.
31. Misaghi A, Mahmoud MAH, Arkader A, Baldwin KD: Fracture characteristics predict
suboptimal alignment in preschool femoral shaft fractures treated with spica casting: A
retrospective chart review. Curr Orthop Pract 2020;31(4):379-384. This is a retrospective
review of 132 pediatric femoral shaft fractures treated with closed reduction and spica casting.
In patients aged 3 to 6 years, fractures with high-energy patterns (transverse and
comminuted), proximal fracture location, and initial coronal angulation greater than 8° predict
unacceptable alignment in a spica cast. Level of evidence: IV.
32. Parikh SN, Nathan ST, Priola MJ, Eismann EA: Elastic nailing for pediatric subtrochanteric
and supracondylar femur fractures. Clin Orthop Relat Res 2014;472(9):2735-2744.
33. Basa CD, Kacmaz IE, Zhamilov V, Reisoglu A, Agus H: Can titanium elastic nail be safely
used for paediatric subtrochanteric femur fractures? J Pediatr Orthop B 2021;30(1):1-5. This
is a retrospective review of 20 patients treated with retrograde titanium elastic nails for
subtrochanteric femur fractures. All fractures went on to union. Three patients had a malunion,
but angulation was less than 5°. Fourteen patients underwent routine hardware removal.
Titanium elastic nailing can safely be used for treatment of pediatric subtrochanteric femur
fractures. Level of evidence: IV.
34. Cha SM, Shin HD, Joo YB, Lee WY: Enhancing stability by penetrating the apophysis of
greater trochanter or the posterior neck cortex during titanium elastic nailing of paediatric
subtrochanteric femoral fractures in children aged 5-12 years. J Pediatr Orthop B
2020;29(5):478-484. This is a retrospective review of 17 children ages 5 to 12 years with
subtrochanteric femoral fractures. The authors used a modified technique in which they buried
the ends of the titanium elastic nails into the greater trochanteric apophysis and the femoral
neck cortex to increase the stability of the construct. Three patients had malunion between 5°
and 10° of angulation. Five patients had a limb length discrepancy between 1 and 2 cm at final
follow-up. Simple technique modification led to satisfactory results in the management of
pediatric subtrochanteric femoral fractures. Level of evidence: IV.
35. Xu Y, Bian J, Shen K, Xue B: Titanium elastic nailing versus locking compression plating
in school-aged pediatric subtrochanteric femur fractures. Medicine (Baltim)
2018;97(29):e11568.
36. Kocher MS, Sink EL, Blasier RD, et al: Treatment of pediatric diaphyseal femur fractures.
J Am Acad Orthop Surg 2009;17(11):718-725.
37. Flynn JM, Schwend RM: Management of pediatric femoral shaft fractures. J Am Acad
Orthop Surg 2004;12(5):347-359.
38. Schwend RM, Werth C, Johnston A: Femur shaft fractures in toddlers and young children:
Rarely from child abuse. J Pediatr Orthop 2000;20(4):475-481.
39. American Academy of Orthopaedic Surgeons: Treatment of Pediatric Diaphyseal Femur
Fractures: Evidence-Based Clinical Practice Guideline. 2021. Available at:
https://www.aaos.org/globalassets/quality-and-practice-resources/pdff/pdffcpg.pdf. Accessed
September 16, 2022.
40. Weltsch D, Baldwin KD, Talwar D, Flynn JM: Expert consensus for a principle-based
classification for treatment of diaphyseal pediatric femur fractures. J Pediatr Orthop
2020;40(8):e669-e675. This two-stage study comprised a survey of 17 thought leaders and a
retrospective review of 289 consecutive pediatric patients to assess consensus for principle-
based classification for treatment of diaphyseal femur fractures. Agreement was obtained
among experts for different treatments. Surgical treatment led to 4.2 times higher hospital
charges than nonsurgical care. Level of evidence: III.
41. Nielsen E, Skaggs DL, Ryan D, Andras LM: Molding spica casts to maintain alignment of
femur fractures. J Pediatr Orthop 2018;38(5):e267-e270.
42. Brnjos K, Lyons DK, Hyman MJ, Patel NM: Spica casting results in more unplanned
reoperations than elastic intramedullary nailing: A national analysis of femur fractures in the
preschool population. J Am Acad Orthop Surg Glob Res Rev 2020;4(10):e20.00169. This is a
retrospective review of PHIS database with 4,059 patients aged 3 to 6 years with femoral
fractures who underwent spica casting or elastic stable intramedullary nailing. Eight percent of
children treated with spica casting required unplanned revision surgery compared with only 3%
of kids treated with nailing. Children ages 5 to 6 years treated with spica casting were twice as
likely to require another procedure than 3- to 4-year-olds. Level of evidence: III.
43. Barnett SA, Song BM, Yan J, Leonardi C, Gonzales JA, Heffernan MJ. Intraoperative
Burden of Flexible Intramedullary Nailing and Spica Casting for Femur Fractures in Young
Children. J Pediatr Orthop 2021; May 13 [Epub ahead of print]. This is a retrospective review
of 143 patients ages 2 to 6 years with femoral fracture treated with either a spica cast or
flexible intramedullary nails. Patients treated with flexible nails had significantly increased
intraoperative burden compared with spica including longer anesthetic and radiation exposure.
Level of evidence: III.
44. Lewis RB, Hariri O, Elliott ME, Jo CH, Ramo BA: Financial analysis of closed femur
fractures in 3- to 6-year-olds treated with immediate spica casting versus intramedullary
fixation. J Pediatr Orthop 2019;39(2):e114-e119. This retrospective review compared 41
patients treated with spica casting with 32 patients treated with flexible intramedullary nailing for
pediatric femoral fractures. Treatment with intramedullary nailing is associated with longer
hospital course and follow-up in addition to greater hospital charges and more clinic visits than
spica casting. Level of evidence: III.
45. Siddiqui AA, Abousamra O, Compton E, Meisel E, Illingworth KD: Titanium elastic nails
are a safe and effective treatment for length unstable pediatric femur fractures. J Pediatr
Orthop 2020;40(7):e560-e565. This retrospective review of 58 pediatric patients compared
outcomes of length-stable versus length-unstable femoral fractures managed with titanium
elastic nails. There was no difference between groups in time to union or in complications.
Titanium elastic nails are safe and effective for length-unstable femoral fractures in pediatric
patients. Level of evidence: III.
46. Atassi O, Fontenot PB, Busel G, et al: “Unstable” pediatric femoral shaft fractures treated
with flexible elastic nails have few complications. J Orthop Trauma 2021;35(2):e56-e60. This is
a retrospective review of 101 femoral fractures in pediatric patients treated with flexible elastic
nailing with 50% of fractures being length unstable. All fractures in the cohort went on to union,
and none had a leg-length discrepancy greater than 1 cm. Three patients required unplanned
surgery. No characteristics of the patients, fractures, or treatment were predictive of
complications. Level of evidence: IV.
47. Heffernan MJ, Shelton W, Song B, Lucak TJ, Leonardi C, Kadhim M: Predictors of open
reduction in pediatric femur fractures treated with flexible nails. J Pediatr Orthop
2020;40(7):e566-e571. This is a retrospective review of 85 pediatric femoral fractures treated
with either open versus closed reduction and flexible intramedullary nailing. Three predictors of
needing an open reduction were identified: initial fracture displacement in the coronal plane,
fractures of the distal third of the femur, and fractures caused by high-energy trauma. Level of
evidence: III.
48. Makarewich CA, Talwar D, Baldwin KD, Swarup I: Flexible intramedullary nailing of femoral
shaft fractures in children weighing ≥40 kg: A systematic review and meta-analysis. J Pediatr
Orthop 2020;40(10):562-568. This is a systematic review and meta-analysis of flexible
intramedullary nailing of femoral fractures in pediatric patients weighing greater than 40 kg. A
total of 172 studies were included in the analysis. Heavier children experienced higher rates of
radiographic nonunion and malunion in addition to higher complication and reoperation rates.
Level of evidence: III.
49. Al-Mahdi W, Ibrahim MM, Spiegel DA, Arkader A, Nance M, Baldwin K: Is systemic
inflammatory response syndrome relevant to pulmonary complications and mortality in
multiply injured children? J Pediatr Orthop 2020;40(1):1-7. This is a retrospective review of a
trauma database at a level I pediatric hospital of patients with an Injury Severity Score greater
than 16. System Inflammatory Response Syndrome (SIRS) criteria were tracked from days 1
to 4 using the electronic medical record comparing patients with and without an orthopaedic
injury. Independent predictors of SIRS were increasing Injury Severity Score and increasing
patient age. Rates of SIRS in children mimic those of adults, but mortality rates remain higher
in adult patients than in children. Level of evidence: III.
50. Basener CJ, Mehlman CT, DiPasquale TG: Growth disturbance after distal femoral growth
plate fractures in children: A meta-analysis. J Orthop Trauma 2009;23(9):663-667.
51. Arkader A, Warner WCJr, Horn BD, Shaw RN, Wells L: Predicting the outcome of physeal
fractures of the distal femur. J Pediatr Orthop 2007;27(6):703-708.
52. Bellamy JT, Ward LA, Fletcher ND: Evaluation of pediatric distal femoral physeal fractures
and the factors impacting poor outcome requiring further corrective surgery. J Pediatr Orthop
B 2021;30(1):6-12. This is a retrospective review of 101 patients with distal femur physeal
fractures. Physeal arrest occurred in 26 patients with 76% of these cases requiring
subsequent surgery to address either an angular deformity or leg length discrepancy. Amount
of fracture displacement was associated with development of physeal arrest, whereas sex,
age, and Salter-Harris classification were not. Level of evidence: III.
53. Pennock AT, Ellis HB, Willimon SC, et al: Intra-articular physeal fractures of the distal
femur: A frequently missed diagnosis in adolescent athletes. Orthop J Sports Med
2017;5(10):2325967117731567.
54. Carroll P, McGoldrick N, O’Toole P: Triplane fracture of the distal femur in the paediatric
population: A case report and literature review. Cureus 2020;12(3):e7416. A case report of
pediatric distal femoral triplane fracture is provided. CT scan of the knee should be obtained to
evaluate the degree of intra-articular displacement and help in preoperative planning. The
patient underwent open reduction with surgical fixation using cannulated compression screws.
There were no immediate postoperative complications, but a 1.8-cm leg length discrepancy
was found 1 year after injury. Level of evidence: IV.
55. Adams AJ, Mahmoud MAH, Wells L, Flynn JM, Arkader A: Physeal fractures of the distal
femur: Does a lower threshold for surgery lead to better outcomes?. J Pediatr Orthop B
2020;29(1):40-46. This is a retrospective review of pediatric distal femur physeal fractures at a
single level I pediatric trauma center that compared outcomes with a previously reported
multicenter cohort. Fractures were most commonly Salter-Harris II, and complication rate was
40%, which was consistent with the results of the prior cohort. Fractures resulting from high-
energy mechanisms of injury and greater initial fracture displacement were independently
predictive of higher complication rates. Level of evidence: III.
C H AP T E R 6 2

Pediatric Knee, Lower

Extremity, and Ankle Fractures
Jaime R. Denning MD, MS, FAAOS

Dr. Denning or an immediate family member serves as a board member, owner, officer, or
committee member of Pediatric Orthopaedic Society of North America.

ABSTRACT
Lower extremity fractures are common in children and adolescents,
ranging from extremely rare talar fractures and floating knees to
commonplace ankle fractures and tibial shaft fractures. Many
pediatric fracture pa erns (patellar sleeve, tibial tubercle, proximal
and distal tibia physeal fractures) are related to the weaknesses or
imbalances of the growing skeleton coupled with the increased
sporting and physical activity of young people. Treatment
principles of reducing and stabilizing intra-articular fractures are
similar in children compared with adults, but treatment principles
of other pediatric lower extremity fractures are unique to growing
bone such as flexible nailing of of tibial shaft fractures to avoid
hardware crossing an open physis and allowing some imperfection
in closed reduction of tibial fractures because of children’s
remarkable remodeling potential. Avoidance of pediatric-specific
complications such as premature physeal closure requires specific
knowledge of growing bone.
Keywords: patellar sleeve; pediatric foot fracture; pediatric tibia
fracture; physeal fracture; tibial tubercle fracture
Introduction
Lower extremity fractures are common in children and adolescents.
These injuries can range from low-energy falls from standing
height such as toddler fractures to moderate-energy sports-related
injuries such as tibial tubercle fractures to high-energy motor
vehicle injuries such as floating knees. Many of the unique fracture
pa erns that occur in growing children are a ributable to their
changing bony and physeal anatomy. Although growing bone and
open physes can allow remodeling after certain fractures, these
open physes also provide distinct opportunities for postinjury
complications such as premature physeal closure. Pediatric patients
are vulnerable to compartment syndrome like adults, particularly
after tibial shaft fractures, but they present with increased anxiety,
agitation, and increased analgesia requirement.

Patellar Sleeve Fracture

Patellar fractures in skeletally immature patients are rare and
account for less than 2% of all patellar fractures. Patellar sleeve
fractures, specifically, make up 57% of patellar fractures in children
with a peak incidence at 12.7 years of age. Boys sustain patellar
sleeve fractures at a ratio of 3:1 compared with girls. 1 Most patellar
sleeve fractures occur at the inferior pole, but superior pole sleeve
fractures have been reported. 2
The pathogenesis of patellar sleeve fractures occurs because of
the direct a achment/blending of extensor mechanism tendon
collagen into the cartilage portion of the osteochondral rim at the
periphery of the growing patella. Therefore, the mechanism of
injury of a patellar sleeve fracture is not a direct blow to the patella,
but rather a powerful contraction of the extensor mechanism that
separates a circumferential cuff of articular cartilage (deep) and
periosteum (superficial) off the bony patella. 3
On examination, a patient with a patellar sleeve fracture will have
knee swelling/effusion, pain on palpation of the patella, possibly a
palpable gap in the extensor mechanism, patella alta (or baja), and
inability to perform a straight leg raise. Plain radiographs can
usually diagnose the condition, but the findings can be subtle
(Figure 1). MRI can confirm the diagnosis and demonstrate the
extent of cartilage injury and amount of fragment displacement. 4
 Figure 1 Plain lateral radiograph from a 12-year-old boy with patellar sleeve
fracture demonstrates tiny ossific fragments off the inferior pole of patella, subtle
missing sleeve off both articular and periosteal sides of patella on the lower pole,
and patella alta.

In general, treatment for patellar sleeve fractures is surgical, with

the goals of restoring articular surface alignment, reconstructing
the extensor mechanism, and correcting patella alta. Surgical
treatment (open reduction and internal fixation [ORIF]) can be
accomplished using transosseous fixation with nonabsorbable
sutures, tension band wiring with Kirschner wires and
nonabsorbable sutures, or reconstruction with suture anchors. 1 , 3

Proximal Tibia Physeal Fractures

Proximal tibia physeal fractures are rare, accounting for less than
1% of pediatric fractures. 5 , 6 These fractures are classified by the
Salter-Harris classification system, with Salter-Harris II being the
most common (Figure 2). The mechanism of injury is
hyperextension of the knee (with resulting posterior displacement
of the epiphysis) or hyperflexion (with anterior displacement of the
epiphysis).

Figure 2 Series of AP/lateral radiographs from a 7-year-old girl with proximal

tibial Salter-Harris II fracture at the time of injury (A), after closed
reduction/smooth pinning (B), and 18-month follow-up without growth arrest (C).

Salter-Harris I/II fractures can generally be diagnosed on

AP/lateral knee radiographs and can be managed with closed or
open reduction and long leg cast (LLC) immobilization alone or
crossed smooth Kirschner wire fixation and long leg casting for 4 to
6 weeks. Salter-Harris III/IV fractures can also be diagnosed on
plain AP/lateral knee radiographs, but CT can be added to evaluate
articular displacement. MRI is not routinely used in acute
evaluation of this injury but can be used for suspected associated
ligamentous injuries. Treatment for Salter-Harris III/IV proximal
tibial fractures is closed or open reduction to achieve articular
displacement less than 2 mm and stabilization with screws placed
parallel to the knee joint avoiding the physis. LLC immobilization
should also be used.
There is a high incidence of neurovascular injury (14%) among
these proximal tibia physeal fractures (similar to knee dislocation)
because the popliteal artery at its trifurcation is tethered to the
posterior tibia just below the physis. Therefore, a thorough
neurovascular and compartment examination needs to accompany
evaluation of this injury. 7
There is also a high incidence of growth disturbance (premature
physeal closure) in approximately 25% of these injuries. Therefore,
after healing is achieved, growth of the proximal tibial physis
should be followed with knee radiographs and/or full-length
weight-bearing radiographs until the patient reaches skeletal
maturity. 5 , 8

Tibial Tubercle Fracture

Tibial tubercle fractures occur with an incidence of less than 1% to
2.7%. They most commonly occur in males nearing skeletal
maturity (age 14 to 17 years). In a 2019 study, 63% of the patients
with tibial tubercle fractures were overweight. 9 The mechanism of
injury is a forceful eccentric contraction of the extensor mechanism
pulling suddenly on a partially open tibial tubercle apophysis. The
proximal tibia physis closes from posterior to anterior leaving the
anterior portion weaker and susceptible to these injuries with
initiating or landing a jump such as during basketball, as discussed
in a 2020 study. 10 Osgood-Schla er disease coexists in 23% of
patients with tibial tubercle fractures. 11
There are many systems for the classification of tibial tubercle
fractures. The classic system is the Watson-Jones classification
system: type I is a distal tubercle avulsion, type II is a secondary
ossification center fracture that hinges upward at the proximal
tibial physis, and type III (the most common type) is a fracture that
exits out of the proximal tibial physis into the knee joint. The
Ogden modification of this system is frequently used; each of the
three types can be classified as either A, nondisplaced/minimally
displaced, or B, displaced/comminuted. There are modifications by
Ryu/Debenham to add a type IV fracture that exits out the posterior
proximal physis and McKoy/Stanitski to add a type V fracture that
is a combination of IIIB and IV 12 , 13 (Figure 3).

Figure 3 A radiographic representation of the Watson-Jones classification

types I-III and the modifications of Ryu/Debenham (type IV) and McKoy/Stanitski
(type V).

Clinical examination includes assessment of knee pain,

significant swelling, patella alta, and often inability to perform a
straight leg raise. Plain radiographs can diagnose the injury, but CT
scan delineates intra-articular extension of the fracture for bony
surgical decision making. 14 Because intra-articular injuries can
occur along with the fracture in 12% of patients, MRI or direct
visualization with arthroscopy/arthrotomy at the time of surgical
fixation can help identify these associated soft-tissue injuries. 15
Associated injuries that can occur with tibial tubercle fractures
are patellar tendon/quadriceps tendon avulsion (2%), meniscal tear
(2%), and compartment syndrome (4% to 20%). 5 , 11 , 15
Compartment syndrome can occur if the anterior tibial recurrent
artery is torn at the time of fracture; and the anterior compartment
can be released at the time of ORIF if needed.
Management of nondisplaced tibial tubercle fractures is with
long leg casting for 4 to 6 weeks. Treatment of displaced tibial
tubercle fractures is with ORIF. The usual screw configuration is at
least two anterior-to-posterior partially threaded 4.0-mm
cannulated screws (with or without washers) placed parallel to the
physis. 14 Useful surgical pearls for placing these screws are to
obtain a perfect lateral fluoroscopic image of the tibial tubercle by
slightly internally rotating the leg and to remember that the
anatomically reduced apophysis may look slightly wide on
fluoroscopy because the cartilage of the apophysis looks like a gap
(Figure 4).

Figure 4 Images from a 13-year-old boy with tibial tubercle fracture sustained
playing basketball.Lateral radiographs showing type IIIB tibial tubercle fracture at
the time of injury (A), at the time of open reduction and internal fixation (ORIF)
showing the anatomically reduced apophysis (arrow) although it looks gapped
(B), 1 year after ORIF (C), and 2.5 years after ORIF (D). The patient also had
concurrent bipartite acute patellar fracture that healed uneventfully, and returned
to full previous level of sport in football and basketball.
 Outcomes after tibial tubercle fractures are generally very good.
A union rate of 98% to 100% is reported, with 94% of patients able
to return to preinjury level of activity and 98% achieving full knee
range of motion. 11 In a 2019 functional outcomes paper, 26% of
patients with tibial tubercle ORIF had clinically significant
quadriceps weakness and 37% had loss of thigh girth at average 3-
year follow-up. These objective findings did not correlate with
lower patient-reported outcomes. 9
Complications occur in 28% of patients with tibial tubercle
fractures treated with ORIF: painful hardware necessitating
removal (56%), tubercle prominence (18%), refracture (6%),
infection (3%), genu recurvatum (4%, all patients were younger
than 13 years at the time of injury), and leg length difference (5%).
11

Floating Knee
Ipsilateral simultaneous fractures of the tibia and femur are
referred to as a floating knee. This is a rare combination of injuries
that occurs via high-energy mechanisms such as motor vehicle
accidents as a passenger (45%) or pedestrian (33%) and all-terrain
vehicle (9%) injuries. 16 In a 2019 multicenter study of floating
knees, the average age of these patients was 10.2 years, 63% were
male, one-third of the patients had at least one open fracture, 90%
of the femoral fractures were shaft fractures, and 87% of the tibial
fractures were shaft fractures, and the hospital length of stay was 9
days. 16
Classification of floating knees is by the Le s-Vincent
classification system: A, both femur and tibia are closed diaphyseal
fractures; B, one fracture is diaphyseal and other is metadiaphyseal
and both are closed; C, one fracture is epiphyseal and the other is
diaphyseal and both are closed; and D, either femoral or tibial
fracture is open; E, both femoral and tibial fractures are open. 17
 Treatment of floating knees has changed over time toward more
surgical treatment. Comparison of a historical pediatric floating
knee group (1975 to 2003) with a more modern group (2004 to 2014)
showed there was more casting done historically. In the more
modern group, 91% of the femoral fractures were managed
surgically (38% flexible nails, 31% rigid intramedullary nails) and
27% of the tibias were managed with a cast only, whereas 25% of
tibias were managed with flexible nailing. 16
Although 93% of the floating knees in the 2019 multicenter study
had either excellent or good outcomes after at least 1 year follow-
up, complications did occur. The complications were: nonunion
(3%), malunion (9%), and wound complications (10%). 16 In a
systematic review of floating knees, complications were: leg length
discrepancy (33%), malunion (20%), secondary surgeries (13%),
infection (9%), nonunion (7%), and premature physeal closure (3%).
18

Tibial Shaft Fracture

As discussed in a 2019 study, tibial shaft fractures account for 15%
of all long bone injuries in children, and average age at time of
injury is 8 years. 19 Thirty percent of tibial shaft fractures have an
associated fibular fracture, usually caused by a higher energy
mechanism than isolated tibial fractures. This pa ern has a
tendency to progress into valgus alignment because of anterolateral
muscle overpull. Of the tibial shaft fractures with an intact fibula
(lower energy/usually torsional mechanism), varus alignment
eventually develops in 60% because of tethering of the fibula and
posterior muscle overpull even if the fracture was minimally
displaced initially. 20 The mechanism of injury ranges from low-
energy spiral tibial fractures in younger children who sustain a
torsional force with a planted foot to higher energy motor vehicle
and collision sports injuries in older adolescents.
A typical presentation of patients with a tibial fracture is pain at
the fracture site, possible deformity, variable amount of swelling,
and inability to bear weight. The diagnosis of a tibial fracture is
made by AP and lateral tibia/fibula radiographs. Sometimes
dedicated ankle and knee radiographs are necessary to look for
ipsilateral fractures. In a 2020 study of 517 tibial shaft fractures,
4.3% had ipsilateral distal tibial fractures (36% of which were not
diagnosed until chart review for the study). The highest incidence
of these concurrent fractures occurred in the middle-distal third
shaft fracture with spiral or oblique fracture pa erns. 21
Acceptable alignment parameters for tibial shaft fracture in
patients younger than 8 years is up to 10° varus or apex anterior
(procurvatum) angulation, up to 5° valgus or apex posterior
(recurvatum) angulation or rotation, one shaft width (100%)
translation, and 10 mm of shortening. In patients older than 8
years, acceptable parameters are up to 5° varus/valgus, apex
anterior angulation or rotation, 0% apex posterior angulation, 50%
translation, and 5 mm of shortening. 18 , 21 , 22
Treatment for many tibial shaft fractures is closed reduction
within aforementioned tolerances and casting with weekly
radiographic monitoring for 3 weeks to ensure maintenance of
acceptable alignment. Traditionally an LLC is worn for 4 to 6 weeks
followed by a short leg walking cast or boot for another 4 to 6
weeks. 23 If there is loss of reduction during the course of casting,
remanipulation or cast-wedging can be performed. In a 2020 study,
21% of the 75 adolescents treated with closed reduction and casting
of tibial shaft fractures needed either remanipulation or cast-
wedging in the clinic. A total of 60% of these patients required
casting longer than 3 months, especially when both the tibia/fibula
were fractured. Only 4% of these patients needed surgical
treatment. 21 This is a much smaller percentage compared with an
earlier study of 74 patients with tibial shaft fractures in which 40%
needed surgical treatment for loss of reduction during cast
treatment. Predictors of failure of casting were initial displacement
greater than 20% and presence of both a tibial and fibular fracture.
24
Position of the ankle in the cast is important; slight plantar
flexion to prevent recurvatum deformity is preferred. The position
of the knee in an LLC and weight-bearing status were studied in a
prospective randomized study of 81 patients. There was no
difference in final angulation or time to union in the group with 10°
of knee flexion and weight bearing as tolerated versus the group
with 60° of knee flexion and no weight bearing. 25 A 2021
comparison of patients age 5 to 17 years with distal third tibial shaft
fracture treated with 50 LLCs and 35 short leg casts (SLC) showed
that SLC had shorter time to weight bearing (3.3 weeks in SLC
group compared with 6.4 weeks in LLC group), shorter time to
union (7.4 weeks SLC versus 9.0 weeks LLC) without a difference in
final angulation. There were also more cast complications in the
LLC group (12% versus 6% in SLC group). 26
Consideration for noncast treatment of tibial shaft fractures
should be given for loss of reduction in the cast, a floating knee,
patient obesity, open fracture, or polytrauma. Techniques include
external fixation, flexible nailing, rigid intramedullary nailing, and
ORIF with plates and screws.
Flexible nails can be used to stabilize tibial fractures in patients
with open physes. The proximal medial and lateral starting points
for insertion of these flexible nails avoid disturbing the proximal
physis and causing recurvatum deformity. Flexible nails can be
used for stable fracture pa erns and can be used for length-
unstable pa erns, especially if a cast is added for extra stability.
Flexible nailing of a tibial fracture with an intact fibula has
outcomes similar to cast use alone, but decreases the time of
immobilization from 10.3 to 6.6 weeks 27 (Figure 5, A).
Figure 5 Example radiographs of three different fixation methods for displaced
tibial fractures are shown.A, A 7-year-old boy sustained a segmental tibia/fibula
fracture after being hit by a car. Flexible nailing was used along with a cast to
reduce and stabilize the fractures while sparing his physes. Nearly 1 year after
injury, he had healed fully; Park-Harris lines demonstrated no growth
disturbance. B, A 16-year-old boy sustained an unstable tibia/fibula shaft fracture
on a trampoline. He was treated with reamed intramedullary nail and his 1-year
follow-up radiographs show complete healing. C, A 12-year-old boy sustained a
distal third tibia/fibula fracture in a sledding accident. Closed reduction and
casting were unable to keep the reduction stable because of the very distal
fracture falling into recurvatum even with plantar flexion positioning of the foot.
The patient was treated with plate osteosynthesis of the tibia and fibula, went on
to heal, and his 7-year follow-up radiographs are shown.
 Reamed rigid intramedullary nailing of tibial fractures can be
used in older adolescents without significant growth remaining.
More data are needed on which patients are safe to perform this
technique and simple knee-specific radiographic bone age
parameters. 28 There are new techniques that appear safe in small
pilot studies, which avoid crossing an open proximal tibial physis
by using an entry point approximately 3 cm distal to the proximal
tibial physis and medial to the tibial tubercle apophysis 29 (Figure 5,
B).
ORIF with plate and screws is not used as frequently as other
stabilization techniques in pediatric tibial fractures, but for certain
very distal or comminuted pa erns and open fractures, it is a useful
technique. A recent study showed be er alignment at final follow-
up with ORIF compared with utilization of flexible nails and
decreased the need for future surgery, although there was increased
surgical time with ORIF and more wound complications 30 (Figure
5, C).
Open tibial fractures should be managed with antibiotics as soon
as possible, then irrigation/débridement and stabilization of the
fracture to protect the traumatized soft tissue. The literature
supports giving antibiotics within 3 hours of open fracture, which
decreases the chance of infection. 31 A large systematic review with
more than 3,500 open fractures demonstrated no correlation
between time to débridement for open fractures and incidence of
infection following open fracture as long as prophylactic antibiotics
were administered in a timely fashion. 32 Pediatric open tibial
fractures can be stabilized immediately with flexible nails or
external fixation. 33 , 34 Wound closure/coverage should occur as
soon as possible via delayed primary closure, vacuum-assisted
closure, skin graft, or flap.
Complications after tibial shaft fracture include delayed union or
nonunion, which can occur in up to 25% of tibial shaft fractures
(especially in older children and open fractures); malunion; and
compartment syndrome. 20 Malunion can occur though children can
remodel tibial fractures to some extent. Rotational deformity does
not remodel. Apex posterior, valgus, and multiplanar deformities
do not remodel well. Children younger than 8 years can experience
complete remodeling of coronal or sagi al angulation of 10°,
children age 9 to 13 years can have 50% correction, and in children
older than 13 years, only 25% correction is expected. 19 , 23

Compartment Syndrome
Compartment syndrome occurs when there is increased interstitial
pressure within a closed fascial space, which results in decreased
perfusion to the tissues within that space. Tissue ischemia occurs
within 4 hours of increased compartment pressures, which results
in tissue death within 8 hours if not treated. Etiology of pediatric
acute compartment syndrome (PACS) can be traumatic or
atraumatic. 35 , 36 The most common sites for PACS to occur are
lower leg (60%) and forearm (22%). Tibial shaft fractures account
for 40% of all PACS. 37 In a study, the incidence of PACS was 11.6%
for all tibial fractures (9.5% for shaft fractures). 38 In a 2020 study of
515 tibial shaft fractures in patients age 5 to 17 years, the rate of
PACS was lower (1.7%). Predictors of PACS are age older than 14
years, high-energy mechanism of injury (motor vehicle or
motorcycle crash), weight more than 50 kg, comminuted or
segmental fracture pa erns, and presence of ipsilateral fibular
fracture and other orthopaedic injuries. 39
Diagnosis of PACS is clinical by using the 3 A’s: anxiety,
agitation, and increased analgesia requirement. 23 Compartment
pressure measurement can be performed with the same thresholds
for diagnosis as adults, but a 2019 study found that clinical
suspicion is more important in children than compartment
pressure measurements as some kids can tolerate pressure
measurements of greater than 30 mm Hg and gradient less than 30
mm Hg without the development of PACS. 40
In an a empt to prevent PACS, avoidance of circumferential
dressings and bivalving casts in high-risk injuries is recommended.
The limb can be elevated to heart level and supplemental oxygen
can be administered to increase tissue perfusion. Patients should
be admi ed for serial examination. Fasciotomy is the definitive
treatment when PACS does occur. After fasciotomy, vacuum-
assisted closure can be used with washout and vacuum-assisted
closure change every 2 to 3 days until delayed closure or skin
grafting can occur (usually after three serial washouts).
Approximately 85% of children will achieve full functional recovery
after PACS. 37

Toddler Fracture
A toddler fracture is a nondisplaced oblique distal third tibial shaft
fracture that occurs in ambulatory children (usually 9 months to 6
years of age) by a twisting mechanism of the foot. The injury may
occur via an unwitnessed fall, and the patient demonstrates a limp
or refusal to bear weight, possibly with tenderness over the tibial
shaft or pain with foot external rotation. 41 A tibia/fibula radiograph
may be negative for visible fracture 39% of the time. 42 Treatment
for toddler fracture is with a walking boot or weight-bearing cast
(either above or below the knee) for 3 to 4 weeks. There is earlier
return to weight bearing and less risk of skin breakdown with a
boot compared with cast treatment. 42 Radiographs at follow-up can
show callus formation to confirm occult fractures but are not found
to affect treatment decisions. 42 Therefore, follow-up radiographs
are not necessarily needed for toddler fractures.

Distal Tibia Physeal Fracture

After wrist or forearm fractures, ankle injuries are the second most
common in adolescents. 43 The pathogenesis of a distal tibia physeal
fracture is usually a twisting injury. On presentation, a patient with
a distal tibial injury usually has inability to bear weight, bony
tenderness, swelling, or deformity near the ankle. Because distal
tibial bony injuries can present similarly to ligamentous
injuries/sprains of the ankle, both the clinical examination to
pinpoint location of tenderness if possible and three-view
radiographs (AP, lateral, and mortise) of the ankle can be helpful
for diagnosis. Low Risk Ankle Rules (similar to O awa rules in
adults) help guide which patients need radiographs at the time of
ankle injury. If patients have a low-risk examination with
tenderness, swelling, ecchymosis only located on the lateral
malleolus below the joint line or the anterior talofibular
ligament/posterior talofibular ligament/calcaneofibular ligament
area, radiographs are not needed, and patients can be treated
symptomatically without risk of missing a high-risk ankle injury. 44
Distal tibia physeal fractures are classified by the Salter-Harris
system: type I (3% to 15%), type II (40% to 49%, most common),
type III (17% to 25%), type IV (25%), type V (<1%). 45 - 48 Premature
physeal closure (PPC) is most common after type III and type IV
fractures. The distal tibial physis contributes 3 to 4 mm of growth
per year. 45
Treatment goals for distal tibia physeal fractures are to reduce
and stabilize any physeal displacement greater than or equal to 3
mm (as this is a risk factor for PPC) and reduce and stabilize any
joint surface displacement greater than 2 mm (to prevent future
arthritis). Salter-Harris I/II fractures can be closed reduced and
casted for 4 to 6 weeks if the reduction remains stable. The
reduction should be undertaken with adequate anesthesia to
prevent multiple a empts, which can cause further physeal
damage. If unable to reduce the fracture closed, interposed
periosteum or tendon can be removed with open reduction, and if
the fracture needs to be stabilized with something in addition to a
cast, smooth Kirschner wires or a screw into a large-enough
Thurston-Holland fragment can be used. 43 Salter-Harris III/IV
fractures often have specific predictable pa erns similar to Tillaux
and triplane fractures. These intra-articular injuries should be
closed reduced with an LLC or splint, and CT performed to
delineate the intra-articular pa ern and displacement. If the physis
is displaced greater than 3 mm or the joint surface greater than 2
mm, open reduction/internal fixation should be performed with one
epiphyseal screw and possibly one to two metaphyseal screws if the
Thurston-Holland fragment is large enough to avoid crossing the
physis with screws.
One of the main complications after distal tibial physeal fractures
is PPC; either angular deformity or leg length discrepancy can
occur. When broken down by Salter-Harris type, PPC occurs 2% to
38% of the time after Salter-Harris I or II fractures and 7% to 38%
after Salter-Harris III and IV fractures. 49 In a 2021 study, the overall
rate of PPC after distal tibia physeal fractures was 13%. The risk of
PPC was highest in Salter-Harris IV fractures (20%) and next
highest in Salter-Harris II fractures (12%). The most likely
predictors of PPC were residual displacement after reduction and
possibly higher number of reduction a empts. Open reduction of
displaced fractures seemed to decrease the risk of PPC. 48 In
another 2021 study of 195 children with distal tibia/fibula fractures,
11% ultimately had PPC and 6% needed surgical intervention for
angular deformity or leg length discrepancy a mean 14 months after
the original fracture. In this study, a higher number of a empted
reductions increased the risk of PPC as did greater initial
displacement and presence of a concomitant fibular fracture. 50
Another factor that increases the risk of PPC is physeal
displacement greater than or equal to 3 mm, which results in PPC
60% of the time. 51 Patients who have sustained distal tibia/fibula
physeal fractures should be followed for the appearance of Park-
Harris growth arrest lines for at least 2 years after injury to screen
for PPC. If growth disturbance is suspected on plain radiographs,
CT or MRI can be used to identify and quantify the site of physeal
bridging (most commonly in the anteromedial physis). Treatment
for PPC is based on size of the physeal bar and the patient’s
remaining growth potential and may include: completion
epiphysiodesis of the distal tibia (and fibula), physeal bar resection,
and corrective osteotomy (Figure 6).
 Figure 6 An AP radiograph from an 11-year-old girl who sustained a left distal
tibia Salter-Harris II fracture in soccer (A). She underwent open
reduction/percutaneous pinning (B). The Kirschner wire was passed 5 times
across the physis during the case and was removed after healing 4 weeks later.
The patient was followed up at regular intervals and by 1 year postinjury,
evidence of physeal bar without angular deformity was noted (C). By 2 years
after injury, varus angular deformity was noted (D). CT scan confirmed large
anteromedial physeal bar (E). Weight-bearing films were obtained (F).
Completion epiphysiodeses of tibia and fibula were performed along with
corrective osteotomy of the tibia/fibula (G). One-year weight-bearing films
showed healed osteotomy site and neutral ankle alignment (H).

Ankle Fractures
In addition to the distal tibia/fibula physeal fractures described in
the previous section, there are other specific ankle fracture types
that occur during the transition of the distal tibial physis from
skeletally immature to mature. Over the last 18 months of growth
(age 14 years in girls and 16 years in boys), the distal tibial physis
closes predictably from central to medial to lateral and this
accounts for the pa erns of Tillaux and triplane fractures.
 Triplane fractures are two-part, three-part, or four-part fractures
that occur in sagi al, coronal, and transverse planes. They account
for 7.3% of distal tibia/fibula fractures. 46 CT scans can be a useful
adjunct to plain radiographs for three-dimensional surgical
planning and quantifying the articular displacement.
Tillaux fractures are an avulsion of the anterolateral distal tibial
epiphysis by the anterior inferior tibiofibular ligament by an
external rotation mechanism. Tillaux fractures are 2.9% of distal
tibia/fibula fractures. 46
Transitional ankle fractures can be managed with closed
reduction and long leg casting if the articular displacement is less
than 2 mm or open reduction and stabilization with a cannulated
screw for displaced/unstable fractures. The reduction maneuver is
generally traction and internal rotation of the foot relative to the
leg.
In addition to the Salter-Harris classification system and the
transitional ankle fractures, the Dias-Tachdjian classification system
describes ankle fracture pa erns in skeletally immature patients
with position of the foot and direction of force at the time of injury
similar to the Lauge-Hansen classification system in adults. The
four types are supination-inversion, pronation-eversion–external
rotation, supination–plantar flexion, and supination–external
rotation (Figure 7). PPC occurs in supination–external rotation
fractures 35% of the time and in 54% of pronation–external rotation
injuries. 49 , 52 Predictors of negative functional outcome at 4 or more
years after ankle fractures are larger gap after closed reduction,
nonsurgical treatment, and complications of the fracture or
treatment. 53
 Figure 7 The Dias-Tachdjian ankle fracture (fx) classification is useful as it
reflects the pathomechanism of injury.Supination-inversion fx can be subdivided
into lower energy grade I injuries in which the distal fibula fails in tension. As
more energy is imparted to the ankle, a grade II injury with medial malleolus tibial
fx results. In pronation-eversion–external rotation (PER) injury, the tibia sustains
a Salter-Harris II fx with a lateral Thurston-Holland fragment, then a higher,
transverse fibular fx occurs. A supination–plantar flexion injury opens up the
physis anteriorly and has a small Thurston-Holland fracture posteriorly; thus this
fx is hard to see on AP radiographs. Supination–external rotation (SER) fx can
be subdivided into lower energy grade I injury where a Salter-Harris II tibial fx
occurs, but if the ankle continues to fail, a spiral distal fibular fx occurs indicating
a grade II injury.

Chronic regional pain syndrome (CRPS) is an amplified pain

condition that can complicate ankle fractures. Patients with CRPS
demonstrate pain out of proportion to the injury along with edema,
sensory, vasomotor, and autonomic changes. It is most common in
adolescent girls and occurs after lower extremity injuries more
often than after upper extremity injuries (87% versus 13%). A total
of 73% of children with CRPS in one study specifically began having
symptoms after a foot or ankle injury. 49 In addition to orthopaedic
treatment of the inciting injury, CRPS treatment should be
multimodal and involve physical therapy for desensitization, pain
service for use of pharmacologic treatments such as gabapentin and
nonpharmacologic treatment modalities, and psychological
counseling. Although children respond be er to physical therapy
and noninvasive treatments for CRPS than adults, they have
recurrences more often. 49
 Growth arrest/PPC are not usually a problem with transitional
ankle fractures because these fractures occur in a specific age group
that is close to skeletal maturity. Rarely extensor retinaculum
syndrome may occur with ankle fractures. A patient with extensor
retinaculum syndrome shows decreased sensation in the first web
space, extensor hallucis longus/extensor digitorum longus
weakness, and pain with passive toe flexion. Treatment is release of
the superior retinaculum if symptoms do not resolve after
reduction of the inciting fracture.

Foot Fractures
Calcaneal fractures are extremely rare in the pediatric population
(0.0005% incidence). 54 Calcaneal fractures occur in 11- to 13-year-
olds the most. In a systematic review of 284 pediatric patients with
calcaneal fracture from 26 studies, 208 had intra-articular fractures
and 78 were extra-articular or occult. Very young patients had
mostly extra-articular fractures (92% of fractures in those younger
than 7 years were extra-articular) and were treated nonsurgically. 54 ,
55
Of the intra-articular fractures, the tongue-type pa erns had
similar outcomes with surgical and nonsurgical treatment. The
joint depression-type fractures had be er outcomes with surgical
treatment; the patients with joint depression treated nonsurgically
had 21% poor outcomes. 54 In another study of 23 calcaneal
fractures in 22 skeletally immature patients, 78% had intra-articular
fractures and 22% extra-articular. Nine of these patients were
followed for 4 or more years; 8 were treated nonsurgically and 1 was
treated with ORIF. Seven of 9 patients were pain free and had
unrestricted motion and activity. 56 It is important to look for
associated fractures among calcaneal fracture patients, especially in
those older than 13 years. It is more common to have associated
fractures in these pediatric patients than in adults with calcaneal
fractures.
Talar fractures are 0.1% of pediatric fractures. The mechanism of
injury is usually a fall from a height with a dorsiflexed ankle. The
literature on osteonecrosis (and even ability to use Hawkins sign
like in adults) is conflicting, so all talar fractures, even
nondisplaced, should be followed long term. There were 3 of 12
patients with pos raumatic arthritis in one study of pediatric talar
fractures. As with calcaneal fractures, concurrent injuries to the
ipsilateral extremity are common (7 of 15 patients had ipsilateral
injuries in one study). 57 Displaced talar fractures should be treated
with ORIF and should be followed long term for any signs of
osteonecrosis.

Summary
Fractures of the lower extremity are common in children and
adolescents. Outcomes for most of these fractures are
good/excellent in this age group, but special knowledge of the
growing skeleton can help guide treatment of the fractures to
harness the remodeling power of open physes while avoiding the
pitfalls of injury-induced angular deformity or limb-length
discrepancy.

Key Study Points

Tibial tubercle fractures generally have good outcomes, with 94% or more returning
to preinjury activity levels, 98% achieving full knee range of motion, and 98% union
though quadriceps strength deficit persists in 26% 3 years after injury.
Because of the open physes at the proximal and distal end of the tibia, injuries
involving the physis in growing children can have long-term effects even after
fractures have healed because of PPC. Angular deformity can result from partial
PPC and leg length discrepancy from total PPC.
Toddler fractures are low-energy minimally displaced oblique distal third tibial
fractures that have earlier return to weight bearing and less skin complications when
treated in a walking boot versus in a cast.
PACS can occur with 1.7% to 9.5% of tibial shaft fractures. Risk factors that
increase the risk of PACS are age older than 14 years, higher body mass index,
high-energy injuries (motor vehicle or motorcycle crashes), and
comminuted/segmental tibial fracture patterns. Treatment of compartment
syndrome is with complete four-compartment fasciotomy.
Annotated References
1. Ray JM, Hendrix J: Incidence, mechanism of injury, and
treatment of fractures of the patella in children. J Trauma
1992;32(4):464-467.
2. Ge ys FK, Morgan RJ, Fleischli JE: Superior pole sleeve fracture
of the patella: A case report and review of the literature. Am J
Sports Med 2010;38(11):2331-2336.
3. Hunt DM, Somashekar N: A review of sleeve fractures of the
patella in children. Knee 2005;12(1):3-7.
4. Bates DG, Hresko MT, Jaramillo D: Patellar sleeve fracture:
Demonstration with MR imaging. Radiology 1994;193(3):825-827.
5. Mayer S, Albright JC, Stoneback JW: Pediatric knee dislocations
and physeal fractures about the knee. J Am Acad Orthop Surg
2015;23(9):571-580.
6. Peterson HA, Madhok R, Benson JT, Ilstrup DM, Melton LJIII:
Physeal fractures: Part 1. Epidemiology in Olmsted County,
Minnesota, 1979-1988. J Pediatr Orthop 1994;14(4):423-430.
7. Zionts LE: Fractures around the knee in children. J Am Acad
Orthop Surg 2002;10(5):345-355.
8. Gautier E, Ziran BH, Egger B, Slongo T, Jakob RP: Growth
disturbances after injuries of the proximal tibial epiphysis. Arch
Orthop Trauma Surg 1998;118(1-2):37-41.
9. Riccio AI, Tulchin-Francis K, Hogue GD, et al: Functional
outcomes following operative treatment of tibial tubercle
fractures. J Pediatr Orthop 2019;39(2):e108-e113. This study looked
at 42 patients with tibial tubercle fractures treated with ORIF.
Twenty-six percent of patients were found to have a deficit in
quadriceps extension strength compared with the uninjured side,
and 37% had loss of thigh girth at average 3-year follow-up. Level
of evidence: III.
10. Bailey MEA, Wei R, Bolton S, Richards RH: Paediatric injuries
around the knee: Bony injuries. Injury 2020;51(3):611-619. This
study is a review of diagnosis, management, and pitfalls of bony
 injuries around the skeletally immature knee including tibial
tubercle fractures and patellar sleeve fractures. Level of evidence:
V.
11. Pretell-Mazzini J, Kelly DM, Sawyer JR, et al: Outcomes and
complications of tibial tubercle fractures in pediatric patients: A
systematic review of the literature. J Pediatr Orthop 2016;36(5):440-
446.
12. Ryu RK, Debenham JO: An unusual avulsion fracture of the
proximal tibial epiphysis. Case report and proposed addition to
the Watson-Jones classification. Clin Orthop Relat Res
1985;194:181-184.
13. McKoy B, Stanitski CL: Acute tibial tubercle avulsion fractures.
Orthop Clin North Am 2003;34(3):397-403.
14. Franz P, Luderowski E, Tuca M: Tibial tubercle avulsion
fractures in children. Curr Opin Pediatr 2020;32(1):86-92. A review
of tibial tubercle fractures is presented. Diagnosis can be made
by radiographs, but CT scans are useful for visualizing the extent
of the fracture. The classification, associated injuries, preferred
surgical treatment with ORIF, and outcomes/complications are
also discussed. Level of evidence: V.
15. Pandya N, Edmonds E, Roocroft J, Mubarak S: Tibial tubercle
fractures: complications, classification, and the need for intra-
articular assessment. J Pediatr Orthop 2012;32:749-759.
16. CORTICES. The pediatric “Floating Knee” injury: A State-of-
the-Art Multicenter Study. J Bone Joint Surg Am 2019;101(19):1761-
1767. A multicenter study of 130 floating knees in 129 patients
from 11 pediatric trauma centers demonstrates a change from
previously reported literature on pediatric floating knees from
historically more nonsurgical treatment to more common
surgical fixation of at least the femoral fracture. This approach
led to good or excellent results in 93.1%. Level of evidence: III.
17. Le s M, Vincent N, Gouw G: The “floating knee” in children. J
Bone Joint Surg Br 1986;68(3):442-446.
18. Anari JB, Neuwirth AL, Horn BD, Baldwin KD: Ipsilateral femur
and tibia fractures in pediatric patients: A systematic review.
World J Orthop 2017;8(8):638-643.
19. Hogue GD, Wilkins KE, Kim IS: Management of pediatric tibial
shaft fractures. J Am Acad Orthop Surg 2019;27(20):769-778. The
authors present a review of pediatric tibial shaft fractures
discussing in-depth treatment strategies such as closed
reduction/casting, flexible nailing, external fixation, and ORIF.
Discussion of acceptable parameters for sagi al and coronal
alignment was based on age and remodeling potential. Level of
evidence: V.
20. Mashru RP, Herman MJ, Pizzutillo PD: Tibial shaft fractures in
children and adolescents. J Am Acad Orthop Surg 2005;13(5):345-
352.
21. Sheffer BW, Villarreal ED, Ochsner MGIII, Sawyer JR, Spence
DD, Kelly DM: Concurrent ipsilateral tibial shaft and distal tibial
fractures in pediatric patients: Risk factors, frequency, and risk of
missed diagnosis. J Pediatr Orthop 2020;40(1):e1-e5. The authors
present a study of 517 tibial shaft fractures where 4.3% had
ipsilateral distal tibial fractures (36% of which were not
diagnosed until chart review for the study). The highest incidence
of these concurrent fractures occurred in middle-distal third
shaft fracture with spiral or oblique fracture pa erns. Level of
evidence: III.
22. Ho CA, Dammann G, Podeszwa DA, Levy J: Tibial shaft
fractures in adolescents: Analysis of cast treatment successes and
failures. J Pediatr Orthop B 2015;24(2):114-117.
23. Herman MJ, Martinek MA, Abzug JM: Complications of tibial
eminence and diaphyseal fractures in children: Prevention and
treatment. J Am Acad Orthop Surg 2014;22(11):730-741.
24. Kinney MC, Nagle D, Bastrom T, Linn MS, Schwar AK,
Pennock AT: Operative versus conservative management of
displaced tibial shaft fracture in adolescents. J Pediatr Orthop
2016;36(7):661-666.
25. Silva M, Eagan MJ, Wong MA, Dichter DH, Ebramzadeh E,
Zionts LE: A comparison of two approaches for the closed
treatment of low-energy tibial fractures in children. J Bone Joint
Surg Am 2012;94(20):1853-1860.
26. Barne SA, Fontenot B, Leonardi C, Gonzales JA, Gargiulo D,
Heffernan MJ: Comparison of short-leg and long-leg casts for the
treatment of distal third tibial shaft fractures in children. J Pediatr
Orthop 2021;41(3):e259-e265. This study looked at 87 pediatric
patients with distal third tibial shaft fractures and compared SLC
with LLC and found a higher percentage of cast complications in
the LLC (12%) versus SLC (6%) group, and the SLC group had
earlier time to weight bearing and shorter time to fracture union
when compared with LLC. Level of evidence: III.
27. Canavese F, Botnari A, Andreacchio A, et al: Displaced tibial
shaft fractures with intact fibula in children: Nonoperative
management versus operative treatment with elastic stable
intramedullary nailing. J Pediatr Orthop 2016;36(7):667-672.
28. Weltsch D, Baldwin KD: Rigid locked nail fixation for pediatric
tibia fractures – Where are the data? World J Orthop
2019;10(8):299-303. This study discusses, despite the paucity of
evidence in literature, rigid intramedullary nails causing growth
arrest and posits that rigid intramedullary nailing of tibial shaft
fractures could potentially be used more often in nearly skeletally
mature if there was a reliable and easily applicable skeletal
maturity measure for the proximal tibia. Level of evidence: V.
29. Williams KA, Thier ZT, Mathews CG, Locke MD: Physeal-
sparing rigid intramedullary nailing in adolescent tibial shaft
fractures: A Pilot Study. Cureus 2021;13(3): e13893. This study
compared outcomes of tibial shaft fractures in two groups: 13
reamed intramedullary nails placed in adolescents average age
13.8 years by a physeal sparing approach approximately 3 cm
distal to the proximal tibial physis and medial to the tibial
tubercle apophysis. These patients were compared with another
group treated with flexible nails and ORIF with average age 11.5
years. The reamed intramedullary nail group had quicker time to
 weight bearing and less reoperations than the other group. Level
of evidence: IV.
30. Pennock AT, Bastrom TP, Upasani VV: Elastic intramedullary
nailing versus open reduction internal fixation of pediatric tibial
shaft fractures. J Pediatr Orthop 2017;37(7):e403-e408.
31. Pa akis MJ, Wilkins J: Factors influencing infection rate in open
fracture wounds. Clin Orthop Relat Res 1989;243:36-40.
32. Schenker ML, Yannascoli S, Baldwin KD, Ahn J, Mehta S: Does
timing to operative debridement affect infectious complications
in open long-bone fractures? A systematic review. J Bone Joint
Surg Am 2012;94(12):1057-1064.
33. Pandya NK, Edmonds EW, Mubarak SJ: The incidence of
compartment syndrome after flexible nailing of pediatric tibial
shaft fractures. J Child Orthop 2011;5(6): 439-447.
34. Laine JC, Cherkashin A, Samchukov M, Birch JG, Rathjen KE:
The management of soft tissue and bone loss in Type IIIB and
IIIC pediatric open tibia fractures. J Pediatr Orthop 2016;36(5):453-
458.
35. Livingston KS, Glo becker MP, Shore BJ: Pediatric acute
compartment syndrome. J Am Acad Orthop Surg 2017;25(5):358-
364.
36. Livingston K, Glo becker M, Miller PE, Hresko MT, Hedequist
D, Shore BJ: Pediatric nonfracture acute compartment syndrome:
A review of 39 cases. J Pediatr Orthop 2016;36(7):685-690.
37. Lin JS, Balch Samora J: Pediatric acute compartment syndrome:
A systematic review and meta-analysis. J Pediatr Orthop B
2020;29(1):90-96. In this systematic review, the authors note PACS
to be most common in the lower leg. Eighty-five percent of
patients achieved full recovery, with the most common deficit
being range of motion. Level of evidence: IV.
38. Shore BJ, Glo becker MP, Zurakowski D, Gelbard E, Hedequist
DJ, Matheney TH: Acute compartment syndrome in children and
teenagers with tibial shaft fractures: Incidence and multivariable
risk factors. J Orthop Trauma 2013;27(11):616-621.
39. Villarreal ED, Wrenn JO, Sheffer BW, Sawyer JR, Spence DD,
Kelly DM: Do patient-specific or fracture-specific factors predict
the development of acute compartment syndrome after pediatric
tibial shaft fractures? J Pediatr Orthop 2020;40(3):e193-e197. The
authors found in 517 tibial shaft fractures in pediatric patients,
PACS occurred in 1.9% of these fractures. Factors associated with
PACS were: age older than 14 years, higher body mass index,
motorized vehicle accidents, comminuted fractures, presence of
an ipsilateral fibular fracture, and other orthopaedic injuries.
Level of evidence: III.
40. Bussell HR, Aufdenbla en CA, Subotic U, et al: Compartment
pressures in children with normal and fractured lower
extremities. Eur J Trauma Emerg Surg 2019;45(3):493-497. The
authors of this prospective study evaluated compartment
pressures in children age 16 years and younger with lower
extremity fractures requiring reduction. The authors found that
children have higher normal compartment pressures than adults
and are able to tolerate higher absolute compartment pressures
and gradients than adults before clinically significant acute
compartment syndrome occurs. Level of evidence: IV.
41. Schuh AM, Whitlock KB, Klein EJ: Management of toddler’s
fractures in the pediatric emergency department. Pediatr Emerg
Care 2016;32(7):452-454.
42. Bauer JM, Lovejoy SA: Toddler’s fractures: Time to weight-bear
with regard to immobilization type and radiographic monitoring.
J Pediatr Orthop 2019;39(6):314-317. In this retrospective review of
192 patients with toddler fractures, the authors found that
children treated in a boot returned to walking sooner and had
less risk of skin breakdown than those treated in a cast. Ninety-
eight percent of all patients were walking by 4 weeks. Level of
evidence: III.
43. Wuerz TH, Gurd DP: Pediatric physeal ankle fracture. J Am Acad
Orthop Surg 2013;21(4):234-244.
44. Boutis K, von Keyserlingk C, Willan A, et al: Cost consequence
analysis of implementing the low risk ankle rule in emergency
departments. Ann Emerg Med 2015;66(5):455-463.e4.
45. Su AW, Larson AN: Pediatric ankle fractures: Concepts and
treatment principles. Foot Ankle Clin 2015;20(4):705-719.
46. Spiegel PG, Cooperman DR, Laros GS: Epiphyseal fractures of
the distal ends of the tibia and fibula. A retrospective study of
two hundred and thirty-seven cases in children. J Bone Joint Surg
Am 1978;60(8):1046-1050.
47. Leary JT, Handling M, Talerico M, Yong L, Bowe JA: Physeal
fractures of the distal tibia: Predictive factors of premature
physeal closure and growth arrest. J Pediatr Orthop 2009;29(4):356-
361.
48. Jalkanen J, Sinikumpu JJ, Puhakka J, et al: Physeal fractures of
distal tibia: A systematic review and meta-analysis. J Pediatr
Orthop 2021; April 12 [Epub ahead of print]. The authors
performed a systematic review of distal tibia physeal fractures
and found an overall rate of PPC of 13%. The most likely
predictors of PPC were Salter-Harris IV fractures, residual
displacement after reduction, and possibly higher number of
reduction a empts. Open reduction might reduce PPC. Level of
evidence: V.
49. Denning JR: Complications of pediatric foot and ankle fractures.
Orthop Clin North Am 2017;48(1):59-70.
50. Stenroos A, Puhakka J, Jalkanen J, et al: Risk of premature
physeal closure in fractures of distal tibia. J Pediatr Orthop B
2021;30(1):25-31. The authors studied 195 children with distal
tibia/fibula fractures; 11% ultimately had PPC and 6% needed
surgical intervention for angular deformity or leg length
difference on average 14 months after injury. A higher number of
a empted reductions increased the risk of PPC. Level of
evidence: IV.
51. Barmada A, Gaynor T, Mubarak SJ: Premature physeal closure
following distal tibia physeal fractures: A new radiographic
 predictor. J Pediatr Orthop 2003;23(6):733-739.
52. Rohmiller MT, Gaynor TP, Pawelek J, et al: Salter-Harris I and II
fracture of the distal tibia: Does mechanism of injury relate to
premature physeal closure? J Pediatr Orthop 2006;26(3):322-328.
53. Lurie B, Van Rysselberghe N, Pennock AT, Upasani VV:
Functional outcomes of Tillaux and triplane fractures with 2 to 5
millimeters of intra-articular gap. J Bone Joint Surg Am
2020;102(8):679-686. The authors retrospectively reviewed 34
patients with triplane fractures and 23 with Tillaux fractures
(average 4.5-year follow-up). Predictors of negative functional
outcome after ankle fractures were larger gap after closed
reduction, nonsurgical treatment, and complications of the
fracture or treatment. Level of evidence: III.
54. Najefi AA, Najefy A, Vemulapalli K: Paediatric calcaneal
fractures: A guide to management based on a review of the
literature. Injury 2020;51(7):1432-1438. The authors reviewed a
total of 284 patients across the literature. They found that
outcomes seem to be poorer in those without adequate anatomic
reduction. Displaced intra-articular fractures in all age groups
should undergo reduction of the articular surface to a empt to
prevent future pain and arthritis. Extra-articular fractures in
children are less severe and do well with nonsurgical treatment.
Level of evidence: V.
55. Schmidt TL, Weiner DS: Calcaneal fractures in children. An
evaluation of the nature of the injury in 56 children. Clin Orthop
Relat Res 1982;171:150-155.
56. Mora S, Thordarson DB, Zionts LE, Reynolds RAK: Pediatric
calcaneal fractures. Foot Ankle Int 2001;22(6):471-477.
57. Meier R, Kre ek C, Griensven M, et al: Fractures of the talus in
the pediatric patient. Foot Ankle Surg 2005;11:5-10.
C H AP T E R 6 3

Pediatric Hip Disorders

Vidyadhar V. Upasani MD, FAAOS, FAOA, Jessica L.
Hughes MD

Dr. Upasani or an immediate family member has received royalties from Orthofix, Inc. and
OrthoPediatrics; serves as a paid consultant to or is an employee of Daedalus Medical
Solutions, Inc., DePuy, a Johnson & Johnson Company, Orthofix, Inc., OrthoPediatrics, and
Stryker; serves as an unpaid consultant to Indius and Pacira; has stock or stock options held in
Imagen; has received research or institutional support from EOS Imaging, nView,
OrthoPediatrics, and Zimmer; and serves as a board member, owner, officer, or committee member
of Pediatric Orthopaedic Society of North America and Scoliosis Research Society. Neither Dr.
Hughes nor any immediate family member has received anything of value from or has stock or
stock options held in a commercial company or institution related directly or indirectly to the
subject of this chapter.

ABSTRACT
Pediatric hip disorders encompass a wide range of pathologies
affecting the proximal femur, acetabulum, or both. Developmental
dysplasia of the hip is described as the abnormal development of
the hip joint ranging from joint laxity to dislocation. Early diagnosis
and intervention are the keys to successful treatment. Slipped
capital femoral epiphysis is a rotational deformity through the
proximal femoral capital physis. The goal of treatment is to prevent
further slip progression and reduce deformity. In situ fixation with
a single screw is the mainstay of treatment for stable slips. Legg-
Calvé-Perthes disease is a pediatric hip condition characterized by
idiopathic osteonecrosis of the proximal femoral epiphysis leading
to joint deformity, incongruity, and subsequent dysfunction. The
disease has a prolonged predictable course of osteonecrosis,
revascularization and fragmentation, reossification, and finally,
remodeling. Femoral acetabular impingement is the result of
abutment between the proximal femur and acetabulum during
physiologic range of motion. Symptomatic femoroacetabular
impingement with concomitant chondrolabral pathology for which
nonsurgical measures are unsuccessful can benefit from hip
arthroscopy or an open procedure, but the effect of surgical
intervention on the natural history of the hip remains unknown.
Keywords: developmental dysplasia of the hip; femoroacetabular
impingement; Legg-Calvé-Perthes; slipped capital femoral
epiphysis

Introduction
Pediatric hip disorders involve anatomic changes to the proximal
femur, acetabulum, or both that affect the normal development of
the hip joint. The triradiate cartilage ossification centers all appear
by the age of 8 to 9 years and fuse by age 17 to 18 years. Therefore,
much of the shape of the acetabulum, which plays an important
role in the prognosis of hips disorders, is determined by age 8
years. Although the overall height and width of the acetabulum
occurs through interstitial growth of the triradiate cartilage, the
depth and shape of the acetabulum occurs through the interaction
with the femoral head. The resultant deformity can lead to pain,
dysfunction, and premature arthritis. Prompt recognition and
intervention of the specific disorder leads to improved outcomes.

Developmental Dysplasia of the Hip

Developmental dysplasia of the hip (DDH) is described as the
abnormal development of the hip joint and represents a wide
spectrum of pathology, ranging from joint laxity or acetabular
dysplasia on ultrasonography to hip instability and dislocation.
Some form of hip instability is found in 1 in 1,000 newborns on
examination, and up to 5 in 1,000 are ultimately managed. 1 Risk
factors include female sex, intrauterine breech presentation,
swaddling as a newborn, 2 positive family history, first born,
oligohydramnios, and ethnicity. Commonly associated conditions
include other packaging disorders such as congenital torticollis,
metatarsus adductus, and congenital knee dislocations. DDH is
involved in 20% to 40% of patients with osteoarthritis of the hip and
up to 8% of patients undergoing total hip arthroplasty (THA).
Subluxation is a stronger predictor of early arthritis than a lower
center-edge angle.
Normal development of the proximal femur and acetabulum in
newborns is interdependent, requiring congruency and free
motion. In DDH, this congruent relationship is lost as a result of
hip instability. An abnormal relationship between the femoral head
and the acetabulum leads to altered development of these
structures, that is, shallow socket with anterolateral deficiency and
pathologic anteversion. Repetitive instability episodes result in a
cartilaginous thickened ridge on the edge of the acetabulum called
the neolimbus. Intra-articular blocks to reduction include a
thickened pulvinar and ligamentum teres and hypertrophic
transverse acetabular ligament. Extra-articular blocks to reduction
include contraction of the joint capsule in an “hourglass
configuration” secondary to the iliopsoas and adductor longus
tendons. Although hip dysplasia affects mostly the acetabulum, the
pathologic changes to the femur can occur secondary to subluxation
or dislocation and abnormal contact with the acetabulum because
of excessive anteversion.

Diagnosis
Diagnosis of DDH in the newborn involves a discerning clinical and
ultrasonographic examination. Commonly, newborns do not have
pain, clinical deformity, or loss of motion, so any abnormal
examination finding can be quite subtle. The natural history of
untreated DDH can vary from spontaneous resolution, or
subclinical instability leading to dysplasia after childhood, or
progressive subluxation and eventual dislocation. Therefore, all
newborns undergo a clinical examination at birth to evaluate for
possible instability, which is repeated throughout the newborn
period as examination findings can become normal within 4 weeks.
A positive Ortolani maneuver (clunk on entry of the femoral head
into the hip joint) is appreciated with gentle pressure on the
posterior greater trochanter pushing the hip anteriorly with the
hips flexed and abducted and signifies a dislocated hip that can be
reduced. A negative Ortolani maneuver is a hip that is irreducible
and remains dislocated. A positive Barlow maneuver (clunk on exit
of the femoral head out of the hip joint) is appreciated with gentle
posterior pressure with the hip and knee flexed with neutral
rotation and abduction. 3 Whereas many joints have subtle clicks
through an arc of motion, a clunk is a more significant audible and
palpable change in femoral head position signifying either femoral
head dislocation or reduction depending on the maneuver
performed. Diagnosing DDH after 6 months of age with physical
examination can be more challenging as the Barlow and Ortolani
maneuvers become less reliable. After 3 months of age, limited hip
abduction in the flexed position becomes the most reliable
diagnostic sign. The examiner may also see asymmetric groin,
gluteal, or thigh folds in dislocated hips in infants older than 3
months. Unilateral dislocations will present with a positive
Galeazzi sign and leg length discrepancy. Once the child reaches
walking age, a dislocated hip will cause a Trendelenburg gait
secondary to abductor insufficiency or toe walking to make up for
the leg length discrepancy.
There is controversy regarding the use of diagnostic imaging
during screening. Some countries universally screen all newborns
with ultrasonography of the hip in conjunction with clinical
examination. However, this risks overtreatment and high false-
positive rates as a result of physiologic laxity. In North America,
selective ultrasonography screening of only high-risk infants has
been determined as the optimal strategy for early detection. High-
risk newborns are those with positive family history, intrauterine
breech position, or abnormal clinical examination results. Of those
screened, 1 in 100 have clinical signs of hip instability and only 1.5
in 1,000 hips have true dislocation. 4
Ultrasonography is the imaging modality of choice in the first 4
to 6 months of life before the secondary ossification center of the
femoral head has ossified. The initial ultrasonographic examination
should be performed at 2 and 8 weeks of age because the results
have prognostic implications, with more severely dysplastic hips
responding poorly to treatment if the diagnosis is delayed. Those
with positive Ortolani or Barlow maneuvers should be evaluated
within the first couple of weeks of life to begin early treatment.
Those with a negative examination but risk factors can wait up to 6
to 8 weeks to reduce the possibility of a false-positive image.
Patients with risk factors for DDH but normal findings on initial
ultrasonography should be followed and undergo radiographic
examination at 6 months of age because there is a 29% chance of
having residual dysplasia despite the initial normal
ultrasonography findings. 5
The Graf method of ultrasonography is well accepted for analysis
of hip dysplasia. The alpha angle is the measurement of the
acetabular inclination. Osseous coverage of the femoral head can
also be measured. The beta angle represents the cartilaginous
femoral head coverage or chondrolabral angle. In normal hips the
alpha angle is greater than 60° and the beta angle is less than 55°;
the severity of dysplasia is worse with increasing Graf grade (Figure
1).
 Figure 1 Ultrasonographic imaging of the hip in a newborn showing the main
anatomic landmarks for developmental dysplasia of the hip screening including
the ilium and osseous roof of the acetabulum, the labrum, and the femoral head
(A); the alpha angle, the percentage of femoral head coverage, and the
pubofemoral distance (B); and the subluxation with the instability maneuver (C).

Most physicians use the dynamic standard minimum

examination, which combines evaluating the static hip morphology
as well as dynamic stability (Figure 2). This real-time
ultrasonographic assessment of the hip is performed with and
without stress maneuvers in both the coronal and transverse planes
of a hip in neutral and in flexion. 6 Femoral head coverage is
measured, and any value greater than 50% is considered normal.
The ultrasonographic pubofemoral distance has recently been
shown to have be er interrater reliability than the Graf method.
The pubofemoral distance correlates with femoral head coverage
and can be followed with DDH treatment. Cutoff values are 6.0 mm
in hip flexion and adduction, 4.6 mm in neutral, and 4.9 mm in
flexion. 7 A newborn younger than 4 weeks can have up to 4 mm of
displacement when stressed, less than 50% coverage, and a
subluxated femoral head more than 2 mm secondary to physiologic
laxity. The most recent clinical practice guidelines do not
recommend ordering hip ultrasonography after 4 months of age, 8
because the femoral head ossific nucleus is often large enough to
obscure the acetabulum.
 Figure 2 Dynamic transverse ultrasonographic view.A, Demonstration of infant
and transducer position. B, The dynamic component uses a Barlow maneuver
to view the proximal femoral shaft and head, with a normal hip or stable
dysplastic hip not displacing past the ischium.(Copyright San Diego Pediatric
Orthopedics.)

Multiple classifications and measurements have been established

to be er characterize the severity of hip dysplasia. To be
implemented before the ossific nucleus of the proximal femur is
present, the International Hip Dysplasia Institute developed a
classification based on the location of the proximal femoral
metaphysis relative to the Hilgenreiner line, the Perkin line, and a
dividing line at 45° (Figure 3). The Tönnis classification uses the
presence of the ossific nucleus and its location relative to the
quadrants formed by the Hilgenreiner and Perkin lines. The Tönnis
grade correlates with long-term outcomes; each increase in
one Tönnis grade will double the likelihood of failure of
nonsurgical management. 9 , 10 Acetabular index is more commonly
measured in infantile DDH, and it is particularly more reliable in
children younger than 8 years. In a normal developing hip, this
value decreases with age, but in DDH it remains elevated. As the
pediatric acetabulum ossifies and further develops, other
radiographic measures can be used to further describe the shape of
the acetabulum. The Tönnis angle of acetabular inclination is
measured from the medial to lateral edge of the sourcil and is
measured relative to the horizontal. A normal Tönnis angle is 0° ±
10°. The lateral center-edge angle (center-edge angle of Wiberg) and
the anterior center-edge angle (angle of Lequesne) are useful
measurements (Figure 4), obtained on AP and false-profile
radiographs of the pelvis, respectively; in patients older than 5
years, the measurements can characterize femoral head coverage
and acetabular deficiency. These are more commonly used in older
patients with hip dysplasia, as discussed later in this section.
Patients with a history of DDH should be followed to skeletal
maturity because there is a risk for residual dysplasia even with
successful treatment as infants.

Figure 3 AP pelvic radiograph from a 6-month-old girl with developmental

dysplasia of the left hip and complete dislocation.A, The Hilgenreiner line, Perkin
line, and acetabular index are important tools to assess hip dysplasia in children.
B, The Tönnis classification modified by the International Hip Dysplasia Institute,
in which the superior midpoint of the metaphysis is used and the inferolateral
quadrant is divided into two parts through a 45° line.
 Figure 4 AP (A) and false-profile (B) pelvic radiographs with measures of
lateral center-edge angle (LCEA), Tönnis angle, and anterior center-edge angle.
(Copyright San Diego Pediatric Orthopedics.)

Management
Treatment outcomes are directly related to age of initial treatment
and severity of the dysplasia with the best long-term results for
those patients treated without surgery during infancy. Once the
femoral head is concentrically reduced and the reduction is
maintained, the innate growth potential in a young child will allow
for development of the acetabulum. In the otherwise typically
developing newborn, the Pavlik harness successfully treats
approximately 90% of hips with stable dysplasia and 73% of hips
with a positive Ortolani test. 11 The harness dynamically places the
hips in a flexed and abducted position that has been shown to aid
in a concentric reduction and maintenance of that reduction to
allow acetabular remodeling. The success rates of the Pavlik
harness are significantly lower in the populations with
neuromuscular and myelomeningocele disorders, patients with
arthrogryposis, in infants with extreme ligamentous laxity (severe
Ehlers-Danlos syndrome), and in infants older than 12 months.
There is still debate regarding the duration and protocol of
treatment with a Pavlik harness. A 2021 study that compared
patients who were weaned out of the harness with those who had
immediate cessation once the ultrasonography findings were
normal demonstrated no difference in risk of residual hip dysplasia
at 1 year despite the weaned group wearing the brace longer. 12
During treatment with a Pavlik harness, patients are monitored
using clinical examination and repeat ultrasonography. If the hip
remains dislocated with no improvement in head position by 3 to 4
weeks, the harness is discontinued, and a closed or open reduction
is often required to reduce the hip. If the hip is reducible in a Pavlik
harness but remains unstable on examination, the patient can be
transitioned into a rigid abduction brace for an additional 3 to 4
weeks. Some patients who are too large or strong for a Pavlik
harness can be started in an abduction brace. There have been
variable results regarding the residual acetabular dysplasia
following use of a Pavlik harness. One study demonstrated that 29%
of hips had greater than two standard deviations above the mean
almost 15 months after a normal ultrasonographic assessment after
treatment with the Pavlik harness. 13 Potential complications of the
Pavlik harness are osteonecrosis and femoral nerve palsy. A
femoral nerve palsy is likely related to excessive hip flexion (>120°)
and is predictive of treatment failure because treatment of a
femoral nerve palsy requires discontinuation of the harness until
resolution of the palsy.
Patients up to walking age with persistently dislocated hips in
whom bracing was unsuccessful should undergo a closed reduction
with arthrography (Figure 5) to assess whether the femoral head
can be successfully reduced within the Ramsey safe zone. The
Ramsey safe zone is the minimum range of hip abduction and
flexion required to keep the hip reduced. Traction is one approach
to aid in closed reduction to allow gentle stretching of the
contracted muscles before a empted reduction. Soft-tissue
lengthening can also be performed on the psoas and adductors to
ease reduction and broaden the safe zone. 14 Following concentric
reduction, a hip spica cast is applied to be worn for 4 to 6 weeks
followed by a repeat hip arthrogram to confirm maintenance of
reduction and repeat casting. Following casting, the patient usually
wears an abduction brace until the acetabular dysplasia has
resolved radiographically.

Figure 5 A, AP pelvic radiograph from a 1.5-year-old child with left

developmental dysplasia of the hip and dislocation. Arthrogram of left hip (B)
demonstrating blocks to reduction including hypertrophic labrum, pulvinar, and
ligamentum teres (C).

Long-term outcomes of closed reduction using historical

treatment algorithms have demonstrated relatively high rates of
residual dysplasia, need for secondary reconstructive surgery, and
early arthroplasty. 15 A 2021 study using contemporary algorithms
showed that after 10 years, hips that underwent closed reduction,
despite less severe disease, had significantly higher rates of
requiring secondary surgery than open reduction (47% and 30%,
respectively). 16 The Iowa group reported their long-term results in
patients with DDH who underwent closed reduction and noted that
after a mean of 48 years, 50% of hips underwent THA, with bilateral
disease in older patients posing a greater risk for surgery. 17
If the hip cannot be concentrically reduced within the safe zone,
an open reduction is required to remove any blocks to reduction.
Open reduction can be performed through an anteromedial or
anterior approach. The anteromedial approach is typically
performed in infants younger than 1 year because it provides more
direct access to removing the blocks to reduction. This approach is
ideal for management of bilateral dislocations secondary to ease of
positioning and minimal blood loss. However, caution must be
taken when performing surgery near the medial femoral circumflex
artery. Also, the stability of the reduction depends on the hip spica
in the “human position” if a ligamentum teres reconstruction is not
performed. An anterior approach can be performed in children
older than 12 months with the addition of a capsulorraphy for
added stability. After walking age, a femoral shortening osteotomy
may be required to facilitate the reduction by decreasing tension
and reducing the risk of osteonecrosis. With the femoral osteotomy,
excessive femoral anteversion can be corrected as well. One study
demonstrated that 54% of patients who underwent an open
reduction received a THA after an average of 45 years. 18
After 18 months of age, a concurrent pelvic osteotomy (Salter,
Dega, or Pemberton) can be performed to aid in reduction and
improve acetabular coverage. Remodeling of acetabular dysplasia
occurs mostly in the first 4 years of life. There is minimal change
after age 4 years; thus, patients with severe dysplasia may require a
pelvic osteotomy. Regardless of the type of osteotomy, the goal is
increased anterolateral coverage. The Salter innominate osteotomy
is described as a rotational complete osteotomy that can obtain on
average 15° of anterior and 25° of lateral coverage as it hinges off
the pubic symphysis. The Dega and Pemberton procedures are
incomplete osteotomies that hinge off the open triradiate cartilage.
The Pemberton osteotomy disrupts both the inner and outer tables
of the pelvis, stopping just before the sciatic notch and creating a
posterior hinge to create more anterolateral coverage. The Dega
osteotomy disrupts less of the inner table and is ideal for more
lateral coverage. Overcorrection should be avoided to reduce the
risk of femoroacetabular impingement (FAI).
Hip redislocations are one of the most dreaded complications
related to the management of DDH. Management of a redislocation
depends on the underlying cause. With early redislocation after
treatment, any technical perioperative errors must be ruled out; any
identified should be addressed promptly. Osteonecrosis or
proximal femoral growth disturbance is another potential
challenging complication following treatment. A meta-analysis
demonstrated no additional risk of osteonecrosis for the following
factors: open or closed treatment, delay in treatment up to 1 year of
age, or surgical approach (anterior versus anteromedial). 19
Historically, there has been controversy as to whether the presence
of the ossific nucleus was protective or if it increased the risk of
osteonecrosis during treatment of DDH. A meta-analysis
demonstrated that the presence of the ossific nucleus during
management of DDH in infants did not increase the risk of
osteonecrosis. 20 Some have suggested evaluating femoral head
perfusion with a perfusion MRI to assess the risk of osteonecrosis
after surgical treatment.

Adolescent or Young Adult Hip Dysplasia

Even with neonatal screening for hip dysplasia, there are cases that
are not diagnosed until adolescence or adulthood. Although most
of these patients may be asymptomatic, it is thought that early
correction of the dysplasia would reduce the potential for
degenerative hip disease. The abnormal motion results in altered
contact pressures and can lead to early osteoarthritis. Thus, even
mild dysplasia and slight lateralization of the hip center can
increase risk for early-onset osteoarthritis. The deformity is usually
multiplanar, with not only anterolateral acetabular deficiency, but
also the potential for posterior and global deficiency as well as
decreased acetabular depth. Coxa valga and excessive femoral
anteversion are also commonly associated with hip dysplasia.
Patients may present with hip pain, particularly in the groin or
along the inguinal crease (the C sign). The pain is usually insidious
in onset, and lateral-based pain with a Trendelenburg gait
secondary to abductor fatigue may develop in patients. Most of
these patients are otherwise healthy and active but can present with
concurrent back pain and depression. 21 The more severe the
dysplasia is and the higher the activity levels are, the earlier these
patients will present. An anterior apprehension test has a positive
result if the patient has discomfort or apprehension with
progressive external rotation and extension of the hip.
Imaging is an important tool in the characterization of adolescent
dysplasia, so good-quality radiographs are essential for accurate
diagnosis. Slight variation or rotation of the pelvis can alter the
interpretation. Adolescent hip dysplasia is defined as a lateral
center-edge angle (angle of Wiberg) of less than 20° or Tönnis angle
greater than 10° on an AP pelvic radiograph. Other measurements
obtained from the AP radiograph are the extrusion index, Shenton
line, and femoral neck shaft angle. The femoroepiphyseal
acetabular roof index is the angle between the acetabular index
relative to the horizontal portion of the proximal femoral physeal
scar (Figure 6, A). A femoroepiphyseal acetabular roof index of less
than 5° represents a stable hip that does not require surgical
intervention. 22 On a false-profile view, anterior coverage is
measured by the anterior center-edge angle (angle of Lequesne),
and dysplasia is defined as an angle of less than 20°. Advanced
imaging has greatly enhanced the understanding of dysplasia.
Three-dimensional CT reconstruction of the pelvis facilitates
accurate characterization of the morphology of the acetabulum for
diagnosis and surgical planning (Figure 6, B). Magnetic resonance
arthrography facilitates interpretation of labral pathology, whereas
a cartilage-sensitive sequence shows cartilage damage. Positive
findings of cartilage damage on MRI are predictors of poor
outcomes after periacetabular osteotomy (PAO).
 Figure 6 A, The femoroepiphyseal acetabular roof (FEAR) index. If the angle
opens medially, the hip joint is likely stable. B, If the angle opens laterally, the
joint may be unstable. C, Three-dimensional CT scans can be used to
understand the three-dimensional pathology present in patients with
developmental dysplasia of the hip.(Copyright San Diego Pediatric Orthopedics.)

Management of adolescent hip dysplasia depends on the severity

of the dysplasia, presence of arthritis, and the symptoms and
activity level of the patient. By adolescence, the hip no longer
maintains its plasticity for remodeling, and surgical intervention
may often be required. Nonsurgical management for symptomatic
hip dysplasia, especially hip subluxation, is less successful given
the known risk of premature arthritis leading to early hip
arthroplasty. However, for patients with mild acetabular dysplasia
and symptoms who want to avoid surgery, anti-inflammatory
agents and physical therapy focused on core and hip abductor
strengthening with activity modifications may relieve symptoms in
the short term. Most adolescents with hip dysplasia without the
presence of arthritis undergo pelvic osteotomies to improve hip
joint congruence and stability. Hip arthroscopy can be considered
as an adjuvant treatment for intra-articular chondral and labral
pathology. Hip arthroscopy alone is not well supported as the
definitive treatment of DDH because of its inability to treat the
underlying osseous acetabular deficiency and version. In addition,
osteochondroplasty of a pincer lesion could increase hip instability.
A 2019 study demonstrated that at 5 years after hip arthroscopy and
concurrent PAO, all patients had improved patient-reported
outcomes and pain scores, with no conversions to hip arthroplasty.
23
With longer term follow-up, the rate of THA increases.
Many pelvic reconstructive osteotomies have been described to
treat patients with DDH. Steel, Sutherland, and Dial osteotomies
have all been described for closed triradiate cartilage, but each has
limitations. The most commonly used osteotomy after skeletal
maturity is the Ganz PAO, which uses three complete osteotomies,
with preservation of the posterior column, and facilitates
multidirectional correction. Femoral osteotomies to alter the varus
or valgus alignment of the proximal femur may also be performed
to change the stress along compromised articular cartilage.
However, this is rarely used in isolation. These procedures can be
used after a pelvic osteotomy to improve range of motion and joint
congruence because relative femoral retroversion greatly limits hip
motion and may be seen in patients with hip dysplasia. At 10- and
20-year follow-up, 86% and 60% of hips survived, respectively; the
risks for PAO failure were older patient age and higher Tönnis
grade. 24 One study compared THA in patients with DDH, with or
without prior pelvic osteotomies, at a high-volume arthroplasty
center and found that patients with prior pelvic osteotomies
required more bone grafting, more screw fixation, and had longer
surgical times and greater blood loss. 25
Although treatment of DDH remains challenging, great strides
have been made in the understanding of morphology, surgical
technique, and patient outcomes. Further research is warranted
given advances in imaging from the specific effects of interventions
on the developing pelvis.

Slipped Capital Femoral Epiphysis

Slipped capital femoral epiphysis (SCFE) is a rotational deformity
at the level of the vulnerable proximal femoral capital physis with
extension and external rotation of the proximal femoral metaphysis
relative to the epiphysis. The reported incidence is 10 per 100,000,
and it is more common in African Americans and Polynesians. It is
more common in males (2:1.4), and disease onset is usually around
12 years of age, but in girls, the condition is usually present 2 years
earlier. Some studies report up to 18% to 50% of cases are bilateral,
whereas a subsequent contralateral SCFE occurs in up to 40% of
cases. 26
Although the exact cause of SCFE is unknown, there appear to be
morphologic changes to the proximal femur and acetabulum.
Metabolic disorders and/or mechanical overloading are thought to
weaken the physis and predispose toward rotational deformity.
Metabolic disorders (eg, renal osteodystrophy and obesity) and
endocrine disorders (eg, hypothyroidism, hyperleptinemia, and
growth hormone deficiency) limit the ability of the physis to
withstand mechanical stress, causing the epiphysis to be
susceptible to slipping. 10 Obesity is the more common underlying
condition leading to SCFE, in which the increased weight causes
metabolic dysfunction and mechanical overload of an excessively
vertical physis. 9 Prevention of obesity is effective in lowering the
risk of an SCFE and a contralateral slip. However, it should be
noted that not all SCFEs occur in the overweight population. There
is a less common form of SCFE in nonobese children who tend to
be older at presentation, more likely female, who present with more
severe, unstable slips. 27
There are anatomic differences about the hip joint in a patient
with SCFE that make the proximal femoral physis more susceptible
to shear stresses. Specific femoral morphology such as relative
femoral retroversion, posterior epiphyseal inclination, and
decreased head-neck offset lead to increased shear stress. Studies
have reported excessive relative acetabular retroversion and a
higher crossover sign on CT in patients with SCFE that cause a
shear stress across the physis. Recent research has focused on the
epiphyseal physeal plate and associated epiphyseal cupping and
the epiphyseal tubercle. The epiphyseal tubercle is an osseous
prominence located in the posterosuperior epiphysis that
interdigitates with the metaphysis and provides stability to the
epiphysis (Figure 7). Peripherally, the epiphysis expands, creating
the impression of cupping and in theory is protective of the
epiphysis, providing stability, as discussed in a 2020 study. 28
Therefore, more cupping provides increased stability to the
epiphysis, but excessive amounts can result in a cam lesion and
impingement. The slip occurs through the zone of provisional
calcification within the hypertrophic zone of the physis. It is
thought that the tubercle provides stability to the epiphysis, and
with SCFE, the metaphysis rotates about this tubercle. This tubercle
potentially protects the posterior vascularity against trauma.
Remodeling then occurs at the metaphyseal interdigitation with
chronic stress and micromotion. Signs of lucency about the tubercle
seen on plain radiographs suggest early signs of SCFE. 29 In acute
slips, sudden displacement of the epiphysis in this region poses a
risk of compromising the nearby vascularity to the femoral head.
After a slip the anteriorly displaced metaphysis impinges on the
anterolateral acetabular rim during flexion, causing impingement.
This impingement leads to anterior acetabular labral and articular
cartilage damage. Some acetabular remodeling can occur, but these
changes to the acetabulum are usually still present.

Figure 7 A, Graph representing the normal growth of the physeal surface

anatomy of capital femoral epiphysis from 8 to 15 years old. B, Three-
dimensional CT reconstructions at ages 8, 10, 12, and 15 years. The epiphyseal
tubercle (black arrows) is a bony prominence located at the posterosuperior
quadrant of the epiphysis, and the epiphyseal cupping is the peripheral bone
extension of the epiphysis into the metaphysis (white arrows). In comparison
with the epiphysis diameter, the epiphyseal tubercle size decreases with the
skeletal growth, whereas the epiphyseal cupping increases.(Reprinted from
Novais EN, Maranho DA, Kim YJ, Kiapour A: Age- and sex-specific morphologic
variations of capital femoral epiphysis growth in children and adolescents
without hip disorders. Orthop J Sports Med 2018;6[6]:2325967118781579.)

Diagnosis
Early diagnosis and treatment have been proven to have be er
outcomes; however, late presentation after the deformity and
subsequent articular damage have occurred is not uncommon.
Symptoms are usually vague, and the pain can sometimes be
intermi ent or even referred pain to another location (eg, the thigh
or knee). Overweight children and patients with endocrine or
metabolic disorders or Down syndrome should be screened for
SCFE when reporting hip or knee pain. During the examination, a
patient with SCFE will have decreased internal rotation and passive
flexion because of either synovitis or impingement. A Drehmann
sign, which is obligate external rotation and abduction of the hip
with flexion, may be seen. Patients can present suddenly with acute
dissociation of the head from the physis. Some patients present
with the clinical signs and symptoms of an SCFE but radiographs
are negative. In these patients, MRI can be helpful to diagnose a
preslip condition with edema around the proximal femoral physis.
There are several methods of classifying an SCFE. Temporal
classification describes the length of pain symptoms between time
of onset to presentation: acute (<3 weeks) versus chronic (>3 weeks).
With acute-on-chronic slips, the patient reports chronic pain that
had a sudden exacerbation. The stability status of the epiphysis is
another method to classify the slip and has prognostic value and
can affect treatment decision making. The Loder classification
defines stable slips when the patient can ambulate with or without
crutches and unstable slips when the patient is unable to ambulate
even with an assistive device. The stability of the hip correlates with
risk of osteonecrosis. Although one study found a 47% chance of
osteonecrosis in unstable hips versus zero in stable hips, more
contemporary literature reports the risk of osteonecrosis is closer to
23.9% in unstable hips. 30 Another study questioned the definition
of stability when it was reported that 17 of 58 patients who were
able to ambulate preoperatively were found to have unstable slips
intraoperatively, and 13 of 24 patients who were unable to bear
weight preoperatively were found to have stable slips
intraoperatively. 31 SCFE can also be classified based on the degree
of deformity seen on plain AP and frog-leg radiographs using the
percent of slip and the Southwick angle. A mild slip refers to a 33%
slip or Southwick angle of less than 30°, a moderate slip represents
a 33% to 66% slip or Southwick angle between 30° to 60°, and a
severe slip is greater than 66% slip or Southwick angle greater than
60°.
However, plain radiographs may underappreciate the magnitude
of deformity, so advanced imaging modalities such as CT or MRI
can be used. In addition, MRI can be used for diagnosis of a preslip,
SCFE without displacement of the epiphysis but widening at the
physis or lucency at the epiphyseal tubercle. 29 MRI would also be
useful to be er appreciate the articular cartilage and labral
pathology because of existing impingement. In acute-on-chronic or
chronic SCFEs, CT can help visualize the posterior callus formation
and aid in surgical planning for any reconstruction procedure. 32

Management
Contemporary management of SCFE is surgical fixation of the
epiphysis, with the goal to provide stability to protect the posterior
retinacular vasculature with least risk of complication
(chondrolysis, osteonecrosis, and progression). Percutaneous in situ
fixation is the preferred treatment for a stable SCFE. One
cannulated screw has been found to provide good stability with the
fewest complications as long as the screw is placed in the center of
the epiphysis, perpendicular to the physis with at least five threads
across the physis on orthogonal views. 33 Historically, this has
resulted in epiphysiodesis, but a 2021 study discusses more recent
technology that is under investigation using telescoping fixation to
limit the leg length discrepancy and need for additional procedures
after an epiphysiodesis in younger patients. 34 Some surgeons have
even performed epiphysiodesis with bone grafting to ensure
physeal closure and stability of the epiphysis. The degree of slip
and resultant deformity predicted the risk of hip osteoarthritis and
functional outcomes; more severe slips had worse outcomes and
greater risk of hip osteoarthritis. However, even mild slips may
demonstrate radiographic arthritic changes with decreased
functional outcomes. Multiple screws for in situ fixation risk
protrusion and chondrolysis. 33 Once healed, the deformity has a
risk of impingement and subsequent chondral damage. To correct
the deformity, some surgeons argue for performing a realignment
of the epiphysis. Therefore, several procedures have been proposed
for epiphyseal realignment via osteotomies either at the physis,
neck, intertrochanteric or subtrochanteric region. The closer the
osteotomy is performed at the physis (site of deformity), the greater
the degree of correction that can be obtained, but there is also a
higher risk of osteonecrosis.
Unstable SCFE is a difficult condition to manage, with higher risk
of complications. The acute epiphyseal displacement and
associated hemarthrosis places the posterior retinacular vessels at
risk, resulting in higher risk of osteonecrosis and complications.
Most surgeons argue for intervention within 24 hours. Management
of unstable SCFE remains a topic of debate. Some argue for
serendipitous reduction and percutaneous screw fixation with two
screws. Decompression of the hemarthrosis to decrease the
tamponade effect on the epiphyseal perfusion and intraoperative
perfusion monitoring have been recommended. Instead, serial
radiographs, watchful waiting for signs of osteonecrosis, and a bone
scan or perfusion MRI after surgery to evaluate for vascular
compromise have gained support. 35 An open approach via an
anterior or anterolateral approach with a partial gentle digital
reduction has been reported with only a 4.7% incidence of
osteonecrosis. 36 Neither approach fully corrects the deformity, and
although low, the risk of osteonecrosis remains. To reduce the
deformity, a modified Dunn procedure is another procedure to
realign the epiphysis after creating a retinacular flap that protects
the vessels. However, although the original results were
encouraging, studies report a 26% to 29% rate of osteonecrosis in
unstable SCFEs. 37 , 38
Another controversial aspect of SCFE management is whether to
fix the contralateral hip to reduce the risk of a contralateral injury.
There are reports of one-third of patients who have bilateral or a
subsequent contralateral slip within 18 to 24 months of the index
SCFE. 30 Younger patients (girls younger than 10 years and boys
younger than 12 years) were at higher risk of developing a
contralateral slip. The Modified Oxford score, which accounts for
multiple ossification centers around the hip joint, has been found
to be the best predictor of a contralateral slip. The posterior slope,
another measurement obtained on a frog-leg lateral view, is the
slope of the epiphysis relative to a line perpendicular to the long
axis of the femoral neck. If the posterior slope is greater than 15° to
18° on the unaffected side, contralateral fixation is recommended.
Patients with higher-than-normal weight and those with Down
syndrome or an endocrinopathy are at higher risk of a contralateral
slip, and prophylactic fixation is recommended. One study
evaluated the risk and cost of prophylactic fixation and found it to
be financially responsible in high-risk patients. 30
After the initial slip and fixation, a residual deformity at the
femoral metaphysis can lead to chondral injury and premature
osteoarthritis. 39 Symptomatic FAI secondary to an SCFE should be
corrected, particularly in severe slips (Figure 8). There is
controversy as to whether severe slips should be corrected acutely
or wait until they are healed. This can be performed with an
osteochondroplasty, or several types of osteotomy can be
performed at various levels of the proximal femur, including at the
epiphysis with capital realignment (surgical hip dislocation and
modified Dunn), 37 , 38 femoral neck (Kramer and Barmada),
intertrochanteric (Imhauser [flexion]) or Southwick [flexion and
valgus]), and subtrochanteric osteotomies. The farther from the
epiphysis, there is less risk of osteonecrosis, but there is also less
degree of deformity correction. After a modified Dunn procedure,
one study demonstrated that as the severity of the slip increased, so
did the risk of osteonecrosis, with a total incidence of 37%. 40
 Figure 8 AP (A) and lateral (B) radiographs of the hip of a 12-year-old girl with
a 4-month history of left hip pain because of slipped capital femoral epiphysis. In
situ epiphysiodesis was performed (C and D); however, there was persistent
metaphyseal deformity leading to pain and limited range of motion. After screw
removal, a CT scan (E) and MRI (F) were obtained, showing the cam deformity
and chondrolabral abnormalities (F).

SCFE is a difficult condition to manage, with a long-lasting effect

on the patient’s function. Great care and surgical planning is
required for these patients. Appropriate education should be
provided to the patients and their family that the condition has
lasting effects into early and late adulthood.

Legg-Calvé-Perthes Disease
Legg-Calvé-Perthes (LCP) disease is a pediatric hip condition
characterized by idiopathic osteonecrosis of the proximal femoral
epiphysis leading to gross deformity and joint incongruity and
subsequent dysfunction. The disease has a prolonged predictable
course of osteonecrosis, revascularization, and fragmentation
followed by reossification and then remodeling. The onset of LCP
disease typically is between ages 4 to 8 years of age with a delay in
skeletal age up to 1 year. Patients with LCP disease are more
commonly Caucasian males of Northern European descent. Both
hips are involved in 10% to 20% of cases. LCP disease can be
considered a form of subtle epiphyseal dysplasia, especially in
children with bilateral involvement.
Despite that LCP disease was described more than 100 years ago,
the exact cause is still debated. An impairment of the blood supply
to the femoral epiphysis occurs, but specific factors leading to that
impairment remain ill defined. Recent literature has suggested a
genetic link in familial LCP disease to a mutation in the COL2A1
gene leading to abnormal collagen type II and compromised
epiphyseal blood supply. Although historically thrombophilia has
also had a potential link to LCP disease, more recent prospective
studies have shown no link between LCP disease and coagulopathy,
but there was a higher prevalence of Factor V Leiden and
anticardiolipin in the LCP disease cohort. One study reported an
increase in leptin resistance in patients with LCP disease. Leptin
has been found to be angiogenic and may alter bone metabolism. 41
, 42

The common finding in patients with LCP disease is disruption

of the vascular supply of the proximal femoral epiphysis,
potentially from environmental factors affecting the epiphysis of a
genetically susceptible individual. Although the physis is open, the
vascularity between the epiphysis and metaphysis is separated by
the avascular physis. Once the physis closes, the vessels of the
epiphysis and metaphysis anastomose. Thus, the proximal femoral
physis is a watershed region and vulnerable to injury. In LCP
disease, particularly, the anterior superior femoral head is most
commonly affected; this is the region of the femoral head most
susceptible to hypoxia given its blood supply from the lateral
retinacular vessels. It is suggested that the vascular insufficiency is
chronic rather than acute given most patients do not describe any
traumatic event or injury. In addition, environmental factors that
cause microvascular injury, such as smoking, are now thought to be
risk factors for LCP disease.

Diagnosis
Histologic studies have shown that once the vascular insult has
occurred, the articular cartilage, epiphysis, physis, and metaphysis
can all be affected. Articular cartilage changes occur, causing
necrosis of the deep layer and termination of endochondral
ossification. The cartilage separates from the underlying
subchondral bone, and eventually there is revascularization of that
region leading to reossification. The femoral head hypoxemia leads
to chondrification and fragmentation of bone with decreased
mechanical strength and femoral head deformity. Ultimately,
vascular invasion and resorption of the necrotic bone further
weakens the infrastructure, leading to trabeculae fracture and
formation of cysts (Figure 9).
 Figure 9 Illustration of a hypothesis on the pathogenesis of Legg-Calvé-
Perthes disease.(Copyright 2010, Texas Scottish Rite Hospital for Children,
Dallas, Texas, All Rights Reserved.)

The Waldenström radiographic classification describes the

natural course of LCP disease. Stage I is represented by sclerosis
and necrosis of the bone within the epiphysis. This is followed by
stage II where fragmentation of the epiphysis occurs with bone
resorption and metaplastic changes to the cartilaginous anlage. At
stage II, weight bearing can result in weakening of the bone and
femoral head deformity. Then, in stage III, reossification occurs
secondary to revascularization, which may lead to normal hip
vascularity or to vascularity across the physis and physeal bar
formation. 42 Lastly, in stage IV, the femoral head has reossified
representing the final healed stage of Perthes disease. Long-term
studies of untreated LCP disease with less than 40-year follow-up
report that most patients are asymptomatic and active despite the
femoral head deformity. However, longer term follow-up
demonstrates progressive deterioration of the hip joint, in which
after a mean of 47.7 years, 40% of patients required arthroplasty,
40% still remain active, 10% had disabling pain, and the last 10%
scored poorly on patient-reported outcomes. 43
LCP disease classification is performed using serial radiographic
analysis. As previously described, the Waldenström classification
established four stages of the disease based on the radiographic
appearance and progression of the disease, and it has been
modified to improve reliability (Figure 10). Joint congruency and
morphology of the femoral head after femoral head healing, which
correlate with risk of early osteoarthritis of the mature hip, are
classified using the Stulberg classification. 42 The severity of the hip
osteoarthritis worsens with each subsequent stage as the hip
becomes more aspherical and the joint incongruent. The
interobserver reliability provided more objective stage parameters.
44
The Ca erall classification classified LCP disease in hips based on
the location and extent of femoral head involvement during
fragmentation. Radiographic signs of the head at risk that have
been associated with poor outcomes were described. These signs
include lateral subluxation of the head, lateral calcification, diffuse
metaphyseal reaction, horizontal physis, and the Gage sign. The
Gage sign is a V-shaped lucency laterally at the edge of the
epiphysis or metaphysis. 42 , 44 One study described a classification
based on the height of the lateral column of bone on the femoral
head during early fragmentation, which usually occurs
approximately 6 months after onset of symptoms. A disadvantage
of this classification is that it is only reliable during the
fragmentation stage, and serial radiographs are required to
temporally classify the hip, thus risking missing the window for
less invasive treatment measures. The Herring lateral pillar
classification places hips with an intact lateral pillar height into
group A, hips with more than 50% lateral pillar height into group B,
and hips with less than 50% lateral pillar height into group C. These
groupings have prognostic value, with patients in group A usually
having good outcomes, whereas group B patients older than 6 years
and all of group C patients have poor results. Prognostic indicators
of poor outcome in LCP disease are the Stulberg and Ca erall
classification groups, age of onset, two or more Ca erall at-risk
signs, and premature physeal closure. 42
Figure 10 AP and frog-leg lateral radiographs of the right hip and
representative illustrations of each stage of the modified Waldenström
classification system for Legg-Calvé-Perthes disease.(Reprinted with
permission from Hyman JE, Trupia EP, Wright ML, et al: Interobserver and
intraobserver reliability of the modified Waldenstrom classification system for
staging of Legg-Calve-Perthes disease. J Bone Joint Surg Am 2015;97[8]:643-
650.)
 Advanced imaging can help to be er characterize the femoral
and acetabular changes. Conventional MRI may underestimate the
cartilage damage and osteonecrosis if performed within the first 6
months because ischemic findings are delayed. Perfusion MRI
be er illustrates the vascularity and can delineate the extent of
femoral head vascular necrosis and revascularization. 45 However, it
should be noted that perfusion MRI usually requires sedation in
younger patients and remains controversial. Hip arthrography is
commonly used intraoperatively for a dynamic assessment of range
of motion, particularly hinged abduction. CT and three-
dimensional reconstructions can provide valuable information
regarding the gross deformity of the femoral head and acetabulum
for surgical planning (Figure 11).
 Figure 11 AP radiograph (A), CT image (B), magnetic resonance image (C),
and three-dimensional reconstruction (D) of the right hip of an 8-year-old boy
with Legg-Calvé-Perthes disease. There is central necrosis with less than 50%
of head involvement (Salter-Thompson group A) and about 50% of lateral pillar
involvement (Herring group B). However, the child is older, there is lateral
subluxation, and the lateral pillar is extruded, exposing the necrotic area to
increased loading, risk of collapse, and worse prognosis.

A child with LCP disease typically presents with a limp that early
on may or may not be associated with insidious onset of pain. As
the disease progresses and enters fragmentation, more pain is
localized to the hip. Pain is usually intermi ent and can be
localized to the groin, hip, thigh, or knee. The disease has a varied
protracted course that takes 2 to 5 years to reach the healing phase.
There is progressive loss of motion, in particular, internal rotation
and abduction. As the femoral head collapses, there is shortening
of the abductor moment and a Trendelenburg gait. With further
collapse and deformity of the head, a leg length difference and
contracture of the hip adductors are noted. Although bilateral
involvement of the disease is possible, skeletal dysplasia must be
ruled out.

Management
The goal of management is to contain the hip and preserve motion
to minimize residual femoral head deformity. Taking advantage of
the plasticity of the femoral head during the younger years by
keeping the head reduced in the concave acetabulum will ideally
maintain the sphericity of the femoral head (Figure 12). One study
demonstrated a correlation between femoral head lateralization
and dysplastic changes of the acetabulum during fragmentation. 46
Thus, the position of the femoral head relative to the acetabulum
contributes to the growth and development of the acetabulum.
 Figure 12 AP (A) and frog-leg (B) radiographs from an 8-year-old girl with
Legg-Calvé-Perthes disease of the right hip, with an extensive necrotic area.
Coronal magnetic resonance image of the hip (C) confirmed a necrosis
proportion greater than 50%. The patient was initially treated with an abduction
orthosis, as shown by the AP pelvis radiograph (D). After 6 months of follow-up,
the femoral head collapsed, developing lateral superior extrusion and subluxation
(E, AP radiograph), raising a concern for the presence of the hinged abduction
phenomenon. An AP arthrogram (F) with the hip in abduction confirmed the
hinged abduction, in which the femoral head moved eccentrically with a
peripheral fulcrum and farther from the acetabular fossa (medial contrast pooling
with hip abduction). However, the labrum was still covering the lateral pillar, and
the head reduced under the acetabular labrum on the frog lateral view of the hip
(G). A Petrie cast was applied for 6 weeks; then a removable abduction cast
was used for hygiene and physical therapy for 6 more weeks. A nighttime brace
was used for 1 extra year. At 11 years, the hip was almost spherical, congruent,
and concentric on the AP radiographs (H).

This containment can be achieved through various measures.

Adductor lengthening and Petrie casting followed by management
with an A-frame has satisfactory outcomes. Hip motion,
particularly hip abduction (at least 30°), should be preserved to
reduce the risk of head extrusion. The benefits of soft-tissue
procedures, therapy, and bracing include avoidance of limb
shortening and abductor dysfunction related to femoral
osteotomies. Nevertheless, bracing has a protracted duration and
may be cumbersome to the patient and family.
When management with a brace fails, there is no universally
accepted algorithm to follow. Some surgeons prefer performing a
femoral varus derotational osteotomy (VDRO), whereas others
perform pelvic osteotomies (Salter, triple, shelf) to provide
containment. Much of the femoral head and metaphyseal deformity
and lateral extrusion has been found to occur during the
fragmentation phase. One study recommended VDRO before
advanced fragmentation occurs to shorten the length of the
fragmentation phase and improve the sphericity of the femoral
head. 47 Recently, there has been debate on the ideal timing of the
femoral osteotomy to maximize remodeling potential. A 2020 study
redemonstrated the principle that patients who underwent VDRO
had a shorter fragmentation phase and less lateral pillar narrowing;
however, few patients completely bypassed fragmentation. 48
Redirectional osteotomies such as the Salter or Triple are effective
interventions for containment. The shelf and Chiari osteotomies are
extracapsular procedures to increase the lateral head coverage as
well. One retrospective study showed no difference in outcomes
when comparing patients with LCP disease who underwent
combined femoral and Salter osteotomies compared with those
receiving a pelvic osteotomy or VDRO alone. 49
Multicenter prospective studies have demonstrated that the age
of onset may be an essential factor to determine outcomes. In
patients younger than 6 years, 80% have a good outcome regardless
of whether they underwent surgical or nonsurgical management,
particularly patients in lateral pillar group A or B. In this same
cohort, patients between the ages of 4 to 6 years were more likely to
have a poor outcome if they were classified as lateral pillar B/C or
C41. This does not mean that all patients do well when age of onset
is younger than 6 years; 1 in 5 patients had a Stulberg III or worse
outcome.
For children who present between 6 and 8 years of age,
multicenter studies have demonstrated no significant difference
between patient outcomes for surgical (68% to 69% success) and
nonsurgical (bracing, 62% success) management. 44 A 2020 study
demonstrated that within this age group, bracing was less effective
than a pelvic osteotomy. Patients at skeletal maturity after pelvic
osteotomy performed between ages 6 and 8 years had less femoral
head lateralization and be er acetabular indices, Sharp angle, and
acetabular depth-to-width ratio. However, there was no difference
in hip pain or motion between the groups. 50 After age 8 years, there
is less acetabular remodeling potential. In a prospective
multicenter study, there was no difference in outcomes in patients
with hips described as lateral pillar C who underwent surgery
compared with those who underwent nonsurgical management.
However, patients classified as lateral pillar B or B/C did
demonstrate beneficial effects, although modest. 44 Therefore, there
are still unidentified factors contributing to the limited remodeling
process in some of these older patients.
Hinged abduction is a unique phenomenon whereby the
extruded femoral head hinges on the lateral acetabulum during hip
abduction. No procedure has proved best for hinged abduction
once the head is deformed. Improving hip abduction and a valgus-
producing osteotomy is one method in which to correct this
abnormal motion. Hip arthrodiastasis via an external fixator is an
alternative surgical procedure. Additionally, a surgical hip
dislocation with an osteochondroplasty or a femoral head reduction
osteotomy can be considered to improve femoral head sphericity.
For residual deformity after LCP disease, an osteochondroplasty,
either arthroscopically or open, can be performed to shape the
femoral head back to normal or at least congruent with the hip
joint. A relative femoral neck lengthening can also be performed to
correct the high-riding greater trochanter and relative coxa vara. A
combination of these two procedures has been performed, with
75% reporting improved symptoms and only 10% requiring THA. 51
A PAO is performed if there is concern about instability. There
have been encouraging early results with femoral head reduction
osteotomies to improve congruency and sphericity, but these
procedures are challenging, and long-term outcomes have yet to be
elucidated. If osteoarthritis is present, the standard procedure with
good predictable results is a hip arthroplasty that can add length to
the affected side. At follow-up, a 2021 study reported 98.4%
revision-free outcomes with average lengthening of the affected
side of 1.4 cm without any nerve palsies and a postoperative Harris
hip score of 85.3. 51 However, at 20-year follow-up, one study
reported the overall survival of THA to be only 70%. 52
LCP disease is a difficult condition to manage if not diagnosed
early. Although great strides have been made in our understanding
of the condition, further research is warranted. Future studies are
looking further into disease-modifying interventions to reduce joint
deformity.

Femoroacetabular Impingement
FAI is the result of abutment between the proximal femur and
acetabulum during physiologic range of motion. The most common
form is from intra-articular abnormal contact between the femoral
head-neck junction and the acetabulum causing pain and
chondrolabral damage. The proximal femoral head-neck junction
can have a cam lesion possibly caused by repetitive high-impact
flexion activity during adolescents. The repetitive stress on the
proximal femoral physis is thought to lead to increased epiphyseal
cupping to provide stability. The increased bone and remodeling
lead to a convex femoral neck surface rather than the typical
concavity seen in typically developing hips (Figure 13). The cam
lesion can also be secondary to LCP disease and SCFE healed
deformities. A pincer lesion describes excessive pathologic
acetabular overcoverage, which can be focal as in acetabular
retroversion or global as in coxa profunda/protrusion. The
impingement can be from either the dysmorphology of the
proximal femur or acetabulum or more commonly from both.
 Figure 13 AP radiographs (A and B), coronal CT reconstruction (C), and
magnetic resonance images (D) of the left hip from a patient who had
experienced slipped capital femoral epiphysis at age 12 years. At age 14 years
(A), there were no radiographic signs of a contralateral slip. At age 16 years, the
patient experienced onset of right hip pain; radiographic (B) and CT images (C)
showed periosteal reaction (arrowheads) and superior ossification (arrows) at
the femoral neck. At age 17 years, magnetic resonance image showed an
evident cam deformity and a labral tear (D).

Diagnosis
Classic presentation of FAI is activity-related groin or anterior hip
pain that is worse with flexion. Lateral hip pain located near the
greater trochanter can be related to aberrant gait mechanics. Pain is
exacerbated with passive flexion (>90°), adduction, and internal
rotation (anterior impingement test). Standing AP, lateral, false-
profile, and modified Dunn radiographs can help assess the
aspherical femoral head-neck junction and acetabular overcoverage.
Cam impingement is suggestive with an alpha angle greater than
50° to 55° or a head-neck ratio greater than 0.17. Images of a pistol
grip deformity are indicative of cam impingement. Signs of pincer
impingement are acetabular protrusio, coxa profunda, and/or
retroversion. A crossover sign indicates acetabular retroversion.
Greater lateral or anterior center edge angles are also indicative of a
pincer lesion. CT with three-dimensional reconstructions help
characterize the deformity. MRI with arthrogram is the optimal
modality to evaluate intra-articular cartilage or labral pathology.

Management
The first line of management for FAI should be a trial of
nonsurgical treatment. Activity modifications include avoiding
aggravating hip maneuvers, particularly flexion greater than 90°.
Physical therapy and nonsteroidal anti-inflammatory drugs are
helpful adjuvants. Symptomatic FAI with concomitant
chondrolabral pathology can benefit from hip arthroscopy or an
open procedure. FAI can lead to hip osteoarthritis, but
management can result in reduced cartilage degeneration. A
randomized controlled trial found that hip arthroscopy and
physical therapy both improved quality of life in symptomatic FAI,
but arthroscopy had be er outcomes. 53 At midterm follow-up when
comparing arthroscopic with surgical hip dislocation for
management of FAI, both had good results at 93% in the
arthroscopic group and 90% in the surgical dislocation group. The
only statistically significant difference was a higher general health
quality of life score in the arthroscopic group compared with the
open group. 54 However, for chondrolabral pathology in the
presence of severe cam deformity, hip dysplasia, and/or instability,
arthroscopy also is likely inadequate. The strongest predictor of
failure of FAI management is the presence of cartilage damage or
osteoarthritis. The risk for conversion to a THA is greater with
older age, duration of symptoms more than 1.5 years, and worse
Harris Hip Scores. 55 Long-term comparative studies are needed to
further evaluate the effect of surgical intervention on FAI.

Summary
Pediatric hip disorders can be challenging conditions to manage
without early recognition and intervention. Resultant deformity can
lead to dysfunction, pain, and premature arthritis. Early diagnosis
and bracing in DDH are highly effective in the newborn population.
Prompt recognition and management of SCFE can prevent slip
progression with good surgical technique and a well-placed
implant. LCP disease is a challenging condition to care for, and
treatment goals should focus on containment.

Key Study Points

Early diagnosis and intervention of DDH in the newborn has high rates of success,
and patients should be monitored radiographically until skeletal maturity.
The most commonly used pelvic osteotomy is the Ganz PAO in adolescent or young
adult hip dysplasia.
Timely management of SCFE with in situ screw fixation can prevent slip progression
and eventual residual deformity.
LCP disease is a challenging condition to treat, with the goal of care being
containment of the hip joint. Most children younger than 4 years do well with just
observation.
FAI is abutment of either a cam or pincer lesion that results in impingement during
flexion. The first line of treatment is nonsurgical.

Annotated References
1. Roposch A, Liu LQ, Protopapa E: Variations in the use of
diagnostic criteria for developmental dysplasia of the hip. Clin
Orthop Relat Res 2013;471(6):1946-1954.
2. Mahan ST, Kasser JR: Does swaddling influence developmental
dysplasia of the hip? Pediatrics 2008;121(1):177-178.
3. Weinstein SL, Mubarak SJ, Wenger DR: Developmental hip
dysplasia and dislocation: Part I. Instr Course Lect 2004;53:523-530.
4. Weinstein SL: Developmental hip dysplasia and dislocation, in
Weinstein SL, Flynn JM, eds: Lovell and Winter’s Pediatric
Orthopedics, ed 7. Lippinco Williams & Wilkins, Wolters Kluwer,
2014, pp 983-1111.
5. Imrie M, Sco V, Stearns P, Bastrom T, Mubarak SJ: Is
ultrasound screening for DDH in babies born breech sufficient? J
Child Orthop 2010;4(1):3-8.
 6. Edmonds EW, Hughes JL, Bomar JD, Brooks JT, Upasani VV:
Ultrasonography in the diagnosis and management of
developmental dysplasia of the hip. JBJS Rev 2019;7(12):e5. This
review of hip ultrasonography in the diagnosis, monitoring, and
screening of DDH describes the static Graf method as well as the
more contemporary dynamic ultrasonographic method. Level of
evidence: V.
7. Teixeira SR, Dalto VF, Maranho DA, Zoghbi-Neto OS, Volpon JB,
Nogueira-Barbosa MH: Comparison between Graf method and
pubo-femoral distance in neutral and flexion positions to
diagnose developmental dysplasia of the hip. Eur J Radiol
2015;84(2):301-306.
8. Mulpuri K, Song KM: AAOS Clinical Practice Guideline. J Am
Acad Orthop Surg 2015;23(3):206-207.
9. Novais EN, Shefelbine SJ, Kienle KP, et al: Body mass index
affects proximal femoral but not acetabular morphology in
adolescents without hip pathology. J Bone Joint Surg Am
2018;100(1):66-74.
10. Halverson SJ, Warhoover T, Mencio GA, Lovejoy SA, Martus JE,
Schoenecker JG: Leptin elevation as a risk factor for slipped
capital femoral epiphysis independent of obesity status. J Bone
Joint Surg Am 2017;99(10):865-872.
11. Novais EN, Kestel LA, Carry PM, Meyers ML: Higher Pavlik
harness treatment failure is seen in Graf type IV Ortolani-
positive hips in males. Clin Orthop Relat Res 2016;474(8):1847-
1854.
12. Bram JT, Gohel S, Castañeda PG, Sankar WN: Is there a benefit
to weaning Pavlik harness treatment in infantile DDH? J Pediatr
Orthop 2021;41(3):143-148. This comparative review between two
centers evaluated whether there is a difference in outcomes in
dislocated and stable newborn hips treated with a Pavlik harness
and if either underwent immediate cessation or weaning of the
harness. Although the weaned group wore the harness longer,
 there was no difference between the cohorts regarding acetabular
index at 1-year follow-up. Level of evidence: III.
13. Dornacher D, Cakir B, Reichel H, Neli M: Early radiological
outcome of ultrasound monitoring in infants with developmental
dysplasia of the hips. J Pediatr Orthop B 2010;19(1):27-31.
14. Kaneko H, Kitoh H, Mishima K, Matsushita M, Ishiguro N:
Long-term outcome of gradual reduction using overhead traction
for developmental dysplasia of the hip over 6 months of age. J
Pediatr Orthop 2013;33(6):628-634.
15. Terjesen T, Horn J, Gunderson RB: Fifty-year follow-up of late-
detected hip dislocation. J Bone Joint Surg 2014;96(4):e28.
16. Morris WZ, Hinds S, Worrall H, Jo CH, Kim HKW: Secondary
surgery and residual dysplasia following late closed or open
reduction of developmental dysplasia of the hip. J Bone Joint Surg
Am 2021;103(3):235-242. Patients from 6 to 24 months of age with
DDH were evaluated following closed reduction and casting for
DDH. Older patients, particularly those older than 12 months
despite worse preoperative International Hip Dysplasia Institute
classification, were at higher risk of requiring secondary surgery
and having residual dysplasia. Level of evidence: III.
17. Sco EJ, Dolan LA, Weinstein SL: Closed vs. open
reduction/salter innominate osteotomy for developmental hip
dislocation after age 18 months. J Bone Joint Surg
2020;102(15):1351-1357. This study directly compared dislocated
hips treated with closed reduction (CR) to those treated with
open reduction and Salter innominate osteotomy (OR/IO) to
estimate the relative hazard of total hip arthroplasty (THA) and
the THA-free survival time. In this series, 45 patients (58 hips)
underwent CR and 58 patients (78 hips) were treated with OR/IO.
At 48 years of follow-up, 29 (50%) of the hips survived after CR
compared with 54 (69%) after OR/IO. Osteoarthritis and THA
were more likely after CR than OR/IO, but the data do not
indicate a difference in unadjusted hip-survival time. Both
treatments provided substantial benefit relative to the natural
 history of DDH, but THA is the expected outcome in middle
adulthood. Level of evidence: III.
18. Thomas SR, Wedge JH, Salter RB: Outcome at forty-five years
after open reduction and innominate osteotomy for late-
presenting developmental dislocation of the hip. J Bone Joint Surg
2007;89(11):2341-2350.
19. Novais EN, Hill MK, Carry PM, Heyn PC: Is age or surgical
approach associated with osteonecrosis in patients with
developmental dysplasia of the hip? A meta-analysis. Clin Orthop
Relat Res 2016;474(5):1166-1177.
20. Chen C, Doyle S, Green D, et al: Presence of the ossific nucleus
and risk of osteonecrosis in the treatment of developmental
dysplasia of the hip: A meta-analysis of cohort and case-control
studies. J Bone Joint Surg Am 2017;99(9):760-767.
21. Sankar WN, Duncan ST, Baca GR, et al: Descriptive
epidemiology of acetabular dysplasia. J Am Acad Orthop Surg
2017;25(2):150-159.
22. Wya M, Weidner J, Pfluger D, Beck M: The Femoro-Epiphyseal
Acetabular Roof (FEAR) index: A new measurement associated
with instability in borderline hip dysplasia? Clin Orthop Relat Res
2017;475(3):861-869.
23. Maldonado DR, LaReau JM, Perets I, et al: Outcomes of hip
arthroscopy with concomitant periacetabular osteotomy,
minimum 5-year follow-up. Arthrosc J Arthrosc Relat Surg
2019;35(3):826-834. This retrospective 5-year outcomes study
described patients who underwent simultaneous hip arthroscopy
and PAO for concomitant acetabular dysplasia and intracapsular
hip pathology. At final follow-up there was no progression of
arthritis and lateral center-edge angle, and Tönnis angles
improved from preoperative values. In addition, there was a
significant improvement in patient-reported outcomes and visual
analog scale scores, and no patient underwent subsequent THA.
Level of evidence: IV.
24. Ziran N, Varcadipane J, Kadri O, et al: Ten- and 20-year
survivorship of the hip after periacetabular osteotomy for
acetabular dysplasia. J Am Acad Orthop Surg 2019;27(7):247-255.
This cross-sectional retrospective study evaluated the functional
and radiographic outcomes at 10 and 20 years following PAO for
acetabular dysplasia. The 10-year survival was 86% and 20-year
survival was 60%. Individuals who underwent PAO at younger
ages had lower Tönnis angle at the time of index procedure, and
female patients had higher survivorship. Level of evidence: III.
25. Wells J, Millis M, Kim YJ, Bulat E, Miller P, Matheney T:
Survivorship of the Bernese periacetabular osteotomy: What
factors are associated with long-term failure? Clin Orthop Relat
Res 2017;475(2):396-405.
26. Kim Young-Jo, Ramachandran M: Slipped capital femoral
epiphysis, in Weinstein SL, Flynn JM, Crawford H, eds: Lovell and
Winter’s Pediatric Orthopaedics, ed 8. Lippinco Williams &
Wilkins, Wolters Kluwer, 2014, pp 1162-1210.
27. Obana KK, Siddiqui AA, Broom AM, et al: Slipped capital
femoral epiphysis in children without obesity. J Pediatr
2020;218:192-197.e1. This study further characterized the rates of
SCFE in patients without obesity. The study authors found that
the rate of SCFE in nonobese children were more likely to present
with severe slips and unstable slips. Level of evidence: IV.
28. Morris WZ, Liu RW, Marshall DC, Maranho DA, Novais EN:
Capital femoral epiphyseal cupping and extension may be
protective in slipped capital femoral epiphysis: A dual-center
matching cohort study. J Pediatr Orthop 2020;40(7):334-339. This is
a two-center study with matched control patients comparing the
peripheral cupping of the epiphysis in unilateral SCFE and
normal hips on plain radiographs. Hips with more epiphyseal
cupping around the metaphysis were less likely to have SCFE in
contralateral hips without subsequent slip versus those
contralateral hips with subsequent slips. Level of evidence: III.
29. Maranho DA, Miller PE, Novais EN: The peritubercle lucency
sign is a common and early radiographic finding in slipped
capital femoral epiphysis. J Pediatr Orthop 2018;38(7):e371-e376.
30. Clement ND, Vats A, Duckworth AD, Gaston MS, Murray AW:
Slipped capital femoral epiphysis. Bone Joint J 2015;97-B(10):1428-
1434.
31. Ziebarth K, Domayer S, Slongo T, Kim YJ, Ganz R: Clinical
stability of slipped capital femoral epiphysis does not correlate
with intraoperative stability. Clin Orthop Relat Res
2012;470(8):2274-2279.
32. Bland DC, Valdovino AG, Jeffords ME, Bomar JD, Newton PO,
Upasani VV: Evaluation of the three-dimensional translational
and angular deformity in slipped capital femoral epiphysis. J
Orthop Res 2020;38(5):1081-1088. This radiologic study describes
how to measure the three-dimensional deformity of the epiphysis
relative to the femoral neck in patients with SCFE. This study
provides valuable information for surgeons preparing for
deformity correction and hip reconstruction in SCFE hips. Level
of evidence: IV.
33. Karol LA, Doane RM, Cornicelli SF, Zak PA, Haut RC, Manoli A:
Single versus double screw fixation for treatment of slipped
capital femoral epiphysis: A biomechanical analysis. J Pediatr
Orthop 1992;12(6):741-745.
34. Morash K, Orlik B, El-Hawary R, Gauthier L, Logan K: Femoral
neck growth and remodeling with free-gliding screw fixation of
slipped capital femoral epiphysis. J Pediatr Orthop
2021;41(4):e309-e315. This is a retrospective review comparing
free-gliding SCFE screw versus standard screw fixation of SCFE.
The free-gliding screw had less deformity on the affected side as
well as continued growth on the prophylactically treated
contralateral side. Level of evidence: III.
35. Sucato DJ: Approach to the hip for SCFE: The North American
perspective. J Pediatr Orthop 2018;38(suppl 1):S5-S12.
36. Parsch K, Weller S, Parsch D: Open reduction and smooth
Kirschner wire fixation for unstable slipped capital femoral
epiphysis. J Pediatr Orthop 2009;29(1):1-8.
37. Souder CD, Bomar JD, Wenger DR: The role of capital
realignment versus in situ stabilization for the treatment of
slipped capital femoral epiphysis. J Pediatr Orthop 2014;34(8):791-
798.
38. Sankar WN, Vanderhave KL, Matheney T, Herrera-Soto JA,
Karlen JW: The modified Dunn procedure for unstable slipped
capital femoral epiphysis: A multicenter perspective. J Bone Joint
Surg Am 2013;95(7):585-591.
39. Örtegren J, Peterson P, Svensson J, Tiderius CJ: Persisting CAM
deformity is associated with early cartilage degeneration after
Slipped Capital Femoral Epiphysis: 11-year follow-up including
dGEMRIC. Osteoarthritis Cartilage 2018;26(4):557-563.
40. Upasani VV, Matheney TH, Spencer SA, Kim YJ, Millis MB,
Kasser JR: Complications after modified Dunn osteotomy for the
treatment of adolescent slipped capital femoral epiphysis. J
Pediatr Orthop 2014;34(7):661-667.
41. Lee JH, Zhou L, Kwon KS, Lee D, Park BH, Kim JR: Role of
leptin in Legg-Calvé-Perthes disease. J Orthop Res
2013;31(10):1605-1610.
42. Kim HKW: Legg-Calvé-Perthes disease. Am Acad Orthop Surg
2010;18(11):676-686.
43. McAndrew MP, Weinstein SL: A long-term follow-up of Legg-
Calvé-Perthes disease. J Bone Joint Surg Am 1984;66(6):860-869.
44. Herring JA, Kim HT, Browne R: Legg-Calve-Perthes disease. Part
II: Prospective multicenter study of the effect of treatment on
outcome. J Bone Joint Surg Am 2004;86(10):2121-2134.
45. Sebag G, Ducou Le Pointe H, Klein I, et al: Dynamic
gadolinium-enhanced subtraction MR imaging—A simple
technique for the early diagnosis of Legg-Calvé-Perthes disease:
Preliminary results. Pediatr Radio 1997;27(3):216-220.
46. Grzegorzewski A, Synder M, Kozłowski P, Szymczak W, Bowen
RJ: The role of the acetabulum in Perthes disease. J Pediat Orthop
2006;26(3):316-321.
47. Joseph B, Rao N, Mulpuri K, Varghese G, Nair S: How does a
femoral varus osteotomy alter the natural evolution of Perthesʼ
disease? J Pediatr Orthop B 2005;14(1):10-15.
48. Sankar WN, Lavalva SM, Mcguire MF, Jo C, Laine JC, Kim HKW:
Does early proximal femoral varus osteotomy shorten the
duration of fragmentation in Perthes disease? Lessons from a
prospective multicenter cohort. J Pediatr Orthop 2020;40(5):e322-
e328. This is a prospective multicenter study evaluating the 2-year
outcomes of patients with LCP disease in early fragmentation
stage following proximal femoral osteotomy. There was 1 patient
(2%) who completely bypassed and 8 (17%) who partially
bypassed the fragmentation phase following the osteotomy.
These patients had less collapse and be er outcomes than
patients who still experienced the fragmentation stage. Level of
evidence: IV.
49. Mosow N, Ve orazzi E, Breyer S, Ridderbusch K, Stücker R,
Rupprecht M: Outcome after combined pelvic and femoral
osteotomies in patients with Legg-Calvé-Perthes disease. J Bone
Joint Surg Am 2017;99(3):207-213.
50. Kaneko H, Kitoh H, Mishima K, et al: Comparison of surgical
and nonsurgical containment methods for patients with Legg-
Calvé-Perthes disease of the onset ages between 6.0 and 8.0 years:
Salter osteotomy versus a non-weight-bearing hip flexion-
abduction brace. J Pediatr Orthop B 2020;29(6):542-549. This
retrospective review compared outcomes between patients with
LCP disease between ages 6 and 8 years who were treated with
either abduction bracing or Salter osteotomy. Patients who
underwent Salter osteotomy had be er acetabular shape with
less femoral head lateralization. There was no difference in
Stulberg classification, pain, or motion at final follow-up. Level of
evidence: III.
51. Anthony CA, Wasko MK, Pashos GE, Barrack RL, Nunley RM,
Clohisy JC: Total hip arthroplasty in patients with osteoarthritis
associated with Legg-Calve-Perthes disease: Perioperative
complications and patient-reported outcomes. J Arthroplasty
2021;36(7):2518-2522. This retrospective review evaluated the
patient-reported outcomes and complications following primary
total hip arthroplasty in patients with residual deformity and
arthritis secondary to LCP disease. There was an improvement in
the modified Harris Hip Score postoperatively and 98.4% were
revision-free at a mean follow-up of 5.6 years. Level of evidence:
IV.
52. Masrouha KZ, Callaghan JJ, Morcuende JA: Primary total hip
arthroplasty for Legg-Calvé-Perthes syndrome: 20 year follow-up
Study. Iowa Orthop J 2018;38:197-202.
53. Griffin DR, Dickenson EJ, Wall PDH, et al: Hip arthroscopy
versus best conservative care for the treatment of
femoroacetabular impingement syndrome (UK FASHIoN): A
multicentre randomised controlled trial. Lancet
2018;391(10136):2225-2235.
54. Nwachukwu BU, Rebolledo BJ, McCormick F, Rosas S, Harris
JD, Kelly BT: Arthroscopic versus open treatment of
femoroacetabular impingement. Am J Sports Med 2016;44(4):1062-
1068.
55. Saadat E, Martin SD, Thornhill TS, Brownlee SA, Losina E, Ka
JN: Factors associated with the failure of surgical treatment for
femoroacetabular impingement: Review of the literature. Am J
Sports Med 2014;42(6):1487-1495.
C H AP T E R 6 4

Pediatric Lower Extremity and

Foot Disorders
Jill C. Flanagan MD, FAAOS, Jaclyn F. Hill MD, FAAOS,
Raymond W. Liu MD, FAAOS

Dr. Flanagan or an immediate family member serves as a paid consultant to or is an employee of

NuVasive and Orthofix, Inc. and serves as a board member, owner, officer, or committee member
of American Academy of Orthopaedic Surgeons and Limb Lengthening and Reconstruction
Society. Dr. Hill or an immediate family member is a member of a speakers’ bureau or has made
paid presentations on behalf of NuVasive and OrthoPediatrics and serves as a board member,
owner, officer, or committee member of Limb Lengthening and Reconstruction Society and
Pediatric Orthopaedic Society of North America. Dr. Liu or an immediate family member serves
as a board member, owner, officer, or committee member of American Academy of Orthopaedic
Surgeons, Limb Lengthening and Reconstruction Society (LLRS), and Pediatric Orthopaedic
Society of North America.

ABSTRACT
Conditions affecting the lower extremity from birth to skeletal
maturity are a common reason for referral to an orthopaedic
surgeon. Differentiating between age-appropriate development and
pathologic conditions in pediatric patients requires an
understanding of normal skeletal growth and development. Work-
up of lower extremity conditions starts with a thorough medical
history and physical examination. Radiographs and advanced
imaging should be used judiciously.
Observation and familial reassurance are indicated in benign
variations known to have a favorable natural history. Numerous
management options exist for pathologic conditions expected to
adversely affect patient health-related quality of life. Several of
these modalities take advantage of physeal growth and/or the
remarkable plasticity of the pediatric musculoskeletal system to
achieve deformity correction.
Keywords: clubfoot; genu valgum; genu varum; limb deficiency;
tibial bowing

Introduction
Pediatric lower extremity anomalies represent a diverse set of
conditions, ranging from normal musculoskeletal development and
physiologic variations to severe limb deficiencies. These may occur
in isolation or be part of a more global condition. Understanding
age-appropriate development and normal musculoskeletal growth
is essential to proper diagnosis. A thoughtful evaluation and a
patient-centered approach are critical to optimizing health-related
quality of life while minimizing the cost, burden, and morbidity of
management.

Rotational Variations
The internal or external positioning of the foot during gait (intoeing
or out-toeing) or the foot progression angle is the summation of the
torsional contributions from the lower extremity segments (femur,
tibia, and foot). Deviations in foot progression are a frequent source
of caregiver anxiety and reason for referral. Determining normal
versus pathologic rotational abnormalities is dependent on the
child’s age at the time of evaluation as norms change throughout
skeletal growth.
Femoral version refers to the angle of the femoral neck relative to
the transcondylar axis of the distal femur. Femoral version can be
inferred clinically by assessing hip range of motion with the patient
prone and the pelvis level. A hip arc of motion skewed toward
internal rotation relative to external rotation suggests a greater
degree of anteversion. Femoral anteversion averages approximately
40° at birth and typically decreases to an average of 10° to 15° by 8
to 10 years of age. 1
Tibial torsion is defined as the rotational relationship between
the proximal and distal articular axes of the tibia around its
longitudinal axis. Tibial torsion is typically quantified on physical
examination by measuring a patient’s thigh-foot angle while prone
with the knee flexed 90°. Using this technique, tibial torsion
averages approximately 5° internal at birth, changing to
approximately 10° external by 8 years of age. 2
Evaluation of a perceived rotational abnormality in a child should
begin with a thorough history and physical examination. It is
important to elucidate the perceived influence of the rotational
abnormality on the patient’s functional status with respect to pain,
balance, and function. Functional difficulties such as frequent
tripping should be understood with knowledge of a typical
evolution of gait. A gradual deterioration in gait over time should
alert the provider to the possibility of an underlying neuromuscular
condition.
Physical examination of a perceived rotational abnormality
should include evaluation of the patient’s rotational profile. 2 This
includes measuring the patient’s internal rotation and external
rotation of the hip, thigh-foot angle, heel-bisector angle, and foot
progression angle during gait. A neutral foot progression angle
does not exclude the presence of abnormalities in multiple
segments. For example, the combination of external tibial torsion
with excessive femoral anteversion would result in a neutral foot
progression angle but can place increased stress at the
patellofemoral joint and has been termed miserable malalignment
syndrome.
Radiographs are not typically required for assessment of
torsional profile. CT has historically been used to quantify
pathologic femoral version and tibial torsion. However, CT exposes
the child to significant radiation exposure. To avoid this exposure,
some institutions have switched to MRI in patients who can tolerate
the procedure without sedation. In the future, EOS imaging
technology may become more common for radiographic rotational
profiles. 3
Because most rotational abnormalities in young children improve
with growth, reassurance and observation are the mainstays of
management. Further, in the general adult population, persistent
abnormalities in torsional profile, such as increased femoral
anteversion or tibial torsion, have not been associated with long-
term conditions such as osteoarthritis of the knee or hip. 4 The
parents should be counseled that nonsurgical management of
benign childhood torsional abnormalities (eg, physical therapy or
orthoses) has not been shown to be effective and may be associated
with adverse psychological effects.
Surgical management of torsional abnormalities in otherwise
healthy children can be considered for functional issues or severe
cosmetic abnormalities deemed unacceptable to patients and their
families in children older than 10 years. Abnormal femoral version
and tibial torsion may require treatment in older patients who
present with hip and/or knee pain, patellofemoral dysfunction, or
deviations of gait pa ern. Abnormal femoral version has been cited
as contributing to symptomatic femoroacetabular impingement. 5
Femoral anteversion is also known to exacerbate hip dysplasia.
Abnormal tibial torsion negatively affects muscle lever arms and
force production during gait. In patients with neuromuscular
conditions, such as spina bifida and cerebral palsy, abnormal
torsion can negatively affect the ability to ambulate.
Surgical management of tibial torsion generally consists of a
supramalleolar osteotomy unless there is additional deformity,
whereas surgical management of femoral rotational abnormalities
can be considered through a variety of approaches, generally
proximally or distally if there is associated proximal coronal or
sagi al plane deformity at the same region, versus proximally,
distally, or midshaft if there is not associated deformity.
Coronal Plane Variations of the Knee
An understanding of the normal coronal or frontal plane lower
extremity development is critical in differentiating normal
variations from pathologic conditions. Infants are born with mild
genu varum (approximately 10° to 15° of varus). This typically
decreases to neutral tibial-femoral alignment by 18 to 24 months of
age and progresses to genu valgum thereafter. Knee valgus reaches
a maximum at approximately 3 years of age (10° to 15° of valgus),
after which knee valgus generally decreases to adult norms
(approximately 7° to 8°) by age 6 years. 6 Further changes in coronal
plane knee alignment are uncommon in late childhood or
adolescence in the absence of physeal disturbance.
Evaluation of coronal plane abnormalities of the knee begins with
a detailed history and physical examination. History should focus
on the perceived change in alignment with growth, underlying
medical conditions, nutrition (eg, vitamin D deficiency in babies
who are breastfed exclusively), and potential prior insults to the
physis (eg, trauma or infection). Physical examination should be
performed with the patient non–weight bearing and in both static
and dynamic weight bearing if possible. The patient’s growth and
stature should be scrutinized for any evidence of skeletal dysplasia.
It is important to assess for the presence of concomitant rotational
and/or sagi al plane abnormalities, ligamentous laxity, and leg-
length discrepancy.
When pathologic coronal plane variations are suspected,
radiographic evaluation should include full-length lower extremity
radiographs with the patient standing (if possible). Imaging is
obtained with the patella facing forward to minimize distortion
caused by rotational abnormalities. Radiographs allow the provider
to evaluate mechanical axis deviation (MAD), location of deformity,
physeal disturbance, and limb-length discrepancy. Any identified
deformity should also undergo imaging in an orthogonal plane to
look for potential sagi al plane deformity.
 The mechanical axis of the limb is measured with a line
connecting the center points of the hip and ankle, with the normal
range from 1 to 15 mm relative to the center of the joint and the
ideal being 0 ± 3 mm. Medial MAD greater than 15 mm is
considered varus and any lateral MAD is considered valgus. The
knee can also be categorized into zones to help describe the degree
of deformity (Figure 1).

Figure 1 AP radiograph of the knee showing mechanical axis zones.

Surgical techniques to correct valgus and varus deformities are

similar. Growth modulation can be performed for functional physes
with sufficient growth remaining with either tension band plating
or transphyseal screws. 7 In patients presenting closer to skeletal
maturity, osteotomy with acute or gradual correction may be
indicated.

Genu Valgum
Genu valgum is considered physiologic until age 8 years.
Persistence of moderate to severe valgus past this age is pathologic
and may be idiopathic in nature or may be secondary to metabolic
disorders, skeletal dysplasias, congenital limb deficiency associated
with hypoplasia of the lateral femoral condyle, or injury to the
lateral femoral and/or tibial physes.
A 2019 study has demonstrated that although Cozen
phenomenon does occur in metaphyseal proximal tibial fractures,
patients are at low risk of having persistent clinically significant
genu valgum and therefore do not all need regular clinical follow-
up or radiographic screening. Patients with an initial valgus
deformity of greater than 4° with an ipsilateral fibular fracture or
with a medial metaphyseal gap are at a higher risk of the
development of deformity and should be followed more closely. 8
Nonsurgical modalities such as orthoses or physical therapy have
not been demonstrated to change the natural history of genu
valgum. Typical indications for surgical intervention include a
clinically unacceptable deformity and/or lateral deviation of the
mechanical axis lateral to the tibial plateau. Surgical intervention
with mild MAD (zone 2) can also be considered but is mainly an
aesthetic indication because there is no evidence of increased risk
of future arthritis. 9 For patients with this degree of deformity,
treatment should be deferred unless it is paired with pain or
functional issues.
Surgical options for pathologic genu valgum include medial
hemiepiphysiodesis (temporary or permanent) or acute osteotomy,
with careful a ention paid to any stretching of the peroneal nerve
with acute correction. Goals of surgical management for pathologic
genu valgum include restoration of a normal mechanical axis and
joint orientation while minimizing complications. Guided growth is
dependent on sufficient growth potential of the lateral-side physes
to correct deformity with time. Therefore, it is not a reliable option
for patients who are at (or near) skeletal maturity or in patients
with pathologic lateral physes.

Genu Varum
Genu varum is considered normal until age 2 years. Physiologic
genu varum frequently demonstrates gradual bowing in the distal
femur and proximal tibia without physeal abnormalities on
radiographs and often resolves spontaneously with growth.
Therefore, observation and reassurance are recommended. 10
Persistence of genu varum beyond age 2 years is abnormal and
warrants further evaluation. 7 Etiologies of pediatric pathologic
genu varum include metabolic bone diseases, skeletal dysplasias,
and physeal growth disturbances.
Idiopathic tibia vara (Blount disease) is characterized by an
abrupt varus deformity at the proximal tibia. Although defined
primarily based on the coronal plane deformity, Blount disease is
frequently associated with internal rotation and flexion of the
proximal tibia. The specific etiology of Blount disease is unknown,
but it is thought to be related to deceleration of growth in the
posteromedial proximal tibial physis secondary to genetic
predisposition, obesity, early walking, and other nutritional factors.
Left untreated, Blount disease is associated with progressive
coronal deformity, leg-length discrepancy (in unilateral cases), gait
abnormality, and premature arthritis.
Blount disease is classified based on the age of onset; two forms
are most common: infantile (onset before age 5 years) and
adolescent (onset after age 10 years). A third form, juvenile, has
been described for patients aged 5 to 10 years at diagnosis with
intermediate findings.
 Infantile Blount disease is bilateral in approximately 50% of
patients. Imaging findings of infantile Blount disease include
physeal changes and medial metaphyseal beaking. The
metaphyseal-diaphyseal angle, defined as the angle between the
proximal tibial metaphysis and a line perpendicular to the long axis
of the tibial diaphysis, can help distinguish between physiologic
and pathologic genu valgum 11 (Figure 2). An angle of up to 9° is
associated with a 95% chance of spontaneous resolution, whereas
angles of 9° or greater have a 95% likelihood of pathologic and
progressive tibia vara. 12 Infantile Blount disease has historically
been classified according to the Langenskiöld classification. 13 A
modified classification that correlates extreme sloping of the medial
metaphyseal defect to a poor prognosis has been proposed in a
2019 study. 14
 Figure 2 AP radiograph of the lower extremity of a patient with infantile Blount
disease showing metaphyseal beaking.A metaphyseal-diaphyseal angle of 37° is
demonstrated.

Orthotic management with the goal of unloading the medial

tibial physis can be considered for a young patient (age 3 years or
younger), although the evidence for this is poor. For children older
than 3 years and with progressive deformity, surgical intervention
is recommended. Surgical options include growth modulation
and/or physeal bar resection if there is skeletal growth remaining.
In patients with li le growth remaining, proximal tibial osteotomy
with or without a midshaft fibular osteotomy is used for acute
versus gradual deformity correction.
Adolescent Blount disease typically is less severe than infantile
forms and is more often unilateral. Adolescent Blount disease may
be associated with varus deformities of the distal femur and/or
valgus deformities of the distal tibia. Recognition and concomitant
management of these deformities are important to successful
outcomes. Adolescent Blount disease is strongly associated with
obesity and has been associated with increased rates of
hypertension and obstructive sleep apnea. 15 , 16 Because of the
limited growth potential and a frequent association of obesity,
nonsurgical management has no role in the management of
adolescent Blount disease. Surgical options include growth
modulation or a proximal tibial osteotomy with either acute or
gradual correction. Skeletal age is frequently advanced in patients
with adolescent Blount disease, so bone age should be assessed
before a empted guided growth.

Congenital Limb Deficiency

Congenital limb deficiencies are rare conditions that are
challenging to treat. Treatment of these patients is best done using
a multidisciplinary approach with the goal of creating a functional
lower extremity for the patient. Care should be taken to minimize
physical and emotional morbidity during this process.

Congenital Femoral Deficiency

Congenital femoral deficiency (CFD) is a comprehensive term that
encompasses both the diagnosis of proximal femoral focal
deficiency as well as a congenitally short femur. The incidence of
CFD is approximately 1 in 50,000 to 200,000 births. 17 The severity of
CFD can be widely variable, ranging from a modest limb-length
difference because of a short femur to a limb that has no
discernible hip joint and complete absence of the femur. A
constellation of limb anomalies may be associated with CFD,
including acetabular dysplasia, femoral retroversion, a complex
coxa vara, hypoplasia of the lateral distal femoral condyle, knee and
patellar instability, as well as fibular hemimelia and its associated
findings. The Paley classification of CFD is helpful in
understanding the underlying pathology and dictating treatment
options 17 (Figure 3). A patient with less severe CFD (Paley type 1
and 2) is most likely to be a candidate for reconstruction, which
consists of joint reconstruction followed by femoral and possibly
tibial lengthening (Figure 4). Although tibial lengthening in
patients with CFD can be associated with more complications than
in patients with other etiologies, good outcomes can still be
achieved. 18 , 19 For patients with more severe CFD, other
reconstruction options include rotationplasty or a Syme amputation
with knee fusion.
Figure 3 Paley classification for congenital femoral deficiency.This
classification is divided based on anatomic descriptions as well as
reconstruction options. The type 1 and 2 femurs are more amenable to hip
reconstruction and lengthening options, whereas the type 3 and 4 femurs often
benefit from a combination of reconstruction and prosthetic wear.(Reproduced
from Paley D, Guardo F: Chapter 13, Lengthening and reconstruction surgery for
congenital femoral deficiency, in Kocaoğlu M, Tsuchiya H, Eralp L, eds:
Advanced Techniques in Limb Reconstruction Surgery. Springer, 2015, pp 245-
299. Image is Figure 13.1, p 247.)
 Figure 4 Radiographic appearance of a left Paley type 1A congenital femoral
deficiency before hip reconstruction, demonstrating coxa vara, acetabular
dysplasia, and decreased size of the left proximal femur.A, AP pelvic view. B,
Frog-leg lateral pelvic view.

Fibular Hemimelia
Fibular hemimelia is the most common long bone deficiency with
an incidence of 1 to 2 per 100,000 live births. 20 , 21 These patients
present with a short limb, commonly with anteromedial tibial
bowing, valgus at the knee, tarsal coalitions, a ball-and-socket ankle
joint, cruciate deficiencies, femoral deficiencies, and possible
absent lateral rays 20 , 21 (Figure 5).

Figure 5 Clinical photographs and corresponding foot and ankle radiographs of

a patient with severe fibular deficiency demonstrating absence of the fibula,
severe equinus, and flatfoot, as well as multiple deficiencies in the foot.
 There are several classifications used to describe fibular
hemimelia. 22 The Birch classification 6 focuses on foot
reconstruction, the Achterman and Kalamchi classification 23 is
based on the shape of the fibula, and the Paley classification 24
emphasizes that the foot and ankle deformities should dictate
management.
Management consists of either an amputation of the foot with
application of a prosthesis or joint reconstructions followed by
tibial lengthening. 20 - 22 , 24 , 25 A 2020 meta-analysis reviewing seven
retrospective cohort studies concluded that limb ablation resulted
in be er patient satisfaction and fewer surgeries. 21 However, the
study noted that the limb reconstructions were performed with
older techniques instead of those in current use. A 2019 study
focused on quality of life and physical functioning in childhood
compared patients who had amputation with those who had limb
reconstruction using more modern techniques. It was concluded in
this preliminary study that there were no differences in function or
psychosocial outcome. 25
Regardless of treatment, valgus at the knee is a common finding
because of lateral femoral condyle hypoplasia. Guided growth can
be an effective treatment method, but patients need to be followed
closely because rebound deformity is relatively common. 26

Tibial Hemimelia
Tibial hemimelia, also known as congenital tibial deficiency, is the
rarest of the congenital limb deficiencies with an incidence of
1:1,000,000 live births. 27 - 29 A 2019 study found that tibial
hemimelia is more likely than other congenital limb deficiencies to
be associated with syndromes. 27 Tibial hemimelia can vary in
presentation with regard to tibial shortening and different knee and
foot abnormalities. In the most severe forms, the knee is unstable,
and the extensor mechanism is absent. The knee tends to have a
fixed flexion contracture, and the feet are often supinated and in a
rigid equinovarus position. 27 - 29
 The Jones classification 29 is based on radiographic appearance,
dividing patients into four groups based on morphology from worst
to best (Figure 6), whereas the Paley classification 30 describes the
deficiencies in more detail and provides a treatment and prognosis
algorithm. Given the higher risk of visceral involvement, before any
treatment is implemented, a genetics referral may be worthwhile.
Afterward, management is typically dictated by the stability of the
knee and the integrity of the extensor mechanism. With an absent
extensor mechanism, knee disarticulations are often performed, 27 ,
28 , 30
and with the extensor mechanism intact, centralizing
procedures such as the Brown procedure or the Weber patellar
arthroplasty are described. 31 , 32 In general, surgery should focus on
optimizing functional outcome, and this is based on how much
deficiency is present at baseline. As technology and techniques
continue to evolve and improve, additional reconstruction options
will likely become available for this challenging subset of patients.
 Figure 6 Jones classification for tibia hemimelia.The classification is divided
based on presence or absence of various portions of the tibia.(Adapted from
Turker R, Mendelson S, Ackman J, Lubicky JP: Anatomic considerations of the
foot and leg in tibial hemimelia. J Pediatr Orthop 1996;16[4]:445-449.)

Posteromedial Bowing of the Tibia

Congenital posteromedial bowing of the tibia is a rare birth
condition first described in 1949. 33 Children present with an
obvious oblique plane posteromedial bowing deformity of the
distal tibia along with a calcaneovalgus foot deformity. According
to one series, children who presented before 6 months of age had
an average apex medial bowing of 43° (5° to 70°), and apex posterior
bowing of 35° (7° to 71°). 34 Spontaneous correction occurred most
rapidly in the first year of life, with most improvement occurring by
the fourth year of life. After age 4 years, no further important
remodeling occurred.
The degree of initial bowing corresponds to the final predicted
limb-length discrepancy. Recent literature suggests a mean growth
inhibition of 14% compared with the other side, 34 with average
projected limb-length differences closer to 7 cm at skeletal maturity
34 , 35
(Figure 7).

Figure 7 Radiographs showing posteromedial bowing of the tibia.A, The

angular deformity was persistent at age 8 years; the deformity and 5-cm limb-
length difference were causing significant functional impairment. B, Deformity
correction and lengthening were achieved with a hexapod external fixator. C,
Years later the deformity remains corrected, with only a mild residual limb length
difference managed with contralateral epiphysiodesis.

Management considerations for posteromedial bowing of the

tibia should factor in the bowing deformity along with the final
projected limb-length discrepancy. Hemiepiphysiodesis at the
ankle can be considered after age 4 years. Osteoplasty with gradual
correction and lengthening with a hexapod external fixator or acute
correction with an internal lengthening nail can be considered,
depending on the magnitude of bowing as well as skeletal maturity.
34 , 35
A well-timed epiphysiodesis is also a treatment option for
smaller limb-length differences, especially in patients in whom
bowing deformities have adequately resolved.

Anterolateral Bowing and Congenital

Pseudarthrosis of the Tibia
Congenital pseudarthrosis of the tibia is a rare and challenging
anterolateral bowing disorder of the leg, with 50% of cases
associated with neurofibromatosis type 1. The prefractured state,
also known as congenital tibial dysplasia, is at risk for fracture
because of the bowing of the bone itself along with its inherent
dysplasia.
The periosteum is central to the congenital pseudarthrosis of the
tibial disorder, 36 with studies demonstrating higher osteoclastic
activity and less osteoblastic activity of the periosteum. Thus,
modern treatments have used diphosphonate infusions and
biologics to supplement surgical reconstruction, 36 , 37 although
prospective controlled studies will be necessary to determine the
true utility of these adjuvants.
The biomechanical challenges of congenital pseudarthrosis of the
tibia include the bowing deformity, proximal migration of the
fibula, and the small cross-sectional area of the bones at the
atrophic site. 36 Failure to correct fibular length can lead to poorer
outcomes, especially with regard to ankle valgus. 38
Management in the prefracture state previously focused on brace
use for as long as possible, but a 2020 retrospective review noted
that guided growth in the oblique plane of the distal tibial
deformity may correct the deformity without performing an
osteotomy. 39 There are multiple treatment options for patients with
nonunion, with the two most promising newer techniques focusing
on achieving a cross-union between the tibia and fibula. 40 , 41

Foot Conditions

Congenital Vertical Talus

Congenital vertical talus is a rare foot condition (incidence of 1 per
10,000) that typically presents in an infant with a rigid flatfoot and
rocker-bo om plantar foot. The key pathoanatomy is dorsolateral
dislocation of the navicular on the talus, with associated ankle
equinus, hindfoot valgus, forefoot dorsiflexion, and forefoot
abductus. As congenital vertical talus is frequently associated with
other conditions, MRI of the spine and referral to neurology and
genetics specialists should be considered in all children with
congenital vertical talus based on their clinical findings.
Congenital vertical talus can be differentiated from
calcaneovalgus foot based on rigid hindfoot equinus in congenital
vertical talus. A lateral plantar flexion radiographic stress view is
necessary to distinguish congenital vertical talus from oblique
talus. Although the talonavicular dislocation is not visible because
the navicular is not ossified in infants, the finding that the first
metatarsal will not reduce to the axis of the talus confirms
congenital vertical talus (Figure 8, A and B).
 Figure 8 Images from a female infant with right congenital vertical talus.A, At 9
days of age the AP foot radiograph shows abductus in the forefoot. B, Lateral
radiograph shows a vertical talus that is not co-linear with the first metatarsal on
a plantar flexion view. C, After two casts there is notable improvement in the
relationship between the talus and first metatarsal on a lateral radiograph in cast.
D, Intraoperative fluoroscopy shows the lateral foot alignment after talonavicular
pinning and Achilles tenotomy. E and F, Follow-up weight-bearing radiographs
obtained at 3 years of age show acceptable positioning with some residual
forefoot abductus on the AP view (E), and mild and acceptable plantar flexion of
the talus compared with the first metatarsal on the lateral view (F).

Treatment is necessary to avoid long-term functional issues with

the foot because the dislocation does not reduce spontaneously.
Prior described surgical treatments for congenital vertical talus
included single-stage releases, two-stage releases, navicular
excision with soft-tissue releases, as well as the Grice-Green
subtalar fusion after release. Treatment has shifted from these
more extensive open procedures to a more minimally invasive
approach. 42 Serial casting of the foot is performed first to correct
the talonavicular joint, and then surgery involving pinning of the
talonavicular joint and Achilles tenotomy is done (Figure 8, C
through F). The child’s foot is placed in a cast, which is
subsequently converted to a brace. The Dobbs method has
demonstrated improved pain and foot flexibility compared with
more extensive surgical releases. 43 This technique is successful in
management of both idiopathic and syndromic congenital vertical
talus, although a 2021 study has shown that recurrence is more
common with syndromic deformity. 44

Clubfoot
Clubfoot, also known as talipes equinovarus, is composed of cavus,
forefoot adductus, hindfoot varus, and equinus. The incidence is
approximately 1 in 1,000 with a predilection for males and is
approximately 50% bilateral. Although it is generally idiopathic,
multiple associated conditions are described. Worse outcomes are
noted with many of these, most notably arthrogryposis. Complex
clubfoot, with a short first metatarsal, severe plantar flexion of all
metatarsals, rigid equinus, and deep folds of the sole and heel, also
carries a high recurrence rate. 45
The Ponseti technique, which consists of weekly serial casting,
Achilles tenotomy, and then use of a brace, has largely replaced
more extensive surgical approaches, particularly surgeries involving
posteromedial intra-articular releases. A study of adults previously
treated with the Ponseti technique versus comprehensive release
found greater long-term foot deformity and hindfoot loading time
in the comprehensive release group. 46 Duration of brace wear can
vary, although bracing longer than 36 months was associated with
improved mobility and functional outcome scores according to a
2020 study. 47
The French method, which uses physiotherapy instead of casting,
was found to be associated with higher running speed/agility, body
coordination, and strength and agility in patients age 10 years
compared with the Ponseti technique, 48 although the French
method requires a substantial number of visits during infancy. A
three-phase physiotherapy program has been used in children
previously treated with the Ponseti technique and has
demonstrated improved ankle range of motion, functional status,
and treatment satisfaction. 49
 Relapse is often managed initially with additional casting.
Tibialis anterior tendon transfer is a common surgery to manage
dynamic supination. When surgery for relapse is performed, an a la
carte approach that treats patients’ key pathologic findings in the
foot and minimizes surgery in the joints is preferred. Children
treated with posteromedial rather than posterior release had
decreased plantar flexion and dorsiflexion strength and worse
parent-reported global function scores. 50 For severe cases, a 2019
study has shown that an external fixator-based approach can
achieve improvement in functional outcome scores and a
plantigrade foot in most cases. 51

Tarsal Coalition
Tarsal coalition is an abnormal connection between two bones in
the hindfoot or midfoot and can be fibrous, cartilaginous, or
osseous. Children typically present with pain or repeated ankle
sprains, and physical examination is notable for decreased hindfoot
and midfoot range of motion and rigid flatfoot. A 2021 study of a
population-based database found annual incidence rates of 1.9 per
100,000 children for calcaneonavicular coalition, 1.2 for
talocalcaneal coalition, and 0.4 for all other coalitions combined. 52
Calcaneonavicular coalition is best seen on the oblique foot
radiograph, whereas talocalcaneal coalition is suspected based on a
C sign on a lateral radiograph (Figure 9). CT and MRI are helpful to
confirm a suspected diagnosis, characterize the lesion for surgical
resection, and rule out other coalitions.
 Figure 9 A, Oblique radiograph of the foot of a 12-year-old boy demonstrating
a calcaneonavicular coalition. B, Lateral radiograph of the foot of a 14-year-old
boy demonstrating a C sign, which suggests a talocalcaneal coalition.

Initial management is conservative, including immobilization,

orthotics, NSAIDs, physical therapy, and activity modification. If
unsuccessful, then resection and interposition with fat graft,
extensor digitorum brevis for calcaneonavicular coalition, flexor
hallucis longus or posterior tibialis tendon for talocalcaneal
coalition, or bone wax are reasonable options. Some surgeons
advocate for combined resection and osteotomy to correct severe
flatfoot deformities, whereas others advocate for a staged approach
because rehabilitation after resection involves quick mobilization
as opposed to immobilization for osteotomy. In a 2020 study, it was
demonstrated that patients treated with resection were less likely to
report symptoms at a median 14-year follow-up compared with
patients treated nonsurgically. 53 Although there is concern about
worse outcomes for talocalcaneal coalitions given their intra-
articular nature, a 2019 comparison of calcaneonavicular and
talocalcaneal coalitions managed surgically found no difference
between the two groups in terms of range of motion or outcome
scores at a minimum 5-year follow-up. 54 Arthrodesis can be
considered for failed resections or talocalcaneal coalitions involving
a substantial portion of the joint.

Cavovarus Foot
Cavovarus foot is characterized by a plantarflexed first ray, elevated
medial longitudinal arch, and hindfoot varus. Unilateral cavovarus
foot is concerning for a potential intraspinal etiology, and MRI of
the lumbar spine should be considered. Bilateral cavovarus foot is
concerning for an underlying neurologic condition, usually
hereditary motor and sensory neuropathies such as Charcot-Marie-
Tooth disease, and neurology consultation is considered.
Physical examination is notable for a high medial arch, plantar
callosities under the first and fifth metatarsal heads, and neurologic
findings such as plantar intrinsic wasting. Flexibility of the hindfoot
is classically examined using the Coleman block test, where varus of
the heel in stance resolves when a block is placed under the heel
and lateral foot to allow the first ray to avoid contact with the floor.
The heel varus also can be assessed with the patient prone. In
either case, if the hindfoot is flexible, the heel varus is driven by the
forefoot and a calcaneal osteotomy is not necessary during
correction.
Initial management is conservative with a foot orthotic that
recesses the first ray and elevates the entire lateral foot. This is
more successful with flexible hindfoot varus. Surgery can involve
osteotomies, plantar fascia release, and tendon transfers.
Combinations of these procedures have been shown to improve
foot alignment, ankle flexibility, and self-reported trips and falls in
children with Charcot-Marie-Tooth disease. For a fixed deformity, a
salvage surgical approach with dorsal tarsectomy, calcaneal
osteotomy, plantar fascia release, and first metatarsal osteotomy
when necessary demonstrated a decrease in callosities and sprains,
although only 58% of patients had very good or good Wicart and
Seringe functional outcome scores. 55 A recent description of dorsal
hemiepiphysiodesis of the first metatarsal and plantar fascia
release presents a less invasive option in children with adequate
skeletal growth remaining with improvement in heel varus, plantar
callosities, and functional outcomes. 56
Summary
Evaluation of the pediatric lower extremity and foot requires a
thorough approach and knowledge of normal pediatric
development. Physeal tethering (hemiepiphysiodesis) is a viable
option for coronal plane (genu varum/valgum) deformities in the
growing child. Those with congenital limb differences need a
thorough evaluation. A multidisciplinary team approach to
treatment is imperative for success whether reconstruction or limb
ablation is the treatment option. Congenital pediatric foot
disorders such as clubfoot and congenital vertical talus, which have
historically been managed with extensive releases, can more
optimally be managed with serial casting first followed by limited
soft-tissue releases.

Key Study Points

Knowledge of normal developmental patterns is critical in the assessment and
treatment of patients with pediatric limb deformity.
Patients with congenital limb deficiency have multiple potential associated
deformities, so close follow-up and subsequent treatment are important regardless
of whether that treatment is reconstruction or ablation.
Hemiepiphysiodesis is a powerful treatment option for the growing child with coronal
and sometimes sagittal plane deformities in a multitude of conditions, including
fibular hemimelia, posteromedial bowing of the tibia, and congenital pseudarthrosis
of the tibia in its prefracture stage.
For clubfoot and congenital vertical talus, management protocols including casting
and limited surgery result in improved foot flexibility and function compared with
extensive surgical releases.

Annotated References
1. Lincoln TL, Suen PW: Common rotational variations in children.
J Am Acad Orthop Surg 2003;11(5):312-320.
2. Staheli LT: Rotational problems in children. Instr Course Lect
1994;43:199-209.
 3. Folinais D, Thelen P, Delin C, et al: Measuring femoral and
rotational alignment: EOS system versus computed tomography.
Orthop Traumatol Surg Res 2013;99(5):509-516.
4. Weinberg DS, Park PJ, Morris WZ, Liu RW: Femoral version and
tibial torsion are not associated with hip or knee arthritis in a
large osteological collection. J Pediatr Orthop 2017;37(2):e120-e128.
5. Tonnis D, Dortmund , Heinecke A: Acetabular and femoral
anteversion: Relationship with osteoarthritis of the hip. J Bone
Joint Surgery Am 1999;81-A(12):1747-1770.
6. Salenius P, Vankka E: The development of the tibiofemoral angle
in children. J Bone Joint Surg Am 1975;57(2):259-261.
7. Park H, Park M, Kim SM, Kim HW, Lee DH: Hemiepiphysiodesis
for idiopathic genu valgum: Percutaneous transphyseal screw
versus tension-band plate. J Pediatr Orthop 2018;38:325-330.
8. Yang BW, Shore BJ, Rademacher E, May C, Watkins CJ,
Glo becker MP: Prevalence of Cozen’s phenomenon of the
proximal tibia. J Pediatr Orthop 2019;39:e417-e421. In this study,
181 patients with proximal tibial fractures were evaluated for
valgus deformity. No patients in the series required surgical
correction of valgus deformity. Level of evidence: IV.
9. Randall RM, Balch Samora J, Shannon C, Humbyrd CJ: Ethical
considerations in limb lengthening and deformity correction: Do
aesthetics ma er? J Bone Joint Surg Am 2019;101(15):1428-1431.
The authors discuss a case presentation of an 11-year-old girl
with genu valgum. Ethical analysis was performed, considering a
corrective surgery for a deformity that would have likely not
caused functional difficulties or degenerative changes. Level of
evidence: V.
10. Brooks WC, Gross RH: Genu varum in children: Diagnosis and
treatment. J Am Acad Orthop Surg 1995;3(6):326-335.
11. Levine AM, Drennan JC: Physiological bowing and tibia vara.
The metaphyseal-diaphyseal angle in the measurement of bowleg
deformities. J Bone Joint Surg Am 1982;64(8):1158-1163.
12. Feldman MD, Schoenecker PL: Use of the metaphyseal-
diaphyseal angle in the evaluation of bowed legs. J Bone Joint Surg
Am 1993;75(11):1602-1609.
13. Langenskiold A, Riska EB: Tibia vara (osteochondrosis
deformans tibiae): A survey of seventy-one cases. J Bone Joint Surg
Am 1964;46:1405-1420.
14. Lamont LE, McIntosh AL, Jo CH, et al: Recurrence after surgical
intervention for infantile tibia vara: Assessment of a new
modified classification. J Pediatr Orthop 2019;39(2):65-70. The
authors proposed a new three-stage classification for infantile
tibia vara based on radiographic findings of the medial tibial
metaphysis. This classification was applied to 82 patients and 115
limbs and rates of recurrence were analyzed. Extreme vertical
sloping of the medial tibial metaphysis was associated with a
high rate of recurrence. Level of evidence: II.
15. Taussig MD, Powell KP, Cole HA, et al: Prevalence of
hypertension in pediatric tibia vara and slipped capital femoral
epiphysis. J Pediatr Orthop 2016;36:877-883.
16. Jardaly A, McGwin G, Gilbert SR: Blount disease and
obstructive sleep apnea: An under-recognized association? J
Pediatr Orthop 2020;40:604-607. The prevalence of patients with
obstructive sleep apnea undergoing corrective surgery for Blount
disease was identified from the authors’ institution (23%) and the
Kids’ Inpatient Database (3%). A total of 4.4% of patients with
Blount disease experienced complications, including hypoxemia,
respiratory insufficiency, atelectasis, and arrhythmias. Level of
evidence: III.
17. Paley D, Chong D, Prince D: Congenital femoral deficiency
reconstruction and lengthening surgery, in Sabharwal S, ed:
Pediatric Lower Limb Deformities. Springer, 2016, pp 361-425.
18. Szymczuk VL, Hammouda AI, Gesheff MG, et al: Lengthening
with monolateral external fixation versus magnetically motorized
intramedullary nail in congenital femoral deficiency. J Pediatr
Orthop 2019;39(9):458-465. This retrospective study compared
 clinical outcomes of patients with congenital femoral deficiency
after limb lengthening with an external fixator versus limb
lengthening nail. Patients who used the internal lengthening nail
had superior range of motion during lengthening while
maintaining comparable distraction and healing indices. Level of
evidence: IV.
19. Prince DE, Herzenberg JE, Standard SC, et al: Lengthening with
external fixation is effective in congenital femoral deficiency. Clin
Orthop Relat Res 2015;473:3261-3271.
20. Kulkarni RM, Arora N, Saxena S, et al: Use of Paley classification
and SUPER ankle procedure in the management of fibular
hemimelia. J Pediatr Orthop 2019;39(9):e708-e717. This
retrospective review of patients with a staged ankle
reconstruction followed by tibial lengthening demonstrated a
decrease in limb lengthening complications and a decrease in
ankle stiffness. Level of evidence: IV.
21. Elmherig A, Ahmed AF, Hegazy A, et al: Amputation versus
limb reconstruction for fibula hemimelia: A meta-analysis. J
Pediatr Orthop 2020;40(8):425-430. An analysis of seven
retrospective cohort studies concluded that the combined
evidence suggests that there are fewer procedures, be er patient
satisfaction, and fewer surgical complications with ablation for
fibular hemimelia when compared to limb salvage. Level of
evidence: III.
22. Birch JG, Lincoln TL, Mack PW, et al: Congenital fibular
deficiency: A review of thirty years’ experience at one institution
and a proposed classification system based on clinical deformity.
J Bone Joint Surg Am 2011;93:1144-1151.
23. Achterman C, Kalamchi A: Congenital deficiency of the fibula. J
Bone Joint Surg Br 1979;61-B:133-137.
24. Paley D: Surgical reconstruction for fibular hemimelia. J Child
Orthop 2016;10:557-583.
25. Birch JG, Paley D, Herzenberg JE, et al: Amputation versus
staged reconstruction for severe fibular hemimelia: Assessment
 of psychosocial and quality-of-life status and physical functioning
in childhood. JB JS Open Access 2019;4(2):e0053. This retrospective
review comparing children in mid-childhood age with
amputation versus limb reconstruction demonstrated no
differences in psychological nor functional outcomes. Level of
evidence: III.
26. Westberry DE, Carpenter AM, Prodoehl J: Correction of genu
valgum in patients with congenital fibular deficiency. J Pediatr
Orthop 2020;40(7):367-372. This retrospective review of patients
after amputation demonstrated that valgus about the knee was
common and that guided growth can successfully correct the
mechanical axis deviation for improved prosthetic fi ing. Caution
exists for rebound valgus deformity if deformity is corrected at a
young age. Level of evidence: IV.
27. Litrenta J, Young M, Birch JG, Oetgen ME: Congenital tibial
deficiency. J Am Acad Orthop Surg 2019;27(6):e268-e279. This
review article discusses tibia hemimelia and provides
information regarding associated disorders, associated clinical
findings, and historical as well as newer treatment options
available. Level of evidence: V.
28. Chong DY, Paley D: Deformity reconstruction surgery for tibial
hemimelia. Children (Basel) 2021;8(6):461. This review article
provides an extensive review of the literature regarding tibial
hemimelia. It also provides up-to-date information regarding
patient pathology, physical examination findings, and treatment
recommendations. Level of evidence: V.
29. Jones D, Barnes J, Lloyd-Roberts GC: Congenital aplasia and
dysplasia of the tibia with intact fibula: Classification and
management. J Bone Joint Surg Br 1978;60:31-39.
30. Paley D: Tibial hemimelia: New classification and reconstructive
options. J Child Orthop 2016;10(6):529-555.
31. Brown FW: Construction of a knee joint in congenital absence of
the tibia (paraxial hemimelia tibia): A preliminary report. J Bone
Joint Surg 1965;47:695-704.
32. Weber M: A new knee arthroplasty versus Brown procedure for
congenital absence of the tibia. J Pediatr Orthop B 2002;11:53-59.
33. Heyman CH, Herndon CH: Congenital posterior angulation of
the tibia. J Bone Joint Surg Am 1949;31-A:571-580.
34. Wright J, Hill RA, Eastwood DM, et al: Posteromedial bowing of
the tibia: A benign condition or a case for limb reconstruction? J
Child Orthop 2018;12(2):187-196.
35. Gordon JE, Schoenecker PL, Lewis TR, et al: Limb lengthening
in the treatment of posteromedial bowing of the tibia. J Child
Orthop 2020;14(5):480-487. This retrospective review discusses a
series of patients at a single institution successfully treated with
gradual deformity correction and lengthening with an external
fixator device. The authors reported that symptomatic ankle
valgus may need to be treated after initial deformity correction
and lengthening. Level of evidence: IV.
36. Paley D: Congenital pseudarthrosis of the tibia: Biological and
biomechanical considerations to achieve union and prevent
refracture. J Child Orthop 2019;13(2):120-133. This is a
comprehensive review discussing both the biologic and
biomechanical considerations of congenital pseudarthrosis of the
tibia as well as the success of utilizing a cross union technique for
reconstruction. Level of evidence: V.
37. Birke O, Schnideler A, Ramachandran M, et al: Preliminary
experience with the combined use of recombinant bone
morphogenetic protein and bisphosphonates in the treatment of
congenital pseudarthrosis of the tibia. J Child Orthop
2010;4(6):507-517.
38. Zargarbashi R, Bagherpour A, Keshavarz-Fathi M, et al:
Prognosis of congenital pseudarthrosis of the tibia: Effect of site
of tibial pseudarthrosis and fibular involvement. J Pediatr Orthop
2021;41(7):422-427. This case series of 12 patients discusses a 67%
union rate for reconstructions performed at a young age, with the
goal of a cross union. The study authors described increased risk
of ankle valgus if a fibular pseudarthrosis is ignored, especially if
 the abnormality is in the middle and distal one-third. Level of
evidence: IV.
39. Laine JC, Novotny SA, Weber EW, et al: Distal tibial guided
growth for anterolateral bowing of the tibia: Fracture may be
prevented. J Bone Joint Surg Am 2020;102(23):2077-2086. This
retrospective review describes 10 patients with congenital tibial
dysplasia achieving deformity correction and improved bone
quality with a distal tibia hemiepiphysiodesis in the oblique
plane. Level of evidence: IV.
40. Choi IH, Lee SJ, Moon HJ, et al: ‘4-in-1 Osteosynthesis’ for
atrophic-type congenital pseudarthrosis of the tibia. J Pediatr
Orthop 2011;31:697-704.
41. Paley D: Congenital pseudarthrosis of the tibia: Combined
pharmacologic and surgical treatment using bisphosphonate
intravenous infusion and bone morphogenic protein with
periosteal and cancellous autogenous bone grafting, tibiofibular
cross union, intramedullary rodding and external fixation, in
Zorzi A, ed: Bone Grafting. InTech, 2012, pp 91-106.
42. Dobbs MB, Purcell DB, Nunley R, Morcuende JA: Early results
of a new method of treatment for idiopathic congenital vertical
talus. J Bone Joint Surg Am 2006;88(6):1192-1200.
43. Yang JS, Dobbs MB: Treatment of congenital vertical talus:
Comparison of minimally invasive and extensive soft-tissue
release procedures at minimum five-year follow-up. J Bone Joint
Surg Am 2015;97(16):1354-1365.
44. Hafez M, Davis N: Outcomes of a minimally invasive approach
for congenital vertical talus with a comparison between the
idiopathic and syndromic feet. J Pediatr Orthop 2021;41(4):249-254.
At mean 6.5-year follow-up, 5 of 17 feet with syndromic
congenital vertical talus had recurred compared to none of 13
idiopathic feet. Level of evidence: IV.
45. Allende V, Paz M, Sanchez S, et al: Complex clubfoot treatment
with ponseti method: A latin american multicentric study. J
Pediatr Orthop 2020;40(5):241-245. Six centers combined 124 feet
 with complex clubfoot, 122 of which were initially treated with
Ponseti technique. The study authors reported a relapse rate of
30%. Feet that relapsed required more initial casts. Level of
evidence: III.
46. Graf AN, Kuo KN, Kurapati NT, et al: A long-term follow-up of
young adults with idiopathic clubfoot: Does foot morphology
relate to pain? J Pediatr Orthop 2019;39(10):527-533. Patients with
clubfoot previously treated with posteromedial release versus the
Ponseti technique were compared with control patients at adult
age. Foot morphology was related to pain, and there were greater
measures of foot deformity in the surgical versus Ponseti group.
Level of evidence: III.
47. Khan AA, Abarca N, Cung NQ, Lerman JA: Use of PROMIS in
assessment of children with Ponseti-treated idiopathic clubfoot:
Be er scores with greater than 3 years of brace use. J Pediatr
Orthop 2020;40(9):526-530. A retrospective study of 77 children
found that those who underwent more than 36 months of brace
treatment had be er mobility functional outcomes scores
compared with children who wore a brace for less time. Level of
evidence: III.
48. Zapata KA, Karol LA, Jeans KA, Jo CH: Gross motor function at
10 years of age in children with clubfoot following the French
physical therapy method and the Ponseti technique. J Pediatr
Orthop 2018;38(9):e519-e523.
49. Tarakci D, Leblebici G, Tarakci E, Bursali A: The effectiveness of
three-phase physiotherapy program in children with clubfoot
after Ponseti treatment. Foot Ankle Surg 2022;28(2):181-185. A
total of 57 patients with clubfoot were treated with a 3-month
physiotherapy program with improvements noted in ankle range
of motion, functional outcome scores, and treatment satisfaction.
Level of evidence: IV.
50. Jeans KA, Karol LA, Erdman AL, Stevens WRJr: Functional
outcomes following treatment for clubfoot: Ten-year follow-up. J
Bone Joint Surg Am 2018;100(23):2015-2023.
51. Riganti S, Coppa V, Nasto LA, et al: Treatment of complex foot
deformities with hexapod external fixator in growing children and
young adult patients. Foot Ankle Surg 2019;25(5):623-629. Ten
patients were retrospectively reviewed after hexapod external
fixator treatment for complex ankle and foot deformities, with a
plantigrade foot in eight and recurrence in two patients, and
significant overall improvement in functional outcome scores.
Level of evidence: IV.
52. Jackson TJ, Larson AN, Mathew SE, Milbrandt TA: Incidence of
symptomatic pediatric tarsal coalition in olmsted county: A
population-based study. J Bone Joint Surg Am 2021;103(2):155-161.
A population-based database from 1966 to 2018 identified 58
patients with 79 symptomatic tarsal coalitions, with 43 of these
calcaneonavicular and 27 talocalcaneal, giving estimated annual
incidences of 1.9 and 1.2 per 100,000 children, respectively. Level
of evidence: III.
53. Jackson TJ, Mathew SE, Larson AN, Stans AA, Milbrandt TA:
Characteristics and reoperation rates of paediatric tarsal
coalitions: A population-based study. J Child Orthop
2020;14(6):537-543. A comparison of 46 coalitions treated
surgically and 39 treated conservatively found at 14-year median
follow-up that patients treated surgically were less likely to
report persistent symptoms, with a low reoperation rate of 8.7%.
Level of evidence: III.
54. Yildiz KI, Misir A, Kizkapan TB, Keskin A, Akbulut D:
Functional and radiological outcomes after tarsal coalition
resections: A minimum 5-year follow-up. J Foot Ankle Surg
2019;58(6):1223-1228. This study investigated 24 talocalcaneal and
9 calcaneonavicular coalitions with minimum 5-year follow-up
after resection and found similar functional and radiographic
outcomes between the groups. There was subtalar osteoarthritis
in all talocalcaneal and most calcaneonavicular coalitions,
although the study authors found no notable functional
impairment with this. Level of evidence: IV.
55. Simon AL, Seringe R, Badina A, Khouri N, Glorion C, Wicart P:
Long term results of the revisited Meary closing wedge
tarsectomy for the treatment of the fixed cavo-varus foot in
adolescent with Charcot-Marie-tooth disease. Foot Ankle Surg
2019;25(6):834-841. Twenty-six feet in 20 patients with severe
cavovarus feet were treated with a dorsal tarsectomy across the
midfoot with plantar fascia release, Dwyer osteotomy of the
calcaneus, and first metatarsal osteotomy as necessary. The
authors reported improvement in radiographic parameters and
acceptable functional outcomes in this difficult treatment group.
Level of evidence: IV.
56. Sanpera IJr, Frontera-Juan G, Sanpera-Iglesias J, Corominas-
Frances L: Innovative treatment for pes cavovarus: A pilot study
of 13 children. Acta Orthop 2018;89(6):668-673.
C H AP T E R 6 5

Pediatric Athletic Injuries

Eric W. Edmonds MD, FAAOS

Dr. Edmonds or an immediate family member serves as a board member, owner, officer, or
committee member of the American Academy of Orthopaedic Surgeons and the Pediatric
Orthopaedic Society of North America.

ABSTRACT
Children can sustain injuries that are very similar to those of
adults, but their growth potential, activity level, lack of physiologic
maturity, and lack of life experience regarding best choices place
them at particular risk for recurrent pathology, failure to return to
full activity, or long-term disability. Although the breadth of
pediatric athletic injuries is quite substantial, it is important for the
orthopaedic surgeon to be knowledgeable about the most common
injuries, which include Li le Leaguer’s shoulder, Li le Leaguer’s
elbow, anterior shoulder instability, and medial epicondyle
avulsion fractures, to guide practice and educate patients.
Keywords: anterior cruciate ligament; childhood; medial
epicondyle; osteochondritis dissecans; patellofemoral instability;
shoulder instability

Introduction
Pediatric athletic injuries are steadily increasing, especially as a
result of early sport specialization. It is important to discuss the
prevalence of these injuries and be aware of the most common
types of injuries to implement prevention strategies and to provide
the best method of management.

Prevalence of Injury
Injury prevalence in the pediatric athlete appears to be increasing
over recent years, and it is believed to be, at least in part, because of
youth athletes’ specialization. 1 A 2020 systematic review found that
the mean age of an injured athlete was 14.5 years, and that sport
specializers were at significantly higher risk than those who were
only sampling a sport. However, other factors related to age may
play a role in both the risk for type and pa ern of injury seen in this
group, 2 particularly during periods of rapid growth. Injuries
associated with sports participation in children often occur in the
shoulder, elbow, knee, and ankle.

Shoulder

Little Leaguer’s Shoulder

When young athletes sustain an injury that is a result of overuse,
they are most often engaged in an activity involving overhead
throwing. Proximal humeral epiphysiolysis, or Li le Leaguer’s
shoulder, is a common childhood sports injury that tends to occur
in children ages 13 to 16 years, and the treatment is always
nonsurgical. Recognizing the condition and how to prevent it from
occurring can be difficult.
A 2020 study that prospectively enrolled 10- to 12-year-old
baseball players and followed them over time found that
approximately 60% of them had positive dominant shoulder MRI
findings not present in their nondominant shoulder. 3 Factors that
appeared to contribute to the MRI changes included year-round
play (P = 0.016), increased number of innings pitched (P = 0.046),
spending rest innings as the catcher (P = 0.039), and a higher pitch
count (P = 0.033). Single-sport athletes were significantly more
likely to have abnormal MRI findings (P = 0.043) when compared
with multisport athletes.
Although it is important to recognize epiphysiolysis and treat
patients appropriately to reduce the risk of physeal closure, it is
even more important to educate families on how to avoid overuse
of the arm, thus preventing the injury. One study demonstrated at 2
months of rest that one-fifth of the athletes still reported the
presence of pain. 4 For those who did return to sport, 43%
completely resumed play, 33% partially resumed play, and 24%
failed to return to sport. After 6 months, 25% of the participants
had a recurrence of pain in the shoulder. Factors associated with
poor outcomes included longer period from initial presentation to
throwing prohibition and poor shoulder flexibility. Therefore,
recommendations for management include complete rest from
throwing as soon as the pathology is identified and the initiation of
an upper body stretching program before resumption of throwing
at 2 months.

Anterior Shoulder Instability

Shoulder instability in the young athlete is understood to be a
complex problem, with many factors playing into both the etiology
and the outcomes. Because one-fifth of all shoulder dislocations
occur in people younger than 20 years, it is important to
understand the natural history of this pathology in children. 5 A
2019 review highlighted that several systematic reviews reported
the recurrence rate for young patients to be higher than 70%. 5 The
authors indicated that even though the historical approach to
treatment for patients with first-time dislocations has been
nonsurgical, there is a current shift in the literature advocating for
early surgery in this high-risk population because of the high risk
of joint damage with recurrent instability.
There may yet be room for a more conservative approach to
management if there is a be er understanding of underlying
pathology. A 2020 study a empted to describe the concept of
functional shoulder instability. 6 Through a robust investigation
that included a pathology-specific questionnaire, standardized
clinical scores, clinical examination, psychological evaluation, video
and dynamic fluoroscopy MRI, the authors proposed that most of
the functional instability (78%) was based on certain positions of
the shoulder and that 72% was not controllable. Moreover, most
patients (approximately 78%) had posterior instability, with only
17% having anterior instability and 6% showing multidirectional
instability. It was also noted that there were often glenoid shape
alterations or hyperlaxity that may have contributed to the findings
of functional instability.
Some factors that play into outcomes are not all based on
physiology. A 2020 study explored the effect of insurance status as a
potential barrier to successful outcomes in children with shoulder
instability. 7 The study authors found that privately insured patients
were both evaluated and obtained magnetic resonance images at a
rate of about four to five times faster (P < 0.001) than publicly
insured patients. Presumably because of the delay in care, the
publicly insured patients were twice as likely to have secondary
bony injuries (P = 0.016). The risk of recurrent instability, even after
stabilizing surgery, was still significantly greater in the publicly
insured patients (P = 0.022), indicating that even after establishing
care and initiating treatment these patients are still at a higher risk
for poor outcomes.
Therefore, surgical stabilization in this younger cohort, in its
current state, may not solve the issue of recurrent instability. Two
studies demonstrated evidence that recurrence may be as high as
50% in the adolescent population after surgery, especially as the
patients are followed for more than 10 years 8 or if they participate
in a contact sport such as rugby. 9 There may be an association with
age, with a particular cutoff at approximately 16 years of age for the
recurrence seen in contact sports (P = 0.0002). 9 These same study
authors noted a higher incidence of Hill-Sachs lesions (P = 0.0002)
and bony Bankart lesions (P = 0.009) compared with adult control
patients; however, they concluded that age was a more significant
contributor to recurrent instability after surgery than the presence
of bone loss. Specific to youth rugby players, it was concluded that
at the time of index surgery, those younger than 16 years would
have 2.2 times the risk of further instability with a potential
recurrence rate as high as 93%.
In contrast to the previous study, another study published in
2021 that evaluated the risk factors for recurrence in those with
early failure (<2 years) compared with a matched cohort without
recurrent shoulder instability during that early time frame (mean
follow-up, almost 5.5 years) found that bone loss, morphology,
and patient age were factors significant to outcomes. 10 The study
authors found with univariate analysis that increased glenoid bone
loss (P = 0.039), decreased glenoid retroversion (P = 0.024), and
more than one instability event before surgery (P = 0.017) were risk
factors for subsequent recurrent instability after surgery. A
multivariate regression analysis revealed values that could predict
future recurrence, independent of each other: glenoid retroversion
less than 6°, skeletal immaturity, and more than one prior
instability event. Interestingly, the risk of recurrence increased
threefold in patients with two of those independent risk factors and
increased fourfold in patients with all three risk factors.
Although contact sports have been implicated in the risk for
recurrent instability, as noted previously, another study from 2019
with findings of recurrent instability in one-third of patients
studied less than 4 years after stabilization surgery did not find that
type of sport was associated with risk for recurrent instability in
this adolescent age group. 11 Although contact sport participation
trended to be important, it was not significant. However, the study
authors did find that 89% of those who redislocated the shoulder
had a Hill-Sachs lesion (P = 0.048). In conjunction with the previous
study, the associated osseous pathology seen in this age group may
be the more predictive factor. Another study that compared the
outcomes of remplissage performed in adolescents with anterior
instability with a matched control cohort found a significantly
higher rate of recurrence in patients undergoing Bankart repair
only (47%) compared with patients undergoing Bankart repair plus
remplissage (13%, P = 0.04). 12 It was concluded that the addition of
the remplissage procedure to a Bankart repair may not only fill the
Hill-Sachs defect, but it may also augment stability through a
mechanism of posterior capsulorrhaphy (Figure 1).

Figure 1 Line drawing demonstrating the potential posterior capsulorrhaphy

effect of a remplissage procedure (arrows demonstrate direction of tightening) in
the setting of anterior shoulder stabilization surgery that limits the forward
excursion of the humerus on the glenoid without sacrificing shoulder range of
motion.

Another approach to minimize the risk for recurrence after

surgery is the conversion to open repair versus the current
mainstay of arthroscopic Bankart repair. 13 With shorter follow-up
(minimum 2 years), the adolescent patients in this cohort had no
instability events and excellent outcome scores. The only poor
outcome in the group, a ributed to the open surgical approach, was
a small loss of external rotation. Therefore, the authors
recommended that an open stabilization procedure was a be er
treatment option in the contact athlete than in the overhead or
throwing athlete.
 With such high rates of recurrent instability after primary
surgery in these young athletes, it is important to consider possible
courses of management for recurrence. A 2020 review highlighted
that surgery is still an option (just the same as in adult patients)
with particular focus on revising the Bankart repair but further
treating all the bony pathology even to the point of considering a
Latarjet procedure. 14 The rate of recurrence after a repeat
stabilization surgery remains at approximately one-third of those
undergoing the second procedure. However, in a systematic review
published in 2019, it was found that despite the high rate of
recurrent instability and revision surgery, approximately 80% of
adolescent athletes who undergo Bankart repair for traumatic
anterior shoulder instability return to their preinjury level of play. 15

Elbow

Little Leaguer’s Elbow

The spectrum of this pathology can range for the classic medial
epicondyle apophysitis (edema and widening), fragmentation of the
medial epicondyle, edema of the distal humeral metaphysis, and
partial disruption of the ulnar collateral ligament. 16 Management
tends to be conservative in nature and twofold: education with an
intent to prevent pathology (such as applying pitch-counts to youth
baseball) and modifications of activity once the symptoms start (no
throwing, casting, and/or medial scapular stabilizing physical
therapy). Surgery is rarely indicated.
Recent evidence regarding Li le Leaguer’s elbow is discussed in
a 2020 study. 17 MRI findings in a single season were reviewed in
another study by the same authors. 3 , 16 The natural history of those
findings with repeat MRI after 3 years was reviewed. The authors
discovered that in 58% of the children studied, MRI revealed
pathology of the dominant arm, with 80% demonstrating either
progressive lesions or new lesions (43%). Year-round play was a
significant predictor of tenderness to elbow palpation (P = 0.027),
and during that 3-year period, 12% of the players required active
treatment for elbow pain (including casting for pain). The authors
also noted that in the cohort that continued to play baseball, there
was a statistically significant change in the dominant arm’s internal
and external rotation compared with that of the nondominant arm.

Medial Epicondylar Avulsion

The management of medial epicondylar fracture of the humerus
has evolved over the past decade or so, as radiographic assessment
and potential risk to outcomes have been studied. A recent discrete
choice experiment evaluating preferences for management via
clinical case vigne es identified that associated elbow dislocation
and the amount of fracture displacement were the only a ributes
that significantly influenced surgeons’ decision to perform surgery.
18
The study found that for every 1-mm increase in displacement,
surgeons tended to favor a surgical approach by a factor of 0.09.
One-half of the surgeons in the study preferred a surgical approach
for all the clinical vigne es. Interestingly, for the other half, the
decision to perform surgery was significantly based on the degree
of fracture displacement but without standardization regarding
how much displacement would affect patient outcomes. An
association with dislocation is considered by some to be an
appropriate indication to achieve relative elbow stability with bone
fixation in the se ing of surrounding soft-tissue disruption, but the
validity of this indication remains untested.
Many publications have highlighted the inability to accurately
define the true amount of displacement on standard AP and lateral
elbow plain radiographs, so a ention has been directed to be er
evaluation of this fracture and its displacement. 19 A 2019 study
a empted to validate findings using an axial radiographic view to
identify the anatomic orientation of the medial elbow epicondylar
physis in children. On average, the medial epicondylar apophysis
was angled distally 36° and posteriorly 45° relative to the distal
humerus, which is helpful in understanding the orientation for
surgical reduction. Moreover, the authors confirmed that the AP
radiograph significantly underestimated displacement relative to
the axial radiograph at all displacements greater than 5 mm.
Perhaps more important than recognizing the ability of plain
radiographic views to assess this fracture is the ability of CT to
change the treatment decision according to a 2019 study. 20 First, the
authors confirmed the aforementioned failure of the AP radiograph
to accurately represent the amount of displacement for medial
epicondylar fractures, with significant differences from measures
on the axial CT scans. Second, treatment plans were changed
because of the increased amount of displacement seen on CT scans
compared with plain radiographs. The findings of past studies
evaluating the inadequacy of plain radiograph and the potential
benefit of three-dimensional imaging should prove valuable in
a empts to understand forthcoming studies comparing outcomes
related to the amount of displacement on an AP radiograph,
because it is now understood that the direction of displacement is
not truly observable on an AP radiograph (Figure 2).
 Figure 2 Fracture displacement occurs along vectors of muscle attachment
pull.In the line drawing, the AP view presumes that the elbow is fully extended to
achieve an orthogonal view to the vector of the attached flexor-pronator mass
(arrow). The lateral view demonstrates that same muscle vector, but with the
elbow flexed 90°. Most children do not hold their elbow fully extended in the
setting of an acute fracture, so an AP radiograph likely will underestimate
displacement.

With improved understanding of medial epicondylar fracture

pa erns and displacement have come advances in fracture
management. A 2020 biomechanical and clinical study recently
compared three different fracture fragment fixation methods in
children because the physis and the fracture pa ern can dictate the
need to use something other than a screw, such as Kirschner wires
or suture anchors. 21 The study authors found that from a
biomechanics standpoint (via a pig model), screws were stronger
and stiffer, and this reached statistical significance. However, all
three fixation strategies resulted in radiographic union, and only a
single patient (in the screw group) lost reduction. Of note, the
suture-anchor group was less likely to require a second surgery for
implant removal (P < 0.05), which was calculated to be a cost savings
of 10% compared with screw fixation.
 In another study, the ability of washers to affect the outcome of
medial epicondylar fracture fixation was assessed. 22 It is thought
that the washer-screw construct may prevent fracture
fragmentation and penetration, but concerns exist that it will
increase the rate of secondary surgery for implant removal for
painful prominence. The study authors found that 31 of 137
children (23%) underwent implant removal; this group did not have
a washer nor were they athletes. Moreover, the addition of the
washer did not affect subsequent recovery of elbow range of
motion. Therefore, the recommendation is to use a washer-screw
construct when risk of fragmentation is noted in preoperative
planning.
A 2021 study compared the patient position (supine versus
prone) in the management of medial epicondylar fractures, with the
understanding that prone positioning improves exposure of the
fragment (as a posterior structure) but with the need for extensive
repositioning. 23 The positioning process added an average of
approximately 30 minutes to each case (P < 0.001), but with no
difference in actual tourniquet time. Despite a statistical difference
of 1 mm in the ability to achieve a reduction being noted, with
be er results with prone positioning, it remains to be seen whether
that statistical difference is clinically meaningful.
Ultimately, the question remains as to whether surgery improves
outcomes in children with medial epicondylar fractures. One group
a empted to compare those treated with and without surgery by
developing propensity scores (probability of surgical treatment)
and creating a matched cohort of patients. 23 No significant
difference was found in the ability to return to sports or the median
time to return to play. Moreover, there were no noted differences in
pain, the need for physical therapy, or complications. A second
group a empted a similar study but used AP radiographs as the
main contributor to matching cohorts and followed patients for a
mean of 2.5 years. 24 With mean displacements of approximately 8
mm in both cohorts, it was determined that the children who
underwent nonsurgical treatment had less pain (based on PedsQL
Pediatric Pain) and be er cosmetic outcomes (visual analog scale
score of 95 versus 87, P = 0.007). Moreover, the nonsurgically treated
children all returned to preinjury sports participation, whereas 15%
of the children treated surgically had to scale back their sporting
activities. Therefore, the results of this study suggest that surgery
does not improve outcomes in children with this injury. It should
be noted that the role of measured displacement (or how
displacement is measured) may yet still prove to be important in
future studies.

Hip, Knee, and Ankle

Pelvis Hip Avulsion Fracture

Historically, the management of hip avulsion fractures has been
nonsurgical, but a recent study made an assessment of surgery on
apophyseal avulsions of the ischial tuberosity in adolescents to
improve outcomes. 25 Adolescents with a mean fragment
displacement of approximately 3 mm underwent surgical
intervention with good to excellent outcome scores on the Perth
Hamstring Assessment Tool, with 91% returning to preinjury
sports participation. However, only about two-thirds of the patients
were able to participate in those sports at a full or nearly full level
of participation.

Anterior Cruciate Ligament Injury

Children are particularly at significant risk for complications after
anterior cruciate ligament (ACL) reconstruction because of activity
levels and open physes. One particular complication after
reconstruction is an injury to the contralateral ACL, and a 2020
study evaluating almost 500 children found that 7% sustained this
complication type after their index ACL surgery. 26 The risk factors
driving this complication were female sex and younger age. In
multivariate analysis, female patients had 3.5 times higher odds
compared with males, and each year of youth increased the odds by
1.3.
Some authors have a empted to improve the risk of having a
narrow-diameter autograft via allograft augmentation for
hamstring ACL reconstruction. A recent study in patients within 2
years of complete skeletal maturity found that when compared with
upsizing the autograft, the augmented with allograft constructs
failed at a higher rate (20%) compared with the four-strand or five-
strand autografts (14% and 12%, respectively). 27 Therefore, the
authors recommend tripling the semitendinosus autograft rather
than augmenting the autograft with an allograft. Interestingly,
similar to the previous study evaluating contralateral ACL
pathology, this group also found a 7% rate of ACL tears.
Another unique issue related to childhood ACL is the congenital
absence of the ligament. A 2019 study evaluated the surgical
management of this group (mean age 12.6 years) with a mean
follow-up of almost 3 years. 28 Reconstructions were performed with
intra-articular/extra-articular physeal sparing reconstruction with
either iliotibial band, autograft hamstring, bone-patellar tendon-
bone, or allograft; half of the knees required additional ligamentous
reconstruction for their associated deficiencies. All the patients
experienced improvement in their International Knee
Documentation Commi ee (IKDC) scores, Lachman test, and pivot
shift test, and only one child required revision surgery to
reconstruct the posterior cruciate ligament. Therefore, hypoplasia
or agenesis of the ACL may be successfully reconstructed with at
least early outcomes of restored knee stability.
Failure of ACL reconstruction is not uncommon, as noted
previously. A 2019 study evaluated the outcomes of revision ACL
reconstruction in children compared with a primary reconstruction
cohort. 29 At a mean follow-up of 4.4 years, the revision cohort had a
greater number of meniscal tears and cartilage injuries and lower
Single Assessment Numeric Evaluation scores, Lysholm scores, and
overall satisfaction. Unfortunately, the revision cohort also had a
higher rate of graft failure compared with the primary cohort (21%
versus 9%, respectively). Moreover, less than one-third of the
revision ACL cohort ultimately returned to the same level of sports
participation.
Perhaps the best approach is not performing a reconstruction but
instead undertaking what has been termed a bridge-enhanced ACL
repair that combines suture repair with a specific extracellular
matrix scaffold. 30 Early results comparing the repair group to
standard four-strand hamstring autograft demonstrated no failures
in either group at 2 years. Although the sample size was small (10
patients in each cohort), there were no differences in 2-year laxity
testing or single leg hop testing, but there was a difference in the
hamstring strength, with the repair cohort having significantly
higher strength with their preserved muscles.
One confounding factor to outcomes of ACL reconstruction is
patients’ ability to restore normal lower extremity kinematics.
Therefore, most patients undertake extensive postoperative
rehabilitation, yet there is no true standardization in the protocols.
A poll was taken, asking surgeons who specialize in pediatric sports
medicine to identify when key transitional points should be made
in their patients undergoing ACL reconstruction. 31 There was
substantial agreement (80%) that jogging could be initiated after 3
months postoperatively; progression to modified sports activity and
release to full sports participation varied significantly (with full
sports participation occurring within 6 to 12 months). Knee
strength was identified as the main determinant to progress to
modified sports activity, but without any consistency in method of
testing. Finally, one-half of the surgeons recommended using a
functional ACL brace upon release to full activity.

Tibial Spine Fracture

Displaced tibial spine/eminence fractures are most commonly
managed with either suture or screw fixation; many biomechanics
studies have been performed trying to determine the best method.
A 2019 clinical study directly comparing the two methods
demonstrated no differences in instability, range of motion,
arthrofibrosis, ability to return to sport, or the duration of return. 32
However, the suture cohort did demonstrate more postoperative
fragment elevation on imaging compared with the screw cohort;
yet, the screw cohort had a higher reoperation rate, primarily for
implant removal (P < 0.001), with an odds ratio of 2.9 (P = 0.03).
As with ACL injuries, high rates of reported injuries such as
meniscal tear (40% to 70%) occurring in association with tibial
spine fractures are reported in the literature. A 2020 multicenter
study found that 35% of tibial spine fractures had a concomitant
injury, and the importance of preoperative MRI was assessed. 33
Interestingly, patients undergoing preoperative MRI demonstrated
concomitant injuries 45% of the time, whereas those who did not
have preoperative MRI demonstrated these injuries only 27% of the
time. The only associated pathology noted more frequently without
preoperative MRI was soft-tissue entrapment within the fracture
site. Given the propensity for lateral meniscal tear in association
with tibial spine fractures, and the fact that almost 90% of the
associated injuries required intervention, preoperative MRI was
recommended to identify concomitant injuries that may necessitate
subsequent management.

Meniscal Injury
The discoid meniscus is the most commonly seen disorder of the
knee in children. Patients may be asymptomatic and the condition
found incidentally, or they may be symptomatic after sustaining a
tear or instability (anteriorly or posteriorly based). A 2021 study
a empted to ascertain the ability of clinical examination, MRI, or
patient-reported outcomes to predict pathology of the discoid
meniscus (either torn or unstable). 34 At a mean age at surgery of
approximately 10 years, it was noted that neither physical
examination nor patient-reported outcomes could distinguish
between the torn or the unstable discoid meniscus. MRI was only
75% sensitive and 50% specific at identifying a torn discoid
meniscus. Therefore, when discoid pathology is considered,
arthroscopy becomes the standard by which to determine the type
of pathology (tear or instability). This understanding may be
important when counseling families regarding postoperative
management, as the different pathologies often require different
surgical measures.
Sometimes, however, both saucerization and repair of the discoid
meniscus are required for successful management, and the authors
of a 2021 study reported results at a mean follow-up of 4.5 years. 35
These authors found that at a mean age of 12 years, only 9% of
patients underwent revision meniscus surgery, with no indication
of type of repair playing a role in those outcomes. Mean IKDC score
was 96%, and 89% of patients reported returning to the same or
higher level of activity.
Children do sustain meniscal injuries that are not related to the
discoid lateral meniscus, and one type of tear that is currently
seeing increased clinical interest is the ramp lesion of the posterior
horn of the medial meniscus. It is considered a contributor to
anterior tibial translation that may play a role in ACL pathology
and outcomes. Because of the nature of the ramp lesion (hidden
near the meniscocapsular junction posteriorly), it runs the risk of
being missed during clinical workup (Figure 3). Another 2021 study
a empted to compare MRI with arthroscopy in identifying the
ramp lesion. 36 The radiologists were blinded to the arthroscopic
findings, and it was determined that knees with a ramp lesion
identified by arthroscopy were more likely to have MRI findings of
medial meniscal tear (P = 0.005), peripheral meniscal irregularity (P
= 0.001), junctional T2-weighted signal (P < 0.001), or
meniscocapsular ligament tear (P < 0.001). Therefore, changes near
the posterior horn of the medial meniscus on MRI should be an
indicator for surgical vigilance during arthroscopy.
 Figure 3 Line drawing representing cross-sectional views of the various types
of ramp lesions in the posterior horn of the medial meniscus: from left to right, a
tear in the adjacent posterior capsule, a tear in the posterior horn itself, or a
partial undersurface tear of the posterior horn.Unrecognized, all varieties can
promote instability with increased anterior translation of the medial tibia,
especially in the setting of anterior cruciate ligament pathology.

Patellofemoral Instability
The pathoanatomy of patellar instability is complex, and one of the
factors that may play a role is underlying genu valgum. A 2019
study evaluated isolated hemiepiphysiodesis in children to treat
recurrent patellofemoral instability and found success in 80% of
cases at 1-year follow-up. 37 Outcomes were further assessed based
on radiographic parameters known to play a role in risk for
instability, and both the tibiofemoral angle and patellar tilt angle
were found to be significantly improved. This technique may be
considered for those with only genu valgum as a risk factor and in
those with enough skeletal immaturity to undergo growth
correction.
Most children have more than one risk factor for instability, and
therefore most published studies on surgical correction of
patellofemoral instability appear to incorporate a reconstruction of
the medial retinacular structures, particularly the medial
patellofemoral ligament (MPFL). A recent study looked to combine
a reconstruction of the MPFL and the slightly larger medial
quadriceps tendon-femoral ligament 38 (Figure 4). Children with
this combined construct also underwent concomitant
hemiepiphysiodesis 20% of the time, and one-fourth of them had
already undergone an ipsilateral surgery for the same diagnosis. At
a mean follow-up of 2 years, the mean Kujala score was 86 and the
Pedi-IKDC was 81.5; 8% of the children required a revision surgery
in the form of a tibial tubercle osteotomy. The success noted
reduces the risk of patellar fracture by minimizing tunnel
placement, and it allowed three-fourths of the athletes to return to
sports at a mean of 6 months.
Figure 4 The confluence of the stabilizing medial retinacular structures are
represented in this line drawing demonstrating a conjoint origin on the femur with
spread from mid-patella (medial patellofemoral ligament [MPFL]) to the lower
medial quadriceps tendon (medial quadriceps tendon–femoral ligament
[MQTFL]).
 The tibial tubercle osteotomy is an option in patients with high
tibial tubercle–trochlear groove (TT-TG) intervals, but it is not
always possible in young athletes because of their open or closing
tubercle apophyses. Therefore, a 2019 study of 90 patients who
underwent isolated MPFL reconstruction without a tibial tubercle
osteotomy with a mean TT-TG interval of approximately 15 mm
found that after 2 years only 4% reported patellofemoral instability.
39
For athletes, return to sports participation occurred in
approximately 90% at a mean 9 months, with a Kujala score of 89.5
and IKDC of 82.6 at 2 years. Therefore, even with a few children
with TT-TG greater than the nominal 20-mm cutoff, an isolated
MPFL reconstruction proved successful.
However, some controversy still exists regarding when MPFL
reconstruction should be performed: whether it is be er to wait
until the patient demonstrates recurrent instability or to proceed
with surgical intervention even after a first-time patellar
dislocation. One scenario indicative of surgical management is
when first-time patellar dislocations result in an associated
chondral or osteochondral loose body. A 2019 study evaluated
adolescents who underwent surgical management for the loose
fragment both with and without concomitant MPFL reconstruction.
40
Of the 14 children enrolled, almost two-thirds experienced
recurrent instability at a mean of 4 years, with approximately 40%
ultimately undergoing MPFL reconstruction. TT-TG intervals did
play a role in this overall risk for recurrence, with those having a
TT-TG interval greater than 15 mm experiencing recurrence at a rate
of 75% and those with TT-TG interval greater than 20 mm having
recurrence rates of 86%. Repair of the ligament or plication of the
medial retinaculum at the time of the index procedure did not
change the overall risk for recurrence. The authors concluded that
MPFL reconstruction during surgery for a loose articular fragment
secondary to patellofemoral instability should be considered.
So who is at risk for a second patellofemoral dislocation? The
authors of a 2021 study a empted to determine which patients are
at risk for a second patellofemoral dislocation by evaluating known
radiographic risk factors on MRI in patients who presented after a
first dislocation. 41 At a median age of 14 years, and just over a
median follow-up of 1 year, a second event was noted in almost 60%
of patients. Similar to the aforementioned study regarding surgery
for loose intra-articular fragments, the TT-TG had excellent
correlation (intraclass correlation coefficient >0.8) with predicting a
second event, as did the tangential axial width of the patella, the
tangential axial trochlear width, the axial width of the patellar
tendon beyond the lateral trochlear ridge, and the tibial tubercle to
lateral trochlear ridge distance. However, after multivariable
logistic regression analysis, only the tibial tubercle to lateral
trochlear ridge distance proved to be an independent predictor of
recurrent instability, P = 0.003. Perhaps these measures can help
determine when an MPFL reconstruction should be performed in
the adolescent with first-time patellofemoral dislocation.

Osteochondritis Dissecans of the Knee

Management of osteochondritis dissecans (OCD) of the knee has
been consistent over the past century, but the question remains
regarding when the surgeon should a empt nonsurgical
management or proceed to surgical management. One factor that
often plays into the decision tree is cost-effectiveness of treatment;
in 2021 a group a empted to answer the question. 42 Multiple
factors were taken into consideration: transition probabilities, costs
(in 2019 US dollars), health state utility data, and duration to
healing. From these values the incremental cost-effectiveness ratio
was derived and the quality-adjusted life-year determined. The
authors identified that early drilling (within 6 weeks of the first
evaluation in clinic) was more effective (quality-adjusted life-year,
2.51) compared with conservative management (quality-adjusted
life-year, 2.27), but it was more costly and yet more cost-effective for
both the payor and society. Therefore, even though historical
literature suggests that management of OCD of the knee should
begin with nonsurgical measures, the study authors concluded that
that surgery may be cost-effective from both payor and societal
perspectives.
Despite the cost-effectiveness study, there is still opportunity to
consider nonsurgical management that ranges from activity
modification to casting. One treatment method that is often used is
the unloader brace that is believed to achieve the objective of
shifting the biology at the OCD site but still allowing play by
children with this pathology. Therefore, in a 2020 study, more than
300 children with OCD of the knee were studied, comparing one-
half who received an unloader brace and the other half who
underwent other nonsurgical management. 43 The mean age was
11.5 years, and successful treatment was achieved in almost 60% of
children at a median duration of 9 months. However, the authors
concluded that the unloader brace did not improve the odds of
avoiding surgical intervention because those with the brace
underwent surgery 50% of the time compared with those without
the brace at 35% of the time, P = 0.02.
When surgery is being considered, it is important for the
orthopaedic surgeon to be prepared for lesions with stable intact
articular cartilage and those with unsalvageable cartilage. In a 2020
study assessing 10- to 25-year follow-up (mean, 19 years) on
autologous chondrocyte implantation for unsalvageable OCD
lesions, survivorship was 87% at 10 years, 85% at 15 years, and 82%
at 20 years. 44 During those years, 20% of the knees required an
additional open surgery, but only two knees (3%) underwent
arthroplasty. The authors concluded that autologous chondrocyte
implantation for unsalvageable OCD is a very durable option.
Another 2020 study looked at the rate of arthroplasty at a mean
of 14 years’ follow-up for children with OCD treated with surgery
(56%) or without surgery during childhood. 45 The authors found
that 14% of patients had persistent knee pain, 6% had symptomatic
osteoarthritis, and 3% had ultimately undergone a conversion to
total knee arthroplasty. Risk factors for persistent knee pain were
female sex, patellar lesions, and unstable lesions. Those who did
undergo arthroplasty did so at a significantly younger age (mean 52
years) in comparison to patients who did not have OCD (P = 0.004).
The long-term consequence of childhood knee OCD appears to be
early osteoarthritis, but perhaps not in every patient.

Osteochondritis Dissecans of the Ankle

OCD of the talus appears to be different in nature than that of the
knee, even to the point that the literature considers ankle OCD part
of the spectrum of osteochondral lesions of the talus.
Differentiating between the various forms that these lesions may
manifest has proven difficult, but authors of a 2021 study a empted
to discern whether the morphology of the ankle could predict the
development of OCD of the talus. 46 The authors performed an age-
matched and sex-matched cohort study of patients with childhood
talar OCD and those without, using MRI measurements of tibial
anterior surface angle, tibial shaft-both malleoli angle, tibial axis-
medial malleolus angle, anterior opening angle of the talus,
malleolar width, tibial lateral surface angle, maximal tibial
thickness, length of trochlea tali arc, and height of trochlea tali arc.
Only an increase in length of the trochlea tali arc was associated
with OCD of the talus (P = 0.015).
Another study in 2020 a empted to determine whether MRI
could distinguish between an unstable and stable osteochondral
lesion of the talus, based on radiographic measurements. 47 The
authors found that an open physis correlated with a stable
osteochondral lesion of the talus (P = 0.01), but none of the other
radiographic measures (including an effusion, an intra-articular
body, cartilage changes, subchondral disruption, T2-weighted
signal intensity rim, cysts, marginal sclerosis, or marrow edema)
could help predict whether OCD of the ankle was going to be
unstable. Therefore, further research into the ability to assess
osteochondral lesions of the talus is needed.
When surgery is ultimately performed for an osteochondral
lesion of the talus in childhood, one measure of success is the risk
for reoperation. In a 2021 study, the authors found that regardless
of initial surgical management type, one-fourth of children required
reoperation at a median duration of 31 months. 48 It seems that the
only significant finding between those who required reoperation
and those who did not was that those who required reoperation had
a lower International Cartilage Repair Society classification (P =
0.001). Compared with the success seen in OCD of the knee,
management of OCD of the talus appears to have a higher failure
rate even with surgery.
Another 2020 study evaluated the risk of osteoarthritis
developing in children treated with surgery for an osteochondral
lesion of the talus. 49 The authors evaluated only stable
osteochondral lesions of the talus and found that that the Kellgren-
Lawrence scores worsened in one-fourth of the children at less than
2 years of follow-up. No risk factors (preoperative classification,
age, physeal patency) were associated with advancing radiographic
evidence of articular degeneration (Figure 5); however, a
classification and regression tree analysis revealed that age older
than 11.5 years at index procedure could be predictive of advancing
Kellgren-Lawrence scores, with one-third of older children having
worse scores (P = 0.038). In contrast to the studies presented on
OCD of the knee with low rates of osteoarthritis, this study
suggests that OCD of the ankle carries a much greater risk of
degenerative disease in a distinctly youthful population, despite
active treatment of osteochondral lesion of the talus.
 Figure 5 A line drawing demonstrating the changes that occur with worsening
Kellgren-Lawrence grading in the ankle; highlighted areas are osteophyte
formation on the talus, distal fibula, medial malleolus, anterior/posterior plafond,
anterior talus, and narrowing of the joint space.

Summary
Childhood sports injuries run the gamut from the shoulder to the
ankle, from overuse to traumatic, and from the unstable to the
necrotic. It is important to highlight current concepts and
important new findings.

Key Study Points

Shoulder and knee instability share a common theme in that surgical management
carries a high risk of failure in children compared with adults with the same
pathology.
Surgical procedures for shoulder instability and ACL injury continue to experience a
renaissance regarding the full complement of what those surgeries should entail to
obtain better outcomes.
OCD continues to evade etiologic understanding, so treatments remain good but not
excellent.
Historical ideas about nonsurgical management for medial epicondylar fractures of
the humerus, first-time shoulder instability, and first-time patellar instability are falling
to contemporary evidence that overall outcomes may be improved with early
surgical intervention.
Annotated References
1. Carder SL, Giusti NE, Vopat LM, et al: The concept of sport
sampling versus sport specialization: Preventing youth athlete
injury—a systematic review and meta-analysis. Am J Sports Med
2020;48(11):2850-2857. A systematic review evaluated the risk of
injury secondary to sport specialization. Level of evidence: IV.
2. Wik EH, Martínez-Silván D, Farooq A, Cardinale M, Johnson A,
Bahr R: Skeletal maturation and growth rates are related to bone
and growth plate injuries in adolescent athletics. Scand J Med Sci
Sports 2020;30(5):894-903. This is a prospective comparative
analysis of children of various ages and the risk of sports injuries.
Level of evidence: II.
3. Holt JB, Stearns PH, Bastrom TP, Dennis MM, Dwek JR, Pennock
AT: The curse of the all-star team: A single-season prospective
shoulder MRI study of Li le League baseball players. J Pediatr
Orthop 2020;40(1):e19-e24. This is a prospective comparative
analysis of children who played baseball assessed over time by
repeat MRI. Level of evidence: II.
4. Harada M, Takahara M, Maruyama M, et al: Outcome of
conservative treatment for Li le League shoulder in young
baseball players: Factors related to incomplete return to baseball
and recurrence of pain. J Shoulder Elbow Surg 2018;27(1):1-9.
5. Franklin CC, Weiss JM: The natural history of pediatric and
adolescent shoulder dislocation. J Pediatr Orthop 2019;39(6, suppl
1):S50-S52. This is a meta-analysis and literature review assessing
the outcomes of shoulder instability in children. Level of
evidence: IV.
6. Moroder P, Danzinger V, Maziak N, et al: Characteristics of
functional shoulder instability. J Shoulder Elbow Surg
2020;29(1):68-78. A prospective comparative study a empted to
use fluoroscopy, video, and MRI to ascertain the existence of
functional instability in the shoulder. Level of evidence: II.
7. Hung NJ, Darevsky DM, Pandya NK: Pediatric and adolescent
shoulder instability: Does insurance status predict delays in care,
 outcomes, and complication rate? Orthop J Sports Med
2020;8(10):2325967120959330. This is a retrospective review of two
cohorts of patients treated for their shoulder instability based on
insurance status. Level of evidence: III.
8. Flinkkila T, Knape R, Sirnio K, Ohtonen P, Leppilahti J: long-
term results of arthroscopic Bankart Repair: Minimum 10 years of
follow-up. Knee Surg Sports Traumatol Arthrosc 2018;26:94-99.
9. Torrance E, Clarke CJ, Monga P, Funk L, Walton MJ: Recurrence
after arthroscopic labral repair for traumatic anterior instability
in adolescent rugby and contact athletes. Am J Sports Med
2018;46(12):2969-2974.
10. Cheng TT, Edmonds EW, Bastrom TP, Pennock AT: Glenoid
pathology, skeletal immaturity, and multiple preoperative
instability events are risk factors for recurrent anterior shoulder
instability after arthroscopic stabilization in adolescent athletes.
Arthroscopy 2021;37(5):1427-1433. This is a retrospective case-
control study that identifies risk factors that contribute to
recurrent instability in adolescents with anterior shoulder
instability. Level of evidence: IV.
11. Kramer J, Gajudo G, Pandya NK: Risk of recurrent instability
after arthroscopic stabilization for shoulder instability in
adolescent patients. Orthop J Sports Med
2019;7(9):2325967119868995. This retrospective case series
evaluated risk factors for recurrent instability after stabilization
surgery in teenage patients. Level of evidence: IV.
12. Hughes JL, Bastrom T, Pennock AT, Edmonds EW: Arthroscopic
Bankart Repairs with and without remplissage in recurrent
adolescent anterior shoulder instability with Hill-Sachs
deformity. Orthop J Sports Med 2018;6(12):2325967118813981.
13. Hatch MD, Hennrikus WL: The open Bankart repair for
traumatic anterior shoulder instability in teenage athletes. J
Pediatr Orthop 2018;38(1):27-31.
14. Bonazza NA, Riboh JC: Management of recurrent anterior
shoulder instability after surgical stabilization in children and
 adolescents. Curr Rev Musculoskelet Med 2020;13(2):164-172. This
is a systematic review of surgical stabilization procedures in
skeletally immature patients. Level of evidence: IV.
15. Kasik CS, Rosen MR, Saper MG, Zondervan RL: High rate of
return to sport in adolescent athletes following anterior shoulder
stabilisation: A systematic review. J ISAKOS 2019;4(1):33-40. A
systematic review of literature evaluated the ability to return to
sport after surgery for anterior shoulder instability. Level of
evidence: IV.
16. Pytiak AV, Stearns P, Bastrom TP, et al: Are the current li le
league pitching guidelines adequate? A single-season prospective
MRI study. Orthop J Sports Med 2017;5(5):2325967117704851.
17. Holt JB, Pedowi JM, Stearns PH, et al: Progressive elbow
magnetic resonance imaging abnormalities in li le league
baseball players are common: A 3-year longitudinal evaluation.
Am J Sports Med 2020;48(2):466-472. A prospective cohort study
followed children beyond a single season of baseball to assess for
elbow pathology. Level of evidence: II.
18. Hughes M, Dua K, O’Hara NN, et al: Variation among pediatric
orthopaedic surgeons when treating medial epicondyle fractures.
J Pediatr Orthop 2019;39(8):e592-e596. An expert opinion study
determined if there was consensus regarding the management of
medial epicondyle humerus fractures. Level of evidence: V.
19. Cao J, Smetana BS, Carry P, Peck KM, Merrell GA: A pediatric
medial epicondyle fracture cadaveric study comparing standard
AP radiographic view with the distal humerus axial view. J Pediatr
Orthop 2019;39(3): e205-e209. A radiographic study evaluated
the reproducibility of the axial view in the assessment of medial
epicondyle fractures via cadaver assessment. Level of evidence:
III.
20. Onay T, Aydemir AN, Okay E, Topkar OM, Gulabi D, Erol B:
Does computerized tomography change the treatment decision
in pediatric medial epicondyle fractures? Acta Orthop Belg
2019;85(1):79-85. A retrospective case series evaluated the
 importance of findings by CT scan to directly affect the decision-
making process regarding management choice in medial
epicondyle fractures. Level of evidence: IV.
21. Rickert KD, Sarrel KL, Sanders JS, et al: Medial epicondyle
fractures: Biomechanical evaluation and clinical comparison of 3
fixation methods used in pediatric patients. J Pediatr Orthop
2020;40(9):474-480. A cadaver comparative study evaluated
various fixation techniques for medial epicondyle fractures with
evidence from the clinical se ing. Level of evidence: III.
22. Patel NM, Gajewski CR, Ascoli AM, Lawrence JTR: Washers do
not affect the rate of implant removal or elbow motion in medial
epicondyle fractures. J Pediatr Orthop B 2019;28(6):526-529. A
retrospective case series evaluated the risk of requiring implant
removal secondary to the utilization of a washer in the fixation
construct for medial epicondyle fractures. Level of evidence: IV.
23. Baghdadi S, Weltsch D, Arkader A, Harwood K, Lawrence JTR:
Open reduction of medial epicondyle fractures in the pediatric
population: Supine versus prone position. J Pediatr Orthop
2021;41(5):273-278. A retrospective review of cases compared the
surgical approach to management of medial epicondyle fractures.
Level of evidence: III.
24. Grahn P, Hämäläinen T, Nietosvaara Y, Ahonen M: Comparison
of outcome between nonoperative and operative treatment of
medial epicondyle fractures. Acta Orthop 2021;92(1):114-119. This
is a retrospective comparative study looking at the outcomes
after the management of medial epicondyle fractures. Level of
evidence: III.
25. Best R, Meister A, Huth J, Becker U, Meier M: Surgical repair
techniques, functional outcome, and return to sports after
apophyseal avulsion fractures of the ischial tuberosity in
adolescents. Int Orthop 2021;45(7): 1853-1861. A retrospective
case series evaluated the outcomes after surgical management of
pelvic avulsion fractures. Level of evidence: IV.
26. Patel NM, Bram JT, Talathi NS, DeFrancesco CJ, Lawrence JTR,
Ganley TJ: Which children are at risk for contralateral anterior
cruciate ligament injury after ipsilateral reconstruction? J Pediatr
Orthop 2020;40(4):162-167. A case-control study evaluated the risk
of contralateral limb injury rate following ACL reconstruction.
Level of evidence: IV.
27. Perkins CA, Busch MT, Christino M, Herzog MM, Willimon SC:
Allograft augmentation of hamstring anterior cruciate ligament
autografts is associated with increased graft failure in children
and adolescents. Am J Sports Med 2019;47(7):1576-1582. A
retrospective cohort study compared hybrid graft (allograft and
autograft) versus increasing strands of autograft in ACL
reconstruction. Level of evidence: III.
28. Sachleben BC, Nasreddine AY, Nepple JJ, Tepolt FA, Kasser JR,
Kocher MS: Reconstruction of symptomatic congenital anterior
cruciate ligament insufficiency. J Pediatr Orthop 2019;39(2):59-64.
A retrospective case series evaluated the outcomes of ACL
reconstruction in the se ing of ACL congenital insufficiency.
Level of evidence: IV.
29. Ouille e R, Edmonds E, Chambers H, Bastrom T, Pennock A:
Outcomes of revision anterior cruciate ligament surgery in
adolescents. Am J Sports Med 2019;47(6):1346-1352. A retrospective
case series evaluated the outcomes of revision ACL surgery in
adolescent patients. Level of evidence: IV.
30. Murray MM, Kalish LA, Fleming BC, et al: Bridge-enhanced
anterior cruciate ligament repair: Two-year results of a first-in-
human study. Orthop J Sports Med 2019;7(3):2325967118824356. A
prospective cohort study evaluated an enhanced ACL repair
outcome. Level of evidence: II.
31. Greenberg EM, Greenberg ET, Albaugh J, Storey E, Ganley TJ:
Anterior cruciate ligament reconstruction rehabilitation clinical
practice pa erns: A survey of the PRiSM Society. Orthop J Sports
Med 2019;7(4): 2325967119839041. This is an expert opinion
survey from a society of pediatric sports medicine providers
 evaluating for practice pa erns in the management of ACL
injury. Level of evidence: V.
32. Callanan M, Allen J, Flutie B, et al: Suture versus screw fixation
of tibial spine fractures in children and adolescents: A
comparative study. Orthop J Sports Med
2019;7(11):2325967119881961. A retrospective comparative study
evaluated the fixation of tibial eminence fractures in children.
Level of evidence: III.
33. Shimberg JL, Aoyama JT, Leska TM, et al: Tibial spine fractures:
How much are we missing without pretreatment advanced
imaging? A multicenter study. Am J Sports Med 2020;48(13):3208-
3213. A multicenter retrospective cohort study evaluated the
importance of preoperative MRI in the assessment of tibial spine
fractures. Level of evidence: III.
34. Hampton M, Hancock G, Christou A, Ali F, Nicolaou N: Clinical
presentation, MRI and clinical outcome scores do not accurately
predict an important meniscal tear in a symptomatic discoid
meniscus. Knee Surg Sports Traumatol Arthrosc 2021;29(9):3133-
3138. A retrospective cohort study evaluated the ability of MRI to
predict the presence of discoid meniscus tear. Level of evidence:
III.
35. Perkins CA, Busch MT, Christino MA, Willimon SC:
Saucerization and repair of discoid lateral menisci with
peripheral rim instability: Intermediate-term outcomes in
children and adolescents. J Pediatr Orthop 2021;41(1):23-27. A
retrospective case series evaluated the outcomes of repair in the
se ing of discoid rim instability after saucerization. Level of
evidence: IV.
36. Nguyen JC, Bram JT, Lawrence JTR, et al: MRI criteria for
meniscal ramp lesions of the knee in children with anterior
cruciate ligament tears. AJR Am J Roentgenol 2021;216(3):791-798.
This is a retrospective review to determine the ability for MRI to
determine the presence of a ramp lesion of the medial meniscus
in children with ACL tears. Level of evidence: IV.
37. Tan SHS, Tan LYH, Lim AKS, Hui JH: Hemiepiphysiodesis is a
potentially effective surgical management for skeletally
immature patients with patellofemoral instability associated with
isolated genu valgum. Knee Surg Sports Traumatol Arthrosc
2019;27(3):845-849. This is a prospective cohort study evaluating
the ability for growth modulation surgery to manage patellar
instability in the skeletally immature patient. Level of evidence:
II.
38. Spang RC, Tepolt FA, Paschos NK, Redler LH, Davis EA, Kocher
MS: Combined reconstruction of the medial patellofemoral
ligament (MPFL) and medial quadriceps tendon-femoral
ligament (MQTFL) for patellar instability in children and
adolescents: Surgical technique and outcomes. J Pediatr Orthop
2019;39(1):e54-e61. This is a retrospective case review of teenagers
who underwent a modification of the MPFL reconstruction with
addition of medial quadriceps tendon–femoral ligament
reconstruction. Level of evidence: IV.
39. Erickson BJ, Nguyen J, Gasik K, Gruber S, Brady J, Shubin Stein
BE: Isolated medial patellofemoral ligament reconstruction for
patellar instability regardless of tibial tubercle-trochlear groove
distance and patellar height: Outcomes at 1 and 2 years. Am J
Sports Med 2019;47(6): 1331-1337. This is a retrospective case
review evaluating the outcomes of MPFL reconstruction without
concomitant tibial tubercle osteotomy. Level of evidence: IV.
40. Pedowi JM, Edmonds EW, Chambers HG, Dennis MM,
Bastrom T, Pennock AT: Recurrence of patellar instability in
adolescents undergoing surgery for osteochondral defects
without concomitant ligament reconstruction. Am J Sports Med
2019;47(1):66-70. This is a retrospective case series evaluating the
outcomes of children treated for osteochondral fractures
sustained during a patellar instability event. Level of evidence:
IV.
41. Weltsch D, Chan CT, Mistovich RJ, et al: Predicting risk of
recurrent patellofemoral instability with measurements of
extensor mechanism containment. Am J Sports Med
 2021;49(3):706-712. This is a retrospective cohort assessing
parameters related to recurrence of patellar instability. Level of
evidence: III.
42. LeBrun DG, DeFrancesco CJ, Fabricant PD, Lawrence JTR: Cost-
effectiveness analysis of nonoperative management versus early
drilling for stable osteochondritis dissecans lesions of the knee in
skeletally immature patients. Arthroscopy 2021;37(2):624-634.e2.
This is an economic and decision analysis regarding the
management of OCD lesions of the knee. Level of evidence: III.
43. Tepolt FA, Kalish LA, Heyworth BE, Kocher MS: Nonoperative
treatment of stable juvenile osteochondritis dissecans of the
knee: Effectiveness of unloader bracing. J Pediatr Orthop B
2020;29(1):81-89. This is a retrospective review of children treated
with bracing for OCD of the knee compared with those managed
without a brace. Level of evidence: III.
44. Carey JL, Shea KG, Lindahl A, Vasiliadis HS, Lindahl C,
Peterson L: Autologous chondrocyte implantation as treatment
for unsalvageable osteochondritis dissecans: 10- to 25-year follow-
up. Am J Sports Med 2020;48(5):1134-1140. This is a retrospective
case series of ACI treatment with long-term follow-up in OCD
lesions. Level of evidence: IV.
45. Hevesi M, Sanders TL, Pareek A, et al: Osteochondritis
dissecans in the knee of skeletally immature patients: Rates of
persistent pain, osteoarthritis, and arthroplasty at mean 14-years’
follow-up. Cartilage 2020;11(3):291-299. A retrospective case series
evaluated the long-term outcomes of management for OCD.
Level of evidence: IV.
46. Masquijo JJ, Allende F, Carabajal M: Ankle morphology and
Juvenile Osteochondritis Dissecans (JOCD) of the Talus: Is there
an association? An MRI study. J Pediatr Orthop 2021;41(2):e147-
e152. A cross-sectional study evaluated the utility of MRI to
predict the development of OCD in the talus based on various
ankle morphologies. Level of evidence: III.
47. Patel M, Francavilla ML, Lawrence JTR, et al: Osteochondral
lesion of the talus in children: Are there MRI findings of
instability? Skeletal Radiol 2020;49(8):1305-1311. A retrospective
diagnostic comparative study a empts to identify predictive
factors for ankle instability in children. Level of evidence: III.
48. Körner D, Gonser CE, Döbele S, Konrads C, Springer F, Keller
G: Re-operation rate after surgical treatment of osteochondral
lesions of the talus in paediatric and adolescent patients. J Orthop
Surg Res 2021;16(1):187. This is a retrospective case series of
children treated with surgery for osteochondral lesions of the
talus and the rate of reoperation. Level of evidence: IV.
49. Edmonds EW, Phillips L, Roocroft JH, Bastrom TP, Pennock AT,
Chambers HG: Stable childhood osteochondral lesions of the
talus: Short-term radiographic outcomes suggest risk for early
osteoarthritis. J Pediatr Orthop B 2020;29(4):363-369. This is a
retrospective case series that demonstrates the rate of early
arthritis changes in children treated for osteochondral lesions of
the talus surgically. Level of evidence: IV.
C H AP T E R 6 6

Pediatric Spine Disorders and

Trauma
Craig R. Louer MD, R. Carter Clement MD, MBA, Joshua B.
Holt MD

None of the following authors or any immediate family member has received anything of value
from or has stock or stock options held in a commercial company or institution related directly or
indirectly to the subject of this chapter: Dr. Louer, Dr. Clement, and Dr. Holt.

ABSTRACT
The most common spine conditions requiring treatment in children
are spinal deformities. Adolescent idiopathic scoliosis is the most
common of these, but sagi al plane deformities such as kyphosis,
or deformities in multiple planes, must be understood as well.
Bracing can be used to limit curve progression in some cases.
Severe, progressive deformities are often halted and partially
corrected by spinal fusion procedures. In young children with early-
onset scoliosis from multiple etiologies, where fusion has
significant drawbacks, a variety of procedures that facilitate spinal
growth while maintaining control of the curve can be used.
Spondylolysis and spondylolisthesis can be managed nonsurgically
in most cases, although high-grade spondylolisthesis may
necessitate surgical treatment. Congenital anomalies or soft-tissue
laxity can lead to cervical spine instability with neurologic
deterioration. Children can also sustain traumatic injuries to the
cervical and thoracolumbar spine, with unique diagnostic and
treatment considerations based on anatomic differences.
Keywords: adolescent idiopathic scoliosis; atlantoaxial instability;
early-onset scoliosis; kyphosis; spondylolisthesis

Introduction
Pediatric spine disorders comprise a large part of pediatric
orthopaedic care, as they are commonly encountered and lead to
uncertainty for many parents and referring doctors. Familiarity
with these conditions, their associated syndromes, and the basics of
their treatment is essential for accurate diagnosis and timely
treatment or referral. It is important to summarize key concepts
and recent developments in spinal deformity, congenital spinal
anomalies, and traumatic or acquired spine conditions often seen in
children.

Adolescent Idiopathic Scoliosis

Epidemiology
Adolescent idiopathic scoliosis (AIS) is defined as a coronal plane
radiographic angulation greater than 10°. AIS is the most common
spinal deformity encountered in children, with 2% to 3% of the
population meeting this criterion. Only approximately 0.1% to 0.3%
of the population have curves greater than 30°, with 0.03% having
severe scoliosis and undergoing surgery for deformities greater
than 45° to 50°.

Etiology
The etiology of AIS is largely unknown, although genetics,
environment, and bone health have all been implicated. 1 Relative
anterior column overgrowth is commonly appreciated in AIS, with
the subsequent buckling of the spine resulting in the complex
three-dimensional deformity of AIS: coronal curvature, axial
rotation, and relative lordosis 2 (Figure 1). Other causative
conditions, such as congenital malformations, neuromuscular
diseases, and syndromes, need to be ruled out to reach a diagnosis
of AIS.
Figure 1 Three-dimensional (3D) drawings depicting scoliosis.A, 3D
reconstruction of thoracic adolescent idiopathic scoliosis (AIS) curve where the
sagittal profile appears similar to that of an unaffected spine. B, Restacking the
vertebra by eliminating the rotational and coronal plane segmental deformities
 clearly demonstrates the relative lordosis due to relative anterior column
overgrowth. Thus, the predictable 3D deformity of AIS is an accommodation that
most spines experience to deal with this discrepancy in growth.(Copyright San
Diego Pediatric Orthopedics.)

Natural History
Like other asymptomatic pediatric conditions, understanding the
natural history of untreated AIS informs management strategy.
Small curves may progress in severity as patients grow; thus,
skeletally immature patients have more potential for deformity
progression. Curves that reach greater than 45° to 50° are thought
to progress even in patients without remaining growth, presumably
from degenerative mechanisms. Severe, progressive curves appear
to be associated with morbidity (possible pain, pulmonary
restriction, and appearance concerns) when not addressed. 3
Nevertheless, these large untreated curves notably are not
associated with physical disability, unemployment, or mortality.
These presumed truths that underpin modern scoliosis
management are derived from best-available evidence, although
limitations exist.

Evaluation
Clinical evaluation for spinal deformity should screen for other
causes and thoroughly assess the deformity. Painful conditions
(herniated nucleus pulposus, some tumors), chest wall deformity,
and compensatory posture (limb-length difference) can also present
as a scoliotic deformity. Severe back pain is not explained by the
presence of a minor deformity and warrants further workup. Minor
to moderate deformities have classically not been thought to cause
back pain, although recent work has demonstrated an association
between back pain and curve severity and psychosocial factors. 4
Deformity characteristics, such as pelvic and shoulder heights,
trunk shift, and truncal rotation, are important to recognize when
initiating treatment. Assessment of skeletal maturity through serial
height measurements, menarche status (in females), or
radiographic assessment is essential in AIS.
Because growth is a critical component of planning treatment,
methods for determining growth need to be accurate, reproducible,
and convenient. Skeletal maturity scoring using a hand radiograph
(also referred to as Sanders scoring) has become popular for its
close association with peak height velocity during the adolescent
growth spurt 5 (Figure 2). The proximal humerus ossification system
has also garnered recent interest for prediction of growth
remaining. 6 The Risser classification (grading of iliac apophysis
ossification) is a canonical scheme for maturity determination,
although its accuracy has been questioned in a 2020 study. 7
 Figure 2 Graphic shows peak growth velocity/age is accurately predicted by
Sanders score.Humans are one of the few species who experience an
acceleration of growth as they near maturity. The period of fastest growth
correlates with adolescent idiopathic scoliosis (AIS) curve progression and is
termed peak height velocity (PHV), which has been demonstrated to occur when
height is at 90% of final make 90% full size height (peak growth age 90, or
PGA90% ). Fusion of the hand growth plates is reliably distributed around PHV,
making Sanders scoring a convenient method to determine relative growth
remaining (and thereby determine appropriate treatment). PHV occurs between
stages 2 and 3, when the phalangeal epiphysis caps the metaphysis. Note that
both menarche and the appearance of the Risser sign generally do not occur
until well after PHV, which limits their usefulness in AIS treatment decisions.
(Adapted from Sanders JO, Qiu X, Lu X, et al: The uniform pattern of growth and
skeletal maturation during the human adolescent growth spurt. Sci Rep
2017;7[1]:16705 and Sanders JO, Khoury JG, Kishan S, et al: Predicting
scoliosis progression from skeletal maturity: A simplified classification during
adolescence. J Bone Joint Surg Am 2008;90[3]:540-553.)

Nonsurgical Treatment
Mild scoliotic curves can be observed clinically or radiographically
for progression. Progressive curves between 20° and 40° are
indicated for brace wear in patients with growth remaining.
Patients with moderate curves who have Risser sign of 2 or less and
Sanders score of 5 or less are considered candidates for brace wear
because of significant growth remaining. Although previously
controversial, there is now strong evidence that brace wear prevents
curve progression to a surgical threshold. Treatment success
increases from 48% to 72% with proper bracing. 8 The effect of brace
wear is dose dependent—at least 12.9 hours of daily brace wear is
needed to have an effect. Scoliosis-specific exercises are being
explored as an adjunctive treatment for treatment of moderate
curves in addition to brace wear. Early studies show some promise
to these therapies, but more evidence is needed. 9
A ention to detail is important when starting brace treatment.
There are numerous brace designs, but there is no strong evidence
that any one brace is superior to others. It is likely that brace
comfort and correction achieved are more critical than brace
design. The psychological effects of brace wear are debated. The
duration of brace wear has not been linked to differences in quality
of life and body image. 10 Still, avoiding unnecessary brace
treatment is a common patient concern. There is no consensus on
when brace wear can be discontinued, although many surgeons will
cease brace wear at Sanders 7 or Risser 4. Recent publications have
demonstrated continued curve progression with these criteria, but
it is unclear whether a longer bracing interval would have
prevented this progression. 11 , 12 New clinical tools that consider
three-dimensional deformity parameters can be er predict those at
risk of progression and may help guide initial treatment and
reshape bracing criteria. 13 , 14

Surgical Treatment
Curves progressing to 45° to 50° are considered severe scoliosis and
may be offered surgery based on the aforementioned natural
history of progression, even if the patient is asymptomatic.
Posterior spinal fusion (PSF) with segmental instrumentation using
predominantly pedicle screws is the most common treatment for
AIS in the modern era (Figure 3, A and B), although anterior
techniques may still have a role in treatment. Successful fusion
surgery will prevent curve progression of the involved vertebra
while also resulting in significant deformity correction. There are
likely advantages to having scoliosis surgery as an adolescent
compared with having surgery as an adult. A 2019 matched
comparison study of adults versus adolescents undergoing PSF
found increased levels fused (including 36% fused to the pelvis)
and increased major complications (25% versus 5.4% at 2 years) in
the adult patients with deformity. 15 In a 2019 study, health-related
quality-of-life scores in patients who have undergone spine fusion
demonstrate that pain, activity, and self-image scores were
improved at 5 years postoperatively in comparison with an
untreated AIS group; they were also similar to those of healthy
population control, except for decreased function subscores. 16
Long-term outcomes data are not yet available for modern
segmental fixation, but average 24.5-year data on fusions performed
with nonsegmental Harrington rod fixation demonstrate health-
related quality-of-life scores to be similar to those of the general
population.
 Figure 3 Surgical management of adolescent idiopathic scoliosis (AIS).A and
B, Preoperative and 2-year postoperative radiographs from a 15-year-old girl
with AIS and main thoracic curve measuring 50° who underwent posterior spinal
fusion with segmental fixation. C and D, Preoperative and 2-year postoperative
radiographs from a 11-year-old girl with AIS and curve of similar appearance and
severity who underwent anterior vertebral body tethering.(Copyright San Diego
Pediatric Orthopedics.)

Emerging technologies are reshaping surgical paradigms for

surgery and recovery. Enhanced recovery after surgery programs
have reduced average length of stay to 2.2 days after spinal fusion,
stressing multimodal pain regimens and early mobilization. 17 CT
navigation technologies allow visual augmentation of freehand
screw placement techniques and are becoming more popular in
complex deformity as well as AIS spine fusions. Navigation appears
to result in more accurate screw trajectory, although the clinical
importance of screw malposition is debated. A 2019 series has
demonstrated that navigation technology decreased rate of return
to the operating room without increasing surgery times or blood
loss. 18 Anterior vertebral body tethering (VBT) is an emerging
nonfusion strategy for select patients with AIS with growth
remaining. This technology uses screws thoracoscopically placed in
the vertebral body and connected with a flexible polyethylene
tether that corrects the curve through tensile forces but still allows
movement between spinal segments. The differential growth
created theoretically results in growth modulation and continued
correction of the scoliotic curve (Figure 3, C and D). Minimum 2-
year comparative results comparing PSF with VBT demonstrate that
PSF results in more sustained correction and less reoperation (zero
versus 30%). However, 74% of VBT patients successfully avoided
fusion in a 2020 study. 19 Further research is required to determine
durability of these results and how these approaches compare long
term in terms of function, flexibility, health-related quality of life,
and adjacent segment disease.

Early-Onset Scoliosis
Early-onset scoliosis (EOS) refers to curves that develop before age
10 years. There are four etiologies: idiopathic, congenital,
neuromuscular, and syndromic. Recently, a generally accepted
classification system, C-EOS, has been developed that is primarily
for research. Although there are unique considerations for each
individual patient and etiology, there is significant overlap in
treatment strategies.

EOS Treatment Strategies

When EOS progresses, but the patient is too young for definitive
PSF, the surgical options are usually referred to by terminology
such as growth friendly, growth preserving, or growing spine
instrumentation. This category can generally be divided between
guided growth or distraction-based options (Figure 4), with the
la er being more popular. There is currently no specific definition
of too young for PSF. One proposed goal is to achieve 22 cm of
thoracic height, which is the average height of a 10-year-old child, to
optimize lung function. 20 However, there seems to be a trend
toward earlier PSF (as early as 7 to 8 years old) to avoid the physical,
mental, and socioeconomic burden of growth-preserving implants.
21 - 23

Figure 4 Flowchart shows growth-preserving surgery can generally be

considered in two broad categories: distraction-based procedures and guided
growth surgeries.MCGR = magnetically controlled growing rods, TGR =
traditional growing rod, VEPTR = vertical expandable prosthetic titanium rib.

Casting for EOS

The traditional casting technique is referred to as Mehta casting or
elongation-derotation-flexion casting and was performed on a
Mehta table. Some have simplified the process by applying smaller
casts that do not extend over the shoulders, which does not seem to
sacrifice outcomes. 24 Others have simplified cast application by
suspension of the spine with a single fulcrum. Casting is most
beneficial when aggressive: beginning very early (eg, before age 3
years) and avoiding cast holidays. 25
Distraction-Based Growing Rods
Historically, the most commonly used distraction-based implant
has been traditional growing rods (TGRs). TGRs are anchored to the
spine (or ribs or pelvis) proximally and distally, and the spine
between the anchors is left unfused so it can continue to grow.
Patients with TGR typically undergo surgery every 6 months to
distract the implants. TGRs carry a high rate of complications,
especially infection, as well as financial and psychosocial burden. 26
Distraction-based treatment is also plagued by the law of
diminishing returns—the spine stiffens and sometimes autofuses
during treatment. As a result, each lengthening is progressively
shorter and obtaining additional correction during the eventual
fusion procedure may require more aggressive releases or
osteotomies compared with a primary fusion.
The vertical expandable prosthetic titanium rib functions
similarly to TGRs. It was initially developed as a rib-to-rib construct
to expand the concave side of the chest to help lung development in
patients with severe thoracic insufficiency syndrome. Subsequently,
though, it has been used similarly to TGRs with the ability to
connect to either the ribs or the spine. 27 Magnetically controlled
growing rods have been developed as a promising alternative to
TGR (Figure 5, A and B). They are lengthened through the skin
(Figure 5, C), which may reduce the physical, mental, logistical, and
financial toll on the patient and family. 26 However, the law of
diminishing returns still ultimately tends to impede the process,
although it may occur more gradually than seen with TGR. 28
 Figure 5 Illustration (A) and radiograph (B) of dual magnetically controlled
growing rods for early-onset scoliosis. Photograph (C) showing magnetic
lengthening in clinic.(A and C used with permission from Nuvasive.
https://www.nuvasive.com/wp-content/uploads/2020/06/MAGEC-Patient-
Education-Brochure.pdf - Figure of spine on pages 4 and 10.)

It remains unclear whether all patients with EOS undergoing

distraction-based treatment require eventual revision to PSF. Most
surgeons elect to perform definitive fusion, but many spines have
autofused at that point. Thus, avoiding final fusion seems to be a
viable option as long as the deformity is balanced and acceptable
and the implants are intact. Certain implants, such as magnetically
controlled growing rods, may carry additional risk if left implanted.

Guided Growth
Guided growth procedures are designed to allow the spine to keep
growing as straight as possible. Compared with traditional
distraction-based treatment, guided growth can reduce the number
of surgeries. Unfortunately, they do not typically seem to be as
effective, possibly because distracting the spine actually accelerates
growth beyond the physiologic rate through the Hueter-Volkmann
principle. A historic example of guided growth for EOS was the
Luqué trolley; rods were anchored to the spine proximally and
distally and wrapped together with sublaminar wires. With growth,
the wires would theoretically slide along the rods, holding the spine
straight while allowing expansion. Unfortunately, the results were
not reliable. Some authors still advocate for the Luqué trolley to
treat patients with myelomeningocele with a gibbus deformity after
kyphectomy. A modern version of the Luqué trolley has been
described with pedicle screws rather than sublaminar wires at the
proximal and distal ends of the construct, but results still remain in
question. 29
A more recent concept for guided growth is the Shilla technique.
Rather than anchoring to short, fused segments proximally and
distally, the apex of the curve is fused and rods extend proximally
and distally to screws with open eyelets that can slide along the
rods as the spine grows. This has the theoretical benefit of
straightening and fusing the part of the curve with the most
deformity (the apex). Although some early reports compared
favorably with TGR, 30 , 31 more recent, larger studies have
demonstrated less spinal growth and curve correction. 32 Another
subcategory of guided growth is compression-based growth
modulation, such as staples or anterior VBT. Perhaps in the future,
these techniques will be refined to accommodate the EOS
population.

Limited Fusion
Finally, some authors advocate for limited fusion in EOS,
particularly neuromuscular cases. For example, fusing a lumbar
curve allows the thoracic spine to keep growing, and the construct
can be extended to the thoracic region closer to skeletal maturity.
Limited anterior fusion has the benefit of sparing the posterior
spine, which prevents scar tissue and makes the definitive fusion
procedure easier.

Idiopathic EOS
Idiopathic EOS is a diagnosis of exclusion, necessitating MRI of the
spine to rule out intraspinal anomalies. There are two
subcategories: infantile idiopathic scoliosis (IIS, ages 0 to 3 years)
and juvenile idiopathic scoliosis (JIS, ages 4 to 9 years). Juvenile
idiopathic scoliosis presents in a manner similar to AIS, whereas
IIS has several notable differences 33 (Table 1).

Table 1
Characteristics of Idiopathic Scoliosis

Juvenile Idiopathic Adolescent

Infantile Idiopathic Scoliosis
Scoliosis Idiopathic Scoliosis
0-3 years old 4-9 years old 10-18 years old
Mostly boys Mostly girls
Usually left thoracic Usually right thoracic
Often resolves (but progressive cases Gradually progresses (at least until skeletal
can be life threatening) maturity)

Although IIS has the potential to resolve, it also has the potential
to be much more severe than JIS and AIS by progressing at an early
age and restricting lung development, a condition that is
sometimes called thoracic insufficiency syndrome. In these cases,
early intervention, especially casting, can be life-altering or even
lifesaving. Much of the pioneering work on IIS treatment is
described in a study that identified risk factors for progression that
should prompt early casting: Cobb magnitude, rib vertebral angle
difference, and rib vertebra overlap 34 (Figure 6).
 Figure 6 Illustrations showing rib overlap that occurred in advanced early-
onset scoliosis (EOS) (phase 2) and that indicates substantial risk of
progression rather than spontaneous resolution (A). B, The measure
demonstrated is the rib vertebral angle, which is measured in early EOS (phase
1) before rib-vertebral overlap occurs. When the difference between the rib
vertebral angle on the left and right at the apical vertebra is over 20°, there is
substantial risk of progression, and casting should be initiated.(Reproduced with
permission from Mehta MH: The rib-vertebra angle in the early diagnosis
between resolving and progressive infantile scoliosis. J Bone Joint Surg Br
1972;54[2]:230-243, Figures 2 and 4.)

Congenital Scoliosis
There are two important causes of congenital scoliosis: failure of
formation and failure of segmentation of vertebrae (Figure 7, A).
The most severe cases occur when there is simultaneous failure of
formation and segmentation at the same level of the spine, which
leads to rapid progression (Figure 7, B). Like all cases of EOS,
congenital anomalies should be evaluated with MRI of the entire
spine to rule out intrathecal pathology, especially tethered cord,
syringomyelia, and Chiari malformation; these pathologies have a
higher incidence in congenital cases. Congenital scoliosis is unique
for the risk of associated anomalies in the genitourinary and cardiac
systems that develop concomitantly with the spine (approximately
8 weeks of gestation). These possible anomalies require workup
with appropriate referrals and/or imaging, typically including
echocardiogram and renal ultrasonography, although some MRI
sequences can evaluate the kidneys and lower genitourinary tract.

Figure 7 Congenital scoliosis with unilateral failure of formation resulting in a

hemivertebra (A). Unilateral failure of segmentation with a bar spanning the disk
space (B). Unilateral failure of formation with contralateral failure of
segmentation, which creates a very high risk of rapid progression (C).
(Reproduced from Hedequist D, Emans J: Congenital scoliosis. J Am Acad
Orthop Surg 2004;12[4]:266-275, Figures 1B, 2B, 2C.)

Some cases of congenital scoliosis can be treated similar to other

types of EOS; the goal is to delay surgery as much as possible.
Although bracing and casting were not historically used in this
population, casting can help delay surgery in some cases, especially
in relatively young children. 35 Cases with contralateral failures of
formation and segmentation at the same level often require early
fusion, preferably involving only short segments of the spine.
Growing spine implants can be effective in slightly older children,
although according to a 2020 study there are no established
treatment guidelines given the heterogeneity of this population. 36
As in all EOS populations, spinal fusion is delayed as close to
skeletal maturity as possible. Hemivertebra resection is frequently
performed concomitantly with fusion, increasing the procedure’s
complexity and risk.

Neuromuscular and Syndromic Scoliosis

A broad range of neuromuscular and syndromic conditions can
result in progressive scoliosis secondary to muscle weakness or
imbalance, soft-tissue contracture or incompetence, or a lack of
coordination. Like idiopathic curves, initial treatment of these
curves is generally a empted with external support (ie, bracing or
casting) if the patient has significant growth remaining. Bracing has
not been studied as rigorously in these individual conditions as it
has in AIS, but the principles are often extrapolated to these
populations, with a few notable exceptions. Multiple studies have
shown bracing to be ineffective in spinal muscular atrophy and
quadriplegic cerebral palsy. The use of a soft brace may provide
functional benefit by improving position and facilitating a patient’s
interaction with their environment, even if the brace does not slow
curve progression. PSF is a common treatment option for
progressive, severe curves once a patient nears or enters
adolescence, even if asymptomatic. The pelvis is often included as
the caudal anchor in nonambulatory patients to correct obliquity
and improve si ing balance. This is a fragile patient population
where preoperative optimization is critical in mitigating
complications. The overall complication rate is estimated at
approximately 50% at 5 years, yet the benefits of surgery often
outweigh the risks. 37 In a 2020 study of a cohort of nonambulatory
patients with cerebral palsy, spinal fusion resulted in meaningful
improvement in quality of life for 36% of patients. 38

Kyphosis
The sagi al balance of the spine in the skeletally mature individual
has reciprocal curvatures, including cervical lordosis, thoracic
kyphosis, and lumbar lordosis. These develop as an adaptation to
the bipedal position and help to minimize energy expenditure
during upright stance. Newborns, however, have only a single
kyphotic curve through all regions of the spine. As infants begin to
hold their heads up, a secondary lordotic curve develops in the
cervical spine. Similarly, lumbar lordosis typically develops
secondary to upright stance.
Sagi al plane deformity of the spine (ie, kyphosis) is less
common than severe scoliosis but can result in similar symptoms
and concerns, such as back pain, deformity, psychosocial distress,
and neurologic compromise. Normal thoracic kyphosis in children
ranges from 20° to 40°, although deformity up to 70° is often
asymptomatic and may not require treatment. As thoracic kyphosis
progresses in severity, so does the frequency of patient symptoms
and need for surgical intervention.
Increased kyphosis has been reported in the medical literature
since the 19th century. Multiple causes of hyperkyphosis have been
identified and described (Table 2). The underlying cause of
increased kyphosis can typically be identified by plain radiography
of the spine. Other less common causes of kyphosis can be
differentiated on the basis of the history and physical examination
findings.

Table 2
Causes of Kyphosis

Postural
Scheuermann disease
Congenital
Traumatic
Neuromuscular
Myelomeningocele
Postlaminectomy
Postradiation
Metabolic
Skeletal dysplasia
Neoplastic
Postinfectious
Chronic recurrent multifocal osteomyelitis

Congenital
Congenital kyphotic deformities can result from vertebral
formation and/or segmentation anomalies. In addition to screening
for renal and cardiac abnormalities, a congenital kyphosis should
be monitored closely as they can be rapidly progressive and result
in severe spinal stenosis and myelopathy. Similarly, great care
should be taken when surgical management for congenital
kyphosis is pursued because it is among the conditions with
highest risk of overall complications and neurologic injury.
Pediatric patients with newly presenting kyphoscoliosis should be
assessed for associated syndromes such as skeletal dysplasia,
mucopolysaccharidoses, and metabolic disease.

Lumbar Hypoplasia
As opposed to congenital kyphosis where the typical sagi al
contours of the spine are disrupted secondary to a fixed, persistent
failure of spine formation or segmentation, infantile thoracolumbar
kyphosis is the result of hypoplasia of a single lumbar vertebra and
has a benign course with spontaneous resolution as bipedal
posture is adopted. This typically occurs before the age of 3 years.
Key differentiating features when trying to distinguish between
lumbar hypoplasia and congenital kyphosis are the lack of
malformations in the posterior elements, the involvement of a
single lumbar vertebra (typically L1 or L2), and a defect limited to
the superior aspect of the anterior half of the vertebrae (described
previously as a beaked, notched, or hooked vertebra) (Figure 8).
Because spontaneous resolution of the resulting kyphosis is
expected by the age of 3 years, a period of observation is advised for
otherwise normal children who present with this deformity during
infancy or early childhood with additional imaging, workup, or
treatment only if deformity persists beyond this age.
Figure 8 A and B, AP and lateral radiographs from a 2-year-old child with
incidental finding of L2 hypoplasia. Notice the notched or hooked appearance. C
and D, AP and lateral radiographs obtained 11 months later with improving
kyphosis.
Scheuermann Kyphosis
Originally described in 1920, Scheuermann kyphosis is an
idiopathic kyphosis of the spine, associated with 5° of wedging of
three consecutive vertebrae. Despite more than 100 years of
research on the entity, the etiology is still largely unknown because
of inconsistent histopathology and only sporadic signs of juvenile
osteoporosis or metabolic bone disease. Radiographs often show
associated Schmorl nodes (ie, intraosseous disk herniation) and
other end plate irregularities; however, these findings are similarly
inconsistent. Consideration for preoperative MRI of the entire
spine to assess for disk herniation or other intrathecal pathology
should be part of any treatment algorithm.
Management of Scheuermann kyphosis is not as uniform or
established as idiopathic scoliosis. Although successful short-term
management of Scheuermann kyphosis with nearly full-time
bracing has been reported, this is rarely tolerated and lacks
evidence for long-term deformity stabilization. Most treatment
consists of routine observation for curve progression during
development with surgical management offered when pain, clinical
deformity, psychosocial concerns, and radiographic findings
become more severe. Unlike idiopathic scoliosis, there is not an
established measure of angular deformity to serve as a threshold
for surgical recommendation, although surgical management of
Scheuermann kyphosis is typically reserved for rigid curves greater
than 70° and refractory pain, psychosocial concerns, or
unacceptable clinical appearance. 39
Before pursuing surgical management, supine hyperextension
imaging should be obtained with a bump placed under the apex of
the deformity to assess curve flexibility. The goal of surgical
correction of kyphosis should be to obtain a stable, solidly fused,
well-balanced spine without neurologic complication. Maximal
curve correction should not be pursued. The degree of curve
reduction should be planned relative to the overall sagi al balance
of the patient with no more than 50% correction of the preoperative
curve magnitude. This will help to avoid neurologic complications
and avoid junctional kyphosis at the cranial and caudal extents of
fusion 40 (Figure 9). When comparing patients undergoing surgical
treatment with those who maintain nonsurgical treatment for
Scheuermann kyphosis, surgical patients generally have more pain
and kyphotic deformity and are of older age. 39 There are higher
surgical complication rates in the surgical management of
Scheuermann kyphosis than in AIS.
 Figure 9 A and B, AP and lateral radiographs from a 13-year-old child with
Scheuermann kyphosis. C, Lateral radiograph obtained with the patient supine
with a bump under the area of maximal kyphosis. D and E, AP and lateral
radiographs following T2-L3 posterior spinal fusion with multiple posterior
osteotomies at the apex of kyphosis.

Cervical Spine Conditions in Children

The anatomy of the growing spine and generally increased
ligamentous laxity in children leads to some unique considerations
for the cervical spine evaluation and treatment. Benign conditions
may appear hazardous, whereas subtle yet significant injuries can
be overlooked. Younger children have larger heads, weaker
muscles, and more horizontal facet joints. As such, children 0 to 9
years old are more likely to sustain injuries to their upper cervical
spine than older children (occiput to C2, 78% versus 30% upper
injuries). Additionally, these injuries are less likely to involve a
fracture and instead commonly involve pure subluxation or spinal
cord injury without radiographic anomaly, or SCIWORA (spinal
cord injury without radiographic abnormality). Injury pa erns in
older children will be more analogous to adult-pa ern injuries.
Certain instability pa erns and conditions may be congenital or
acquired via minimal trauma, particularly in pediatric conditions
that predispose to ligamentous laxity or bony dysplasia.

Upper Cervical Spine

Atlanto-occipital dissociation (AOD) is a high-energy, severe injury
involving disruption of the occiput-C1 articulation. Mortality and
morbidity can be substantial, although more patients are surviving
this injury and requiring treatment at trauma centers. Atraumatic
occiput-C1 instability can also be seen in conditions associated with
ligamentous laxity, such as Down syndrome. Dynamic imaging
(lateral cervical spine radiographs, MRI with neck in multiple
positions) can help confirm the diagnosis of atraumatic occiput-C1
instability when suspected. Recommended treatment is posterior
occiput-cervical fusion with instrumentation, although newer
reports have presented halo-vest immobilization as an acceptable
treatment for traumatic atlanto-occipital dissociation. 41
Atlantoaxial instability describes instability of the atlas on the
axis (C1 on C2). This may be a result of high-energy trauma
typically developing in children secondary to injury to the
transverse ligament or with dens pathology such as fracture or os
odontoideum. More commonly, this is seen as an atraumatic
condition in various conditions (ligamentous laxity, inflammatory
arthropathies, skeletal dysplasias). The atlanto-dens interval (space
between the anterior dens and posterior aspect of the anterior C1
arch) may be up to 5 mm in children without deformity; an atlanto-
dens interval greater than 5 mm indicates relative instability. The
space available for the cord (posterior aspect of the dens to anterior
aspect of the posterior arch of C1) is important to consider in
evaluating stenosis. Atlantoaxial instability can be seen in up to
20% of patients with Down syndrome, although only 2% to 3% will
display neurologic symptoms. Because of the insignificant number
of patients with Down syndrome who have traumatic injury and
neurologic decline as a result of atlantoaxial instability, routine
radiographic screening in the absence of symptoms is no longer
recommended. Symptomatic instability can be managed with C1-C2
fusion (Figure 10).
 Figure 10 Atlantoaxial Instability causing central apnea in Down syndrome.A
and B, Flexion-extension lateral radiographs from a 2-year-old girl with Down
syndrome. She had respiratory failure 2 weeks following tonsillectomy. After
airway compromise was ruled out, radiographs revealed atlantoaxial instability.
C, Magnetic resonance image demonstrated significant myelomalacia and
stenosis. D, CT angiogram defined bony and vascular anatomy for preoperative
planning. E, Sagittal CT image demonstrating normal atlanto-dens interval (<5
mm) but with significantly limited space available for cord (6 mm), thereby
showing limitations of absolute measures in small patients. F and G,
Postoperative radiographs revealing alignment following C1-C2 posterior spinal
fusion with autograft and halo-vest placement performed with CT navigation.
(Used with permission of Vanderbilt Pediatric Orthopedics.)

Atlantoaxial rotary subluxation is a unique type of C1-2 instability

due primarily to rotation and translation as opposed to flexion-
extension. This typically presents after minor trauma, repetitive
stress/positioning, or upper respiratory infection (Grisel disease)
and can be persistent because of sternocleidomastoid spasm
preventing spontaneous reduction. Many cases can be treated
nonsurgically initially, but if symptoms persist beyond 1 week,
traction, reduction, and immobilization should be used (Figure 11).
Persistently unstable or irreducible cases may require C1-2 fusion,
although closed treatment can be effective even in chronic
subluxations longer than 3 months in duration.
Figure 11 Atlantoaxial rotatory subluxation (AARS).A, Three-dimensional
reconstructed CT images from a 4-year-old girl with Down syndrome who had
head tilt and fixed rotation to the right after a school bus ride 4 months prior
during which she was sleeping with her head leaned forward. Workup revealed
AARS with left C1-C2 joint dislocation. The patient was treated with traction
followed by closed reduction (obtained by turning the head slightly to the left) with
reduction verified by CT scan (B). Reduction was maintainted with a halo vest
for 10 weeks. At 2 years follow-up, the patient has not experienced recurrence
despite C1-C2 joint dysplasia and ligamentous laxity.(Courtesy of Vanderbilt
Pediatric Orthopedics.)
Subaxial Cervical Spine
Below the level of C2, the increased bony constraint affords more
stability and behavior similar to that of the adult spine. Subaxial
injuries such as disk injury, jumped facets, and fracture-
dislocations can occur in high-energy trauma, but is more common
in adolescents where adult treatment principles will generally
apply. One notable exception is the 20% incidence of pediatric
pseudosubluxation, which is a benign condition where anterior
listhesis of C2 on C3 can be observed (C3 on C4 less common). This
can occur in patients up to age 8 years and can be differentiated
from traumatic injury on the basis of demographics, history, and
radiographic features such as correction in extension posture or the
absence of soft-tissue swelling or associated injury.

Surgical Considerations
Treatment of cervical spine pathology in pediatrics has seen rapid
evolution from the nonrigid wiring techniques of decades past.
Rigid internal fixation improves fusion rates in varied pathologies
and has precipitously dropped implant-related complications to
approximately 3%. 42 Because of the tremendous healing response
in children, allograft has been demonstrated to have equivalent
efficacy to autograft in the subaxial spine and reduces donor site
morbidity. 43 Bony dimensions and anatomic variants need to be
considered in surgical planning (particularly in C2), although
modern screw and rod constructs are feasible in 95% of patients
older than 2 years. 44 , 45

The Special Case of Down Syndrome

Upper cervical fusions in patients with Down syndrome warrant
special a ention, as outcomes remain suboptimal. Early reports
yielded 18% mortality with 100% complications, which has seen
modest improvement (42% complications) with modern
instrumentation. 46 In patients with Down syndrome with C1-C2
instability, some authors recommend routine fusion to the occiput
for improved fixation strength and decreased risk of missing occult
occiput-C1 instability or basilar invagination. The use of structural
allograft and postoperative immobilization in a halo vest are other
useful adjuncts. 46 The use of intraoperative CT to evaluate screw
position allows for immediate revision of malpositioned screws, 47
or navigation techniques can be used for augmented screw
placement.

Lumbar Spine Conditions in Children

Spondylolysis and Spondylolisthesis

The prefix spondylo refers to a vertebra, lysis refers to a rupture
(stress fracture), and listhesis means slipping. Most cases are
asymptomatic and develop by age 6 years. 48 The incidence in the
general population is 6% and most cases do not progress, especially
after childhood. 48 The listhesis is graded by the Meyerding
classification (Figure 12). There are multiple types of
spondylolisthesis: isthmic, dysplastic, degenerative, neoplastic, and
traumatic. Isthmic listhesis is the most common and involves a
fracture through the pars interarticularis, typically of L5. Stress in
this area is accentuated with back extension, so these conditions
commonly present in athletes with repetitive loading in extension,
such as gymnasts and football linemen. Because the posterior
elements are separated from the slipped vertebral body, isthmic
listhesis rarely results in central canal compromise, although nerve
root compression can occur. Dysplastic listhesis is notable because
the ring of bone around the dural sac remains intact and there is
greater risk of neural compression as the vertebra slips forward.
Neurologic claudication and cauda equina syndrome are more
common in dysplastic listhesis compared with isthmic listhesis.
 Figure 12 Illustration showing Meyerding classification of spondylolisthesis,
grade I-V.(Reproduced with permission from Mai HT, Hsu WK: Management of
sports-related lumbar conditions. Oper Tech Orthop 2015;25[3]:164-176, Figure
3.)

Workup begins with biplanar radiographs. Historically, oblique

radiographs were included but are no longer considered to be of
value considering the radiation exposure. Cross-sectional imaging
is often helpful, and CT is the most common choice, although MRI
has recently gained popularity, especially for very early
spondylolysis where edema may be the only finding. Historically,
single-photon emission CT was the gold standard for cross-
sectional evaluation, although it is no longer preferred, largely
because of the relatively high radiation.
Treatment for spondylolysis and low-grade spondylolisthesis
(Meyerding I-II) begins with activity modification (especially
avoiding back extension while symptomatic) and, usually, physical
therapy with a focus on hamstring stretching and abdominal
strengthening. Brace treatment remains controversial, as true
immobilization of the lumbosacral region requires a back brace
with leg extensions, which is cumbersome and is not used in most
studies. Although brace use may be helpful in some acute cases
when needed for pain relief, critics argue it is unnecessary and may
contribute to core weakness; meta-analysis has failed to show any
benefit from brace wear. 49 Surgery is generally recommended for
high-grade spondylolisthesis (Meyerding 3+) and when symptoms
persist for more than 6 months despite appropriate nonsurgical
interventions, regardless of severity (including spondylolysis
without listhesis), although some patients with high-grade slips can
have good long-term results without surgery. Numerous surgical
techniques exist (Figure 13) and there is no universally accepted
algorithm, although some common procedures and indications are
shown in Table 3.
 Figure 13 Illustration showing that spondylolysis or grade I listhesis above L5
can be treated with direct repair. Existing techniques include lag screws (A),
Scott wiring (B), and pedicle screws connected to laminar hooks via rods (C).
(Reproduced from Cheung EV, Herman MJ, Cavalier R, Pizzutillo PD:
Spondylolysis and spondylolisthesis in children and adolescents: II. Surgical
management. J Am Acad Orthop Surg 2006;14[8]:488-498, Figure 1.)

Table 3
Surgical Options for Spondylolysis and Spondylolisthesis a

Diagnosis Treatment Option

Spondylolysis or Direct pars repair
grade I listhesis Lag screws
above L5 Wiring
Pedicle screws connected to laminar hooks via rods
U rods
Listhesis > grade I Single-level fusion
above L5
L5/S1 spondylolysis L5-S1 fusion
or grade I listhesis
L5/S1 grade II L4-S1 fusion with TLIF/PLIF or ALIF
listhesis
L5/S1 grade III/IV L4-ilium fusion with TLIF/PLIF or ALIF
listhesis
L5/S1 grade V Consider adding complete diskectomy, sacral dome osteotomy, wide
listhesis decompression, L5 vertebral column resection, or fibular dowel graft
(spondyloptosis)
a
Currently, there is insufficient evidence to devise a full treatment algorithm, so multiple
options exist for many of these diagnoses. This list is simply a means of presenting numerous
procedures described in the literature.
ALIF = anterior lumbar interbody fusion, PLIF = posterior lumbar interbody fusion, TLIF =
transforaminal lumbar interbody fusion

Thoracolumbar Trauma/Fractures
Many of the fractures encountered in children and adolescent
patients are comparable to those seen in their adult counterparts.
Flexion/distraction injuries, bony chance injuries, and other such
traumatic injuries occurring in the thoracolumbar spine of children
and adolescents are imaged and treated similar to their adult
counterparts. However, children and adolescent patients have
unique and growing/developing anatomy that allows for improved
healing and remodeling of some injuries and puts them at risk for
other injury pa erns not seen in skeletally mature patients as
discussed in the following paragraphs.

Apophyseal Ring Fractures

The avulsion of a bony fragment from the posterior caudal or
cephalad rim of the vertebral body into the spinal canal is a variant
of a herniated nucleus pulposus that is well described in the
adolescent population. Instead of herniation of disk material
through the anulus fibrosus and posterior longitudinal ligament
into the spinal canal, an apophyseal ring avulsion involves
separation of the partially ossified rim of the posterior vertebral
apophysis at its osteocartilaginous junction. Both the apophysis
and the contiguous disk are then displaced posteriorly. Typically,
the central herniated disk adjacent to the avulsed apophyseal ring
protrudes posteriorly while the bony rim fragment stays a ached to
the posterior vertebral body by a periosteal sleeve. The posterior
longitudinal ligament generally remains intact.
Apophyseal ring avulsion can occur as a single traumatic event or
as a cumulative process in sports such as weightlifting, gymnastics,
or wrestling. A rotational moment through a spine that is in
extreme flexion appears to increase the risk of apophyseal injury.
As the vertebral ring apophysis develops at the age of 6 years and
typically fuses to the vertebral body by the age of 17 years, ring
avulsion injuries are seen only in this age range. Most apophyseal
ring avulsion injuries in adolescents have been reported in the L4-5
or L5-S1 levels. The injury is more common in males, likely because
of the increased age at which skeletal maturity is obtained and the
resulting longer period of exposure to trauma than their female
counterparts.
Clinical features of apophyseal ring avulsions are like those of
herniated lumbar disks. Intermi ent but progressive lower back
pain, with or without radiating symptoms, is the most prominent
complaint. Paraspinal muscle spasms and limitation in back motion
result in stiffness and a change in gait. Pain is exacerbated by lifting
or straining when coughing or sneezing. Radiographic findings
include fracture of the vertebral ring apophysis best seen as a small
bony fragment posterior to the vertebral body on a lateral view of
the lumbar spine. CT, MRI, and CT with myelogram can be useful
when investigating these injuries. MRI alone may not clearly
identify the thin bony component and only identify the disk
herniation. The amount of canal encroachment is often dramatic,
with near complete occlusion of the spinal canal by the avulsed
fragment and associated disk (Figure 14).
 Figure 14 A and B, Paired sagittal and axial CT and MRI demonstrating an L4-
L5 apophyseal ring avulsion injury. (Courtesy of Vanderbilt Pediatric
Orthopedics.)

Surgical treatment is typically recommended based on the

severity of pain and neurologic findings as well as persistence of
symptoms despite nonsurgical treatment. Surgical management
often requires a bilateral laminotomy with central laminectomy
because a more limited microdiskectomy approach often does not
allow safe or complete removal of the large amount of avulsed
bone, cartilage, and disk material. For this reason, scrutiny of
imaging is required preoperatively, so alterations in surgical
exposure can be anticipated.
Thoracolumbar Compression Injury
Acute trauma to the developing spine can result in compression
deformity of the vertebral body, comparable to that in adult
patients. Plain radiographs may show mild wedging of multiple
consecutive vertebrae without obvious bony fracture or discrete
end plate irregularities. Patient history of injury and pain localized
to this location can help to distinguish between traumatic versus
developmental etiologies. When traumatic compression of the
vertebrae does occur, surgical management is typically reserved for
patients with neurologic symptoms because continued growth and
remodeling of the vertebrae, with reconstitution of vertebral height,
can often be observed in the skeletally immature patient (Figure
15).
 Figure 15 A and B, AP and lateral radiographs from a 4-year-old child with
vertebral plana and mild focal kyphosis at L2. C and D, AP and lateral
radiographs obtained 8 years later demonstrating reconstitution of vertebral
height and resolution of focal kyphosis.

Summary
AIS and kyphosis can be progressive when significant growth
remains. These conditions are managed with observation, bracing,
and surgery. EOS can be fatal when untreated, and the small
patient size and need for continued growth demand alternative
treatment strategies from fusion. Cervical spine conditions can be
traumatic or acquired, and surgical stabilization is feasible even in
young children with modern techniques. Low-grade
spondylolisthesis and spondylolysis can be managed nonsurgically
to improve symptoms, although high-grade spondylolisthesis is at
risk for further deformity and neurologic compromise and should
be addressed surgically.

Key Study Points

Patients with AIS with curves 20° to 40° and significant growth remaining (Sanders
score ≤ 5) are candidates for bracing to help prevent curve progression and reduce
the risk of surgery.
The effects of bracing have been found to be dose dependent and require at least 13
hours of daily brace wear.
EOS is a potentially fatal condition where the treatment is focused on control of the
spinal deformity while still permitting growth of the thorax and facilitating respiration.
A patient with congenital scoliosis should have a spine MRI and renal and cardiac
ultrasonography to detect commonly associated spinal and organ abnormalities.
Low-grade spondylolisthesis does not commonly progress (<5% of cases), but
younger patients at peak growth velocity are at risk. Initial treatment for low-grade
slips should be nonsurgical.

Annotated References
1. Yip BHK, Yu FWP, Wang Z, et al: Prognostic value of bone
mineral density on curve progression: A longitudinal cohort
study of 513 girls with adolescent idiopathic scoliosis. Sci Rep
2016;6:39220.
2. Newton PO, Fujimori T, Doan J, Reighard FG, Bastrom TP,
Misaghi A: Defining the “Three-Dimensional Sagi al Plane” in
thoracic adolescent idiopathic scoliosis. J Bone Joint Surg Am
2015;97(20):1694-1701.
3. Weinstein SL: The natural history of adolescent idiopathic
scoliosis. J Pediatr Orthop 2019;39(6, suppl 1):S44-S46. Summary of
AIS natural history findings from the author’s longitudinal
cohort provides a basis of evidence to make informed decisions.
Level of evidence: III.
4. Wong AYL, Samar is D, Cheung PWH, Cheung JPY: How
common is back pain and what biopsychosocial factors are
associated with back pain in patients with adolescent idiopathic
scoliosis? Clin Orthop Relat Res 2019;477(4):676-686.
Biopsychosocial factors such as depression and poor sleep were
associated with chronic back pain in patients with AIS. Level of
evidence: II.
5. Sanders JO, Qiu X, Lu X, et al: The uniform pa ern of growth
and skeletal maturation during the human adolescent growth
spurt. Sci Rep 2017;7(1):16705.
6. Li DT, Linderman GC, Cui JJ, et al: The proximal humeral
ossification system improves assessment of maturity in patients
with scoliosis. J Bone Joint Surg Am 2019;101(20):1868-1874.
Humeral head ossification can be reliably assessed in patients
with AIS and percent growth remaining can be predicted with
high accuracy when combined with other factors. Level of
evidence: III.
7. Minkara A, Bainton N, Tanaka M, et al: High risk of mismatch
between sanders and risser staging in adolescent idiopathic
scoliosis: Are we guiding treatment using the wrong
classification? J Pediatr Orthop 2020;40(2):60-64. Compared with
 Sanders scoring to determine brace eligibility, use of Risser score
results in mistreatment of one in four patients, with most being
undertreated. Level of evidence: III.
8. Weinstein SL, Dolan LA, Wright JG, Dobbs MB: Effects of
bracing in adolescents with idiopathic scoliosis. N Engl J Med
2013;369(16):1512-1521.
9. Kwan KYH, Cheng ACS, Koh HY, Chiu AYY, Cheung KMC:
Effectiveness of Schroth exercises during bracing in adolescent
idiopathic scoliosis: results from a preliminary study-SOSORT
Award 2017 Winner. Scoliosis Spinal Disord 2017;12:32.
10. Schwieger T, Campo S, Weinstein SL, Dolan LA, Ashida S,
Steuber KR: Body image and quality of life and brace wear
adherence in females with adolescent idiopathic scoliosis. J
Pediatr Orthop 2017;37(8):e519-e523.
11. Cheung JPY, Cheung PWH, Luk KDK: When should we wean
bracing for adolescent idiopathic scoliosis? Clin Orthop Relat Res
2019;477(9):2145-2157. Of 144 patients 29% had progression of
curve following brace weaning. Patients with Sanders 7 hand
maturity were more likely to progress, whereas Sanders 8
maturity was protective. Level of evidence: II.
12. Grothaus O, Molina D, Jacobs C, Talwalkar V, Iwinski H,
Muchow R: Is it growth or natural history? Increasing spinal
deformity after sanders stage 7 in females with AIS. J Pediatr
Orthop 2020;40(3):e176-e181. Fifty-one percent of patients showed
curve progression greater than 5° after reaching Sanders maturity
score of 7, with 12% of patients reaching a surgical range despite
being thought skeletally mature. Level of evidence: III.
13. Nault ML, Beauséjour M, Roy-Beaudry M, et al: A predictive
model of progression for adolescent idiopathic scoliosis based on
3D spine parameters at first visit. Spine 2020;45(9):605-611. A
linear model using three-dimensional spine parameters was able
to predict progression of AIS with R = 0.64 by adding disk
wedging and angle of plane of maximal curvature to classic
criteria such as Cobb angle and maturity. Level of evidence: II.
14. Dolan LA, Weinstein SL, Abel MF, et al: Bracing in Adolescent
Idiopathic Scoliosis Trial (BrAIST): Development and validation
of a prognostic model in untreated adolescent idiopathic scoliosis
using the simplified skeletal maturity system. Spine Deform
2019;7(6):890-898.e4. A logistic regression model using unbraced
patients from BrAIST study found that increased Cobb angle,
thoracic curve location, and relative skeletal immaturity were
associated with curve progression. Level of evidence: I.
15. Lonner BS, Ren Y, Bess S, et al: Surgery for the adolescent
idiopathic scoliosis patients after skeletal maturity: Early versus
late surgery. Spine Deform 2019;7(1):84-92. Patients with AIS
treated during adulthood experience more complications and
require more levels fused compared with matched patients with
AIS treated in adolescence. Level of evidence: III.
16. Helenius L, Diarbakerli E, Grauers A, et al: Back pain and
quality of life after surgical treatment for adolescent idiopathic
scoliosis at 5-year follow-up: Comparison with healthy controls
and patients with untreated idiopathic scoliosis. J Bone Joint Surg
Am 2019;101(16):1460-1466. Patients with AIS who underwent PSF
with pedicle screws had improved health-related quality of life
compared with untreated AIS, with comparable health-related
quality of life to patients without scoliosis in all domains except
function, which was lower than the unaffected population. Level
of evidence: II.
17. Fletcher ND, Andras LM, Lazarus DE, et al: Use of a novel
pathway for early discharge was associated with a 48% shorter
length of stay after posterior spinal fusion for adolescent
idiopathic scoliosis. J Pediatr Orthop 2017;37(2):92-97.
18. Baky FJ, Milbrandt T, Echternacht S, Stans AA, Shaughnessy
WJ, Larson AN: Intraoperative computed tomography-guided
navigation for pediatric spine patients reduced return to
operating room for screw malposition compared with
freehand/fluoroscopic techniques. Spine Deform 2019;7(4):577-
581.3.3% of free-hand or fluoroscopically guided pedicle screws
were severely malpositioned compared with 1% of those placed
 with CT navigation, resulting in 3.6% return to the operating
room versus 0% in the navigation group. Level of evidence: III.
19. Newton PO, Bartley CE, Bastrom TP, Kluck DG, Saito W, Yaszay
B: Anterior spinal growth modulation in skeletally immature
patients with idiopathic scoliosis: A comparison with posterior
spinal fusion at 2 to 5 years postoperatively. J Bone Joint Surg Am
2020;102(9):769-777. VBT resulted in less correction and 30% more
reoperations than PSF but yielded a clinically successful result in
74% of patients who avoided a spine fusion. Level of evidence: II.
20. Karol LA, Johnston C, Mladenov K, Schochet P, Walters P,
Browne RH: Pulmonary function following early thoracic fusion
in non-neuromuscular scoliosis. J Bone Joint Surg Am
2008;90(6):1272-1281.
21. Li Y, Swallow J, Gagnier J, et al: Growth-friendly surgery results
in more growth but a higher complication rate and unplanned
returns to the operating room compared to single fusion in
neuromuscular early-onset scoliosis: A multicenter retrospective
cohort study. Spine Deform 2021;9(3):851-858. Patients with
neuromuscular EOS treated with growth-friendly surgery
achieved more spinal growth but experienced eight times more
complications and nine times more unplanned returns to the
operating room than patients treated with a single PSF. Level of
evidence: III.
22. Xu L, Sun X, Du C, et al: Is growth-friendly surgical treatment
superior to one-stage posterior spinal fusion in 9- to 11-year-old
children with congenital scoliosis? Clin Orthop Relat Res
2020;478(10):2375-2386. PSF may be a be er choice than growth-
friendly surgery in 9- to 11-year-old children with long-span
congenital scoliosis because there are fewer complications,
superior deformity correction, and no important difference in
outcome scores or pulmonary function. Level of evidence: III.
23. Keil LG, Nash AB, Stürmer T, et al: When is a growth-friendly
strategy warranted? A matched comparison of growing rods
versus primary posterior spinal fusion in juveniles with early-
 onset scoliosis. J Pediatr Orthop 2021;41(10):e859-e864. In patients
age 7 to 11 years with EOS, growth rods afford 2 cm of additional
thoracic height over PSF at the cost of poorer deformity and
additional complications. Level of evidence: III.
24. Fedorak GT, Stasikelis PJ, Carpenter AM, Nielson AN,
D’Astous JL: Optimization of casting in early-onset scoliosis. J
Pediatr Orthop 2019;39(4):e303-e307. Outcomes were similar
between patients casted for EOS with and without shoulder
straps. Level of evidence: III.
25. Fedorak GT, Dreksler H, MacWilliams BA, D’Astous JL: What is
the cost of a “Cast Holiday” in Treating Children with Early
Onset Scoliosis (EOS) With Elongation Derotation Flexion (EDF,
“Mehta”) casting? J Pediatr Orthop 2020;40(8):396-400. Patients
treated for EOS who had a cast holiday in the first 18 months of
serial casting were less likely to achieve scoliosis less than 15°.
Level of evidence: III.
26. Matsumoto H, Skaggs DL, Akbarnia BA, et al: Comparing
health-related quality of life and burden of care between early-
onset scoliosis patients treated with magnetically controlled
growing rods and traditional growing rods: A multicenter study.
Spine Deform 2021;9(1):239-245. Magnetically controlled growing
rods, which reduce the number of surgeries, may have be er
psychosocial effects than TGRs, including pain, emotion, and
satisfaction scores. Level of evidence: III.
27. Larson AN, Baky FJ, St Hilaire T, et al: Spine deformity with
fused ribs treated with proximal rib- versus spine-based growing
constructs. Spine Deform 2019;7(1):152-157. Growing spine devices
with spine anchors controlled kyphosis and corrected Cobb angle
more effectively than rib-based constructs in patients with EOS
with rib fusions. Level of evidence: III.
28. Ahmad A, Subramanian T, Panteliadis P, Wilson-Macdonald J,
Rothenfluh DA, Nnadi C: Quantifying the “law of diminishing
returns” in magnetically controlled growing rods. Bone Joint J
2017;99-B(12):1658-1664.
29. Mehdian H, Haddad S, Pasku D, Nasto LA: Mid-term results of
a modified self-growing rod technique for the treatment of early-
onset scoliosis. Bone Joint J 2020;102-B(11):1560-1566. A self-
growing rod construct with parallel rods anchored proximally
and distally with pedicle screws and linked centrally with
sublaminar wires demonstrates good correction and growth but
frequent complications including rod breakage. Level of
evidence: III.
30. Luhmann SJ, McCarthy RE: A comparison of SHILLA GROWTH
GUIDANCE SYSTEM and growing rods in the treatment of
spinal deformity in children less than 10 years of age. J Pediatr
Orthop 2017;37(8):e567-e574.
31. Luhmann SJ, Smith JC, McClung A, et al: Radiographic
outcomes of shilla growth guidance system and traditional
growing rods through definitive treatment. Spine Deform
2017;5(4):277-282.
32. Nazareth A, Skaggs DL, Illingworth KD, et al: Growth guidance
constructs with apical fusion and sliding pedicle screws
(SHILLA) results in approximately 1/3rd of normal T1-S1 growth.
Spine Deform 2020;8(3):531-535. Shilla procedures achieved only
one-third of predicted normal thoracic growth and less than one-
third of the growth reported in previous studies. Level of
evidence: IV.
33. Gillingham BL, Fan RA, Akbarnia BA: Early onset idiopathic
scoliosis. J Am Acad Orthop Surg 2006;14(2):101-112.
34. Mehta MH: The rib-vertebra angle in the early diagnosis
between resolving and progressive infantile scoliosis. J Bone Joint
Surg Br 1972;54(2):230-243.
35. Demirkiran HG, Bekmez S, Celilov R, Ayvaz M, Dede O, Yazici
M: Serial derotational casting in congenital scoliosis as a time-
buying strategy. J Pediatr Orthop 2015;35(1):43-49.
36. Clement RC, Yaszay B, McClung A, et al: Growth-preserving
instrumentation in early-onset scoliosis patients with multi-level
congenital anomalies. Spine Deform 2020;8(5):1117-1130. Patients
 with early-onset congenital scoliosis are treated with a wide
variety of growth-preserving implants, which can successfully
prevent progression but have limited capacity to fully correct
deformity. Level of evidence: III.
37. Miyanji F, Nasto LA, Sponseller PD, et al: Assessing the risk-
benefit ratio of scoliosis surgery in cerebral palsy: Surgery Is
Worth It. J Bone Joint Surg Am 2018;100(7):556-563.
38. Miller DJ, Flynn JJM, Pasha S, et al: Improving health-related
quality of life for patients with nonambulatory cerebral palsy:
Who stands to gain from scoliosis surgery? J Pediatr Orthop
2020;40(3):e186-e192.36.3% of 157 patients with cerebral palsy
who underwent spinal fusion had improvement in Caregiver
Priorities and Child Health Index of Life With Disabilities scores
of more than 10. Those with lower preoperative comfort,
emotions, and behavior subscores were more likely to show
improvement. Level of evidence: II.
39. Green C, Brown K, Caine H, Dieckmann RJ, Rathjen KE:
Prospective comparison of patient-selected operative versus
nonoperative treatment of scheuermann kyphosis. J Pediatr
Orthop 2020;40(8):e716. Patients who select surgical treatment for
Scheuermann kyphosis have improved radiographic and Scoliosis
Research Society 22 parameters (including pain and satisfaction)
at 2-year follow-up compared with patients who elect nonsurgical
treatment. Level of evidence: II.
40. Lowe TG, Kasten MD: An analysis of sagi al curves and balance
after Cotrel-Dubousset instrumentation for kyphosis secondary
to Scheuermann’s diease. A review of 32 patients. Spine
1994;19(15):1680-1685.
41. Abel TJ, Yan H, Canty M, et al: Traumatic atlanto-occipital
dislocation in children: Is external immobilization an option?
Childs Nerv Syst 2021;37(1):177-183. Eight patients with atlanto-
occipital dissociation were treated with halo vest immobilization
and did not require subsequent fusion. Level of evidence: IV.
42. O’Neill NP, Hresko MT, Emans JB, et al: Acute implant-related
complications in pediatric cervical spine fusion. J Pediatr Orthop
2020;40(7):e662-e666. Acute implant-related complications
occurred in 5 of 166 of pediatric cervical fusions (3%) requiring
surgical revision. Level of evidence: IV.
43. Murphy RF, Glo becker MP, Hresko MT, Hedequist D: Allograft
bone use in pediatric subaxial cervical spine fusions. J Pediatr
Orthop 2017;37(2):e140-e144.
44. Bauer JM, Dhillon ES, Kamps SE, et al: Classifying vertebral
artery anatomy abnormality in children with skeletal dysplasia.
Spine Deform 2021;9(3):833-839. Cervical vascular anatomy for 14
patients with skeletal dysplasia was compared with that of 32
control patients and found no systematic variations, although
individual anomalies existed within both groups. Level of
evidence: III.
45. Xu S, Ruan S, Song X, Yu J, Xu J, Gong R: Evaluation of vertebral
artery anomaly in basilar invagination and prevention of vascular
injury during surgical intervention: CTA features and analysis.
Eur Spine J 2018;27(6):1286-1294.
46. Yang BW, Hedequist DJ, Proctor MR, Troy M, Hresko MT,
Glo becker MP: Surgical fixation using screw-rod construct
instrumentation for upper cervical instability in pediatric down
syndrome patients. Spine Deform 2019;7(6):957-961. Twelve
patients with Down syndrome undergoing cervical fusions for
instability with modern techniques were found to have 5 of 12
major complications, with 4 of 12 being nonunions. Level of
evidence: IV.
47. Verhofste BP, Glo becker MP, Hresko MT, et al: Intraoperative
use of O-arm in pediatric cervical spine surgery. J Pediatr Orthop
2020;40(4):e266-e271. Intraoperative CT scan performed following
pediatric cervical fusions revealed 4 of 272 screws were
misplaced, allowing immediate revision at time of recognition.
Level of evidence: IV.
48. Fredrickson BE, Baker D, McHolick WJ, Yuan HA, Lubicky JP:
The natural history of spondylolysis and spondylolisthesis. J Bone
Joint Surg Am 1984;66(5):699-707.
49. Klein G, Mehlman CT, McCarty M: Nonoperative treatment of
spondylolysis and grade I spondylolisthesis in children and
young adults: A meta-analysis of observational studies. J Pediatr
Orthop 2009;29(2):146-156.
C H AP T E R 6 7

Pediatric Skeletal Dysplasias,

Connective Tissue Disorders,
and Other Genetic Conditions
W. G. Stuart Mackenzie MD, FAAOS, Kevin A. Morash MD,
MEd, FRCSC, Jeanne M. Franzone MD, FAAOS

Dr. Mackenzie or an immediate family member serves as a paid consultant to or is an employee of

Stryker. Dr. Franzone or an immediate family member serves as a paid consultant to or is an
employee of Orthopediatrics and serves as a board member, owner, officer, or committee member
of American Orthopaedic Association, Limb Lengthening and Reconstruction Society, and
Pediatric Orthopaedic Society of North America. Neither Dr. Morash nor any immediate family
member has received anything of value from or has stock or stock options held in a commercial
company or institution related directly or indirectly to the subject of this chapter.

ABSTRACT
It is important for surgeons to be up to date on the identification
and orthopaedic treatment options of the more common forms of
skeletal dysplasia, connective tissue disorders, and other genetic
disorders. This collection of syndromes results from disruption of
the typical development or growth of cartilage, bone, muscle, or
connective tissues. By understanding the presenting clinical and
radiographic features of these disorders, along with their natural
history, surgeons can provide safe and effective care for these
children.
Keywords: connective tissue disorders; genetics; orthopaedic
syndromes; skeletal dysplasia
Introduction
Skeletal dysplasias and connective tissue disorders represent a
heterogenous group of orthopaedic pathologies resulting from an
array of genetic mutations and chromosomal anomalies affecting
the growth and development of connective tissues, including bone.
Minute changes to the structure of the physis, composition of
connective tissues, or the process of ossification can have far-
reaching effects on skeletal development. Orthopaedic surgical
management of these children requires insight into their potential
for growth and development, as well as consideration of their
medical comorbidities.

Marfan Syndrome
Marfan syndrome results from a mutation in the gene encoding for
fibrillin, an extracellular glycoprotein involved in the formation of
elastic fibers in connective tissues. A consequent increase in growth
factor availability is responsible for changes in the mechanical
properties of soft tissues in patients with Marfan syndrome, most
importantly affecting the aortic root and the ocular lens. Classically,
patients with Marfan syndrome have tall stature, with long thin
limbs and spiderlike digits (ie, arachnodactyly). Inheritance is
commonly autosomal dominant, although spontaneous mutations
occur in 15% to 30% of cases. 1
The revised Ghent nosology emphasizes family history, aortic
root aneurysm, and ectopia lentis as cardinal features of Marfan
syndrome 2 (Table 1). Diagnosis also involves a systemic score,
including the following musculoskeletal manifestations: reduced
elbow extension, wrist and thumb signs, pectus deformity, pes
planovalgus, protrusio acetabuli, and scoliosis. Spine deformity is a
common presenting feature of Marfan syndrome and,
consequently, orthopaedic surgeons should be prepared to screen
for this underlying condition. Patients with findings of Marfan
syndrome should be referred for genetic workup, as well as
ophthalmologic and cardiac evaluations to rule out associated
abnormalities (eg, lens dislocation, aortic dilatation) that can lead
to significant morbidity and mortality.

Table 1
Revised Ghent Criteria (2010)

Absence of Family History

Aortic diameter Z-score ≥ 2 + ectopia lentis
Aortic diameter Z-score ≥ 2 + FBN1 mutation
Aortic diameter Z-score ≥ 2 + systemic score ≥ 7
Ectopia lentis + FBN1 mutation

With known aortic dilatation

Presence of Family History

Ectopia lentis
Systemic score ≥ 7
Aortic diameter Z-score ≥ 2 (age > 20 yr)
Aortic diameter Z-score ≥ 3 (age < 20 yr)
Systemic Scoring System
Wrist and thumb signs: 3

Wrist or thumb sign: 1

Pectus carinatum: 2

Pectus excavatum or chest asymmetry: 1

Hindfoot deformity: 2

Plain pes planus: 1

Pneumothorax: 2
Dural ectasia: 2
Protrusio acetabuli: 2
Reduced US/LS and increased arm span/height and no severe scoliosis: 1
Facial features (3/5): 1

Dolichocephaly, enophthalmos, downslanting palpebral fissures, malar hypoplasia,

retrognathia

Skin striae: 1
Myopia > 3 diopters: 1
Mitral valve prolapse (all types): 1
US/LS = upper segment/lower segment ratio
 Although treatment algorithms for scoliosis in Marfan syndrome
are comparable with those of idiopathic scoliosis, several
distinguishing features should be noted. From an anatomic
standpoint, patients with Marfan syndrome can have dural ectasia,
associated small pedicles, and osteopenia, all of which add
challenge to spinal instrumentation. Preoperative axial imaging (CT
and MRI) is therefore recommended for this population (Figure 1).
According to a 2021 study, females and patients with positive wrist
signs have been noted to be at particular risk for progression to
severe scoliosis. 3 Hypokyphosis, increased Cobb angle, and chest
wall deformity are associated with reduced preoperative pulmonary
function. 4 Brace treatment appears to be less effective than for
idiopathic scoliosis, with reported success of only 17% for mild to
moderate curves. 5
 Figure 1 Sagittal (A) and axial (B) magnetic resonance images from a patient
with Marfan syndrome demonstrating dural ectasia. Axial CT (C) demonstrates
alteration of the bony anatomy, with absence of or all-cortical pedicles,
precluding the use of pedicle screw instrumentation.

From a surgical standpoint, a 2019 study showed that patients

with Marfan syndrome have a 2.4% risk of neurologic complication
from spinal fusion. 6 Surgeons should be cautious if using traction
because vertebral subluxation can occur or worsen, especially in the
presence of kyphosis. 4 Other surgical risks include dural tear,
infection, pseudarthrosis, curve decompensation, and
cardiovascular complication. In combination, these factors lead to a
10% rate of readmission within 90 days of discharge after spinal
fusion. 7 Although growth-friendly spinal instrumentation
effectively increases thoracic height in patients with Marfan
syndrome with early-onset scoliosis, a 2021 study has shown that
there is a particularly high rate of implant failure during their
treatment. 8
Osteogenesis Imperfecta
Osteogenesis imperfecta is a genetic connective tissue disorder
with a suspected incidence of 1:20,000 characterized by low bone
density, fractures, spine and extremity deformity, and several
extraskeletal manifestations. 9 , 10 It is genetically and
phenotypically heterogeneous with a wide range of clinical severity.
The widely used Sillence classification was initially described in
1979 based on clinical features before the characterization of the
underlying genetic etiology. 11 Four types were described: type I:
mild, nondeforming; type II: lethal perinatal; type III: severe,
progressively deforming; and type IV: phenotypically variable,
white sclera.
In the early 1980s, type I collagen mutations were first associated
with autosomal dominant osteogenesis imperfecta. COL1A1 and
COL1A2 code for type I collagen, a heterotrimer containing two
alpha1 chains and one alpha2 chain that form a triple helix and
provide strength to the extracellular matrix of bone. Osteogenesis
imperfecta may be caused by an issue with the quality or quantity
of type I collagen. A clinically distinct form of osteogenesis
imperfecta, type V, was identified in patients demonstrating
calcification of the interosseous membrane, hyperplastic callus, and
an autosomal dominant inheritance not associated with type I
collagen mutations, subsequently found to be related to an IFITM5
mutation. 12 Over the past decade, an expanding number of
recessive forms of osteogenesis imperfecta responsible for
approximately 15% of cases have been identified, mostly caused by
mutations in genes encoding proteins involved in the synthesis or
processing of type I collagen. 13
There is currently no cure for osteogenesis imperfecta. The
mainstays of medical management include nutritional optimization
of calcium intake and vitamin D levels and activity. There is a
known positive correlation between muscle strength and bone
strength in the se ing of osteogenesis imperfecta. Diphosphonates
are a class of antiresorptive drugs shown to increase bone mass,
improve vertebral size and shape, potentially reduce fracture
frequency, and anecdotally improve bone pain. 14 Additional agents
are currently being investigated in the se ing of osteogenesis
imperfecta, including sclerostin antibody as an anabolic treatment
and denosumab, a human monoclonal antibody that blocks
RANKL, an essential cytokine in the osteoclastogenesis pathway.
Most fractures in children with osteogenesis imperfecta may be
managed nonsurgically with a period of immobilization. To avoid a
cycle of muscle weakness, disuse osteopenia, and a fracture cluster,
immobilization periods should be as brief as possible permi ed by
early healing. Surgical intervention in the form of realignment and
intramedullary rodding is indicated for progressive long bone
deformity interfering with motor development or function or
associated with recurrent fractures, otherwise operatively indicated
fractures and symptomatic nonunions 15 , 16 (Figure 2). The concept
of multiple osteotomies and intramedullary fixation has long been
used, and this surgical concept continues to be used with less
invasive osteotomies. Both fixed-length rods and telescopic rods,
currently most commonly the Fassier-Duval implant, have been
described. 17 - 19 A 2020 multicenter review demonstrated that most
individuals with moderate and severe forms of osteogenesis
imperfecta undergo rodding procedures and that individuals with
severe osteogenesis imperfecta who underwent rodding have
improved mobility outcomes and lower fracture rates. 20 A meta-
analysis of 359 primary nonelongating rodding procedures of
femurs and tibias in children with osteogenesis imperfecta with a
mean follow-up of 63 months showed a revision surgery rate of
39.4%. 21 The aim of telescopic rods such as the Fassier-Duval rod is
to reduce the number of revisions required because of growth;
however, telescopic rods are notable for a similar revision and
complication rate. The authors of a 2019 study 22 reported the use of
Fassier-Duval rods over static implants in pediatric patients with
osteogenesis imperfecta to demonstrate a higher implant survival
during the first 48 months after index surgery as well as a decrease
in the incidence of total number of surgeries (planned and
unplanned) among Fassier-Duval rods compared with static rods.
Additionally, transfixion pin backout and prominence are common
in the se ing of Fassier-Duval rods. 23 Center-center position of the
male component of the Fassier-Duval rod in the epiphysis of the
distal femur and tibia contributes to rod longevity. 24 There is a
growing body of data that tourniquets and noninvasive blood
pressure cuffs may be used for children with osteogenesis
imperfecta. 25 , 26

Figure 2 AP view of the bilateral lower extremities (A) and lateral views of the
femurs (B and C) of a 2-year-old boy with severe osteogenesis imperfecta who
underwent realignment and intramedullary rodding of the bilateral femurs and
tibias with telescopic intramedullary rods (D through G). H and I, Bilateral lower
extremity radiographs at age 5 years. J and K, Realignment and intramedullary
rodding of his humeri with a threaded male component of a telescopic rod and a
retrograde telescopic rod, respectively.

Acetabular protrusio, more common in those with more clinically

severe osteogenesis imperfecta, is progressive over time and
remains a challenging problem. 27 , 28 It is also associated with
femoral neck fractures and there is to be a high index of suspicion
in diagnosing nondisplaced femoral neck fractures, particularly
when nondisplaced. 29 Elbow deformities are also common in the
se ing of osteogenesis imperfecta including radial head
dislocation, most common in patients with osteogenesis imperfecta
type V. Another issue about the elbow includes olecranon fractures.
A 2019 review of 358 patients found an incidence of olecranon
fractures of 8.1%, predominantly in type I patients with a 41%
chance of sustaining a contralateral olecranon fracture within the
subsequent 5 months. 30
Spinal manifestations in osteogenesis imperfecta include
scoliosis, kyphosis, craniocervical junction abnormalities (ie, basilar
invagination), spondylolysis, and spondylolisthesis. The prevalence
of scoliosis in the population of patients with osteogenesis
imperfecta ranges from 39% to 80%, more prevalent in the more
severe forms of osteogenesis imperfecta. It is known to progress if
untreated well into adulthood. Spinal fusion to halt curve
progression is considered when curves reach 45°, but the patient’s
age and truncal height need to be considered to avoid thoracic
insufficiency syndrome. Contemporary techniques and a
multimodal strategy to address the poor bone quality have shown
promising results for spinal fusion in the se ing of osteogenesis
imperfecta. There have also been recent reports of growth-friendly
surgical treatment of scoliosis in the se ing of osteogenesis
imperfecta. 31
Craniocervical junction abnormalities are seen in 37% of patients
with osteogenesis imperfecta, including basilar invagination (13%),
basilar impression (15%), and platybasia (29%). 32 Skull base
abnormalities are correlated with the severity of disease and older
age. Advanced imaging modalities including CT and MRI are
recommended to best understand the complex anatomy that can be
quite difficult to discern on plain radiography. Basilar invagination
may incur debilitating neurologic consequences, and ongoing
screening of the osteogenesis imperfecta population, particularly
those more severely affected, is an important aspect of care. 33
Management of basilar invagination may be by odontoid resection,
foramen magnum decompression, or both and may require
occipitocervical fusion with adjunctive preoperative halo traction.

Neurofibromatosis Type 1
Neurofibromatosis type 1 is a common, autosomal dominant
single-gene disorder affecting production of neurofibromin, a
protein implicated in skeletal growth and development. It is
defined using criteria established in 1987 by the National Institutes
of Health (Table 2), with at least two such findings required for
diagnosis. Notably, these features may develop at different ages,
meaning that orthopaedic surgeons should maintain suspicion for
this underlying condition as they follow very young patients
meeting only one criterion (eg, tibial dysplasia). Common
orthopaedic manifestations of neurofibromatosis type 1 include
scoliosis, dysplasia of long bones, limb overgrowth, and malignant
transformation of tumors.

Table 2
National Institutes of Health Diagnostic Criteria for NF-1

Criteria are Met With Two or More of the Following:

≥6 café-au-lait spots

Macules >5 mm in children, >15 mm in adults

≥2 neurofibromas or 1 plexiform neurofibroma

Axillary or inguinal freckling
Optic glioma
≥2 Lisch nodules (iris hamartomas)
Distinctive osseous lesion

Sphenoid dysplasia

Thinning of long bone, with or without pseudarthrosis

First-degree relative with NF-1

NF-1 = Neurofibromatosis type 1
Data obtained from Neurofibromatosis. Conference Statement. National Institutes of Health
Consensus Development Conference. Arch Neurol 1988;45:575-578.

Scoliosis in neurofibromatosis type 1 can be categorized as

dystrophic or nondystrophic. Dystrophic curves are typically short,
sharp thoracic curves that progress rapidly and are associated with
characteristic radiographic findings (Table 3). When these features
are present, preoperative CT and MRI provide valuable information
regarding the presence of dural ectasia, rib head dislocations, and
paraspinal masses (Figure 3). Early surgical management is
generally undertaken for dystrophic scoliosis, although there
remains some debate surrounding the relative merits of definitive
fusion versus growth-friendly surgery in the early-onset
neurofibromatosis type 1 population. 34 - 36 When growing rods are
used, dual-rod constructs are preferred because of a high rate of
implant-related complications. 37 In contrast, nondystrophic curves
can be managed with similar principles to idiopathic scoliosis, with
careful observation for potential modulation (ie, development of
dystrophic features) over time.

Table 3
Dystrophic Radiographic Changes in NF-1 Scoliosis

Vertebral scalloping
Rib pencilling
Transverse process spindling
Vertebral wedging
Paravertebral soft-tissue mass
Short curve with severe apical rotation
Foraminal enlargement
Widened interpediculate distance
Dysplastic pedicles
NF-1 = Neurofibromatosis type 1
 Figure 3 Preoperative radiograph (A) from a patient with neurofibromatosis
type 1 and dysplastic scoliosis, who required combined anterior and posterior
instrumentation and fusion. B, Careful preoperative planning including CT scan
is important to identify dysplastic elements, such as dural ectasia, abnormal
pedicles, neurofibromas, and migration of rib heads into the spinal canal (C).

Tibial dysplasia is commonly associated with neurofibromatosis

type 1 and can present in infancy as an anterolateral tibial bow,
with or without pseudarthrosis (ie, congenital pseudarthrosis of the
tibia). In this condition, the dysplastic site is surrounded by
hamartoma that predisposes to fracture and complicates healing.
When tibial dysplasia presents in a prefracture state, treatment has
traditionally involved protective clamshell bracing; however, distal
tibial guided growth has recently shown encouraging results in
preventing fracture while promoting remodeling. 38 Once fracture
occurs, surgical treatment generally aims to achieve and maintain
union, while correcting the underlying deformity. Therefore,
aggressive débridement of the pathologic tissue is advocated,
followed by autografting and stabilization with intramedullary rods
or external fixation. 39 , 40 Recent literature has emphasized the
importance of fibular procedures (including intentional cross
union) in achieving union, as well as the potential adjunctive value
of diphosphonate infusions and off-label use of bone
morphogenetic protein. 41 , 42 Patients undergoing multiple
surgeries have been treated with vascularized fibular autografts,
Ilizarov frames, and induced-membrane techniques, although
amputation remains a possibility in these challenging scenarios. 37 ,
43 , 44

Ehlers-Danlos Syndrome
Ehlers-Danlos syndrome (EDS) is a heterogeneous group of
heritable connective tissue disorders affecting collagen production
and metabolism. The most recent classification of EDS (2017)
includes 13 subtypes, of which the classic (cEDS) and hypermobile
(hEDS) subtypes are most commonly encountered in clinical
practice. 45 Although each subtype is unique in its genetic basis,
presenting symptomatology and diagnostic criteria, prominent
features generally include joint hypermobility, skin hyperelasticity,
and tissue fragility. Both cEDS and hEDS have autosomal dominant
inheritance pa erns, although the specific molecular basis of hEDS
remains unknown. 45 Patients with EDS often present to
orthopaedic surgeons with recurrent joint dislocations (eg,
glenohumeral, patellofemoral) and chronic musculoskeletal pain. 41
, 46 , 47
Less commonly, EDS can manifest with spinal deformity or
instability. 42
The Beighton score is used in the clinical evaluation of
generalized joint hypermobility and is also included in diagnostic
criteria for EDS 45 (Table 4). The following Beighton score cutoffs are
used (among other criteria) for hEDS: more than 6 points for
prepubertal children, more than 5 for adults up to age 50 years, and
more than 4 for patients older than 50 years. 45 Certainly, there
exists a wide spectrum of joint laxity among orthopaedic patients,
and principles relevant to EDS can likely be applied when treating
other patients with high Beighton scores. 47

Table 4
Beighton Score
Passive dorsiflexion of fifth metacarpophalangeal joint ≥90° 1 point per
side
Passive apposition of thumb to volar forearm (shoulder flexed 90°, elbow 1 point per
extended, hand pronated) side
Passive elbow extension ≥10° 1 point per
side
Passive knee extension ≥10° 1 point per
side
Forward flexion of trunk (knees extended), so that palms of both hands rest 1 point
flat on floor
Total possible score 9 points

Management of recurrent joint instability in EDS often begins

with physical therapy, focusing on improving active range of
motion while strengthening dynamic stabilizers. If surgical
management is considered, patients should be counseled regarding
the potential for poor results with standard soft-tissue
reconstructions. 46 , 47 Although various adjunctive procedures (eg,
allografts, bony augmentations, osteotomies) have been developed
to enhance joint stability in patients with EDS, there are few high-
quality studies reporting on their outcomes. 46 Similar principles
should be used when planning arthroplasty for patients with EDS,
including consideration of constrained components (eg, dual-
mobility cups) to account for lax soft tissues. 48 , 49 Careful,
multilayered closure and appropriate postoperative immobilization
can help to optimize wound healing.
Chronic joint pain can be a challenging problem in EDS, limiting
function and affecting health-related quality of life. 45 A 2019 study
has also shown higher rates and durations of opioid use among
patients with EDS compared with matched control patients. 41
These issues highlight the importance of maintaining a broad,
multidisciplinary approach when treating patients with connective
tissue disorders.

Achondroplasia
Achondroplasia is the most common form of skeletal dysplasia,
affecting approximately 250,000 people worldwide. This form of
disproportionate dwarfism is the result of a gain-of-function
mutation in the fibroblast growth factor receptor 3 (FGFR3) gene, 50
resulting in increased tyrosine kinase activity and impaired
cartilage differentiation and endochondral ossification. The
resulting phenotype is characterized by short stature, rhizomelia,
macrocephaly, and frontal bossing.
Other mutations of the FGFR3 gene can result in various
associated skeletal dysplasias, including thanatophoric dysplasia,
severe achondroplasia with developmental delay and acanthosis
nigricans, hypochondroplasia, and Crouzon syndrome.
Thanatophoric dysplasia is usually fatal by age of 2 years because of
cardiopulmonary failure and is associated with severe rhizomelia,
protuberant abdomen, and a small, restrictive thoracic cavity
leading to cardiopulmonary failure.
Infants with achondroplasia historically had an increased risk of
mortality, likely because of foramen magnum stenosis resulting in
cervico medullary compression and central sleep apnea, although
mortality rates now approach those of unaffected infants because of
improved surveillance. Comprehensive care of these children
requires regular clinical assessment for symptoms of compression,
including detailed history of motor development, neurologic
examination, and polysomnography. MRI is not necessary for every
child with achondroplasia and should only be obtained to confirm
suspected cases. Foramen magnum stenosis and treatment with
surgical decompression is required in 20.5% of children with
achondroplasia, with 10% requiring a second decompression. 51
Thoracolumbar kyphosis develops in nearly all infants with
achondroplasia and usually progresses until children are able to
ambulate independently. 52 This deformity is flexible in infants, and
progression can be limited by educating the family on si ing
modifications. Although treatment with bracing has been
considered in the past, the evidence is hard to interpret in light of
the natural history of thoracolumbar kyphosis in achondroplasia,
with 73% spontaneous resolution within 1 year of walking 53 and
89% resolution by 10 years of age. 54 As the thoracolumbar kyphosis
decreases in these children, there is a compensatory increase in
lumbar lordosis and sacral slope, maintaining overall sagi al
balance. 55 In those patients with persistent kyphosis, there is a risk
of progression and exacerbation of existing spinal stenosis leading
to myelopathy, progressing rarely to paraplegia. Although
correction of thoracolumbar kyphosis can be performed by a
combined anterior-posterior approach, most modern treatment is
performed using an all-posterior approach with osteotomies,
achieving correction without lengthening the spinal cord. Kyphosis
that involves wedged and posteriorly translated apical vertebrae
can be managed with vertebral column resection, but according to a
2021 study, rates of neurologic injury and failure of instrumentation
remain high (57%) 56 (Figure 4). Historically, indication for surgical
correction of thoracolumbar kyphosis was deformity greater than
45°, and although modern indications remain undefined, surgery
should be considered for progressive deformity greater than 60°
and symptomatic spinal stenosis.
 Figure 4 A 16-year-old boy with achondroplasia with progressive
thoracolumbar kyphosis seen on lateral radiograph (A), with apical vertebral
body wedging and posterior translation, resulting in spinal stenosis on a
magnetic resonance image. B, He was treated with posterior vertebral column
resection to shorten the spinal column and safely correct his sagittal deformity
(C).

Spinal stenosis is a characteristic of achondroplasia and can be

present at any level of the spine, with symptoms in up to 68% of
patients with first onset at an average age of 33 years. 57 In patients
with residual thoracolumbar kyphosis, symptomatic spinal stenosis
can present as early as the second decade. Symptoms of stenosis
can include radicular pain, paresthesias, leg weakness or decreased
endurance, and bladder or bowel dysfunction. Evaluation by MRI of
the entire spine is recommended, but interpretation can be
challenging because of preexisting asymptomatic stenosis.
Urodynamics to assess bladder function can be useful to determine
if a patient’s lower extremity symptoms are secondary to spinal
stenosis.
Modern treatment involves laminectomy to decompress the
symptomatic levels of stenosis, without the need for prophylactic
decompression from the thoracolumbar junction to the sacrum. In
skeletally immature patients, and any patient with residual
thoracolumbar kyphosis, fusion of the decompressed levels is
required to prevent postlaminectomy kyphosis.
 Genu varum is another classic feature of achondroplasia, usually
associated with internal tibial torsion and ligamentous laxity. Lower
extremity malalignment is often asymptomatic and can be observed
as it does not appear to be linked to degenerative osteoarthritis.
Indications for treatment include progressive knee, ankle, or foot
pain and dynamic varus instability on gait analysis. In skeletally
immature patients, hemiepiphysiodesis of the distal femur and
proximal tibia is effective for treatment of genu varum. Older
patients can be treated with multilevel osteotomies to restore limb
alignment, with the use of a hexapod external fixator for gradual
correction of proximal tibial deformity. Of note, when assessing a
patient with knee pain, consideration of symptomatic discoid
meniscus is important because of increased prevalence in
achondroplasia.
In addition to trident or starfish hands, individuals with
achondroplasia will often have elbow flexion contractures and
subluxated radial heads. When combined with rhizomelia, elbow
contractures can limit patients’ ability to perform activities of daily
living, in turn limiting their independence. Reach may be increased
by humeral osteotomy with a uniplanar external fixator, achieving
an average of 55% lengthening with low complication rates. 58
In recent years, medical treatment for achondroplasia has made
great strides. Vosoritide, a C-type natriuretic peptide analog,
inhibits the FGFR3-mediated mitogen-activated protein kinase
pathway to improve endochondral bone formation. Vosoritide has
been studied in a 2020 randomized, phase 3, double-blind, placebo-
controlled trial and is shown to be safe, with increase in
longitudinal growth of 1.57 cm per year. 59 Although this increase in
height is promising, there are no data on the effects on
thoracolumbar kyphosis, spinal stenosis, or genu varum. Soluble
FGFR3 is also currently under investigation and is hypothesized to
work by competitively binding FGF, reducing the activation of the
mitogen-activated protein kinase pathway.
Pseudoachondroplasia
Although pseudoachondroplasia may appear similar to
achondroplasia, these are two distinct pathologies with misleading
nomenclature, originally differentiated in 1959.
Pseudoachondroplasia is the second most common form of skeletal
dysplasia, characterized by a short-limb and short-trunk
disproportionate dwarfism inherited in an autosomal dominant
manner. Mutation of the collagen oligomeric matrix protein results
in accumulation within the rough endoplasmic reticulum, with
premature chondrocyte apoptosis and impaired endochondral bone
growth.
Diagnosis of pseudoachondroplasia tends to be delayed, between
2 and 4 years old, and individuals present with normal facial
features, rhizomelia, joint laxity, lower extremity malalignment, and
progressive osteoarthritis. Radiographs demonstrate several
characteristic features, including platyspondyly with beaking of the
anterior vertebral bodies, brachydactyly, long bone epiphyseal
dysplasia, and metaphyseal flaring.
Pseudoachondroplasia has a 12% rate of atlantoaxial instability
and 58% rate of thoracolumbar scoliosis, and surveillance with
regular examinations and imaging is necessary. Instability,
myelopathy, and progression of deformity are all indications for
surgical treatment.
Proximal femoral epiphyseal dysplasia leads to the loss of
femoral head sphericity in pseudoachondroplasia, resulting in
degenerative arthritis by the early third decade. The principle
component of hip perseveration is improving joint containment,
and in the only publication to date, containment of the femoral
head with Chiari osteotomy improved hip function, reduced pain,
and delayed the need for arthroplasty. 60
The classic lower extremity malalignment associated with
pseudoachondroplasia is a windswept deformity, and the legs may
have either varus or valgus alignment. In skeletally immature
patients, correction can be achieved using hemiepiphysiodesis or
osteotomy, but maintenance of alignment until maturity is
challenging and can require revision surgery. 61 Following maturity,
osteotomies are required, and careful consideration must be paid to
alignment to help limit degenerative arthritis.

Diastrophic Dysplasia
Diastrophic dysplasia is a rare, autosomal recessive form of skeletal
dysplasia that occurs because of a genetic mutation in the SLC26A2
gene, which encodes for the diastrophic dysplasia sulfate
transporter protein. There is variability in phenotypic expression,
with the most mild form considered autosomal recessive multiple
epiphyseal dysplasia (MED). Diastrophic, meaning distorted, refers
to the pathognomonic features of hitchhiker thumbs and
cauliflower ears, joint contractures, and deformities of the spine,
long bones, and feet.
Serious, life-threatening spine deformity can develop in
individuals with diastrophic dysplasia, beginning with cervical
kyphosis in 24% of patients, presenting at an average age of 10
months. 62 Fortunately, up to 75% of these cases resolve
spontaneously, but children must be observed closely because of
the risk of deformity progression with spinal cord compression,
with published reports of paralysis and cardiopulmonary failure. 63
At greatest risk are those children with kyphosis greater than 60°
and hypoplastic apical vertebrae. 62 Patients can be temporized
using halter traction or cervicothoracic orthoses, but persistent
deformity and spinal cord compression requires decompression via
anterior corpectomy of the hypoplastic apical vertebrae, followed
by posterior fusion. Many of these children will require treatment
at age younger than 5 years, preventing screw and rod constructs,
and sublaminar wiring is limited because of spina bifida in the
subaxial cervical spine (Figure 5).
 Figure 5 Lateral radiograph from a 3-year-old patient with diastrophic
dysplasia demonstrating persistent cervical kyphosis.A, Treatment required
anterior corpectomy for decompression, followed by posterior fusion with
sublaminar band C2-6 due to bifid posterior spinal elements (B).

Kyphoscoliosis is the more prevalent spinal deformity, reported

in 33% to 88% of individuals with diastrophic dysplasia. Most
deformities are hyperkyphotic double thoracic curves, which often
present in early childhood. Kyphoscoliosis can progress quickly in
these children, becoming rigid with potential to affect pulmonary
function. Early treatment can involve bracing or casting, and several
growth-friendly spine constructs have been used successfully. 54
Thoracic kyphosis can make for challenging implant positioning,
and surgeons can consider preoperative halo-gravity traction to
improve sagi al alignment. There is limited longitudinal growth of
the spinal column after age 10 years, and larger, more stiff
deformities in older children should be managed with posterior
spinal instrumentation and fusion.
In the lower extremities, young adults can have symptomatic
degenerative disease of their hips related to epiphyseal dysplasia.
Genu valgum can develop, with progressive lateral
subluxation/dislocation of the patella, resulting in significant knee
flexion contractures. Gait analysis of patients with diastrophic
dysplasia and dislocated patellas demonstrates increased crouched
gait. 64 Treatment with soft-tissue releases and patellar
centralization can restore active knee extension, and improving the
ambulatory status of these children. 64
Children with diastrophic dysplasia have also been reported to
have clubfeet at birth, but close three-dimensional anatomic study
reveals that associated foot deformity bears li le resemblance to
idiopathic clubfoot. 65 Variations of equinus, metatarsus adductus,
and equinovarus can be seen, but most common is a skewfoot-type
deformity with both metatarsus adductus and hindfoot valgus.
Correction of foot deformity with serial casting yields limited
results. Often there is persistent equinus that requires
tendoachilles lengthening, posteromedial release, or consideration
of supramalleolar osteotomies depending on the range of motion
through the tibiotalar joint. A ention must be paid to the overall
limb kinematics when addressing equinus because there are often
concomitant hip and knee flexion contractures. 64

Cleidocranial Dysplasia
Cleidocranial dysplasia is a skeletal dysplasia characterized by a
failure of intramembranous ossification, resulting in a midline
deficiency of the clavicles and pelvis and delayed closure of the
cranial fontanels. It results from an autosomal dominant
deactivating mutation in runt-related transcription factor 2,
resulting in impaired differentiation of osteoblasts. 66 The most
characteristic clinical feature is narrow shoulders, which may be
brought to the midline because of clavicle deficiency. Patients are
often of short stature, with delayed closure of the pubic symphysis,
coxa vara or valga, scoliosis in 28% of patients, and spondylolysis in
up to 24%. 67 Management of scoliosis and hip deformity has only
been described in small series and case reports or as small subsets
in larger series.

Down Syndrome
Down syndrome, caused by trisomy 21, is a common chromosomal
condition occurring in approximately 1 in 800 live births. 68 Down
syndrome presents more frequently with advanced maternal age
and is associated with many systemic manifestations, including
intellectual disability, congenital heart disease, pulmonary
hypertension, hypothyroidism, arthropathy of Down syndrome,
and an increased risk of leukemia. 68 From a musculoskeletal
standpoint, joint hypermobility and variations in bony anatomy can
contribute to a variety of orthopaedic issues. These range in severity
from benign, nonsurgically managed problems (eg, pes planus in
91% of patients with Down syndrome) to potentially life-
threatening conditions (eg, atlantoaxial instability with
myelopathy). 69
Although up to 30% of patients with Down syndrome may
demonstrate radiographic hypermobility of the upper cervical
spine, this only leads to neurologically symptomatic instability in
approximately 1% of patients. 69 Importantly, patients with Down
syndrome with bony abnormalities at the craniocervical junction
(eg, os odontoideum) are at particular risk for the development of
symptomatic instability. 70 Many radiographic measurements have
been proposed to screen for symptomatic atlantoaxial instability,
including the atlantodental interval, space available for the cord
(SAC), and a C1/C4 SAC ratio. 71 Recent evidence has suggested
that neutral upright lateral radiographs might be more efficient
than flexion-extension views in screening for upper cervical
instability in Down syndrome, using cutoff values of atlantodental
interval greater than 6 and SAC less than 14. MRI provides
important information when evaluating patients with symptoms or
significant radiographic findings, and some authors have recently
applied dynamic MRI to this population. 70 Although surgical
management of upper cervical instability in Down syndrome has
traditionally been associated with a high complication rate, modern
screw-rod fixation strategies have been reported to improve
outcomes. 72 , 73
 The incidence of scoliosis in Down syndrome is between 5% and
21%, with most patients exhibiting double major curve pa erns
resembling idiopathic scoliosis. 69 In this population, scoliosis can
occur with or without a history of cardiac surgery, so screening is
generally advised. Although brace treatment is controversial in
patients with Down syndrome, some authors have noted success
with this treatment. Ultimately, posterior spinal fusion can be
performed for large curves, although complication rates are higher
than for idiopathic scoliosis.
Hip instability is associated with Down syndrome and can
significantly reduce mobility if it is not appropriately addressed
during childhood. This entity is distinct from congenital dysplasia
because hips with initially normal radiographic appearances can
progressively dislocate over time, acquiring posterior acetabular
deficiency. 74 Other contributing factors to this pathology include
the generalized ligamentous laxity of Down syndrome, as well as
abnormal proximal femoral anatomy (eg, femoral neck
anteversion). Early surgical treatment should be considered once
hip instability is identified. Various proximal femoral and pelvic
osteotomies have been used for this indication, although older
children benefit most from acetabular reorientation to address the
posterior deficiency 75 (Figure 6). According to a 2019 study, good
outcomes have been reported for adults with Down syndrome
undergoing total hip arthroplasty, although the revision rate is 7.5%
at 5 years in this population. 76
 Figure 6 A, AP pelvic radiograph from a 13-year-old boy with Down syndrome
demonstrating a progressively subluxated left hip with a capacious dysplastic
acetabulum. B, Treatment with a Bernese periacetabular osteotomy allows
excellent coverage of the femoral head and medialization of the hip.

Patients with Down syndrome often have genu valgum which, in

combination with their generalized ligamentous laxity, predisposes
them to patellofemoral instability. In symptomatic patients, first-
line treatment includes activity modification, bracing, and physical
therapy. 69 Numerous surgical techniques have been used to
address patellofemoral instability in Down syndrome, with varying
success. 77 Ultimately, surgical treatment should be tailored to
address the specific anatomic factors relevant to each case.

Mucopolysaccharidoses
Mucopolysaccharidoses (MPS) are a group of lysosomal storage
disorders characterized by the progressive accumulation of
glycosaminoglycans (GAG). There are six autosomal recessive
subtypes and one X-linked recessive subtype, each with a single-
gene mutation affecting a different enzyme responsible for GAG
degradation (Table 5). Accumulation of GAG in organs leads to
systemic cellular dysfunction and damage. Specific to the
musculoskeletal system, GAG accumulation in the soft tissue,
bone, and cartilage leads to atypical intramembranous and
endochondral bone formation and remodeling, commonly resulting
in short stature with a short, broad trunk, thoracolumbar gibbus
deformity (kyphosis), and bilateral hip dysplasia, which can be
mistaken for Legg-Calvé-Perthes disease.

Table 5
The Mucopolysaccharidoses

Substance Inheritance
Designation Syndrome Enzyme Defect
Stored Pattern
MPS IH Hurler α-l-Iduronidase HS, DS Autosomal
recessive
MPS 1HS Hurler/Scheie — — —
MPS 1S Scheie — — —
MPS II Hunter Iduronidase-2-sulfatase HS, DS X-linked
recessive
MPS IIIA Sanfilippo A Heparin-sulfatase HS Autosomal
(sulfamidase) recessive
MPS IIIB Sanfilippo B α-N-acetylglucosaminidase HS Autosomal
recessive
MPS IIIC Sanfilippo C Acetyl-CoA: α-glucosaminide- HS Autosomal
N-acetyltransferase recessive
MPS IIID Sanfilippo D Glucosamine-6-sulfatase HS Autosomal
recessive
MPS IVA Morquio A N-acetyl galactosamine-6- KS, CS Autosomal
sulfate sulfatase recessive
MPS IVB Morquio B β-d-Galactosidase KS, CS Autosomal
recessive
MPS VI Maroteaux- Arylsulfatase B, N- HS, DS Autosomal
Lamy acetylgalactosamine-4- recessive
sulfatase
MPS VII Sly β-d-Glucuronidase CS, HS, Autosomal
DS recessive
MPS VIII no eponym Glucosamine-6-sulfatase CS, HS Autosomal
recessive
CS = chondroitin sulfate, DS = dermatan sulfate, HS = heparan sulfate, KS = keratan sulfate,
MPS = mucopolysaccharidosis

The radiographic features of these changes are referred to as

dysostosis multiplex. These features include platyspondyly with
anterior vertebral beaking, broad iliac wings, acetabular dysplasia,
coxa valga with progressive epiphyseal dysplasia and fla ening,
Madelung deformity of the distal radius with negative ulnar
variance, and short metacarpals with proximal tapering (Figure 7).

Figure 7 Radiographs from a 9-year-old boy with Morquio syndrome

demonstrate thoracolumbar kyphosis with vertebral body beaking at the apex
(A), ulnar deviation of the forearm with tapered metacarpal bases (B), and
progressive bilateral hip dysplasia leading to dislocation (C). Hip reconstruction
with bilateral proximal femoral osteotomies and shelf acetabuloplasty with
improved hip containment in this patient led to painless, unlimited ambulation at
15 years follow-up (D).

A nonorthopaedic feature of Morquio syndrome with surgical

significance is tracheal narrowing and deviation that can prohibit
safe intubation and result in perioperative death. According to a
2021 study, the trachea is narrowed an average of 63.9% at the
thoracic inlet, worse in older children, and associated with position
of the brachiocephalic artery and thyroid gland. 78 Clinicians should
consider CT angiogram to assess the airway in children older than 8
years.
Patients with MPS can have spinal stenosis anywhere from the
occipitocervical junction to the cervicothoracic junction, with
associated atlantoaxial instability. Stenosis can result from
extradural deposition of GAG, dural thickening, multilevel disk
herniation, and atlantoaxial instability secondary to odontoid
hypoplasia or ligamentous laxity. 79 Although careful neurologic
examinations are a key component of care, patients can have spinal
cord compression without abnormal findings. 80 With specific
a ention paid to MPS IV, expert consensus recommends early,
serial MRIs, with flexion and extension views to detect atlantoaxial
instability. 81 Indications for surgery are most commonly
progressive neurologic symptoms, as well as myelomalacia on MRI,
and dynamic instability. 79 Stenosis with myelomalacia can be
managed with decompression alone, such as laminectomy or
laminoplasty, but any concern for atlantoaxial instability requires
fusion.
Thoracolumbar kyphosis in MPS requires less urgent treatment,
but can be progressive and is managed with serial examinations
and imaging. These patients rarely become myelopathic, as the
apex of kyphosis tends to be distal to the conus medularis, but they
can develop spinal stenosis with pain and neurologic dysfunction.
Expert consensus recommends surgical treatment for any patient
with progressive thoracolumbar kyphosis, intractable pain, and
neurologic deterioration. 80 Bracing can be considered in children
with a flexible deformity, with a goal of delaying surgery, 82 and the
use of growth-friendly spinal instrumentation can be considered.
Modern treatment of skeletally immature patients involves short
posterior pedicle screw and rod constructs (at least two levels
cephalad and caudal to the apex), allowing for safe and effective
correction of thoracolumbar kyphosis although there is risk for
proximal junctional kyphosis. 79
Untreated hip dysplasia in MPS can lead to progressive hip
subluxation and dislocation, associated with pain and decreased
endurance. In patients with femoral head coverage less than 50%
with hip pain and dysfunction, the combination of proximal
femoral osteotomy with pelvic osteotomy provides excellent
radiographic outcomes. In young patients with MPS type I,
improved femoral head coverage by Pemberton osteotomy has been
shown to allow spherical remodeling of the fla ened proximal
femoral epiphysis. 83 Consideration of surgical technique is
dependent on the anatomy, and CT scan helps demonstrate the
extent of acetabular deficiency. Patients with substantial dysplasia
may be best served with a salvage shelf acetabuloplasty because of
the risk of progressive subluxation (Figure 7). Hip dysplasia with
pain and dysfunction in adults with MPS is reliably treated with
arthroplasty, even in cases of previous hip reconstruction. 84
Genu valgum in MPS can be assessed by radiographs, but the
contribution of external tibial torsion and knee instability is best
evaluated using three-dimensional gait analysis. 85 Genu valgum
treatment using hemiepiphysiodesis is proven safe and effective in
MPS type IV, correcting malalignment and improving physical
function. 86 Observation is required following correction until
skeletal maturity, as recurrence of deformity is common.
Osteotomies may be considered in older patients, with total knee
arthroplasty reserved for patients with advanced degenerative
arthritis. Total knee arthroplasty requires consideration of lateral
releases and constrained prostheses because of instability, with a
role for custom-designed implants.
GAG deposition in MPS types I, II, VI, and VII can also result in
upper extremity compression neuropathies and triggering of the
digits. Most common is median nerve compression, but reliance on
clinical examination results in delayed diagnosis of carpal tunnel
syndrome in these children. Early median nerve decompression is
associated with improved outcomes, and nerve conduction studies
should be performed at initial diagnosis of MPS, with annual
follow-up thereafter. 87 , 88

Multiple Epiphyseal Dysplasia

MED is composed of a heterogenous group of dysplasias
characterized by irregularity of the epiphyses of long bones, mild
short stature, genu valgum, and early-onset arthritis of the hips and
knees. Autosomal dominant forms of MED are the result of
mutations in the COMP, COL9A1, COL9A2, COL9A3, and MATN3.
By adolescence, most epiphyses appeared fla ened, with
progressive osteoarthritis. The autosomal recessive form of MED
(rMED) is related to mutations in the SLC26A2 gene, and these
patients can present not only with fla ened epiphyses and joint
pain, but are noted to have double-layer patellas. rMED is similar to
a mild form of diastrophic dysplasia, and many individuals are
born with clubfeet.
The management of MED classically involves the use of weight
management, low-impact exercises, and analgesics, along with
correction of lower extremity malalignment, to limit joint pain.
Surveillance of the hips during childhood allows opportunity for
salvage osteotomies to improve hip containment, which can be
effective at delaying total hip arthroplasty. 60 Untreated patients
often require arthroplasty in the third and fourth decades, which
can provide excellent pain relief and improved quality of life for
patients with MED (Figure 8).

Figure 8 A, AP pelvic radiograph from a 29-year-old man with multiple

epiphyseal dysplasia demonstrates bilateral proximal femoral epiphyseal
dysplasia with flattening and progression to severe osteoarthritis and hip
subluxation. B, Treatment with bilateral hip arthroplasty can lead to drastic
improvement in quality of life with resolution of hip pain.
X-Linked Hypophosphatemic Rickets
X-linked hypophosphatemic rickets (XLH) is the most common
inherited form of rickets, occurring in 1 in 20,000 live births. XLH
has an X-linked dominant inheritance pa ern and results in renal
phosphate wasting (with consequent hypophosphatemia), causing
rachitic changes despite a normal vitamin D level. 89 In this
condition, mutations of the PHEX gene lead to increased fibroblast
growth factor 23 (FGF23) activity, suppression of renal phosphate
reabsorption, and decreased production of 1,25-OH vitamin D.89
Ultimately, these factors impair bone mineralization at the physeal
zone of provisional calcification, resulting in a variety of
musculoskeletal manifestations, including short stature, bowing of
the lower extremities, torsional deformities, gait abnormalities,
enthesopathy, and joint pain. 90 , 91 From a nonorthopaedic
standpoint, XLH predisposes to dental abscesses, hearing loss, and
premature fusion of the frontal and parietal bones.90 XLH can vary
considerably in its phenotypic severity, ranging from isolated
biochemical hypophosphatemia to advanced skeletal deformities.
In the absence of family history, patients with XLH often present
in early childhood with short stature, delayed walking, or lower
extremity malalignment (eg, genu varum or valgum). 89 ,92 With
progressive weight bearing, the lower extremities become
disproportionately shortened and increasingly bowed. If XLH is
suspected, radiographic evaluation of the lower extremities can
support its diagnosis, while ruling out other pathologies such as
skeletal dysplasias.89 Radiographic findings of XLH are most
pronounced at areas of rapid growth and can closely resemble
nutritional rickets. Such findings include indistinct or widened
metaphysis, thickened physes, and pseudofractures (ie, Looser
zones).90 Laboratory testing is required to distinguish XLH from
other forms of rickets, typically demonstrating low serum
phosphate and elevated alkaline phosphatase, with normal levels of
calcium, cholecalciferol, and parathyroid hormone. Urine studies
can then confirm renal phosphate wasting, whereas FGF23 levels
and molecular genetic testing are diagnostic.90
Patients with XLH require comanagement with endocrinologists
or nephrologists interested in metabolic bone diseases. Medical
treatment is most effective when initiated at an early age and can
support longitudinal growth, along with remodeling of lower
extremity deformities. 92 Conventional therapy involves
supplementation of phosphate and activated vitamin D, titrated to
the desired phenotypic response; however, this strategy can be
complicated by nephrocalcinosis and secondary
hyperparathyroidism. 90 ,93 Recently, there has been significant
interest in burosumab, a monoclonal antibody inhibiting FGF23. A
2019 phase 3 clinical trial found that burosumab treatment resulted
in improved linear growth and mobility compared with
conventional therapy. 93 The potential benefit of adjunctive growth
hormone therapy is less clear. 90 Regardless of which medical
treatment strategies are chosen, patients with XLH require regular
orthopaedic surveillance, particularly during periods of rapid
growth.
Lower extremity surgery is considered in XLH when deformities
result in ongoing pain and functional disturbance despite 1 year of
optimal medical management.90 In general, such procedures aim to
normalize alignment and equalize limb lengths, while avoiding
complications.90 Guided growth can be considered in younger
children, with reported improvement of periarticular and
diaphyseal deformities (Figure 9). In older children with more
severe bowing, there remains a role for osteotomies to correct
mechanical axis deviation. Such deformities can be quite complex,
with multiple apices and associated torsional abnormalities, so
careful preoperative planning is advised. Correction can be
achieved with various reported internal or external fixation options,
including fixator-assisted nailing. 89 , 94 Recurrence is less likely
when osteotomies can be delayed to an older age. Postoperatively,
patients with XLH often require reduced dosing of their phosphate
and vitamin D supplements to avoid systemic toxicity, reinforcing
the importance of ongoing multidisciplinary care.89

Figure 9 Weight-bearing AP radiographs from a 4-year-old boy with X-linked

hypophosphatemic rickets demonstrating bilateral genu varum with metaphyseal
cupping and diaphyseal varus bowing of the femur (A). Treatment consisted of
hemiepiphysiodesis of the distal femur and proximaltibia (B), with correction of
deformity in 2 years (C).

Summary
Skeletal dysplasias, connective tissue disorders, and genetic
disorders will present in every orthopaedic practice, requiring a
familiarity with diagnosis and treatment of these uncommon
conditions. Understanding the pathology and natural history is
essential to providing safe and comprehensive orthopaedic care
that transcends subspecialty interests. As medical treatment
continues to evolve for these patients, so must surgical
management, maintaining a focus on limiting risk and improving
function in these children.

Key Study Points

 Genetic conditions with associated orthopaedic pathology make for a heterogenous
group of disorders, many with limited evidence for best practice in surgical
management. Understanding the natural history of the disorder and applying
fundamental orthopaedic principles is key to proper care.
Every orthopaedic surgeon will benefit from being familiar with uncommon genetic
disorders as accurate identification is necessary for safe and appropriate care when
these patients present to a busy practice.
Although surgical indications can vary, establishing a relationship with the family,
understanding the patient’s needs and limitations, and drawing on the existing
literature provide for good outcomes.

Annotated References
1. Pyeri RE, McKusick VA: The Marfan syndrome: Diagnosis and
management. N Engl J Med 1979;300(14):772-777.
2. Loeys BL, Die HC, Braverman AC, et al: The revised Ghent
nosology for the Marfan syndrome. J Med Genet 2010;47(7):476-
485.
3. Taniguchi Y, Matsubayashi Y, Kato S, et al: Predictive physical
manifestations for progression of scoliosis in Marfan syndrome.
Spine 2021;46(15):1020-1025. A retrospective study of 131 patients
with Marfan syndrome compared physical manifestations with
the presence of severe scoliosis (>40° or requiring surgical
treatment). Female gender and positive wrist sign were
significantly associated with severe scoliosis. Level of evidence:
III.
4. Otremski H, Widmann RF, DiMaio MF, Ovadia D: The
correlation between spinal and chest wall deformities and
pulmonary function in Marfan syndrome. J Child Orthop
2020;14:343-348. This is a retrospective multicenter study of 26
patients with Marfan syndrome and spinal deformity.
Preoperative pulmonary function tests were compared with
radiographic measurements of spinal and chest wall deformities.
Decreased FEV1/FVC was noted with thoracic kyphosis <15° and
chest wall deformity. Increased thoracic curve magnitude
 displayed moderate negative correlation with total lung capacity.
Level of evidence: IV.
5. Sponseller PD, Bhimani M, Solacoff D, Dormans JP: Results of
brace treatment of scoliosis in Marfan syndrome. Spine
2000;25(18):2350-2354.
6. Kurucan E, Bernstein DN, Ying M, et al: Trends in spinal
deformity surgery in Marfan syndrome. Spine J 2019;19:1934-1940.
This is a retrospective database study of 314 patients with Marfan
syndrome treated with spinal fusion surgery. There was a
significant increase in the proportion of surgeries performed
posteriorly, from 66.7% in 2003 to 92.0% in 2014. Compared with
matched patients, patients with Marfan syndrome were more
likely to have neurologic complications (2.4% versus 0.79%). Level
of evidence: III.
7. Fields MW, Lee NJ, Ball JR, et al: Spinal fusion in pediatric
patients with Marfan syndrome: A nationwide assessment on
short-term outcomes and readmission risk. Eur Spine J
2020;30:775-787. This is a retrospective database study of 249
patients with Marfan syndrome who underwent spinal fusion
surgery. Overall, 59.7% of patients experienced at least one
complication during their index admission, while 10.1% were
readmi ed within 90 days of discharge. Wound dehiscence was
the most common complication requiring readmission (3.2%).
Level of evidence: IV.
8. Bellaire LL, Zhang C, Smith JT, et al: Growth-friendly spinal
instrumentation in Marfan syndrome achieves sustained gains in
thoracic height amidst high rates of implant failure. J Pediatr
Orthop 2021;41:e204-e210. This is a retrospective review of a
prospective database including 42 patients with Marfan
syndrome and early-onset scoliosis who underwent rib-based or
spine-based growing instrumentation. Final thoracic height
measured 23.8 cm. Patients experienced a mean of 2.6
complications, of which 42% were implant failures. Level of
evidence: III.
 9. Marom R, Rabenhorst BM, Morello R: Osteogenesis imperfecta:
An update on clinical features and therapies. Eur J Endocrinol
2020;183(4):R95-R106. A review of current expert opinion on
multidisciplinary care for patients with osteogenesis imperfecta
and an update on therapy options are provided. Level of
evidence: V.
10. Franzone JM, Shah SA, Wallace MJ, Kruse RW: Osteogenesis
imperfecta a pediatric orthopaedic perspective. Orthop Clin North
Am 2019;50(2):193-209. A review of current management
principles and orthopaedic treatment for children with
osteogenesis imperfecta is provided. Level of evidence: V.
11. Sillence DO, Rimoin DL, Danks DM: Clinical variability in
osteogenesis imperfecta-variable expressivity or genetic
heterogeneity. Birth Defects Orig Artic Ser 1979;15(5B):113-129.
12. Glorieux FH, Rauch F, Plotkin H, et al: Type V osteogenesis
imperfecta: A new form of bri le bone disease. J Bone Miner Res
2000;15(9):1650-1658.
13. Nijhuis WH, Eastwood DM, Allgrove J, et al: Current concepts
in osteogenesis imperfecta: Bone structure, biomechanics and
medical management. J Child Orthop 2019;13(1):1-11. A review of
the bone biomechanics in the se ing of osteogenesis imperfecta
is provided. Level of evidence: V.
14. Tauer JT, Robinson ME, Rauch F: Osteogenesis imperfecta: New
perspectives from clinical and translational research. JBMR Plus
2019;3(8):e10174. An update on medical treatment options for
patients with osteogenesis imperfecta, including new advances in
translational animal research models, is provided. Level of
evidence: V.
15. Fassier FR: Osteogenesis imperfecta-Who needs rodding
surgery? Curr Osteoporos Rep 2021;19(3):264-270. This is a review
of the current evidence and indications for diphosphonate
treatment and intramedullary rodding for patients with
osteogenesis imperfecta intended for primary care pediatricians.
Level of evidence: V.
16. Sakkers RJ, Montpetit K, Tsimicalis A, et al: A roadmap to
surgery in osteogenesis imperfecta: Results of an international
collaboration of patient organizations and interdisciplinary care
teams. Acta Orthop 2021;92(5):608-614. Expert consensus
generated from an international group of 12 surgeons and 3
patient advocates to provide guidelines for multidisciplinary
approach to surgery in patients with osteogenesis imperfecta. It
is intended to improve standardization of care and allow for
comparison of treatment outcomes between sites. Level of
evidence: V.
17. Gaume M, Duprot E, De Tienda M, et al: Tibial sliding elastic
nailing technique in moderate-to-severe osteogenesis imperfecta:
Long-term outcomes. J Pediatr Orthop 2021;42(1):47-52. This is a
single-center retrospective review of 22 children with
osteogenesis imperfecta with an average age of 4.7 years who
underwent tibial sliding elastic nailing (one antegrade, one
retrograde) with an average follow-up of 8.6 years. Level of
evidence: IV.
18. Musielak BJ, Woźniak Ł, Sułko J, Oberc A, Jóźwiak M:
Problems, complications, and factors predisposing to failure of
Fassier-Duval rodding in children with osteogenesis imperfecta:
A double-center study. J Pediatr Orthop 2021;41(4):e347-e352. This
is a retrospective review of 58 rod segments (femurs and tibias)
in 19 patients with osteogenesis imperfecta with a total
complication rate of 44.8%: migration of male or female implant
(45.7% and 25.7% of total number of complications, respectively),
bone fracture with bending of rod (8.6%), and rotational
deformities (8.6%). Level of evidence: IV.
19. Persiani P, Ranaldi FM, Martini L, et al: Treatment of tibial
deformities with the Fassier-Duval telescopic nail and minimally
invasive percutaneous osteotomies in patients with osteogenesis
imperfecta type III. J Pediatr Orthop B 2019;28(2):179-185. This is a
review of 14 patients with osteogenesis imperfecta type III
treated for tibial deformities with minimally invasive
percutaenous osteotomy technique and a Fassier-Duval telescopic
 nail versus 18 patients with osteogenesis imperfecta type III with
open osteotomies and a Fassier-Duval telescopic nail. In the
percutaneous group, the surgical duration was shorter, and
postoperative pain lower. Level of evidence: IV.
20. Rodriguez Celin M, Kruger KM, Caudill A, et al: A multicenter
study of intramedullary rodding in osteogenesis imperfecta. JB JS
Open Access 2020;5(3):e20.00031. A retrospective multicenter
cohort was analyzed to determine rodding status and functional
outcomes in patients with type III and IV osteogenesis
imperfecta. Intramedullary rodding in moderate and severe
osteogenesis imperfecta showed improved mobility and lower
fracture rates than control patients, suggesting a benefit to early
bilateral long bone rodding in children with type III osteogenesis
imperfecta. Level of evidence: III.
21. Scollan JP, Jauregui JJ, Jacobsen CM, Abzug JM: The outcomes
of nonelongating intramedullary fixation of the lower extremity
for pediatric osteogenesis imperfecta patients: A meta-analysis. J
Pediatr Orthop 2017;37(5):e313-e316.
22. Spahn KM, Mickel T, Carry PM, et al: Fassier-duval rods are
associated with superior probability of survival compared with
static implants in a cohort of children with osteogenesis
imperfecta deformities. J Pediatr Orthop 2019;39(5):e392-e396. This
is a retrospective analysis of 21 patients with osteogenesis
imperfecta, in which a total of 64 limbs underwent
intramedullary rodding with either Fassier-Duval rods or static
implants. The hazard of implant failure was 13.2 times greater in
the static implant group, requiring 7.8 times the surgery rate,
when compared with limbs treated with Fassier-Duval rods. Level
of evidence: II.
23. Suresh KV, Vankara A, Len JM, Sponseller PD: Interlocking
fixation in Fassier-Duval rods: Performance and success factors. J
Pediatr Orthop 2021;41(8):525-529. This is a retrospective review of
patients with osteogenesis imperfecta treated at a single center
with lower extremities treated with Fassier-Duval rods. Twenty-
four single-interlocking pin Fassier-Duval rods were identified
 (21 tibia, 3 femur); obturator proximal migration observed in 3 of
24 rods (13%). Revision for pin backout was observed in 42% of
rods and pin prominence in 46%; bending interlocking pins was
associated with decreased pin backout and prominence. Level of
evidence: III.
24. Holmes K, Gralla J, Brazell C, et al: Fassier-duval rod failure: Is
it related to positioning in the distal epiphysis? J Pediatr Orthop
2020;40(8):448-452. This is a retrospective review demonstrating
Fassier-Duval rod placement within the distal epiphysis has
significant effect on increasing rod survival. Level of evidence: III.
25. Sullivan BT, Margalit A, Garg VS, Njoku DB, Sponseller PD:
Incidence of fractures from perioperative blood pressure cuff use,
tourniquet use, and patient positioning in osteogenesis
imperfecta. J Pediatr Orthop 2019;39(1):e68-e70. This is a
retrospective review of pediatric patients with osteogenesis
imperfecta treated at a single center demonstrating
intraoperative use of noninvasive blood pressure cuffs and
tourniquets was not associated with iatrogenic fracture. Level of
evidence: IV.
26. Ross KE, Gibian JT, Crocke CJ, Martus JE: Perioperative
considerations in osteogenesis imperfecta: A 20-year experience
with the use of blood pressure cuffs, arterial lines, and
tourniquets. Children 2020;7(11):214. A single-center retrospective
study over 20 years found 49 children with osteogenesis
imperfecta underwent a total of 273 procedures. The routine use
of extremity tourniquets, blood pressure cuffs and arterial lines
did not result in any iatrogenic fractures. Level of evidence: III.
27. Ahn J, Carter E, Raggio CL, Green DW: Acetabular protrusio in
patients with osteogenesis imperfecta: Risk factors and
progression. J Pediatr Orthop 2019;39(10):e750-e754. This is a
series of 109 hips (55 patients) with a 45% incidence of acetabular
protrusio; risk factors associated with greater odds of developing
acetabular protrusio included age younger than 12 years, body
mass index > 25kg/m2, presence of acetabular protrusio of
contralateral hip, and female gender. Level of evidence: IV.
28. Song MH, Kamisan N, Lim C, et al: Pseudo-protrusio acetabular
deformity in osteogenesis imperfecta patients. J Pediatr Orthop
2021;41(3):e285-e290. This is a review of 590 hips of 295 patients
with osteogenesis imperfecta older than 5 years; 21% showed
deformed acetabula; incidence of deformed acetabula correlated
with disease severity. Level of evidence: IV.
29. Hong WK, Lee DJ, Chung H, et al: Pa erns of femoral neck
fracture and its treatment methods in patients with osteogenesis
imperfecta. J Pediatr Orthop B 2021;31(2):e114-e121. A
retrospective study of patients with osteogenesis imperfecta at a
tertiary care center identified 15 femoral neck fractures in 10
patients including 1 Sillence type I, 1 type III, and 8 type IV. This
study grouped them into three pa erns with suggested treatment
strategies. Level of evidence: IV.
30. Tayne S, Smith PA: Olecranon fractures in pediatric patients
with osteogenesis imperfecta. J Pediatr Orthop 2019;39(7):e558-
e562. This is a retrospective review of 358 patients with
osteogenesis imperfecta with incidence of olecranon fracture of
8.1%; olecranon fractures occurred predominantly in type I
patients (27 of 29). Forty-one percent of children with one
olecranon fracture sustained a contralateral olecranon fracture
within a mean time period of 5 months. Level of evidence: IV.
31. Karlin LI, McClung A, Johnston CE, et al: The growth-friendly
surgical treatment of scoliosis in children with osteogenesis
imperfecta using distraction-based instrumentation. Spine Deform
2021;9(1):263-274. This is a retrospective review of two multi-
center databases for children with osteogenesis imperfecta who
underwent growing rod or vertical expandable prosthetic
titanium rib surgery with minimum of 2-year follow-up and three
lengthening procedures. The results varied in the heterogeneous
population; complications were similar to those in other series of
growth-friendly surgery. Level of evidence: IV.
32. Arponen H, Mäkitie O, Haukka J, et al: Prevalence and natural
course of craniocervical junction anomalies during growth in
 patients with osteogenesis imperfecta. J Bone Miner Res
2012;27(5):1142-1149.
33. Wadanamby S, El Garwany S, Connolly D, et al: Monitoring
skull base abnormalities in children with osteogenesis imperfecta
– Review of current practice and a suggested clinical pathway.
Bone 2021;154:116235. This is a retrospective review proposing a
suggested clinical pathway for monitoring and imaging skull
base abnormalities in children with osteogenesis imperfecta.
Level of evidence: IV.
34. Bouthors C, Dukan R, Glorion C, Miladi L: Outcomes of growing
rods in a series of early-onset scoliosis patients with
neurofibromatosis type 1. J Neurosurg Spine 2020;33:373-380. This
is a retrospective study of 18 patients with neurofibromatosis
type 1, treated with growing rods for a minimum of 2 years.
Scoliosis improved from 57° preoperatively to 36° at a mean
follow-up of 5 years. Thirteen patients experienced 26
complications, including 17 implant-related complications. Ten of
14 patients with single growing rods were later converted to dual
rods, with no conversion to definitive fusion. Level of evidence:
IV.
35. Tauchi R, Kawakami N, Castro MA, et al: Long-term surgical
outcomes after early definitive spinal fusion for early-onset
scoliosis with neurofibromatosis at mean follow-up of 14 years. J
Pediatr Orthop 2020;41:42-47. This is a retrospective study of 11
patients with neurofibromatosis type 1 treated with early
definitive fusion at a mean age of 8.3 years. At a mean follow-up
of 14 years, mean Cobb angle was 23.5°, decreased from 71.2°
preoperatively. Mean forced vital capacity at final follow-up was
74.4% predicted, and mean T1-T12 height was 21.9 cm. Level of
evidence: IV.
36. Tauchi R, Kawakami N, Suzuki T, et al: Comparison of early
definitive fusion and traditional growing rods in early-onset
dystrophic scoliosis in neurofibromatosis type 1: A preliminary
report. J Pediatr Orthop 2020;40:569-574. This is a retrospective
study of 26 patients with neurofibromatosis type 1, where 16
 patients were treated with early definitive fusion, and 10 were
treated with growing rods. Patients with early fusion had greater
major curve correction (59% versus 41%) and forced vital capacity
(2.23L versus 1.46L), despite a decreased rate of T1-S1 growth
(19% versus 34%). Level of evidence: III.
37. Westberry DE, Carpenter AM, Tisch J, Wack LI: Amputation
outcomes in congenital pseudarthrosis of the tibia. J Pediatr
Orthop 2018;38:e475-e481. This is a retrospective study of 17
patients treated with amputation (mean age 4.5 years) for
congenital pseudarthrosis of the tibia associated with
neurofibromatosis type 1, with mean clinical follow-up of 11.1
years. Boyd amputations were performed for 13 patients, whereas
4 patients had transtibial amputations. Twelve of 13 patients with
Boyd amputations achieved union of their pseudarthrosis,
requiring revision in 4 patients. Level of evidence: IV.
38. Laine JC, Novotny SA, Weber EW, Georgiadis AG, Dahl MT:
Distal tibial guided growth for anterolateral bowing of the tibia:
Fracture may be prevented. J Bone Joint Surg Am 2020;102:2077-
2086. This is a retrospective study of 10 patients presenting with
congenital tibial dysplasia before pseudarthrosis, treated with
distal tibial growth modulation at a mean age of 2.6 years. At
mean 5.1 years follow-up, no patient sustained a fracture or
developed pseudarthrosis. Level of evidence: IV.
39. Shannon CE, Huser AJ, Paley D: Cross-union surgery for
congenital pseudarthrosis of the tibia. Children 2021;8:547. This is
a retrospective study of 39 cases of congenital pseudarthrosis of
the tibia treated with the Paley cross union protocol, involving
internal fixation, autogenous bone grafting, diphosphonate
infusion, and bone morphogenic protein 2 insertion. The tibia
united in all cases, with two persistent fibular pseudarthroses.
There were no refractures during follow-up. Fourteen patients
underwent late surgical procedures for deformity or leg-length
discrepancy. Level of evidence: IV.
40. Singer D, Johnston CE: Congenital pseudarthrosis of the tibia:
Results, at skeletal maturity, of the Charnley-Williams procedure.
 JBJS Open Access 2019;4(2):e0004. This is a retrospective
comparative study of 34 patients treated with intramedullary
rodding for congenital pseudarthrosis of the tibia. At final follow-
up, 82% of patients had a functional extremity at maturity,
whereas 18% requested amputation. Inferior results were noted
in patients whose surgical procedure did not address the fibula.
Level of evidence: III.
41. Schubart JR, Schilling A, Schaefer E, Bascom R, Francomano C:
Use of prescription opioid and other drugs among a cohort of
persons with Ehlers-Danlos syndrome: A retrospective study. Am
J Med Genet 2019;179A:397-403. A retrospective study compared
prescription opioid use among 4,294 patients with EDS with a
cohort of matched control patients over a 10-year period. The
EDS cohort demonstrated higher opioid use in both children and
adults, while also having higher cumulative doses once opioids
were prescribed. Level of evidence: III.
42. Matur AV, Nouri A, Huang S, et al: Complications in children
with Ehlers-Danlos syndrome following spine surgery: Analysis
of the pediatric national surgery quality improvement program
databse. World Neurosurg 2020;133:e473-e478. A retrospective
study compared complications from spine surgery in 56 patients
with EDS with a cohort of matched control patients. No
significant differences in bleeding, wound healing issues, or
other complications were identified between cohorts. Level of
evidence: III.
43. El-Gammal TA, El-Sayed A, Kotb MM, et al: Crawford type IV
congenital pseudarthrossis of the tibia: Treatment with
vascularized fibular grafting and outcome at skeletal maturity. J
Pediatr Orthop 2021;41:164-170. This is a retrospective study of 39
patients with congenital pseudarthrosis of the tibia and
neurofibromatosis type 1 treated with vascularized fibular
grafting. Although 96% of patients achieved primary bone union,
51% later developed stress fractures. Ipsilateral ankle valgus was
noted in 54%, averaging 10°. Level of evidence: IV.
44. Meselhy MA, Elhammady AS, Singer MS: Outcome of induced
membrane technique in treatment of failed previously operated
congenital pseudarthrosis of the tibia. Orthop Traumatol Surg Res
2020;106:813-818. In a restrospective study, 19 patients of failed,
previously operated congenital pseudarthrosis of the tibia were
treated with an induced-membrane technique. Union was
achieved in all patients, with no refractures at a mean follow-up
of 5 years. Level of evidence: IV.
45. Malfait F, Francomano C, Byers P, et al: The 2017 international
classification of the Ehlers-Danlos syndromes. Am J Med Genet C
Semin Med Genet 2017;175(1):8-26.
46. Homere A, Boila JK, Juhan T, Weber AE, Hatch GF: Surgical
management of shoulder and knee instability in patients with
Ehlers-Danlos syndrome: Joint hypermobility syndrome. Clin
Orthop Surg 2020;12:279-285. This review article examines current
evidence in surgical management of shoulder and knee
instability in patients with EDS. Authors reinforce the
importance of thorough preoperative assessment because of the
risk of inferior outcomes with standard techniques in EDS. Level
of evidence: V.
47. Sacks HA, Prabhakar P, Wessel LE, et al: Generalized joint laxity
in orthopaedic patients: Clinical manifestations, radiographic
correlates, and management. J Bone Joint Surg Am 2019;101:558-
566. This review article discusses current evidence surrounding
the evaluation and treatment of orthopaedic patients with
generalized joint laxity. Emphasis is placed on diagnosis of
underlying syndromes to provide preoperative counseling. Level
of evidence: V.
48. Guier C, Shi G, Ledford C, Taunton M, Heckman M, Wilke B:
Primary total hip arthroplasty in patients with Ehlers-Danlos
syndrome: A retrospective matched-cohort study. Arthroplast
Today 2020;6:386-389. This retrospective, single-center study
compared 13 patients with EDS who underwent total hip
arthroplasty with a cohort of matched control patients. Outcomes
improved significantly after total hip arthroplasty in both
 cohorts, with two postoperative dislocations in the EDS group,
but no difference in revision rate. Level of evidence: III.
49. Tibbo ME, Wyles CC, Houdek MT, Wilke BK: Outcomes of
primary total knee arthroplasty in patients with Ehlers-Danlos
syndromes. J Arthroplasty 2019;34:315-318. A retrospective, single-
center study compared 16 patients with EDS who underwent total
knee arthroplasty with a cohort of matched control patients.
Patients with EDS were more likely to receive constrained
components, with no difference in outcome score, reoperation, or
revision rates. Level of evidence: III.
50. Oberklaid F, Danks DM, Jensen F, Stace L, Rosshandler S:
Achondroplasia and hypochondroplasia. Comments on
frequency, mutation rate, and radiological features in skull and
spine. J Med Genet 1979;16(2):140-146.
51. Legare JM, Liu C, Pauli RM, et al: Achondroplasia natural
history study (CLARITY): 60-year experience in cervicomedullary
decompression in achondroplasia from four skeletal dysplasia
centers. J Neurosurg Pediatr 2021;28(2):229-235. In this
retrospective cohort study, 1374 patients with achondroplasia
were followed up at 4 centers over 60 years. Of the total, 20.5% of
patients required cervicomedullary decompression, with a 10.3%
revision rate. Over time, patients were identified at a younger
age, more commonly using neuroimaging and polysomnography.
Level of evidence: III.
52. Kopits SE: Thoracolumbar kyphosis and lumbosacral
hyperlordosis is in achondroplastic children. Basic Life Sci
1988;48:241-255.
53. Margalit A, McKean G, Lawing C, et al: Walking out of the
curve: Thoracolumbar kyphosis in achondroplasia. J Pediatr
Orthop 2018;38(10):491-497.
54. White KK, Bompadre V, Shah SA, et al: Early-onset spinal
deformity in skeletal dysplasias: A multicenter study of growth-
friendly systems. Spine Deform 2018;6(4):478-482.
55. Abousamra O, Shah SA, Heydemann JA, et al: Sagi al
spinopelvic parameters in children with achondroplasia. Spine
Deform 2019;7(1):163-170. This is a retrospective evaluation of
spinopelvic parameters of 81 children with achondroplasia with 5
years of follow-up. Thoracolumbar kyphosis was found to
increase until 3 years of age, then decrease until 10 years of age.
As thoracolumbar kyphosis decreased, a compensatory increase
in lumbar lordosis and pelvic incidence was observed. Level of
evidence: III.
56. Wang H, Wang S, Wu N, et al: Posterior vertebral column
resection (pVCR) for severe thoracolumbar kyphosis in
achondroplasia. Global Spine J 2022;12(8):1804-1813. This is a
single-center retrospective case series of seven patients with
achondroplasia who underwent posterior vertebral column
resection to manage thoracolumbar kyphosis. Five of eight
patients presented with neurologic symptoms, and all improved,
but 57% had surgical complications. Level of evidence: IV.
57. Fredwall SO, Steen U, de Vries O, et al: High prevalence of
symptomatic spinal stenosis in Norwegian adults with
Achondroplasia: A population-based study. Orphanet J Rare Dis
2020;15:123. This cross-sectional, population-based study
reported on the incidence of symptomatic spinal stenosis in
Norwegian adults with achondroplasia. Sixty-eight percent
(34/50) were symptomatic at an average age of 33, with greater
pain, decreased walking endurance, and more activity
modifications. Level of evidence: III.
58. Arenas-Miquelez A, Arbeola-Gutierrez L, Amaya M, et al: Upper
limb lengthening in achondroplasia using unilateral external
fixator. J Pediatr Orthop 2021;41(4):E328-E336. This is a
retrospective series of 50 humeri lengthenings in 25 patients with
achondroplasia using unilateral external fixator. Lengthening an
average of 54.8% had low rate of complications, without
compromise of range of motion or stability. Complications were
associated with distal humeral osteotomy (versus proximal) and
fracture displacement. Level of evidence: IV.
59. Savarirayan R, Tofts L, Irving M, et al: Once-daily subcutaneous
vosoritide therapy in children with achondroplasia: A
randomized, double-blind, phase 3, placebo-controlled,
multicentre trial. Lancet 2020;396:684-692. This is a randomized
phase 3 trial of children with achondroplasia, with 60 patients
treated with daily vosoritide compared with placebo. Children
who received vosoritide had an increase in longitudinal growth
averaging 1.57 cm per year. It is unclear how it will affect their
final height and orthopaedic pathology, including spinal stenosis.
Level of evidence: I.
60. Andrzejewski A, Pejin Z, Finidori G, et al: Can Chiari osteotomy
favourably influence long-term hip degradation in multiple
epiphyseal dysplasia and pseudoachondroplasia? J Pediatr Orthop
2021;41(2):E135-E140. This is a retrospective review of 20 patients
with hip dysplasia and MED or pseudoachondroplasia treated
with Chiari osteotomy. Long-term follow-up demonstrates
maintained femoral head containment, less pain, improved
function, and 80.7% survivorship at 24 years. Level of evidence:
IV.
61. Yilmaz G, Oto M, Thabet AM, et al: Correction of lower
extremity angular deformities in skeletal dysplasia with
hemiepiphysiodesis: A preliminary report. J Pediatr Orthop
2014;34(3):336-345.
62. Remes V, Mar inen E, Poussa M, et al: Cervical kyphosis in
diastrophic dysplasia. Spine 1999;24(19):1990-1995.
63. Jalanko T, Remes V, Peltonen J, Poussa M, Helenius I: Treatment
of spinal deformities in patients with diastrophic dysplasia: A
long-term, population based, retrospective out- come study. Spine
2009;34(20):2151-2157.
64. Bayhan IA, Er MS, Nishnianidze T, et al: Gait pa ern and lower
extremity alignment in children with diastrophic dysplasia. J
Pediatr Orthop 2016;36(7):709-714.
65. Weiner DS, Jonah D, Kopits S: The 3-dimensional configuration
of the typical foot and ankle in diastrophic dysplasia. J Pediatr
 Orthop 2008;28(1):60-67.
66. Jaruga A, Hordyjewska E, Kandzierski G, Tylzanowski P:
Cleidocranial dysplasia and RUNX2-clinical phenotype- genotype
correlation. Clin Genet 2016;90(5):393-402.
67. Berkay EG, Elkanova L, Kalayci T, et al: Skeletal and molecular
findings in 51 cleidocranial dysplasia patients from Turkey. Am J
Med Genet 2021;185(8):2488-2495. This series of 51 individuals
reported on the incidence of clinical, radiographic, and genetic
findings in patients with cleidocranial dysplasia. Level of
evidence: IV.
68. Bull MJ: Down syndrome. N Engl J Med 2020;382:2344-2352. This
is a review article providing in-depth discussion of medical
conditions associated with Down syndrome and suggesting
relevant clinical orthopaedic interventions. Level of evidence: V.
69. Foley C, Killeen OG: Musculoskeletal anomalies in children with
Down syndrome: An observational study. Arch Dis Child
2019;104:482-487. This is an observational study of 503 children
with Down syndrome to determine incidence of musculoskeletal
conditions. Pes planus was noted in 91%, while inflammatory
arthritis (7%) and scoliosis (5%) were also common. Median age
to walking was 28 months, and average Beighton score was 4, with
59% scoring >4. Level of evidence: IV.
70. Tu A, Melamed E, Krieger E: Dynamic MRI in the evaluation of
atlantoaxial stability in pediatric Down syndrome patients.
Pediatr Neurosurg 2019;54:12-20. This is a retrospective study
comparing static and dynamic craniocervical MRI results of 36
patients with Down syndrome. The authors proposed that
dynamic changes in the SAC and atlantodental interval of >5 mm
and >3 mm, respectively, warrant further investigation and
treatment. Level of evidence: III.
71. Bouchard M, Bauer JM, Bompadre V, Krengel WF: An updated
algorithm for radiographic screening of upper cervical instability
in patients with Down syndrome. Spine Deform 2019;7:950-956.
This is a retrospective review of cervical spine radiographs in
 patients with Down syndrome, comparing several radiographic
measurements on neutral upright lateral and flexion-extension
lateral views. Authors propose that the use of neutral
radiographs only is an efficient and sensitive method of screening
for upper cervical instability. Level of evidence: IV.
72. Hofler RC, Pecoraro N, Jones GA: Outcomes of surgical
correction of atlantoaxial instability in patients with Down
syndrome: Systematic review and meta-analysis. World Neurosurg
2019;126:e125-e135. A systematic review and meta-analysis of 51
small series noted variability in fixation strategies and outcomes.
Constructs with screws and rods resulted in greater bony union
and lower rates of revision surgery and neurologic decline
compared with wiring alone. Level of evidence: III.
73. Yang BW, Hedequist DJ, Proctor MR, Troy M, Hresko MT,
Glo becker MP: Surgical fixation using screw-rod construct
instrumentation for upper cervical instability in pediatric Down
syndrome patients. Spine Deform 2019;7:957-961. This is a
retrospective study of 12 patients with Down syndrome who
underwent cervical fusion using modern screw-rod
instrumentation. Complication rate was 41.7%, with four patients
requiring repeat surgery for nonunion. Level of evidence: IV.
74. Sankar WN, Schoenecker JG, Mayfield ME, Kim YJ, Millis MB:
Acetabular retroversion in Down syndrome. J Pediatr Orthop
2012;32:277-281.
75. Sankar WN, Millis MB, Kim YJ: Instability of the hip in patients
with Down syndrome: Improved results with complete
redirectional acetabular osteotomy. J Bone Joint Surg Am
2011;93:1924-1933.
76. Sha S, Abdelsabour H, Vijimohan SJ, Board T, Alshryda A: Total
hip arthroplasty in patients with Trisomy 21: Systematic review
and exploratory patient level analysis. Surgeon 2019;17:52-57. This
is a systematic review of 9 studies reporting 321 patients with
Down syndrome undergoing total hip arthroplasty. Significant
improvement was noted in functional hip scores postoperatively,
 although the 5-year cumulative revision rate was 7.5%. Level of
evidence: III.
77. Ruzzini L, Donati F, Russo R, Costici PF: Modified Roux-
Goldthwait procedure for management of patellar dislocation in
skeletally immature patients with Down syndrome. Indian J
Orthop 2019;53:122-127. This is a retrospective case series of 19
patients with Down syndrome treated with modified Roux-
Goldthwait procedures for patellar instability. Postoperatively,
there was no recurrent dislocation, while authors noted a
tendency toward normalization of trochlear angle and
patellofemoral congruence angle. Level of evidence: IV.
78. Averill LW, Kecskemethy HH, Theroux MC, et al: Tracheal
narrowing in children and adults with mucopolysaccharidosis
type IVA: Evaluation with computed tomography angiography.
Pediatr Radiol 2021;51:1202-1213. Tracheal narrowing in MPS IVA
was characterized using CT angiograms of 37 patients. Narrowing
was most common at the thoracic outlet, associated with position
of the thyroid gland and impingement by the brachiocephalic
artery. Level of evidence: IV.
79. Remondino RG, Tello CA, Noel M, et al: Clinical manifestations
and surgical management of spinal lesions in patients with
mucopolysaccharidosis: A report of 52 cases. Spine Deform
2019;7(20):298-303. This is a retrospective review of 52 patients
with MPS treated for spinal pathology at one institution,
representing the largest published series. Preoperative
neurologic deficits improved in a minority of patients, likely
because of delayed diagnosis. Level of evidence: IV.
80. Lins CF, de Carvalho TL, de Moraes Carneiro ER, et al: MRI
findings of the cervical spine in patients with
mucopolysaccharidosis type IV: Relationship with neurological
physical examination. Clin Radiol 2020;75(6):441-447. This is a
cross-sectional study of 12 patients with MPS IV who underwent
cervical MRI. Of patients with spinal cord compression, only 33%
had an abnormal neurologic examination, indicating the need for
 screening MRIs at an early age in children with MPS IV. Level of
evidence: IV.
81. Akyol MU, Alden TD, Amartino H, et al: Recommendations for
the management of MPS IVA: Systemic evidence- and consensus-
based guidance. Orphanet J Rare Dis 2019;14:137. A modified
Delphi method was used to obtain consensus on the
management of MPS IVA among multidisciplinary health care
providers and patient advocates to provide guidance statements
in five medical domains. Level of evidence: V.
82. Kuiper G, Langereis EJ, Breyer S, et al: Treatment of
thoracolumbar kyphosis in patients with mucopolysaccharidosis
type 1: Results of an international consensus procedure. Orphanet
J Rare Dis 2019;14:17.
83. Van der Veer EL, Gielis WP, Weinans H, et al: Quantifying the
effects of hip surgery on the sphericity of the femoral head in
patients with mucopolysaccharidosis type I. J Bone Joint Surg Am
2021;103(6):489-496. A retrospective case-control study of children
with MPS I and hip dysplasia compared control patients with 12
patients who underwent hip reconstruction. Postoperative
radiographs demonstrated maintained containment and
spherical remodeling of the proximal femoral epiphysis
compared with progressive epiphyseal fla ening in the control
group. Level of evidence: III.
84. Van den Eeden YNT, Ecker NU, Kleiner H, et al: Total hip
arthroplasty in a patient with mucopolysaccharidosis type IVB.
Case Rep Orthop 2021;2021:5584408. This case report of a 23 year
old patient with Morquio B Syndrome describes the progression
of hip dysplasia and femoral head osteonecrosis requiring total
hip arthroplasty. This patient had poor bone quality and
sustained an intraoperative fracture, and the authors advocate for
consideration of cemented components, and specialized
anesthesia for the cardiopulmonary considerations in these
patients. Level of evidence: V.
85. Salazar-Torres JJ, Church C, Shields T, et al: Evaluation of gait
pa ern and lower extremity kinematics of children with Morquio
syndrome (MPS IV). Diagnostics (Basel) 2021;11(8):1350. Three-
dimensional gait analysis was used to evaluate 33 children with
MPS IV and compare them with typically developed controls,
demonstrating increased pelvic tilt and knee flexion. Level of
evidence: IV.
86. Cooper GA, Southorn T, Eastwood DM, Bache CE: Lower
extremity deformity management in MPS IVA, morquio-
brailsford syndrome: Preliminary report of hemiepiphysiodesis
correction of genu valgum. J Pediatr Orthop 2016;36(4):376-381.
87. Van Heest AE, House J, Krivit W, Walker K: Surgical treatment
of carpal tunnel syndrome and trigger digits in children with
mucopolysaccharide storage disorders. J Hand Surg Am
1998;23(2):236-243.
88. Dabaj I, Gitiaux C, Avila-Smirnow D, et al: Diagnosis and
management of carpal tunnel syndrome in children with
mucopolysaccharidosis: A ten year experience. Diagnostics (Basel)
2020;10:5. This is a retrospective review of 48 consecutive children
with MPS who underwent electrodiagnostics to detect carpal
tunnel syndrome, with an 88% incidence and estimated onset at
26 months of age. Authors recommend early testing and annual
follow-up, with prompt median nerve decompression for best
outcomes. Level of evidence: IV.
89. Sharkey MS, Grunseich K, Carpenter TO: Contemporary
medical and surgical management of X-linked
hypophosphatemic rickets. J Am Acad Orthop Surg 2015;23:433-
442.
90. Haffner D, Emma F, Eastwood DM, et al: Clinical practice
recommendations for the diagnosis and management of X-linked
hypophosphataemia. Nat Rev Nephrol 2019;15:435-456. European
evidence-based guideline for the diagnosis and management of
XLH is provided. Authors recommend molecular genetic analysis
or measurement of FGF23 levels before treatment by a
 multidisciplinary team. Suggested algorithms are presented for
both conventional and burosumab treatment plans. Level of
evidence: V.
91. Skrinar A, Dvorak-Ewell M, Evins A, et al: The lifelong impact of
X-linked hypophosphatemia: Results from a burden of disease
survey. J Endocr Soc 2019;3:1321-1334. This is a survey-based study
reporting on demographics, disease manifestations, treatment
history, and patient-reported outcomes of 232 adults with XLH,
with high reported incidences of abnormal gait (80% of adults
and 86% of children), bowing of the tibia/fibula (72% and 78%),
and bone or joint pain/stiffness (97% and 80%). Level of evidence:
IV.
92. Mao M, Carpenter TO, Whyte MP, et al: Growth curves for
children with X-linked hypophosphatemia. J Clin Endocrinol
Metab 2020;105:3243-3249. This is a retrospective study of 228
patients with XLH, pooling data from four prior studies to create
growth curves from birth to adolescence. In patients with XLH,
decreased height gain is manifested by 1 year of age and
subsequently remains below population norms, suggesting the
need for early initiation of therapy. Level of evidence: IV.
93. Imel EA, Glorieux FH, Whyte MP, et al: Burosumab versus
conventional therapy in children with X-linked
hypophosphatemia: A randomised, active-controlled, open-label,
phase 3 trial. Lancet 2019;393:2416-2427. This is a multicenter,
randomized controlled trial of 61 children with XLH assigned to
receive subcutaneous burosumab or continued conventional
therapy over a 64-week period. Patients in the burosumab group
showed significantly greater improvement in rickets, linear
growth, mobility, and biochemical parameters than the
conventional therapy group at 40 weeks. Level of evidence: I.
94. Erlap L, Kocaoglu M, Toker B, Balci HI, Awad A: Comparison of
fixator-assisted nailing versus circular external fixator for bone
realignment of lower extremity angular deformities in rickets
disease. Arch Orthop Trauma Surg 2011;131:581-589.
C H AP T E R 6 8

Pediatric Neuromuscular
Disorders
Colyn Watkins MD, Benjamin J. Shore MD, MPH, FRCSC

Dr. Shore or an immediate family member serves as a board member, owner, officer, or committee
member of American Academy for Cerebral Palsy and Developmental Medicine and Pediatric
Orthopaedic Society of North America. Neither Dr. Watkins nor any immediate family member has
received anything of value from or has stock or stock options held in a commercial company or
institution related directly or indirectly to the subject of this chapter.

ABSTRACT
Children with neurologic complex chronic conditions are a
vulnerable population with underlying diagnoses including, but not
limited to, cerebral palsy, myelomeningocele, congenital brain and
spinal cord malformations, spinal muscular atrophy, hereditary
sensory motor neuropathy, muscular dystrophy, and Friedreich
ataxia. Many of these conditions result in muscle imbalance, which
leads to progressive muscular contractures, torsional abnormalities,
hip dysplasia, and scoliosis. Treatment is tailored to the child’s
gross motor functional level. Orthopaedic interventions designed to
improve ambulation are reserved for ambulatory children;
orthopaedic interventions to improve seating and standing
tolerance and comfort or pain relief are designed for
nonambulatory children. To achieve the best results from surgical
management, orthopaedic surgeons must be knowledgeable about
recent medical and genetic treatments and be familiar with current
surgical techniques, risk stratification, and expected patient-
reported outcomes.
Keywords: cerebral palsy; Duchenne muscular dystrophy;
myelomeningocele; spina bifida

Introduction
Remarkable advances in pediatric healthcare over the past several
decades have enabled children with complex chronic conditions to
live longer. Complex chronic neurologic conditions in children
encompass static, progressive, central, and peripheral neurologic
diseases including, but not limited to, cerebral palsy,
leukodystrophy, muscular dystrophy, spinal muscular atrophy, and
spina bifida. Although etiology, natural history, and treatment
requirements vary in these children, certain commonalities exist in
terms of their musculoskeletal manifestations and orthopaedic
pathologies. In all of these conditions, a combination of muscular
imbalance, weakness, and altered underlying tone results in
diminished initial function, delayed motor milestones, subsequent
contracture development, eventual torsional abnormalities leading
to gait disturbances, hip subluxation, and scoliosis. Recent medical
advances and targeted gene therapy have demonstrated
tremendous promise in decreasing the burden of disease and
subsequently increasing life expectancy. The orthopaedic surgeon
must be up to date on the orthopaedic interventions required to
improve quality of life, function, and participation.

Cerebral Palsy

Background
Cerebral palsy is the most common cause of physical disability
affecting children in developed countries. 1 It is an umbrella term
for a group of heterogeneous conditions in terms of etiology, brain
pathology, and clinical features. Cerebral palsy is a static
encephalopathy, but the musculoskeletal pathology is progressive.
Children with cerebral palsy have complex needs and are usually
treated by a multidisciplinary team. In a classic study, the term
tenotomy was popularized to correct deformity in cerebral palsy,
and the link was identified between brain injury and deformity,
thus bridging the gap between neurology and orthopaedics. 2
The development of gross motor function in children with
cerebral palsy can be described by a series of curves that were
derived from longitudinal measurements of gross motor function,
using the Gross Motor Function Measure. 3 The curves show rapid
acquisition of gross motor function in infants, with a progressive
separation of the curves especially between the ages of 2 and 4
years. The curves plateau between the ages of 3 and 6 years. The five
gross motor curves constitute the five levels of the Gross Motor
Function Classification System (GMFCS) 4 (Figure 1). Children
classified as GMFCS I-III are considered to be independently
ambulatory, whereas children classified as GMFCS IV-V primarily
use a wheelchair for mobility and function. Therefore, treatment is
dichotomized according to gross motor function. The goal of
medical and surgical treatment for ambulatory children and adults
classified as GMFCS I-III is to improve gait efficiency, participation,
and community mobility; treatment goals for those classified as
GMFCS IV and V include improving seating balance or tolerance,
standing ability, and assistance with activities of daily living.
Orthopaedic management includes tone management, surgery,
physical and occupational therapy, and brace treatment.
Figure 1 Illustration showing Gross Motor Function Classification System
(GMFCS), which is a five-level ordinal classification system for children with
cerebral palsy based on walking and sitting ability, where GMFCS level I denotes
children who walk, run, and jump in all settings children at GMFCS level V are
transported in a wheelchair for all settings and demonstrate minimal head and
trunk control.(Reproduced with permission from GMFCS descriptors copyright ©
Palisano R, Rosenbaum P, Walter S, Russell D, Wood E, Galuppi B:
Development and reliability of a system to classify gross motor function in
children with cerebral palsy. Dev Med Child Neurol 1997;39[4]:214-223.
 CanChild: www.canchild.ca. Illustrations copyright © Kerr Graham, Bill Reid and
Adrienne Harvey, The Royal Children’s Hospital, Melbourne.)

Tone Management
Spasticity is common in individuals with cerebral palsy and is the
result of a lesion affecting the pyramidal system, which causes a
velocity-dependent increase in muscle tone with increased spastic
tonic stretch reflexes. Spasticity is often associated with premature
birth and the characteristic lesion of periventricular leukomalacia
on MRI. 5 Untreated spasticity can lead to discomfort, decreased
range of motion, subsequent contracture development, and
ultimate torsional abnormalities. The newborn child with cerebral
palsy does not have contractures or lower limb deformities, and
most do not show signs of spasticity. 5 With time, spasticity
develops, activity levels remain low, the growth of muscle-tendon
units lags behind bone growth, and contractures develop. An
important therapeutic window exists for spasticity management
before the development of fixed contractures. Spasticity
management can be classified as focal or generalized, whereas the
intervention effect is either temporary or permanent. Oral baclofen
provides generalized temporary spasticity management, whereas
botulinum toxin A injections provide a more focal temporary
intervention. In comparison, selective dorsal rhizotomy (SDR)
represents the most permanent example of global spasticity
reduction. Often children require a combination of focal and
generalized therapy to achieve optimal tone reduction.
Botulinum toxin A helps provide muscle relaxation by selectively
blocking the release of acetylcholine at the neuromuscular junction.
There is strong evidence that injection of botulinum toxin A results
in a reduction in muscle stiffness as measured by the Modified
Ashworth Scale and a reduction in spasticity, as measured by the
Modified Tardieu Scale. Unfortunately, a change in the Modified
Ashworth Scale or Modified Tardieu Scale does not result in a
predictable improvement in more meaningful outcome measures
such as Gross Motor Function Measure, gait, activity, or
participation. The paradox of clinical trials of botulinum toxin A is
strong evidence for improvement in surrogate outcomes (Modified
Ashworth Scale and Modified Tardieu Scale) and weak evidence or
no evidence for improvement in clinically relevant outcomes. 6 In
the past decade, a large body of work has been performed in
animals and humans investigating the effects of botulinum toxin A
injections. Injection of botulinum toxin A in animal models is
followed by acute muscle atrophy, replacement of contractile
elements of muscle with fat, and upregulation of molecular
pathways leading to fibrosis. 7 Injection of botulinum toxin A may
have adverse effects in the muscle injected that may not be fully
reversible, such as persistent atrophy, fa y infiltration, and fibrosis.
7
Careful consideration of the risks and benefits of botulinum toxin
A injection must be considered, and recommendations for
application will continue to evolve.
Baclofen is an agonist at the beta subunit of gamma-aminobutyric
acid on the monosynaptic and polysynaptic neurons at the spinal
cord level and brain. 8 Baclofen works to reduce the release of
excitatory neurotransmi ers in the presynaptic neurons and
stimulates inhibitory neuronal signals in the postsynaptic neurons
with resultant relief of spasticity. Although oral baclofen can be
effective for spasticity reduction, it results in global spasticity
reduction, which can lead to constipation, drooling, and decreased
axial tone and head control. 8
The limited solubility of baclofen when administered orally can
be overcome by intrathecal administration using a programmable,
ba ery-operated surgically implanted pump connected to a catheter
and delivery system into the intrathecal space; the blood-brain
barrier is bypassed and the systemic adverse effect profile is
decreased. Intrathecal baclofen (ITB) pump application has been
shown in a 2021 study to be effective in reducing spasticity and is
most frequently used for nonambulatory children and youth with a
diagnosis of cerebral palsy who experience spasticity and/or
dystonia 9 (Figure 2, A and B). Although invasive and without
morbidity, ITB is the most effective current method available for the
management of severe spasticity, dystonia, and mixed movement
disorders in cerebral palsy and commonly used for patients
categorized as GMFCS IV and V. 10
 Figure 2 A, Photograph of a baclofen pump including the medication
reservoir/battery, which is placed deep to the external oblique musculature, with
associated intrathecal tubing that is tunneled along the flank and into the
intrathecal space. B, PA radiograph showing scoliosis in a patient after
implantation of a baclofen pump for function-limiting spasticity.

SDR is a neurosurgical procedure in which 30% to 50% of the

dorsal rootlets between L1 and S1 are transected for the permanent
relief of spasticity in a select group of children with primarily
spastic diplegia (GMFCS I-III). SDR is most effective for young
ambulatory children, ranging in age from 2 to 10 years. 11 Although
there have been a handful of case series investigating the outcome
of SDR in GMFCS IV and V children, superiority compared with ITB
has not been demonstrated. 11 A comparison of functional outcomes
10 years after intervention found that both patients who underwent
SDR and those who did not undergo SDR had significant
improvement in gait pathology; however, the non-SDR group
experienced significantly be er gait improvement but also
underwent more orthopaedic interventions than the SDR group,
highlighting that different treatment courses may result in similar
outcomes into young adulthood. 12

Spine Surgery
Gross motor functional status is correlated with the risk of
development of scoliosis, with nonambulatory children (GMFCS IV-
V) being at greatest risk compared with ambulatory children who
have a risk similar to that of the general population. 13 The cause of
scoliosis in cerebral palsy remains speculative, but spasticity,
dystonia, muscle imbalance, weakness, postural impairment, and
immobility have been suggested as contributing factors. Previous
studies have suggested that bracing rarely prevents progression of
spinal deformity for nonambulatory children categorized as GMFCS
IV. 14 Newer technology with compression suits with stays to
provide additional truncal support has been commercially
promoted for patients with scoliosis, although there is no
convincing evidence to date to support effective prevention of curve
progression at this time.
Typical scoliotic curves in cerebral palsy will begin to progress at
the start of the preadolescent growth spurt and usually progress
faster than idiopathic curves. The rate of progression accelerates
when the curve reaches 40° to 50° and especially as the child enters
pubertal growth. Spinal curves in cerebral palsy are more likely to
continue to progress after skeletal maturity if the curve is more than
40°. In skeletally mature individuals with curves less than 50º, the
progression was 0.8° per year and 1.4° per year for curves greater
than 50°. 15 Segmental fixation along the entire course of the spine
using strong double rods is necessary to distribute the corrective
forces throughout the length of the segments to be fused. The
segmental anchors may be sublaminar wires, hooks, or pedicle
screws, or a combination of these. Fusion should include the pelvis
when pelvic obliquity exceeds 10° to 15° on an AP radiograph of the
pelvis with the patient in the si ing position. 16
Despite acceptable outcomes in terms of deformity correction
after spinal fusion, a 2021 prospective, longitudinal study has
demonstrated at 5-year follow-up that sustained improvements in
health-related quality of life were noted in children who underwent
hip reconstruction but not in children who underwent spinal fusion;
their scores initially improved at 1 year but by 2 years returned to
baseline and remained at baseline 5 years after spinal fusion. 17

Hip Surveillance and Surgery

The early stage of neuromuscular hip displacement is silent, and
formal screening by radiographs of the hips with careful
positioning is advised. Indications for referral to hip surveillance
programs are based on GMFCS level, the extent of topographic
involvement, and ambulatory status. 18 Untreated hip displacement
and dislocation may lead to pain and functional impairment
affecting the ability to sit, stand, or walk, and impaired quality of
life. A 2021 prospective longitudinal study has demonstrated that
for nonambulatory children with cerebral palsy who undergo hip
reconstruction surgery, at 2 and 5 years after surgery there were
long-lasting increases in the overall Caregiver Priorities and Child
Health Index of Life with Disabilities total score and improvements
in specific scores related to positioning and mobility, comfort and
emotions, and health. 17 A similar population-based study in adults
with cerebral palsy found that 72% experienced pain when their
migration percentage was greater than 30%. 19
Population-based hip surveillance has demonstrated that the
overall risk of hip displacement (defined as a migration percentage
greater than 30%) is approximately 30%. 20 Preventive surgery,
defined as soft-tissue release of the adductor, gracilis, and iliopsoas
muscles, is typically indicated for children with a migration
percentage between 30% and 40%, and although helpful in
achieving improvements in range of motion, long-term studies have
demonstrated an overall survivorship of approximately 30% at 7
years, with nonambulatory children experiencing the highest
revision rates. 21 Osseous reconstruction is recommended for a
migration percentage greater than 40%, which includes femoral
varus derotational osteotomy with or without associated pelvic
osteotomy. Well-performed hip reconstruction has the potential to
improve Caregiver Priorities and Child Health Index of Life with
Disabilities scores, which remain improved 5 years after the index
procedure 17 (Figure 3). For hips that present with late, painful
dislocations or associated femoral head deformity, salvage surgery
is indicated. A 2021 review comparing four different salvage surgical
procedures found that the highest parent satisfaction was
associated with a proximal femoral resection. The study authors
found that steroid injections were also effective but need to be
repeated and are less effective over time. 22 A previous systematic
review came to similar conclusions demonstrating comparable pain
outcomes among salvage procedures, with patients who have had
arthrodesis having greater pain and a higher complication rate. 23
Ultimately there is no single optimal procedure for salvage, but hip
arthrodesis should be avoided.
 Figure 3 A, AP pelvis radiograph from a 6-year-old girl with spastic quadriplegia
and a painful right hip dislocation. B, Postoperative radiograph demonstrating
reduction of the hip and improved acetabular coverage.

Similar to spine surgery, hip reconstruction is associated with

medical complications and surgical risk. A large retrospective
cohort study reported a 65% complication rate following bony hip
surgery, but only 15% required a return to the operating room, and
2% were associated with a life-threatening complication, with no
reported perioperative deaths. 24

Knee Surgery
The principal gait dysfunctions are stiffness and excessive flexion.
Recurvatum is sometimes seen after excessive hamstring
lengthening with an equinus contracture. Hamstring spasticity and
contracture are often evaluated by measuring the popliteal angle.
Unfortunately, the popliteal angle has li le correlation with knee
flexion during gait. The natural history of gait is progressive
deterioration including increasing stiffness throughout the lower
limb joints and increasing tendency to flexed knee gait and
ultimately crouched gait. Crouched gait is characterized by
excessive knee flexion during stance, incomplete extension at the
hip, and excessive ankle dorsiflexion. Knee stiffness during swing is
common.
Understanding the biomechanics of crouched gait has led to
improved surgical management in recent years, with the
development of more effective techniques to achieve lasting
correction. This can be summarized by classifying surgical
techniques as first-generation techniques, second-generation
techniques, and hybrid techniques. 25 First-generation techniques
involve lengthening of proximal contractures (psoas, hamstrings)
and correction of lever arm deformities. External support using
ground reaction ankle-foot orthoses is required until adaptive
shortening of the quadriceps occurs. This mechanism is more
effective in growing children with mild deformity of knee flexion
contracture less than 10°. First-generation techniques, such as
hamstring lengthening, cannot correct knee flexion deformity
greater than 10°; second-generation techniques here include distal
femoral extension osteotomy and patellar tendon advancement. For
growing children with fixed contractures of small magnitude (10° to
20°), guided growth with soft-tissue lengthening can be considered.
Distal femoral extension osteotomy and patellar tendon
advancement/imbrication have been shown to improve clinical
outcomes (knee flexion contracture, stance phase knee extension,
and extensor lag) for larger deformity (>20° knee flexion
contracture) 26 (Figure 4, A and B).
 Figure 4 A, AP and lateral radiographs from a 13-year-old boy with spastic
diplegia and bilateral significant knee flexion contracture resulting in crouched
gait, with associated patella alta. B, Postoperative radiographs from the same
patient after bilateral distal femoral extension osteotomies and patellar
distalization with soft-tissue procedure only.

For swing phase dysfunction and stiff knee gait secondary to

rectus spasticity, treatment directed to the rectus has been
advocated. Rectus femoris transfer has been recommended for
children with delayed peak knee flexion in mid stance and
overactivity of the rectus muscle on electromyographic study.
Rectus femoris transfer or rectus intramuscular lengthening are two
procedures that have been indicated for this clinical scenario. A
recent systematic review found improved knee kinematics after
rectus femoris transfer and distal release. However, only rectus
femoris transfer has a small positive kinematic effect size, whereas
the effect of distal release/intramuscular lengthening could not be
assessed because of publication bias and variable description of the
surgical technique. 27

Foot and Ankle Surgery

The ultimate treatment goal for foot and ankle deformities, which
occur often in children with cerebral palsy, is tailored to a child’s
functional level but for children categorized as GMFCS I-III the goal
is to achieve a painless, plantigrade foot that provides a stable foot
in stance and adequate clearance in swing; for children categorized
as GMFCS IV-V, the goals are to provide a painless, braceable foot
that can facilitate standing and transfers. The gastrocnemius muscle
is always more contracted than the soleus muscle in children with
spastic diplegia, and selective lengthening of the gastrocnemius
muscle is best for most children. In hemiplegia, children often have
contractures of both the gastrocnemius and soleus muscles, and
lengthening of both muscles is often necessary to achieve a
plantigrade foot with less likelihood of the development of crouch-
type gait. 28
Pes planovalgus and pes equinovalgus are common in children
with spastic diplegia; equinovarus deformities are more common in
children with hemiplegia. General management principles begin
with physical therapy and bracing. Surgical management can be
considered for patients with deformities not suitable for bracing or
in patients who cannot tolerate a brace. Equinovarus foot
deformities must first be defined as being flexible or fixed. Flexible
equinovarus foot deformities can be managed with a combination of
muscular rebalancing procedures including calf lengthening,
tibialis posterior lengthening, and split tibialis anterior tendon
transfer. More fixed deformities resulting in equinovarus often
require corrective calcaneal and midfoot osteotomies as necessary.
Planovalgus results from a series of segmental malalignments of the
hindfoot, midfoot, and forefoot; specifically valgus of the heel,
pronation of the midfoot and fla ening of the medial longitudinal
arch, pronation and abduction of the forefoot with hallux valgus.
The flexibility of the deformity should be checked by placing the
foot in an equinovarus position, while palpating the medial arch
with special a ention to the talonavicular joint. The midfoot can be
stabilized and deformity corrected by lengthening of the lateral
column of the foot (os calcis lengthening) or extra-articular fusion of
the subtalar joint. 29 - 31 Os calcis lengthening corrects subtalar joint
eversion and midfoot breaching by elongating the lateral column of
the foot, driving the heel out of valgus into relative varus, and
raising the medial arch; it is effective for patients categorized as
GMFCS I-II. The limits of calcaneal lengthening in cerebral palsy
have been radiographically described. Talonavicular subluxation
greater than 24° on the AP radiograph and a calcaneal pitch angle
less than −5° on the lateral radiograph were independent predictors
for poor results after calcaneal lengthening osteotomy. 32 In patients
categorized as GMFCS III and IV with moderate to severe
planovalgus collapse, stabilization of the medial column with
concomitant lateral column lengthening has demonstrated superior
radiographic results compared with isolated lateral column
lengthening 33 (Figure 5).
 Figure 5 AP (A) and lateral (B) standing foot radiographs demonstrating severe
planovalgus collapse, ankle equinus, and talonavicular uncoverage. C and D,
Postoperative radiographs after calcaneal lengthening and talonavicular
arthrodesis.

Single-Event Multilevel Surgery

Single-event multilevel surgery (SEMLS) is the standard of care for
the treatment of ambulatory children with cerebral palsy. SEMLS
corrects anatomic deformities based on clinical and radiologic
examination and a biomechanical analysis of gait deviations. The
goal is to approach gait pa erns of children with cerebral palsy in a
single-session surgery, albeit more intensive than a series of
individual surgeries. Research has consistently demonstrated that
SEMLS is a safe and effective surgical intervention that improves
the overall kinematic gait pa erns in the short term (1 to 2 years)
and midterm (5 to 7 years). 34 In a 10-year study published in 2021,
the overall gait pa ern improved after SEMLS; however, specific
aspects of the gait study deteriorated, and most participants
required secondary surgery to maintain their functional
improvements. 34

Myelomeningocele
Myelomeningocele and spina bifida comprise a spectrum of
congenital malformations of the spinal column and spinal cord
resulting from a failure of closure of the neural crests at 3 to 4
weeks after fertilization. Myelomeningocele is the most common
major birth defect, occurring in 0.9 per 1,000 live births. 35 Prenatal
diagnosis is often made through assay of alpha-fetoprotein
concentration in maternal serum. The diagnosis may also be made
via ultrasonography. Women of childbearing age should be
encouraged to have a diet with adequate folic acid.
Supplementation with folic acid decreases the risk of spina bifida
but must be done soon after conception. The incidence of spina
bifida has decreased since the addition of folic acid to many foods,
including breads and cereal. 35
In myelomeningocele, the tissues overlying the spinal cord are
not contained by the unfused posterior bony spine. These neural
elements are covered with a pouch of skin, with dura, or entirely
exposed. It is injury to these neural elements that causes major
motor and sensory deficits. Spina bifida most frequently occurs in
the lumbosacral region of the spine but can occur at any level. The
most distal functioning level most often determines function.
Quadriceps power, or L4 level, is an important differentiator for
function as this allows for active knee extension and community
ambulation. 36
Most children with myelomeningocele benefit from
multidisciplinary care. Neurosurgery is critical for diagnosis and
treatment of children with associated hydrocephalus, Chiari
malformation, and tethered cord. Many patients also benefit from
the care of a urologist because there is a very high incidence of
bowel and bladder dysfunction. 37

Spinal Deformity
Delivery of infants with myelomeningocele is done by cesarean
section to avoid further neurologic damage to the vulnerable neural
elements. Neurosurgical closure of the myelomeningocele is
typically done within 48 hours after delivery, with a shunt used to
manage hydrocephalus. There may be benefits to prenatal closure
of myelomeningocele with improved motor function and reduced
need for a shunt. 38
Bony deformity of the spinal column including scoliosis,
kyphosis, and lordosis is common. 39 One study suggested a more
than 50% prevalence of scoliosis in myelomeningocele. 39 Short-term
complications are common, with postoperative infection developing
in up to one-third of patients. 40 Tethering of the spinal cord in a
child with myelomeningocele can cause progressive scoliosis,
change the child’s functional capacity, or generate spasticity.
Tethering must always be considered with new changes in function,
scoliosis, or neurologic function.
Syrinx, shunt issues, or new hydrocephalus can cause upper
extremity symptoms, such as weakness or spasticity. Brace
treatment in this population may not reliably prevent progression
of deformity but may be helpful for si ing posture and trunk
control.

Hip Deformity
Hip dysplasia and dislocation of the hip occur frequently in patients
with mid lumbar neurologic levels. Surgical hip reduction for
dysplastic or dislocated hips is not recommended because
redislocation and stiffness are common. 41 , 42 Hip range of motion
should be the focus of treatment.
Knee Deformity
Flexion deformity at the knee can be functionally limiting for
ambulatory children with myelomeningocele. Contractures
exceeding 20° can be managed with open capsular release, guided
growth, or distal femoral extension osteotomy. Extension
contracture of the knee, although less common, can be managed
with serial casting or V-Y quadriceps lengthening. Knee valgus,
often with associated external tibial torsion and femoral
anteversion, is common in patients with midlumbar-level
involvement by myelomeningocele because they lack functional hip
abductors and have a substantial trunk shift when walking with
ankle-foot orthoses. 43 This is often best approached with the use of
a knee-ankle-foot orthosis or forearm crutches with ankle-foot
orthoses.

Foot Deformity
In patients with myelomeningocele, clubfoot is the most common
foot deformity and may occur in up to 30% of patients. 44 Clubfeet in
these patients tend to be more rigid than idiopathic feet and require
more casts to obtain correction, and the recurrence rate is higher. 45 ,
46
Despite being more challenging to manage, the Ponseti method
remains the mainstay of treatment for clubfoot in
myelomeningocele. In a retrospective study investigating the
Ponseti method for clubfoot in myelomeningocele, the study
authors found that they were able to correct 100% of feet, but had a
68% rate of recurrence. These recurrences were managed with
further casting and avoided extensive surgical release. 45 With
surgical treatment, portions of the tendons of the foot (eg, Achilles
tendon, tibialis posterior, flexor hallucis longus, flexor digitorum
communis) may be resected rather than lengthened to decrease the
risk of recurrence of deformity. Joint fusions should be avoided in
general for the insensate foot because of the increased risk for
ulceration.
Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is the most common
inherited pediatric muscle disorder and is characterized by the
absence of dystrophin, resulting in progressive muscle atrophy and
weakness (Table 1). Musculoskeletal management goals for patients
with DMD include preservation of mobility, minimization of joint
contractures, maintenance of a straight spine, and promotion of
bone health. The early management goal of the orthopaedic
surgeon is to prevent contracture development with the use of
nigh ime orthoses and knee-ankle-foot orthoses to preserve
walking and mobility. The orthopaedic surgeon should be cautioned
regarding the use of tendon lengthening for the management of
contracture; this procedure can weaken the muscle and hasten the
loss of ambulation. Typically, patients with DMD are often
wheelchair-dependent by adolescence and contractures can develop
rapidly when nonambulatory. Scoliotic curves can progress rapidly
in the nonambulatory phase, and surgery is generally
recommended for curves measuring greater than 30°. Surgical
correction has been shown to improve quality of life, reduce pain,
improve si ing balance, and enhance function. 47 There is no cure
for DMD; however, the mainstay of medical management is
corticosteroid therapy, which should be initiated before functional
deterioration.

Table 1
Inheritable Neuromuscular Conditions

Location
Protein Nonorthopaedic
Prevalence Inheritance Gene of
Involved Manifestations
Pathology
DMD 1/4,000 X-linked DMD Dystrophin Muscle Cardiomyopathy,
— respiratory
Xp21 insufficiency
SMA 1/11,000 AR SMN 1 Survival Anterior Dysarthria,
—5q motor motor dysphagia,
neuron 1 neurons respiratory
(SMN1) compromise
 Location
Protein Nonorthopaedic
Prevalence Inheritance Gene of
Involved Manifestations
Pathology
FDRA 1/30,000 AR FXN— Frataxin Cerebellum Cardiomyopathy,
9q glucose
metabolism
dysfunction,
dysarthria,
dysphagia
CMT 1/2,500 AD PMP22 Peripheral Peripheral —
a
myelin nerves
protein 22
AD = autosomal dominant, AR = autosomal recessive, CMT = Charcot-Marie-Tooth disease,
DMD = Duchenne muscular dystrophy, FDRA = Friedreich ataxia, SMA = spinal muscular
atrophy
Type 1a, most common form.
a

Summary
Children and young adults with neuromuscular conditions often
experience spinal and lower extremity orthopaedic deformity.
Although the underlying neuromuscular condition is not curable,
the associated orthopaedic interventions have the potential to
positively affect the function and quality of life. The overall
incidence of cerebral palsy is slowly increasing with improved
neonatal care, but many other neuromuscular conditions are static
in terms of their prevalence. With the advancement of targeted
genetic therapy, the medical management and ultimate outcome of
several neuromuscular conditions have improved. Cures for many
of these neuromuscular conditions remain elusive, but the potential
for cure is more likely now than ever before.

Key Study Points

SDR should be indicated for the management of spasticity in ambulatory children
with cerebral palsy (GMFCS I-III).
ITB should be considered for management of spasticity and dystonia in
nonambulatory children with cerebral palsy (GMFCS IV-V).
Outcomes of hip reconstruction surgery in nonambulatory children with cerebral
palsy at 2 and 5 years have demonstrated stable and improved health-related quality
 of life scores, whereas in comparison spinal fusion for nonambulatory children with
cerebral palsy results in stable but not improved health-related quality of life scores.
Early intervention for scoliosis surgery in DMD (>30°) should be considered to
maintain improved quality of life and prevent or mitigate respiratory decline.

Annotated References
1. Oskoui M, Coutinho F, Dykeman J, Je e N, Pringsheim T: An
update on the prevalence of cerebral palsy: A systematic review
and meta-analysis. Dev Med Child Neurol 2013;55(6): 509-519.
2. Li le WJ: On the incidence of abnormal parturition, difficult
labour, premature birth and asphyxia neonatorum on the mental
and physical condition of the child, especially in relation to
deformities. Clin Orthop Relat Res 1966;46:7-22.
3. Palisano R, Rosenbaum P, Walter S, Russell D, Wood E, Galuppi
B: Development and reliability of a system to classify gross motor
function in children with cerebral palsy. Dev Med Child Neurol
1997;39(4):214-223.
4. Palisano RJ, Rosenbaum P, Bartle D, Livingston MH: Content
validity of the expanded and revised gross motor function
classification system. Dev Med Child Neurol 2008;50(10):744-750.
5. Bax M, Tydeman C, Flodmark O: Clinical and MRI correlates of
cerebral palsy: The European Cerebral Palsy Study. J Am Med
Assoc 2006;296(13):1602-1608.
6. Hastings-Ison T, Sangeux M, Thomason P, Rawicki B, Fahey M,
Graham HK: Onabotulinum toxin-A (Botox) for spastic equinus in
cerebral palsy: A prospective kinematic study. J Child Orthop
2018;12(4):390-397.
7. Fortuna R, Vaz MA, Youssef AR, Longino D, Herzog W: Changes
in contractile properties of muscles receiving repeat injections of
botulinum toxin (Botox). J Biomech 2011;44(1):39-44.
8. Ghanavatian S, Derian A: Baclofen, in StatPearls, 2021. This is a
review article on the indications, pharmacokinetics, and
 mechanisms of action for oral and intrathecal baclofen. Level of
evidence: IV.
9. Lodh R, Amin S, Ammar A, et al: Intrathecal baclofen pumps in
the management of hypertonia in childhood: A UK and Ireland
wide survey. Arch Dis Child 2021;106(12): 1202-1206. An
electronic survey was sent to all pediatric centers in the United
Kingdom and Ireland, where most use of ITB (93%) was in
nonambulatory children with a diagnosis of cerebral palsy (73%).
The study authors concluded that there is a need to create
national standards for referral and clinical care for ITB. Level of
evidence: IV.
10. Butler C, Campbell S: Evidence of the effects of intrathecal
baclofen for spastic and dystonic cerebral palsy. AACPDM
treatment outcomes commi ee review panel. Dev Med Child
Neurol 2000;42(9):634-645.
11. Kudva A, Abraham ME, Gold J, et al: Intrathecal baclofen,
selective dorsal rhizotomy, and extracorporeal shockwave therapy
for the treatment of spasticity in cerebral palsy: A systematic
review. Neurosurg Rev 2021;44(6):3209-3228. This is a systematic
review investigating the efficacy of ITB, SDR, and extracorporeal
shock wave therapy for spasticity reduction in children with
cerebral palsy. The study authors concluded that ITB is best for
GMFCS IV and V children, and SDR is indicated for younger
children (younger than 10 years) (GMFCS I-III). Further study is
needed to establish indications for extracorporeal shock wave
therapy. Level of evidence: I.
12. Munger ME, Aldahondo N, Krach LE, Novacheck TF, Schwar
MH: Long-term outcomes after selective dorsal rhizotomy: A
retrospective matched cohort study. Dev Med Child Neurol
2017;59(11):1196-1203.
13. Persson-Bunke M, Hagglund G, Lauge-Pedersen H, Wagner P,
Westbom L: Scoliosis in a total population of children with
cerebral palsy. Spine (Phila Pa 1976) 2012;37(12):E708-E713.
14. Rang M, Douglas G, Bennet GC, Koreska J: Seating for children
with cerebral palsy. J Pediatr Orthop 1981;1(3):279-287.
15. Jevsevar DS, Karlin LI: The relationship between preoperative
nutritional status and complications after an operation for
scoliosis in patients who have cerebral palsy. J Bone Joint Surg Am
1993;75(6):880-884.
16. Yazici M, Asher MA, Hardacker JW: The safety and efficacy of
Isola-Galveston instrumentation and arthrodesis in the treatment
of neuromuscular spinal deformities. J Bone Joint Surg Am
2000;82(4):524-543.
17. DiFazio RL, Vessey JA, Miller PE, Snyder BD, Shore BJ: Health-
related quality of life and caregiver burden after hip
reconstruction and spinal fusion in children with spastic cerebral
palsy. Dev Med Child Neurol 2021;64(1):80-87. This prospective
longitudinal cohort study of nonambulatory children with
cerebral palsy who underwent hip reconstruction and spinal
fusion presenting 2- and 5-year follow-up outcomes related to
health-related quality of life and caregiver burden. The study
authors concluded that both hip reconstruction and spinal fusion
improve health-related quality of life, especially for hip instability
but does not change caregiver burden. Level of evidence: II.
18. Shore B, Spence D, Graham H: The role for hip surveillance in
children with cerebral palsy. Curr Rev Musculoskelet Med
2012;5(2):126-134.
19. Wawrzuta J, Willoughby KL, Molesworth C, et al: Hip health at
skeletal maturity: A population-based study of young adults with
cerebral palsy. Dev Med Child Neurol 2016;58(12):1273-1280.
20. Soo B, Howard JJ, Boyd RN, et al: Hip displacement in cerebral
palsy. J Bone Joint Surg Am 2006;88(1):121-129.
21. Shore BJ, Yu X, Desai S, Selber P, Wolfe R, Graham HK:
Adductor surgery to prevent hip displacement in children with
cerebral palsy: The predictive role of the gross motor function
classification system. J Bone Joint Surg Am 2012;94(4):326-334.
22. Koch A, Krasny J, Dziurda M, Ratajczyk M, Jozwiak M: Parents
and caregivers satisfaction after palliative treatment of spastic hip
dislocation in cerebral palsy. Front Neurol 2021;12:635894. This is a
case series of children with cerebral palsy who underwent either
steroid hip injection, interposition arthroplasty with shoulder
spacer, valgus subtrochanteric osteotomy (Shan ), or proximal
femoral resection (Castle). The study authors compared
radiologic outcomes and pain scores as per visual analog scale.
All procedures provided some pain relief, but no significant
superior procedure was identified. Level of evidence: III.
23. Kolman SE, Ruzbarsky JJ, Spiegel DA, Baldwin KD: Salvage
options in the cerebral palsy hip: A systematic review. J Pediatr
Orthop 2016;36(6):645-650.
24. DiFazio R, Vessey JA, Miller P, Van Nostrand K, Snyder B:
Postoperative complications after hip surgery in patients with
cerebral palsy: A retrospective matched cohort study. J Pediatr
Orthop 2016;36(1):56-62.
25. Young JL, Rodda J, Selber P, Ru E, Graham HK: Management
of the knee in spastic diplegia: What is the dose? Orthop Clin
North Am 2010;41(4):561-577.
26. Hyer LC, Carpenter AM, Saraswat P, Davids JR, Westberry DE:
Outcomes of patellar tendon imbrication with distal femoral
extension osteotomy for treatment of crouch gait. J Pediatr Orthop
2021;41(5):e356-e366. This is a case series of 28 children who
underwent distal femoral extension osteotomy and patellar
tendon imbrication, which demonstrated improved short-term
results in clinical (knee flexion contracture, knee extensor lag, and
popliteal angle), radiographic, and gait analysis variables of the
knee. Level of evidence: IV.
27. Josse A, Pons C, Printemps C, et al: Rectus femoris surgery for
the correction of stiff knee gait in cerebral palsy: A systematic
review and meta-analysis. Orthop Traumatol Surg Res 2021; July 24
[Epub ahead of print]. A meta-analysis, using PRISMA criteria,
compared the efficacy between rectus femoris transfer and distal
rectus femoris release. Results demonstrated a small positive
 kinematic effect size with rectus femoris transfer, but the effect of
distal rectus release could not be assessed because of publication
bias. Level of evidence: I.
28. Shore BJ, White N, Kerr Graham H: Surgical correction of
equinus deformity in children with cerebral palsy: A systematic
review. J Child Orthop 2010;4(4):277-290.
29. Mosca VS: Calcaneal lengthening for valgus deformity of the
hindfoot. Results in children who had severe, symptomatic
flatfoot and skewfoot. J Bone Joint Surg Am 1995;77(4):500-512.
30. Rathjen KE, Mubarak SJ: Calcaneal-cuboid-cuneiform osteotomy
for the correction of valgus foot deformities in children. J Pediatr
Orthop 1998;18(6):775-782.
31. Dogan A, Zorer G, Mumcuoglu EI, Akman EY: A comparison of
two different techniques in the surgical treatment of flexible pes
planovalgus: Calcaneal lengthening and extra-articular subtalar
arthrodesis. J Pediatr Orthop B 2009;18(4):167-175.
32. Luo CA, Kao HK, Lee WC, Yang WE, Chang CH: Limits of
calcaneal lengthening for treating planovalgus foot deformity in
children with cerebral palsy. Foot Ankle Int 2017;38(8):863-869.
33. Huang CN, Wu KW, Huang SC, Kuo KN, Wang TM: Medial
column stabilization improves the early result of calcaneal
lengthening in children with cerebral palsy. J Pediatr Orthop B
2013;22(3):233-239.
34. Visscher R, Hasler N, Freslier M, et al: Long-term follow-up after
multilevel surgery in cerebral palsy. Arch Orthop Trauma Surg
2022;142(9):2131-2138. The authors studied the gait cycles of 13
children with bilateral spastic cerebral palsy after single-event
multilevel surgery. The movement analysis profile and gait profile
score improved after surgery for all participants; however, 8 of 13
patients required additional surgeries to maintain improvements
during the 10-year follow-up period.
35. Dukhovny S, Wilkings-Haug L: Open neural tube defects: Risk
factors, prenatal screening and diagnosis and pregnancy
management, in Barss V, Levine D, Simpson LL, eds: UpToDate.
 2022. Accessed May 2022.
h ps://www.uptodate.com/contents/open-neural-tube-defects-
risk-factors-prenatal-screening-and-diagnosis-and-pregnancy-
management?
search=neural%20tube%20defects&source=search_result&selecte
dTitle=1∼150& usage_type=default&display_rank=1#H27. This
online book chapter reviews neural tube defects, prenatal
screening and evaluation, and pregnancy management. This
review focuses on terminology, screening protocols, etiology,
pregnancy management, and risk of recurrence.
36. Asher M, Olson J: Factors affecting the ambulatory status of
patients with spina bifida cystica. J Bone Joint Surg Am
1983;65(3):350-356.
37. Barden GA, Meyer LC, Stelling FHIII: Myelodysplastics–fate of
those followed for twenty years or more. J Bone Joint Surg Am
1975;57(5):643-647.
38. Heuer GG, Moldenhauer JS, Sco Adzick N: Prenatal surgery for
myelomeningocele: Review of the literature and future directions.
Childs Nerv Syst 2017;33(7):1149-1155.
39. Mummareddy N, Dewan MC, Mercier MR, Naftel RP, Wellons
JCIII, Bonfield CM: Scoliosis in myelomeningocele:
Epidemiology, management, and functional outcome. J Neurosurg
Pediatr 2017;20(1):99-108.
40. Ollesch B, Brazell C, Carry PM, Georgopoulos G: Complications,
results, and risk factors of spinal fusion in patients with
myelomeningocele. Spine Deform 2018;6(4): 460-466.
41. Feiwell E, Sakai D, Bla T: The effect of hip reduction on
function in patients with myelomeningocele. Potential gains and
hazards of surgical treatment. J Bone Joint Surg Am 1978;60(2):169-
173.
42. Sherk HH, Uppal GS, Lane G, Melchionni J: Treatment versus
non-treatment of hip dislocations in ambulatory patients with
myelomeningocele. Dev Med Child Neurol 1991;33(6):491-494.
43. Williams JJ, Graham GP, Dunne KB, Menelaus MB: Late knee
problems in myelomeningocele. J Pediatr Orthop 1993;13(6):701-
703.
44. Swaroop VT, Dias L: Orthopaedic management of spina bifida-
part II: Foot and ankle deformities. J Child Orthop 2011;5(6):403-
414.
45. Gerlach DJ, Gurne CA, Limpaphayom N, et al: Early results of
the Ponseti method for the treatment of clubfoot associated with
myelomeningocele. J Bone Joint Surg Am 2009;91(6):1350-1359.
46. Janicki JA, Narayanan UG, Harvey B, Roy A, Ramseier LE,
Wright JG: Treatment of neuromuscular and syndrome-
associated (nonidiopathic) clubfeet using the Ponseti method. J
Pediatr Orthop 2009;29(4):393-397.
47. Suk KS, Lee BH, Lee HM, et al: Functional outcomes in
Duchenne muscular dystrophy scoliosis: Comparison of the
differences between surgical and nonsurgical treatment. J Bone
Joint Surg Am 2014;96(5):409-415.
C H AP T E R 6 9

Pediatric Musculoskeletal Infection,

Inflammatory Conditions, and
Nonaccidental Trauma
Stephanie N. Moore-Lotridge PhD, Nathaniel Lempert MD, Jonathan
G. Schoenecker MD, PhD, FAAOS

Dr. Moore-Lotridge or an immediate family member serves as a board member, owner, officer, or committee
member of Orthopaedic Research Society. Dr. Schoenecker or an immediate family member has received
research or institutional support from Ionis Pharmaceuticals, OrthoPediatrics, and PXE International and
serves as a board member, owner, officer, or committee member of Pediatric Orthopaedic Society of North
America. Neither Dr. Lempert nor any immediate family member has received anything of value from or has
stock or stock options held in a commercial company or institution related directly or indirectly to the subject
of this chapter.

ABSTRACT
Few conditions in pediatric orthopaedics provoke greater apprehension than
a child with a suspected musculoskeletal infection (MSKI). In addition to the
potential for adverse medical and musculoskeletal outcomes, the pathogenic
organisms are continuously evolving, resulting in increased incidence and
severity of MSKI in children and adolescents. Thus, it is essential that
pediatric orthopaedic surgeons be up to date on the current epidemiologic
trends, diagnosis strategies, and treatment strategies in children with
suspected MSKI. Specifically, how serial monitoring of the acute-phase
response can aid physicians in determining the severity of an infection,
directing treatment, and prognosticating adverse medical and
musculoskeletal outcomes is important information. There are alternative
pathologies that an orthopaedic surgeon must distinguish from MSKIs to
direct appropriate care, including inflammatory conditions, neoplasms, and
nonaccidental trauma.
Keywords: acute-phase response; musculoskeletal infection; nonaccidental
trauma
Introduction
In pediatric medicine, few conditions are as enigmatic or carry higher stakes
for a child than a musculoskeletal infection (MSKI). Pediatric orthopaedic
surgeons are frequently called on to evaluate children with suspected MSKI,
accounting for nearly 1 in 10 orthopaedic consultations at academic pediatric
tertiary care centers in the United States. 1 Fortunately, modern medicine
has dramatically reduced childhood mortality from MSKI, which was
estimated to be as high as 40% in the preantibiotic era. 2 , 3 However, MSKIs
still pose a great risk to children given their capacity to drive adverse
medical and musculoskeletal outcomes with potentially lasting effects on
the child.

Threats to Effective Treatment in the 21st Century

Clinical advancements over the past 2 decades have markedly improved the
physician’s capacity to identify MSKIs from noninfectious etiologies,
thereby supporting timely antibiotic administration and surgical
interventions. Together, these effective treatment strategies have led to a
dramatically reduced risk of mortality from MSKI; however, threats to
effective treatment still remain, such that following an MSKI, children can
experience striking morbidity because of adverse outcomes. Adverse
medical outcomes can include thrombotic events such as deep vein
thrombosis, pulmonary emboli, or septic emboli, as well as the need for
interventions such as intensive care unit admission or placement on
extracorporeal membrane oxygenation. Given the essential role for
vascularity in developing bone, a thrombotic complication following an
exuberant acute-phase response (APR) can also lead to adverse
musculoskeletal outcomes including osteonecrosis of the epiphysis,
metaphysis, or diaphysis, potentially leading to loss of joint function and
abnormal limb development that can have lifelong implications for the
child.
To limit adverse medical and musculoskeletal outcomes, rapid
identification, diagnosis, and treatment of an MSKI are essential given that
the risk for adverse outcomes is proportional to disease severity. The
severity of an infection is a summation of the virulence and dissemination of
the pathogen, combined with the level to which the body responds to the
pathogen, referred to as the APR 4 (Figure 1, A). In response to a severe
MSKI, an exuberant APR can drive inflammation and coagulation to
pathologic levels, leading to thrombotic complications (Figure 1, B) such as
septic pulmonary emboli, deep vein thrombosis, and potentially death. 5 For
these reasons, rapid diagnosis and treatment of the infection is essential to
mitigate an exuberant or prolonged APR (Figure 1, C). Monitoring the APR
can aid in the care of children with MSKI.
Figure 1 Schematic representation of the acute-phase response (APR) following
musculoskeletal infection.A, Following the establishment of an infection and the associated
tissue destruction, the body must first stop bleeding and contain the infection. This is
accomplished through the coordinated activities of the coagulation and survival inflammatory
systems during the survival phase of the APR. B, As the infection progresses, the survival
phase of the APR will progressively increase in magnitude as it attempts to respond to the
growing infection and tissue destruction. The duration and severity of activation of
coagulation and survival inflammation proportionally increase the patient’s risk for adverse
medical outcomes such as thrombosis, acute respiratory distress syndrome (ARDS),
multiorgan dysfunction (MOD), and ultimately, death. C, Through intervention with surgical
débridement and antibiotic administration, the pathogen onslaught can be reduced. This
allows the survival phase of the APR to be sufficient to stop bleeding and trap the remaining
bacteria. However, as a result of the exuberant survival APR activated in response to
 infection, patients may still experience adverse musculoskeletal outcomes such as
osteonecrosis (AVN), limb-length discrepancies, joint deformity, or impaired tissue healing
following the resolution of the infection.(Figure permission: Schoenecker Laboratory.)

MSKI Epidemiology
Under the category of pediatric MSKI, there are numerous diagnoses based
on tissue location, such as pyomyositis (muscle), osteomyelitis (bone),
cellulitis (skin), or septic arthritis (joint space). Importantly, the severity of
the infection can vary relative to the pathogen’s virulence and
dissemination. For example, MSKI can happen both focally at a single site
(Figure 2) or multifocally throughout multiple tissue types (Figure 3).
Additionally, it may be simultaneously disseminated within the
bloodstream. As highlighted previously, given that the APR is activated in
proportion to the severity of the infection, identifying the location(s) of the
MSKI and if dissemination has occurred can greatly aid in directing
treatment and predicting a patient’s risk of adverse outcomes.

Figure 2 Magnetic resonance images showing examples of focal musculoskeletal

infection.Septic arthritis surrounding the knee (A) and hip (B) indicated by magnetic
resonance images. C, Magnetic resonance image showing intraosseous osteomyelitis
lesion of the proximal tibia. D, Magnetic resonance image showing pyomyositis lesions within
the musculature of the hip. Yellow arrows indicate the infection site.(Figure permission:
Schoenecker Laboratory.)
 Figure 3 Images showing examples of infection involving multiple tissues surrounding the
elbow.Most severe cases of musculoskeletal infection do not involve an isolated tissue type.
Radiographic evaluation (A) did not reveal diagnostic information and ultrasonography (not
shown) was suggestive of a septic joint. Fast-sequence MRI (B and C) of the elbow was
performed without sedation in less than 15 minutes, revealing invaluable diagnostic
information for culture and débridement. T1-weighted coronal short-tau inversion recovery
(STIR) sequence (B) and axial T2-weighted fat-saturated (C) magnetic resonance images
show evidence of simultaneous subperiosteal osteomyelitis, septic arthritis, and
pyomyositis. Without this information, culture and surgical débridement would have been
primarily focused on the intra-articular space and potentially intraosseous, whereas the
primary focus of the infection was extra-articular in the muscle and subperiosteal space.
(Figure permission: Schoenecker Laboratory.)

Pyogenic organisms are the most common causative pathogens of

pediatric MSKI, with Staphylococcus aureus being responsible for 40% to 90%
of cases. 3 , 6 Importantly, S aureus is continuously evolving, conferring
virulence factors and antibiotic resistance that can markedly alter the
severity of the MSKI and affect which pharmacologic interventions will be
efficacious. In a 2020 multicenter study of pediatric tertiary care centers
conducted by the Children’s Orthopaedic Trauma and Infection Consortium
for Evidence-Based Studies (CORTICES) group, it was found that S aureus
accounted for 65.1% of all culture-positive infections at the time of
consultation by orthopaedic providers, of which 37.4% were found to be
methicillin-resistant S aureus (MRSA). 1 Aligning with these findings,
another large national study between 2009 and 2012 reported that 38% of
pediatric osteomyelitis cases were caused by MRSA, with the remaining 62%
being caused by methicillin-sensitive S aureus (MSSA). 7
In addition to variation over time, there are marked geographic
differences in rates of MRSA and MSSA infections in the United States and
Europe. 8 , 9 Aligning with trends reported in the national CORTICES study,
pediatric patients with MSKI in the southern United States experienced a
greater incidence of MSKI from MRSA compared with other regions. 7 , 10 It
has been hypothesized that the variance between regions and sites may be
the product of variable antibiotic utilization pa erns, varying patient
demographics, or endemic bacteria. 7 , 11 , 12 From the nationwide CORTICES
assessment, an average MSSA:MRSA ratio of 1.84 was observed at the time
of consultation for MSKI across 18 institutions. 1 This information can be
used as a benchmark value for the anticipated rate of MRSA and MSSA,
such that if an institution experiences a markedly greater ratio of MRSA at
the time of consultation, this may indicate the need for an intervention to
address a disproportionately higher relative rate.

Severity of MRSA Versus MSSA

The severity of an infection is a summation of the virulence and
dissemination of the pathogen, combined with the level to which the body
responds to the pathogen, known as the APR. As such, with the emergence
of MRSA in the community in the early 2000s, numerous studies focused on
assessing the virulence and infection severity of MRSA relative to MSSA.
Importantly, early studies reported that patients with MRSA infections had
poorer outcomes than patients with MSSA infections. However, the
continuous evolution and gain of virulence factors in MSSA has led more
recent reports to conclude similar virulence and patient outcomes. For
example, a study of 91 pediatric MSKI cases reported similar clinical severity
and outcomes for patients with confirmed MRSA or MSSA infections. 13
Furthermore, when a previously effective 2009 logistic regression model
based on C-reactive protein (CRP) level, temperature, white blood cell
(WBC) count, pulse, and respiratory rate at presentation was applied in 2017,
it no longer possessed the ability to effectively differentiate between MRSA
and MSSA infections. 13 Together, these recent findings suggest that
pathogen type is but one factor that affects MSKI severity and subsequently
the risk of adverse patient outcomes. Given the variance in epidemiology by
region and over time, physicians should not limit their assessment of
disease severity to the identity of the pathogen. Although pathogen
identification is essential for applying antibiotic therapy, both MSSA and
MRSA can drive the body’s APR to exuberant levels, increasing the risk of
adverse medical and musculoskeletal outcomes.

Diagnosis and Directing Management of MSKI

Paramount to caring for children with suspected MSKI, there are four tasks
that all members of the medical and surgical team should accomplish when
working up a suspected MSKI. 14 The team should address the following four
questions: (1) Where is the suspected infection? (2) Is it an infection and if
so, what is the pathogen? (3) How severe is the infection (ie, how will the
infection drive the APR)? (4) How to best treat the infection? Given the
heterogeneity of MSKI from one institution to another, it is beneficial for all
pediatric orthopaedic surgeons who care for these children to understand
the philosophy and tools of these tasks to maximize the benefit to both the
child and other services involved in the child’s care.

Identifying Where the Infection Is Located

The child’s developing musculoskeletal system is an ideal target for
bacteria, given that bacteria, similar to mesenchymal stem cells or cancers,
have a tropism for damaged and regenerating tissues. Molecularly, growing
bone and muscle mimic regenerative tissue, predisposing it to similar
relative risk of being targeted by bacteria. 4 Additionally, unique
characteristics of the physis, such as robust tortuous vascularity and its
relative immune-privileged nature, can likewise predispose this site to
initiation of infection. 14 Together, these molecular factors support the long-
standing observation that developing children are susceptible to
spontaneous infections predominately at or around major joints. For
reasons not completely understood, lower extremities are far more
susceptible to spontaneous MSKI than upper extremities, with the femur
(hip and knee) being the most susceptible.
Armed with the understanding that bacteria target developing
musculoskeletal tissue, the most important goal of the medical and surgical
team is to quickly determine which tissues and/or joint(s) are involved. In
the past, an irritable joint with other diagnostic criteria suggesting MSKI
was thought to be an intra-articular process, specifically septic arthritis. This
previous clinical intuition was supported by use of radiographs and
ultrasonography, which are excellent at revealing intra-articular effusions
but poor at detecting early osteomyelitis or pyomyositis. MRI has become a
practical tool in the arsenal of MSKI workup; it has been found that this
prevailing clinical intuition is limited by anatomic ascertainment bias,
leading to a one-dimensional understanding of this disease process. For
example, as MRI has quickly become the gold standard modality for three-
dimensional evaluation of MSKI, it has been shown that many cases of joint
irritability—previously assumed to be isolated infections—are rather
multifocal, extending into the surrounding bone and muscle. Together,
these studies have changed the understanding of the incidence and
heterogeneity of MSKI and markedly improved the ability to direct culture
collection and treatment. Perhaps most importantly, MRI has enhanced the
ability to localize the true extent of MSKI.
In pediatric care, fast-sequence MRI can be performed in nonsedated
children, 14 thereby allowing for relatively quick three-dimensional
assessment of the intra-articular space, bone, and muscle suspected to be
infected. However, the most effective tool in an orthopaedic surgeon’s
toolbox remains the ability to perform a thorough physical examination and
delineate musculoskeletal pain generators. Identifying and communicating
where an infection may exist allows standard MRI to be performed at the
region of interest as opposed to protocols requiring scanning of an entire
limb, which can take hours and necessitate sedation of the child. For
instance, a simple “X” marked on the region of interest can make fast-
sequence, nonsedated MRI more practical in an emergency department
workup of a child with suspected MSKI.

Determining the Pathogen

Rapid diagnosis of infection and identification of the causative organism is
essential to properly treat pediatric patients with suspected MSKI. In cases
of presumed MSKI, rapid identification of the causative organisms by
culturing allows for earlier narrowing of antibiotic therapy, thus decreasing
the overuse of broad-spectrum antibiotics. In addition to directing
pharmacologic intervention, knowledge of the causative pathogen can
likewise inform the clinical care team about the severity of the infection
given that pathogens vary in their expression of virulence factors and
capacity to hijack the APR. For example, the two most common bacteria that
infect children, Streptococcus pyogenes and S aureus, produce virulence factors
that increase disease severity by allowing the pathogen to rapidly
disseminate across tissue planes and into the bloodstream. 15 Alternatively,
pathogens such as Kingella kingae, which has been rising in incidence as a
causative pathogen for septic arthritis in children younger than 2 years,
express relatively fewer virulence factors and are often associated with a
minimal APR. 16 For these reasons, knowledge of the causative pathogen not
only aids in directing antibiotic therapy but likewise can inform treating
physicians about disease severity and risk of adverse outcomes.
Current methodology and tools available for the identification of
infectious organisms are frequently limited to standard bacterial blood and
tissue cultures, which can take days, or weeks in cases such as K kingae, to
produce results. Prior studies have reported culture positivity rates for
patients with confirmed MSKI ranging between approximately 40% and 80%.
In the 2020 multicenter CORTICES study, it was found that, on average, only
one in three pediatric MSKI-related consultations produced a culture-
positive identification at the time of orthopaedic consultation. 14
Importantly, negative culture results may occur because the child does not
have an infection, the causative organism is difficult to culture, the incorrect
tissue was sampled, or the infection is disseminated without abscess.
Clearly, this remains an area of pediatric MSKI care that requires
improvement. Working within these shortcomings, the most important role
of the pediatric orthopaedic surgeon is to provide a sufficient sample of the
most likely infected tissue. As highlighted previously, MRI in conjunction
with physical examination is vital in localizing the infected tissues and
directing where cultures should optimally be obtained. Furthermore, MRI
may prevent inoculation of sterile tissue by inadvertently traversing through
infected tissue (such as muscle) on the way to obtain cultures of the bone or
intra-articular space.

Determining How Severe an MSKI is and the Risk

for Adverse Outcomes
Unlike an acute injury, tissue damage as a result of MSKI is continuous as
the infection worsens or spreads (Figure 1). Although knowledge of the
causative pathogen and location of the MSKI is essential to direct treatment,
an understanding of the MSKI severity is also essential to mitigate adverse
medical and musculoskeletal outcomes.

Classification System for MSKI Severity in Pediatric Patients

Currently, many studies assessing pediatric MSKI divide patient
populations relative to their diagnosis based on the tissue type that is
infected. 14 , 17 An inherent limitation of this practice is that clinical
presentation, treatment, and patient prognosis are highly variable within
each diagnostic cohort, 18 and as discussed previously, MSKIs are often not
isolated to a single tissue type. For these reasons, classification systems
based on MSKI severity and degree of dissemination have been developed 19
, 20
to stratify patients with suspected MSKI into three categories:
inflammation (noninfectious), local infection, and disseminated infection 19
(Table 1). Using these criteria, cases of disseminated disease were found to
be positively correlated with both prolonged hospital stays and elevated
markers of the APR. As such, a subsequent study demonstrated that CRP
 q y
level, pulse rate, and temperature together could accurately predict MSKI
severity classification at the time of presentation. 20 Specifically, this model
found that the odds of a more severe adverse outcome increased by 30% for
every 10-U increase in CRP. 20 Improving on this classification system, it was
noted in a 2019 study that pediatric patients with disseminated disease had
varying APR profiles, which allowed for differentiation of complication rates
21
; thus, a fourth category (disseminated infection + complication) has been
established (Table 1). Because this classification system does not rely on
anatomic diagnosis or identification of tissue involvement, early
identification of disease severity, and therefore patient prognosis, is
possible. Future prospective studies are warranted to validate the clinical
utility of this classification system and model.

Table 1
Classification System for Musculoskeletal Infection Severity

Inflammatory Disseminated Disseminated Infection +

Local Infections
(Noninfectious) Infections Complication
 Inflammatory Disseminated Disseminated Infection +
Local Infections
(Noninfectious) Infections Complication
Definition All of the following One of the For two or more In addition to meeting the
(if available) must following must be anatomic sites, at criteria for disseminated
be TRUE: TRUE: least one of the infections, at least one of
following must be the following must be
Negative Imaging TRUE: TRUE:
blood culture diagnostic for
Negative osteomyelitis Imaging Thromboembolic
local culture or diagnostic diseases such as:
The criteria pyomyositis for Deep vein
for local or in one osteomyelitis thrombosis
disseminated anatomic site or Pulmonary
infections are Local culture pyomyositis embolism
not met positive Local culture Osteonecrosis
AND/OR positive Multiorgan failure
fluid/tissue AND/OR Pleural effusion
consistent fluid/tissue Pathologic fracture
with infection consistent Limb/joint deformity
(grossly with infection Amputation
purulent, cell (grossly Sequestration/
count purulent, cell involucrum
>50,000, count Death
and/or >50,000,
positive and/or
PCR) positive
One positive PCR)
blood culture Two or more
The criteria positive
for blood
disseminated cultures
infections are
not met

Example Transient synovitis Isolated distal Distal fibular Patient with proximal femur
femoral osteomyelitis with osteomyelitis with
osteomyelitis with subperiosteal subperiosteal abscess and
no subperiosteal abscess adjacent pyomyositis who
abscess Septic hip with experiences multiple
Isolated septic hip surrounding venous
pyomyositis thromboembolisms

Laboratory Measure of the APR to Assess MSKI

Severity
Accurately determining the severity of an MSKI is essential to managing
patient morbidity and the risk of adverse medical and musculoskeletal
outcomes. In addition to identifying the causative pathogen and locating the
site(s) of the infection, clinical laboratory draws can be used to assess the
exuberance of the infection-provoked APR, both at the time of admission
and throughout the course of care. One such well-validated laboratory
measure, CRP is a dynamic acute-phase reactant that becomes elevated in
response to inflammation. 14 In current clinical practice, CRP is used as both
a diagnostic and prognostic tool at the time of consultation for MSKI. In
prior studies, CRP was found to be effective for early diagnosis of an
infection within 4 to 6 hours of symptom onset. Given that CRP levels
rapidly elevate in proportion to the amount of tissue inflammation,
admission CRP levels have been demonstrated to sensitively predict the
severity of an MSKI, 19 whereas assessment of peak CRP levels has been
demonstrated to be a strong predictor of adverse vascular outcomes in
patients with MSKI, such as venous thromboembolism. Specifically, it was
found in a 2019 study that for every 20 mg/L increase in peak CRP, the risk of
thrombosis increased by 29%. 21
Beyond prognosticating the severity of MSKI and risk of adverse
outcomes, serial measures of CRP have been proposed as a means to assess
response to treatment. In MSKIs, if a treatment is effective, the CRP and
other acute-phase reactants should begin to return to normal levels. 5 If
values do not return to baseline or continue to increase within
approximately 48 hours of intervention, this may indicate to the medical
team that the prior treatment was insufficient and further intervention is
likely necessary (Figure 4).
 Figure 4 Schematic representation of the utility of serial laboratory values of the acute-
phase response (APR).Trends, or the delta, in C-reactive protein (CRP) can be useful in
assessing disease progression and treatment efficacy in pediatric patients with
musculoskeletal infection (MSKI). Early treatment is essential in treating MSKI, with
antibiotics and surgery leading to a decrease in CRP over the first few days. A, Illustration of
an anticipated CRP trend when an MSKI is sufficiently cared for, resulting in decreasing CRP
over 48 hours following intervention (antibiotics and/or surgery). B, Illustration shows that,
however, when CRP continues to increase 48 hours after intervention, this can indicate to
the treating physician that further intervention may be necessary, such as a change in
antibiotics or additional surgery. Once treatment has sufficiently addressed the infectious
burden, the body then enters the convalescent stage where tissue repair can begin.(Figure
permission: Schoenecker Laboratory.)

Another classically measured plasma APR value is the erythrocyte

sedimentation rate (ESR). In the context of injury or infection, ESR has been
examined as a surrogate measure for fibrinogen and the ongoing
containment of the injury to prevent bleeding and reduce susceptibility to
infection (Figure 5). Compared with CRP, ESR is a less sensitive marker for
the APR and can also produce misleading data for assessing infections given
that confounding conditions, such as pregnancy, obesity, and anemia, all
result in an elevated ESR. 22 , 23 Furthermore, reflective of fibrinogen’s role in
containment, ESR is a longer acting and less dynamic acute-phase reactant.
Therefore, although ESR may not perform well at admission for predicting
the presence of an infection, monitoring ESR may be useful to assess disease
severity and risk of adverse medical and musculoskeletal outcomes.

Figure 5 Acute-phase response (APR) markers and infection.Levels of the acute phase
change dramatically and rapidly during infection. Interleukins (yellow curve) are the first
acute-phase reactants to increase, followed closely by procalcitonin (not depicted) and then
C-reactive protein (CRP) (pink curve). In cases of severe musculoskeletal infection, CRP
levels can reach more than 100 times baseline, noninfectious, levels. Fibrinogen (also
measured as erythrocyte sedimentation rate [ESR]) increases to a lesser degree and takes
weeks to return to its preinjury levels. Albumin (not shown) decreases in response to the
APR by up to approximately 40% and often inversely correlates with CRP. The extent and
duration of an APR is dependent on the severity of a tissue injury and the resulting production
of inflammatory cytokines. Thus, serial monitoring of acute-phase reactants can aid clinical
decision-making. Only after the infection has been controlled by antibiotics and surgery can
the convalescence phase begin with tissue repair following clearance of infection.(Figure
permission: Schoenecker Laboratory.)

Cellular Markers of the APR

In addition to plasma acute-phase reactants, changes in cellular effectors can
also be sensitive indicators of the survival APR. Broadly, WBC counts are
commonly used to assess the presence of an infection. However, WBC
counts are one of the least sensitive measures for the diagnosis of a pediatric
MSKI. In addition to being variable with age, prior studies have
demonstrated a wide range in the incidence of elevated WBC counts (25% to
73%) among patients with osteomyelitis. Furthermore, similar WBC values
have been reported in pediatric patients with inflammatory (noninfectious)
etiologies, local infections, and disseminated infection. This demonstrates
that elevated WBC counts alone are not sufficient to confirm the presence or
assess the severity of an MSKI.
Alternatively, analysis of specific subtypes of leukocytes, such as
neutrophils, lymphocytes, and their relative proportions, has been found to
be more sensitive for assessing the presence or severity of an infection.
Neutrophils are an essential cellular player in innate immunity that activate
in response to the APR and bacterial invasion. In addition to directly
binding and phagocytosing pathogens, neutrophils also aid in trapping and
killing bacteria in the extracellular space by producing neutrophil
extracellular traps, reactive oxygen species, and other cytotoxic molecules. 4 ,
24
Given these essential roles, neutrophils are the most abundant leukocytes
in circulation and their levels are tightly regulated. 25 As such, an elevation
in the neutrophil number has long been used as a prognostic indicator of
infection. However, when evaluating the severity of infection, neutrophil
count alone does not perform well. 26 For these reasons, many studies have
begun to examine cellular ratios, such as the neutrophil to lymphocyte ratio,
as a more sensitive predictor of disease severity and prognosticator of
patient outcomes.
Finally, a small but essential cellular marker of the APR is platelets. As
the first line of defense against pathogen invasion, platelets are capable of
directly interacting with bacteria, 27 , 28 engulfing bacteria, 29 and releasing
bactericidal molecules from their granules. Furthermore, platelets can also
interface with the innate immune response, leading to the release of a
myriad of chemokines and cytokines and the formation of platelet-
lymphocyte aggregates, which together play an essential role in supporting
the containment and removal of pathogens by the innate immune response
that is critical to survival. 30 , 31 As part of these activities, both abnormally
high as well as abnormally low platelet counts have been associated with
detection of infection and adverse outcomes.

Determining How to Best Treat the MSKI

As noted previously, regulation of the APR is critical, as continuous
exuberant activation can lead to devastating complications accounting for
most of the morbidity and mortality in pediatric patients with MSKI. 5 Thus,
the most effective means to prevent and manage an exuberant APR is to
mitigate the infection with antibiotics and surgical débridement. 4 , 5 To
complement these efforts, numerous studies in the adult population have
begun to examine the therapeutic benefit of correcting hyperinflammation
and the coagulopathies with the aim of reducing the morbidity and
mortality from infections. 32 Future studies are still necessary to determine
whether such therapeutics would likewise improve outcomes in pediatric
patients with severe MSKIs when administered in conjunction with
antibiotics and surgical débridement.

Antibiotic Administration
Antibiotics continue to be the first line of therapy for MSKI. In addition to
culture results, patient factors can also inform antibiotic selection. As
discussed previously, rapid identification of the causative organisms is
important given that it allows for earlier narrowing of antibiotic therapy,
thereby decreasing the overuse of broad-spectrum antibiotics. Thus, in
addition to collaborating with colleagues who specialize in infectious
disease, it is important for pediatric orthopaedic surgeons to have a broad
understanding of the advantages and disadvantages of common antibiotics
used to manage MSKI. These include beta-lactams, glycopeptides,
lincosamides, lipopeptides, rifampin, and to a lesser degree,
aminoglycosides.
Traditionally, the duration and route of antibiotics administered are
dependent on the institutional experience, the patient’s response, and the
type of tissue affected. For example, 2 to 4 weeks of intravenous (IV)
antibiotics are often recommended for osteomyelitis followed by oral
antibiotics for a total of 6 to 8 weeks. Some institutions have promoted
shorter durations of IV antibiotics until CRP has decreased by 50% followed
by 2 to 4 weeks of oral antibiotics. 33 In either case, IV antibiotics are
commonly administered through a peripherally inserted central catheter
(PICC). Beyond providing a secure route for vascular delivery of antibiotics,
the use of a PICC line in pediatric patients is riddled with complications
ranging from occlusion of the line to more serious complications such as
infection or thrombosis. 34 For these reasons, physicians have begun to
compare the effectiveness (ie, treatment failure) of oral versus IV antibiotic
administration in pediatric patients with MSKI. A retrospective cohort study
showed that across 36 participating children’s hospitals, PICC and oral
antibiotic administration after discharge were equally as effective in patients
with acute hematogenous osteomyelitis, yet patients with a PICC had a
higher risk of returning to the emergency department or hospitalization for
an adverse outcome. 35 This study highlights the need for physicians to
challenge the long-standing belief that a PICC is essential for antibiotic care.
As oral antibiotics continue to improve in efficacy and tissue penetration, IV
administration beyond the time of hospitalization may not offer increased
efficacy. Future prospective studies in cases of more severe, disseminated,
infections will be essential for understanding the true potential for negating
use of a PICC and their associated complications in pediatric patients with
MSKI.
Given that culture results are paramount for narrowing antibiotic therapy,
it has long been suggested that antibiotics be held until cultures are
obtained with the anticipated benefit of improving culture yields. Recent
reports have challenged this long-held tenet, demonstrating that prior
antibiotic administration had no effect on culture sensitivity in patients with
either local or disseminated MSKI. Furthermore, in patients with local
infections, earlier antibiotic administration was found in a 2019 study to be
correlated with a shorter length of stay. 36 Likewise, in pediatric patients
with a diagnosis of osteomyelitis, prior antibiotic administration did not
affect positive identification of the pathogen in bone biopsy cultures,
although the overall culture yields were found to be lower and inversely
correlated with the duration of antibiotic therapy. 37 For these reasons, the
current recommendation is to refrain from delaying antibiotics, particularly
in patients experiencing an exuberant APR given the limited effect on tissue
culture success and the potential benefit of antibiotic administration in
reducing the risk for complications. A caveat to this recommendation is that
it is currently unknown how the duration of antibiotics may affect culture
rates. In many of the previously mentioned studies, the time from antibiotic
administration to culture was less than 24 hours. Thus, if the child is
anticipated to be taken to the operating room for débridement and
simultaneous obtainment of tissue cultures in the near future, prior
antibiotic administration is anticipated to only improve patient outcomes
and not affect the capacity to obtain a successful tissue culture.

Indications for Surgical Management—Culture,

Excise, and Source Control
In collaboration with antibiotic administration, to obtain cultures, reduce
the infectious burden, and mitigate the associated APR, surgical
débridement of the infected tissue is often required. Numerous factors
should be considered when directing surgical intervention in these patients.
For example, relative to assessing the severity of disease, any patient who is
physiologically unstable secondary to an MSKI should be considered for
urgent surgical débridement. This is particularly important in cases of
rapidly progressing and destructive infections, such as necrotizing fasciitis.
38
Beyond these cases, the indications for surgery become less defined. In
general, abscesses will not resolve on their own; thus, drainage and
débridement are required. Depending on the location and severity of the
MSKI, drainage and débridement can be performed at the bedside or with a
small radiographically guided procedure; however, when the infection lies
deeper within tissues behind vital structures, involves multiple tissues, or
has formed more complex fluid collections, surgical débridement might be
necessary to clear the infection. 39

When It Is Not an MSKI—Pathologies That Can

Mimic MSKI
A critical first step in the workup of a child with MSKI is the identification of
noninfectious mimicries of MSKI, such as inflammatory conditions,
malignancy, or nonaccidental trauma (NAT), to both prevent unneeded
treatment and direct critical therapy. Unfortunately, the signs and
symptoms of MSKI, focal trauma (accidental or nonaccidental), and
malignancy may present in a similar manner—pain, tenderness, swelling,
and radiographic abnormalities. To help differentiate these conditions, there
are several distinguishing features that an astute physician can use to
delineate these conditions and direct appropriate and timely treatment.

Inflammation or Infection
One of the most difficult differentials from an infection is discerning these
from inflammatory, or reactive, conditions. The physical signs of
inflammatory pathologies are similar, including joint pain and limp with
prolonged changes in ambulation, progressing to difficulty to bear weight.
Traditionally, the Kocher criteria 40 have been used to help distinguish
between septic arthritis and transient synovitis in the hip, two conditions
that have markedly variable clinical severities and effects on patient
outcomes if misdiagnosed. Importantly, although these criteria provide a
valuable framework to consider when evaluating a child with an inflamed
hip, there are limitations given that they do not always effectively translate
to joints beyond the hip or distinguish septic arthritis from other infections
such as osteomyelitis or pyomyositis. 41 Thus, in such clinical conditions,
physicians must rely on their clinical intuition to ensure cases of MSKI are
not missed.
Although less common than toxic synovitis, juvenile idiopathic arthritis
(JIA) and rheumatic fever can likewise present with pain and swelling of the
afflicted joint and an associated fever. JIA is an autoimmune-mediated
version of chronic arthritis commonly seen in children 7 to 12 years of age (6
per 100,000). 42 Although commonly mistaken for infection, JIA can be
distinguished by its gradual onset, polyarticular nature (akin to leukemia),
and radiographic presentation in which the joint typically appears worse
than it functions. In cases of rheumatic fever, joint pain is typically greater
than cases of JIA, yet the joint will appear seemingly normal. Rheumatic
fever, a sequela of group A streptococcal infection, predominantly affects
the knees, ankles, elbows, and wrists. 43 Pain secondary to rheumatic fever is
typically evanescent and migratory in nature. Although the Jones criteria
can be used to help diagnose rheumatic fever, the diagnosis of
poststreptococcal reactive arthritis can likewise be applied to patients with a
documented history of group A strep, but fail to meet all components of the
Jones criteria. 44 Although the incidence of complications from
poststreptococcal reactive arthritis remains unclear, the implementation of
long-term antibiotics remains controversial.

Infection or Malignancy
As with pediatric patients with MSKI, pediatric patients with a neoplasm
can present with similar, nonspecific systemic symptoms, such as pallor,
malaise, fever, weight loss, lymphadenopathy, hemorrhagic events, and
hepatosplenomegaly. Adding to the difficult task of distinguishing
neoplasia from MSKI, patients in both cohorts may complain of body pain,
neurologic symptoms, palpable masses, and bone pain that awakens the
child from sound sleep. Although differentiating tumors from infection may
be challenging, there are a few key points that can assist in making this
differentiation, including epidemiologic trends and diagnostic criteria.

Infection or Trauma
Musculoskeletal injuries are exceedingly common in children and
adolescents, and a prevalent cause for evaluation by an orthopaedic provider
in either the clinic or emergency department. As such, an important role of
pediatric orthopaedic providers is to identify cases in which a child’s
injuries are suspected to be a result of physical abuse rather than accidental
mechanisms, termed nonaccidental trauma (NAT). NAT continues to be a
significant source of morbidity and mortality in children, with more than 4
million instances of abuse and more than 1,770 abuse-related deaths in 2018
alone in the United States. In prior large data sets, common characteristics
of patients with NAT include young age (younger than 1 year: 71% of cases;
younger than 5 years: 95% of cases), male gender, and the presence of
fractures to one or more bones. In children, certain fracture locations, such
as the femur, posterior rib, or humeral shaft, are classically associated with
NAT; 45 , 46 however, location and fracture morphology in isolation are often
insufficient to distinguish NAT from an accidental trauma. Rather, a
thorough history and physical examination can reveal common indicators
that raise the suspicion of NAT, including injuries inconsistent with the
caregiver’s history, a reported mechanism of injury that is unexpected for
the child’s developmental status, or delayed presentation.
Despite the emphasis placed on reporting fractures suspicious for NAT,
cases of NAT are still misidentified as accidental in up to one-fifth of
children younger than 3 years. 47 Thus, when evaluating children who
present with pain, tenderness, or swelling to a limb, MSKI, inflammatory
conditions, and malignancies should be suspected, but astute physicians
should also vigilantly assess for NAT, particularly when information
gathered during the history and physical examination does not align.

Summary
Pediatric orthopaedic surgeons are commonly consulted for cases of
suspected MSKIs. Unlike other emergent consultations, such as fracture
care, MSKIs can present with marked heterogeneity in disease location,
causative organism, disease severity, and required treatment. Timely and
accurate evaluation of patients with suspected MSKI, along with the
delineation from inflammatory pathologies, malignancies, and traumatic
injuries, is essential to direct treatment to limit the possibility of an
exuberant APR, thereby reducing the risk of adverse medical and
musculoskeletal outcomes.

Key Study Points

Although cases of isolated MSKI do occur, infections that are more severe and lead to adverse
outcomes typically involve infection of multiple tissues or systemic infections involving multiple
body parts. When disseminated disease is suspected, the investigative team must be sure to
avoid satisfaction of search and look beyond the most painful joint.
 The severity of an infection is a summation of the virulence and dissemination of the pathogen,
combined with the level to which the body responds to the pathogen (ie, APR).
Trending measures of the APR are useful in determining whether an infection is worsening or
improving with treatment, whereas peak values prognosticate adverse medical and
musculoskeletal outcomes in patients with MSKI, especially thrombotic pathology.
S aureus, one of the most prevalent pathogens responsible for MSKI, is continuously evolving.
Although these changes will affect which antibiotics will be most effective, physicians should not
rely on these designations alone to determine disease severity.
The orthopaedic surgeon should be vigilant for pathologies that can mimic MSKI, including
inflammatory conditions, neoplasms, and NAT.

Annotated References
1. Schoenecker JG, CORTICES Group: Defining the volume of consultations
for musculoskeletal infection encountered by pediatric orthopaedic
services in the United States. PLoS One 2020;15(6):e0234055. This
multicenter study evaluated the effect care for pediatric MSKIs has on
pediatric orthopaedic providers at academic pediatric tertiary care centers.
Level of evidence: III.
2. Ciampolini J, Harding KG: Pathophysiology of chronic bacterial
osteomyelitis. Why do antibiotics fail so often? Postgrad Med J
2000;76(898):479-483.
3. Song KM, Sloboda JF: Acute hematogenous osteomyelitis in children. J
Am Acad Orthop Surg 2001;9(3):166-175.
4. An TJ, Benvenuti MA, Mignemi ME, Thomsen IP, Schoenecker JG:
Pediatric musculoskeletal infection: Hijacking the acute-phase response.
JBJS Rev 2016;4(9):e4.
5. Benvenuti M, An T, Amaro E, et al: Double-edged sword: musculoskeletal
infection provoked acute phase response in children. Orthop Clin North
Am 2017;48(2):181-197.
6. Blyth MJ, Kincaid R, Craigen MA, Bennet GC: The changing
epidemiology of acute and subacute haematogenous osteomyelitis in
children. J Bone Joint Surg Br 2001;83(1):99-102.
7. Davis WT, Gilbert SR: Comparison of methicillin-resistant versus
susceptible Staphylococcus aureus pediatric osteomyelitis. J Pediatr Orthop
2018;38(5):e285-e291.
8. Voss A, Milatovic D, Wallrauch-Schwarz C, Rosdahl VT, Braveny I:
Methicillin-resistant Staphylococcus aureus in Europe. Eur J Clin Microbiol
Infect Dis 1994;13(1): 50-55.
 9. Su er DE, Milburn E, Chukwuma U, Dzialowy N, Maranich AM,
Hospenthal DR: Changing susceptibility of Staphylococcus aureus in a US
pediatric population. Pediatrics 2016;137(4):e20153099.
10. Kuehnert MJ, Hill HA, Kupronis BA, Tokars JI, Solomon SL, Jernigan
DB: Methicillin-resistant-Staphylococcus aureus hospitalizations, United
States. Emerg Infect Dis 2005;11(6):868-872.
11. Schneider-Lindner V, Quach C, Hanley JA, Suissa S: Antibacterial drugs
and the risk of community-associated methicillin-resistant Staphylococcus
aureus in children. Arch Pediatr Adolesc Med 2011;165(12):1107-1114.
12. Hicks LA, Bartoces MG, Roberts RM, et al: US outpatient antibiotic
prescribing variation according to geography, patient population, and
provider specialty in 2011. Clin Infect Dis 2015;60(9):1308-1316.
13. An TJ, Benvenuti MA, Mignemi ME, et al: Similar clinical severity and
outcomes for methicillin-resistant and methicillin-susceptible
Staphylococcus aureus pediatric musculoskeletal infections. Open Forum
Infect Dis 2017;4(1):ofx013.
14. Moore-Lotridge SN, Gibson BH, Duvernay MT, Martus JE, Thomsen IP,
Schoenecker JG: Pediatric musculoskeletal infection. JPOSNA 2020;2(2). A
current concept review of MSKIs is presented, with a focus on the four
pillars of critical care and immunothrombotic similarities with COVID-19.
Level of evidence: V.
15. Rosenfeld S, Bernstein DT, Daram S, Dawson J, Zhang W: Predicting the
presence of adjacent infections in septic arthritis in children. J Pediatr
Orthop 2016;36(1):70-74.
16. Wong M, Williams N, Cooper C: Systematic review of Kingella kingae
musculoskeletal infection in children: Epidemiology, impact and
management strategies. Pediatr Health Med Ther 2020;11:73-84. The authors
present a review of 144 studies on MSKIs caused by K kingae in the
pediatric population. Level of evidence: III.
17. Fayad LM, Carrino JA, Fishman EK: Musculoskeletal infection: Role of
CT in the emergency department. Radiographics 2007;27(6):1723-1736.
18. Calhoun JH, Manring MM, Shirtliff M: Osteomyelitis of the long bones.
Semin Plast Surg 2009;23(2):59-72.
19. Mignemi ME, Benvenuti MA, An TJ, et al: A novel classification system
based on dissemination of musculoskeletal infection is predictive of
hospital outcomes. J Pediatr Orthop 2018;38(5):279-286.
20. Benvenuti MA, An TJ, Mignemi ME, et al: A clinical prediction algorithm
to stratify pediatric musculoskeletal infection by severity. J Pediatr Orthop
 2019;39(3):153-157. This study discusses a clinical prediction algorithm
that accurately stratifies infection severity based on clinical and laboratory
data at presentation to the emergency department, including CRP level,
pulse, temperature, and an interaction term for pulse and temperature.
Level of evidence: III.
21. Amaro E, Marvi TK, Posey SL, et al: C-reactive protein predicts risk of
venous thromboembolism in pediatric musculoskeletal infection. J Pediatr
Orthop 2019;39(1):e62-e67. In children with confirmed MSKIs, peak and
total CRP levels were strong predictors of thrombosis. Level of evidence:
III.
22. Bo iger LE, Svedberg CA: Normal erythrocyte sedimentation rate and
age. Br Med J 1967;2(5544):85-87.
23. Sox HCJr, Liang MH: The erythrocyte sedimentation rate. Guidelines for
rational use. Ann Intern Med 1986;104(4):515-523.
24. Kobayashi SD, Voyich JM, Burlak C, DeLeo FR: Neutrophils in the innate
immune response. Arch Immunol Ther Exp (Warsz) 2005;53(6):505-517.
25. Kobayashi SD, Malachowa N, DeLeo FR: Influence of microbes on
neutrophil life and death. Front Cell Infect Microbiol 2017;7:159.
26. de Jager CPC, van Wijk PTL, Mathoera RB, de Jongh-Leuvenink J, van der
Poll T, Wever PC: Lymphocytopenia and neutrophil-lymphocyte count
ratio predict bacteremia be er than conventional infection markers in an
emergency care unit. Crit Care 2010;14(5):R192.
27. Kerrigan SW: The expanding field of platelet-bacterial interconnections.
Platelets 2015;26(4):293-301.
28. Ali RA, Wuescher LM, Dona KR, Worth RG: Platelets mediate host
defense against Staphylococcus aureus through direct bactericidal activity
and by enhancing macrophage activities. J Immunol 2017;198(1):344-351.
29. McNicol A, Israels SJ: Beyond hemostasis: The role of platelets in
inflammation, malignancy and infection. Cardiovasc Hematol Disord Drug
Targets 2008;8(2):99-117.
30. Klinger MHF, Jelkmann W: Review: Role of blood platelets in infection
and inflammation. J Interferon Cytokine Res 2002;22(9):913-922.
31. Kral JB, Schro maier WC, Salzmann M, Assinger A: Platelet interaction
with innate immune cells. Transfus Med Hemother 2016;43(2):78-88.
32. Saracco P, Vitale P, Scolfaro C, Pollio B, Pagliarino M, Timeus F: The
coagulopathy in sepsis: Significance and implications for treatment.
Pediatr Rep 2011;3(4):e30.
33. Castellazzi L, Mantero M, Esposito S: Update on the management of
pediatric acute osteomyelitis and septic arthritis. Int J Mol Sci
2016;17(6):855.
34. Venkataraman ST: To PICC or Not to PICC, That Is the Question! Pediatr
Crit Care Med 2018;19(12):1168-1169.
35. Keren R, Shah SS, Srivastava R, et al: Comparative effectiveness of
intravenous vs oral antibiotics for postdischarge treatment of acute
osteomyelitis in children. JAMA Pediatr 2015;169(2):120-128.
36. Benvenuti MA, An TJ, Mignemi ME, Martus JE, Thomsen IP,
Schoenecker JG: Effects of antibiotic timing on culture results and clinical
outcomes in pediatric musculoskeletal infection. J Pediatr Orthop
2019;39(3):158-162. In children with local or disseminated MSKI, culture
sensitivity was not affected by the administration of antibiotics; yet, earlier
antibiotic administration led to shorter length of stay in children with
local MSKI. Level of evidence: III.
37. Zhorne DJ, Altobelli ME, Cruz AT: Impact of antibiotic pretreatment on
bone biopsy yield for children with acute hematogenous osteomyelitis.
Hosp Pediatr 2015;5(6):337-341.
38. Hysong AA, Posey SL, Blum DM, et al: Necrotizing fasciitis: Pillaging the
acute phase response. J Bone Joint Surg Am 2020;102(6):526-537. This review
article highlights the capacity of necrotizing fasciitis to hijack the APR,
leading to adverse outcomes and death. Level of evidence: V.
39. Mignemi M, Copley L, Schoenecker J: Evidence-based treatment for
musculoskeletal infection, in Paediatric Orthopaedics. Springer
International Publishing, 2017, pp 403-418.
40. Kocher MS, Zurakowski D, Kasser JR: Differentiating between septic
arthritis and transient synovitis of the hip in children: An evidence-based
clinical prediction algorithm. J Bone Joint Surg Am 1999;81(12):1662-1670.
41. Luhmann SJ, Jones A, Schootman M, Gordon JE, Schoenecker PL,
Luhmann JD: Differentiation between septic arthritis and transient
synovitis of the hip in children with clinical prediction algorithms. J Bone
Joint Surg Am 2004;86-A(5):956-962.
42. Behrens EM, Beukelman T, Gallo L, et al: Evaluation of the presentation
of systemic onset juvenile rheumatoid arthritis: Data from the
Pennsylvania Systemic Onset Juvenile Arthritis Registry (PASOJAR). J
Rheumatol 2008;35(2): 343-348.
43. Working Group on Pediatric Acute Rheumatic Fever and Cardiology
Chapter of Indian Academy of Pediatrics, Saxena A, Kumar RK, Gera RP,
 et al: Consensus guidelines on pediatric acute rheumatic fever and
rheumatic heart disease. Indian Pediatr 2008;45(7):565-573.
44. Mignemi ME, Martus JE, Bracikowski AC, Lovejoy SA, Mencio GA,
Schoenecker JG: The spectrum of group A streptococcal joint pathology in
the acute care se ing. Pediatr Emerg Care 2012;28(11):1185-1189.
45. Berthold O, Frericks B, John T, Clemens V, Fegert JM, von Moers A:
Abuse as a cause of childhood fractures. Dtsch Arztebl Int 2018;115(46):769-
775.
46. Barsness KA, Cha ES, Bensard DD, et al: The positive predictive value of
rib fractures as an indicator of nonaccidental trauma in children. J Trauma
2003;54(6):1107-1110.
47. Ravichandiran N, Schuh S, Bejuk M, et al: Delayed identification of
pediatric abuse-related fractures. Pediatrics 2010;125(1):60-66.
S E CT I ON 1 2

Musculoskeletal Oncology and

Pathology
SECTION EDITOR
Cara A. Cipriano, MD, FAAOS
C H AP T E R 7 0

Evaluation and Management of

Musculoskeletal Tumors
Anna R. Cooper MD, MPH, FAAOS, Nicole Montgomery
MD, FAAOS

Neither of the following authors nor any immediate family member has received anything of value
from or has stock or stock options held in a commercial company or institution related directly or
indirectly to the subject of this chapter: Dr. Cooper and Dr. Montgomery.

ABSTRACT
Identification and evaluation of primary musculoskeletal tumors
are essential skills for the practicing orthopaedic surgeon. A careful
history and physical examination in combination with appropriate
use of imaging helps with the efficiency and accuracy of diagnosis.
Early identification, proper biopsy, and appropriate
musculoskeletal oncology referral of soft-tissue and bone sarcomas
can affect patient mortality, morbidity, and the feasibility of limb-
salvage surgery. Important concepts in the management of
musculoskeletal tumors include clinical presentation and history,
imaging modalities, biopsy techniques, staging studies, surgical
management and principles, adjuvant therapies, and functional
outcome measures.
Keywords: evaluation; musculoskeletal tumor; patient-reported
outcomes; staging; workup

Introduction
The clinical manifestations of musculoskeletal tumors are highly
variable. The presentation of bone tumors ranges from an
incidental finding to pathologic fracture. Benign soft-tissue tumors
may be symptomatic, whereas soft-tissue sarcomas are rare but
often deceptively painless. A ention to a detailed history and
physical examination is paramount, as is a critical evaluation of
radiology studies. In addition to diagnostics, consideration of
staging, treatment, and functional outcomes is needed to guide the
management of musculoskeletal tumors.

Clinical Presentation/History and Physical

Examination

Bone Tumors
Bone tumors may present with various signs and symptoms,
including pain, mass, and limb deformity. The incidence of primary
malignant bone tumors is approximately 3,600 cases annually in the
United States. Benign bone tumors are estimated to be 100 times
more common than malignant bone tumors, although the true
prevalence is unknown. The most common presenting symptom of
a malignant bone tumor is pain, often associated with a mass, and
occasionally pathologic fracture. Patients with benign bone tumors
may present with incidental findings noted on radiographs, painful
mass/lesion, or pathologic fracture. 1
The patient’s age must be considered when determining the
differential diagnosis. Diagnoses for pediatric patients differ
significantly from those for young and older adults (Table 1).
Common bone tumors in pediatric patients include nonossifying
fibromas, unicameral bone cysts, aneurysmal bone cysts,
osteosarcoma, and Ewing sarcoma. By comparison, in a patient
older than 40 to 50 years, bone lesions are more commonly
metastatic carcinoma, multiple myeloma, lymphoma,
chondrosarcoma, and secondary osteosarcomas.
Table 1
Common Bone Tumor Diagnoses by Age

Patient Age (years) Benign Malignant

0-5 Histiocytosis Metastatic neuroblastoma
5-20 Infection Osteosarcoma
NOF Ewing sarcoma
UBC, ABC
Osteoid osteoma
Osteochondroma
20-40 GCT Lymphoma
FD Ewing sarcoma
Enchondroma
>40 Enchondroma Metastatic carcinoma
Bone infarct Multiple myeloma/lymphoma
Infection Chondrosarcoma
Secondary osteosarcoma
ABC = aneurysmal bone cyst, FD = fibrous dysplasia, GCT = giant cell tumor, NOF =
nonossifying fibroma, UBC = unicameral bone cyst

It is imperative to obtain a detailed history evaluating the

location of the symptom(s), onset and duration, rate of growth,
alleviating or exacerbating factors, pain history, trauma history, and
infection history. In general, pain related to benign entities is
relatively mild, often related to activity and relieved by NSAIDs. If
the bony lesion is active or aggressive, such as aneurysmal bone
cyst or giant cell tumor, it may cause progressive pain or fracture.
In contrast, malignant bony lesions usually cause pain that is more
severe and unresponsive to anti-inflammatory treatments. Patients
often characterize the pain as dull, deep, or achy that is present
with activity but also at rest and at night. An associated soft-tissue
mass may cause distal extremity swelling or nerve compression
with neurologic symptoms.
The history should also include questions regarding
constitutional symptoms, such as fever, chills, night sweats,
unintentional weight loss, fatigue, lymphadenopathy, breast or
other palpable masses, and diphosphonate use. Approximately 20%
to 30% of patients with Ewing sarcoma present with fever. 2 In
adults, metastatic disease to bone is vastly more common than
primary bone malignancies, and a carcinoma or hematopoietic
malignancy may present with a painful lesion or pathologic
fracture. Any personal history of cancer, even diagnosed several
decades prior, is a risk factor for metastatic bone disease. It is also
important to identify any history of radiation, as there is a late risk
of radiation-associated sarcomas. A prolonged history of
diphosphonate use is a risk factor for impending or completed
atypical femoral fractures, which are considered pathologic even
though not neoplastic.
Physical examination can identify additional signs associated
with the patient’s symptoms. The location, approximate size, and
proximity to important structures should be noted. Palpation can
reveal if the mass is soft, firm, or hard and if it is mobile or fixed. It
is often possible to discern whether a soft-tissue mass is superficial
or deep to the fascia by asking the patient to tense their muscles in
the extremity; if the mass remains mobile, it is superficial, whereas
if it becomes more immobile, it is below the fascia. A careful
neurovascular assessment distal to the lesion is critical. For
incidentally noted bone lesions, physical examination can diagnose
the true problem that prompted medical a ention. For example, if a
patient presents with shoulder pain and radiographs reveal an
enchondroma of the proximal humerus but the examination is
consistent with subacromial impingement, the bone lesion can be
designated an incidental finding, and the patient can be treated for
rotator cuff pathology. The patient should also be examined for
signs of systemic diseases and syndromes; for example, café-au-lait
cutaneous lesions may indicate McCune-Albright syndrome, or
clubbing of the fingertips may result from a pulmonary
parenchymal process such as lung cancer. Other findings, such as
lymphadenopathy and solid organ masses (particularly breast),
may also be detected on physical examination and used to direct
further diagnostics.

Soft-Tissue Tumors
Similar to bone tumors, the prevalence of benign soft-tissue masses
far exceeds malignant diagnoses; however, most soft-tissue
sarcomas are painless, making them diagnostic challenges.
Rhabdomyosarcoma is the most common malignant soft-tissue
sarcoma in children, whereas undifferentiated pleomorphic
sarcoma, liposarcoma, fibrosarcoma, and leiomyosarcoma are more
common soft-tissue sarcoma subtypes in adults.
The history should include onset, duration, temporality,
alleviating and exacerbating factors, and associated symptoms.
Distal paresthesias may suggest a nerve sheath tumor or nerve
compression. Masses or symptoms that fluctuate with activity may
suggest a vascular or cystic component; inflammatory lymph nodes
can also vary in size over time. In a patient who taking an
anticoagulant medication, a growing mass might be an acute or
chronic hematoma, although in these situations, malignancy must
also be considered and ruled out.
The history should include inquiry into constitutional symptoms,
a personal or family history of cancer, and syndromes associated
with soft-tissue masses. For example, neurofibromatosis results in
multiple tumors and risk of malignancy, and 5% to 10% of desmoid
tumors are associated with familial adenomatous polyposis. 3 A
history of traumatic brain injury may lead to heterotopic
ossification, and chronic renal failure can be associated with
tumoral calcinosis. 4
Physical examination can suggest a tumor’s size and depth to
fascia. It is important to note whether the mass itself and the
overlying skin are mobile. Any areas of compromised skin where
the tumor is threatening to fungate may influence decisions about
secondary coverage and preoperative or postoperative radiation.
Peripheral nerve sheath tumors or masses compressing nerves can
have a positive Tinel sign. Highly vascular lesions may have a bruit
or thrill on auscultation. Regional lymph node metastases can occur
in rhabdomyosarcoma, synovial sarcoma, angiosarcoma, epithelioid
sarcoma, and clear cell sarcoma; therefore, evaluation for
lymphadenopathy should be performed.

Imaging

Plain Radiographs
Radiographs are the first step in the workup of bone tumors
because they are accessible, quick, and inexpensive. In any
potentially malignant case, orthogonal views of the whole bone as
well as the joints above and below the symptomatic area should be
obtained and closely examined. In combination with the history
and physical examination, radiographic characteristics can typically
lead to a narrow differential diagnosis. Enneking described the
following factors that can be determined from radiographs: (1)
skeletal maturity; (2) tumor location; (3) what the tumor is doing to
the bone; (4) the bone’s response; and (5) if the tumor is producing
any matrix. Patient age, skeletal maturity, and the location of the
bone lesion can suggest certain pathologies. For example, Ewing
sarcoma and chondrosarcoma are common in flat bones, whereas
osteogenic osteosarcomas are common in the distal femoral and
proximal tibial metaphyseal regions (Table 2). It is important to
note whether the lesion is located in the epiphysis, metaphysis, and
diaphysis, as well as the medullary, cortical, or periosteal spaces.
Other relevant questions include: Are there polyostotic lesions? Is
the tumor destroying cancellous and/or cortical bone? Is the lesion
expanding the cortex? Features of containment, that is, a narrow
zone of transition and a reactive or sclerotic rim, suggest an
indolent process. In contrast, features such as a wide zone of
transition, moth-eaten or permeative destruction, cortical
expansion and erosion, or an associated soft-tissue mass suggest an
aggressive process. The presence of irregular periosteal reaction
such as lamellated, spiculated, interrupted pa erns (eg,
perpendicular/sun-burst, Codman triangle) is suggestive of an
aggressive underlying process (Figure 1 shows multiple types of
aggressive periosteal reactions in a primary lymphoma of bone).
Finally, the type of matrix produced can strongly influence the
differential diagnosis; for example, a bone-forming aggressive bone
lesion in a pediatric patient is very likely an osteosarcoma.

Table 2
Common Bone Tumor Diagnoses by Location

Anatomic Site Benign Malignant

Pelvis UBC, ABC Metastatic carcinoma
Infection Ewing sarcoma
Histiocytosis Chondrosarcoma
Spine (anterior) Infection Metastatic carcinoma
Hemangioma Lymphoma
Histiocytosis Ewing sarcoma
Spine (posterior) ABC Metastatic carcinoma
Osteoid osteoma
Osteoblastoma
Long bones
Diaphyseal FD, OFD Metastatic carcinoma
Histiocytosis Multiple myeloma
Osteoid osteoma Lymphoma
Infection Adamantinoma
Ewing sarcoma
Metaphyseal NOF Metastatic carcinoma
UBC Osteosarcoma
ABC Chondrosarcoma
Enchondroma
Osteochondroma
Epiphyseal Chondroblastoma Clear cell chondrosarcoma
GCT Metastatic carcinoma
Infection
Geode/synovial cyst
ABC = aneurysmal bone cyst, FD = fibrous dysplasia, GCT = giant cell tumor, NOF =
nonossifying fibroma, OFD = osteofibrous dysplasia, UBC = unicameral bone cyst
 Figure 1 AP and lateral radiographs of the distal femur (A) and proximal femur
(B) of a 12-year-old boy who presented with 6 months of progressively
worsening right thigh pain. This is an example of an aggressive bone lesion with
interrupted periosteal reactions. The final diagnosis was primary diffuse large B
cell lymphoma of bone.

For soft-tissue masses, radiographs are useful to determine

whether there is a mineralized or osseous component, such as
myositis ossificans or an osteochondroma with an associated bursa.
If calcifications are present, the pa ern may suggest certain
pathologies such as phleboliths for hemangiomas and peripheral
calcification for myositis ossificans. Most soft-tissue tumors cannot
be fully seen on radiograph, so additional imaging is warranted.

Ultrasonography
Ultrasonography is quick, relatively inexpensive, does not require
sedation, and does not involve exposure to ionizing radiation. 5 It is
useful for characterizing superficial soft-tissue tumors, particularly
in children. If a soft-tissue mass is not palpable on physical
examination, ultrasonography is useful to determine whether a
defined mass is present. Doppler ultrasonography can provide
information regarding intralesional vascular flow and the degree of
vascularity. Ultrasonography can also identify lipomas and
differentiate cystic from solid components of a lesion.

Computed Tomography
Axial imaging can be very useful in evaluating bone tumors when
radiographs do not provide sufficient information (eg, seeing occult
lesions, determining location in axial or flat bones). CT can further
characterize bony involvement, tumor matrix, periosteal reaction,
and pathologic fractures. 6 CT can assess bone loss to help
determine pathologic fracture risk 7 as well as assist with
preoperative planning. CT with and without contrast can also be an
acceptable alternative imaging modality for soft-tissue masses for
patients who cannot undergo MRI.
CT is also routinely used for systemic staging. In patients with a
bone or soft-tissue sarcoma, a chest CT should be obtained to
evaluate for pulmonary metastases (Figure 2). For myxoid
liposarcoma, which has a propensity for extrapulmonary metastases
such as the retroperitoneum and axial skeleton, CT of the chest,
abdomen, and pelvis and MRI of the whole spine or whole body
have been suggested for staging and surveillance. 8 For patients
with suspected metastatic carcinoma, CT of the chest, abdomen,
and pelvis should be obtained to evaluate for solid organ masses
and to assess disease burden.

Figure 2 Axial-cut CT scan of the chest performed for osteosarcoma

staging.Multiple pulmonary nodules indicative of metastatic disease.

Magnetic Resonance Imaging

MRI is useful to evaluate intramedullary and extramedullary
masses, providing anatomic detail, neurovascular invasion or
proximity, medullary involvement or edema, and matrix character.
When a primary bone sarcoma is suspected, it is important to
communicate with the radiologist so that the image will include the
entire affected bone to identify any skip metastases. MRI permits
local staging by defining tumor size, extracompartmental extent,
and proximity to adjacent structures. Intravenous gadolinium
contrast can assist with the diagnosis as well as identify the best
areas for biopsy placement. Moreover, a 2019 radiology study of 130
adults with nonmetastatic soft-tissue sarcomas identified three MRI
characteristics that were predictive of high-grade, metastasis-free
survival and overall survival: necrosis, heterogeneity on T2
sequences, and peritumoral contrast enhancement. 9
With increased availability of whole-body MRI, the role of this
imaging modality for staging of primary bone tumors is under
investigation but thus far is not being used routinely. A 2021 study
in patients with osteosarcoma and Ewing sarcoma found no
significant differences between whole-body 18F-fluorodeoxyglucose
positron emission tomography/CT, technetium Tc-99 methylene
diphosphonate skeletal scintigraphy, and whole-body MRI in
sensitivity, specificity, positive predictive value, and negative
predictive value in detecting skeletal metastases. 10

Nuclear Imaging
Whole-body bone scans are most commonly used in the workup
and staging of primary and secondary bone malignancies to detect
polyostotic disease. By identifying areas of the skeleton with high
turnover, bone scans can identify additional lesions that might be
optimal for tissue biopsy. In the se ing of primary bone tumors,
bone scans can evaluate for skip as well as distant metastases. For
patients with metastatic carcinoma, bone scans quantify the burden
of osseous disease and identify other lesions at potential risk of
fracture. Hematopoietic malignancies may have lesions that are not
detectable on bone scans, so skeletal surveys or low-dose, whole-
body CT scans are more appropriate for diseases such as multiple
myeloma.
Positron emission tomography CT is useful in monitoring
response to systemic therapy. 11 It is also used to monitor
conditions such as neurofibromatosis, because it has a role in
distinguishing malignant transformation. 12

Biopsy, Grading, Molecular Diagnostics, and

Staging
Biopsy
A biopsy is often needed to establish or confirm a diagnosis and
must be performed before treatment. Ideally, this should be
performed or directed by the surgeon who will be definitively
treating the patient because the biopsy technique and approach
have prognostic and therapeutic implications. Unplanned excision
of sarcomas leads to increased local disease recurrence, need for
advanced soft-tissue reconstruction, and amputation. 13 , 14
Moreover, patients with unexpected positive margins have worse
oncologic outcomes of local recurrence-free survival and cause-
specific survival. 15
All local imaging and staging studies should be completed
before the biopsy, as these data help form a differential diagnosis
and may identify an optimal area of the tumor to sample. In
general, there is very li le utility in fine-needle aspiration for
musculoskeletal lesions because the diagnoses require examination
of tissue architecture. Thus, biopsy procedures are typically core
needle, incisional, or excisional. Core biopsies are minimally
invasive and can be performed with image guidance (Figure 3).
Incisional open biopsies are performed in the operating room and
can yield a larger amount of tissue; the surgical principles of biopsy
must be followed to avoid contamination of the surrounding
tissues, which could compromise oncologic and survival outcomes.
Excisional open biopsies are appropriate for small, superficial soft-
tissue lesions that can be easily removed with a wide margin.
 Figure 3 Fluoroscopic AP image of the knee demonstrating a percutaneous
core biopsy of the distal femur for a suspected osteosarcoma.The biopsy is
performed from a lateral approach to allow direct access to tissue sampling of
the soft-tissue mass.

The workup of a bone lesion is presented in Figure 4.

 Figure 4 Flow diagram of workup for bone lesion.

Grading
Based on the biopsy, it is often possible for specialty-trained
musculoskeletal pathologists to determine grade; however, there is
the potential for sampling error. There are several grading systems
available; commonly, the American Joint Commi ee on Cancer
system is used: grade 1, well differentiated; grade 2, moderately
well differentiated; grade 3, poorly differentiated; and grade 4,
dedifferentiated. Grading has prognostic implications because
higher grade tumors tend to be more clinically aggressive with
increased growth and incidence of metastases. 16

Molecular Diagnostics
Although many musculoskeletal pathologies can be determined by
hematoxylin and eosin stains, immunohistochemistry and
molecular diagnostics are increasingly used to determine and verify
diagnoses. For example, up to 95% of giant cell tumors of bone have
a H3F3A gene mutation; both primary and malignant versions can
be verified by immunohistochemistry staining with antibodies
against H3.3 G34W/R/V. 17

Staging
There are several staging systems to describe benign and malignant
bone and soft-tissue tumors. Enneking described staging systems
for benign and malignant bone tumors, and these systems were
adopted by the Musculoskeletal Tumor Society (MSTS). The other
commonly used system for malignant bone tumors and malignant
soft-tissue tumors was developed by the American Joint Commi ee
on Cancer. None of the staging systems are comprehensive; there is
debate regarding true prognostic variables; however, they provide a
framework that is useful for prognostication and management.

Enneking Staging System

Benign bone tumors have varied biologic activity, and the Enneking
staging system reflects those differences. Stage 1 tumors are latent
tumors, which are typically asymptomatic and found incidentally. If
observed over time, these lesions remain stable and may even
regress; examples include nonossifying fibromas, enchondromas,
and osteochondromas. Questionable lesions should be followed,
and if there is a clinical or radiographic suggestion of more
aggressive behavior, the surveillance interval should be shortened,
with consideration of advanced imaging and potentially a biopsy.
Stage 2 tumors are active and can be mildly symptomatic. These
lesions can grow slowly and cause cortical expansion or plastic
deformation; examples include osteoid osteoma, chondromyxoid
fibroma, and unicameral bone cysts. Stage 3 tumors are aggressive
and can display rapid growth with cortical destruction and an
associated soft-tissue mass. These lesions are more likely to present
with pathologic fractures than latent or active tumors.
Osteoblastoma, giant cell tumor, and aneurysmal bone cyst are
examples of aggressive benign bone tumors.
American Joint Committee on Cancer
For malignant bone and soft-tissue tumors, the American Joint
Commi ee on Cancer staging systems delineate tumors by size,
grade, depth/compartment, and metastasis (Tables 3 and 4). The
size threshold for small versus large bone tumors is 8 cm, whereas
for soft-tissue tumors the threshold is 5 cm. Tumors with multiple
distinct foci within the same bone, that is, skip metastases, are
associated with a worse prognosis than localized tumors and are
therefore characterized as stage III for bone sarcomas. The most
common location for distant metastases for sarcomas is the lung
parenchyma. A subset of soft-tissue sarcomas (synovial, epithelioid,
clear cell, angiomyosarcoma, and rhabdomyosarcoma) also have a
tendency for lymphatic spread.

Table 3
Malignant Bone Tumor Classification by the American Joint
Commission on Cancer

Stage Grade Size Nodes Mets

IA G1-2 T1 (<8 cm) N0 M0
IB G1-2 T2 (>8 cm) N0 M0
IIA G3-4 T1 N0 M0
IIB G3-4 T2 N0 M0
III Any T3 (skip mets) N0 M0
IVA Any Any N0 Lung mets
IVB Any Any Any M+ (other than lung)
Mets = metastasis

Table 4
Malignant Soft-Tissue Tumor Classification by the American
Joint Committee on Cancer

Stage Grade Size Nodes Mets

IA G1-2 Superficial/deep, <5 cm N0 M0
IB G1-2 Superficial, >5 cm N0 M0
IIA G1-2 Deep, >5 cm N0 M0
 Stage Grade Size Nodes Mets
IIB G3-4 Superficial/deep <5 cm N0 M0
IIC G3-4 Superficial, >5 cm N0 M0
III G3-4 Deep, >5 cm N0 M0
IV Any Any Any M+
Mets = metastasis

Surgical Principles

Margins
With active and aggressive benign bone tumors, surgical
techniques are as varied as the diagnoses. For pathologic fractures
of unicameral bone cysts, nonsurgical management is typically
sufficient to heal the fracture and often leads to resolution of the
underlying cyst. If the cyst remains at risk for subsequent
refracture, cure age with bone graft or absorbable bone void filler
may be indicated. For giant cell tumor of bone or aneurysmal bone
cysts, once the diagnosis has been verified by biopsy, surgery
includes intralesional extended cure age with burr, cautery, and
other adjuvant treatments to remove as much of the tumor and
reactive zone as possible. Management of the resultant bone defect
depends on the size of the lesion and the anatomic location.
Polymethacrylate or cancellous allograft is commonly used to fill
the defect, sometimes with plate/screw fixation if augmentation is
needed; however, if there is insufficient bone remaining to salvage
the joint, allograft or prosthetic reconstruction may be necessary.
Benign soft-tissue masses are often removed with a marginal
resection. One exception is desmoid (fibromatosis) tumors, which
are aggressive, benign tumors that require a generous wide margin
to minimize local disease recurrence. 3
A wide surgical margin is most appropriate for malignant bone
and soft-tissue sarcomas. The definition of a wide margin is a
subject of much debate and research. Traditionally, this consisted
of greater than 1 cm of normal surrounding tissue without
infiltration by neoplastic cells; however, the use of adjuvant
radiation has allowed the resection to approach the tumor more
closely without compromising local control. The tumor may be
carefully dissected directly off critical structures such as nerves,
vessels, and bone, allowing for limb salvage in most cases. Certain
tissue types, such as fascia, are be er barriers to tumor penetration
than others, such as adipose. Moreover, the biology of the tumor
may make it variably infiltrative or responsive to radiation
depending on the diagnosis, and the tumor cells may be responsive
to adjuvant therapies such as radiation. 18 As such, a wide margin is
not determined in terms of absolute thickness but is always
extralesional.

Limb Salvage Versus Amputation

Limb salvage should only be performed when the resultant limb is
more functional than an amputation. With modern treatment
options, approximately 95% of primary bone tumors can be
managed with a limb salvage approach. 19 Indications for
amputation include involvement of major peripheral neurovascular
structures, bone, and soft-tissue, so the tumor cannot be removed
and reconstructed with a clinical and oncologic result that is
superior to amputation. In skeletally immature active patients,
rotationplasty is a form of amputation that may have excellent
functional outcomes if acceptable to the patient and family.
Reconstruction options after tumor resection vary depending on
tumor size, location, and predicted response to adjuvant therapies.
Common reconstruction options for bone resections include bulk
autograft, vascularized autograft (eg, fibula) and endoprosthesis
(Figure 5), whereas secondary soft-tissue coverage can be achieved
with skin grafting, rotational pedicle flaps, or free flaps.
Occasionally, when the tumor encases a critical vessel or nerve,
reconstruction may allow for salvage of a functional limb. Venous
autografts as well as allograft or synthetic grafts can be used, each
with a risk of perioperative complications. 20 Nerve grafting and
transfers are options as well, but there are few data examining the
functional outcomes. 21

Figure 5 A, AP leg-length radiograph from a patient after limb salvage surgery

with a noninvasive expandible distal femur endoprosthesis. B, AP and lateral
radiographs of the right humerus osteoarticular allograft reconstruction after
resection of a proximal humeral osteosarcoma.

Adjuvant Treatment
Adjuvant treatments, including chemotherapy and radiation, play a
pivotal role in the treatment of patients with bone and soft-tissue
sarcomas. As a systemic treatment, chemotherapy has reduced the
incidence of metastasis, significantly increasing the overall survival
of patients with a diagnosis of osteosarcoma and Ewing sarcoma.
Soft-tissue sarcomas are not responsive to traditional
chemotherapy; however, radiation is effective for local control and
has greatly decreased the risk of recurrence after surgical resection.
Sarcomas require a multidisciplinary approach with coordinated
care between the surgeon, medical oncologist, and radiation
oncologist. Not all sarcomas respond to adjuvant treatment; for
example, chondrosarcoma is typically radiation therapy–resistant
and chemotherapy-resistant and therefore managed with wide local
resection alone.

Chemotherapy
For primary malignant bone tumors, multiagent chemotherapy has
a significant benefit in terms of event-free and overall survival. Most
commonly, chemotherapeutic agents work by inducing apoptosis in
rapidly dividing tumor cells. Two complete rounds of neoadjuvant
chemotherapy are typically given before surgery; the tumor is then
reimaged and restaged, and local control is performed, allowing the
pathologist to assess the response to chemotherapy from the
surgical resection specimen. The response to chemotherapy,
reported as percent necrosis, has an important implication on
prognosis, with 90% necrosis or higher considered a favorable
response. Adjuvant chemotherapy is then given postoperatively to
complete the course. The standard regimen for Ewing sarcoma
includes vincristine, doxorubicin, and cyclophosphamide
alternating with ifosfamide and etoposide or
cyclophosphamide/etoposide. There is an improved 5-year event-
free survival rate (73% versus 65%) with interval compression
(chemotherapy given every 2 weeks) versus the previous standard
of every 3 weeks. 22 The regimen for osteosarcoma in children and
young adults includes cisplatin, doxorubicin, and methotrexate
(MAP). In the EURAMOS trial, patients with poor tumor necrosis
after neoadjuvant MAP (<90% necrosis) were randomized to either
continue MAP or add high-dose ifosfamide/etoposide (MAPIE).
The 5-year event-free survival did not differ between the groups,
and the MAPIE group demonstrated greater chemotherapy-related
toxicity, so MAP remains the standard adjuvant regimen regardless
of percent necrosis. 23
Although chemotherapy has greatly improved survival for
patients with bone sarcomas, it carries significant side effects,
including an increased risk of wound complications and infections.
In addition, doxorubicin increases the risk of cardiomyopathy
throughout the life of the patient, so routine echocardiograms are
used to monitor long-term survivors. Cisplatin can accumulate in
the inner ear and cause permanent hearing loss because of cochlear
damage in 40% to 80% of patients receiving the agent.
Chemotherapy for most soft-tissue sarcomas remains
controversial and is considered on a case-by-case basis. Agents
commonly used in the management of soft-tissue sarcoma include
doxorubicin and ifosfamide. There is evidence from the National
Cancer Database that the addition of chemotherapy to radiation in
high-risk, soft-tissue sarcoma showed a trend of increased overall
survival (5-year matched Kaplan-Meier overall survival of 69.8% in
the chemotherapy and radiation group versus 55.4% in the
radiation therapy group). 24 However, use of chemotherapy agents
must be weighed against the acute toxicity of the drugs, and no
consensus on indications for soft-tissue sarcomas exists. Synovial
sarcoma appears to be relatively sensitive, with pooled data from 15
trials demonstrating significantly be er response to chemotherapy
compared with other soft-tissue sarcomas. 25 In adults, disease-
specific survival has been reported at 88% in the cohort receiving
ifosfamide-based chemotherapy versus 67% in the control group. 26
In children and adolescents with intermediate or high-risk synovial
sarcoma, adjuvant or neoadjuvant ifosfamide and doxorubicin are
given; however, in pediatric patients with low-risk tumors (grade 2
or grade 3 < 5 cm), there is no advantage to chemotherapy.

Radiation Therapy
Radiation has several applications in musculoskeletal oncology,
including treatment of soft-tissue sarcomas, metastatic disease, and
Ewing sarcoma. Radiation exposes tumor cells to particles or waves
that lead to DNA damage, which results in apoptosis of rapidly
replicating cells. The surrounding healthy tissues are also exposed
to radiation, which has significant adverse effects. These adverse
effects typically do not result from the doses given for metastatic
disease (20 to 30 Gy), but they are common after sarcoma treatment
(50 to 66 Gy). They include wound healing complications, skin
changes, nerve damage, lymphatic damage and lymphedema,
osteonecrosis, and late radiation-induced sarcoma. The risk of
postradiation sarcoma is 0.06% with a mean latency of 15 years.
Radiation-induced sarcomas carry a poor prognosis (45% 5-year
survival). 27 In addition, there is a risk of pathologic fractures, often
with impaired healing due to compromised biology; therefore,
patients with several risk factors for fracture, including radiation,
subperiosteal dissection, and underlying osteopenia/osteoporosis,
may benefit from prophylactic intramedullary nailing. 28
The use of radiation has greatly improved local control for soft-
tissue sarcomas. By sterilizing the reactive zone around the tumor
itself, radiation allows for closer resection margins and limb salvage
without increased risk of recurrence. Radiation is typically
indicated for intermediate or high-grade soft-tissue sarcomas
greater than 5 cm in the longest dimension. Radiation may be
administered as a neoadjuvant or adjuvant treatment to surgery.
There is no difference in local recurrence rate with preoperative
versus postoperative radiation, but each has advantages and
disadvantages. There is an increased risk of wound complications
with preoperative radiation (35% with preoperative radiation versus
17% with postoperative radiation). 29 With postoperative radiation a
larger dose and larger field is required, which has increased
deleterious effects on the surrounding, healthy tissue. External
beam radiation is also used for local control of lymphoma,
myeloma, and metastatic carcinoma of bone. External beam
radiation is a mainstay of treatment for bony metastases. In weight-
bearing bones, radiation is often combined with surgical
stabilization to prevent pathologic fracture. Prostate and breast
primary are more radiosensitive than lung, renal, or
gastrointestinal tumors.
Intensity-modulated radiation therapy is a type of photon
radiation treatment that uses beams with variable, computer-
controlled intensities. This allows the radiation dose to conform
more precisely to the three-dimensional shape of the tumor. This
technology is particularly useful for complex targets with concave
shapes and when the tumor is close to critically important
structures. Stereotactic radiation therapy is a highly concentrated
form of radiation given in a single fracture to target tissue without
affecting the surrounding tissue. Stereotactic radiation has been
shown especially useful in achieving local control of spinal
metastases without causing toxicity to the spinal cord. However,
stereotactic radiation to the spine does put the patient at risk for
compression fractures because of local osteoradionecrosis. 30
Last, radiation can be used for definitive local control as an
alternative to surgical resection of Ewing sarcoma. The data from
the Children’s Oncology Group have demonstrated a decreased
local failure rate with surgical local control versus radiation in
Ewing sarcoma; however, this has not translated into a significant
difference in event-free survival, overall survival, or overall
metastasis. These data are limited in their retrospective nature and
prone to selection bias as radiation may have been favored over
surgery for more locally advanced tumors requiring more morbid
surgical resections (ie, tumors requiring amputations or
pelvic/sacral resections). 31 Because of the possible increased risk of
local recurrence, as well as concerns about the adverse effects of
radiation, surgery is the preferred method of local control when
morbidity is not unacceptably high.

Immunotherapy and Other Emerging

Therapies
One of the roles of the immune system is to detect and destroy
abnormal cells, including cancer cells. Although the immune
system can prevent or slow cancer growth, cancer cells develop
methods of escaping the normal defenses. Immunotherapy agents
are designed to manipulate the anti-immune response by
overcoming pathways that lead to immune escape. These agents
have led to significant improvement in the treatment of advanced
stage metastatic cancers and have the potential for continued
therapeutic advancement. Immune checkpoint inhibitors including
anti-CTLA4 (ipilimumab), anti-PD1 (pembrolizumab and
nivolumab), and anti-PDL1 (atezolizumab and avelumab) were
among the first approved targeted immunotherapy agents. These
agents have been shown to be efficacious in improving survival in
metastatic melanoma, squamous cell carcinomas, bladder cancers,
breast cancer, colorectal cancer, non-Hodgkin lymphoma, and other
malignancies.
There are currently several hundred clinical trials currently
focused on immunotherapy and next-generation agents targeting
immune-regulatory proteins, including lymphocyte-activation gene
3, T cell immunoglobulin and ITIM domain, and T cell
immunoglobulin and mucin-domain containing-3. 32 CAR T cell
therapy uses engineered T cells with chimeric antigen receptors
(CARs), which are synthetic receptors that enable T cells to
recognize tumor-associated antigens. It is the first genetically
modified cell-based therapy to receive FDA approval. CAR T cell
therapy has had significant success in treating hematologic
malignancies and represents an area of active research interest in
application to other malignancies. The use of these agents to treat
other malignancies requires sophisticated engineering to overcome
tumor-defense mechanisms such as immunosuppression, antigen
escape (loss or downregulation of the target antigen on the cancer
cell), and physical barriers to entry into solid tumors.

Functional Outcome Measures

Musculoskeletal Tumor Society

The MSTS score is a physician-reported outcome that aims to assess
physical function. It was introduced in 1983, revised in 1993, 33 and
remains among the most common outcomes measures in
orthopaedic oncology patients worldwide. The MSTS is limited by
its lack of patient input, as demonstrated in a study of 128 patients
with bone metastases, 100 persons with lower extremity
involvement and 28 persons with upper extremity involvement. 34
The scores as determined by the physicians were found to
overestimate function and emotional acceptance compared with
those completed by the patients. Prior studies find a similar
overestimation of physical function by clinicians relative to patient-
reported outcomes (PROs). 35

Toronto Extremity Severity Score

The Toronto Extremity Severity Score (TESS) is a disease-specific
measure for sarcoma patients undergoing limb salvage surgery.
Unlike the MSTS score, the TESS evaluates physical disability based
on the patient’s report of function and has become the most
commonly reported PRO in orthopaedic oncology literature. In
addition, because the TESS instrument was designed for adult
patients, the pediatric Toronto Extremity Salvage Score (pTESS) was
developed and validated specifically for a pediatric cohort. 36 Higher
scores indicate be er function. A 2021 study of Finnish patients
with lower extremity soft-tissue sarcomas further validated the
TESS relative to the MSTS score, the QLQ-C30 Function and Quality
of Life modules. 37 A 2020 study calculated minimal clinically
important differences in the TESS based on statistical
measurements at 6- and 12-month intervals. The minimal clinically
important differences at 6 months were 4.9 to 7.8 by distribution-
based methods and 4.3 to 4.4 by anchor-based methods. The
minimal clinically important differences at 12 months were 4.0 to
6.9 by distribution-based methods and 10.6 to 11.6 by anchor-based
methods. 38

Patient-Reported Outcomes Measurement

Information System
The National Institutes of Health Common Fund Initiative “Patient
Reported Outcomes Measurement Information System” (PROMIS)
is a series of instruments that aim to measure patient-reported
symptoms and health-related quality-of-life measures across
various conditions and health populations. 39 Rather than
instruments that are specific to a disease, such as sarcoma, these
instruments permit comparisons across patient populations and
conditions, for example, sarcoma, metastatic carcinoma, acute
coronary syndrome, or chronic kidney disease. 40 A major advantage
of these instruments is the computer adaptive tests (CATs), which
use item response theory to dynamically administer questions
based on the subject’s answer. 41 Thus, the instrument length and
depth varies based on the subject’s responses, and this minimizes
the length of the instrument while retaining its validity. PROMIS
measures not only physical but also mental and social health. The
physical health domains capture the patient’s perception of
function, fatigue, and pain interference (ie, behavior altered
because of pain). The mental health domains focus on symptoms
related to depression, anxiety, and anger. The social health domains
include satisfaction with participation or role in social activities,
which is a powerful line of inquiry into resilience and adaptation
that is seldom included in other PROs measures.
Several studies have explored applications of PROMIS in the
musculoskeletal oncology population. One line of inquiry focuses
on comparisons between PROMIS measures and TESS scores. 42 The
performance of these instruments has been the focus of several
papers examining floor and ceiling effects and comparing scores to
a generalized US population. 43 , 44 In addition to comparisons
across diagnoses and health states, recent studies have examined
temporal changes in PROMIS scores, in particular postoperatively.
45 , 46

Although improved compared with legacy measures, ceiling and

floor effects remain a critique of certain PROMIS instruments in
orthopaedic patients. This occurs when a number of the patients
score the highest or lowest scores for a given measure, which affects
the validity of the survey instrument. 47 A study of diverse
orthopaedic patients seen in a variety of outpatient clinics from one
institution examined the floor effect of the CAT for depression,
where a large number of the patients were reporting the lowest
possible score. The study authors found a significantly decreased
amount of time spent per question in that instrument compared
with the CAT for physical function, leading them to posit hasty
completion of the depression CAT may explain the high floor effect.
48

Use of the PROMIS instruments is in its infancy; however, they

appear to be powerful comparative tools to MSTS and TESS for
orthopaedic oncology patients. Further studies into their validity
and interpretation with minimal clinically important differences are
underway.

Surveillance
Following initial multimodal treatments for bone and soft-tissue
sarcomas, disease progression can occur in the form of local
recurrence or metastatic spread. Surveillance is important because
detecting disease progression early has the potential to reduce
morbidity and mortality. Metastasis, which may or may not be
associated with local recurrence, is the cause of disease-related
mortality. Sarcoma metastases most commonly occur in the lungs
but may also be seen in the viscera, soft-tissue, lymphatic system,
or bone. Synovial sarcoma, clear cell sarcoma, angiosarcoma,
rhabdomyosarcoma, and epithelioid sarcoma also demonstrate
lymphatic metastasis; therefore, initial staging and surveillance
must include lymphatic examination. Myxoid liposarcoma is known
for retroperitoneal and abdominal metastasis, so CT of the
abdomen and pelvis is performed as part of routine surveillance.
They also carry the potential for axial distant metastases, making
MRI of the entire spine or whole body appropriate in myxoid
liposarcoma. 49 , 50
For high-grade tumors, the incidence of disease progression
decreases over time; therefore, surveillance recommendations are
most intense (3 to 6 months depending on the guideline and tumor
type) within the first 2 years, with decreasing frequency over time.
Low-grade tumors have a more constant risk of disease
progression. Local recurrence monitoring includes history and
physical examination and advanced imaging, which may be
beneficial in detecting clinically occult recurrences. 51 Both
radiography and CT of the chest are acceptable for monitoring
pulmonary metastatic disease. In general, surveillance continues
for 10 years, although later recurrences have been documented. 52

Summary
The evaluation and management of musculoskeletal tumors is a
complicated process that involves clinical skills with
multidisciplinary collaboration. The history and physical
examination are the foundations of a differential diagnosis and help
guide the workup. Staging is an essential part of the process when a
neoplastic diagnosis is encountered and essential in considering
management options. Determining the optimal treatment is a
collaborative process with the patient and family members. PROs
inform short-term and long-term outcomes beyond the oncologic
outcomes of overall survival and progression-free survival, and
there are exciting new tools in this realm.

Key Study Points

A thorough and thoughtful evaluation of bone lesions and soft-tissue masses
includes history, physical examination, and local imaging, as well as distant imaging
and biopsy as indicated. If there is concern for sarcoma, referral to a tertiary center
with an orthopaedic oncologist and multidisciplinary team is appropriate.
Radiographs are the best initial study in the evaluation of a bone tumor. MRI with and
without contrast is helpful for imaging soft-tissue tumors and bone tumors
suspicious for malignancy on radiograph.
Biopsy of musculoskeletal tumors should only be done with careful attention to
anatomy and surgical principles, as contamination can compromise limb salvage
and oncologic outcomes.
Following initial management of sarcomas, disease progression can occur in the
form of local recurrence or distant metastasis, most commonly to the lungs.
Surveillance strategies, including frequency and imaging modality, vary based on
tumor characteristics and time from initial treatment.
Annotated References
1. Balach T, Stacy GS, Peabody TD: The clinical evaluation of bone
tumors. Radiol Clin North Am 2011;49(6):1079-1093, v.
2. Bacci G, Balladelli A, Forni C, et al: Ewing’s sarcoma family
tumours. differences in clinicopathological characteristics at
presentation between localised and metastatic tumours. J Bone
Joint Surg Br 2007;89(9):1229-1233.
3. Garcia-Ortega DY, Martin-Tellez KS, Cuellar-Hubbe M, et al:
Desmoid-type fibromatosis. Cancers (Basel) 2020;12(7):1851. As a
review of the natural history and molecular biology of desmoid
tumors, this article also details management options, oncologic
outcomes, and functional outcomes.
4. Balach T, Stacy GS, Haydon RC: The clinical evaluation of soft
tissue tumors. Radiol Clin North Am 2011;49(6):1185-1196, vi.
5. Thacker MM: Benign soft tissue tumors in children. Orthop Clin
North Am 2013;44(3):433-444, xi.
6. Errani C, Tsukamoto S, Mavrogenis AF: Imaging analyses of
bone tumors. JBJS Rev 2020;8(3):e0077. This review article
summarizes diagnostic accuracy of imaging modalities in bone
tumors and details specific findings common in certain disease
processes.
7. Damron TA, Mann KA: Fracture risk assessment and clinical
decision making for patients with metastatic bone disease. J
Orthop Res 2020;38(6):1175-1190. This article reviews the
pathologic fracture risk assessment with an emphasis on newer
technologies such as CT-based structural rigidity analysis and
finite element analysis.
8. Visgauss JD, Wilson DA, Perrin DL, et al: Staging and
surveillance of myxoid liposarcoma: Follow-up assessment and
the metastatic pa ern of 169 patients suggests inadequacy of
current practice standards. Ann Surg Oncol 2021;28(12):7903-7911.
This retrospective study examined the staging and surveillance of
169 patients with myxoid liposarcoma to evaluate the
 performance of CT chest abdomen pelvis in metastatic disease
detection. It found a large distribution of metastatic locations
involving different organ systems. Many osseous foci were
undetectable by CT and determined by MRI. Level of evidence:
III.
9. Crombe A, Marcellin PJ, Buy X, et al: Soft-tissue sarcomas:
Assessment of MRI features correlating with histologic grade and
patient outcome. Radiology 2019;291(3):710-721. This retrospective
single-center study examined MRI characteristics of soft-tissue
sarcomas in adults for significant association with high grade;
secondarily, these features were then examined for associations
with progression-free and overall survivals. The study authors
identified necrosis, heterogeneity, and peritumoral enhancement
as MRI characteristics associated with high grade, distant
metastatic-free survival, and overall survival.
10. Aryal A, Kumar VS, Shamim SA, Gamanaga i S, Khan SA:
What is the comparative ability of 18F-FDG PET/CT, 99mTc-MDP
skeletal scintigraphy, and whole-body MRI as a staging
investigation to detect skeletal metastases in patients with
osteosarcoma and Ewing sarcoma? Clin Orthop Relat Res
2021;479(8):1768-1779. This prospective diagnostic study
examined the testing characteristics of PET/CT, whole-body MRI,
or skeletal scintigraphy in detecting skeletal metastases in 54
patients with osteosarcoma and Ewing sarcoma and found no
differences between the three imaging investigations in the 14
patients with skeletal metastases. Level of evidence: II.
11. Errani C, Bazzocchi A, Spinnato P, et al: What’s new in
management of bone metastases? Eur J Orthop Surg Traumatol
2019;29(7):1367-1375. This review article discussed the less
invasive techniques available for bony metastatic foci including
embolization, electrochemotherapy, MRI-guided high-intensity
focused ultrasound, and thermal ablation.
12. Schwabe M, Spiridonov S, Yanik EL, et al: How effective are
noninvasive tests for diagnosing malignant peripheral nerve
sheath tumors in patients with neurofibromatosis type 1?
 Diagnosing MPNST in NF1 patients. Sarcoma 2019;2019:4627521.
This study examined the testing characteristics of clinical
examination, MRI, and PET/CT in a cohort of 41 adult NF1
patients and found MRI and PET/CT to be more effective at
diagnosing malignant peripheral nerve sheath tumors than
clinical features.
13. Fiore M, Casali PG, Miceli R, et al: Prognostic effect of re-
excision in adult soft tissue sarcoma of the extremity. Ann Surg
Oncol 2006;13(1):110-117.
14. Italiano A, Le Cesne A, Mendiboure J, et al: Prognostic factors
and impact of adjuvant treatments on local and metastatic
relapse of soft-tissue sarcoma patients in the competing risks
se ing. Cancer 2014;120(21):3361-3369.
15. O’Donnell PW, Griffin AM, Eward WC, et al: The effect of the
se ing of a positive surgical margin in soft tissue sarcoma. Cancer
2014;120(18):2866-2875.
16. Gilbert NF, Cannon CP, Lin PP, Lewis VO: Soft-tissue sarcoma. J
Am Acad Orthop Surg 2009;17(1):40-47.
17. Yamamoto H, Iwasaki T, Yamada Y, et al: Diagnostic utility of
histone H3.3 G34W, G34R, and G34V mutant-specific antibodies
for giant cell tumors of bone. Hum Pathol 2018;73:41-50.
18. Cable MG, Randall RL: Extremity soft tissue sarcoma: Tailoring
resection to histologic subtype. Surg Oncol Clin N Am
2016;25(4):677-695.
19. Bielack S, Jurgens H, Jundt G, et al: Osteosarcoma: The COSS
experience. Cancer Treat Res 2009;152:289-308.
20. Fujiki M, Kimura T, Takushima A: Limb-salvage surgery with
vascular reconstruction after lower extremity sarcoma resection:
A systematic review and meta-analysis. Microsurgery
2020;40(3):404-413. This meta-analysis examined vascular
reconstruction outcomes in patients with lower extremity
sarcomas treated with limb-salvage resection and reported rates
of perioperative complications.
21. Martin E, Dullaart MJ, Verhoef C, Coert JH: A systematic review
of functional outcomes after nerve reconstruction in extremity
soft tissue sarcomas: A need for general implementation in the
armamentarium. J Plast Reconstr Aesthetic Surg 2020;73(4):621-632.
This review examined 19 studies, describing 26 patients, who
underwent nerve reconstruction or grafting as part of soft-tissue
sarcoma resection and reported motor and sensory outcomes.
22. Womer RB, West DC, Krailo MD, et al: Randomized controlled
trial of interval-compressed chemotherapy for the treatment of
localized ewing sarcoma: A report from the Children’s Oncology
Group. J Clin Oncol 2012;30(33):4148-4154.
23. Marina NM, Smeland S, Bielack SS, et al: Comparison of MAPIE
versus MAP in patients with a poor response to preoperative
chemotherapy for newly diagnosed high-grade osteosarcoma
(EURAMOS-1): An open-label, international, randomised
controlled trial. Lancet Oncol 2016;17(10):1396-1408.
24. Chowdhary M, Chowdhary A, Sen N, Zaorsky NG, Patel KR,
Wang D: Does the addition of chemotherapy to neoadjuvant
radiotherapy impact survival in high-risk extremity/trunk soft-
tissue sarcoma? Cancer 2019;125(21):3801-3809. The authors
reviewed data from the National Cancer Database to evaluate if
adding chemotherapy to neoadjuvant radiation therapy had
survival benefits in patients with large (≥5 cm) high-grade
tumors. The data demonstrate a trend of increased overall
survival. This study is limited by the lack of toxicity information
available in the National Cancer Database. Level of evidence: III.
25. Vlenterie M, Litiere S, Rizzo E, et al: Outcome of chemotherapy
in advanced synovial sarcoma patients: Review of 15 clinical trials
from the European organisation for research and treatment of
cancer soft tissue and bone sarcoma group; se ing a new
landmark for studies in this entity. Eur J Cancer 2016;58:62-72.
26. Eilber FC, Brennan MF, Eilber FR, et al: Chemotherapy is
associated with improved survival in adult patients with primary
extremity synovial sarcoma. Ann Surg 2007;246(1):105-113.
27. Mavrogenis AF, Pala E, Guerra G, Ruggieri P: Post-radiation
sarcomas. Clinical outcome of 52 patients. J Surg Oncol
2012;105(6):570-576.
28. Gor ak Y, Lockwood GA, Mahendra A, et al: Prediction of
pathologic fracture risk of the femur after combined modality
treatment of soft tissue sarcoma of the thigh. Cancer
2010;116(6):1553-1559.
29. O’Sullivan B, Davis AM, Turco e R, et al: Preoperative versus
postoperative radiotherapy in soft-tissue sarcoma of the limbs: A
randomised trial. Lancet 2002;359(9325):2235-2241.
30. Husain ZA, Sahgal A, De Salles A, et al: Stereotactic body
radiotherapy for de novo spinal metastases: Systematic review. J
Neurosurg Spine 2017;27(3):295-302.
31. DuBois SG, Krailo MD, Gebhardt MC, et al: Comparative
evaluation of local control strategies in localized Ewing sarcoma
of bone: A report from the Children’s Oncology Group. Cancer
2015;121(3):467-475.
32. Mazzarella L, Duso BA, Trapani D, et al: The evolving landscape
of ‘next-generation’ immune checkpoint inhibitors: A review. Eur
J Cancer 2019;117:14-31. This article reviews the published
literature on the basic science, clinical, and pharmaceutical
reports of the first-generation immune checkpoint inhibitors that
have reached clinical development.
33. Enneking WF, Dunham W, Gebhardt MC, Malawar M, Pritchard
DJ: A system for the functional evaluation of reconstructive
procedures after surgical treatment of tumors of the
musculoskeletal system. Clin Orthop Relat Res 1993;286:241-246.
34. Janssen SJ, van Rein EA, Paulino Pereira NR, et al: The
discrepancy between patient and clinician reported function in
extremity bone metastases. Sarcoma 2016;2016:1014248.
35. Nelson E, Conger B, Douglass R, et al: Functional health status
levels of primary care patients. J Am Med Assoc 1983;249(24):3331-
3338.
36. Piscione J, Barden W, Barry J, et al: The pediatric Toronto
Extremity Salvage Score (pTESS): Validation of a self-reported
functional outcomes tool for children with extremity tumors. Clin
Orthop Relat Res 2019;477(9): 2127-2141. This study describes the
formation of pediatric-specific upper and lower extremity
versions of the TESS instrument using qualitative and
quantitative survey methods. The authors found no floor or
ceiling effects and high internal consistency. Level of evidence: II.
37. Kask G, Uimonen MM, Barner-Rasmussen I, Tukiainen EJ,
Blomqvist C, Repo JP: Further validation of the Toronto extremity
salvage score for lower extremity soft tissue sarcoma based on
Finnish patients. J Plast Reconstr Aesthetic Surg 2021;74(1):71-78.
This study examined the performance of the TESS instrument in
136 patients with lower extremity sarcomas. Although a high
ceiling effect of 21% was found, the instrument was found to be
reliable compared temporally and to MSTS and other commonly
used health self-reported questionnaires.
38. Ogura K, Uehara K, Akiyama T, et al: Minimal clinically
important differences in Toronto extremity salvage score for
patients with lower extremity sarcoma. J Orthop Sci 2020;25(2):315-
318. This study examined the minimal clinically important
differences for TESS using several statistical methods. The study
authors report that minimal clinically important differences for 6
months were 5 to 8 by distribution methods and 4 by anchor-
based methods; minimal clinically important differences for 12
months were 4 to 7 by distribution-based methods and 10.6 to
11.6 by anchor-based methods.
39. Cella D, Riley W, Stone A, et al: The patient-reported outcomes
measurement information system (PROMIS) developed and
tested its first wave of adult self-reported health outcome item
banks: 2005-2008. J Clin Epidemiol 2010;63(11):1179-1194.
40. Cook KF, Jensen SE, Schalet BD, et al: PROMIS measures of
pain, fatigue, negative affect, physical function, and social
function demonstrated clinical validity across a range of chronic
conditions. J Clin Epidemiol 2016;73:89-102.
41. Fries JF, Wi er J, Rose M, Cella D, Khanna D, Morgan-DeWi E:
Item response theory, computerized adaptive testing, and
PROMIS: Assessment of physical function. J Rheumatol
2014;41(1):153-158.
42. Ploe e KL, Dalton JF, Calfee RP, McDonald DJ, O’Keefe RJ,
Cipriano CA: Patient-reported outcomes measurement
information system physical function correlates with Toronto
extremity salvage score in an orthopaedic oncology population. J
Orthop Translat 2019;19: 143-150. This cross-sectional study of 97
adults with extremity bone or soft-tissue sarcomas compared
PROMIS measures with lower extremity and upper extremity
TESS scores and found the PROMIS instruments were less
burdensome and had lower ceiling effects. Level of evidence: III.
43. Cooper AR, Wilke B, Scarborough M, Gibbs CP, Spiguel A:
Pediatric sarcoma patients with worse physical function but
be er peer relationships and depressive symptoms than U.S.
pediatric population as measured by PROMIS®. Cureus
2020;12(2):e7040. This study examined PROMIS measures in 30
pediatric patients with bone and soft-tissue sarcomas and
compared their responses with those of the general US
population. The patients had worse physical function scores but
be er peer relationship and depression scores than the reference
cohort. Level of evidence: III.
44. Wilke B, Cooper A, Scarborough M, Gibbs CP, Spiguel A: An
evaluation of PROMIS health domains in sarcoma patients
compared to the United States population. Sarcoma
2019;2019:9725976. This study examined PROMIS measures in 138
adult patients with soft-tissue and bone sarcomas who were
treated surgically and compared their results with those of the
general US population. The temporal relationship to time of
surgery was also captured by examining responses of patients
less or more than 2 years from surgery. Patients who underwent
limb salvage surgery had worse physical function scores but
be er depression scores than the reference cohort, and these
differences were maintained over time. Level of evidence: III.
45. Wilke B, Cooper A, Scarborough M, Gibbs P, Spiguel A: A
comparison of limb salvage versus amputation for nonmetastatic
sarcomas using patient-reported outcomes measurement
information system outcomes. J Am Acad Orthop Surg
2019;27(8):e381-e389. This study examined PROMIS measures in
138 adult patients with soft-tissue and bone sarcomas who were
treated with limb-salvage resection or amputation. The temporal
relationship to time of surgery was also captured by examining
responses of patients less or greater than 12 months from
surgery. Improvements in PROMIS measures were reported in
patients who underwent limb salvage surgery and patients more
than 12 months from surgery. Patients who underwent limb
salvage surgery had improved emotional health compared with
the general US population. Level of evidence: III.
46. Newman ET, Lans J, Kim J, et al: PROMIS function scores are
lower in patients who underwent more aggressive local treatment
for desmoid tumors. Clin Orthop Relat Res 2020;478(3):563-577.
This study examined PROs of 85 patients with extremity desmoid
tumors treated at two institutions. Patients treated with local
modalities such as surgery and/or radiation did not experience
improved event-free survival, and those who underwent two or
more surgical treatments had worse PROMIS outcomes. Level of
evidence: III.
47. Bernstein DN, Bakhsh W, Papuga MO, Menga EN, Rubery PT,
Mesfin A: An evaluation of PROMIS in patients with primary or
metastatic spine tumors. Spine (Phila Pa 1976) 2019;44(10):747-752.
This study of 51 patients with metastatic spine tumors compared
PROMIS measures with Oswestry Disability Index and Neck
Disability Index and reported good correlation with similar floor
and ceiling effects. Level of evidence: II.
48. Gua ery JM, Dardas AZ, Kelly M, Chamberlain A, McAndrew
C, Calfee RP: Floor effect of PROMIS depression CAT associated
with hasty completion in orthopaedic surgery patients. Clin
Orthop Relat Res 2018;476(4):696-703.
49. Durr HR, Rauh J, Baur-Melnyk A, et al: Myxoid liposarcoma:
Local relapse and metastatic pa ern in 43 patients. BMC Cancer
2018;18(1):304.
50. Schwab JH, Boland PJ, Antonescu C, Bilsky MH, Healey JH:
Spinal metastases from myxoid liposarcoma warrant screening
with magnetic resonance imaging. Cancer 2007;110(8):1815-1822.
51. England P, Hong Z, Rhea L, Hirbe A, McDonald D, Cipriano C:
Does advanced imaging have a role in detecting local recurrence
of soft-tissue sarcoma? Clin Orthop Relat Res 2020;478(12):2812-
2820. This study retrospectively reviewed the clinical and imaging
surveillance data for 366 patients with soft-tissue sarcoma treated
with radiation and surgery at a single institution over a 20-year
study period and examined local disease recurrence detection by
clinical examination or imaging. It determined approximately
one-third of local disease recurrence cases were detected by
imaging alone, therefore supporting the use of imaging in the
current surveillance guidelines. Level of evidence: III.
52. Cipriano CA, Jang E, Tyler W: Sarcoma surveillance: A review of
current evidence and guidelines. J Am Acad Orthop Surg
2020;28(4):145-156. This review article discusses the evidence and
current international guidelines for extremity sarcoma
surveillance. Level of evidence: V.
C H AP T E R 7 1

Benign Tumors and Tumorlike

Conditions of Bone
Frank E. Chiarappa MD, James H. Flint MD, FACS, FAAOS

Dr. Flint or an immediate family member serves as a board member, owner, officer, or committee
member of American Academy of Orthopaedic Surgeons. Neither Dr. Chiarappa nor any
immediate family member has received anything of value from or has stock or stock options held
in a commercial company or institution related directly or indirectly to the subject of this chapter.

ABSTRACT
Benign bone tumors, along with metabolic bone disease and
osseous infections, are among the most common conditions
encountered by orthopaedic surgeons. Some bone tumors, such as
nonossifying fibroma or osteochondroma, can be diagnosed with
radiographs and do not require intervention. More aggressive bone
tumors, such as chondroblastoma and giant cell tumor of bone,
require surgical management. These conditions have the potential
for local recurrence and, rarely, are associated with benign lung
metastases or malignant transformation. Many benign tumors can
be challenging to diagnose, with features that can resemble
malignancies or tumorlike conditions; therefore, correlation
between clinical, radiographic, and pathologic findings is key.
Keywords: benign; osteomyelitis; tumor; tumor mimickers

Introduction
It is important for orthopaedic surgeons to be aware of relevant
epidemiology, pathophysiology, presentation, imaging, histology,
treatment, and potential for recurrence/transformation of benign
tumors and tumor-like conditions of bone. A review of the most
current literature will provide information relevant to the diagnosis
and management of these challenging conditions.

Cystic Lesions

Unicameral Bone Cyst

Unicameral bone cysts (UBCs), also known as simple or solitary
bone cysts, are frequently seen in the metaphysis of skeletally
immature patients, with a predilection for the proximal humerus
and proximal femur. These lesions are most commonly identified in
the first or second decade of life, and there is a 2:1 male:female
distribution. UBCs are rarely found in adults, suggesting resolution
during or after skeletal maturity. Lesions abu ing the physis are
classified as active, whereas those not directly adjacent are
considered latent. The pathophysiology of UBC is thought to be
related to a local increase in pressure due to venous obstruction;
therefore this lesion represents a reactive condition rather than a
true neoplasm. This is corroborated by histologic analysis of the
cyst lining, which shows a bland fibrous lining without endothelial
cells. The fluid contained within the cyst is proteinaceous,
containing interleukins, prostaglandins, and matrix
metalloproteinases. UBCs are often found incidentally or after a
pathologic fracture. Radiographs are usually diagnostic.
Occasionally, after a fracture, a pathognomonic fallen leaf sign (a
small piece of cortical bone floating within the cyst) can be
appreciated.
Treatment is based on the size and location of the lesion, as well
as the age of the patient. Patients with symptomatic or high-risk
lesions are generally treated with injection (sometimes requiring
serial injections) or cure age and autologous bone grafting.
According to a 2020 study, aspiration and injection of bioresorbable
bone cements (porous beta-tricalcium phosphate and
hydroxyapatite/calcium sulfate) have been investigated with good
healing and a low reoperation rate, 1 but there are no data showing
a clinical advantage of these materials over conventional
treatments. Fractures can usually be managed nonsurgically,
although internal fixation may be appropriate in some locations,
such as the proximal femur. Some lesions will resolve after fracture;
if they persist and remain at risk for repeat fracture, prophylactic
surgical treatment as mentioned previously should be considered.

Aneurysmal Bone Cyst

Aneurysmal bone cysts (ABCs) are seen in the metaphysis of
children typically between 8 and 14 years of age, with a slight
female preponderance. Although most lesions occur in the
proximal humerus or about the knee, ABCs are also seen in the
spine, pelvis, and clavicle. Unlike UBCs, which are not wider than
the adjacent physis, ABCs expand and thin the cortex and can
become quite large, as the name aneurysmal suggests. There are
often septations appreciated on radiographs and fluid-fluid levels
on MRI. However, it is important to note that fluid-fluid levels are
not pathognomonic and may be seen in other conditions including
telangiectatic osteosarcoma. ABCs can be primary or secondary,
arising from another lesion. The pathophysiology is related to a
translocation causing upregulation of USP-6, which in turn
increases matrix metalloproteinases via nuclear factor kappa B.
Treatment consists of observation, injections (such as
doxycycline, which demonstrates inhibition of matrix
metalloproteinases), or surgery. The mainstay of surgical treatment
is thorough cure age and grafting, with or without an adjuvant
such as argon beam, ethanol, or phenol. Some lesions require
internal fixation or even resection if they become extremely large.
Approximately one-third of these lesion may recur, likely related to
inadequate surgical treatment, aggressive biology, or a combination
of both factors. A 2019 review of 65 patients treated with cure age
with or without phenol suggests that phenol use does not decrease
the risk of local recurrence as previously concluded. 2 A 2021 review
of the literature suggested that primary and secondary ABCs may
have a different clinical course and concluded that polidocanol (a
local anesthetic and sclerosing agent) injection is an effective
minimally invasive treatment for primary ABCs. 3

Chondroid Lesions

Osteochondroma
Osteochondromas are among the most common bone tumors. The
true incidence is unknown as many lesions are asymptomatic.
Osteochondromas often present as firm, painless masses and can
be pedunculated or sessile. They often present with discomfort
related to muscle, tendon, or nerve irritation; contact with the bone
prominence; or fracture of the pedunculated stalk. More rarely, they
can cause deformity or limb-length discrepancy by interfering with
normal skeletal growth. The pathophysiology is thought to be a
physeal aberrancy or extrusion. Like the normal physis, these
lesions will continue to grow until skeletal maturity is reached.
Osteochondromas appear to grow away from the joint; however, the
adjacent joint is actually growing away from the base of the
osteochondroma. Imaging and histology reveal a confluence of
medullary contents between the bone itself and the tumor.
Osteochondromas have a cartilage cap within which endochondral
ossification occurs. If the cartilage cap exceeds 2 cm, transformation
into chondrosarcoma should be considered.
Asymptomatic lesions do not require treatment. Surgical
resection is indicated for symptomatic lesions, or those causing
growth disturbances, such as angular deformity or limb-length
discrepancy. Occasionally they may require treatment in adulthood
if late symptoms such as impingement or an inflamed bursa
overlying the lesion develop. Multiple hereditary exostosis is an
autosomal dominant condition affecting 1:50,000 individuals
because of mutations in genes EXT1, EXT2, or EXT3. Multiple
hereditary exostosis results in numerous osteochondromas, which
are often much more severe and debilitating than isolated lesions.
A recent study evaluated full-body MRI as a screening method for
assessing malignant transformation in multiple hereditary
exostosis and enchondromatosis. 4 It was concluded that MRI may
be an effective screening tool but caution that long-term follow-up
and cost analysis need to be performed before recommending this
for all patients. 2

Enchondroma and Other Chondromas

Enchondroma
Enchondromas are benign cartilaginous bone tumors.
Approximately half occur in the hands and feet, but they are also
found in the central portion of the metaphysis of long bones,
particularly about the knee and proximal humerus. Most are
painless, incidental findings without risk of fracture or malignancy.
Pain can be a sign of malignant transformation, but a thorough
examination should rule out other sources, such as rotator cuff
symptomology. Imaging findings that may suggest potential
malignancy include eccentric location, cortical breakthrough, large
lucent areas, periosteal reaction, soft-tissue mass, or perilesional
edema. Histologically, enchondromas cannot be readily
distinguished from low-grade chondrosarcoma; therefore, biopsy is
not performed routinely.
Treatment of enchondromas without concerning features
generally consists of observation. When surgery is required,
cure age and grafting with or without internal fixation is effective
with a low rate of local recurrence. Local recurrence should raise
concern for chondrosarcoma.

Periosteal Chondromas
Also known as juxtacortical chondromas, these surface-based
benign chondral tumors arise from the periosteum. Surgical
treatment consisting of cure age is indicated for symptomatic
lesions.

Enchondromatosis (Ollier Disease and Maffucci

Syndrome)
Ollier disease is a disfiguring condition resulting from numerous
enchondromas (Figure 1) and is usually first diagnosed in
childhood. Maffucci syndrome is even more rare and is
characterized by extensive enchondromas as well as soft-tissue
angiomas. Both conditions carry an approximately 30% risk of
malignant transformation of enchondroma to chondrosarcoma.
However, the risk of development of a malignancy by early
adulthood, including visceral malignancies and leukemia, in
patients with Maffucci syndrome is almost 100%. 5
 Figure 1 A, Radiograph of the hand of a patient with a painful fifth digit. An
enchondroma can be seen at the base of the middle phalanx (remote united
metacarpal fracture is noted). B, Radiograph of the hand of a patient with Ollier
disease. Note the soft-tissue mass (increased density) suspicious for malignant
transformation into chondrosarcoma.

Chondroblastoma
Chondroblastoma is a benign-aggressive cartilaginous tumor
arising in the epiphysis of long bones. Patients present at a mean
age of 18 years (range, 8 to 48 years). 6 Involvement of the femoral
head is rare (4.5%) and occurs in slightly younger patients (mean
age, 13.9 years). 6 Patients often present with pain and occasionally
joint stiffness or effusion. Radiographs reveal a well-marginated
lucent lesion usually abu ing the subchondral surface. There may
be central mineralization and/or cortical destruction. A
representative magnetic resonance image is shown in Figure 2, with
the corresponding histology slide of a subsequent biopsy in Figure
3.
Figure 2 A, T1 coronal MRI sequence and B, T2-STIR coronal MRI sequence
demonstrating a lesion in the talus of a 15-year-old patient presenting with ankle
pain. A large lesion is seen abutting the subchondral surface of the medial ankle.
Cystic changes are apparent within the tumor. Chondroblastoma was confirmed
with biopsy.
 Figure 3 Histologic specimen (20× magnification) from the patient described in
Figure 2.The tumor is highly cellular, consisting of sheets of round to polygonal
cells. Immature chondroid matrix is appreciated as well as the distinct chicken-
wire calcification pattern. Scattered multinucleated giant cells are present as
well.

Treatment usually consists of extended cure age and local

adjuvant treatment with bone grafting, with an effort being made to
spare the physis. Although this lesion is benign, like giant cell
tumor of bone, it can be associated with risk of local recurrence
and, very rarely, pulmonary metastasis. A 2019 single-center review
of 177 cases revealed 14% local recurrence at an average of 10
months.6 Another single-institution retrospective review of 38 cases
showed a higher proportion of recurrence (11.8%) with cure age
and hydrogen peroxide compared with cure age and grafting
alone. 7 This study was not randomized, and there is potential for
selection bias for peroxide use based on surgeon preference, tumor
size, and tumor location.

Chondromyxoid Fibroma
Chondromyxoid fibroma is an extremely rare bone tumor. It is
often misdiagnosed and in some cases is a diagnosis of exclusion. 8
This lesion is usually found in the metaphysis of patients in the
second and third decades of life. Radiographs reveal an eccentric
lucent lesion with well-defined sclerotic borders. MRI is useful in
identifying the juxtaposed chondroid and myxoid components of
this lesion. The mainstay of treatment includes cure age and
grafting, with a 15% to 20% risk of local recurrence.

Fibrous Lesions

Nonossifying Fibroma
Nonossifying fibromas (NOFs), also known as fibrous cortical
defects or fibroxanthomas, are among the most common bone
tumors. It has been suggested that one-third of skeletally immature
individuals have a nonossifying fibroma, although the true
prevalence is unknown because most lesions are asymptomatic and
thus found incidentally. NOFs are rarely seen in adults, and when
they are incidentally identified in this population, they appear
sclerotic rather than lucent. Radiographs will show a cortically
based lucent lesion with well-defined sclerotic borders and often a
soap bubble appearance without aggressive features. NOFs were
previously thought to represent a reactive condition (such as UBC),
but new data show activation of the RAS-MAPK pathway in 80% of
cases, suggesting a true neoplastic etiology. 9 The postpubertal
regression remains enigmatic. Biopsy is not necessary as the
diagnosis can be made radiographically. Surgery is rarely indicated,
generally being reserved for lesions that become large enough to
cause pain or fracture risk, particularly in young patients with
significant skeletal growth remaining.

Fibrous Dysplasia
Fibrous dysplasia is a developmental abnormality that can be either
monostotic (80%) or polyostotic, most commonly involving the
femur. The monostotic variety usually presents before the age of 40
years, most commonly in the second decade, and is often identified
incidentally. Patients with more extensive skeletal disease may
present at a younger age with pain or deformity. Radiographs
reveal a central lesion of the diaphysis or metaphysis with variably
defined borders, ground-glass intramedullary matrix, cortical
thinning/expansion, and possible skeletal deformity such as varus
(ie, shepherd’s crook) of the proximal femur. The MRI appearance
is heterogeneous and therefore, in the absence of plain
radiographs, can be misleading for a malignant condition.
Histology reveals a pathognomonic lack of osteoblastic rimming
adjacent woven bone. Observation is the mainstay of treatment for
asymptomatic patients. Diphosphonates may be used for
symptomatic lesions that do not require surgery or cannot be
managed surgically. Surgical treatment is indicated for stabilization
of impending or actual pathologic fractures, particularly in high-
risk areas such as the femoral neck, or for correction of severe
deformity. 10 Of note, autologous bone graft is not beneficial
because it will be quickly converted to dysplastic fibrous tissue.
Although rare, there is a slight (1%) risk of malignant
transformation into secondary bone sarcoma. There are some rare
associated conditions. McCune-Albright syndrome consists of
unilateral polyostotic fibrous dysplasia, café-au-lait spots (irregular
“coast of Maine” borders), and precocious puberty. 11 Mazabraud
syndrome is a combination of polyostotic fibrous dysplasia and
numerous soft-tissue myxomas. The true incidence of these
syndromes is unknown with estimates of approximately 1 in
1,000,000. However, the incidence of Mazabraud syndrome among
patients with fibrous dysplasia is about 2%.

Giant Cell Tumor of Bone

Giant cell tumor (GCT) of bone is a benign-aggressive tumor of
bone. GCT typically presents in the third or fourth decade of life,
most commonly adjacent to the knee or in the distal radius.
Pulmonary metastasis can occur in 1% to 2% of patients, but these
are considered benign. A rare, malignant variant of GCT also exists;
this, as well as giant-cell-rich osteosarcoma, should be ruled out
during evaluation. Symptoms consist of progressive pain,
particularly with weight bearing, and sometimes local swelling or a
soft-tissue mass. Radiographs reveal an eccentric, geographic lesion
with cortical destruction, located in the subchondral bone, directly
adjacent to a joint. GCTs may form an expanded pseudocortex, but
even this is often destroyed as the tumor grows larger.
Histologically, the lesion consists of sheets of stromal cells (the
true neoplastic cells) and many large multinucleated giant cells.
Some giant cells in GCT of bone can have 30+ nuclei. The nuclei of
the giant cells appear very similar to those of the stromal cells; this
similarity is a defining feature of GCT. Of note, the presence of
giant cells in a neoplasm is not pathognomonic for GCT, as giant
cells can be seen in many benign and malignant bone conditions.
Mitoses and osteoid production can be present, requiring clinical
and radiographic correlation to rule out malignant conditions such
as osteosarcoma. Malignant transformation has been described and
is usually associated with radiation treatment. 12 , 13
When adequate bone stock is available to salvage the joint,
surgical treatment consists of extended cure age, as standard
cure age alone affords unacceptably high rates of local recurrence.
Current surgical technique typically involves aggressive cure age
with extended mechanical cure age using a high-speed burr,
adjuvant treatments such as argon beam or phenol, and polymethyl
methacrylate with or without internal fixation.
Adjuvants have been widely used, including liquid nitrogen,
argon beam coagulation, phenol, ethanol, and hydrogen peroxide.
Polymethyl methacrylate also provides some adjuvant effect on
tumor cells through its exothermic reaction. In the absence of
randomized clinical trials, there is no definitive evidence comparing
treatment strategies. Some authors advocate bone grafting along
the articular surface to avoid thermal injury to the articular surface.
Figure 4 demonstrates the treatment of a GCT of bone with
extended cure age, argon beam, bone grafting along the articular
surface, cement augmentation, and internal fixation. Even with
current treatment strategies, local recurrence remains a problem at
5% to 30%. Wide excision is sometimes required but generally
reserved for massive bone loss, recurrent disease, or intra-articular
fracture.
Figure 4 A, Radiograph from a 22-year-old patient presenting with a large
ankle mass and increasing difficulty bearing weight for 6 months. B,
Intraoperative photograph of the tumor cavity left behind after extended
curettage; only a thin layer of cartilage remains on the distal tibia at the ankle
 joint. C, Photograph after argon beam, bone grafting the articular surface,
polymethyl methacrylate cement, and internal fixation. D, Postoperative
radiograph showing placement of polymethyl methacrylate and hardware.

Denosumab, a monoclonal antibody that inhibits the receptor

activator of nuclear factor kappa B ligand, was FDA-approved for
treatment of GCT in 2013. Clinical trials have shown it to be
effective for managing unresectable disease; when used
neoadjuvantly, it can also reduce the size of the soft-tissue mass
and restore bone stock, decreasing the morbidity of surgery by
avoiding the need for joint replacement. The optimal treatment
timeline and duration have yet to be determined. In spite of these
apparent benefits, there are many concerns about its use,
particularly related to the increased risk of early local recurrence, as
described in a 2020 systematic review. 14 Unfortunately, the current
literature is limited by potential indication bias (patients with more
advanced/severe tumors are more likely to be treated with
denosumab), and as of 2021 there were no randomized clinical
trials evaluating denosumab in GCT.

Osteoid Osteoma and Osteoblastoma

Osteoid Osteoma
Osteoid osteoma is a benign bone tumor occurring within the
cortex of long bones, with approximately 10% arising in the spine,
typically the posterior elements. The age of presentation ranges
from 5 to 30 years, with 75% of patients being younger than 20
years. Osteoid osteoma is characterized by nocturnal pain,
classically alleviated with NSAIDs. Radiographically, they are
characterized by a central radiolucent nidus and a rim of reactive,
sclerotic bone; 15 this subtle nidus cannot always be appreciated on
radiographs, so CT is considered the imaging modality of choice for
definitive diagnosis (Figure 5). NSAIDs provide reliable relief in
most cases, but given the inconvenience and side effects associated
with long-term use, intervention is typically recommended.
Radiofrequency ablation and cryotherapy are high-accuracy,
minimally invasive options with >90% success rates. 15 These
treatments can pose a risk to surrounding tissues; therefore,
arthroscopy has been well-described for treatment of juxta-articular
and intra-articular lesions. 16 This approach couples the benefits of
minimally invasive technique with en bloc excision of the nidus.
One study in 2021 reported universal pain relief in all arthroscopic
cases, with no recurrence at 24 months. 16

Figure 5 Axial CT image of the tibia demonstrating the classic appearance of

osteoid osteoma, with a rim of reactive, sclerotic bone around a central, lytic
nidus.

Osteoblastoma
Osteoblastoma is a rare entity, representing approximately 1% of all
bone tumors, and is often described as a larger form of osteoid
osteoma, using 1.5-cm diameter as an arbitrary threshold. It is more
common in adolescents and young adults, and most often
encountered in the spine or long bones, as well as the short bones
of the hands and feet. Because these lesions are too large to
effectively treat percutaneously, open cure age or en bloc resection
is indicated. A 2021 article reviewed 34 cases of pelvic
osteoblastoma, 4 of which were treated with radiofrequency
ablation. 17 The authors found that although radiofrequency
ablation allowed a minimally invasive approach, the recurrence rate
at 3 and 5 years was higher than treatment with cure age or open
excision (50% versus 81% and 88.9%, respectively). Other treatment
strategies to minimize morbidity have been reported but not widely
adopted.

Langerhans Cell Histiocytosis

Langerhans cell histiocytosis (LCH) is a rare disease with a
heterogeneous presentation that can involve the skin, visceral
organs, and bones. Although typically presenting in children, two
recent studies demonstrated that isolated bony involvement is
more common in adults. 18 , 19 Bone lesions are the most common
form of single organ involvement, typically presenting in the skull,
vertebral column, chest wall, and long bones. 22 , 23 Radiographs
commonly show a lytic diaphyseal or metaphyseal lesion with or
without periosteal reaction. LCH has been nicknamed the great
mimicker because it can have a radiographic appearance similar to
Ewing sarcoma, osteomyelitis, fibrous dysplasia, or lymphoma.
Vertebra plana may be seen in the spine. Once thought to be
pathognomonic for LCH, vertebra plana can have several etiologies.
Histopathologically, LCH is characterized by accumulation of
dendritic (Langerhans) cells. Nonsurgical management is generally
indicated for isolated lesions with low risk of pathologic fracture.
Surgical indications include actual or impending fracture or
progressive spine deformity. A 2021 systematic review including 64
such cases demonstrated that the treatment approach varies widely
based on the anatomic location and disease extent. 18 In this review,
unifocal bone lesions were commonly treated with complete
excision, cure age, or observation, whereas multifocal lesions were
typically treated with systemic chemotherapy. A 2020 study
evaluated the utility of indomethacin in managing Langerhans cell
histiocytosis of bone, whether primarily or in conjunction with
other treatment modalities. 19 The 3- and 5-year recurrence-free
survival rates were 85.4% and 71.4%, respectively, and were
significantly be er in patients receiving indomethacin as first-line
treatment, those receiving single-agent indomethacin, and those
with unifocal bone involvement.. 19 The superior outcomes in
patients treated with indomethacin and unifocal bone involvement
likely represent a less aggressive form of the disease.

Hemangioma of Bone
Hemangioma of bone, or intraosseous hemangioma, is a rare
vascular lesion most commonly encountered in the spine and
craniofacial bones, although it also can occur in the long bones. 20
Because of its lytic appearance on radiographs and uptake on
positron emission tomography, it can sometimes be confused with
metastatic disease, especially when located in the spine. 21 For these
reasons, CT and MRI are useful advanced diagnostic imaging
modalities. CT reveals thickened bony trabeculae (corduroy sign)
on sagi al views, and a polka-dot appearance on axial slices. 21
Contrast-enhanced MRI is particularly helpful, as these lesions tend
to be consistent with surrounding blood vessels (of note, spinal
hemangiomas often have increased T1 signal because of a higher
fat content). 20 Asymptomatic lesions can be observed, whereas
either percutaneous (sclerotherapy or embolization) or open
treatment is indicated for symptomatic lesions.
Epithelioid hemangioma is a locally aggressive vascular lesion
and can be found in soft tissue or bone. Unlike typical
hemangioma, this tumor is more common in long bones. 22 A 2019
article presented a case of multifocal, metachronous epithelioid
hemangioma, highlighting a unique FOS gene rearrangement in
this lesion that distinguishes it from a malignant tumor. 23 In this
case, open cure age of the lesion was recommended and
performed, with no recurrence of the initial bony lesion after 17
years. A nonsurgical approach was pursued in a 2019 case report,
using diphosphonates to manage diffuse bony involvement of
epithelioid hemangioma. Diphosphonate therapy was effective in
improving metabolic bone markers and pain, although spinal
surgical intervention was also warranted for pathologic fracture. 22

Myositis Ossificans
Myositis ossificans results from heterotopic ossification within
skeletal muscle. It is commonly seen in young, active individuals,
and commonly associated with local trauma. In the largest reported
case series of 68 patients, published in 2021, it was observed that
myositis ossificans most often occurs within the quadriceps and
brachialis muscles. 24 Causes cited include trauma, burns, spinal
cord injury, and stroke. Neurogenic causes are well documented,
and a 2021 study highlighted three severe cases after brain or spinal
cord injury. 25 Although it is a reactive rather than neoplastic
process, myositis ossificans can mimic more concerning conditions.
In the initial phase, significant inflammation and osteoid are
present, mimicking osteosarcoma and making histologic diagnosis
difficult. History, physical examination, and imaging are more
reliable diagnostic measures early on, until the affected area has
matured. Maturation takes approximately 1 year, at which point the
lesion resembles mature bone, with a characteristic cortical and
trabecular component. 24 Asymptomatic lesions are observed,
whereas excision is preferred for symptomatic myositis ossificans
after maturation (Figure 6). Radiation and NSAIDs are described
adjuncts to reduce the risk of recurrence after surgery. 24 , 25
 Figure 6 Plain radiograph (A) and three-dimensional reconstruction from a
pelvic CT scan (B) revealing heterotopic ossification of the quadriceps origin.

Osteomyelitis
Bone infection is most commonly caused by Staphylococcus aureus
and can present as unifocal or multifocal disease, the la er being
more common in children. Osteomyelitis can be caused by trauma
(open fractures), surgical contamination, hematogenous spread, or
contiguous spread such as open wounds or diabetic ulcers.
Hematogenous seeding primarily affects the lumbar spine or
physes about the knee, whereas contiguous spread is related to the
particular location of the wound or surgical site. A broad
differential diagnosis should be considered, as the presentation of
osteomyelitis can be very similar to that of malignancies,
particularly Ewing sarcoma.
Osteomyelitis can be challenging to treat, as bacteria have several
means to evade both immune response and antibiotic treatment,
including the formation of biofilms and abscess cavities. Surgery is
typically required for definitive management in the se ing of an
identifiable abscess or sequestrum. Surgery may also be required in
the case of recalcitrant disease, to remove hardware, or provide soft-
tissue coverage of open wounds. A novel classification system for
long bone osteomyelitis was reported in 2020, taking into account
bone involvement, antibiotic options, soft-tissue coverage, and host
factors, with the aim of guiding management and subspecialty
referral. 26 A follow-up study in 2020 demonstrated the usefulness
of this system in predicting outcomes and discussing prognosis
with patients. 27 Recent data show that children with septic arthritis
and contiguous osteomyelitis are more difficult to successfully
treat, with more associated complications and worse adverse
outcomes; as such, MRI in patients with septic arthritis suspected
to have concomitant osteomyelitis may help with earlier
identification and treatment. 28 Host factors such as diabetes, renal
disease, treatment compliance, and nutrition are key in the
successful treatment of osteomyelitis. Successful outcomes often
require a multidisciplinary approach with infectious disease,
dieticians, wound care specialists, and plastic surgeons.

Metabolic Conditions

Renal Osteodystrophy
Renal osteodystrophy represents a spectrum of abnormalities in
bone metabolism resulting from chronic kidney disease, including
mineralization and remodeling. 29 Renal osteodystrophy is one of
the main complications of chronic kidney disease and occurs
invariably in patients with end-stage renal disease. Radiographs
reveal diffuse osteopenia and may show bony sclerosis, “rugger
jersey” spine, subperiosteal resorption of the index/long phalanges,
brown tumors (lytic expansile lesion), or insufficiency fractures.
Soft-tissue calcifications, particularly of the vasculature, may be
appreciated. Impaired bone metabolism from renal osteodystrophy
can lead to pathologic fracture and the associated complications.
Patients with elevated corrected calcium and decreased parathyroid
hormone were more likely to sustain a pathologic fracture.
Pathologic fracture is associated with increased mortality in these
patients. Iliac bone biopsy after tetracycline labeling, followed by
histomorphometric analysis, is the gold standard for diagnosis. 30
Treating the underlying chronic kidney disease is necessary, and
identifying high and low bone turnover states is important to guide
additional treatment, such as antiresorptive therapy. In some cases,
tetracycline labeling can be unsuccessful; a 2021 study
demonstrated that histomorphometric analysis alone can be
sufficient for distinguishing between low and high bone turnover
states to guide treatment decisions. 30

Paget Disease
Paget disease of bone is another metabolic bone disorder
characterized by abnormality in bone remodeling. It can manifest
as monostotic or polyostotic disease, and is more common among
men, individuals older than 50 years, and those of white ethnicity. 31
The estimated prevalence of Paget disease in the United States is
1% to 2% of the population. The exact etiology is unclear and likely
multifactorial, with environmental, metabolic, and genetic
associations described, and there has been an overall decline in
incidence over the past several decades. 31 , 32 A 2019 systematic
review provided updated clinical recommendations for diagnosis
and management, including: (1) use of radiographs and bone scans
for defining the extent of active disease; (2) use of laboratory tests,
including serum alkaline phosphatase and liver function tests, to
screen for active disease; (3) use of a diphosphonate (zoledronic
acid favored) for management of symptomatic bone pain; (4)
treatment directed toward symptoms instead of normalizing
laboratory values; and (5) treatment of symptomatic osteoarthritis
with hip or knee arthroplasty. 31 A 2020 study concluded that
procollagen type 1 amino-terminal propeptide level is a be er
diagnostic and prognostic marker of active disease compared with
C-terminal telopeptides or alkaline phosphatase levels. It also
specifically evaluated the long-term effects of single-dose
zoledronic acid on bone markers and found it to be effective for
inducing biochemical remission in 97% of patients, although
symptomatic relief was not reported. 32 Surgical indications in Paget
disease include impending or completed pathologic fracture and
progressive deformity. The surgeon should be aware that bone of
these patients is often extremely hard yet bri le, and surgery is
often associated with increased blood loss.

Summary
All orthopaedic surgeons should be knowledgeable about the
epidemiology and evaluation of benign bone lesions to avoid
unnecessary testing, minimize patient anxiety, and recognize when
referral to an orthopaedic oncologist is indicated. The most current
literature on diagnostic and therapeutic strategies should be taken
into consideration when determining the best course of
management.

Key Study Points

Benign bone tumors and cysts are frequently encountered by orthopaedic surgeons.
A basic understanding of the most common diagnoses is critical to proper
management and good outcomes.
Some benign bone tumors can mimic malignant conditions and vice versa, so
referral to an orthopaedic oncologist is recommended for any patient with
concerning findings.
The understanding of bone infection and metabolic bone disease continues to evolve
and improve as novel diagnostic and therapeutic techniques become available.

Annotated References
1. Dong C, Klimek P, Abacherli C: Percutaneous cyst aspiration
with injection of two different bioresorbable bone cements in
treatment of simple bone cyst. J Child Orthop 2020;14(1):76-84.
This study evaluates aspiration combined with either porous
beta-tricalcium phosphate or hydroxyapatite/calcium sulfate bone
cement for the treatment of bone cysts. Both agents proved
effective, with a low risk of fracture/reoperation and good
incorporation. Level of evidence: IV.
2. Grahneis F, Klein A, Baur-Melnky T, et al: Aneurysmal bone cyst:
A review of 65 patients. J Bone Oncol 2019;18:100255. A review of
65 patients treated with cure age with or without phenol
adjuvant concluded that phenol did not affect the risk of local
recurrence. Level of evidence: IV.
3. Deventer N, Gosheger G, de Vaal M, Vogt B, Budny T: Current
strategies for the treatment of solitary and aneurysmal bone
cysts: A review of the literature. J Bone Oncol 2021;30:100384. A
recent literature review evaluated current treatment strategies
available for ABC. Polidocanol injection was found to be an
effective treatment with low morbidity. Level of evidence: III.
4. Jurik AG, Jorgensen PH, Mortensen MM: Whole-body MRI in
assessing malignant transformation in multiple hereditary
exostoses and enchondromatosis: Audit results and literature
review. Skeletal Radiol 2020;49(1):115-124. The authors evaluated
MRI as a screening tool in multiple hereditary exostosis and
enchondromatosis. It was found to be effective in identifying
chondrosarcoma but lacks long-term follow-up to determine if
this affects overall survival and does not take cost into
consideration. Level of evidence: IV.
5. Jurik AG: Multiple hereditary exostoses and enchondromatosis.
Best Pract Res Clin Rheumatol 2020;34(3):101505. This review article
provides the most current understanding and treatment
recommendations based on the current literature for multiple
hereditary exostosis and enchondromatosis. Level of evidence:
IV.
6. Laitinen MK, Stevenson JD, Evans A, et al: Chondroblastoma in
pelvis and extremities – A single centre study of 177 cases. J Bone
Oncol 2019;17:100248. A single-center review of chondroblastoma
describes a high local recurrent rate of 14% at an average of 10
months after surgery. Level of evidence: IV.
7. Deventer N, Gosheger G, de Vaal M, et al: Chondroblastoma: Is
intralesional cure age with the use of adjuvants a sufficient way
of therapy? J Bone Oncol 2021;26:100342. A total of 38 cases of
 chondroblastoma were evaluated from a single institution. A
decreased rate of local recurrence was seen with the addition of
hydrogen peroxide as an adjuvant to cure age. Level of evidence:
IV.
8. HemanthaKumar G, Sathish M: Diagnosis and literature review
of chondromyxoid fibroma – A pathological puzzle. J Orthop Case
Rep 2019;9(4):101-105. A histologic review of chondromyxoid
fibroma is presented, along with tips to making the diagnosis
while avoiding potential pitfalls. Level of evidence: IV.
9. Bovee JV, Hogendoorn PC: Non-ossifying fibroma: A RAS-
MAPK driven benign bone neoplasm. J Pathol 2019;248(2):127-
130. In this review of nonossifying fibroma histology, 80% of
these lesions had an upregulated RAS-MAPK pathway,
suggesting a true neoplastic etiology. Level of evidence: IV.
10. Reif TJ, Ma hias J, Fragomen AT, Rozbruch SR: Limb length
discrepancy and angular deformity due to benign bone tumors
and tumor-like lesions. J Am Acad Orthop Surg Glob Res Rev
2021;5(3):e00214. An extensive review on surgical correction of
skeletal deformity secondary to benign bone tumors and
conditions is presented. Level of evidence: IV.
11. Boyce AM, Collins MT: Fibrous dysplasia/McCune-albright
syndrome: A rare, mosaic disease of Gα s activation. Endocr Rev
2020;41(2):345-370. This review article discusses the histologic,
radiographic, and clinical features of McCune-Albright
syndrome. Level of evidence: IV.
12. Palmerini E, Picci P, Reichardt P, Downey G: Malignancy in
giant cell tumor of bone: A review of the literature. Technol Cancer
Res Treat 2019;18. This article reviews the literature on malignant
transformation of GCT of bone, which they estimate to occur in
4% of cases. Level of evidence: IV.
13. Palmerini E, Seeger L, Gambaro i M, et al: Malignancy in giant
cell tumor of bone: Analysis of an open-label phase 2 study of
denosumab. BMC Cancer 2021;21(1):89. An evaluation of
malignant transformation in a phase 2 study of denosumab for
 GCT of bone did not find an increased risk associated with
treatment. Level of evidence: III.
14. Tsukamoto S, Tanaka Y, Mavrogenis AF, Kido A, Kawagucki M,
Errani C: Is treatment with denosumab associated with local
recurrence in patients with giant cell tumor of bone treated with
cure age? A systematic review. Clin Orthop Relat Res
2020;478(5):1076-1085. A meta-analysis of denosumab treatment
for GCT of bone showed minimal benefit and concern for
increased local recurrence rates, noting potential for indication
bias. Level of evidence: III.
15. Tepelenis K, Skandalakis G, Papathanakos G, et al: Osteoid
osteoma: An updated review of epidemiology, pathogenesis,
clinical presentation, radiological features, and treatment option.
In Vivo 2021;35(4):1929-1938. A comprehensive review of osteoid
osteoma is presented, including diagnosis, imaging
characteristics, and treatment options. Level of evidence: IV.
16. Plecko M, Mahnik A, Dimnjakovic D, Bojanic I: Arthroscopic
removal as an effective treatment option for intra-articular
osteoid osteoma of the knee. World J Orthop 2021;12(7):505-514. A
case series and literature review of arthroscopic management of
intra-articular osteoid osteoma is presented. Level of evidence:
IV.
17. Fiore M, Sambri A, Calamelli C, et al: Surgical treatment
scenario for osteoblastoma of the pelvis: Long-term follow-up
results. J Orthop Sci 2021; May 25 [Epub ahead of print]. A review
of 34 cases of pelvic osteoblastoma is presented, comparing
outcomes of radiofrequency ablation, cure age, and open
excision. Level of evidence: IV.
18. Reisi N, Raeissi P, Harati Khalilabad T, Moafi A: Unusual sites
of bone involvement in Langerhans cell histiocytosis: A
systematic review of the literature. Orphanet J Rare Dis
2021;16(1):1. The authors provide a systematic review of 64 cases
of Langerhans cell histiocytosis presenting in bone and discuss
 presentation and treatment options in adults and children. Level
of evidence: IV.
19. De Benedi is D, Mohamed S, Rizzo L, et al: Indomethacin is an
effective treatment in adults and children with bone Langerhans
cell histiocytosis (LCH). Br J Haematol 2020;191(5):e109-e113. A
review of 63 cases of Langerhans cell histiocytosis treated with
indomethacin demonstrates effectiveness of this treatment
option. Level of evidence: III.
20. Zhou Q, Lu L, Yang Z, Su S, Hong G: Hemangioma of long
tubular bone: Imaging characteristics with emphasis on magnetic
resonance imaging. Skeletal Radiol 2020;49(12):2029-2038. A
review of the imaging characteristics of hemangioma of long
bones is presented. Level of evidence: IV.
21. Vertenten B, Goethals L, De Geeter F: 68Ga DOTATATE uptake
in hemangioma simulating metastasis on PET imaging: CT helps
characterize bone hemangioma that could be wrongly interpreted
as skeletal metastases on 68Ga DOTATATE PET imaging. J Belg
Soc Radiol 2019;103(1):38. This study discusses the challenges of
distinguishing metastatic disease from hemangioma in the spine
and how CT scan can help differentiate between the two. Level of
evidence: IV.
22. Tang L, Chen G, Wang Q, John J, Lu C: Bisphosphonates as a
therapeutic choice for multifocal epithelioid hemangioma of
bone: A case report. Medicine (Baltimore) 2019;98(48):e18161. This
case report describes the effective use of disphosphonate in a
case of multifocal epithelioid hemangioma. Level of evidence: IV.
23. Xian J, Righi A, Vanel D, Baldini N, Errani C: Epithelioid
hemangioma of bone: A unique case with multifocal
metachronous bone lesions. J Clin Orthop Trauma 2019;10(6):1068-
1072. The authors review epithelioid hemangioma, with
presentation of a unique case with metachronous bone
involvement. Level of evidence: IV.
24. Saad A, Azzopardi C, Patel A, Davies AM, Botchu R: Myositis
ossificans revisited – The largest reported case series. J Clin
 Orthop Trauma 2021;17:123-127. A review of 68 cases of myositis
ossificans is presented, with a discussion of demographics,
diagnostic features, and treatment. Level of evidence: IV.
25. Hammad Y, Akiely R, Hajjaj N, Tahboub F, Al-Ajlouni J: The
surgical management of the rare neurogenic myositis ossificans
of the hip: A report of 3 cases. J Orthop Case Rep 2021;11(3):45-51.
A review of three cases of myositis ossificans arising after brain
or spinal cord injury is presented. Level of evidence: IV.
26. Hotchen AJ, Dudareva M, Ferguson J, Sendi P, McNally M: The
BACH classification of long bone osteomyelitis. Bone Joint Res
2019;8(10):459-468. A novel classification system of osteomyelitis
with long bone involvement is discussed. Level of evidence: V.
27. Hotchen AJ, Dudareva M, Corrigan R, Ferguson J, McNally M:
Can we predict outcome after treatment of long bone
osteomyelitis? Bone Joint J 2020;102-B(11):1587-1596. This study
evaluated the usefulness of a novel classification system in
predicting outcomes and discussing prognosis in long bone
osteomyelitis. Level of evidence: III.
28. Hamilton EC, Villani M, Klosterman M, Jo C, Liu J, Copley L:
Children with primary septic arthritis have a markedly lower risk
of adverse outcomes than those with contiguous osteomyelitis. J
Bone Joint Surg Am 2021;103(13):1229-1237. This study evaluated
the outcomes of primary septic arthritis versus septic arthritis
with contiguous osteomyelitis, demonstrating more
complications and worse outcomes in the la er group. Level of
evidence: III.
29. Martin A, David V: Transcriptomics: A solution for renal
osteodystrophy? Curr Osteoporos Rep 2020;18(3):254-261. The
authors present a review of transcriptomic analysis of RNA in
renal osteodystrophy. Level of evidence: IV.
30. Jorgensen HS, Behets G, Viaene L, et al: Static
histomorphometry allows for a diagnosis of bone turnover in
renal osteodystrophy in the absence of tetracycline labels. Bone
2021;152:116066. A study of 205 bone biopsies demonstrates the
 effectiveness of static histomorphometry in distinguishing
between low and high bone turnover states in renal
osteodystrophy when tetracycline labeling is insufficient. Level of
evidence: IV.
31. Ralston SH, Corral-Gudino L, Cooper C, et al: Diagnosis and
management of Paget’s disease of bone in adults: A clinical
guideline. J Bone Miner Res 2019;34(4):579-604. This updated,
comprehensive review of Paget disease of bone presents clinical
recommendations for diagnosis and management. Level of
evidence: IV.
32. Rodriguez-Olleros Rodriguez C, Blanes Jacquart D, Arboiro
Pinel R, de la Piedra Gordo C, Moro Alvarez M, Diaz Curiel M:
Long term effects on biochemical bone markers of a single
infusion of zoledronic acid in Paget disease of bone. J Orthop Sci
2020;25(4):715-718. A study evaluating the long-term effects of
single-dose zoledronic acid on bone markers in patients with
Paget disease of bone is presented. Level of evidence: IV.
C H AP T E R 7 2

Sarcomas of Bone
Alexandra K. Callan MD, Jesse L. Roberts MD, Andrew Park
MD

Dr. Callan or an immediate family member is a member of a speakers’ bureau or has made paid
presentations on behalf of Bone Support Inc. Neither of the following authors nor any immediate
family member has received anything of value from or has stock or stock options held in a
commercial company or institution related directly or indirectly to the subject of this chapter: Dr.
Roberts and Dr. Park.

ABSTRACT
Primary bone sarcomas comprise several distinct tumors of
mesenchymal origin and include Ewing sarcoma, osteosarcoma,
chondrosarcoma, adamantinoma, and chordoma. Diagnosis of
these tumors requires an understanding of their radiographic,
histologic, and clinical presentation, and treatments continue to
evolve.
Keywords: adamantinoma; bone sarcoma; chondrosarcoma;
chordoma; Ewing sarcoma

Introduction
Bone sarcomas are primary malignancies of bone arising from
mesenchymal origin. They represent less than 0.2% of malignant
tumors overall, with 3,300 cases diagnosed in the United States
annually. Although particularly rare in adults, they account for 5%
of cancers diagnosed in children younger than 14 years.
Osteosarcoma, Ewing sarcoma, chondrosarcoma, adamantinoma,
and chordoma are the most common types of bone sarcomas, each
with distinct cells of origin. These bone sarcoma subtypes differ
with respect to their workup and treatment algorithms. Patients
should be followed with physical examination, radiographs of the
extremity, and chest radiographs for at least 10 years after surgical
resection because of the risk of late local recurrence or metastatic
disease.

Osteosarcoma
Osteosarcoma is the most common primary bone cancer. With
multidisciplinary treatment including chemotherapy and wide
surgical resection, survival rates approach 70% in patients
presenting with nonmetastatic disease. Unfortunately, patients
with metastatic disease at diagnosis have limited survival of only
20% at 5 years. Survival outcomes have plateaued over the past 40
years, increasing the drive to understand genetic signatures and
options for novel therapies.

Epidemiology
Although osteosarcoma represents less than 1% of all cancers, it is
the most common primary bone cancer in children. 1 - 3
Approximately 1,000 new cases of osteosarcoma are diagnosed
annually in the United States. 4 Osteosarcoma most commonly
presents in the second decade of life, corresponding to periods of
rapid skeletal growth. A lesser peak of incidence occurs during the
seventh and eighth decades of life, when osteosarcoma may arise
secondary to prior radiation therapy or conditions such as Paget
disease. 5 Osteosarcoma has a predilection for the metaphysis of
long bones, specifically about the knee (42% in the distal femur,
19% in the proximal tibia) followed by the proximal humerus (10%);
however, it can be diagnosed in any bone. 5 According to the
National Cancer Institute Surveillance, Epidemiology, and End
Results Program, primary osteosarcoma in patients younger than 25
years had incidence rates that were slightly higher in males or
African-Americans, whereas secondary osteosarcoma was most
common in patients older than 60 years with a slight female or
Caucasian predominance. 3 , 6

Pathophysiology
Osteosarcoma is characterized by malignant spindle cells that
produce osteoid (Figure 1). Although the etiology of osteosarcoma
remains unclear, it most commonly occurs during periods of rapid
skeletal growth; in these situations, osteoblasts are active and may
undergo malignant transformation, especially with an underlying
genetic predisposition for such an event.
 Figure 1 Frozen specimen under 20× magnification with hematoxylin and
eosin stain from open biopsy confirms diagnosis of osteosarcoma with
pleomorphic, hyperchromatic spindle cells and malignant osteoid.(Courtesy of
Alexandra K. Callan, MD.)

Osteosarcoma has a disorganized genome, making it difficult to

elucidate common genetic fingerprints and targeted therapies.
Several inherited syndromes have been implicated as predisposing
factors in the development of osteosarcoma 7 (Table 1). The most
common syndromes associated with osteosarcoma include Li-
Fraumeni syndrome (germline p53 mutation) and hereditary
retinoblastoma syndrome (germline Rb mutation). 8 An estimated
28% of all patients with osteosarcoma carry a germline mutation in
a cancer-susceptibility gene (p53 or Rb), 9 and the p53 mutation is
associated with a decreased 2-year survival. 10 Beyond these rare
mutations, the most common characterization of osteosarcoma is a
structural complexity including chromosomal rearrangements, copy
number variation, kataegis, and chromothripsis. 11 Future research
focused on next-generation sequencing may lead to the
development of targeted treatment options.

Table 1
American Joint Committee on Cancer Staging System of
Malignant Bone Tumors

Stage Tumor Grade Tumor Size

IA Low <8 cm
IB Low >8 cm
IIA High <8 cm
IIB High >8 cm
III Any grade, skip metastasis Any size
IV Any grade, distant metastasis Any size
Reprinted from American Joint Committee on Cancer: Bone, in Edge SB, Byrd DR, Compton
CC, et al, eds: AJCC Cancer Staging Manual, ed 7. Springer, 2010, pp 281-290.

Subtypes
Six subtypes of osteosarcoma were defined in the 2020 World
Health Organization Classification: (1) osteosarcoma not otherwise
specified, (2) low-grade central osteosarcoma, (3) parosteal
osteosarcoma, (4) periosteal osteosarcoma, (5) high-grade surface
osteosarcoma, and (6) secondary osteosarcoma. Conventional
osteosarcoma, telangiectatic osteosarcoma, and small cell
osteosarcoma are included in osteosarcoma not otherwise specified.
2
More than 90% of all osteosarcomas are the conventional, high-
grade intramedullary variety, 2 which has been further subclassified
into osteoblastic, chondroblastic, or fibroblastic subtypes. To date,
there is no definitive evidence that these subtypes differ in terms of
prognosis. 12 , 13 Table 2 presents additional details on incidence,
imaging, histology, and outcomes.

Table 2
Osteosarcoma Predisposition Syndromes

Predisposition Inheritance
Gene Chromosome Tumor Types
Syndrome Pattern
Li-Fraumeni AD TP53 17p13.1 Osteosarcoma, soft-tissue
sarcoma, breast cancer,
leukemia, adrenocortical
carcinoma, brain tumors
Retinoblastoma AD RB1 13q14.2 Osteosarcoma, soft-tissue
sarcoma, melanoma
Rothmund- AR RECQL4 8q24.3 Osteosarcoma, squamous
Thomson and basal cell carcinoma
Werner AR WRN 8p12 Osteosarcoma, soft-tissue
sarcoma, melanoma,
myeloid tumors, thyroid
carcinoma, other epithelial
cancers
Bloom AR BLM 15q26.1 Osteosarcoma, carcinomas,
lymphomas, leukemias
AD = autosomal dominant, AR = autosomal recessive
Reproduced from Hameed M, Mandelker D: Tumor syndroms predisposing to
ostesosarcoma. Adv Anat Pathol 2018;25(4):217-222.

Presentation
Osteosarcoma classically presents as a painful mass in a growing
child. The pain is frequently severe at night and can wake the child
from sleep. Early symptoms may be ignored, as they are easily
a ributable to benign conditions such as trauma or growing pains.
Most patients eventually present with a firm, painful, nonmobile
mass; or much less commonly, a pathologic fracture. Most
commonly, patients’ tumors are classified as American Joint
Commi ee on Cancer stage IIB (Table 1).
Evaluation of an osteosarcoma includes plain radiographs of the
entire bone, MRI (with and without contrast) of the entire bone,
chest CT, whole-body bone scan or PET CT, and biopsy. Laboratory
workup may reveal elevated alkaline phosphatase level and lactate
dehydrogenase levels. Genetic counseling and testing should be
performed if there is any concern for an underlying disorder, and
fertility consultation should be considered. 14

Imaging
Plain radiographs reveal increased osteoid production or a
radiodense bone lesion with poorly defined margins, often
extending beyond the normal cortex. Radiographic signs of an
aggressive bone lesion include periosteal reactions such as a
sunburst pa ern, onion skinning, or Codman triangle. These classic
findings represent irregular periosteal bone formation because of
rapid growth of the tumor beyond the bone itself (Figure 2).
 Figure 2 A and B, AP and lateral radiographs of a right femur in a skeletally
immature 9-year-old girl with classic appearance of osteosarcoma. The
aggressive bone lesion is notable for dense osteoid deposition in the distal
metaphysis and extraosseous extension. The marked periosteal reaction is
characterized by a sunburst pattern and Codman triangle.(Courtesy of
Alexandra K. Callan, MD.)

MRI allows for the detailed assessment of the extent of

intramedullary involvement, extramedullary soft-tissue extension,
and relationship to nearby anatomic structures. Classically,
osteosarcoma is isointense to muscle on T1 sequences,
hyperintense on T2 sequences, and enhances with gadolinium
contrast (Figure 3).
 Figure 3 Magnetic resonance images of osteosarcoma reveal large
extraosseous extension with dense osteoid deposition of the right distal
femur.Osteosarcoma is hypointense on T1 imaging (A, coronal), hyperintense
on T2 imaging (B, axial), and contrast enhancing (C, axial).(Courtesy of
Alexandra K. Callan, MD.)

Chest CT is included in initial staging to identify any pulmonary

metastases and serve as a baseline for treatment (Figure 4). Whole-
body bone scan with technetium 99 (Tc-99) is the standard of care
for evaluation of distant bone metastases (Figure 5). The role of PET
CT continues to evolve for staging osteosarcoma, but it is not used
routinely at this time.
Figure 4 A, PA chest radiograph and B, CT of the chest revealing multiple
metastatic osteosarcoma nodules in the lungs.(Courtesy of Alexandra K. Callan,
MD.)

Figure 5 Whole-body bone scan is part of the staging workup for

osteosarcoma.This scan of a patient with primary osteosarcoma of the right
distal femur reveals skip metastases in the right proximal femur.(Courtesy of
Alexandra K. Callan, MD.)
Histology
Osteosarcoma is a malignancy of mesenchymal cell origin
characterized by malignant spindle cells that produce osteoid.
Histology reveals malignant, light-pink woven osteoid interspersed
with ugly, pleomorphic, hyperchromatic spindle cells (Figure 1).
Depending on the subtype, microscopic evaluation can reveal
various cell types including chondrocytes, fibroblasts, giant cells, or
small round blue cells along with malignant osteoid production
and pleomorphic spindle cells.

Current Treatment
Although only one-fourth of all newly diagnosed patients have
detectable metastases on presentation, all patients are assumed to
have micrometastatic disease. This is based on the observation that,
in the prechemotherapy era, metastatic disease developed in most
patients 3 to 6 months after radical surgical resection of the primary
tumor.
Evidence-based practice supports treatment with multiagent
chemotherapy and surgical resection. 1 , 13 Standard chemotherapy
regimen includes high-dose methotrexate, Adriamycin
(doxorubicin), and cisplatin (MAP therapy). Surgery involves a wide
surgical resection with the goal of removing all malignant cells and
achieving negative margins on pathology. The typical treatment
protocol involves 10 weeks of preoperative (neoadjuvant)
chemotherapy, surgical resection, and then 20 weeks of
postoperative (adjuvant) chemotherapy. This allows for assessment
of chemotherapy effect, estimated by histologic necrosis in the
tumor, at the time of surgical resection. Tumor necrosis of 90% or
higher is considered a favorable response; conversely, necrosis less
than 90% is associated with lower event-free survival rates. 13
Limb salvage surgery is possible for nearly 85% of patients with
osteosarcoma. 15 Even in the se ing of pathologic fracture, limb
salvage surgery remains feasible for most patients. 16 When limb
salvage surgery is not possible or reconstruction options are
limited, amputations, including rotationplasty, continue to be an
important technique for local control. Although limb salvage
surgery is associated with greater psychosocial satisfaction, faster
rate to ambulation, and less oxygen consumption, it is associated
with high complication and revision surgery rates. No long-term
differences have been identified between patients undergoing limb
salvage surgery versus amputation in terms of overall satisfaction,
life success, and functional scores. 17
Reconstruction options include endoprostheses, allografts
(intercalary or osteoarticular), or allograft prosthetic composites.
Each option is tailored to the long-term goals of the patient, taking
into account the various risks and benefits. Skeletal immaturity of
the patient adds to the complexity of this decision; in children with
limited growth remaining, contralateral epiphysiodesis may be
considered, whereas for those with significant growth remaining,
appropriate reconstruction may necessitate custom growing
endoprostheses or rotationplasty (Figure 6).
 Figure 6 A, Standing leg-length radiograph from a child with a noninvasive,
magnetic distal femur growing endoprosthesis for osteosarcoma. B, AP
radiograph of a distal femur that has been lengthened over time using a magnet
in clinic.(Courtesy of Alexandra K. Callan, MD.)

Prognosis
Five-year survival rate is approximately 76% for patients who
present with localized disease, compared with 20% for the 17% of
patients presenting with metastatic disease. 12 Characteristics
associated with a poor prognosis include large tumor size (>8 cm),
axial tumor location, pathologic fracture, metastases (skip or
distant), necrosis less than 90% at time of resection, local
recurrence, older age, and unresectable disease. 12 Osteosarcoma
outcomes have remained relatively static over the past 40 years,
since the advent of current multiagent chemotherapy regimens. 18

Emerging Therapies
Newer drug trials have investigated targeted agents such as
tyrosine kinase inhibitors and immunotherapies. Currently, several
tyrosine kinase inhibitors with anti-angiogenetic targets including
sorafenib or regorafenib seem to provide the most promising
results for relapsed osteosarcoma. 18 - 20 Although overall survival
remains similar, progression-free survival was significantly
improved with regorafenib in patients with metastatic
osteosarcoma. 21

Ewing Sarcoma
Ewing sarcoma was first described in 1921 as a series of unusual
pediatric bone tumors that lacked bone formation, exhibited a
dramatic initial response to radium, and histologically appeared to
be of endothelial origin. 22 Sixty years later, the most common of the
pathognomonic chromosomal translocations of Ewing sarcoma
were discovered, corresponding to a single protein responsible for
tumorigenesis. 23 Current treatment includes chemotherapy for
systemic control in addition to surgery and/or radiation therapy for
local control. Five-year survival rate is 70% for patients with
localized disease but only 30% for patients with metastatic disease
on presentation, and this subset makes up 25% of patients overall.
Clinical trials are ongoing to determine whether selectively
targeting the fusion proteins and their downstream pathways can
improve these outcomes.

Epidemiology
Representing 3% of all pediatric cancers and 10% of all primary
bone cancers, Ewing sarcoma is the second most common pediatric
bone sarcoma (after osteosarcoma) and third most common bone
sarcoma overall (after osteosarcoma and chondrosarcoma). 24 More
than 50% of patients with a diagnosis of Ewing sarcoma are
adolescents; there is a 1.5:1 male-to-female predilection, and the
disease is more prevalent in Caucasian people. Ten to 15% of
patients present with a pathologic fracture. 23 Ewing sarcoma most
frequently arises in marrow-rich locations of the skeleton, such as
the diaphysis of long bones and the pelvis. Primary tumors are
most common in the lower extremity (45%), pelvis (20%), upper
extremity (13%), and axial skeleton and ribs (13%), 25 whereas the
most common sites of metastatic disease are the lungs (50%) and
bone (25%). 26

Pathophysiology
Ewing sarcoma is in the small blue round cell family of tumors,
which also includes neuroblastoma, mesenchymal
chondrosarcoma, synovial sarcoma, and lymphoblastic lymphoma.
It is differentiated from these other tumors by its genetic signature;
in more than 90% of cases, the translocation t(11;22) fuses the
EWRS1 gene on chromosome 22 to the FLI1 gene on chromosome
11, and the remainder of Ewing sarcoma cases result from the
fusion of EWRS1 to another gene from the ETS family. 26 These
fusion oncoproteins act as transcription factors, exert epigenetic
control, and are essential to tumorigenesis.

Subtypes
The Ewing sarcoma family of tumors includes small round cell
tumors with common histologic and genetic features. Extraskeletal
Ewing sarcoma is one such entity that presents in the soft tissues
but arises from the pathognomonic translocations associated with
Ewing sarcoma. 27 , 28 A group of sarcomas similar to Ewing sarcoma
has been described that share morphologic characteristics with
Ewing sarcoma but lack the classic translocation between EWRS1
and the ETS family of transcription factors. The new World Health
Organization Classification of Tumors of Soft Tissue and Bone
identified four groups of undifferentiated round cell sarcomas:
Ewing sarcoma, CIC-rearranged sarcomas, BCOR-altered sarcomas,
and sarcomas with EWRS1-non-ETS fusions. 29 These rare subtypes
have disparate genetic signatures, and few clinical outcomes data
are available given their rarity.

Presentation
Patients with Ewing sarcoma commonly present with several
months of pain and swelling; in addition, more than 20% have a
fever or other systemic symptoms. Laboratory tests are nonspecific
but may show anemia, leukocytosis, elevated erythrocyte
sedimentation rate, or elevated serum lactate dehydrogenase. The
inflammatory symptoms and laboratory findings are unique, as
they do not occur in other bone sarcomas. Finally, bone marrow
biopsy may be performed in patients with metastatic disease to
evaluate for bone marrow involvement, which is present in up to
5% of all patients with a new diagnosis and 17.5% of patients with
metastatic disease. 30

Imaging
Workup begins with plain radiography, then contrast-enhanced
MRI of the entire bone. When in a long bone, Ewing sarcoma
typically affects the diaphysis or metadiaphysis and appears as an
aggressive, permeative intramedullary lesion on plain radiographs.
Bone destruction and periostitis may also be seen. Characteristic
MRI findings include a lesion that appears hypointense on T1,
hyperintense on T2, and avidly enhances; there is a sharp transition
in the bone itself, and often a large soft-tissue mass with
surrounding edema. MRI can detect skip metastases and is of
further value in that it demonstrates the proximity of neurovascular
structures to the tumor (Figure 7). Chest CT is performed to
evaluate for pulmonary metastases, as Ewing sarcoma most
commonly spreads hematogenously to the lungs. Whole-body bone
scan was previously the standard of care to screen for skeletal
metastases, but [18F]fluorodeoxyglucose positron emission
tomography scan is now an alternative.

Figure 7 A through F, Prechemotherapy and postchemotherapy T1 magnetic

resonance images following administration of gadolinium.(Reproduced with
permission from Thévenin-Lemoine C, Destombes L, Vial J, et al: Planning for
bone excision in Ewing Sarcoma: Post-chemotherapy MRI more accurate than
Pre-chemotherapy MRI assessment. J Bone Joint Surg Am 2018;100[1]:13-20,
Figure 1, C and Cʹ.)

Histology
Ewing sarcoma comprises small round cells with hyperchromatic
nuclei and expresses a high degree of CD99 positivity 31 (Figure 8).
Ewing sarcoma may be definitively diagnosed on fluorescence in
situ hybridization or reverse transcription polymerase chain
reaction via the detection of rearrangements of EWRS1 on
chromosome 22q12 and a member from the ETS transcription factor
family. Most commonly, this involves FLI1, but translocations can
also involve ERG, E1AF, FEV, ETV1, and ETV4. 32 RNA-based next-
generation sequencing can be used to confirm the diagnosis if a
gene fusion cannot be identified.

Figure 8 Histology slides of Ewing sarcoma showing monomorphic round

cells with scant cytoplasm.A, A monomorphous round cell proliferation
organized in a solid pattern of growth represents the typical morphology of the
entity. B, Homer-Wright rosettes can be seen in approximately 20% of cases. C,
The presence of abundant necrosis represents a typical histologic feature. D,
Diffuse membrane CD99 immunopositivity is invariably observed. CD99 is not
specific but extremely sensitive.(Reproduced with permission from Sbaraglia M,
Righi A, Gambarotti M, et al: Ewing Sarcoma and Ewing-like tumors. Virchows
Archiv 2019;476[1]:109-119, Figure 1.)
Current Treatment
Treatment for Ewing sarcoma requires multidisciplinary care,
including either surgery or radiation for local control and
multiagent cytotoxic chemotherapy for systemic control. Before the
advent of effective chemotherapy protocols, metastatic disease
developed and was fatal in almost all patients despite adequate
local control; therefore, patients with Ewing sarcoma are assumed
to have subclinical micrometastatic disease on presentation. In the
1970s, the neoadjuvant and adjuvant administration of VAC
(vincristine, adriamycin, cyclophosphamide) improved the 5-year
survival of localized Ewing sarcoma to 50%, and the addition of
ifosfamide and etoposide in the 1980s further improved 5-year
survival to 70%. 31 Despite these improvements, 5-year survival for
patients with metastatic or recurrent Ewing sarcoma is less than
40%, and side effects of chemotherapy include infertility, heart
failure, and secondary malignancies such as leukemia. 24 , 33
Wide surgical resection with negative margins is the most
commonly used strategy to achieve local control. Historically, the
limits of resection were planned based on the prechemotherapy
MRI, but a recent study suggested that the level of bone and soft-
tissue resection can be safely determined based on the T1,
postchemotherapy MRI. 34 Patients whose resected tumors
demonstrate >95% necrosis have longer event-free survival than
those with 70% to 95% necrosis and <70% necrosis (75% versus 48%
versus 20%, respectively). 24 Advances in reconstructive techniques
combined with adjuvant treatments have greatly reduced the need
for amputation. 31
Unlike other bone sarcomas, Ewing sarcoma is radiosensitive, so
radiation is considered an acceptable alternative to wide resection
for local control. Radiation therapy can cause joint contractures,
pathologic fracture, muscle atrophy, and secondary malignancies; 24
therefore, it is typically reserved for situations when surgery would
be highly morbid and/or unlikely to achieve negative margins.
Trials comparing the outcomes of surgery versus radiation therapy
are scarce and subject to considerable selection bias because
surgery is the preferred treatment for resectable tumors, and
unresectable tumors (treated with radiation) are likely to have a
worse prognosis because of their size and location. Given the
paucity of evidence-based guidelines, the use of radiation therapy
must be considered on an individual basis when surgery would
have significant negative effects on the patient’s quality of life. 31

Prognosis
Approximately 75% of patients in whom Ewing sarcoma is
diagnosed have localized disease at the time of presentation. 24
Factors that portend worse prognosis in these patients include
pelvic or axial location, large size, elevated lactate dehydrogenase,
positive surgical margins, and age older than 8 years at
presentation. 23 , 30 Notably, pathologic fracture is not associated
with need for amputation or a worse overall outcome. 24 Five- and
10-year survival for patients with localized disease is 70% and 63%,
respectively, compared with a 5-year survival rate of less than 30%
for patients with clinically evident metastases at presentation.
Patients with isolated lung metastases fare be er than those with
bone or bone marrow metastases. Those who experience disease
relapse have an overall 5-year survival of 10%, with the worst
prognosis for patients with relapse before 2 years. 31 , 35

Emerging Therapies
The chemotherapeutic agents used for Ewing sarcoma have been
largely unchanged since the 1980s, with large clinical trials in the
past 15 years focusing on dose intensification strategies to push the
regimens to their tolerable limits. Although targeting the
pathognomonic oncogenic fusion protein seems to be an obvious
strategy, such treatments have proven elusive given the protein’s
lack of enzymatic activity, complex structure, and absence of a
surface antigen that is homogeneously expressed by and unique to
Ewing sarcoma tumor cells. Furthermore, inhibition of molecules
downstream from the fusion protein that are involved in processes
such as DNA repair and fibroblast has shown promise in in vitro
and pilot studies that has not translated into positive results in
larger clinical trials. 23 Notably, in a 2019 study, 10% of patients in
early trials of insulinlike growth factor 1 receptor inhibitors
responded well to treatment, but efforts to identify the subset of
patients who may respond have failed. 35 Immunotherapy likewise
has failed to demonstrate efficacy. 26 Clinical trials of novel
strategies are ongoing; for example, the transcription of EWRS1-
FLI1 is enhanced on binding to RNA helicase A, and a molecule
called TK216 was discovered that can disrupt this interaction. This
is currently being studied in a phase I clinical trial, and whether
this is shown to be an effective treatment remains to be seen. 35

Adamantinoma
Adamantinoma is a low-grade bone malignancy of epithelial origin
most commonly found in the anterior tibial cortex. It is managed
with wide surgical resection; neither chemotherapy nor radiation is
effective. Ten-year survival rates approach 90%, with the most
common site of metastasis being the lungs.

Epidemiology
Adamantinoma accounts for only 0.1% to 0.5% of all primary bone
tumors. 36 It is most commonly diagnosed in patients 25 to 35 years
of age, although it has been reported in both pediatric patients and
octogenarians alike. 36 , 37

Pathophysiology
The etiology of adamantinoma remains uncertain, although the
most widely accepted theory is displacement of the basal
epithelium of skin during embryologic development, which
undergoes malignant transformation within the bone. 36 It can be
challenging to diagnose osteofibrous dysplasia (OFD) to OFD-like
adamantinoma to classic adamantinoma and predict tumor
propensity to spontaneously regress or progress to malignancy. 36
Cytogenetic studies of adamantinoma have demonstrated extra
copies (trisomy) of chromosomes 7, 8, 12, 19, and/or 21. Trisomy of
chromosomes 7, 8, 12, and 21 have been identified in OFD,
supporting the notion of this diagnosis as a spectrum of related
entities. 36

Subtypes
Three types of adamantinoma exist: classic adamantinoma, OFD-
like adamantinoma, and Ewing-like adamantinoma. 36 Classic
adamantinoma is found in adult patients, most commonly in the
tibia, and has a more aggressive clinical course with the potential to
metastasize, whereas OFD-like adamantinoma is more common in
children and is thought to be relatively benign with only a locally
aggressive course and no malignant potential.

Presentation
Patients frequently present with insidious pain and sometimes
swelling over many years, most commonly in the lower leg.
Approximately 80% to 85% of cases are identified in the tibia with
ipsilateral disease to the fibula in 10% to 15% of cases. 38
Occasionally, anterior tibial bowing can be noted. 36 It can also arise
from other bones, including the humerus, ulna, femur, fibula,
radius, innominate bones, ribs, and spine. 36 There are no
associated systemic symptoms. Metastases have been reported to
lungs or other bones in up to 30% of cases. 37 , 39 Workup should
include radiographs and MRI of the entire bone, chest CT, and a
biopsy.

Imaging
Radiographs reveal multilocular, lytic, intracortical lesions with
sclerotic margins around focal radiolucencies; overall, this can be
described as a soap-bubble appearance 36 , 38 (Figure 9). MRI reveals
a bone lesion with possible soft-tissue extension that is hypointense
on T1-weighted imaging, hyperintense on T2-weighted imaging,
and contrast enhanced (Figure 10). OFD-like adamantinoma cannot
be distinguished from benign OFD radiographically (plain
radiographs or MRI).

Figure 9 A and B, AP and lateral radiographs left tibia/fibula with soap-bubble

changes throughout the bone.(Reproduced with permission from Callan AK,
Singleterry S, Czerniak BA, Selber JC, Satcher RL: Total tibial allograft
reconstruction for adamantinoma: A case report with 2-year follow-up. JBJS
Case Connect 2020;10[4]:e20.00046, Figure 1.)
 Figure 10 Magnetic resonance images of left tibia adamantinoma extending
from the tibial tubercle to distal tibial metaphysis.A, Coronal T2 tibia. B, Coronal
T2 fibula. C, Sagittal T2 tibia/fibula. D, Axial T2 tibial tubercle. E, Axial T2
tibia/fibula diaphysis.(Reproduced with permission from Callan AK, Singleterry
S, Czerniak BA, Selber JC, Satcher RL: Total tibial allograft reconstruction for
adamantinoma: A case report with 2-year follow-up. JBJS Case Connect
2020;10[4]:e20.00046, Figure 2.)

Histology
Classic adamantinoma has a biphasic appearance with nests of
malignant epithelial cells and osteofibrous stroma that stain
positive for keratin 38 (Figure 11). The neoplastic cell appears
similar to epithelial tissue under electron microscopy, with basal
lamina, desmosomes, and gap junctions. 37 All adamantinomas
stain positive for keratins, specifically basal epithelial cell keratin
and vimentin. 36 OFD-like adamantinoma reveals an OFD-like
background with osteoblast-rimmed woven bone and a background
of fibroblast-like spindle cells with sca ered cytokeratin staining. 37
Ewing-like adamantinoma is characterized by both epithelial cells
and small round blue cells that are positive for both cytokeratin
and a 11;22 translocation.
 Figure 11 Photomicrograph showing tubules interconnected and solid nests of
tumor cells in a fibroblastic stroma, magnification 100×.(Reproduced with
permission from Schwarzkopf E, Tavarez Y, Healey JH, Hameed M, Prince DE:
Adamantinomatous tumors: Long-term follow-up study of 20 patients treated at a
single institution. J Surg Oncol 2020;122[2]:273-282, Figure 2.)

Current Treatment
Adamantinoma is managed with wide surgical excision and limb
reconstruction. 36 , 37 Frequently, intercalary allografts can provide
excellent long-term results. Other options for reconstruction
include endoprosthesis, osteoarticular allograft, or allograft
prosthetic composites. Amputation is rarely indicated.
Adamantinoma is a relatively indolent tumor; accordingly,
chemotherapy or radiation therapy has not been effective. If
metastatic disease occurs, surgical resection of metastases is the
mainstay of treatment.
Management of OFD-like adamantinoma remains controversial.
If the condition is diagnosed in childhood, regression is common
by puberty. Observation or intralesional cure age is usually
sufficient. 36 Surveillance is recommended in case more aggressive
surgical resection is required. Ewing-like adamantinoma is typically
managed similar to Ewing sarcoma, with chemotherapy and
surgical resection. 36

Prognosis
Patients can expect overall survival of up to 98.8% at 5 years and
91.5% at 10 years following wide surgical resection. 39 Local
recurrences are reported in up to 32% of patients and found more
commonly in patients with positive surgical margins. 39

Chordoma
Chordomas are slow-growing malignant neoplasms derived from
notochordal tissue, most commonly in the axial skeleton of adults.
They are locally aggressive with high rates of local recurrence. Wide
surgical resection is the treatment of choice, although radiation
may be used for additional local control. Distant metastasis is less
common (up to 43%) than local recurrence (ranging from 19% to
85% depending on the margins obtained at index surgery). 40
Morbidity and mortality remain high especially when initial wide
resection is not achieved. Cytotoxic chemotherapy is ineffective in
chordoma; salvage therapy for recurrent and metastatic disease
relies on molecular targeted therapies.

Epidemiology
Chordomas are rare, with an incidence of 0.08/1,000,000, although
they are the most common malignant primary tumor of the spine
and sacrum. Sacrococcygeal and skull base lesions are the most
frequent, followed by cervical and lumbar spine. Diagnosis is
usually made in the fifth to sixth decade of life, though any age can
be affected. There is a predilection for males, and most patients are
White or of Hispanic ethnicity. 41 , 42

Presentation
Although gluteal or low back pain can be a presenting symptom,
chordomas may not be identified until they cause neurologic
compression with radiculopathy, bowel/bladder dysfunction,
headaches, or cranial nerve palsies. Distant metastasis is rare,
especially at initial presentation. After histologic diagnosis, staging
consists of MRI of the entire spine and CT of the chest, abdomen,
and pelvis.

Imaging
Early radiographic findings can be subtle. Chordomas appear as
lytic lesions centered in the vertebral body. Larger, expansile
lesions significantly obscure the neuroforaminal and sacral
segmental anatomy and may be calcified. MRI is essential in
making the diagnosis and planning treatment. The differential
diagnosis based on location includes intraosseous benign
notochordal tumors, chondrosarcoma, Ewing sarcoma, and giant
cell tumor of bone. In contrast to intraosseous benign notochordal
tumors, which are sclerotic and rarely expand beyond the cortex,
chordomas and other neoplasms on the differential often expand
through the cortex of the vertebral body.

Histology
There are four subtypes of chordomas: classic, chondroid,
dedifferentiated, and poorly differentiated. Chondroid chordomas
have a matrix that mimics hyalin cartilage and a predilection for the
skull base. Dedifferentiated chordoma includes both classic-
appearing areas intermixed with high-grade sarcoma. Poorly
differentiated chordomas lack any classic chordoma morphology
and loss of SMARCB1/INI1. Classic chordoma, the most common
type, is characterized by a myxoid intercellular background. The
cellular component is made up of large ovoid cells with vacuolated
or clear cytoplasm (called physaliferous cells when multiple
vacuoles surround a central nucleus) arranged in nests or chords
against the myxoid background. Nuclear pleomorphism and
occasional mitotic figures help to differentiate from intraosseous
benign notochordal tumors. Immunostaining includes positivity for
S-100 and epithelial markers. T-Brachyury is a transcription factor
expressed in fetal notochord that is highly specific for chordomas.
Research to determine the prognostic significance and potential
targetability of this transcription factor is ongoing. 43

Current Treatment
Wide resection is associated with lower rates of recurrence and
prolonged survival when compared with intralesional or marginal
surgeries. 40 , 44 In addition to surgery, radiation therapy has been
used as an adjuvant treatment or as independent definitive therapy
when the morbidity of definitive surgery is unacceptable. The role
of radiation therapy in the se ing of resectable primary tumors is
controversial. A large retrospective study from 2019 reported that
not receiving radiation is an independent risk factor for relapse. 45
However, a similar large, multi-institutional retrospective study
published in 2019 reported that radiation with mean dose of 61.8 ±
10.9 Gy was not associated with local recurrence, metastasis, or
disease-specific survival, but was associated with increased wound
complications. 46 In the adjuvant, neoadjuvant, and definitive
treatment se ings, radiation modalities continue to evolve. Proton
therapy can be used to allow dose escalation with favorable toxicity.
47
Stereotactic radiosurgery is another modality demonstrating
promising early results, 48 whereas carbon ion therapy does not
appear to offer significant improvements. 49
Prognosis
Median overall survival is 7.7 years, with age-standardized 5-, 10-,
and 20-year survival reported to be 72%, 48%, and 31%, respectively.
41
Metastasis usually occurs late in the disease course and portends
a very poor prognosis.

Emerging Therapies
In the absence of effective cytotoxic chemotherapy or other
systemic treatments, efforts have been directed toward developing
targeted therapies for locally recurrent and metastatic disease.
Immune therapies directed at platelet-derived growth factor
receptor, epidermal growth factor receptor, and vascular
endothelial growth factor receptor have been studied; 50 in
particular, the platelet-derived growth factor receptor inhibitor
imatinib has shown clinical benefit in a phase II study. 51 Although
initial trials of brachyury vaccine trials have not demonstrated
significant benefit, this remains the subject of ongoing trials. 43
Additionally, a portion of chordomas have loss of integrase
interactor 1 allowing for targeted therapy with promising early
results. 52

Chondrosarcoma
Chondrosarcoma is the second most common primary malignancy
of bone, occurring most frequently in the proximal long bones,
pelvis, and ribs of older adults. Chondrosarcomas present unique
diagnostic and treatment challenges because cartilaginous
neoplasms have a wide range of biologic behavior, from benign
latent lesions to rapidly progressive malignancies with high
metastatic potential. Histologic grade directly correlates with
biologic behavior, prognosis, and guiding treatment. 53 , 54 Using
clinical presentation, radiologic, and histologic findings to predict
biologic behavior is essential in guiding treatment; however, this
can be challenging, even with the benefit of experienced
radiologists and pathologists and robust communication with the
clinical team. Chondrosarcomas can arise de novo or emerge from
within benign precursors such as enchondroma or
osteochondroma. The difference between benign and low-grade
lesions can be very subtle on imaging as well as histology.
Furthermore, cartilage tumors are notorious for heterogeneity; as
such, focal tissue sampling (ie, biopsy) often underestimating the
true grade. 55

Epidemiology
Chondrosarcomas are rare entities with an incidence of 1/200,00 per
year. 56 Chondrosarcomas occur most often in patients older than 50
years, less frequently in young adults, and extremely rarely in
children. Extremities are the most common sites, especially the
proximal femur and proximal humerus. Forty percent of cases arise
in the pelvis or ribs, with the ilium representing the most common
truncal site followed by ribs. Acral involvement is rare. 57

Presentation
The most common symptoms of chondrosarcoma include focal,
dull aching pain, often present at night, and localized swelling in
cases with bony expansion or soft-tissue extension. The presence of
these symptoms can be helpful in differentiating chondrosarcomas
from benign cartilaginous lesions, which are often asymptomatic
and found incidentally. However, the symptoms of a low-grade
lesion may be subtle, long-standing, coexisting, and difficult to
distinguish from other benign etiologies of musculoskeletal pain.
Local expansion in deep locations such as the pelvis can progress
undetected, resulting in larger, more advanced tumors at the time
of diagnosis.

Imaging
Because of the frequency of incidental cartilaginous lesions and
microscopic heterogeneity limiting the utility of biopsy, careful
evaluation of imaging plays an essential role in the diagnosis and
management of these neoplasms. Plain radiographs are essential
and offer significant insight into the diagnosis and biologic
behavior. The common, medullary-based metadiaphyseal lytic
lesions with evenly distributed ring and arc calcifications typical of
enchondroma can be difficult to distinguish from low-grade
chondrosarcoma. Higher grade features such as endosteal
scalloping, cortical expansion, cortical destruction, periosteal
reaction, confluent areas of calcification, and larger lytic regions
with permeative borders and extraosseous calcification warrant
further investigation with advanced imaging. MRI is the best test
for characterizing the tumor and visualizing its extent; features of
higher grade lesions include central areas of increased T1 signal
intensity, loss of lobulated structure and internal fat, soft-tissue
extension, and increased peritumoral edema. CT may also be useful
in investigating subtleties in the tumorhost bone interface such as
endosteal scalloping and cortical breakthrough. 58 , 59

Subtypes (including Histology, Treatment,

and Prognosis)
Most chondrosarcomas (90%) are designated primary conventional
chondrosarcomas, with 80% being low to intermediate grade
(G1/G2) and the remaining 20% classified as high grade (G3). 53
These medullary-based tumors are classified according to the
World Health Organization as grade 1, 2, or 3 based primarily on
the histologic findings. Moderate cellularity, hyperchromatic
uniform nuclei, and no mitotic activity are characteristics of grade 1
chondrosarcoma. An infiltrative, bone-entrapping growth pa ern
helps in differentiating grade 1 chondrosarcoma from
enchondroma. Grade 2 chondrosarcomas have increased cellularity,
with enlarged round or oval nuclei and prominent nucleoli. Grade 3
chondrosarcomas have nuclear pleomorphism and atypia with
mitotic figures easily identifiable. This classification system
correlates directly with biologic behavior and helps guide
appropriate treatment. It is generally accepted that grade 1 lesions
in the extremity can be managed in an intralesional fashion with
acceptable local recurrence rates and minimal risk for metastasis, 60
whereas grade 2 and 3 tumors are managed with wide resection. In
the pelvis, some data support intralesional treatment for grade 1
pelvic chondrosarcoma. 61 However, because of higher local
recurrence as well as the possibility of sampling error and
dedifferentiation, many advocate for negative margin resection of
even grade 1 pelvic chondrosarcoma. Studies fairly consistently
report that margin status affects local recurrence, although data are
mixed in regard to its effect on overall survival. 54 , 60 Ten-year
survival rates for grade 1, 2, and 3 chondrosarcoma are reportedly
between 83% to 95%, 64% to 86%, and 29% to 55%, respectively. 53 , 62
- 64

In addition to conventional types, more rare subtypes of

chondrosarcoma include dedifferentiated chondrosarcoma,
mesenchymal chondrosarcoma, clear cell chondrosarcoma,
periosteal or juxtacortical chondrosarcoma, and secondary
chondrosarcomas.
Dedifferentiated chondrosarcoma is characterized by the
juxtaposition of well-differentiated cartilage tumor with a high-
grade sarcomatous component, in which the cartilaginous
architecture is lost. Rapid clinical and radiographic progression is
common with frequent pathologic fracture. Prognosis is very poor,
with survival reported at 47.7% and 11.3% at 1 and 5 years,-
respectively. 65 Surgery with wide resection is the standard of care.
Chemotherapy with both cisplatin-doxorubicin-based and
ifosfamide-based regimens have been used with moderate effects
on progression-free survival. 66 , 67
Mesenchymal chondrosarcoma is characterized by areas of
cartilaginous differentiation admixed with solid cellular areas of
small, round or spindled primitive mesenchymal cells. In contrast
to conventional chondrosarcomas, mesenchymal sarcomas
commonly occur in young adults in the second to third decade of
life and have a propensity for the axial skeleton and craniofacial
bones. These are highly aggressive tumors with 10% to 15%
presenting with metastatic disease and 1- and 5-year survival rates
of 76.1% and 37.6%, respectively. 65 , 68 Wide-margin resection is the
treatment of choice, although data exist to support the routine use
of chemotherapy and radiation therapy if surgical margins are close
or positive. 68 - 70
Clear cell chondrosarcoma is a unique variant identifiable
histologically by sheets of cells with clear, glycogen-containing
cytoplasm and centrally located nuclei intermixed with trabeculae
of woven bone. It is distinguished clinically by its predilection for
the epiphysis of long bones of middle-aged adults.
Radiographically it often appears as a well-defined lucent lesion
abu ing the articular surface, hence resembling chondroblastoma
or giant cell tumor of bone. Although it is often described as having
low-grade or indolent behavior, it has metastatic potential and is
managed with wide resection. Overall survival is reported to be 80%
at 10 years, 71 and metastasis may occur late, at a median time of 8
years after initial diagnosis. 72
Periosteal chondrosarcoma, formerly called juxtacortical
chondrosarcoma, is an extremely rare subtype arising on the
surface of the diaphysis or metaphysis of long bones. Histologically
they appear similar to conventional chondrosarcomas, but their
clinical behavior is less aggressive than other nonconventional
subtypes, with metastasis present at presentation in only 2.1% of
patients compared with 19.8% in dedifferentiated chondrosarcoma
and median survival of 97 months compared with 11 months in
dedifferentiated chondrosarcoma. 65
Secondary chondrosarcomas are histologically indistinguishable
from their primary counterparts but arise from within a preexisting
benign lesion. The most typical presentation is new pain or growth
of a benign cartilage tumor after skeletal maturity. Common
precursor lesions include osteochondromas or enchondromas,
either solitary or associated with syndromes (multiple hereditary
exostoses, Ollier disease, or Maffucci syndrome). Lifetime risk of
malignant transformation of a solitary osteochondroma is reported
to be between 0.4% and 2% 73 with a cartilage cap greater than 2 cm
in an adult being predictive of malignant transformation. 74
Multiple hereditary exostoses is inherited in an autosomal
dominant fashion with most cases having germline loss of function
mutation I neither EXT 1 or EXT 2. These patients carry a lifetime
risk of malignant transformation from 5% to 25%. Most secondary
chondrosarcomas arising from osteochondromas occur in the
pelvis, are low to intermediate grade, and have a good prognosis
when managed appropriately, with 5- and 10-year mortality rates of
1.6 and 4.9 for solitary osteochondromas and 10.9 and 23.9 for
patients with multiple hereditary exostosis, respectively. 73
Although the risk of malignant transformation in solitary
enchondroma is very low, the risk of malignant transformation of
cartilage tumors is 25% to 40% in patients with Ollier disease and
50% in those with Maffucci syndrome, 75 , 76 requiring surveillance
and careful a ention to new symptoms.

Current Treatments
Conventional chondrosarcomas are not responsive to cytotoxic
chemotherapy or radiation therapy, with surgery alone being the
treatment of choice for localized tumors. Grade I chondrosarcomas,
particularly in the extremity, are treated with extended intralesional
cure age; this is substantially less morbid than wide resection with
a relatively low risk of disease recurrence or progression. Treatment
for grade II or III conventional chondrosarcomas is wide-margin
resection because of high risk of local recurrence and lung
metastasis. Radiation therapy is used as an adjuvant for high-grade
primary tumors that are unresectable or resected with positive
margins. Cytotoxic chemotherapy is used in the management of
metastatic disease, and as an adjuvant for dedifferentiated and
mesenchymal subtypes in select patients. Ongoing investigations
are evaluating the role of immunotherapy and molecular targeted
medications in the salvage se ing for all subtypes.

Emerging Therapies
Given that standard chemotherapy is ineffective for conventional
chondrosarcoma, there is great need for novel therapeutic agents,
particularly for management of unresectable, recurrent, and
metastatic disease. Multiple studies are evaluating known immune
checkpoint inhibitors and antiangiogenic agents. 76 Isocitrate
dehydrogenase inhibitors have been the subject of much focus
because of the relatively high rate of isocitrate dehydrogenase
mutations in chondrosarcoma. A 2020 phase I clinical trial of an
oral isocitrate dehydrogenase 1 inhibitor demonstrated minimal
toxicity and durable disease control with short-term follow-up.
Phase II trials are currently evaluating monotherapy and combined
targeted molecular and cytotoxic chemotherapies. 77

Summary
Bone sarcomas are rare, and timely diagnosis with referral to a
designated multidisciplinary sarcoma center is essential to avoid
inappropriate procedures complicating future care, as well as to
ensure that patients have the opportunity to benefit from evolving
treatments. As many patients continue to develop metastatic and
recurrent disease, there remains an urgent need to develop more
effective therapies for this rare and heterogeneous subset of
cancers.

Key Study Points

It is important to formulate a differential diagnosis of bone sarcomas.
The specific workup should be understood when evaluating possible sarcomas of
bone.
The surgeon should know the roles of surgery, chemotherapy, and radiation therapy
for managing various bone sarcomas.
Annotated References
1. Anderson ME: Update on survival in osteosarcoma. Orthop Clin
North Am 2016;47(1):283-292.
2. Choi JH, Ro JY: The 2020 WHO Classification of tumors of bone:
An updated review. Adv Anat Pathol 2021;28(3):119-138. The
authors discuss updates to the World Health Organization bone
tumors classification.
3. Mirabello L, Troisi RJ, Savage SA: Osteosarcoma incidence and
survival rates from 1973 to 2004: Data from the surveillance,
epidemiology, and end results program. Cancer 2009;115(7):1531-
1543.
4. Key Statistics for Osteosarcoma. American Cancer Society. 2020.
Available from:
h ps://www.cancer.org/cancer/osteosarcoma/about/key-
statistics.html. Accessed December 6, 2022. Osteosarcoma
statistics are presented.
5. O aviani G, Jaffe N: The epidemiology of osteosarcoma. Cancer
Treat Res 2009;152:3-13.
6. Pan Y, Chen D, Hu T, Lv G, Dai Z: Characteristics and prognostic
factors of patients with osteosarcoma older than 60 years from
the SEER database. Cancer Control 2019;26(1):1073274819888893.
This study described demographic features and treatment
outcomes in patients with osteosarcoma older than 60 years.
7. Hameed M, Mandelker D: Tumor syndromes predisposing to
osteosarcoma. Adv Anat Pathol 2018;25(4):217-222.
8. Miller CW, Aslo A, Won A, Tan M, Lampkin B, Koeffler HP:
Alterations of the p53, Rb and MDM2 genes in osteosarcoma. J
Cancer Res Clin Oncol 1996;122(9):559-565.
9. Mirabello L, Zhu B, Koster R, et al: Frequency of pathogenic
germline variants in cancer-susceptibility genes in patients with
osteosarcoma. JAMA Oncol 2020;6(5):724-734. This study
examined the germline architecture of patients with
osteosarcoma.
10. Chen Z, Guo J, Zhang K, Guo Y: TP53 mutations and survival in
osteosarcoma patients: A meta-analysis of published data. Dis
Markers 2016;2016:4639575.
11. Roberts RD, Lizardo MM, Reed DR, et al: Provocative questions
in osteosarcoma basic and translational biology: A report from
the Children’s Oncology Group. Cancer 2019;125(20):3514-3525.
This review explores several questions regarding the basic
science of osteosarcoma and what is known to date.
12. Hauben EI, Weeden S, Pringle J, Van Marck EA, Hogendoorn
PC: Does the histological subtype of high-grade central
osteosarcoma influence the response to treatment with
chemotherapy and does it affect overall survival? A study on 570
patients of two consecutive trials of the European Osteosarcoma
Intergroup. Eur J Cancer 2002;38(9):1218-1225.
13. Smeland S, Bielack SS, Whelan J, et al: Survival and prognosis
with osteosarcoma: Outcomes in more than 2000 patients in the
EURAMOS-1 (European and American Osteosarcoma Study)
cohort. Eur J Cancer 2019;109:36-50. This is a randomized phase III
trial that investigated treatment optimization based on response
to neoadjuvant chemotherapy.
14. Biermann JS, Chow W, Reed DR, et al: NCCN guidelines
insights: Bone cancer, version 2.2017. J Natl Compr Canc Netw
2017;15(2):155-167.
15. Rougraff BT, Simon MA, Kneisl JS, Greenberg DB, Mankin HJ:
Limb salvage compared with amputation for osteosarcoma of the
distal end of the femur. A long-term oncological, functional, and
quality-of-life study. J Bone Joint Surg Am 1994;76(5):649-656.
16. Ferguson PC, McLaughlin CE, Griffin AM, Bell RS, Deheshi BM,
Wunder JS: Clinical and functional outcomes of patients with a
pathologic fracture in high-grade osteosarcoma. J Surg Oncol
2010;102(2):120-124.
17. O aviani G, Robert RS, Huh WW, Jaffe N: Functional,
psychosocial and professional outcomes in long-term survivors of
 lower-extremity osteosarcomas: Amputation versus limb salvage.
Cancer Treat Res 2009;152:421-436.
18. Isakoff MS, Bielack SS, Mel er P, Gorlick R: Osteosarcoma:
Current treatment and a collaborative pathway to success. J Clin
Oncol 2015;33(27):3029-3035.
19. Errani C, Longhi A, Rossi G, et al: Palliative therapy for
osteosarcoma. Expert Rev Anticancer Ther 2011;11(2):217-227.
20. Jackson TM, Bi man M, Granowe er L: Pediatric malignant
bone tumors: A review and update on current challenges, and
emerging drug targets. Curr Probl Pediatr Adolesc Health Care
2016;46(7):213-228.
21. Davis LE, Bolejack V, Ryan CW, et al: Randomized double-blind
phase II Study of Regorafenib in patients with metastatic
osteosarcoma. J Clin Oncol 2019;37(16):1424-1431. The authors
determined that regorafenib should be considered a treatment
option for patients with relapsed metastatic osteosarcoma.
22. Ewing J: Classics in oncology. Diffuse endothelioma of bone.
James Ewing. Proceedings of the New York Pathological Society,
1921. CA Cancer J Clin 1972;22(2):95-98.
23. Riggi NSM, Stamenkovic I: Ewing’s sarcoma. N Engl J Med
2021;384(2):154-164. This article discusses the clinical
presentation, pathogenesis, and experimental therapies for
Ewing sarcoma.
24. Maheshwari AV, Cheng EY: Ewing sarcoma family of tumors. J
Am Acad Orthop Surg 2010;18(2):94-107.
25. Burchill S: Ewing’s sarcoma: Diagnostic, prognostic, and
therapeutic implications of molecular abnormalities. J Clin Pathol
2003;56(2):96-102.
26. Hesla ACPA, Papakonstantinou A, Tsagkovis P: Current status
of management and outcome for patients with Ewing sarcoma.
Cancers (Basel) 2021;13(6):1202. This review covers the clinical
presentation, pathogenesis, and management for Ewing sarcoma.
27. Abboud A, Masrouha K, Saliba M, et al: Extraskeletal Ewing
sarcoma: Diagnosis, management and prognosis. Oncol Le
2021;21(5):354. This review discusses the clinical management
and prognosis of extraskeletal Ewing sarcoma.
28. Galyfos G, Karan ikos G, Kavouras N, Sianou A, Palogos K,
Filis K: Extraosseous Ewing sarcoma: Diagnosis, prognosis and
optimal management. Indian J Surg 2016;78(1):49-53.
29. Fletcher C: WHO Classification of Tumours Editorial Board: Soft
Tissue and Bone Tumors, ed 5. IARC Publications, 2020. This text
provides a comprehensive discussion on the diagnosis and
classification of tumors.
30. Campbell KM, Shulman DS, Grier HE, DuBois SG. Role of bone
marrow biopsy for staging new patients with Ewing sarcoma: A
systematic review. Pediatr Blood Cancer 2021;68(2):e28807. This
systematic review discusses the incidence of bone marrow
metastases and the role of bone marrow biopsy and FDG-PET in
the workup of Ewing sarcoma.
31. Zöllner SK, Amatruda JF, Collaud S, et al: Ewing sarcoma-
diagnosis, treatment, clinical challenges and future perspectives.
J Clin Med 2021;10(8):1685. This review covers the clinical
presentation, pathogenesis, and experimental therapies for
Ewing sarcoma.
32. Ng T, O’Sullivan M, Pallen C, et al: Ewing sarcoma with novel
translocation t(2;16) producing an in-frame fusion of FUS and
FEV. J Mol Diagn 2007;9(4):459-463.
33. Just MA, Van Mater D, Wagner LM: Receptor tyrosine kinase
inhibitors for the treatment of osteosarcoma and Ewing sarcoma.
Pediatr Blood Cancer 2021;68(8):e29084. This review describes
phase II trials for receptor tyrosine kinase inhibitors in recurrent
osteosarcoma and Ewing sarcoma.
34. Thévenin-Lemoine C, Destombes L, Vial J, et al: Planning for
bone excision in Ewing sarcoma: Post-chemotherapy MRI more
accurate than pre-chemotherapy MRI assessment. J Bone Joint
Surg Am 2018;100(1):12-20.
35. Van Mater D, Wagner L: Management of recurrent Ewing
sarcoma: Challenges and approaches. OncoTargets Ther
2019;12:2279-2288. This review covers salvage chemotherapies for
recurrent Ewing sarcoma.
36. Jain D, Jain VK, Vasishta RK, Ranjan P, Kumar Y:
Adamantinoma: A clinicopathological review and update. Diagn
Pathol 2008;3:8.
37. Schwarzkopf E, Tavarez Y, Healey JH, Hameed M, Prince DE:
Adamantinomatous tumors: Long-term follow-up study of 20
patients treated at a single institution. J Surg Oncol
2020;122(2):273-282. This case series describes 20 patients with
adamantinomas.
38. Callan AK, Singleterry S, Czerniak BA, Selber JC, Satcher RL:
Total tibial allograft reconstruction for adamantinoma: A case
report with 2-year follow-up. JBJS Case Connect
2020;10(4):e20.00046. This case report describes resection of the
entire tibia and reconstruction with an allograft prosthetic
composite.
39. Aytekin MN, Öztürk R, Amer K: Epidemiological Study of
Adamantinoma from US Surveillance, Epidemiology, and End
Results Program: III Retrospective analysis. J Oncol
2020;2020:2809647. This was a database study describing patients
with adamantinomas.
40. Ruggieri P, Angelini A, Ussia G, Montalti M, Mercuri M:
Surgical margins and local control in resection of sacral
chordomas. Clin Orthop Relat Res 2010;468(11):2939-2947.
41. Smoll NR, Gautschi OP, Radovanovic I, Schaller K, Weber DC:
Incidence and relative survival of chordomas: The standardized
mortality ratio and the impact of chordomas on a population.
Cancer. 2013;119(11):2029-2037.
42. McMaster ML, Goldstein AM, Bromley CM, Ishibe N, Parry DM:
Chordoma: Incidence and survival pa erns in the United States,
1973-1995. Cancer Causes Control 2001;12(1):1-11.
43. DeMaria PJ, Bilusic M, Park DM, et al: Randomized, double-
blind, placebo-controlled Phase II Study of Yeast-Brachyury
Vaccine (GI-6301) in combination with standard-of-care
radiotherapy in locally advanced, Unresectable Chordoma.
Oncologist 2021;26(5):e847-e858. This randomized controlled trial
investigated a brachyury targeting yeast vaccine in patients with
chordoma.
44. Fujiwara T, Tsuda Y, Stevenson J, Parry M, Jeys L: Sacral
chordoma: Do the width of surgical margin and the use of
photon/proton radiotherapy affect local disease control? Int
Orthop 2020;44(2):381-389. This case series demonstrated the
effect of radiation therapy and surgical margins on outcomes in
patients with chordoma.
45. van Wulfften Palthe ODR, Tromp I, Ferreira A, et al: Sacral
chordoma: A clinical review of 101 cases with 30-year experience
in a single institution. Spine J 2019;19(5):869-879. This case series
described 131 patients with sacral chordomas.
46. Houdek MT, Rose PS, Hevesi M, et al: Low dose radiotherapy is
associated with local complications but not disease control in
sacral chordoma. J Surg Oncol 2019;119(7):856-863. This
multicenter case series showed that radiation therapy for
chordomas was associated with local complications.
47. Palm RF, Oliver DE, Yang GQ, Abuodeh Y, Naghavi AO,
Johnstone PAS: The role of dose escalation and proton therapy in
perioperative or definitive treatment of chondrosarcoma and
chordoma: An analysis of the National Cancer Data Base. Cancer
2019;125(4):642-651. This database study demonstrated the effect
of dose escalation and proton therapy.
48. Jin CJ, Berry-Candelario J, Reiner AS, et al: Long-term outcomes
of high-dose single-fraction radiosurgery for chordomas of the
spine and sacrum. J Neurosurg Spine 2019; October 18 [Epub
ahead of print]. This case series described outcomes in patients
with high-dose single-fraction radiosurgery.
49. Bostel T, Ma ke M, Nicolay NH, et al: High-dose carbon-ion
based radiotherapy of primary and recurrent sacrococcygeal
chordomas: Long-term clinical results of a single particle therapy
center. Radiat Oncol 2020;15(1):206. This case series investigated
outcomes following carbon-ion-based radiotherapy.
50. Meng T, Jin J, Jiang C, et al: Molecular targeted therapy in the
treatment of chordoma: A systematic review. Front Oncol
2019;9:30. This systematic review investigated molecular targeted
therapies for chordoma.
51. Stacchio i S, Longhi A, Ferraresi V, et al: Phase II study of
imatinib in advanced chordoma. J Clin Oncol 2012;30(9):914-920.
52. Chi S, Fouladi M, Shukla N, et al: Abstract A175: Phase 1 study
of the EZH2 inhibitor, tazemetostat, in children with relapsed or
refractory INI1-negative tumors including rhabdoid tumors,
epithelioid sarcoma, chordoma, and synovial sarcoma. Mol Cancer
Ther 2018;17(1 suppl):A175.
53. van Praag Veroniek VM, Rueten-Budde AJ, Ho V, et al:
Incidence, outcomes and prognostic factors during 25 years of
treatment of chondrosarcomas. Surg Oncol 2018;27(3):402-408.
54. Donati D, El Ghoneimy A, Bertoni F, Di Bella C, Mercuri M:
Surgical treatment and outcome of conventional pelvic
chondrosarcoma. J Bone Joint Surg Br 2005;87(11): 1527-1530.
55. Roitman PD, Farfalli GL, Ayerza MA, Muscolo DL, Milano FE,
Aponte-Tinao LA: Is needle biopsy clinically useful in
preoperative grading of central chondrosarcoma of the pelvis and
long bones? Clin Orthop Relat Res 2017;475(3):80.
56. Giuffrida AY, Burgueno JE, Koniaris LG, Gutierrez JC, Duncan
R, Scully SP: Chondrosarcoma in the United States (1973 to 2003):
An analysis of 2890 cases from the SEER database. J Bone Joint
Surg Am 2009;91(5):1063-1072.
57. Czerniak B: Dorfman and Czerniak’s Bone Tumors. Elsevier, 2016.
58. Douis H, Saifuddin A: The imaging of cartilaginous bone
tumours. II. Chondrosarcoma. Skeletal Radiol 2013;42(5):611-626.
59. Yoo HJ, Hong SH, Choi JY, et al: Differentiating high-grade from
low-grade chondrosarcoma with MR imaging. Eur Radiol
2009;19(12):3008-3014.
60. Fromm J, Klein A, Baur-Melnyk A, et al: Survival and prognostic
factors in conventional central chondrosarcoma. BMC Cancer
2018;18(1):849.
61. Chen X, Yu LJ, Peng HM, et al: Is intralesional resection suitable
for central grade 1 chondrosarcoma: A systematic review and
updated meta-analysis. Eur J Surg Oncol 2017;43(9):1718-1726.
62. Angelini A, Guerra G, Mavrogenis AF, Pala E, Picci P, Ruggieri
P: Clinical outcome of central conventional chondrosarcoma. J
Surg Oncol 2012;106(8):929-937.
63. Evans HL, Ayala AG, Romsdahl MM: Prognostic factors in
chondrosarcoma of bone: A clinicopathologic analysis with
emphasis on histologic grading. Cancer 1977;40(2):818-831.
64. Bjornsson J, McLeod RA, Unni KK, Ilstrup DM, Pritchard DJ:
Primary chondrosarcoma of long bones and limb girdles. Cancer
1998;83(10):2105-2119.
65. Amer KM, Munn M, Congiusta D, Abraham JA, Basu Mallick A:
Survival and prognosis of chondrosarcoma subtypes: SEER
database analysis. J Orthop Res 2020;38(2):311-319. This database
study described demographic and prognostic features of
chondrosarcoma subtypes.
66. Mitchell AD, Ayoub K, Mangham DC, Grimer RJ, Carter SR,
Tillman RM: Experience in the treatment of dedifferentiated
chondrosarcoma. J Bone Joint Surg Br 2000;82(1):55-61.
67. van Maldegem A, Conley AP, Rutkowski P, et al: Outcome of
first-line systemic treatment for unresectable conventional,
dedifferentiated, mesenchymal, and clear cell chondrosarcoma.
Oncologist 2019;24(1):110-116. This case series described the
outcomes of various chemotherapy regimens for
chondrosarcoma.
68. Frezza AM, Cesari M, Baumhoer D, et al: Mesenchymal
chondrosarcoma: Prognostic factors and outcome in 113 patients.
 A European Musculoskeletal Oncology Society study. Eur J Cancer
2015;51(3):374-381.
69. Cesari M, Bertoni F, Bacchini P, Mercuri M, Palmerini E, Ferrari
S: Mesenchymal chondrosarcoma. An analysis of patients treated
at a single institution. Tumori 2007;93(5):423-427.
70. Kawaguchi S, Weiss I, Lin PP, Huh WW, Lewis VO: Radiation
therapy is associated with fewer recurrences in mesenchymal
chondrosarcoma. Clin Orthop Relat Res 2014;472(3):856-864.
71. Klein A, Tauscher F, Birkenmaier C, et al: Clear cell
chondrosarcoma is an underestimated tumor: Report of 7 cases
and meta-analysis of the literature. J Bone Oncol 2019;19:100267.
This meta-analysis summarized outcomes in patients with clear
cell chondrosarcoma.
72. Itala A, Leerapun T, Inwards C, Collins M, Scully SP: An
institutional review of clear cell chondrosarcoma. Clin Orthop
Relat Res 2005;440:209-212.
73. Ahmed AR, Tan TS, Unni KK, Collins MS, Wenger DE, Sim FH:
Secondary chondrosarcoma in osteochondroma: Report of 107
patients. Clin Orthop Relat Res 2003;411:193-206.
74. Bernard SA, Murphey MD, Flemming DJ, Kransdorf MJ:
Improved differentiation of benign osteochondromas from
secondary chondrosarcomas with standardized measurement of
cartilage cap at CT and MR imaging. Radiology 2010;255(3):857-
865.
75. Verdegaal SH, Bovee JV, Pansuriya TC, et al: Incidence,
predictive factors, and prognosis of chondrosarcoma in patients
with Ollier disease and Maffucci syndrome: An international
multicenter study of 161 patients. Oncologist 2011;16(12):1771-
1779.
76. Schwar HS, Zimmerman NB, Simon MA, Wroble RR, Millar
EA, Bonfiglio M: The malignant potential of enchondromatosis. J
Bone Joint Surg Am 1987;69(2):269-274.
77. Tap WD, Villalobos VM, Cote GM, et al: Phase I study of the
mutant IDH1 inhibitor ivosidenib: safety and clinical activity in
patients with advanced chondrosarcoma. J Clin Oncol
2020;38(15):1693-1701. This is a phase I trial investigating an
isocitrate dehydrogenase 1 inhibitor in patients with advanced
chondrosarcoma.
C H AP T E R 7 3

Metastatic Tumors of Bone

Eugene S. Jang MD, MS, Lee Jae Morse MD, Andrew S.
Fang MD, FAAOS

Dr. Jang or an immediate family member serves as a board member, owner, officer, or committee
member of Accreditation Council for Graduate Medical Education. Neither of the following
authors nor any immediate family member has received anything of value from or has stock or
stock options held in a commercial company or institution related directly or indirectly to the
subject of this chapter: Dr. Morse and Dr. Fang.

ABSTRACT
Orthopaedic surgeons will encounter patients with metastatic
cancer throughout their careers, regardless of subspecialty. A
musculoskeletal complaint can represent the first sign of cancer in
a patient and lead to the diagnosis of metastatic disease. The
orthopaedic surgeon must be prepared to perform the initial
workup and treatment of a patient presenting with musculoskeletal
manifestations of metastatic or hematologic malignancy.
Familiarity with the epidemiology, etiology, and natural history of
metastatic disease is needed to systematically evaluate patients,
minimize the risk of pathologic fracture, and safely manage these
conditions.
Keywords: bone metastasis; hematologic malignancies; metastatic
carcinoma; pathologic fracture; prophylactic fixation

Introduction
The word metastasis, derived from the ancient Greek methistanai
(to change the se ing), was first used in 1829 to describe the
process by which malignancies migrate to other organs. Bone
metastases from carcinoma and hematologic malignancies together
are responsible for most destructive bone lesions in adults older
than 40 years. As advances in systemic cancer treatment strategies
continue to improve survival, the prevalence of patients with
metastatic tumors of bone will steadily increase. Pain from
disseminated cancers is by far the most common oncologic
presentation encountered in orthopaedics. Surgeons of all
subspecialties and practice se ings must therefore be familiar with
the pathophysiology of bone metastases, as well as the
fundamentals of the workup and initial treatment of these patients.

Etiologies for Metastatic Tumors of Bone

Epidemiology
The most common etiologies for a destructive bone lesion in adults
older than 40 years include metastatic carcinoma, multiple
myeloma, and lymphoma. Cancer is diagnosed in more than 1.7
million people in the United States every year; approximately 50%
of these individuals will have bony metastases at some point in
their disease course. 1 Additionally, metastatic disease is a
substantial driver of the overall economic burden of cancer,
accounting for 17% of the total yearly costs for cancer care in the
United States. 2 Because of ongoing improvements in systemic
therapy, patients are surviving longer with metastatic disease, and
the probability of encountering these patients continues to rise. Of
all the locations to which carcinomas tend to metastasize, bone is
the third most common, after the lung and liver. 3 Breast and
prostate cancer are the most frequent cause of metastatic bone
disease, together comprising approximately 80% of all cases, 4
followed by lung, kidney, and thyroid.
Anatomy and Biomechanics
Skeletal metastases most often occur in the axial skeleton (spine,
pelvis, and ribs) and proximal limb girdle (proximal femur and
proximal humerus). 4 Certain subtypes of cancer exhibit
predilections for specific locations, such as the proximal humerus
for renal cell carcinoma (Figure 1) and distal phalanges for lung
cancer. The location, size, number, and destructiveness of
metastatic lesions all affect the biomechanical properties of bone,
which in turn determine the risk of pathologic fracture.
Biomechanical studies have identified that lytic lesions in the
inferomedial femoral neck and the posteromedial proximal femur
near the lesser trochanter pose the highest fracture risk. 5 Several
CT-based scoring systems have been described to apply these
biomechanical and anatomic principles in predicting risk of
pathologic fracture. 6 Proceeding with prophylactic fixation in cases
of impending fracture is associated with improved quality of life
and survival benefit when compared with patients with completed
fractures.
 Figure 1 Renal cell carcinoma with a characteristic metastasis to the proximal
humerus in a 63-year-old woman.A, AP radiograph of the right shoulder showing
significant destruction of the proximal humerus. B, Cortical breakthrough of the
right proximal humerus lesion with a large soft-tissue component seen on
coronal T2 magnetic resonance image. C, AP radiograph shows wide resection
of right proximal humerus with cemented endoprosthetic replacement and
reverse total shoulder arthroplasty.

Pathophysiology of Metastasis of Bone

General Biologic Principles

Metastasis is a complex multistep process leading to a subset of the
malignant cells that develop the ability to evade host defenses,
cross the basement membrane, and intravasate into blood vessels.
Once circulating tumor cells appear in the bloodstream, they can
disseminate to distant sites. Only a small subset of these circulating
cells will produce the necessary proteins (integrins, cadherins, and
matrix metalloproteinases) to adhere to the vascular endothelium
and extravasate into end organs. The tumor cells will then use
growth factors (such as transforming growth factor beta, insulinlike
growth factor, fibroblast growth factor, and bone morphogenetic
protein) to proliferate, thus forming a metastatic focus. Tumor cells
do not directly destroy bone; they will instead express cytokines
that stimulate osteoblasts to secrete nuclear factor kappa-Β ligand
(RANKL), which signals osteoclast precursors to intensify
osteoclastogenesis and tips the balance of bone homeostasis toward
increased bone destruction. The RANKL pathway is central to the
pathophysiology of metastatic bone disease, which also makes it a
critical target for pharmacologic treatment. Both diphosphonates
(which directly inhibit osteoclasts) and denosumab (an anti-
RANKL monoclonal antibody) have been found to delay time to
skeletal-related events (SREs) such as pathologic fracture, spinal
cord compression, or need for radiation therapy/surgery. 7 - 9 These
drugs should thus be considered as part of the treatment plan for
any metastatic bone disease.

Disease-Specific Mechanisms
Breast cancer, the most common cause of metastatic bone disease
in women, can present with either lytic or blastic bone lesions. The
molecular pathways connecting RANKL to bone destruction are a
well-described mechanism in bone metastases. Breast cancer cells
respond to transforming growth factor beta, a naturally occurring
cytokine involved in bone turnover, by secreting parathyroid
hormone–related protein. Parathyroid hormone–related protein
from breast cancer cells serves as a potent activator of the RANKL
pathway, which results in increased osteoclastic activity. The
resulting bony destruction results in the release of more
transforming growth factor beta from bone cells, and this so-called
vicious cycle of bone destruction repeats (Figure 2).
 Figure 2 Illustration of the vicious cycle of bone destruction by metastatic
tumor cells using the receptor activator of nuclear factor kappa-Β ligand
(RANKL) pathway.Osteoblasts respond to molecular signals from metastatic
cells, including parathyroid hormone–related protein (PTHrP), by releasing
RANKL. This in turn increases osteoclastogenesis, which results in higher levels
of bone resorption. Transforming growth factor beta (TGF-β) is then released
from the bone during the process of bone resorption and activated by
osteoclasts, which further stimulates the production of PTHrP and the cycle
continues.(Adapted with permission from Bujis JT, van der Plum G: Osteopathic
cancers: From primary tumor to bone. Cancer Lett 2009;273[2]:177-193.) IGFs
= insulinlike growth factors, IL = interleukin, M-CSF = macrophage colony-
stimulating factor, OPG = osteoprotegerin

Prostate cancer is the most common cause of metastatic bone

disease in men, but pathologic fractures from prostate cancer are
relatively rare because of the classically osteoblastic nature of these
metastases. On a molecular level, the tendency for prostate cancer
metastases to be osteoblastic in nature can be explained by the
expression of endothelin-1 by prostate cancer cells, which directly
stimulates osteoblasts to produce bone.
Lung cancer metastases tend to be osteolytic, with parathyroid
hormone–related protein influencing the RANK/RANKL pathway
in a manner similar to breast cancer. Metastatic lung carcinoma has
a unique predilection for acral metastases (affecting skeletal sites
distal to the elbow and knee), which is uncommon in other
metastatic carcinomas.
Renal cell carcinoma is notable for its unique surgical
implications. Kidney cancers tend to overexpress growth factors
related to angiogenesis and the coagulation cascade: epidermal
growth factor receptor, vascular endothelial growth factor receptor,
and platelet-derived growth factor receptor. 10 These angiogenic
growth factors may explain the propensity for metastases of renal
cell carcinoma to be highly vascularized with the potential for
substantial blood loss during surgery. As a result, patients with
renal cell carcinomas may benefit from embolization before
surgical resection or stabilization, especially in locations such as
the pelvis. 11 Another unique consideration is that for solitary renal
metastases, surgical resection is associated with improved survival
when compared with cure age. 12 Moreover, variable response of
this tumor to radiation and cure age can lead to continued
progression of disease and eventual failure of fixation.
Thyroid cancers are typically localized, but metastasis
significantly lessens the likelihood of long-term survival. Follicular
thyroid carcinoma, the subtype most associated with metastasis to
bone, is characterized by overexpression of fibroblast growth factor
and vascular endothelial growth factor and thus tends to bleed
during surgical intervention.
Plasma cell malignancies (solitary plasmacytoma if a single lesion
or multiple myeloma if multiple sites) commonly occur in red
marrow–rich bones and present with lytic lesions causing pain,
anemia, and renal insufficiency. Similar to breast cancer and lung
cancer, plasma cell tumors create a RANKL-mediated cycle of bone
destruction and have a propensity for hemorrhage because of
vascular endothelial growth factor expression. Primary and
secondary lymphomas of bone have variable survival depending on
pathologic subtype, but are usually treatable. Both RANKL and
vascular endothelial growth factor play a role in the mechanism of
bony destruction in lymphoma.
Although the presentation and underlying biology of these
diseases can vary widely, the evaluation of the patient presenting
with multiple bony lesions concerning for metastatic disease has
been standardized over time. The diagnostic algorithm, which
includes history and physical examination, plain radiographs of the
affected bone, CT of the chest/abdomen/pelvis, laboratory studies,
whole-body bone scan, and biopsy of the most accessible tumor,
has been shown to yield the correct diagnosis and primary tumor
location in 85% of patients 13 (Figure 3).
 Figure 3 Flowchart depicting the evaluation of the patient with suspected bony
metastasis.The combination of history and physical examination, radiograph of
the involved bone, laboratory studies, CT of the chest/abdomen/pelvis, whole-
body bone scan, followed by biopsy of the most accessible lesion has been
shown to yield the correct diagnosis in 85% of cases.

Evaluation of the Patient With Suspected

Bony Metastasis

History and Physical Examination

Evaluating the patient with suspected skeletal metastasis begins
with a detailed history and physical examination. Patients often
present with progressive pain associated with weight bearing,
which should raise concern for an impending pathologic fracture.
Understanding the factors that elicit or exacerbate the pain is
critical; for example, persistent pain at rest may directly result from
the tumor itself, whereas pain related specifically to weight-bearing
activity suggests mechanical weakness of the bone caused by the
tumor. A detailed personal and family cancer history is helpful,
keeping in mind that patients with a previously localized cancer
may be in remission for decades before metastasis occurs
(particularly those with breast, renal, or prostate cancer). Asking
about other symptoms of primary cancers that commonly
metastasize to bone (eg, breast mass, frequent urination related to
enlarged prostate, fatigue, or unintentional weight loss), as well as
history of smoking, environmental exposures, or other risk factors
for cancer, may also be helpful. On examination, patients may have
an antalgic gait, guarding of the affected limb, or discomfort with
range of motion. Straight leg raise against gravity is a useful test of
the integrity of the peritrochanteric region; this maneuver places
more than twice a patient’s body weight across the hip joint, and
the absence of pain with this maneuver is relatively reassuring
against an impending pathologic fracture. 14

Imaging
Radiographs including the entire affected bone should be taken in
two orthogonal planes. Metastases from lung, thyroid, renal, and
gastrointestinal malignancies, as well most hematopoietic
malignancies, tend to be radiolucent on radiographs, indicating an
osteolytic process. Prostate and bladder cancers classically have a
calcified matrix, which appears radiopaque, indicating an
osteoblastic process, whereas breast cancers often have a mixed
osteolytic and osteoblastic appearance (Figure 4). CT of the chest,
abdomen, and pelvis is indicated in the workup for an unknown
primary because the most common primary cancers with a
propensity for bone are primarily within the chest (lung, breast),
retroperitoneum (renal), and pelvis (prostate). 13

Figure 4 Characteristic radiographic appearance of bony metastases.A,

Blastic appearance of metastatic prostate cancer. B, Lytic appearance of
metastatic thyroid cancer.

Technetium-99m phosphate bone scintigraphy is recommended

in the evaluation of an adult patient presenting with a destructive
bone lesion. Whole-body bone scans are used to perform a global
assessment of metastatic burden by detecting osteoblastic activity
throughout the skeleton. This can be helpful in distinguishing a
solitary lesion from a widely metastatic process, particularly when
evaluating a lesion of unknown etiology or staging a new diagnosis.
In diseases without a significant osteoblastic component to the
pathophysiology, or those in which false-negative rates with bone
scan may be significant (eg, multiple myeloma, renal cell
carcinoma), bone scans may be less useful. 15 In general, however,
bone scans are a relatively inexpensive and effective way to detect
other bone lesions that may necessitate weight-bearing
precautions, intervention for impending pathologic fracture,
alterations to patient positioning in the operating room, or special
considerations for anesthesiologists (ie, cervical spine disease
necessitating modified intubation techniques).
Although not part of the standard workup for an unknown
primary tumor, whole-body positron emission tomography
combined with CT has gained more traction recently, with the idea
that it can simultaneously assess for bone metastases and search
for the primary tumor with a single study. However, recent studies
suggest that although positron emission tomography/CT may be
useful in assessing overall metastatic burden, it does not
outperform standard evaluation for identification of the primary
cancer in patients with a skeletal metastasis of unknown primary. 16

Laboratory Studies
Laboratory studies can often assist with narrowing the differential
diagnosis. A complete blood count screens for anemia and unusual
distributions of cell populations, which can be seen in hematologic
malignancies. A complete metabolic panel will determine the levels
of serum calcium, alkaline phosphatase, and lactate dehydrogenase,
which are helpful in assessing for hypercalcemia (a potentially
serious sequelae of metastatic disease) and can also be of
prognostic value. 17 Erythrocyte sedimentation rate and C-reactive
protein are sensitive tests to rule out osteomyelitis, another
etiology of a destructive bone lesion in an adult. Finally, serum and
urine protein electrophoresis together are a highly sensitive and
specific combination of tests for the detection of multiple myeloma.
Serum protein electrophoresis (which detects the heavy chain
monoclonal proteins produced by myeloma) is simple to obtain and
detects approximately 80% of myelomas, whereas urine protein
electrophoresis provides additional sensitivity (10% to 15% of
myelomas produce only light chains, which can only be detected in
urine), and biopsy is often obtained for definitive confirmation of
the diagnosis. 18
 In addition to the aforementioned laboratory tests, some centers
may add thyroid-stimulating hormone and free thyroxine levels to
evaluate for thyroid cancer, as well as a urinalysis for the detection
of microscopic hematuria associated with renal cell cancer. There
are also novel laboratory tests in development with the goal to
detect the onset and progression of metastatic carcinoma to bone. 19

Biopsy
Any solitary bone lesion should be assessed with a biopsy unless
the radiographic findings are pathognomonic. A common error is
to assume that a bone lesion in a patient previously treated for
localized carcinoma represents metastatic disease and treat it as
such without a tissue diagnosis. In these scenarios, there is a 15%
probability that the lesion is a malignancy unrelated to the original
carcinoma. 20 Treating a bone lesion in a patient as a presumed
metastasis without performing an appropriate workup can lead to
catastrophic results. Reaming a bone and placing an intramedullary
device contaminates the length of the bone as well as the
surrounding soft tissues, with a theoretical risk of spreading of the
tumor cells systemically. To avoid this risk, an open biopsy or
needle biopsy (core biopsy) of the lesion should be performed
before surgical stabilization. If this is performed in the operating
room under the same anesthetic, the surgeon must be prepared to
wait for results of a frozen section and abort the case if the findings
are inconclusive or suggest a primary bone malignancy.

Nonsurgical Management

Natural History and Prognosis

Bone metastasis is common, with autopsy studies showing that
more than 70% of patients with prostate and breast carcinoma will
have bone metastasis at time of death. 21 In a 2019 study, bone
metastases from breast cancer were shown to have a favorable
prognosis when compared with other pa erns of spread, including
brain, lung, liver, and multisystem metastases. 22 With the high
prevalence of bone metastases, their comparatively low impact on
overall survival compared with other locations of metastasis, and
continued improvements in systemic therapy, osseous metastasis
has become a common feature in the natural history of carcinoma.
The development of tools to help predict the remaining life span of
patients with metastatic carcinoma has become an area of
significant interest. Studies have proposed numerous prognostic
models for patients with bone metastases from carcinoma (such as
the PATHFx clinical decision support tool) that can be helpful in
deciding on appropriate treatment. 23 - 26 These models generally
agree on the following as significant prognostic factors of survival:
presence of visceral metastasis, multiple metastases, presence of
pathologic fracture, and the type of primary tumor involved. 27 , 28

General Principles of Nonsurgical

Management
After thorough evaluation of a patient’s prognosis and goals of
care, a multidisciplinary approach to care is warranted. Many
patients with metastatic bone disease will be treated with a
combination of nonsurgical modalities, with surgical intervention
being reserved for those in whom nonsurgical measures fail or who
exhibit an imminent risk of pathologic fracture. Achieving pain
control is often more complex in patients with cancer than in other
conditions commonly managed by orthopaedic surgeons.
Multimodal analgesia, involvement of chronic pain specialists, and
judicious use of long-acting pain medications are all elements of a
pain control strategy, which should be considered in patients with
cancer. Walkers are commonly used to restricted weight bearing
and reduce fall risk to protect the lower extremities, whereas
bracing can play a role in protecting or helping pathologic fractures
to heal in the upper extremities.
Chemotherapy
Although cytotoxic chemotherapy is a mainstay in the management
of most disseminated cancers, some malignancies are amenable to
treatment with disease-specific agents. Breast cancer is managed
with a multitude of therapies depending on stage as well as the
hormonal characteristics of the tumor itself. The receptor positivity
status of breast cancer (including receptors for estrogen,
progesterone, and Her2-neu) has significant implications for
prognosis as well as therapeutic options. Similarly, prostate cancer
can be managed with androgen deprivation therapy via surgical
orchiectomy and/or hormone agonists/antagonists. Metastatic lung
and renal malignancies are particularly sensitive to growth factor
inhibitors, whereas patients with multiple myeloma can benefit
from chemotherapy (with the addition of stem cell transplantation
in younger, healthier patients). Lymphoma is typically quite
responsive to systemic chemotherapy.

Radiation Therapy
External beam radiation is a mainstay in the management of
metastatic tumors of bone, either as a definitive treatment or as an
adjunct to surgical intervention. The indications for radiation
therapy include pain, impending pathologic fracture, and
progressive neurologic symptoms. In a 2019 randomized trial,
single-fraction stereotactic body radiation therapy was found to be
noninferior to traditional multifraction external beam radiation in
terms of pain response. 29 If surgical stabilization of long bones is
performed, radiation should be given after wound healing is
complete. In this se ing, radiation should include the entire area
covered by the implant to improve local disease control and thereby
reduce the incidence of fixation failure. Radiopharmaceuticals may
be considered in cases where disseminated disease causes pain
refractory to other measures. Samarium-153 or strontium chloride-
89 radionuclides can deliver radiation to the entire skeleton (FDA-
approved for patients with painful skeletal metastases of diseases
such as prostate cancer and osteosarcoma), and iodine-131 is
commonly used to treat patients with metastatic thyroid cancer.
Additionally, a large thyroid metastasis can preclude effective
management of the primary cancer (ie, a sump effect), in which case
resection of that metastasis may be indicated.

Adjuvant Medical Therapy

Diphosphonates or denosumab should be considered for every
patient presenting with metastatic bone disease. Diphosphonates
function by inhibiting osteoclast activity and are used to decrease
the incidence of SREs in metastatic carcinoma. SREs are defined as
any pathologic fracture, clinically evident spinal cord compression,
necessity for radiation to bone (for pain or impending fracture), or
necessity for prophylactic surgery. Diphosphonates also help to
reduce pain associated with skeletal metastasis, with intravenous
zoledronic acid being most commonly used. The primary
complications associated with diphosphonates include
osteonecrosis of the jaw (although the risk of this complication is
significantly lower in modern diphosphonates), occasional
nephrotoxicity, and atypical femur fractures with prolonged use.
Denosumab, a human monoclonal antibody to RANKL, is an
alternative medication to prevent metastatic bone destruction. It is
given as a subcutaneous injection at intervals ranging from
monthly to every 3 months. Denosumab has been shown to be
superior to zoledronic acid in delaying time to SRE in metastatic
breast and lung cancers, noninferior to zoledronic acid in delaying
SREs for multiple myeloma and other carcinomas, and be er than
zoledronic acid for overall survival in lung cancer. 30 Hypocalcemia
and osteonecrosis of the jaw are rare complications encountered
with denosumab. It is contraindicated during pregnancy because of
the potential for fetal harm. Denosumab also appears to carry a risk
of atypical femur fractures in patients with metastatic disease, such
as those receiving denosumab or diphosphonates for osteoporosis.
31
The cost of the injections is high relative to diphosphonates;
however, a 2019 study concluded that despite the higher drug costs
associated with denosumab compared with zoledronate, the
reduction in SREs makes it a more cost-effective option than
diphosphonates overall. 32 Recent evidence also suggests that the
frequency of denosumab/disphosphonate use (monthly versus
every 3 months) may not significantly affect the efficacy of
preventing SREs, which would decrease the cost and improve the
convenience of these drugs. 33

Treatment Principles and Prediction of

Impending Pathologic Fracture
One of the most important roles of the orthopaedic surgeon in the
care of metastatic bone disease is assessing and minimizing the
risk of pathologic fractures. Patients with hepatobiliary
malignancies, renal cell carcinoma, and multiple myeloma are more
likely to present with completed pathologic fractures. 34 Almost 5%
of hospitalizations related to bone metastases involve fixation of a
completed pathologic fracture of a long bone, which results in a
longer inpatient stay and higher overall costs compared with
prophylactic fixation. Patients requiring fixation of a pathologic
fracture have been shown to have increased pain, worse early
functional outcomes, and poorer oncologic outcomes compared
with those who undergo prophylactic fixation before they fracture.
35
Postfracture stabilization is also associated with higher 30-day
major postoperative complication rates and longer hospital stays
compared with prophylactic stabilization. 36 Finally, there may also
be a survival benefit associated with prophylactic fixation compared
with internal fixation of a completed fracture, although a possible
selection bias exists whereby surgeons may more likely
prophylactically fix those patients with longer expected survival. 37
From a health care economics perspective, the direct costs
associated with managing an acute pathologic fracture are
significantly higher than with successful prophylactic fixation. 38
Although surgical stabilization is not without risks, including the
risks associated with intramedullary reaming of long bones, all of
these factors a est to the importance of detecting and managing
impending pathologic fractures prophylactically.
Several radiographic classifications can help stratify risk of
pathologic fracture in patients with long bone metastases. Mirels
score (Table 1), the most recognized of these systems, was
developed based on a retrospective review of 78 metastatic lesions
to help determine whether prophylactic fixation should be
recommended before initiating radiation therapy. 39 Follow-up
studies have found the Mirels criteria to be reproducible across
clinicians of varying experience levels. They are more sensitive (91%
overall sensitivity) than clinical judgment alone; however, their low
specificity (35%) could lead to overtreatment. 40

Table 1
Mirels Scoring System for Prediction of Pathologic Fracture in
Patients With Metastatic Bone Lesions

Factor Points
1 2 3
Radiographic appearance Blastic Mixed Lytic
Size (as proportion of shaft <⅓ ⅓ to ⅔ >⅔
diameter)
Site Upper Lower Pertrochanteric
extremity extremity
Pain Mild Moderate Functional
A total score of 8 or higher merits consideration for prophylactic fixation before radiation
therapy.
Reproduced with permission from Mirels H: Metastatic disease in long bones a proposed
scoring system for diagnosing impending pathologic fractures. Clin Orthop Relat Res
1989;249:256-264.

There may be a growing role for disease-specific scoring systems

in the future, especially as treatment strategies improve. A 2021
study of a novel multiple myeloma scoring system showed
improved sensitivity compared with the Mirels criteria in predicting
pathologic fracture. 41 There may also be a growing role for machine
learning, CT-based rigidity analysis and/or finite element analysis,
and net benefit analysis as more sophisticated assessments of
fracture risk and need for prophylactic treatment. 42 Despite the
litany of scoring systems available for predicting the risk of
pathologic fracture in the extremities, bone pain is likely the single
most important predictor, as demonstrated by longitudinal studies.
43

Surgical Management

Goals of Surgical Treatment

The primary goals of orthopaedic surgery in metastatic bone
disease are to relieve pain, improve function, restore skeletal
stability, and prevent or manage pathologic fractures. This can
include arthroplasty for symptomatic periarticular lesions or
stabilization of pathologic vertebral compression fractures;
however, most of the surgeries for skeletal metastases are
performed to manage and prevent pathologic long bone fractures.

General Principles of Surgery for Metastatic

Disease
Patient selection is critical when planning surgical intervention,
with comorbidities and timing with respect to chemotherapy and
radiation being a unique consideration in this population. All
weakened areas of the bone in question should be addressed at the
time of surgery. Because the bone quality in patients with
metastatic disease may be compromised by chemotherapy and
radiation, disuse osteopenia, and the presence of tumor itself,
polymethyl methacrylate cement is often used to improve the
immediate construct stability. Given the improved survival
associated with modern treatment strategies for metastatic
carcinoma, the goal should be to achieve both early stability and
also the long-term durability of the planned construct. Highly
vascular lesions such as renal and thyroid carcinomas as well as
multiple myeloma should merit consideration for preoperative
embolization to limit blood loss. Finally, surgical options that allow
for immediate weight bearing and quicker return of function are
preferable in these patients, as months of rehabilitation are
typically not aligned with their goals of care.

Surgical Management of Upper Extremity

Metastatic Disease
Upper extremity metastases are less common than those to the
lower extremity, spine, and pelvis, comprising less than 20% of
osseous disease. Upper extremity metastases may be more
amenable to nonsurgical treatment than lower extremity
metastases; however, upper extremity lesions and fractures can still
affect activities of daily living, impose difficulties with using
ambulatory aids and transferring, and cause significant pain. The
scapula and clavicle are less often affected by metastatic lesions,
and most patients are treated nonsurgically with favorable
outcomes.
The humerus is a common site for metastasis. Cure age and
cementation with internal plate fixation is an effective option with
high biomechanical stability (Figure 5). Intramedullary devices,
which can be supplemented with cure age and/or cementation, are
also commonly used, particularly when the bone is affected
diffusely. Proximal humerus resection and reconstruction with a
hemiarthroplasty, reverse total shoulder, or modular proximal
humerus endoprosthesis is more appropriate in scenarios with
extensive comminution or tumor involvement; these solutions offer
excellent pain relief with variable function. Humeral shaft resection
and reconstruction with an intercalary metal prosthesis is
selectively indicated for extensive diaphyseal destruction and/or
previous implant failure due to uncontrolled local disease. The
distal humerus metastases are rare, as well as difficult to manage
given limited bone stock and reconstructive options. Most are
managed with combined cure age, cement, and fixation with one or
two periarticular plates. Resection and modular distal humerus
endoprosthetic reconstruction is also an option that can restore
distal humeral length and reasonable elbow function, although the
durability of these implants is relatively low.

Figure 5 Radiographs from a 73-year-old man showing surgical management

of proximal humerus metastasis with curettage, structural allograft, cement, and
internal fixation.A, Radiograph showing metastatic lung carcinoma to the left
proximal humerus. B, Postoperative appearance after being treated with
curettage, fibular strut allograft, and polymethyl methacrylate cement and
augmented with a proximal humerus locking plate.

Metastases affecting the forearm, wrist, and hand are rare, and
the management of lesions is individualized based on the anatomic
location. The risks and benefits of surgical intervention must be
weighed against those of nonsurgical management, which can often
be successful in these locations. As with any surgery for metastatic
disease, polymethyl methacrylate cement can be helpful in
reconstructing cavitary defects when combined with a bridging
plate.
Surgical Management of Metastatic Disease
of the Spine and Pelvis
Metastatic disease of the spine can often be managed nonsurgically
with radiation, systemic chemotherapy, and diphosphonates.
However, any progressive neurologic deficit merits consideration
for surgical intervention and/or urgent radiation therapy. The risk
factors for the development of progressive neurologic deficits
include osteolytic lesions, pedicle involvement (as evidenced by the
winking owl sign on radiographs), and posterior column
involvement. Surgical treatment is indicated in patients with
significant or progressive neurologic deficits and should be
considered in those with intractable pain or progression of
deformity despite nonsurgical measures. The surgical options vary
with the location of metastatic disease, as well as the resultant
deformity and the extent of surgery that the patient can safely
tolerate. Anterior vertebrectomy, posterior decompression with
instrumentation, and combined anterior/posterior approaches may
be required, depending on the clinical scenario.
Lesions of the non–weight-bearing areas of the pelvis can often
be managed effectively with radiation, diphosphonates or
denosumab, and chemotherapy, and reconstitution of the bony
anatomy often occurs with time. Minimally invasive techniques (eg,
percutaneous cementoplasty) or limited open resection/cure age
can be helpful in select cases based on location and symptoms.
Lesions about the acetabulum pose unique surgical challenges. The
extent of bony destruction dictates the eventual treatment, and a
wide array of reconstructive options exist. Nonreconstructive
options such as resection arthroplasty (Girdlestone procedure), as
well as limited reconstructions such as ischiofemoral arthrodesis,
can be options for select patients with severe pain and relatively
low functional demands. Standard hip arthroplasty, revision
acetabular components (including cup-cage constructs), 44
Harrington-type cement/rebar constructs, and spinopelvic fixation
may all play a role in the management of periacetabular lesions
(Figure 6).

Figure 6 Metastatic breast cancer in a 59-year-old woman with involvement of

the proximal femur and acetabulum.A, Coronal short tau inversion recovery
magnetic resonance image showing lytic lesions involving the right acetabulum
and right proximal femur. B, Coronal CT image showing significant right
acetabular bone loss. C, Radiograph showing reconstruction of right acetabular
defect with curettage and cement/rebar reconstruction with four 6.5-mm partially
threaded posterior column screws, cemented cup, and cemented femoral stem.

Surgical Management of Lower Extremity

Metastatic Disease
The lower extremity, especially the proximal femur, is a common
location for skeletal metastasis. Patients with a prognosis longer
than 3 months are typically indicated for surgical intervention for
impending fracture, whereas most patients with completed
fractures undergo fixation regardless of prognosis.
Femoral neck lesions pose a high risk for pathologic fracture
because of the mechanical stresses in this location. Prosthetic
reconstruction is often indicated for extensive femoral neck lesions
because the mechanical forces here tend to lead to failure if there is
disease progression. A hemiarthroplasty is generally a sufficient
reconstruction option for patients with metastatic disease given
their relatively low physical demands and limited survival.
However, a total hip arthroplasty may be indicated in more active
patients, those with preexisting degenerative arthritis, or those with
acetabular involvement. Historically, a long-stem cemented implant
was recommended to protect as much of the femur as possible
(Figure 7); however, more recent data on the cardiopulmonary
complications, technical difficulties, and the challenges of
subsequent revision surgeries associated with long-stem cemented
prostheses have suggested that in many cases, short-stem implants
may be appropriate, especially in high-risk patients with more focal
disease. 45 , 46 Similar to the femoral neck, the intertrochanteric and
subtrochanteric regions of the proximal femur are both vulnerable
for mechanical reasons. Most lesions in this area can be effectively
stabilized with intramedullary fixation, including a
cephalomedullary component to protect the femoral neck (Figure
8). Resection and reconstruction with a calcar-replacing prosthesis
or modular proximal femur endoprosthesis may be necessary in
cases of extensive bone destruction, radiation-resistant lesions,
completed pathologic fracture, or failed previous fixation devices.
Figure 7 Renal cell metastasis in the intertrochanteric region, managed with
wide resection and endoprosthetic reconstruction.A, Coronal left hip proton
density magnetic resonance image showing a large renal cell metastasis in the
intertrochanteric region extending into the femoral neck. B, Wide resection of the
lesion was performed and reconstructed with a cemented proximal femur
replacement and total hip arthroplasty.

Figure 8 Impending pathologic fracture of the intertrochanteric region in a 74-

year-old man with metastatic thyroid carcinoma, managed with prophylactic
fixation with a cephalomedullary nail.Preoperative radiograph (A) of the left
proximal femur, and proximal (B) and distal (C) radiographs obtained after
treatment with a prophylactic long femoral nail.
 Lesions of the femoral diaphysis are typically managed with
intramedullary nail fixation. Patients with metastatic disease
affecting the femoral diaphysis without femoral head or neck
involvement may be treated safely with intramedullary nails
without a cephalomedullary component given the relative rarity of
the subsequent development of femoral neck lesions. 47 Metastatic
lesions of the distal femur are generally stabilized with locking
plates and screws, augmented by polymethyl methacrylate cement
for cavitary lesions (Figure 9). Retrograde intramedullary nails may
be useful in certain injury pa erns but have the downsides of
potential tumor extravasation into the knee joint and the creation of
a stress riser at the end of the implant in the proximal femur.

Figure 9 Metastatic pancreatic carcinoma of the distal femur in a 61-year-old

woman.A, Lateral radiograph of right knee and femur showing a large lytic lesion
of the distal femur with impending fracture. B and C, Patient underwent
curettage and cement rebar reconstruction and augmented with a lateral locking
distal femoral plate bridging across the defect and spanning the femur.

Metastatic bone lesions of the tibia, ankle, and foot are relatively
rare, and treatment must be tailored to the size and location of the
lesions. Tibial intramedullary nails offer the advantage of
protecting the entire tibia, whereas smaller lesions may be more
appropriately managed with cure age/cementation/internal fixation
using plates and screws.

Summary
A destructive lesion of bone in an adult older than 40 years is most
likely due to metastatic carcinoma or a hematologic malignancy.
Because of the high prevalence of metastatic disease, all
orthopaedic surgeons are likely to come across this scenario at
some point in their careers. The orthopaedic surgeon’s ability to
recognize the possibility of metastatic disease, initiate a systematic
workup, and provide effective treatment can have a substantial
effect on the patient’s quality and quantity of life.

Key Study Points

The pathophysiology of cancer metastasis determines the epidemiology, location,
and behavior of metastatic carcinoma to bone.
A systematic approach to the workup of an unknown primary includes a history and
physical examination, complete radiographs of the bone at risk, laboratory studies,
whole-body bone scan to assess skeletal disease burden, CT chest/abdomen/pelvis
to identify the primary tumor, and a biopsy to definitively establish the diagnosis.
The risk of pathologic fracture from metastatic disease can be estimated using
scoring systems (such as Mirels criteria) to inform decisions about weight-bearing
status, need for surgical stabilization, and surgical planning.
The effective treatment of patients with metastatic carcinoma and hematopoietic
malignancies affecting bone usually includes both nonsurgical and surgical
interventions, and interdisciplinary coordination of care is crucial for this patient
population.

Annotated References
1. Siegel RL, Miller KD, Jemal A: Cancer statistics, 2018. CA Cancer
J Clin 2018;68(1):7-30.
2. Schulman KL, Kohles J: Economic burden of metastatic bone
disease in the U.S. Cancer 2007;109(11):2334-2342.
 3. Forne i J, Welm AL, Stewart SA: Understanding the bone in
cancer metastasis. J Bone Miner Res 2018;33(12):2099-2113.
4. Hernandez RK, Wade SW, Reich A, Pirolli M, Liede A, Lyman
GH: Incidence of bone metastases in patients with solid tumors:
Analysis of oncology electronic medical records in the United
States. BMC Cancer 2018;18(1):44.
5. Keyak JH, Kaneko TS, Skinner HB, Hoang BH: The effect of
simulated metastatic lytic lesions on proximal femoral strength.
Clin Orthop Relat Res 2007;459:139-145.
6. Nazarian A, Entezari V, Villa-Camacho JC, et al: Does CT-based
rigidity analysis influence clinical decision-making in simulations
of metastatic bone disease? Clin Orthop Relat Res 2016;474(3):652-
659.
7. O’Carrigan B, Wong MHF, Willson ML, Stockler MR, Pavlakis N,
Goodwin A: Bisphosphonates and other bone agents for breast
cancer. Cochrane Database Syst Rev 2017;10(10):CD003474.
8. Stopeck AT, Lipton A, Body JJ, et al: Denosumab compared with
zoledronic acid for the treatment of bone metastases in patients
with advanced breast cancer: A randomized, double-blind study.
J Clin Oncol 2010;28(35):5132-5139.
9. Henry DH, Costa L, Goldwasser F, et al: Randomized, double-
blind study of denosumab versus zoledronic acid in the
treatment of bone metastases in patients with advanced cancer
(excluding breast and prostate cancer) or multiple myeloma. J
Clin Oncol 2011;29(9):1125-1132.
10. Massari F, Ciccarese C, Santoni M, et al: Metabolic alterations in
renal cell carcinoma. Cancer Treat Rev 2015;41(9):767-776.
11. Geraets SEW, Bos PK, van der Stok J: Preoperative embolization
in surgical treatment of long bone metastasis: A systematic
literature review. EFORT Open Rev 2020;5(1):17-25. This
systematic review concluded that preoperative embolization of
renal cell carcinoma metastasis in long bones reduces
perioperative blood loss and blood transfusion requirement in
three of six level III studies. Level of evidence: III.
12. Lin PP, Mirza AN, Lewis VO, et al: Patient survival after surgery
for osseous metastases from renal cell carcinoma. J Bone Joint
Surg Am 2007;89(8):1794-1801.
13. Rougraff BT, Kneisl JS, Simon MA: Skeletal metastases of
unknown origin. A prospective study of a diagnostic strategy. J
Bone Joint Surg Am 1993;75(9):1276-1281.
14. Davy DT, Ko ar GM, Brown RH, et al: Telemetric force
measurements across the hip after total arthroplasty. J Bone Joint
Surg Am 1988;70(1):45-50.
15. Griffin N, Gore ME, Sohaib SA: Imaging in metastatic renal cell
carcinoma. Am J Roentgenol 2007;189(2):360-370.
16. Lawrenz JM, Gordon J, George J, et al: Does PET/CT aid in
detecting primary carcinoma in patients with skeletal metastases
of unknown primary? Clin Orthop Relat Res 2020;478(11):2451-
2457. This single-center retrospective analysis found that
although positron emission tomography/CT may help assess
overall metastatic burden, it offered no benefit over standard
techniques in identifying primary cancer in patients with a
skeletal metastasis of unknown primary. Level of evidence: III.
17. Hu K, Wang Z, Lin P, et al: Three hematological indexes that
may serve as prognostic indicators in patients with primary, high-
grade, appendicular osteosarcoma. Oncotarget 2017;8(26):43130-
43139.
18. Nystrom LM, Buckwalter JA, Syrbu S, Miller BJ: Serum protein
electrophoresis in the evaluation of lytic bone lesions. Iowa
Orthop J 2013;33:114-118.
19. Teng X, Wei L, Han L, Min D, Du Y: Establishment of a
serological molecular model for the early diagnosis and
progression monitoring of bone metastasis in lung cancer. BMC
Cancer 2020;20(1):562. This diagnostic model using serum
cytokine levels was tested in patients with metastatic lung cancer
to bone. Prospective validation showed the model predicts bone
metastasis with high accuracy, on average 9 months earlier than
via bone scan. Level of evidence: II.
20. Clayer M, Duncan W: Importance of biopsy of new bone lesions
in patients with previous carcinoma. Clin Orthop Relat Res
2006;451(451):208-211.
21. Buijs JT, van der Pluijm G: Osteotropic cancers: From primary
tumor to bone. Cancer Le 2009;273(2):177-193.
22. Wang R, Zhu Y, Liu X, Liao X, He J, Niu L: The
Clinicopathological features and survival outcomes of patients
with different metastatic sites in stage IV breast cancer. BMC
Cancer 2019;19(1):1091. A retrospective study using the
Surveillance, Epidemiology, and End Results database found that
breast cancer–specific survival and overall survival in stage IV
breast cancer were highest in patients with bone metastasis
compared with other secondary disease sites. Level of evidence:
IV.
23. Willeumier JJ, van der Linden YM, van der Wal CWPG, et al: An
easy-to-use prognostic model for survival estimation for patients
with symptomatic long bone metastases. J Bone Joint Surg Am
2018;100(3):196-204.
24. Thio QCBS, Karhade AV, Bindels BJJ, et al: Development and
internal validation of machine learning algorithms for
preoperative survival prediction of extremity metastatic disease.
Clin Orthop Relat Res 2020;478(2):322-333. Machine learning
algorithms are described for 90-day and 1-year survival in
patients who received surgical treatment for a bone metastasis of
the extremity, which demonstrated favorable performance on this
internal validation study. Level of evidence: III.
25. Forsberg JA, Wedin R, Boland PJ, Healey JH: Can we estimate
short- and intermediate-term survival in patients undergoing
surgery for metastatic bone disease? Clin Orthop Relat Res
2017;475(4):1252-1261.
26. Anderson AB, Wedin R, Fabbri N, Boland P, Healey J, Forsberg
JA: External validation of PATHFx version 3.0 in patients treated
surgically and nonsurgically for symptomatic skeletal metastases.
Clin Orthop Relat Res 2020;478(4):808-818. The PATHFx clinical
 decision support tool for predicting survival for patients with
skeletal metastases was updated using data from patients
undergoing surgical or nonsurgical treatment for symptomatic
skeletal metastases. Level of evidence: III.
27. Kirkinis MN, Lyne CJ, Wilson MD, Choong PFM: Metastatic
bone disease: A review of survival, prognostic factors and
outcomes following surgical treatment of the appendicular
skeleton. Eur J Surg Oncol 2016;42(12):1787-1797.
28. Kim JH, Seo SW, Chung CH: What factors are associated with
early mortality in patients undergoing femur surgery for
metastatic lung cancer? Clin Orthop Relat Res 2018;476(9):1815-
1822.
29. Nguyen QN, Chun SG, Chow E, et al: Single-fraction stereotactic
vs conventional multifraction radiotherapy for pain relief in
patients with predominantly nonspine bone metastases: A
randomized phase 2 trial. JAMA Oncol 2019;5(6):872-878. A
randomized controlled trial found that single-fraction
stereotactic body radiotherapy resulted in noninferior rates of
pain response compared with traditional multifraction external
beam radiation. Level of evidence: I.
30. Bozzo A, Deng J, Abbas U, et al: Which bone-modifying agent is
associated with be er outcomes in patients with skeletal
metastases from lung cancer? A systematic review and network
meta-analysis. Clin Orthop Relat Res 2021;479(9):2047-2057. A
network meta-analysis of randomized trials found that
denosumab was superior to zoledronic acid for overall survival
and time to SREs, but no difference was found in terms of
incidence of SRE. Level of evidence: I.
31. Takahashi M, Ozaki Y, Kizawa R, et al: Atypical femoral fracture
in patients with bone metastasis receiving denosumab therapy: A
retrospective study and systematic review. BMC Cancer
2019;19(1):980. A multicenter retrospective study found that
atypical femur fractures occurred at a rate of 1.8% in patients
with cancer who had received monthly denosumab treatment,
 and higher rates with long-term (>3.5 years) use. Level of
evidence: IV.
32. Stopeck A, Brufsky A, Kennedy L, et al: Cost-effectiveness of
denosumab for the prevention of skeletal-related events in
patients with solid tumors and bone metastases in the United
States. J Med Econ 2020;23(1):37-47. A cost-effectiveness analysis
found that although the direct drug costs for denosumab are
higher than zoledronic acid, the overall cost associated with
denosumab treatment is lower because of reduced incidence of
fractures and other SREs. Level of evidence: IV.
33. Clemons M, Ong M, Stober C, et al: A randomised trial of 4-
versus 12-weekly administration of bone-targeted agents in
patients with bone metastases from breast or castration-resistant
prostate cancer. Eur J Cancer 2021;142:132-140. A randomized
controlled trial of patients with bone metastases from breast or
prostate cancer found that denosumab or diphosphonate
administered at 12-week intervals was noninferior to 4-week
intervals in terms of rates of symptomatic skeletal events. Level
of evidence: I.
34. Jairam V, Lee V, Yu JB, Park HS: Nationwide pa erns of
pathologic fractures among patients hospitalized with bone
metastases. Am J Clin Oncol 2020;43(10):720-726. A retrospective
study using the Healthcare Cost and Utilization Project database
found that pathologic fractures in patients hospitalized with
bone metastases are associated with longer inpatient stays and
higher health care costs. Level of evidence: IV.
35. Nooh A, Goulding K, Isler MH, et al: Early improvement in pain
and functional outcome but not quality of life after surgery for
metastatic long bone disease. Clin Orthop Relat Res
2018;476(3):535-545.
36. El Abiad JM, Raad M, Puvanesarajah V, Rao SS, Morris CD,
Levin AS: Prophylactic versus postfracture stabilization for
metastatic lesions of the long bones: A comparison of 30-day
postoperative outcomes. J Am Acad Orthop Surg 2019;27(15):E709-
 E716. A retrospective study using the National Surgical Quality
Improvement Program database found that patients who
underwent prophylactic stabilization for impending pathologic
fracture had lower risk of major 30-day complications and shorter
length of hospital stay compared with patients who required
postfracture stabilization. Level of evidence: IV.
37. Philipp TC, Mikula JD, Doung YC, Gundle KR: Is there an
association between prophylactic femur stabilization and survival
in patients with metastatic bone disease? Clin Orthop Relat Res
2020;478(3):540-546. A comparative retrospective study of the
Veterans Administration database found that patients who
underwent prophylactic stabilization for impending pathologic
fracture had higher overall survival than patients who required
postfracture fixation. Level of evidence: III.
38. Blank AT, Lerman DM, Patel NM, Rapp TB: Is prophylactic
intervention more cost-effective than the treatment of pathologic
fractures in metastatic bone disease? Clin Orthop Relat Res
2016;474(7):1563-1570.
39. Mirels H: Metastatic disease in long bones. A proposed scoring
system for diagnosing impending pathologic fractures. Clin
Orthop Relat Res 1989;249:256-264.
40. Damron TA, Morgan H, Prakash D, Grant W, Aronowi J,
Heiner J: Critical evaluation of mirels’ rating system for
impending pathologic fractures. Clin Orthop Relat Res
2003;415:S201-S207.
41. Toci GR, Bressner JA, Morris CD, Fayad L, Levin AS: Can a
novel scoring system improve on the mirels score in predicting
the fracture risk in patients with multiple myeloma? Clin Orthop
Relat Res 2021;479(3):521-530. A novel scoring system specific to
multiple myeloma (incorporating larger lesion size, longer lesion
latency, pain, and metaphyseal location as predictors of fracture
risk) was found to be more sensitive than Mirels criteria with
noninferior specificity. Level of evidence: III.
42. Damron TA, Mann KA: Fracture risk assessment and clinical
decision making for patients with metastatic bone disease. J
Orthop Res 2020;38(6):1175-1190. A review of modern fracture risk
assessment techniques identified the use of big data/machine
learning, CT-based rigidity/finite element analysis approaches,
and clinical and radiographic fracture risk assessment tools as
areas of active ongoing research. Level of evidence: V.
43. Tablazon IL, Howard LE, De Hoedt AM, et al: Predictors of
skeletal-related events and mortality in men with metastatic,
castration-resistant prostate cancer: Results from the Shared
Equal Access Regional Cancer Hospital (SEARCH) database.
Cancer 2019;125(22):4003-4010. A study of patients in the Veterans
Administration database with metastatic prostate cancer found
that bone pain is the strongest predictor of SREs, and the number
of bone metastases was a strong predictor of mortality. Level of
evidence: IV.
44. Rowell P, Lowe M, Sommerville S, Dickinson I: Is an acetabular
cage and cement fixation sufficiently durable for the treatment of
destructive acetabular metastases? Clin Orthop Relat Res
2019;477(6):1459-1465. A retrospective case series of patients with
destructive bony acetabular metastases found that a construct
consisting of acetabular partial pelvic cage and cemented total
hip replacement had a reoperation/revision rate of 16% at 4 years.
Level of evidence: IV.
45. Peterson JR, Decilveo AP, O’Connor IT, Golub I, Wi ig JC:
What are the functional results and complications with long stem
hemiarthroplasty in patients with metastases to the proximal
femur? Clin Orthop Relat Res 2017;475(3):745-756.
46. Xing Z, Moon BS, Satcher RL, Lin PP, Lewis VO: A long femoral
stem is not always required in hip arthroplasty for patients with
proximal femur metastases. Clin Orthop Relat Res
2013;471(5):1622-1627.
47. Moon B, Lin P, Satcher R, Bird J, Lewis V: Intramedullary nailing
of femoral diaphyseal metastases: Is it necessary to protect the
femoral neck? Clin Orthop Relat Res 2015;473(4):1499-1502.
C H AP T E R 7 4

Benign Soft-Tissue Tumors and

Masses
Lisa A. Kafchinski MD, FAAOS, FAOA

Neither Dr. Kafchinski nor any immediate family member has received anything of value from or
has stock or stock options held in a commercial company or institution related directly or
indirectly to the subject of this chapter.

ABSTRACT
Benign soft-tissue tumors range from small, asymptomatic
superficial masses without functional consequence to large,
symptomatic, intramuscular, or intra-articular lesions. Many benign
soft-tissue tumors can be successfully managed with marginal
excision when nonsurgical measures have failed. Some lesions,
such as desmoid tumors, have a high risk of local recurrence, even
when wide surgical margins are achieved. Malignant
transformation of benign soft-tissue tumors is exceedingly rare.
Keywords: benign soft-tissue mass; cysts; lipomatous tumors;
neurogenic tumors; tenosynovial giant cell tumor

Introduction
The soft-tissue tumors most frequently encountered benign by
orthopaedic surgeons are lipomatous tumors, tenosynovial giant
cell tumor, and cysts. These conditions can often be diagnosed with
a combination of physical examination, radiographs, ultrasound,
and MRI. If a mass does not follow the typical presentation,
location, and imaging findings of a benign lesion, biopsy according
to orthopaedic oncologic principles is warranted to rule out a
malignant process.

Lipomatous Tumors
Lipomatous tumors represent the most common benign soft-tissue
masses, although the true prevalence is unknown because of
underreporting of these often-asymptomatic lesions. Lipomatous
tumors are generally classified as lipomas, atypical lipomatous
tumors (ALTs), and other variants (angiolipomas, chondroid
lipomas, hibernomas, lipoma arborescens, lipoblastomas, spindle
cell lipomas, and atypical spindle cell lipomas). Table 1 summarizes
the characteristics of these lipomatous tumor categories.

Table 1
Lipomatous Tumors

Age
Location MRI Finding Other
Sex
Lipoma >40- Superficial Isointense to fat on all Most common
60 yr > deep sequences, lipomatous
M> F nonenhancing lesion
Atypical lipomatous tumor >60 Deep Septations >2 mm +MDM2
yr Small areas of amplification
M= F enhancing nodularity
Variants
Teens Superficial, Prominent vessels Often tender
Angiolipoma to upper within fat
<50 extremity
yr
M> F
>30 Deep, Lobules of cartilage May be
Chondroid lipoma yr proximal within fat confused with
M< F extremities a sarcoma
Teens Superficial, Incomplete fat- Brown fat
Hibernomas to 30 thigh suppression
yr
M> F
 Age
Location MRI Finding Other
Sex
Adults Intra- Intra-articular fat, no Reactive,
Lipoma M= F articular, artifact from intra-articular
arborescens knee hemosiderin

<9 yr Trunk, May contain myxoid Fetal fat

Lipoblastomas M> F extremities areas

40-60 Posterior Nonadipose areas −MDM2

Spindle cell yr neck enhance amplification
lipoma/pleomorphic M> F
lipoma

>50 Hands, feet Heterogeneous on T1- −MDM2

Atypical spindle cell yr and T2-weighted amplification
lipoma/pleomorphic M> F sequences
lipomatous tumor

Appropriate preoperative evaluation according to the principles

of orthopaedic oncology is of the utmost importance. In summary,
if a small mass can be confidently identified as superficial on
physical examination or ultrasonography, it is generally safe to
perform a wide excision without MRI. 1 Lesions that are deep,
abu ing or a ached to fascia, or larger than 5 cm should be
evaluated with MRI with and without contrast before surgery.
Lesions with concerning imaging findings (ie, nodular or
heterogeneous enhancement, large areas of necrosis) should be
biopsied before surgery. 1

Lipoma
Solitary lipomas present most commonly in male patients between
40 and 60 years of age, with equal distribution across races. 2 They
can occur in either superficial or deep locations. Superficial or
subcutaneous lipomas are easier to detect and typically noticed
when the mass is smaller in dimension. Deep lipomas may be
further characterized as intramuscular or intermuscular. Lipomas
are usually asymptomatic, although symptoms may arise from
nerve compression, restricted range of motion, or a sense of
fullness within the extremity. Surgical resection of lipomas is
reserved for symptomatic lesions or for cosmetic purposes.
Lipomas can be excised marginally with a low risk of local
recurrence. Deep and particularly intramuscular lipomas have a
higher risk of local recurrence, possibly related to incomplete
excision. 2 - 4
MRI of lipomas demonstrates homogeneous isointensity to
subcutaneous fat on all sequences, and no abnormal enhancement
on postcontrast imaging. There may be thin (<2 mm),
nonenhancing septations within the lipoma and an occasional
traversing blood vessel. 4 , 5 Thus, lipomas are considered
determinant lesions when imaging is concordant with
subcutaneous adipose, and biopsy is not necessary to confirm the
diagnosis. 5 Lesions with MRI characteristics that are incongruous
to fat warrant a biopsy before surgical intervention; myxoid,
fibrous, nodularity, or heterogeneous areas of enhancement are
more likely to indicate a sarcoma than a simple lipoma. 2 , 4 , 5 Both
grossly and microscopically, lipomas are by definition similar to the
surrounding mature adipose tissue 2 (Figure 1).
 Figure 1 Axial MRI sequences of a forearm intermuscular lipoma (arrow).A,
T1-weighted magnetic resonance image. B, T2-weighted fat-suppressed
magnetic resonance image. C, Gadolinium-enhanced T1-weighted fat-
suppressed magnetic resonance image.

Atypical Lipomatous Tumor

ALTs are histologically identical to well-differentiated
liposarcomas. Differences in location, treatment, and clinical
outcomes led to distinguishing these two entities with separate
nomenclature. The World Health Organization (WHO)
Classification of Tumours of Bone and Soft Tissue defines well-
differentiated liposarcomas as tumors located in the mediastinum,
retroperitoneum, or paratesticular regions. 2 , 3 This entity has a
higher risk of local recurrence because complete surgical resection
may not be a ainable, compared with ALTs that arise in the
extremities.
ALTs are located deep to fascia in the extremities and have a low
risk of either local recurrence or malignant transformation. 2 - 4 , 6
ALTs affect both men and women equally, typically occurring in
patients older than 60 years. 3 , 6 MRI characteristics of ALTs,
compared with those of lipomas, often demonstrate thicker septa
(>2 mm), areas of nodular enhancement on postcontrast imaging,
and large tumor diameters (>130 mm). 7
Histologically, ALTs are composed of mature white adipose
tissue, with areas of focal atypia, hyperchromatic stromal cells, and
multinucleated stromal cells. 2 , 3 ALTs express amplification of
murine double minute 2 (MDM2) in close to 100% of cases via
fluorescence in situ hybridization, 8 with a 92% to 100% specificity
and 97% to 100% sensitivity in differentiating ALT from a simple
lipoma. 9 , 10 CDK4 is often co-amplified with MDM2 in ALT, as both
genes are located within the 12q13-15 region. 2
Because of the low risk of local recurrence or metastatic potential,
marginal resection is recommended for ALTs. 6 , 11 - 14 Reports of
local recurrence range from 8.2% to 50.61%, with recurrence noted
an average of 6 to 8 years after surgery. 11 - 13 , 15 , 16 The largest case
series examining 151 patients had a local recurrence rate of 10%. 12
Reported rates of dedifferentiation and metastasis range from zero
to 5% in the literature. 11 - 13 , 15 , 16

Variants—Benign Lipomatous Tumors

There are several variants of lipomas, all of which can be
categorized as benign lipomatous tumors. The presentation,
location, and imaging findings of each vary from those of a simple
lipoma; however, once a diagnosis is confirmed, marginal excision
remains the standard of care. 4
Angiolipomas most commonly occur in the subcutaneous tissue
of the upper extremities of patients in their second and third
decades; conversely, they are uncommon in children or patients
older than 50 years. 2 Angiolipomas are tender to palpation, which
helps distinguish them from an ordinary lipoma.
 Chondroid lipomas are rare, benign masses that occur more
frequently in women. 2 They are often mistaken for sarcoma
(myxoid liposarcoma or extraskeletal myxoid chondrosarcoma)
because of both histologic and imaging similarities. As such,
accurate diagnosis requires a skilled musculoskeletal pathologist.
Hibernomas are lipomatous tumors composed primarily of
brown fat and have increased vascularity. These lesions tend to be
subcutaneous and occur in the thigh region. They are most
common in patients around the third decade of life, with a slight
male predominance. Hibernomas do not tend to recur after surgical
excision. 2
Lipoma arborescens is considered a lipomalike lesion and is
typically located in the suprapatellar pouch of the knee, and rarely
in the shoulder, hip, or elbow. 2 Lipoma arborescens is most likely a
reactive process, strongly associated with degenerative intra-
articular pathology, where irritated and hypertrophic synovial
tissue becomes infiltrated with fat. 2 , 17 , 18
Lipoblastomas occur in children younger than 3 years and are
rarely seen in children older than 9 years. Histologically, this
benign condition is very similar to fetal adipose tissue and is found
in the extremities, trunk, and the head and neck. 2 Lipoblastomas
may be circumscribed or diffuse, with the la er having a higher rate
of local recurrence after surgical resection, likely because of
incomplete excision. 2
Spindle cell lipomas, also called pleomorphic lipomas, classically
arise (80%) in the posterior shoulder or neck of middle-aged males.
Histologically, these tumors can be challenging to diagnose; they
can include areas of spindle cells, myxoid changes, mast cells, and
collagen fibers, hence the name pleomorphic lipoma. 2 Notably,
spindle cell lipomas/pleomorphic lipomas do not show MDM2
amplification. 2 Surgical excision is typically curative. 4
Atypical spindle cell or pleomorphic lipomatous tumor
constitutes a distinct tumor, separate from spindle
cell/pleomorphic lipomas or ALT as described previously. A recent
addition in the 2020 WHO Classification of Tumours of Bone and
Soft Tissue, this entity chiefly arises in the hands and feet of men
(3:2 male:female ratio), in the fifth decade of life. 19 - 21
Histologically, this tumor is more infiltrative and can vary greatly
with regard to pleomorphism, lipoblasts, and level of nuclear
atypia. 21 MDM2 amplification is negative in atypical spindle
cell/pleomorphic lipomatous tumors. 7

Neurogenic Tumors: Schwannoma and

Neurofibroma
The two most common benign peripheral nerve sheath tumors are
schwannomas and neurofibromas. Treatment options include
observation and nerve-sparing surgical excision, with the la er
being curative for these lesions. 2 , 3 Table 2 summarizes the features
of these tumors.

Table 2
Neurogenic Tumors

Neurofibroma Schwannoma
Age 20-40 yr 20-50 yr
Sex M= F M= F
Associated condition and Neurofibromatosis type I Neurofibromatosis type II
genetics Autosomal dominant Autosomal dominant
NF1 gene, NF2 gene, chromosome 22
chromosome 17 Familial schwannomatosis
Autosomal dominant
SMARCB1 a gene,
chromosome 22
Location Cutaneous Flexor surfaces
Categorization Localized/sporadic Localized/sporadic
Diffuse
Plexiform
Classic MRI finding Target sign Cystic changes
S-100 protein staining Variable Uniform, strong
Malignant potential Rare in localized cases Rare
2%-3% risk in NF1
Previously called INI1.
a

Schwannomas arise from the Schwann cell, which acts as a

physical layer of protection for the axon and maintains the myelin
sheath. 2 Both men and women are equally affected by this tumor,
which is frequently diagnosed in patients aged 20 to 50 years. 2
Schwannomas are commonly found in the flexor surfaces of the
body, and small lesions are often asymptomatic. 2 , 22 On MRI, the
most classic appearance is a round or fusiform mass surrounded by
fat. When arising from a major nerve, continuation of the nerve can
often be appreciated proximal and distal to the lesion; 22 however,
smaller nerves are not always visible. Histologically, within a
distinct capsule, schwannomas consist of a well-ordered cellular
area (Antoni A) and a more haphazard myxoid area (Antoni B), and
stain positive for S-100 protein in a uniform manner. 2 Degenerative
(cystic) and myxoid changes are commonly observed, especially in
ancient schwannomas (Figure 2), which have been present for a
long period of time and are frequently in deep locations. 2 , 22
 Figure 2 Coronal MRI sequences of an ancient schwannoma (arrow) of the
tibial nerve.A, T1-weighted magnetic resonance image. B, T1-fat-suppressed
magnetic resonance image.

Neurofibromas are categorized as localized (sporadic), diffuse, or

plexiform. Diffuse and plexiform neurofibromas are seen in
patients with neurofibromatosis 1 (NF1). Sporadic neurofibromas
are often superficial, asymptomatic, and affect both men and
women equally. Neurofibromas are more likely than schwannomas
to demonstrate a target sign on T2-weighted MRI with fat
suppression. The target sign is a central area of hypointensity
within a hyperintense, fusiform mass along a nerve. 5 , 22 The classic
histologic features of a neurofibroma are gracile collagen fibers
among thicker masses of elongated cells, without a distinct capsule.
S-100 protein staining is not as uniform as in schwannomas. 2

Fibrous Lesions

Desmoid Tumor
Desmoid tumor (extra-abdominal fibromatosis) is a benign but
locally aggressive tumor of muscle that frequently involves
surrounding aponeuroses and fascia. Desmoid tumor is more
common in women than men and is often diagnosed in patients
from ages 10 to 50. 2 , 3 The shoulder girdle, trunk, pelvis, and thigh
are the most frequent anatomic locations for this deep, slow-
growing, often painless mass. Symptoms may arise because of a
limited range of motion or compression of surrounding
neurovascular structures.
MRI is the preferred cross-sectional imaging modality for
evaluation of desmoid tumors. They are often isointense to skeletal
muscle on T1-weighted images and isointense to hyperintense to
skeletal muscle on T2-weighted images. Most desmoid tumors
(90%) have enhancement on postcontrast imaging. 23 Extension of
desmoid tumors along fascia planes is common. Grossly and
microscopically, desmoid tumors are infiltrative with indistinct
margins. Composed of spindle cells, with interspersed collagen,
desmoid tumors do not have hyperchromatic nuclei or atypia,
which is an important distinction between benign extra-abdominal
fibromatosis and fibrosarcoma. 2
Extra-abdominal fibromatosis is a challenging disease to manage.
In a global consensus treatment guideline, when surgery is
indicated, wide surgical excision with negative margins is
preferable to a marginal excision, as long as the surgical morbidity
is not too grave. 24 Local recurrence following surgery is common;
moreover, according to a 2020 study, patient-reported outcomes
have been notably low in patients who underwent two or more
surgeries. 25 Nonsurgical management strategies, including
antihormonal medications, NSAIDs, tyrosine kinase inhibitors
(imatinib, nilotinib, sorafenib, pazopanib), chemotherapy (low-dose
methotrexate, vinblastine, vinorelbine, or anthracycline-based
regimens) and radiation, are all viable but imperfect treatment
options with variable efficacy and side effects. 26 - 28 Cryoablation has
also demonstrated favorable results in symptom relief and
maintaining the disease in a stable state. 27

Nodular Fasciitis
Nodular fasciitis is a self-limiting, solitary mass occurring in the
upper extremities and trunk of young adults (typically less than 40
years). The lesion often grows rapidly over the course of a few
weeks, thus raising the concern of a sarcoma. One-half of patients
report pain at the site of the lesion. 2 Histologically, nodular fasciitis
can also appear aggressive because of the presence of immature
fibroblasts with both increased cellularity and mitotic activity. 2 , 3
The identification of fusion genes associated with nodular fasciitis,
specifically leading to overexpression of ubiquitin-specific
peptidase 6, has aided in making this otherwise challenging
diagnosis. 29 , 30 Nodular fasciitis often spontaneously regresses,
even without surgical intervention. 2 , 3 , 29 , 30

Tendon Sheath Fibroma

Fibroma of tendon sheath typically occurs in the hands and feet
and is seen more commonly in men (male-to-female ratio: 2:1). 2
The clinical history is characterized by a small, slowly growing
nodule that moves with the underlying tendon. These nodules
contain spindle-shaped cells, similar in appearance to fibroblasts,
but overall are hypocellular lesions. 2 , 3 The cellular fibroma of
tendon sheath variant, while still benign, has increased cellularity
and overexpression of ubiquitin-specific peptidase 6. 30 Local
recurrence of both subtypes after surgical excision has been
reported at up to 20% to 24% 2 , 3

Palmar/Plantar Fibromatosis
Palmar fibromatosis (Dupuytren disease or contracture) and
plantar fibromatosis (Ledderhose disease) are frequently seen in
patients older than 60 years, and the incidence increases with age. 2 ,
3
Patients of Northern European descent, particularly men (range of
male-to-female ratio, 3:1 to 4:1) are most commonly affected. The
cause of palmar/plantar fibromatosis is multifarious, including
both genetics and local trauma. Progressive contracture formation
with loss of function, especially of the hand, leads patients to seek
treatment. The age of the lesion determines the histologic findings,
and during the proliferative stage, increased cellularity among
fibroblasts is often noted. 2 Treatment for palmar fibromatosis
ranges from percutaneous needle fasciotomy, fasciotomy,
fasciectomy, dermofasciectomy, and injections with collagenase
Clostridium histolyticum. 31 Recurrence rates vary significantly based
on the extent of disease and treatment type, ranging from 8% with
dermofasciectomy, the most extensive surgery, to 23% recurrence
with collagenase C histolyticum injections. 2 , 31

Infantile Fibromatosis (Lipofibromatosis)

Infantile lipofibromatosis is a rare condition and is seen in the
hands and feet, more commonly in males. 2 , 3 These tumors can be
in either a superficial or deep location, and may affect range of
motion if the mass is large. Most of the tumor is composed of
mature fat and fibroblasts. 3 Mitotic activity is rare. 2 Local
recurrence is common when the lesion is incompletely excised,
which often occurs in anatomically critical areas. Infantile
lipofibromatosis does not metastasize and the cause remains
unknown. 2
Tenosynovial Giant Cell Tumor (Pigmented
Villonodular Synovitis)
The term tenosynovial giant cell tumor (TGCT) encompasses the
entities of pigmented villonodular synovitis, giant cell tumor of
tendon sheath, and pigmented villonodular tumor of tendon
sheath. 3 Location (intra-articular or extra-articular) and growth
pa ern (localized or diffuse) further aid in this descriptive
nomenclature. Overexpression of colony-stimulating factor 1 (CSF1)
in diffuse intra-articular TGCT (ie, pigmented villonodular
synovitis) 32 has recently been identified; this has led to novel
therapies, specifically the tyrosine kinase inhibitor pexidartinib,
which blocks the CSF1 receptor and may be indicated for
unresectable tumors or when surgery may be too morbid. 33
Extra-articular, localized TGCT is often seen in the hand (85% of
cases) and is more common in women, especially in the third to
fifth decades of life. 2 , 3 TGCTs are slowly growing masses that may
affect range of motion and grip strength. Histologically, these
lobulated masses are formed by a mixture of giant cells,
mononuclear cells, hemosiderin deposits, xanthoma cells, and
collagen. 2 Marginal resection is recommended and local recurrence
rates range from 5% to 40%. 34 - 36 Factors that may affect local
recurrence include the location of the lesion, with high recurrence
rates seen in cases with involvement of the extensor or flexor
tendon or joint capsule, likely related to incomplete excision. 36
Diffuse intra-articular TGCT (commonly referred to as pigmented
villonodular synovitis) classically occurs in the knee (75% of cases),
followed by the hip, ankle, elbow, and shoulder. 3 This benign but
locally aggressive tumor can lead to degenerative changes within
the affected joint. Pain, swelling, warmth, and decreased range of
motion are common presenting symptoms. Radiographs may
demonstrate a joint effusion or degenerative changes. MRI of intra-
articular, diffuse TGCT is characterized by nodular/lobular tissue
arising within and occasionally extending beyond the joint capsule.
The tumor classically has low signal intensity on both T1-weighted
and T2-weighted imaging because of the preponderance of
hemosiderin deposition. Gradient echo sequences on MRI typically
display signal void, referred to as susceptibility (or blooming)
artifact, again because of hemosiderin. Moderate enhancement is
seen on postcontrast imaging. 5 , 18 Various surgical options for
diffuse intra-articular TGCT of the knee have been proposed:
arthroscopic partial synovectomy, open partial synovectomy, or
open radical synovectomy. Some posterior knee lesions, in
particular those extending outside the capsule, may not be
accessible through posteromedial arthroscopic portals. If multiple
compartments of the knee are involved, or the patient has recurrent
disease, an open radical synovectomy may be necessary. Although
there is a lack of level I evidence to support one surgical approach
versus another, an arthroscopic anterior synovectomy combined
with an open posterior synovectomy is commonly used. Local
recurrence rates vary greatly in the literature and seem to depend
on the surgical approach and extent of disease. Radiation has also
been used as either an adjuvant to surgery or as a primary
treatment; however, disadvantages include adverse side effects such
as fibrosis, as well as the risk of radiation-induced sarcoma. 37 As
mentioned previously, the novel tyrosine kinase inhibitor
pexidartinib, which blocks colony-stimulating factor 1 receptor, is
now an FDA-approved medication, and may be an option for
recalcitrant cases. 33 Hepatotoxicity (mixed or cholestatic) is a risk of
this medication, and many patients (67%) experienced change in
hair color. 33
Localized intra-articular TGCT is similar to the diffuse type with
regard to presenting symptoms and classically occurs deep to the
patellar tendon in the knee. Painless or minimally symptomatic
lesions can be safely monitored. Because most cases of localized
TGCT occur within the knee, both open and arthroscopic excisions
show favorable outcomes and low recurrence rates. 37

Synovial Chondromatosis
Synovial chondromatosis, also called synovial chondrometaplasia,
is a benign intra-articular and occasionally extra-articular disease
process. The most common location is the knee, followed by the
hip, shoulder, and elbow. Extra-articular disease can occur in
isolation, affecting the tendon sheath or the extra-articular bursae
around the joint (tenosynovial chondromatosis). 2 , 3 , 38 Men are
affected twice as frequently as women. 3 Nodules of cartilage form
within the synovium; they eventually become dislodged and ossify
(with the peripheral margin of the nodules mineralizing first),
making them easily identifiable on radiographs. Cross-sectional
imaging can be useful in the diagnosis of synovial chondromatosis,
especially in the premineralization phase of the disease process
when radiographs are not diagnostic 2 , 18 (Figure 3).

Figure 3 Synovial chondromatosis (arrows) of the left hip.A, AP radiograph of

the pelvis. B, Axial T1-weighted magnetic resonance image. C, Axial T2-
weighted magnetic resonance image.

Symptoms of joint swelling, mechanical symptoms, and

decreased range of motion often lead patients to seek medical
a ention. Synovial chondromatosis is often categorized as either
primary or secondary. The primary form occurs in younger patients
in a normal joint, and the nodules tend to be more uniform in size.
The secondary form occurs in older patients in joints affected by
osteoarthritis, trauma, osteonecrosis, or other disease processes,
and the nodules are more variable in size. 38 Of note, synovial
chondromatosis is a distinct entity from the multiple loose intra-
articular bodies that can occur with osteoarthritis as a product of
the degenerative inflammatory process. The clinical course of
synovial chondromatosis ranges from a self-limiting disease, which
can be successfully managed by activity modification, ice, and
NSAIDs, to a progressive disease with joint destruction. When
nonsurgical measures fail, surgical removal of the loose bodies with
or without a synovectomy may be indicated. There is a paucity of
evidence regarding the necessity of a synovectomy in the treatment
of synovial chondromatosis, and both open and arthroscopic
methods have equivalent recurrence rates (zero to 31%). 18 , 38 Very
rarely, synovial chondromatosis has been reported to degenerate
into synovial chondrosarcoma. 2 , 18 , 38

Cystic Lesions

Ganglion Cysts
Ganglion cysts are the most common soft-tissue lesion of the hand
and wrist, accounting for 50% to 70% of masses in this area. 2 , 34 , 35
Specifically, dorsal ganglion cysts are more common than volar.
These tumor-like masses are benign cystic or myxoid masses,
a ached to the joint capsule or tendon sheath, and can range from
unilocular to multilocular. 2 Ganglion cysts have a presentation
including characteristic location, waxing and waning size, and
transillumination on examination. For lesions with these classic
features, no other imaging modalities aside from radiographs are
necessary. 5 Treatment options range from observation,
compression, aspiration, aspiration and injection with
corticosteroid, or surgical excision. Recurrence rates vary greatly in
the recent literature, ranging from 15% to 89% for aspiration 34 , 35
and 8% to 39% for open or arthroscopic excision, with a trend
toward lower recurrence rates after open excision. 39

Popliteal Cysts
Popliteal or Baker cysts occur in a distinct location, between the
muscle bellies of the medial head of the gastrocnemius and
semimembranosus. The bursa separating these two muscles is
connected to the posterior capsule of the knee, which can become
enlarged with an influx of synovial fluid. 5 , 40 This phenomenon
often occurs with intra-articular pathology such as meniscal tears or
osteoarthritis. Popliteal cysts are often asymptomatic and do not
require treatment, although patients may benefit from reassurance.
Popliteal cysts causing pain and limited range of motion may be
treated with aspiration and corticosteroid injection under
ultrasound guidance. Fenestration of multiloculated cysts may help
decrease local recurrence. 40 When intra-articular pathology is being
surgically treated (ie, arthroscopy for meniscal injury or total knee
arthroplasty for arthritis), it is recommended to address the
symptomatic popliteal cyst concurrently to resolve the pain caused
by the cyst. 40

Meniscal Cysts
Parameniscal cysts are the most common form of meniscal cyst and
develop when synovial fluid enters the soft tissue around a
meniscal tear. 41 Intrameniscal cysts form within the damaged
meniscus itself. These benign cysts are typically treated in
conjunction with the related meniscal pathology.

Intramuscular Hemangioma
Intramuscular hemangiomas are arteriovenous malformations, or
occasionally purely venous malformations. 2 Both men and women
are affected equally, typically before 30 years of age. The most
frequent location is the thigh and, despite patients often relating a
history of trauma, there is no causal association between trauma
and intramuscular hemangiomas. 2 , 3 Symptoms typically include
pain, swelling that fluctuates with activity, and warmth.
Radiographs of the affected area may show phleboliths or areas of
ossification. Histologically, lesions demonstrate a mixture of blood
vessels, fat, thrombus, smooth muscle, as well as fibrous and
myxoid tissue. 2 , 3 Intramuscular hemangiomas are characterized
by low signal intensity on T1-weighted MRI and high signal
intensity on T2-weighted MRI. Lobulations and septations of low-
to-intermediate signal create a lacelike and serpiginous pa ern of
this infiltrative lesion 42 (Figure 4). Treatment of symptomatic
intramuscular hemangiomas can include sclerosing agents and
surgical excision. 43 Sclerosing agents can provide significant pain
relief for patients (success reported in 72% to 86% of cases). 43
Complications from sclerosing agents, which average around 28%,
are determined by what anatomic structures are adjacent to the
lesion being treated, which may include nerve damage, skin
necrosis, or deep vein thrombosis. 43 Surgical excision is often
performed intralesionally to minimize muscle and nerve damage,
with associated recurrence ranging from 18% to 50%; 43 however,
recurrence after wide resection or marginal excision may be as low
as 7%. 44

Figure 4 Intramuscular hemangioma of the thigh.A, Axial T1-weighted

magnetic resonance image. B, Axial T2-weighted magnetic resonance image.
Asterisks indicate areas of disease (not all areas of disease are marked).
Summary
Many benign soft-tissue tumors and masses have a characteristic
clinical presentation and appearance on imaging studies. Once a
diagnosis has been confirmed, marginal excision is the surgical
treatment of choice with few exceptions. Asymptomatic lesions can
be safely monitored, as malignant transformation of benign soft-
tissue tumors is exceedingly rare.

Key Study Points

Lipomas can be diagnosed with MRI; they are homogeneous and isointense to
subcutaneous fat on all sequences, with no abnormal enhancement on postcontrast
imaging.
Atypical lipomatous tumors often are located deep to fascia within the extremities
and have a low risk of either local recurrence or malignant transformation.
Desmoid tumor (extra-abdominal fibromatosis) is an infiltrative, locally aggressive,
but benign lesion. Wide local excision with negative margins is preferable to
marginal excision to decrease local recurrence. Various nonsurgical treatments are
available as alternatives to resection, especially when surgery is likely to result in
morbidity or recurrence.
Nodular fasciitis is a self-limiting, solitary mass with overexpression of ubiquitin-
specific peptidase 6.
Diffuse tenosynovial giant cell tumor, most commonly located in the knee, often
presents with pain and swelling. The finding that it overexpresses colony-stimulating
factor 1 has led to targeted tyrosine kinase inhibitor (pexidartinib) for use in
recalcitrant cases.

Annotated References
1. Mayerson JL, Scharschmidt TJ, Lewis VO, Morris CD: Diagnosis
and management of soft-tissue masses. J Am Acad Orthop Surg
2014;22(11):742-750.
2. Goldblum JR, Folpe AL, Weiss WS, eds: Enzinger & Weiss’s Soft
Tissue Tumors, ed 6. Elsevier, 2014.
3. Fletcher CDM, Bridge JA, Hogendoorn PCW, et al: WHO
Classification of Tumours of Soft Tissue and Bone, ed 4. IARC Press,
2013.
 4. Johnson CN, Ha AS, Chen E, Davidson D: Lipomatous soft-
tissue tumors. J Am Acad Orthop Surg 2018;26(22):779-788.
5. Papp DF, Khanna AJ, McCarthy EF, Carrino JA, Farber AJ,
Frassica FJ: Magnetic resonance imaging of soft-tissue tumors:
Determinate and indeterminate lesions. J Bone Joint Surg Am
2007;89(suppl 3):103-115.
6. Rauh J, Klein A, Baur-Melnyk A, et al: The role of surgical
margins in atypical lipomatous tumours of the extremities. BMC
Musculoskelet Disord 2018;19(1):152.
7. Knebel C, Neumann J, Schwaiger BJ, et al: Differentiating
atypical lipomatous tumors from lipomas with magnetic
resonance imaging: A comparison with MDM2 gene
amplification status. BMC Cancer 2019;19(1):309. The authors
present a retrospective analysis of MRI characteristics of lipomas
versus ALTs with comparison to histologic features and MDM2
amplification after surgical resection. Level of evidence: II.
8. Lee ATJ, Thway K, Huang PH, Jones RL: Clinical and molecular
spectrum of liposarcoma. J Clin Oncol 2018;36(2):151-159.
9. Weaver J, Downs-Kelly E, Goldblum JR, et al: Fluorescence in
situ hybridization for MDM2 gene amplification as a diagnostic
tool in lipomatous neoplasms. Mod Pathol 2008;21(8):943-949.
10. Binh MB, Sastre-Garau X, Guillou L, et al: MDM2 and CDK4
immunostainings are useful adjuncts in diagnosing well-
differentiated and dedifferentiated liposarcoma subtypes: A
comparative analysis of 559 soft tissue neoplasms with genetic
data. Am J Surg Pathol 2005;29(10):1340-1347.
11. Sommerville SM, Pa on JT, Luscombe JC, Mangham DC,
Grimer RJ: Clinical outcomes of deep atypical lipomas (well-
differentiated lipoma-like liposarcomas) of the extremities. ANZ J
Surg 2005;75(9):803-806.
12. Mussi CE, Daolio P, Cimino M, et al: Atypical lipomatous
tumors: should they be treated like other sarcoma or not?
Surgical consideration from a bi-institutional experience. Ann
Surg Oncol 2014;21(13):4090-4097.
13. Mavrogenis AF, Lesensky J, Romagnoli C, Alberghini M, Letson
GD, Ruggieri P: Atypical lipomatous tumors/well-differentiated
liposarcomas: Clinical outcome of 67 patients. Orthopedics
2011;34(12):e893-e898.
14. Dangoor A, Seddon B, Gerrand C, Grimer R, Whelan J, Judson I:
UK guidelines for the management of soft tissue sarcomas. Clin
Sarcoma Res 2016;6:20.
15. Rozental TD, Khoury LD, Donthineni-Rao R, Lackman RD:
Atypical lipomatous masses of the extremities: Outcome of
surgical treatment. Clin Orthop Relat Res 2002;398:203-211.
16. Presman B, Jauffred SF, Kornø MR, Petersen MM: Low
recurrence rate and risk of distant metastases following marginal
surgery of intramuscular lipoma and atypical lipomatous tumors
of the extremities and trunk wall. Med Princ Pract 2020;29(3):203-
210. This retrospective study of 176 patients assessed local
recurrence rates, dedifferentiation, and metastatic disease of
intramuscular lipomas and ALTs treated with surgical excision.
The follow-up time period was 10 years. Level of evidence: IV.
17. Vilanova JC, Barceló J, Villalón M, Aldomà J, Delgado E, Zapater
I: MR imaging of lipoma arborescens and the associated lesions.
Skeletal Radiol 2003;32(9):504-509.
18. Jang E, Danford NC, Levin AS, Tyler WK: Intra-articular
tumors: Diagnosis and management of the most common
neoplasms involving synovial joints. JBJS Rev 2018;6(12):e8.
19. WHO Classification of Tumours Editorial Board: WHO
Classification of Tumours of Soft Tissue and Bone, ed 5. IARC Press,
2020. An update of the 2013 edition is presented.
20. Kallen ME, Hornick JL: The 2020 WHO Classification: What’s
new in soft tissue tumor pathology? Am J Surg Pathol
2021;45(1):e1-e23. This article highlights key changes in the 2020
WHO Classification, especially focusing on molecular genetics.
Level of evidence: V.
21. Mariño-Enriquez A, Nascimento AF, Ligon AH, Liang C,
Fletcher CD: Atypical spindle cell lipomatous tumor:
 Clinicopathologic characterization of 232 cases demonstrating a
morphologic spectrum. Am J Surg Pathol 2017;41(2):234-244.
22. Abreu E, Aubert S, Wavreille G, Gheno R, Canella C, Co en A:
Peripheral tumor and tumor-like neurogenic lesions. Eur J Radiol
2013;82(1):38-50.
23. Braschi-Amirfarzan M, Keraliya AR, Krajewski KM, et al: Role of
imaging in management of desmoid-type fibromatosis: A primer
for radiologists. Radiographics 2016;36(3):767-782.
24. Desmoid Tumor Working Group: The management of desmoid
tumours: A joint global consensus-based guideline approach for
adult and paediatric patients. Eur J Cancer 2020;127:96-107. The
authors present a consensus treatment guideline from the
European Reference Network for rare solid adult cancers,
EURACAN, the European Organization for Research and
Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma
Group (STBSG), Sarcoma Patients EuroNet (SPAEN) and The
Desmoid Tumor Research Foundation (DTRF). Level of evidence:
II.
25. Newman ET, Lans J, Kim J, et al: PROMIS function scores are
lower in patients who underwent more aggressive local treatment
for desmoid tumors. Clin Orthop Relat Res 2020;478(3):563-577.
Published correction appears in Clin Orthop Relat Res.
2020;478(5):1132. Calderon, Santiago Lozano [corrected to
Lozano-Calderon, Santiago A]. This retrospective review of 102
patients with desmoid tumor included both a primary and
recurrence cohort of patients. The authors evaluated patients
treated with localized interventions, systemic treatments, or
both. Specific analysis is presented regarding an event-free
survival and patient-reported outcomes measurement
information system based on treatment modality. Level of
evidence: III.
26. van Broekhoven DLM, Verschoor AJ, van Dalen T, et al:
Outcome of nonsurgical management of extra-abdominal, trunk,
and abdominal wall desmoid-type fibromatosis: A population-
 based study in the Netherlands. Sarcoma 2018; June 21 [Epub
ahead of print].
27. Yan YY, Walsh JP, Munk PL, et al: A single-center 10-year
retrospective analysis of cryoablation for the management of
desmoid tumors. J Vasc Intervent Radiol 2021;32(9):1277-1287. This
retrospective cohort study evaluated cryoablation for either first-
line or subsequent therapy for desmoid tumors. Level of
evidence: III.
28. Cuomo P, Scoccianti G, Schiavo A, et al: Extra-abdominal
desmoid tumor fibromatosis: A multicenter EMSOS study. BMC
Cancer 2021;21(1):437. This is a multicenter, retrospective study
evaluating the effectiveness of various treatment modalities for
desmoid tumors. More than 300 patients were included in the
study. Both observation and local recurrence after surgery had
similar rates of progression of disease. Level of evidence: III.
29. Erickson-Johnson MR, Chou MM, Evers BR, et al: Nodular
fasciitis: A novel model of transient neoplasia induced by MYH9-
USP6 gene fusion. Lab Invest 2011;91(10):1427-1433.
30. Nakayama S, Nishio J, Aoki M, Koga K, Nabeshima K,
Yamamoto T: Ubiquitin-specific peptidase 6 (USP6)-associated
fibroblastic/myofibroblastic tumors: Evolving concepts. Cancer
Genomics Proteomics 2021;18(2):93-101. A review of ubiquitin-
specific peptidase 6-associated fibroblastic/myofibroblastic
tumors is presented, with a specific focus on molecular genetics
and histologic characteristics. Level of evidence: V.
31. Sandler AB, Scanaliato JP, Dennis T, et al: Treatment of
dupuytren’s contracture with collagenase: A systematic review.
Hand (N Y) 2021; January 21 [Epub ahead of print]. A systematic
review of Dupuytren contracture when managed with collagenase
Clostridium histolyticum is presented; treatment-related adverse
events and recurrence of contractures are discussed. Level of
evidence: II.
32. West RB, Rubin BP, Miller MA, et al: A landscape effect in
tenosynovial giant-cell tumor from activation of CSF1 expression
 by a translocation in a minority of tumor cells. Proc Natl Acad Sci
USA 2006;103(3):690-695.
33. Tap WD, Gelderblom H, Palmerini E, et al: Pexidartinib versus
placebo for advanced tenosynovial giant cell tumour (ENLIVEN):
A randomised phase 3 trial. Lancet 2019;394(10197):478-487.
Results from a phase 3 randomized trial of pexidartinib, a
tyrosine kinase inhibitor for patients with diffuse, advanced
TGCT, are presented. Level of evidence: I.
34. Strike SA, Puhaindran ME: Tumors of the hand and the wrist.
JBJS Rev 2020;8(6):e0141. A review of common benign and
malignant tumors of the hand and wrist is presented. Level of
evidence: IV.
35. Hsu CS, Hen VR, Yao J: Tumours of the hand. Lancet Oncol
2007;8(2):157-166.
36. Williams J, Hodari A, Janevski P, Siddiqui A: Recurrence of
giant cell tumors in the hand: A prospective study. J Hand Surg
Am 2010;35(3):451-456.
37. Stephan SR, Shallop B, Lackman R, Kim TW, Mulcahey MK:
Pigmented villonodular synovitis: A comprehensive review and
proposed treatment algorithm. JBJS Rev 2016;4(7):e3.
38. Neumann JA, Garrigues GE, Brigman BE, Eward WC: Synovial
chondromatosis. JBJS Rev 2016;4(5):e2.
39. Konigsberg MW, Tedesco LJ, Mueller JD, et al: Recurrence rates
of dorsal wrist ganglion cysts after arthroscopic versus open
surgical excision: a retrospective comparison. Hand (NY) 2021;
April 1 [Epub ahead of print]. A retrospective review of
recurrence rates of dorsal wrist ganglion cysts treated either open
or arthroscopically is presented. The results from this review of
172 patients indicate that recurrence is lower with open surgical
excision. Level of evidence: III.
40. Van Nest DS, Tjoumakaris FP, Smith BJ, Bea y TM, Freedman
KB: Popliteal cysts: A systematic review of nonoperative and
operative treatment. JBJS Rev 2020;8(3):e0139. The authors review
treatment options for popliteal cysts. Level of evidence: IV.
41. Campbell SE, Sanders TG, Morrison WB: MR imaging of
meniscal cysts: Incidence, location, and clinical significance. AJR
Am J Roentgenol 2001;177(2):409-413.
42. Teo EL, Strouse PJ, Hernandez RJ: MR imaging differentiation of
soft-tissue hemangiomas from malignant soft-tissue masses. AJR
Am J Roentgenol 2000;174(6):1623-1628.
43. Crawford EA, Slotcavage RL, King JJ, Lackman RD, Ogilvie CM:
Ethanol sclerotherapy reduces pain in symptomatic
musculoskeletal hemangiomas. Clin Orthop Relat Res
2009;467(11):2955-2961.
44. Bella GP, Manivel JC, Thompson RCJr, Clohisy DR, Cheng EY:
Intramuscular hemangioma: Recurrence risk related to surgical
margins. Clin Orthop Relat Res 2007;459:186-191.
C H AP T E R 7 5

Soft-Tissue Sarcomas
Tae Won B. Kim MD, CPE, FAAOS, Christina J. Gutowski
MD, MPH, FAAOS, Gord Guo Zhu MD, PhD

Dr. Kim or an immediate family member has received royalties from Adler Ortho; is a member of a
speakers’ bureau or has made paid presentations on behalf of Daiichi Sankyo and OncLive;
serves as a paid consultant to or is an employee of Adler; and serves as a board member, owner,
officer, or committee member of American Academy of Orthopaedic Surgeons and
Musculoskeletal Tumor Society. Dr. Gutowski or an immediate family member has received
royalties from Adler Ortho and serves as a paid consultant to or is an employee of Adler Ortho.
Neither Dr. Zhu nor any immediate family member has received anything of value from or has
stock or stock options held in a commercial company or institution related directly or indirectly to
the subject of this chapter.

ABSTRACT
Soft-tissue sarcomas represent a heterogeneous group of
mesenchymal-derived malignancies with behavior ranging from
indolent to highly aggressive. Their clinical presentations vary,
although the most concerning masses tend to be large, painless,
and deep to fascia, with a history of progressive growth. MRI, with
or without contrast, remains the preferred imaging modality,
whereas core biopsy is the most commonly used method to
establish a tissue diagnosis. Current treatment options include
wide surgical resection and radiation therapy. Although systemic
treatment options such as chemotherapy and immunotherapy can
be used in the management of some soft-tissue sarcomas, they
remain controversial in most. Metastatic disease occurs in 10% and
30% of patients with low-grade and high-grade sarcomas,
respectively, most commonly in the lungs. Overall survival remains
at 60% to 70%, demonstrating a need for more effective therapies,
especially for metastatic disease. Knowledge of the genetic basis of
these sarcomas continues to grow and hopefully will pave the way
to improved outcomes. It is highly recommended that primary
orthopaedic surgeons refer all soft-tissue masses concerning for
sarcoma to their local orthopaedic oncologist to avoid the
complications of inappropriate biopsy or excision.
Keywords: immunotherapy; malignant; soft-tissue sarcoma;
targeted therapy; wide resection

Introduction
Soft-tissue sarcomas make up a heterogeneous group of
malignancies arising from mesenchymal stem cells. They are rare,
with an estimated incidence of 13,460 (0.7% of all new cancers) in
the United States in 2021. 1 The extremities and retroperitoneum
remain the most common sites of disease, accounting for more than
80% of cases (60% extremities, 20% retroperitoneum), with the
remaining 20% in the head/neck and trunk. 2 An analysis of the
National Cancer Database in 2014 showed that soft-tissue sarcomas
are more prevalent in males than females, with a ratio of 1.23 to
1.00. 3 Localized disease remains the most common stage at initial
presentation, with reports of local recurrence from 24% to 40% for
low-grade and high-grade tumors, respectively. 4 Metastatic disease
occurs via hematologic routes, with metastases occurring at 10%
and 30% in low-grade and high-grade sarcomas, respectively. More
than 80% of metastatic disease is found in the lungs, although
certain histologies, such as myxoid liposarcoma, have less
predictable metastatic pa erns. 5 , 6 Management of metastatic soft-
tissue sarcoma is largely palliative. Overall survival is worse with
higher grade tumors and has not improved substantially over
recent decades. 7

Common Sarcoma Types

Soft-tissue sarcomas originate from mesenchymal stem cells and
are categorized by their lines of differentiation, such as adipose,
neural, or myogenic. According to the World Health Organization,
there are more than 100 distinct subtypes of soft-tissue sarcomas. 8
Advances in genomic profiling in cancer have increased knowledge
of the genetic pathogenesis of these soft-tissue sarcomas.
Undifferentiated pleomorphic sarcoma, formerly known as
malignant fibrous histiocytoma, is the most common high-grade
soft-tissue sarcoma. It lacks a clear line of differentiation and is
driven by extreme genomic instability, rather than a specific
mutation. 9 Five other major types of soft-tissue sarcoma and the
recent genetic advancements associated with them are discussed in
the following paragraphs.

Liposarcoma
Liposarcomas are of adipocytic differentiation and account for
approximately 15% to 20% of all soft-tissue sarcomas. 10 , 11 There are
four distinct types of liposarcomas, including well-differentiated
liposarcoma/atypical lipomatous tumor (ALT), dedifferentiated
liposarcoma, myxoid liposarcoma, and pleomorphic liposarcoma. 12

Well-Differentiated Liposarcoma/ALTs
ALTs and well-differentiated liposarcomas present as slowly
enlarging masses within the limbs or retroperitoneum, most
commonly diagnosed in the fifth to seventh decades of life. 13 On
T1-weighted magnetic resonance image, the mass exhibits fat signal
with internal stranding (Figure 1, A). Although histologically
identical, these tumors are designated ALTs when located in the
extremities and well-differentiated liposarcomas when located in
the retroperitoneum. They are also distinct in terms of their clinical
behavior; 14 , 15 ALTs can undergo marginal surgical excision with
low risk of local recurrence, whereas well-differentiated
liposarcomas have a higher likelihood of local recurrence (as high
as 50%) and dedifferentiation (10%). 14 , 15 Well-differentiated
liposarcomas were previously excised with wide margins,
potentially including organ resection, but some studies have
advocated for a less aggressive surgical approach because visceral
involvement is rare. 16 Histologically, ALTs and well-differentiated
liposarcomas are predominantly composed of variable-sized mature
adipocytes with fibrous septa and cells with irregular, enlarged
hyperchromatic nuclei 17 (Figure 1, B). Genomic analysis of well-
differentiated liposarcomas/ALT has shown amplification of
chromosome 12q13-15, with MDM2 and HMGA2 most constantly
included in this amplicon. In 75% to 90% of cases, CDK4 is also
included in the amplicon. Currently, MDM2 (and/or CDK4)
amplification by fluorescence in situ hybridization is clinically used
to diagnose well-differentiated liposarcomas/ALT. 18

Figure 1 Atypical lipomatous tumors/well-differentiated liposarcomas are

shown.A, Coronal T1-weighted magnetic resonance image sequence showing a
lipomatous mass within the left thigh. B, Histologic image showing adipocytes of
variable sizes, fibrous strands in between, and scattered atypical
hyperchromatic nuclei.

Dedifferentiated Liposarcoma
Dedifferentiated liposarcomas occur when well-differentiated
liposarcomas/ALT undergo progression and lose their adipocytic
differentiation. A dedifferentiated liposarcoma can also arise de
novo without an associated well-differentiated liposarcoma/ALT
component. Histologically, dedifferentiated liposarcoma arising
from well-differentiated liposarcoma/ALT shows 2 distinct tissue
components: a high-grade, usually pleomorphic undifferentiated
spindle cell sarcoma, juxtaposed against a well-differentiated
liposarcoma/ALT 19 (Figure 2). Dedifferentiated liposarcoma shares
the same genetic amplification as well-differentiated
liposarcoma/ALT in 12q13-15 but exhibits additional chromosomal
abnormalities that may lead to dedifferentiation. These include the
reamplification of 1p32 and 6q23, and overexpression of replication-
dependent histone mRNA, all of which have been shown to be
associated with poor prognosis. 20 - 22 Dedifferentiated liposarcomas
are associated with high rates of local recurrence and metastases;
they are therefore treated as true soft-tissue sarcomas with wide
excision and radiation therapy.
 Figure 2 Dedifferentiated liposarcoma.Histologic slide showing a high-grade,
pleomorphic spindle cell sarcoma (right on slide) juxtaposed against a low-grade
well-differentiated liposarcoma (left on slide, cellular variant with no fatty
formation).

Myxoid Liposarcoma
Myxoid liposarcoma is a distinct subtype that makes up 30% of all
liposarcomas. This variant exhibits an unusual metastatic pa ern
including the axilla, nonpulmonary soft tissues, and the skeleton. 23
, 24
Staging with CT of the chest/abdomen/pelvis or positron
emission tomography (PET) scan, as well as magnetic resonance
image of the spinal axis, is indicated to evaluate for atypical
metastases. Histologically, immature lipoblasts are seen within a
myxoid background on histologic examination (Figure 3). Primitive
round cells with large blue nuclei are also seen, with the clinical
implications described previously. Myxoid liposarcoma is
characterized by a t(12:16) translocation with expression of the
fusion protein FUS-DDIT3, which is pathognomonic for this tumor.
It has been suggested that the fusion protein prevents adipocytic
differentiation, leading to the uncontrolled proliferation of
lipoblasts that cannot mature. 25 Overall survival of myxoid
liposarcoma is associated with the percentage of round cell
component, with 5- and 10-year survival at 95% and 87%,
respectively, for less than 5% round cell myxoid liposarcoma,
compared with 80% and 80%, respectively, in greater than 5% round
cell myxoid liposarcoma. 26 As such, chemotherapy is indicated if
these round cells comprise greater than 5% of the cell population. 27

Figure 3 Myxoid liposarcoma.Histologic slide showing monomorphic tumor

cells in a myxoid background with prominent vasculature and mucin pools that
do not exhibit high levels of pleomorphism consistent with a translocation-driven
tumor.
Pleomorphic Liposarcoma
Pleomorphic liposarcoma is a rare, aggressive subtype. Patients
typically present with a rapidly enlarging soft-tissue mass in the
extremity, although they have been described in the trunk and
retroperitoneum. 28 , 29 Histologically, it appears as numerous
pleomorphic lipoblasts in a background of high-grade
undifferentiated pleomorphic sarcoma (Figure 4). Pleomorphic
liposarcoma shows no specific genetic profile, although more gains
than losses are noted, and its genome does not share the
amplification of 12q13-15 as well-differentiated liposarcomas/ALT. 30
Although surgical resection, radiation therapy, and chemotherapy
have been used, overall survival is reported to be 57%, which is
significantly lower than that of other liposarcomas. 30
 Figure 4 Pleomorphic liposarcoma.Histologic slide showing highly
pleomorphic lipoblastic tumor cells with cytoplasmic vacuoles indenting the
nuclei.

Angiosarcoma
Angiosarcoma is an aggressive soft-tissue sarcoma arising from
vascular endothelial cells. It accounts for 2% to 3% of all adult soft-
tissue sarcomas and occurs in the sixth and seventh decades of life.
Cutaneous and superficial locations make up 60% to 70% of all
cases. 31 Cutaneous angiosarcomas present as discolored nodules
with or without ulceration. Deeper angiosarcomas in the
abdomen/pelvis can cause nonspecific symptoms such as
abdominal pain, nausea, or vomiting. 32 Although there is no
definitive cause, chronic lymphedema, radiation exposure,
environmental carcinogens, and genetic syndromes all have been
shown to be risk factors. 33 The lung and brain are the most
common sites of metastasis, and this tumor has the capacity for
lymphatic spread as well. 34 Overall survival has been reported to be
6 to 16 months, with 5-year survival being 30% to 40%. 33 , 34 Its
infiltrative growth pa ern within soft tissue makes diagnosis with
imaging difficult, as a palpable mass or crisp radiologic border is
not always present.
Histologically, variations in differentiation are visible in the
vascular channels that are formed, ranging from well-differentiated
to poorly differentiated channels (Figure 5). Polygonal and spindle-
shaped cells with epithelioid and round cell features are also
visible. Stains for vascular markers are positive, including CD31
(gold standard), CD34, ERG, and vascular endothelial growth factor.
35 , 36

Figure 5 Angiosarcoma.Histologic slide showing malignant cells creating

vascular channels.
 Several genes have been shown to be upregulated in
angiosarcoma. The MYC proto-oncogene on chromosome 8q24 is
amplified in 90% of secondary angiosarcomas from radiation
exposure compared with primary angiosarcomas, where MYC
amplification was not a useful diagnostic tool. 37 , 38 Overexpression
of the FLT4 gene (encoding for vascular endothelial growth factor
receptor 4) has been associated with MYC co-overexpression in
angiosarcoma. 39 As described in a 2020 study, the Angiosarcoma
Project, a total of 47 tumors underwent whole-genome sequencing
and showed mutations in the KDR, TP53, and PICK3CA genes. 40

Leiomyosarcoma
Leiomyosarcoma accounts for 10% to 20% of all soft-tissue
sarcomas and is most frequently found in the abdomen, uterus, and
blood vessels. Although the extremity is a less common location,
this tumor accounts for 10% to 15% of extremity sarcomas, with a
preference for the thigh. It is most often seen in the sixth and
seventh decades of life, with a slight male predisposition when
occurring in the limbs. 41
Histologically, leiomyosarcoma has spindle cells arranged in a
fascicular pa ern with varying degrees of pleomorphism. Staining
is positive for smooth muscle actin and desmin, demonstrating its
smooth muscle lineage (Figure 6). Recent advances in whole-exome
sequencing have demonstrated increased copy number alterations
and gene mutations in leiomyosarcoma and hopefully will lead to
the development of targeted therapies to improve outcomes. 42
 Figure 6 Leiomyosarcoma.Histologic slide showing a highly cellular spindle
cell sarcoma with eosinophilic cytoplasm and fascicular arrangement consistent
with leiomyosarcoma.

Surgical resection with radiation remains the treatment for

localized disease in the extremities. Chemotherapy appears
controversial because efficacy has not been strongly established
and is reserved mainly for patients with metastatic disease.
Prognosis is dependent on histologic grade, size, and depth, and
high-risk tumors are often radiated before or after surgical
resection. Five-year survival is reported at 76%, 60%, 45%, and 29%
for stages I, II, III, and IV disease, respectively. 41

Rhabdomyosarcoma
Rhabdomyosarcoma is most commonly found in children younger
than 10 years, although it can develop in adolescents and adults.
Two distinct types, alveolar rhabdomyosarcoma and embryonal
rhabdomyosarcoma, exist; these have a similar incidence, although
the embryonal type has a male predilection.
 Histologically, alveolar rhabdomyosarcoma is one of the small
round blue cell tumors, and embryonal rhabdomyosarcoma
exhibits features of immature skeletal myoblasts (Figure 7). Most
cases of alveolar rhabdomyosarcoma are driven by a genetic
translocation t(2:13) or t(1:13), creating a fusion protein PAX3-
FOXO1 or PAX7-FOXO1. Therapies targeting the PAX3-FOXO1
protein of alveolar rhabdomyosarcoma are currently being studied
in vitro. 43 , 44 Embryonal rhabdomyosarcoma, however, does not
appear to be driven by a fusion protein. 45

Figure 7 Histologic slide showing alveolar rhabdomyosarcoma.Nests of small

blue round tumor cells showing both solid and discohesive areas (alveolar
pattern).

Treatment for both is multimodal with surgical resection,

radiation therapy, and chemotherapy. Studies evaluating the role of
targeted therapy and immunotherapy are ongoing. The 5-year
overall survival for localized disease in alveolar rhabdomyosarcoma
is reported to be 70% to 80%, whereas that for metastatic disease is
less than 20%. 46 Embryonal rhabdomyosarcoma appears to have a
be er prognosis, with 5-year survival reported to be as high as 90%.
47
Unfortunately, an estimated 15% of patients present with
metastatic disease. 45

Synovial Sarcoma
Synovial sarcoma accounts for 10% of soft-tissue sarcomas and
most often occurs in the extremities. It is the most common soft-
tissue sarcoma of the foot and ankle and usually develops in the
second or third decade. Because synovial sarcoma often presents as
a small, painless mass in the distal extremities, it can easily be
mistaken for a benign entity, leading to inappropriate excision and
contamination of surrounding tissues. Therefore, advanced imaging
is indicated for any soft-tissue lesion in the hand/wrist or foot/ankle
without the pathognomonic history, location, and examination of a
classic cyst.
Histologically, synovial sarcoma exhibits a monophasic or
biphasic appearance. The monophasic variant is composed of
spindle cells arranged in dense fascicle with varying pleomorphism.
The biphasic variant has the monophasic spindle cells, surrounding
an epithelial component clustered in nests or glands (Figure 8).
Histologic diagnosis can be challenging to those who are
unaccustomed to musculoskeletal soft-tissue pathology. In more
than 95% of cases, the t(X:18) chromosomal translocation creates
the SS18:SSX fusion protein, which drives tumorigenesis. Hence,
the gold standard for diagnosis is fluorescence in situ
hybridization, reverse transcriptase-polymerase chain reaction, or
next-generation sequencing to identify the translocation or fusion
gene, but these techniques are not readily available in all
laboratories and can miss variants. In a 2020 study, two monoclonal
antibodies that bind specifically to the fusion protein were
developed, which may improve diagnostic capability. 48
 Figure 8 Histologic slides showing synovial sarcoma.A, Monophasic synovial
sarcoma showing predominant spindle cells with fascicular formation. B,
Biphasic synovial sarcoma showing spindle cell component and an epithelial
glandular-appearing component.

Treatment includes wide surgical resection, radiation therapy,

and chemotherapy. Synovial sarcoma is one of the few soft-tissue
sarcomas for which data support the use of chemotherapy,
particularly in the pediatric and young adult population. 49 In spite
of this, the prognosis remains poor, with 5-year overall survival
reported to be 50% to 60%. 49 Understanding of how synovial
sarcoma interacts with the immune system is increasing and
hopefully will lead to the development of additional therapies to
improve overall survival. 50 , 51

Imaging
High-quality imaging is critical in the diagnosis and management
of soft-tissue sarcomas. Radiographs remain the most common first
study performed, and although they can be helpful in cases of
identifying phleboliths in hemangiomas or subtle calcification in
synovial sarcomas, they are rarely diagnostic. Ultrasonography can
evaluate for vascular flow or determine whether the mass is cystic
or solid. A scoring system that could use ultrasonography to
correctly determine if a mass is benign or malignant with 85%
accuracy has been developed, although adoption of this scoring
system remains limited. 52 MRI with and without contrast remains
the preferred diagnostic modality for evaluation of deep soft-tissue
masses and can be diagnostic for certain benign tumors such as
lipoma. However, most soft-tissue sarcomas present with a
common MRI appearance: hypointense to fat on T1-weighted
sequence, hyperintense to fat and muscle on T2-weighted fat-
saturated sequences, and heterogeneous post contrast
enhancement (Figure 9). Because these features are nonspecific,
tissue sampling is needed to distinguish between the various types
of soft-tissue sarcoma. A common misstep in the radiologic
evaluation and diagnosis of soft-tissue masses involves the
traditional teaching that rim enhancement is diagnostic for a cyst,
which should be excised marginally. It is critical for radiologists
and surgeons to understand that soft-tissue sarcomas with
significant internal necrosis may exhibit rim enhancement also
(Figure 10). Furthermore, a non–contrast-enhanced MRI of a
myxoid tissue–dominant sarcoma may be interpreted as a fluid-
filled cyst, leading to inappropriate resection. As such, a high index
of suspicion must be maintained by surgeons interpreting MRI
studies of soft-tissue tumors. Recent studies on the usefulness of
MRI findings to predict the grade of sarcomas have found that
peritumoral enhancement (odds ratio 3.4), presence of necrosis
(odds ratio 2.4), and heterogeneous signal intensities ≥50% on T2-
weighted sequences (odds ratio 2.3) are the best predictors of low-
grade versus high-grade tumors. 53 , 54
Figure 9 Magnetic resonance images of sarcoma.A, Axial magnetic
resonance T2-weighted fat-saturated image showing high fluid intensity signal
within the mass; B, Axial magnetic resonance T2-weighted fat-saturated
postcontrast image showing heterogeneous enhancement with areas of solid
enhancement that is concerning for a soft-tissue sarcoma.
 Figure 10 Cystic soft-tissue sarcoma.Axial magnetic resonance T2-weighted
fat-saturated postcontrast image showing predominant rim enhancement. This
was initially read as a cyst but biopsy was consistent with high-grade soft-tissue
sarcoma with significant necrosis.

Biopsy remains the gold standard for establishing a diagnosis of

soft-tissue sarcoma. Tissue sampling can be obtained via core
biopsy or open biopsy, with core biopsy being preferable to
minimize contamination. Recent studies have shown the sensitivity
and specificity of core biopsy to be 97% and 99%, respectively
(compared with 96% and 100%, respectively, for open biopsy),
justifying its use as the first-line method of obtaining a tissue
sample. 55 , 56
 Imaging studies are used for staging after a diagnosis of soft-
tissue sarcoma is established. The lung remains the most common
site of distant metastases, and therefore, CT of the chest with or
without contrast is required. CT of the abdomen and pelvis remains
controversial because studies have shown the presence of
metastases in these locations range from 2.9% to 16%. 57 , 58
Currently, the National Comprehensive Cancer Network
Guidelines suggest the use of CT of the abdomen and pelvis based
on tumor histology (myxoid liposarcoma, angiosarcoma, and
leiomyosarcoma) because these entities have shown a propensity
for nonpulmonary metastases. 59 The use of PET/CT and PET/MRI in
staging has been accepted in the staging of soft-tissue sarcoma,
which has a propensity to metastasize to lymph nodes such as
rhabdomyosarcoma; however, its use in all soft-tissue sarcomas
remains a topic of debate. A 2020 study supported the use of
PET/CT in a pediatric population with soft-tissue sarcomas by
showing that this study changed management in 5 of 26 patients
(19%). 60

Treatment
The current accepted treatment option for most soft-tissue
sarcomas remains preoperative or postoperative radiation and
achieving a margin-negative surgical resection. The role of radiation
is to manage microscopic disease in tissue beyond the surgical
margin, facilitating complete tumor extirpation without radical
resection of an entire compartment. In most cases, a radiation dose
of 50 to 65 Gy is administered over 5 weeks. Although preoperative
or postoperative radiation therapy is equally effective in achieving
local control, each has its risks and benefits. Preoperative radiation
involves a smaller radiation field and lower overall dose but carries
with it a high rate of postoperative wound complications as high as
30% to 40%. 61 Postoperative radiation requires a larger treatment
volume, as the entire surgical field must be included. Additionally,
a higher overall dose of 60 to 65 Gy is used, although this 10 to 15
Gy difference compared with preoperative doses is not evidence-
based. As a result of the increased volume and dose, postoperative
radiation is associated with greater tissue fibrosis, lymphedema,
and radiation-induced osteonecrosis of bone, as well as the risk of
secondary radiation-induced sarcoma; however, it carries nearly
half the rate of postoperative wound complications. Recent decades
have seen a trend toward increased use of preoperative radiation,
although postoperative radiation should be considered in surgical
locations and patients with high risk of wound complication.
Advanced radiation techniques, such as intensity-modulated
radiation therapy to decrease the exposure of surrounding tissues
and stereotactic body radiation therapy to decrease the number of
treatment strategies needed, have been successfully used. 62 , 63
Brachytherapy to improve local control after surgical resection has
also been successfully implemented. 64 Chemotherapy remains
controversial in the se ing of nonmetastatic disease because of the
lack of significant improvement in overall survival. 65 Doxorubicin
and ifosfamide remain the most common regimen and are used on
an individualized basis, depending on demographics, tumor size,
and histology. As an example, ifosfamide-based chemotherapy in
synovial sarcoma has been shown to improve disease-specific
survival, and therefore is commonly used in nonmetastatic patients.
66

As the understanding of soft-tissue sarcoma pathogenesis has

evolved, so has the ability to use nontraditional systemic treatment
strategies. Targeted therapy, immunotherapy, and cell-based
therapies continue to be studied as alternative and adjuvant
treatment strategies.
Targeted therapy refers to the use of an agent that blocks specific
cellular pathways either altered or overexpressed in specific
malignancies. As an example, studies have shown increased
expression of vascular endothelial growth factor in soft-tissue
sarcomas, so blocking the receptor for this growth factor may
improve systemic control. Pazopanib, an oral agent that blocks the
vascular endothelial growth factor receptors, has been shown to
improve progression-free survival in patients with soft-tissue
sarcoma. Many other targeted therapies are available such as
sorafenib (multikinase inhibitor), imatinib (Bcr-Abl tyrosine kinase
inhibitor), larotrectinib (neurotrophic tropomyosin receptor kinase
selective inhibitor), and many more that are currently being
developed and studied. 67
Immunotherapies are a new class of therapeutics designed to
leverage the patient’s own immune system as treatment.
Malignancies engage the programmed cell death 1 receptor and
programmed death-ligand 1 inhibitor to evade the innate immune
system, and programmed death-ligand 1 inhibitors have
successfully improved survival in many carcinomas. Their efficacy
as monotherapy in soft-tissue sarcomas has been limited; however,
a recent clinical study evaluating a combination of
immunotherapies has shown promise. 68
Cellular immunotherapy is a novel treatment that directly alters
the patient’s immune cells and re-introduces them into the patient.
Revolutionary in the management of leukemia, cellular
immunotherapy genetically modifies dendritic T cells to express
chimeric antigen receptors, which are specific to a tumor. These
cells then recognize the antigens from the tumor cells and destroy
them. Application of cellular immunotherapy in soft-tissue
sarcomas remains in the nascent phases. The results of an early
study are encouraging, but larger studies will be needed to fully
evaluate the application of this technology in soft-tissue sarcoma
care. 69

Prognosis
Although emerging therapies continue to develop and be adopted
for management of soft-tissue sarcomas, overall survival continues
to be between 60% and 70% in patients with localized disease. Site,
size, and grade remain important prognostic variables, with large,
deep, high-grade soft-tissue sarcomas having poorer prognoses
compared with small, superficial, low-grade sarcomas. 70 One study
reported that 7.3% of patients present with metastases and have a
5-year 17% overall survival, even with aggressive surgical
management. Of these patients, more than 80% present with
pulmonary metastases, whereas 20% present with lymph node
metastases. Interestingly, those with lymph node metastases had
be er 5-year and median survivals compared with those with
pulmonary metastases (59% and 30 months versus 8% and 9
months, respectively). 71 Studies have shown improved median
survival for those undergoing pulmonary metastasectomy and, in
select patients, should be considered. 72 , 73

Summary
Soft-tissue sarcomas are a heterogeneous group of mesenchymal
cell–origin malignancies that can occur in any age group and
anatomic location. The diagnosis is made with a combination of
history, physical examination, imaging studies, and histologic
evaluation. Because of the risk of morbidity and mortality
associated with inappropriate treatment and the multidisciplinary
approach needed to provide patients with the best outcomes,
referral to an orthopaedic oncology specialist is recommended.
Margin-negative wide resection, radiation, and, in select cases,
chemotherapy comprise the treatment paradigm. Although the
overall prognosis remains unchanged, emerging therapies show
potential to improve outcomes.

Key Study Points

The management of a soft-tissue sarcoma requires a multidisciplinary approach,
requiring orthopaedic oncology, interventional radiology, musculoskeletal radiology,
medical oncology, radiation oncology, and musculoskeletal pathology.
MRI with and without contrast is the preferred imaging modality (of note, maintain
caution as cystic or hemorrhagic sarcomas may be mistakenly read as benign), and
histology is typically required to distinguish between specific types of soft-tissue
sarcoma.
Negative-margin resection with preoperative or postoperative radiation is required for
local control, whereas chemotherapy is only indicated for adjuvant systemic therapy
in select patients.
Targeted therapy, immunotherapy, and cell-based immunotherapies show promise in
the management of soft-tissue sarcomas.
 Because of the rarity of these malignancies, patients should be treated at an
institution with expertise in multidisciplinary sarcoma care.

Annotated References
1. National Cancer Institute: Cancer Stat Facts: Soft Tissue
including Heart Cancer, 2021. Available at:
h ps://seer.cancer.gov/statfacts/html/soft.html. This website
provides comprehensive epidemiologic data regarding soft tissue
sarcomas. Level of evidence: IV.
2. Clark MA, Fisher C, Judson I, Thomas JM: Soft-tissue sarcomas
in adults. N Engl J Med 2005;353(7):701-711.
3. Corey RM, Swe K, Ward WG: Epidemiology and survivorship of
soft tissue sarcomas in adults: A national cancer database report.
Cancer Med 2014;3(5):1404-1415.
4. Coindre JM, Terrier P, Bui NB, et al: Prognostic factors in adult
patients with locally controlled soft tissue sarcoma. A study of
546 patients from the French Federation of Cancer Centers
Sarcoma Group. J Clin Oncol 1996;14(3):869-877.
5. Hoang NT, Acevedo LA, Mann MJ, Tolani B: A review of soft-
tissue sarcomas: Translation of biological advances into
treatment measures. Cancer Manag Res 2018;10:1089-1114.
6. Canter RJ, Qin L-X, Ferrone CR, Maki RG, Singer S, Brennan MF:
Why do patients with low-grade soft tissue sarcoma die? Ann
Surg Oncol 2008;15(12):3550-3560.
7. Bonvalot S, Levy A, Terrier P, et al: Primary extremity soft tissue
sarcomas: Does local control impact survival? Ann Surg Oncol
2017;24(1):194-201.
8. Kallen ME, Hornick JL: The 2020 WHO classification: What’s
new in soft tissue tumor pathology? Am J Surg Pathol
2021;45(1):e1-e23. This review article analyzes the recent changes
in the World Health Organization’s fifth edition on soft-tissue
and bone tumors published in 2020. These include updates on
 new genetic findings that can aid in diagnosis and
prognostication. Level of evidence: V.
9. Widemann BC, Italiano A: Biology and management of
undifferentiated pleomorphic sarcoma, myxofibrosarcoma, and
malignant peripheral nerve sheath tumors: State of the art and
perspectives. J Clin Oncol 2018;36(2):160-167.
10. Ducimetiere F, Lurkin A, Ranchère-Vince D, et al: Incidence of
sarcoma histotypes and molecular subtypes in a prospective
epidemiological study with central pathology review and
molecular testing. PLoS One 2011;6(8):e20294.
11. Lee ATJ, Thway K, Huang PH, Jones RL: Clinical and molecular
spectrum of liposarcoma. J Clin Oncol 2018;36(2):151-159.
12. Fletcher CDM: The evolving classification of soft tissue tumours
– An update based on the new 2013 WHO classification.
Histopathology 2014;64(1):2-11.
13. Mavrogenis AF, Lesensky J, Romagnoli C, Alberghini M, Letson
GD, Ruggieri P: Atypical lipomatous tumors/well-differentiated
liposarcomas: Clinical outcome of 67 patients. Orthopedics
2011;34(12):e893-e898.
14. Nascimento AG: Dedifferentiated liposarcoma. Semin Diagn
Pathol 2001;18(4):263-266.
15. Laurino L, Furlane o A, Orvieto E, Dei Tos AP: Well-
differentiated liposarcoma (atypical lipomatous tumors). Semin
Diagn Pathol 2001;18(4):258-262.
16. Ikoma N, Roland CL, Torres KE, et al: Salvage surgery for
recurrent retroperitoneal well-differentiated liposarcoma: Early
reoperation may not provide benefit. Ann Surg Oncol
2018;25(8):2193-2200.
17. Forus A, Weghuis DO, Smeets D, et al: Comparative genomic
hybridization analysis of human sarcomas: I. Occurrence of
genomic imbalances and identification of a novel major amplicon
at 1q21-q22 in soft tissue sarcomas. Genes Chromosomes Cancer
1995;14(1):8-14.
18. Assi T, Ka an J, Rassy E, et al: Targeting CDK4 (cyclin-
dependent kinase) amplification in liposarcoma: A
comprehensive review. Crit Rev Oncol Hematol 2020;153:103029. In
this review article, the authors review the findings of CDK4
amplification in well-differentiated and dedifferentiated
liposarcoma. They discuss the ongoing clinical trials and
published studies regarding treatment while exploring the role of
CDK4-specific inhibitors. Level of evidence: V.
19. Dalal KM, Ka an MW, Antonescu CR, et al: Subtype specific
prognostic nomogram for patients with primary liposarcoma of
the retroperitoneum, extremity, or trunk. Ann Surg
2006;244(3):381-391.
20. Chibon F, Mariani O, Derré J, et al: A subgroup of malignant
fibrous histiocytomas is associated with genetic changes similar
to those of well-differentiated liposarcomas. Cancer Genet
Cytogenet 2002;139(1):24-29.
21. Yamashita K, Kohashi K, Yamada Y, et al: Prognostic significance
of the MDM2/HMGA2 ratio and histological tumor grade in
dedifferentiated liposarcoma. Genes Chromosomes Cancer
2021;60(1):26-37. In this study, the authors evaluated the ratio of
expression of MDM2 to HMGA2 in dedifferentiated liposarcoma
as a prognostic marker. After analyzing samples of 44 cases, the
authors found that a high MDM2/HMGA2 ratio was associated
with a poor prognosis. Level of evidence: II.
22. Yoo Y, Park SY, Jo EB, et al: Overexpression of replication-
dependent histone signifies a subset of dedifferentiated
liposarcoma with increased aggressiveness. Cancers (Basel)
2021;13(13):3122. The authors performed genomic sequencing on
38 dedifferentiated liposarcomas against normal tissue and
identified high levels of histone mutations involved in replication
pathways. Overexpression of HMGA2 was shown to be the cause
of the elevated histones. This may represent a subset of
dedifferentiated liposarcomas that behaves aggressively. Level of
evidence: II.
23. Schwab JH, Boland P, Guo T, et al: Skeletal metastases in myxoid
liposarcoma: An unusual pa ern of distant spread. Ann Surg
Oncol 2007;14(4):1507-1514.
24. Antonescu CR, Tschernyavsky SJ, Decuseara R, et al: Prognostic
impact of P53 status, TLS-CHOP fusion transcript structure, and
histological grade in myxoid liposarcoma: A molecular and
clinicopathologic study of 82 cases. Clin Cancer Res
2001;7(12):3977-3987.
25. Perez-Losada J, Pintado B, Gutiérrez-Adán A, et al: The chimeric
FUS/TLS-CHOP fusion protein specifically induces liposarcomas
in transgenic mice. Oncogene 2000;19(20):2413-2422.
26. Muratori F, Be ini L, Frenos F, et al: Myxoid liposarcoma:
Prognostic factors and metastatic pa ern in a series of 148
patients treated at a single institution. Int J Surg Oncol
2018;2018:8928706.
27. Fiore M, Grosso F, Lo Vullo S, et al: Myxoid/round cell and
pleomorphic liposarcomas: Prognostic factors and survival in a
series of patients treated at a single institution. Cancer
2007;109(12):2522-2531.
28. Downes KA, Goldblum JR, Montgomery EA, Fisher C:
Pleomorphic liposarcoma: A clinicopathologic analysis of 19
cases. Mod Pathol 2001;14(3):179-184.
29. Gebhard S, Coindre J-M, Michels J-J, et al: Pleomorphic
liposarcoma: Clinicopathologic, immunohistochemical, and
follow-up analysis of 63 cases – A study from the French
Federation of Cancer Centers Sarcoma Group. Am J Surg Pathol
2002;26(5):601-616.
30. Anderson WJ, Jo VY: Pleomorphic liposarcoma: Updates and
current differential diagnosis. Semin Diagn Pathol 2019;36(2):122-
128. This review paper provides the latest updates on
pleomorphic liposarcoma, a rare soft-tissue sarcoma. Strategies
for obtaining the correct diagnosis are discussed. Level of
evidence: V.
31. Shustef E, Kazlouskaya V, Prieto VG, Ivan D, Aung PP:
Cutaneous angiosarcoma: A current update. J Clin Pathol
2017;70(11):917-925.
32. Omiyale AO, Carton J: Clinical and pathologic features of
primary angiosarcoma of the kidney. Curr Urol Rep 2018;19(2):4.
33. Cao J, Wang J, He C, Fang M: Angiosarcoma: A review of
diagnosis and current treatment. Am J Cancer Res 2019;9(11):2303-
2313. This review paper provides the updates on angiosarcoma
diagnosis and treatment for this difficult-to-treat soft-tissue
sarcoma. Level of evidence: V.
34. Penel N, Marréaud S, Robin Y-M, Hohenberger P:
Angiosarcoma: State of the art and perspectives. Crit Rev Oncol
Hematol 2011;80(2):257-263.
35. Marusic Z, Billings SD: Histopathology of spindle cell vascular
tumors. Surg Pathol Clin 2017;10(2):345-366.
36. Wang L, Lao IW, Yu L, Wang J: Clinicopathological features and
prognostic factors in angiosarcoma: A retrospective analysis of
200 patients from a single Chinese medical institute. Oncol Le
2017;14(5):5370-5378.
37. Fraga-Guedes C, André S, Mastropasqua MG, et al:
Angiosarcoma and atypical vascular lesions of the breast:
Diagnostic and prognostic role of MYC gene amplification and
protein expression. Breast Cancer Res Treat 2015;151(1):131-140.
38. Requena C, Rubio L, Lavernia J, et al: Immunohistochemical
and fluorescence in situ hybridization analysis of MYC in a series
of 17 cutaneous angiosarcomas: A single-center study. Am J
Dermatopathol 2018;40(5):349-354.
39. Cornejo KM, Deng A, Wu H, et al: The utility of MYC and FLT4
in the diagnosis and treatment of postradiation atypical vascular
lesion and angiosarcoma of the breast. Hum Pathol 2015;46(6):868-
875.
40. Painter CA, Jain E, Tomson BN, et al: The Angiosarcoma
Project: Enabling genomic and clinical discoveries in a rare
cancer through patient-partnered research. Nat Med
 2020;26(2):181-187. This multinational, multi-institutional study
evaluated the feasibility of engaging patients with angiosarcoma
in the United States and Canada to submit clinical history and
sample tissue for whole exome sequencing. A total of 338
patients enrolled over 18 months, and 47 specimens were
sequenced. This study showed the feasibility of studying a rare
tumor through the recruitment of patients via an online platform.
Level of evidence: II.
41. George S, Serrano C, Hensley ML, Ray-Coquard I: Soft tissue
and uterine leiomyosarcoma. J Clin Oncol 2018;36(2):144-150.
42. Chudasama P, Mughal SS, Sanders MA, et al: Integrative
genomic and transcriptomic analysis of leiomyosarcoma. Nat
Commun 2018;9(1):144.
43. Rengaswamy V, Zimmer D, Süss R, Rössler J: RGD liposome-
protamine-siRNA (LPR) nanoparticles targeting PAX3-FOXO1 for
alveolar rhabdomyosarcoma therapy. J Control Release
2016;235:319-327.
44. Bharathy N, Berlow NE, Wang E, et al: The HDAC3-SMARCA4-
miR-27a axis promotes expression of the PAX3:FOXO1 fusion
oncogene in rhabdomyosarcoma. Sci Signal
2018;11(557):eaau7632.
45. Miwa S, Yamamoto N, Hayashi K, Takeuchi A, Igarashi K,
Tsuchiya H: Recent advances and challenges in the treatment of
rhabdomyosarcoma. Cancers (Basel) 2020;12(7):1758. This review
article evaluated the recent advances in the management of
rhabdomyosarcoma and highlighted the existing challenges faced
by physician and patients. Level of evidence: V.
46. Yang L, Takimoto T, Fujimoto J: Prognostic model for predicting
overall survival in children and adolescents with
rhabdomyosarcoma. BMC Cancer 2014;14:654.
47. Wang X, Feng J, Li Z, Zhang X, Chen J, Feng G: Characteristics
and prognosis of embryonal rhabdomyosarcoma in children and
adolescents: An analysis of 464 cases from the SEER database.
Pediatr Investig 2020;4(4):242-249. The authors used the
 Surveillance, Epidemiology, and End Results database to
determine factors associated with overall survival in embryonal
rhabdomyosarcoma. They found age, stage on presentation, and
treatment received were associated with overall survival. Level of
evidence: III.
48. Baranov E, McBride MJ, Bellizzi AM, et al: A novel SS18-SSX
fusion-specific antibody for the diagnosis of synovial sarcoma.
Am J Surg Pathol 2020;44(7):922-933. The authors created an
antibody that can detect the specific SS18-SSX fusion protein in
synovial sarcoma to help expedite time to diagnosis. Sensitivity
and specificity were very high, suggesting this antibody may have
promise for widespread adoption. Level of evidence: III.
49. Vlenterie M, Litière S, Rizzo E, et al: Outcome of chemotherapy
in advanced synovial sarcoma patients: Review of 15 clinical trials
from the European Organisation for Research and Treatment of
Cancer Soft Tissue and Bone Sarcoma Group; se ing a new
landmark for studies in this entity. Eur J Cancer 2016;58:62-72.
50. Jerby-Arnon L, Neftel C, Shore ME, et al: Opposing immune
and genetic mechanisms shape oncogenic programs in synovial
sarcoma. Nat Med 2021;27(2):289-300. The authors studied the role
the transfusion protein SS18-SSX has on the cells’ ability to
interact with the immune system. They found that the fusion
protein drives oncogenesis and targeted therapies can activate T
cell–mediated killing of tumor cells. This opens the door for
further evaluation of the interplay translocation-driven sarcomas
have with the immune system. Level of evidence: II.
51. Stacchio i S, Van Tine BA: Synovial sarcoma: Current concepts
and future perspectives. J Clin Oncol 2018;36(2):180-187.
52. Morii T, Kishino T, Shimamori N, et al: Differential diagnosis
between benign and malignant soft tissue tumors utilizing
ultrasound parameters. J Med Ultrason 2018;45(1):113-119.
53. Peeken JC, Spraker MB, Knebel C, et al: Tumor grading of soft
tissue sarcomas using MRI-based radiomics. EBioMedicine
2019;48:332-340. This study evaluated a new grading system based
 on MRI radiomics to determine the grade of the soft-tissue
sarcoma. Combining the T2-weighted fat-saturated radiomics
model with clinical staging provided the best predictions. Level
of evidence: III.
54. Crombe A, Marcellin P-J, Buy X, et al: Soft-tissue sarcomas:
Assessment of MRI features correlating with histologic grade and
patient outcome. Radiology 2019;291(3):710-721. The authors
evaluated MRI features that could help predict high-grade soft-
tissue sarcomas. The study found that the presence of necrosis,
heterogeneity, and peritumoral enhancement were associated
with high-grade sarcomas. Level of evidence: III.
55. Birgin E, Yang C, Hetjens S, Reissfelder C, Hohenberger P,
Rahbari NN: Core needle biopsy versus incisional biopsy for
differentiation of soft-tissue sarcomas: A systematic review and
meta-analysis. Cancer 2020;126(9):1917-1928. This systematic
review evaluated the role of core biopsy versus incisional biopsy.
They found that core biopsy had high diagnostic accuracy with
fewer complications compared with incisional biopsy, although
selection bias existed within the studies. Core biopsy was
recommended as the primary choice for obtaining a tissue
diagnosis. Level of evidence: V.
56. Kubo T, Furuta T, Johan MP, Sakuda T, Ochi M, Adachi N: A
meta-analysis supports core needle biopsy by radiologists for
be er histological diagnosis in soft tissue and bone sarcomas.
Medicine (Baltimore) 2018;97(29):e11567.
57. Thompson MJ, Ross J, Domson G, Foster W: Screening and
surveillance CT abdomen/pelvis for metastases in patients with
soft-tissue sarcoma of the extremity. Bone Joint Res 2015;4(3):45-49.
58. King DM, Hackbarth DA, Kilian CM, Carrera GF: Soft-tissue
sarcoma metastases identified on abdomen and pelvis CT
imaging. Clin Orthop Relat Res 2009;467(11):2838-2844.
59. von Mehren M, Kane JM, Bui MM, et al: NCCN guidelines
insights: Soft tissue sarcoma, version 1.2021. J Natl Compr Canc
Netw 2020;18(12):1604-1612. This is the summary of the National
 Comprehensive Cancer Network Guidelines for soft-tissue
sarcomas published in 2020, including updates to diagnosis and
treatment guidelines. Level of evidence: V.
60. Elmanzalawy A, Vali R, Chavhan GB, et al: The impact of (18)F-
FDG PET on initial staging and therapy planning of pediatric
soft-tissue sarcoma patients. Pediatr Radiol 2020;50(2):252-260. The
authors studied the role PET scans have on changing the
treatment of pediatric patients with soft-tissue sarcomas. A total
of 19% had a change in therapeutic management because of the
detection of nodal metastasis not picked up on diagnostic CT
scan. The authors suggest that PET scan be considered in the
initial staging and therapy planning for soft-tissue sarcomas of
pediatric patients. Level of evidence: III.
61. O’Sullivan B, Davis AM, Turco e R, et al: Preoperative versus
postoperative radiotherapy in soft-tissue sarcoma of the limbs: A
randomised trial. Lancet 2002;359(9325):2235-2241.
62. Kubicek GJ, LaCouture T, Kaden M, et al: Preoperative
radiosurgery for soft tissue sarcoma. Am J Clin Oncol
2018;41(1):86-89.
63. Alektiar KM, Brennan MF, Healey JH, Singer S: Impact of
intensity-modulated radiation therapy on local control in primary
soft-tissue sarcoma of the extremity. J Clin Oncol 2008;26(20):3440-
3444.
64. Nag S, Shasha D, Janjan N, Petersen I, Zaider M: The American
Brachytherapy Society recommendations for brachytherapy of
soft tissue sarcomas. Int J Radiat Oncol Biol Phys 2001;49(4):1033-
1043.
65. Ratan R, Patel SR: Chemotherapy for soft tissue sarcoma. Cancer
2016;122(19):2952-2960.
66. Eilber FC, Brennan MF, Eilber FR, et al: Chemotherapy is
associated with improved survival in adult patients with primary
extremity synovial sarcoma. Ann Surg 2007;246(1):105-113.
67. Miwa S, Yamamoto N, Hayashi K, Takeuchi A, Igarashi K,
Tsuchiya H: Therapeutic targets for bone and soft-tissue
 sarcomas. Int J Mol Sci 2019;20(1):170. This review paper provides
a summary on the new molecular targets that are being found in
soft-tissue sarcomas and how they are shaping the ability to
manage them. Level of evidence: V.
68. D’Angelo SP, Mahoney MR, Van Tine BA, et al: Nivolumab with
or without ipilimumab treatment for metastatic sarcoma
(Alliance A091401): Two open-label, non-comparative,
randomised, phase 2 trials. Lancet Oncol 2018;19(3):416-426.
69. Miwa S, Nishida H, Tanzawa Y, et al: Phase 1/2 study of
immunotherapy with dendritic cells pulsed with autologous
tumor lysate in patients with refractory bone and soft tissue
sarcoma. Cancer 2017;123(9):1576-1584.
70. Brennan MF, Antonescu CR, Moraco N, Singer S: Lessons
learned from the study of 10,000 patients with soft tissue
sarcoma. Ann Surg 2014;260(3):416-421.
71. Ferguson PC, Deheshi BM, Chung P, et al: Soft tissue sarcoma
presenting with metastatic disease: Outcome with primary
surgical resection. Cancer 2011;117(2):372-379.
72. Chudgar NP, Brennan MF, Munhoz RR, et al: Pulmonary
metastasectomy with therapeutic intent for soft-tissue sarcoma. J
Thorac Cardiovasc Surg 2017;154(1):319-330.e1.
73. Okiror L, Peleki A, Moffat D, et al: Survival following pulmonary
metastasectomy for sarcoma. Thorac Cardiovasc Surg
2016;64(2):146-149.
Index
Note: Page numbers followed by ‘f’ indicate figures and ‘t’ indicate
tables.

A
Abdominal trauma, 265
Abductor tears, 523
Acetabular fractures
classification, 319
complications, 320
geriatric pa erns, 319–320
indications, 319, 320f–321f
prevalence, 318, 318f
Achilles tendinosis, 633–634
Achilles tendon rupture, 632–633, 633f
Achondroplasia, 887–889
ACL See Anterior cruciate ligament (ACL)
Acromioclavicular (AC) joint arthritis, 283–284, 365–366
Acute compartment syndrome, 70
Acute flaccid myelitis, 212–213, 214f
Acute nerve injury, 214
Adaptive immunity, 250, 251f
Adductor muscle strains, 524
Adhesive capsulitis, 354–355
Adolescent idiopathic scoliosis (AIS)
epidemiology, 861
etiology, 861, 862f
evaluation, 862, 863f
natural history, 861–862
nonsurgical treatment, 862–863
surgical treatment, 863–865, 864f
Adolescent hip dysplasia, 816–817, 818f
Adult degenerative scoliosis, 688–691, 688f, 689t, 690f–691f
Adverse local tissue reaction, 538–539
Alcohol use, patient optimization, 115
Allogeneic blood transfusion, 84–85
Alternative payment model, 53–54
National Quality Strategy, 53
Ambulatory surgical centers, 56–57
American Joint Commi ee on Cancer, 937, 938t
Amniotic band syndrome, 775, 776f
Amputation, limb salvage vs., 938, 939f
Amyotrophic lateral sclerosis (ALS), 214–215
Angiosarcoma, 1005–1006, 1006f
Ankle, 851Foot
anterior cruciate ligament injury, 851–852
 arthritis, 601–602, 603f
fracture, 304–305, 304f, 804–806, 806f
meniscal injury, 852–853
patellofemoral instability, 853–854, 854f
pelvic hip avulsion fracture, 851
tibial spine fracture, 852
Anterior cruciate ligament (ACL), 851–852
knee, ligament injuries to, 547
Anterior instability, shoulder, 356–358, 357f
Apophyseal avulsion injuries, 783–785, 784f
Apophyseal ring fractures, 873–876, 876f
Articular cartilage, 193–195, 194f–196f
injuries, 512, 512t
knee
augmented microfracture, 563
autologous matrix-induced chondrogenesis, 563
bone marrow aspirate concentrate implantation, 563
chondroplasty, 562
débridement, 562
diagnosis, 560
imaging, 560
marrow stimulation, 562–563, 562f–563f
microanatomy, 559–560
nonsurgical treatment, 560
orthobiologic agents, 560–561
 osteochondral autograft transfer, 565–566, 565f–566f
porcine collagen membrane, autologous cultured chondrocytes
on, 563–565, 564f
surgical treatment, 561
Atypical lipomatous tumor, 1004, 1004f
Autoimmunity, 250
Autologous matrix-induced chondrogenesis, 563
Axial neck pain, 669

B
Benign bone tumors
chondroblastoma, 949, 950f
chondroid lesions
enchondroma, 948
enchondromatosis, 949
osteochondroma, 948
periosteal chondromas, 948
chondromyxoid fibroma, 949
cystic lesions
aneurysmal bone cysts, 948
unicameral bone cysts, 947
fibrous lesions
fibrous dysplasia, 949–951
nonossifying fibromas, 949
giant cell tumor, 951–952, 951f
hemangioma, 953
 Langerhans cell histiocytosis, 952–953
metabolic conditions
Paget disease, 954–955
renal osteodystrophy, 954
myositis ossificans, 953, 954f
osteoblastoma, 952
osteoid osteoma, 952, 952f
osteomyelitis, 953–954
Benign primary spinal tumors, 724–726, 725f–726f
Benign soft-tissue tumors
cystic lesions
ganglion cysts, 997–998
meniscal cysts, 998
popliteal cysts, 998
fibrous lesions
desmoid tumor, 995
infantile fibromatosis, 996
nodular fasciitis, 995
palmar fibromatosis, 996
plantar fibromatosis, 996
tendon sheath fibroma, 995–996
intramuscular hemangioma, 998–999, 998f
lipomatous tumors, 991, 992t
lipoma, 991–992, 993f
variants, 993–994
 neurogenic tumors, 994–995, 995f
synovial chondromatosis, 997, 997f
tenosynovial giant cell tumor, 996–997
Biocompatibility, orthopaedic alloys, 93–94
Biomaterials, 91–93, 91f
corrosion, 94–95, 95f
Biopsy, musculoskeletal tumors, 935–936, 936f–937f
Blood management, 77–85
BoneBone sarcomas
atypical femur fractures, 153, 154f
biologic process of, 143
diseased states
osteogenesis imperfecta, 147–148, 149f
osteomalacia, 151, 152f
osteopetrosis, 148–149, 150f, 150t
osteoporosis, 151–153, 153f
Paget disease, 149–151
skeletal metastases
localization of, 155, 155f
lytic lesions, 155–156, 156f
osteoblastic lesions, 155
pathologic fractures, 153
structural changes in, 154
systemic effect of, 153–154
structure
 cellular components of, 143, 144f
extracellular matrix, 146
ion homeostasis, 146
nutritional status on, 146–147, 147f
osteoblasts, 144
osteoclasts, 144–145
osteocytes, 145
stem cell origin, 145
three-dimensional anatomy of, 146
tumors, 931–932, 932t
Bone marrow aspirate concentrate implantation, 563
Bone sarcomas
adamantinoma
epidemiology, 968
histology, 968
imaging, 968, 969f
pathophysiology, 968
presentation, 968
prognosis, 970
subtypes, 968
treatment, 968
chondrosarcoma
epidemiology, 971
imaging, 971–972
presentation, 971
 subtypes, 972–973
treatment, 973
chordoma
epidemiology, 970
histology, 970
imaging, 970
presentation, 970
prognosis, 971
treatment, 971
Ewing sarcoma, 964
epidemiology, 964–965
histology, 965, 967f
imaging, 965, 966f
pathophysiology, 965
presentation, 965
prognosis, 966–967
subtypes, 965
treatment, 965–966
osteosarcoma
epidemiology, 959
histology, 961, 962f
imaging, 961, 961f–963f
pathophysiology, 959–960, 959f
predisposition syndromes, 961t
presentation, 960, 960t
 prognosis, 964
subtypes, 960
treatment, 961–964, 964f
Brachial plexus birth injury, 215–216, 777–778
Bucket-handle tear, 573
Bunione e deformity, 627

C
Calcific tendinitis, 354, 354f
Cancer immunotherapy, 251–252, 252f
Care reimbursement, 49–51, 50t
Cardiac stents, 68
Carpal instability
adaptive, 463
assessment, 455, 456t
complex
axial fracture-dislocation, 462–463
clinical features, 461
dorsal perilunate dislocation, 461
dorsal perilunate fracture-dislocation, 461–462, 462f
isolated carpal bone dislocation, 463
palmar perilunate dislocation, 462
radiocarpal dislocation, 462
dissociative
lunotriquetral ligament injury, 459–460
 scapholunate ligament injury, 455–459, 459f
nondissociative, 460–461
Carpal tunnel syndrome, 441–443, 442f, 442t
Cartilage tissue engineering, 201–202
Cavovarus foot deformity, 629–630, 630f
Centers for Medicare & Medicaid Services, 45, 55–56, 56f–57f
Cerebral palsy, 216–217
ankle surgery, 908–910, 910f
foot surgery, 908–910, 910f
hip surgery, 907–908, 907f
knee surgery, 908, 909f
single-event multilevel surgery, 910
spine surgery, 906–907
tone management, 904–906
Cervical spine trauma, 326–328, 328f, 328t
Cervical spondylosis
axial neck pain, 669
cervical kyphosis/deformity, 671–672
cervical myelopathy, 670–671, 671f
cervical radiculopathy, 669–670
fusion/motion-sparing procedures, 673–674, 673f
nonsurgical management, 672
surgical management, 672
Charcot arthropathy
nonplantigrade foot, surgical correction of, 619, 619f–621f
 nonsurgical management, 619
staging/diagnosis, 618–619
Chest wall injuries, 267, 268f
Chimeric antigen receptor T cell therapy, 252, 253f
Chondroblastoma, 949, 950f
Chondroid lesions
enchondroma, 948
enchondromatosis, 949
osteochondroma, 948
periosteal chondromas, 948
Chondromyxoid fibroma, 949
Chondroplasty, 562
Chronic ankle instability, 630–631
Chronic kidney disease, 118
Clavicle fractures, 284, 738–739, 739f
Cleft hand, 775, 775t, 776f
Cleidocranial dysplasia, 890
Clinodactyly, 772–773, 774f
Coagulation cascade
clo ing process, 78f
extrinsic pathway, 78
intrinsic pathway, 78–79
Compartment syndrome, 754–756, 803
Comprehensive Care for Joint Replacement model, 54
Compression neuropathies, 217
Computed tomography (CT), 935, 935f
bone density assessment, 103
bone texture analysis, 103
contraindications, 102
elbow, 382, 384
arthritis, 391, 391f
glenohumeral joint arthritis, 367, 368f
hip, 506
image-guided interventions, 102, 103f
intraoperative three-dimensional imaging, 240
neoplasm evaluation, 102
preoperative planning, 101
quantitative, 103
robotic arm–assisted total joint arthroplasty, 239
scapholunate ligament injury, 457
shoulder, 345–346
spinal trauma, 326
surgical guidance, 101
thigh, 239–240, 240f
three-dimensional anatomic models, 238, 238f
Computer-assisted navigation, robotic spine surgery with, 698
Congenital myopathy, 211
Congenital radioulnar synostosis, 769–771, 770f, 770t
Coronavirus disease 2019 (COVID-19), active vs. passive
immunization, 252–255, 254f–255f
CT See Computed tomography (CT)
 p g p y
Cubital tunnel syndrome, 396–398, 397f, 443–444
Cultural competence, 25–28, 26t, 28t
Cystic lesions
aneurysmal bone cysts, 948
ganglion cysts, 997–998
meniscal cysts, 998
popliteal cysts, 998
unicameral bone cysts, 947

D
Dedifferentiated liposarcoma, 1004–1005, 1004f
Deep gluteal syndrome, 525, 526t, 527
Degenerative spondylolisthesis, 684
de Quervain tenosynovitis, 474–475
Developmental dysplasia of the hip (DDH), 811–812
diagnosis, 812–815, 813f–814f
management, 815–816, 815f
DFIS See Dual fluoroscopic imaging systems (DFIS)
Diabetes
abnormal fracture healing, 187, 188f
patient optimization, 112–113
Diabetic foot
amputation, 617
antibiotic therapy, 616
clinical evaluation, 614–615
 grading, 615, 615t
multidisciplinary care, 615
nonsurgical management, 615
nutrition, 616
orthoses/shoe wear, 616, 616f
peripheral neuropathy, 613–614, 614f
primary vs. secondary closure, débridement with, 616–617
risk factors, 614–615
surgical management, 616–617
ulcers, 614–615
vascular intervention, 616
vasculopathy, 613–614, 614f
wound care, 615
Diastrophic dysplasia, 889–890, 890f
Distal biceps injuries, 406–408, 406f
Distal femoral fractures, 298, 300f
Distal femur physeal fractures, 792, 793f
Distal humerus fractures, 285–286
Distal interphalangeal (DIP) joint osteoarthritis, 446
Distal radius fractures, 288–289, 756, 757f
clinical outcomes, 485
nonsurgical management, 483
surgical indications, 484
treatment, 483–485
Distal tibia physeal fracture, 804, 805f
Distal triceps injuries, 408–409
Down syndrome, 890–892, 891f
Drug abuse, patient optimization, 115
Dual-energy X-ray absorptiometry, 100
Dual fluoroscopic imaging systems (DFIS), 179–181, 180f
Duchenne muscular dystrophy (DMD), 209–210

E
EBM See Evidence-based medicine (EBM)
ECG See Electrocardiogram (ECG)
Echocardiogram, 67
ECU tenosynovitis See Extensor carpi ulnaris (ECU) tenosynovitis
Ehlers-Danlos syndrome (EDS), 886–887, 887t
ElbowElbow arthritis; Tendinopathy; Throwing injuries, elbow
anterior shoulder instability, 848–849
bone anatomy, 377, 378f
carrying angle of, 380
center of rotation, 380
computed tomography, 382, 384
dislocation, 743
lateral collateral ligament reconstruction
anatomy, 413
clinical outcomes, 415
indications, 413–414
magnetic resonance imaging, 414, 414f
 rehabilitation, 415
ligamentous anatomy, 378, 379f
Li le Leaguer’s elbow, 849
magnetic resonance imaging, 384
motion of, 379–380
physical examination, 381–382, 383f
plain radiographs, 382
stability of, 380–381
tendinous anatomy, 378–379
ulnar collateral ligament reconstruction, 412f
anatomy, 411
clinical outcomes, 412–413
indications, 411
rehabilitation, 412
surgical intervention, 411
ultrasonography, 384–385
Elbow arthritis
computed tomography, 391, 391f
nerve disorders, 395–396
cubital tunnel syndrome, 396–398, 397f
radial tunnel syndrome, 398–399
nonsurgical treatment, 391
patient evaluation, 390
plain radiographs, 391, 391f
prevalence, 389
 rheumatoid arthritis, 389–390, 390f
surgical treatment
arthroscopic techniques, 392, 393f
capsular release, 391–392
elbow interposition arthroplasty, 393–394
loose body removal, 391–392
open techniques, 392
Electrocardiogram (ECG), 65–66
End-stage hip degeneration
hip osteoarthritis, 533–534
secondary arthritis, 534
total hip arthroplasty, 534–537
Epicondylitis, lateral, 404–406, 405f
Epicondylitis, medial, 403–404
Evidence-based medicine (EBM), 11–12, 12f
Extensor carpi ulnaris (ECU) tenosynovitis, 476–477, 477f
Extra-articular hip impingement syndromes
deep gluteal syndrome, 527
iliopsoas impingement, 527
ischiofemoral impingement, 525–526
pectineofoveal impingement, 527
subspine impingement, 526–527

F
Factor Xa inhibitors, 81
Femoral fractures, 267
Femoral head fractures, 295
Femoral neck fractures, 295–297, 296f
Femoral shaft fractures, 298, 299f, 789–792, 790f
Femoroacetabular impingement (FAI), 510–512, 510f
articular cartilage injuries, 512, 512t
chondrolabral junction, 512
clinical outcomes, 513–514, 513f
diagnosis, 828
labral tears, 512, 513t
management, 828–829
treatment, 513, 513f
Femur fractures, atypical, 153, 154f
Fibrous lesions
desmoid tumor, 995
fibrous dysplasia, 949–951
infantile fibromatosis, 996
nodular fasciitis, 995
nonossifying fibromas, 949
palmar/plantar fibromatosis, 996
tendon sheath fibroma, 995–996
Flexor tendon injury
diagnostic evaluation, 468
pathology, 467–468, 468f
rehabilitation, 470–471
 tendon reconstruction, 470
tendon repair, 468–470, 469f
Flexor tenosynovitis, 432, 477–478
Floating knee, 800–801
Foot
anatomy
ligaments, 591
neurovascular, 590, 591f
osseous, 589, 590f
tendons, 591
fractures, 806–807
hindfoot arthritis, 602–603, 603f
imaging
biomechanics, 594–595
computed tomography, 592, 592f
gait, 595–596
magnetic resonance imaging, 592–593, 593f
nuclear imaging, 593–594, 594f
plain radiographs, 591–592, 592
ultrasonography, 593
metatarsophalangeal joint, 604–605
midfoot arthritis, 603–604, 604f
osteonecrosis, 605–609
Freiberg infraction, 608–609
Kohler disease, 607
 Mueller-Weiss syndrome, 607
navicular, 607, 607f
talus, 605–607, 607f
reconstruction
Achilles tendinosis, 633–634
Achilles tendon disorders, 632–633, 633f
bunione e deformity, 627
cavovarus foot deformity, 629–630, 630f
hallux valgus, 625–627
lesser toe conditions, 627
lesser toe plantar plate injuries, 628, 628t
Lisfranc injuries, 634–635, 635f
Morton neuroma, 627
peroneal tendinopathy, 632
plantar fasciitis, 634
progressive collapsing foot deformity, 628–629
syndesmosis injury, 631–632, 631f
turf toe, 627–628
Forearm fractures, 288
Fracture-dislocations of the elbow, 286, 287f
Fracture healing
abnormal
aging, 188–189
diabetes, 187, 188f
infection, 188, 189f
 mechanical factors, 187
medication, 189
neurofibromatosis type 1, 188
nutritional status, 188
osteogenesis imperfecta, 188
parathyroid hormone, 188
skeletal metastases, 189
smoking, 187–188
primary
contact healing, 185–186
gap healing, 186
secondary, 186, 186f
reactive phase, 186–187
remodeling phase, 187
repair phase, 187
Fractures See individual fractures

G
Galeazzi fractures, 756
Giant cell tumor (GCT) of bone, 951–952, 951f
Glenohumeral instability, 356
Glenohumeral joint arthritis
clinical presentation, 367
complications, 371
computed tomography, 367, 368f
 hemiarthroplasty, 368–369
inflammatory arthritis, 366, 366f
joint-preserving treatment, 368
nonsurgical management, 368
osteoarthritis, 366, 366f
osteonecrosis, 366–367, 366f
physical examination, 367
pos raumatic arthritis, 367
radiographic evaluation, 367, 367f
reverse shoulder arthroplasty, 370–371
rotator cuff arthropathy, 366, 366f
total shoulder arthroplasty, 369–370, 369f
Greater trochanteric pain syndrome, 521–522
abductor tears, 523
external snapping hip, 523
treatment, 523–524
trochanteric bursitis, 522

H
Hallux valgus, 625–627
HandHand arthritis; Tendinopathies; Tendon injuries; Wrist
atypical infections, 434
bony anatomy, 425, 426f
clinical examination, 427
distal radius fractures
 clinical outcomes, 485
nonsurgical management, 483
surgical indications, 484
treatment, 483–485
fractures, 289–290, 758–760, 759f–760f, 759t
fungal infections, 434
magnetic resonance imaging, 428
metacarpal fractures, 487
neurovascular anatomy, 425–426, 426f–427f
nontraumatic vascular conditions, upper extremity
circulation, 434
diagnosis, 434–435
nonsurgical treatment, 435
occlusive disease, 434
physical examination, 434–435
surgical treatment, 435–436, 436t
vasospastic disease, 434
osteomyelitis, 433
phalangeal fractures, 487
replantation, 489, 490t
scaphoid fractures, 485
bone grafting, 486–487
treatment, 486
soft-tissue anatomy, 426–427
soft-tissue infections
 for antibiotic prophylaxis, 431–432
bite wounds, 433
fight bites, 433
flexor tenosynovitis, 432
hand cellulitis and abscesses, 432
necrotizing fasciitis, 432–433, 433t
septic arthritis, 432
surgical indications, 482, 483t
traumatic injury, 487–489
ultrasonography, 428
Hand arthritis
distal interphalangeal joint osteoarthritis, 446
metacarpophalangeal joint arthritis, 448–449, 449f
proximal interphalangeal joint arthritis, 446–448, 448f
Hand cellulitis and abscesses, 432
Head trauma, 265–266
Hemangioma, of bone, 953
Hemiarthroplasty, glenohumeral joint arthritis, 368–369
Hepatitis C, 118
Hindfoot arthritis, 602–603, 603f
Hindfoot fracture, 305
Hip, 851Hip pain
anatomic compartments of, 501, 504
anterior cruciate ligament injury, 851–852
biomechanics, 504
bursitis, 524–525
computed tomography, 506
dislocation, 786–787
dysplasia, 511, 511f
classification, 514
clinical outcomes, 515, 516
nonsurgical treatment, 515
physical examination, 514–515
surgical treatment, 515–516, 516f
treatment, 515
femoroacetabular impingement, 511–512
articular cartilage injuries, 512, 512t
chondrolabral junction, 512
clinical outcomes, 513–514, 513f
labral tears, 512, 513t
treatment, 513, 513f
iliopsoas tendinitis, 524–525
internal snapping hip syndrome, 524
ligamentous anatomy, 499–501
magnetic resonance imaging, 506
meniscal injury, 852–853
muscle function, 504
muscular anatomy, 501, 502t–503t
osseous anatomy, 499–501
osteoarthritis, 533–534
 patellofemoral instability, 853–854, 854f
pelvis/hip avulsion fracture, 851
physical examination, 505
plain radiographs, 505–506
prearthritic hip, radiology of, 509–511
femoroacetabular impingement, 510, 510f
hip dysplasia, 511, 511f
tibial spine fracture, 852
ultrasonography, 506
Hip pain, 522t
adductor muscle strains, 524
flexor problems
bursitis, 524–525
iliopsoas tendinitis, 524–525
internal snapping hip syndrome, 524
greater trochanteric pain syndrome, 521–522
abductor tears, 523
external snapping hip, 523
treatment, 523–524
trochanteric bursitis, 522
peritrochanteric space pathology, 521–522
Human immunodeficiency virus (HIV)
patient optimization, 118–119
Humeral fractures, 285–286, 739–740
I
Iliac wing fractures, 785
Iliopsoas impingement, 527
Iliopsoas tendinitis, 524–525
Infection
abnormal fracture healing, 188, 189f
animal models of, 233
bacterial pathogens, 232–233
osteomyelitis, 225–230, 227t
of the periprosthetic joint, 230–231
prevalence, 225
pyomyositis, 231–232
serologic analysis, 232
Inflammation, 244, 245f, 924–925
chronic, 244, 247t–248t
Inflammatory arthritis, 366, 366f
Inflammatory myopathy, 211–212
Innate immunity, 244, 246f
Intertrochanteric femoral fractures, 297
Intervertebral disk
biomechanics, 655
degeneration, 654–655
forces, 655
functional unit, 655
planes of motion, 655
 structure, 653–654, 654f
Intramuscular hemangioma, 998–999, 998f
Ischiofemoral impingement, 525–526
Isthmic spondylolisthesis, 684

K
Kirner deformity, 774
Knee, 851
anatomy
anterior cruciate ligament, 547
medial collateral ligament, 548
medial patellofemoral ligament, 549
posterior cruciate ligament, 547–548
posterior oblique ligament, 549
posterolateral corner, 548, 548f
anterior cruciate ligament injury, 851–852
imaging
anterior cruciate ligament, 549–550, 549f
multiligamentous knee injuries, 551, 551f
patellofemoral joint, 551–552, 552f
posterior cruciate ligament, 550–551
meniscal injury, 852–853
osteoarthritis
anatomy, 579–580
continuum of care, 580
 diagnosis, 580
nonsurgical modalities, 580–582
pathophysiology of, 579–580
risk factors for, 579–580
surgical approach, 582–583
patellofemoral instability, 853–854, 854f
pelvic hip avulsion fracture, 851
surgery
anterior cruciate ligament, 552–554, 553f
medial collateral ligament, 554–555
medial patellofemoral ligament, 556, 556f
posterior cruciate ligament, 554
posterolateral corner, 555, 555f
tibial spine fracture, 852

L
Labral tears, 512, 513t
Langerhans cell histiocytosis, 952–953
Lateral collateral ligament reconstruction, elbow
anatomy, 413
clinical outcomes, 415
indications, 413–414
magnetic resonance imaging, 414, 414f
rehabilitation, 415
Lateral condyle fractures, 742, 742f
Legg-Calvé-Perthes (LCP) disease, 821–823
diagnosis, 823–824, 823f, 825f–826f
management, 824–828, 825f–826f, 827f
Leiomyosarcoma, 1006, 1006f
Lesser toe plantar plate injuries, 628, 628t
Limb salvage, amputation vs., 938, 939f
Lipomatous tumor, 991, 992t
lipoma, 991–992, 993f
Liposarcoma
atypical lipomatous tumor, 1004, 1004f
dedifferentiated liposarcoma, 1004–1005, 1004f
myxoid liposarcoma, 1005, 1005f
pleomorphic liposarcoma, 1005, 1005f
well-differentiated liposarcoma, 1004, 1004f
Lisfranc injury, 634–635, 635f
Lower extremity fractures
ankle fractures, 804–806, 806f
compartment syndrome, 803
distal tibia physeal fracture, 804, 805f
floating knee, 800–801
foot fractures, 806–807
patellar sleeve fracture, 797–798, 798f
proximal tibia physeal fractures, 798–799, 798f
tibial shaft fracture, 801–803, 802f
tibial tubercle fracture, 799–800, 799f–800f
 toddler fracture, 803
Lower extremity metastatic disease, 985–986, 986f–987f
Lower extremity trauma
ankle fracture, 304–305, 304f
distal femoral fractures, 298, 300f
femoral head fractures, 295
femoral neck fractures, 295–297, 296f
femoral shaft fractures, 298, 299f
hindfoot fracture, 305
intertrochanteric femoral fractures, 297
midfoot fracture, 305
patellar fractures, 298, 301f–302f
pilon fractures, 302, 303f, 304
subtrochanteric femoral fractures, 297–298
tibial plateau fractures, 298, 300
tibial shaft fractures, 300–302
Lumbar disk herniations
clinical presentation, 680–681
nonsurgical management, 681
surgical management, 681–682
Lumbar hypoplasia, 869, 870f
Lumbar spinal stenosis
clinical presentation, 682–683
nonsurgical management, 683
surgical management, 683
Lumbar spondylolisthesis, 683–684
clinical presentation, 685–687, 686f
degenerative spondylolisthesis, 684
isthmic spondylolisthesis, 684
nonsurgical management, 687
spondylolisthesis, classification of, 684–685
surgical management, 687–688
Lunotriquetral ligament injury, 459–460

M
Macrodactyly, 776–777
Magnetic resonance imaging (MRI), 935
elbow, 384
hand, 428
hip, 506
indications for, 105–106
scapholunate ligament injury, 457
shoulder, 344
spinal trauma, 326
throwing injuries, elbow, 410, 410f
Malnutrition, patient optimization, 113
Marfan syndrome, 881–882, 882t
MAT See Meniscal allograft transplantation (MAT)
MCP joint arthritis See Metacarpophalangeal (MCP) joint arthritis
Mechanical instability, predicting, 727–728, 728t
Medial collateral ligament (MCL), 548
Medial epicondyle fractures, 742–743, 743f
Medial meniscus, ramp lesions of, 574–575
Medicaid, 48
Medical device legislation
adverse event reporting, 39–40
approval processes, 35–37, 35t
biologics and drugs, 38–39
biologics license application vs. new drug application, 39
classification, 34–35
custom devices, 37–38
device recalls, 40
human cell and tissue products, 38–39
Medical optimization, 534–535
Medicare, 47–48
Meniscal allograft transplantation (MAT), 575
anatomy, 571, 572f
imaging, 571–572
nonsurgical management, 572–573
surgical management
bucket-handle tears, 573
horizontal cleavage tears, 574
medial meniscus, ramp lesions of, 574–575
meniscal allograft transplantation, 575
pediatric meniscus tears, 575
 radial tears, 574
root tears, 573–574
Meralgia paresthetica, 528
Metacarpal fractures, 289, 487
Metacarpal synostosis, 774–775
Metacarpophalangeal (MCP) joint arthritis, 448–449, 449f
Metastatic epidural cord compression, 729–730
Metastatic spinal disease, 726–727
diagnosis, 727
en bloc surgery, wide margin, 731
mechanical instability, 727–728, 728t
metastasectomy, 731
metastatic epidural cord compression, 729–730
prognosis, 728–729, 729f
radiosensitivity, 727
Metastatic tumors, 721
bony metastasis
biopsy, 982
history, 980
imaging, 980–981
laboratory studies, 981–982
physical examination, 980
etiologies for
anatomy, 977–978
biomechanics, 977–978
 epidemiology, 977
nonsurgical management
adjuvant medical therapy, 983
chemotherapy, 982
natural history, 982
prognosis, 982
radiation therapy, 982–983
pathologic fracture, 983–984, 984t
pathophysiology of, 978–980, 979f
surgical management
lower extremity metastatic disease, 985–986, 986f–987f
spine and pelvis, 985, 986f
upper extremity metastatic disease, 984–985, 985f
Metatarsophalangeal (MTP) joint, 604–605
Midfoot arthritis, 603–604, 604f
Midfoot fracture, 305
Monteggia fracture-dislocation, 751–752, 752t, 753f
Monteggia fractures, 286
Morton neuroma, 627
MRI See Magnetic resonance imaging (MRI)
Multidirectional instability (MDI), 358
Multiple epiphyseal dysplasia (MED), 894, 894f
Multiple sclerosis, 217–218
Muscle disorders
congenital myopathy, 211
 Duchenne muscular dystrophy, 209–210
inflammatory myopathy, 211–212
myasthenia gravis, 210
spinal muscular atrophy, 210–211, 211t
volumetric muscle loss, 212
Muscle rupture, shoulder, 358–359
Musculoskeletal biomechanics
joint kinetics, 89–90, 90f
rigid body mechanics, 89–90, 90f
solid mechanics, 90–91, 90f, 90t
Musculoskeletal imaging
computed tomography
bone density assessment, 103
bone texture analysis, 103
contraindications, 102
dual-energy, 100
image-guided interventions, 102, 103f
neoplasm evaluation, 102
preoperative planning, 101
quantitative, 103
surgical guidance, 101
conventional radiography, 97, 98t
atraumatic evaluation, 98–99, 100f–101f
dual-energy X-ray absorptiometry, 100
fluoroscopy, 99–100
 neoplastic evaluation, 99
trauma evaluation, 97–98, 98f–99f
magnetic resonance imaging
indications, 105–106
magnet strength, 105
sequences, 103, 104f–105f, 104t, 105
nuclear medicine, 106
bone scan, 107–108
positron emission tomography-computed tomography, 107,
107f
radiation safety, 108
ultrasonography, 106, 107f
Musculoskeletal infection
adverse outcomes, risk for, 920
antibiotic administration, 923–924
cellular markers of, 921–922
culture, 924
diagnosis, 918
epidemiology, 916, 918f
inflammation, 924–925
laboratory measure of, 921, 922f–923f
malignancy, 925
pathogen, 919
pediatric patients, 920–921, 920t
surgical management, 924
trauma, 925
Musculoskeletal mechanics
clinical applications of, 176, 177f, 178t
dual fluoroscopy, 179–181, 180f
force, 171–172, 172f
free body diagrams, 172–173, 172f–173f
of hip joints, 174–176, 175f
of knee joints, 174–176, 176f
of ligaments, 174
moment arm of, biceps muscle, 172
motion capture technology, 176–179, 178f–179f
stress-strain curve, of bone, 173, 174f
of tendons, 174
wearable devices, 181
Musculoskeletal tumors
adjuvant treatment, 939
chemotherapy, 939–940
immunotherapy, 941
radiation therapy, 940–941
American Joint Commi ee on Cancer, 937, 938t
biopsy, 935–936, 936f–937f
clinical presentation
bone tumors, 931–932, 932t
soft-tissue tumors, 932–933
Enneking staging system, 936–937
functional outcome measures
 Musculoskeletal Tumor Society, 941
patient-reported outcomes measurement information system,
941–942
Toronto Extremity Severity Score, 941
grading, 936
imaging, 933
computed tomography, 935, 935f
magnetic resonance imaging, 935
nuclear imaging, 935
plain radiographs, 933, 933t, 934f
ultrasonography, 933
molecular diagnostics, 936
staging, 936
surgical principles, 937–938, 939f
surveillance, 942
Myasthenia gravis, 210
Myelomeningocele, 910–911
Myositis ossificans, 953, 954f
Myxoid liposarcoma, 1005, 1005f

N
Necrotizing fasciitis, 432–433, 433t
Nemaline myopathy, 211
Nerve disorders
acute flaccid myelitis, 212–213, 214f
acute nerve injury, 214
 amyotrophic lateral sclerosis, 214–215
brachial plexus birth injury, 215–216
cerebral palsy, 216–217
compression neuropathies, 217
elbow, 395–396
cubital tunnel syndrome, 396–398, 397f
radial tunnel syndrome, 398–399
multiple sclerosis, 217–218
Neurofibromatosis type 1, 188, 885–886, 885t, 886f
Neurogenic tumors, 994–995, 995f
Neuromuscular scoliosis, 868
Nuclear imaging, 935
Nuclear medicine, 106
bone scan, 107–108
positron emission tomography-computed tomography, 107, 107f

O
OA See Osteoarthritis (OA)
Obesity, patient optimization
body mass index benefits, 112
classification, 111–112
metabolic syndrome, 112
pathophysiology, 112
Olecranon fracture, 286, 743, 744f
Open fracture, 70, 267
 antibiotic management, 274–276
classification, 273–274, 274f
clinical management, 274
clinical outcomes, 278
definitive soft-tissue management, 277–278
prevalence, 273
surgical management, 276–277, 276f
Orthopaedic implant and instrument technologies, 123
artificial intelligence, 134–137
image-guided vs. non–image-guided, 125
medical ethics, 124
robotic surgery, 124–125
Orthopaedic trauma
emergency room evaluation, 69
geriatric trauma, 70–71
hip fracture care, 70–71
injury severity assessment, 68–69
resuscitation, 69
triaging care, 69–70
Osteoarthritis (OA), 366, 366f
articular cartilage, 193–195, 194f–196f
cartilage tissue engineering, 201–202
distal interphalangeal joint, 446
etiology, 195f, 197
aging, 197
 epigenetics, 198
genetics, 198
gut microbiome, 197–198
obesity, 197–198
sex differences, 197
hyaluronic acid, 199
joint degeneration in
bone, 195
cartilage, 195
ligaments, 196–197
meniscus, 196–197
synovium, 196
tendons, 196–197
platelet-rich plasma, 199–200
prevalence, 193
stem cell–based therapies, 200–201
Osteoblastoma, 952
Osteochondral autograft transfer, 565–566, 565f–566f
Osteodiskitis
diagnosis, 706–707
epidemiology, 705, 706f
pathogenesis, 705–706
treatment, 707
Osteogenesis imperfecta, 147–148, 149f, 882–885, 884f
abnormal fracture healing, 188
Osteoid osteoma, 952, 952f
Osteomalacia, 151, 152f
Osteomyelitis, 433, 953–954
antimicrobial therapy for, 229–230
bacterial virulence mechanisms, 228–229
classification, 226
diagnosis, 706–707
epidemiology, 705, 706f
etiologies of, 227–228
microbiology of, 226, 227t
pathogenesis, 705–706
pathophysiology, 225–226
treatment, 707
Osteonecrosis, 366–367, 366f, 605–609
Kohler disease, 607
lesser metatarsals/Freiberg infraction, 608–609
Mueller-Weiss syndrome, 607
navicular, 607, 607f
Osteopetrosis, 148–149, 150f, 150t
Osteoporosis, 151–153, 153f

P
Paget disease, 149–151
Parsonage-Turner syndrome, 445–446
Patellar fractures, 298, 301f–302f
Patellar sleeve fracture, 797–798, 798f
Patient-centered care, 23–24, 24t
Patient optimization
alcohol use, 115
diabetes, 112–113
drug abuse, 115
hepatitis C, 118
human immunodeficiency virus, 118–119
limitations of, 119
malnutrition, 113
modifiable risk factors, 111
obesity
body mass index benefits, 112
classification, 111–112
metabolic syndrome, 112
pathophysiology, 112
perioperative management, 111
peripheral vascular disease, 116, 118
psychiatric disease, 115–116
renal disease, 118
rheumatoid arthritis, 116, 117t
smoking, 114–115
vitamin D deficiency, 113–114
Patient Protection and Affordable Care Act (PPACA), 51–53
Patient-reported outcome-based performance measures (PRO-PMs),
15
Patient-reported outcome measures (PROMs), 11, 14
Patient-reported outcomes (PROs), 14, 941–942
Patient-specific instruments, 238–239, 239f
PCFD See Progressive collapsing foot deformity (PCFD)
Pectineofoveal impingement, 527
Pediatric athletic injuries
ankle, osteochondritis dissecans of, 855–856, 856f
anterior cruciate ligament injury, 851–852
elbow
Li le Leaguer’s elbow, 849
medial epicondylar avulsion, 849–851
knee, osteochondritis dissecans of, 854–855
meniscal injury, 852–853
patellofemoral instability, 853–854, 854f
pelvis hip avulsion fracture, 851
prevalence, 847
shoulder
anterior shoulder instability, 848–849
Li le Leaguer’s shoulder, 847–848
tibial spine fracture, 852
Pediatric fractures
compartment syndrome, 754–756
distal radius, 756, 757f
femoral neck fracture, 787, 787f–788f
Galeazzi fractures, 756
 hand and finger fractures, 758–760, 759f–760f, 759t
Monteggia fracture-dislocation, 751–752, 752t, 753f
radius/ulna diaphyseal forearm fractures, 753–754, 753t, 755f
scaphoid fractures, 757–758
Pediatric hip disorders
adolescent hip dysplasia, 816–817, 818f
developmental dysplasia of the hip, 811–812
diagnosis, 812–815, 813f–814f
management, 815–816, 815f
femoroacetabular impingement
diagnosis, 828
management, 828–829
Legg-Calvé-Perthes disease, 821–823
diagnosis, 823–824, 823f, 825f–826f
management, 824–828, 825f–826f, 827f
slipped capital femoral epiphysis, 817–820, 819f
diagnosis, 820
management, 820–821, 822f
Pediatric lower extremity anomalies
congenital femoral deficiency, 837, 837f–838f
congenital limb deficiency, 836–837
fibular hemimelia, 838–839
foot conditions
cavovarus foot, 843
clubfoot, 842
 congenital vertical talus, 841–842, 841f
tarsal coalition, 842–843, 842f
genu valgum, 835
genu varum, 835–836, 836f
knee, coronal plane variations of, 834, 835f
rotational variations, 833–834
tibia
anterolateral bowing, 840–841, 840f
congenital pseudarthrosis, 840–841, 840f
posteromedial bowing of, 840, 840f
tibial hemimelia, 839, 839f
Pediatric meniscus tears, 575
Pediatric neuromuscular disorders
cerebral palsy
background, 903–904, 905f
hip surgery, 907–908, 907f
knee surgery, 908, 909f
single-event multilevel surgery, 910
spine surgery, 906–907
tone management, 904–906
Duchenne muscular dystrophy, 911–912, 912t
myelomeningocele, 910–911
Pediatric pelvic fractures, 783, 784f
Pediatric spine disorders
adolescent idiopathic scoliosis
 epidemiology, 861
etiology, 861, 862f
evaluation, 862, 863f
natural history, 861–862
nonsurgical treatment, 862–863
surgical treatment, 863–865, 864f
apophyseal ring fractures, 873–876, 876f
children, cervical spine conditions in, 870
congenital, 869
distraction based, 865–866, 866f
early-onset scoliosis, 865
casting for, 865
congenital, 867–868, 868f
idiopathic, 867, 867f, 867t
treatment strategies, 865, 865f
lumbar hypoplasia, 869, 870f
neuromuscular scoliosis, 868
Scheuermann kyphosis, 869–870, 869f, 871f
thoracolumbar compression injury, 876, 876f
thoracolumbar trauma, 873
upper cervical spine, 870–871, 872f–873f
Pediatric upper extremity disorders
amniotic band syndrome, 775, 776f
brachial plexus birth injury, 777–778
cleft hand, 775, 775t, 776f
 clinodactyly, 772–773, 774f
congenital radioulnar synostosis, 769–771, 770f, 770t
Kirner deformity, 774
macrodactyly, 776–777
metacarpal synostosis/carpal coalition, 774–775
postaxial polydactyly, 771–772
preaxial polydactyly, 771, 771f
radial longitudinal deficiency, 767, 768t, 769f
symbrachydactyly, 766, 767f, 767t
syndactyly, 772
thumb hypoplasia, 768–769, 770t
trigger finger, 777
trigger thumb, 777
ulnar longitudinal deficiency, 769
upper extremity, embryology of, 765, 766t, 767t
Pediatric upper extremity trauma
clavicle fractures, 738–739, 739f
elbow dislocation, 743
humeral shaft fractures, 739–740
lateral condyle fractures, 742, 742f
medial epicondyle fractures, 742–743, 743f
olecranon fractures, 743, 744f
proximal humerus fractures, 739, 740f
radial head/neck fractures, 744–745, 744f
shoulder dislocation, 739
 sternoclavicular joint injuries, 737–738
supracondylar humerus fractures, 740–742, 740f
Volkmann ischemia, 745
Pelvic fractures
acute management, 786
apophyseal avulsion injuries, 783–785, 784f
distal femur physeal fractures, 792, 793f
femoral shaft fractures, 789–792, 790f
hip dislocation, 786–787
iliac wing fractures, 785
pediatric femoral neck, 787, 787f–788f
pediatrics, 783, 784f
pelvic ring injuries, 785–786
subtrochanteric femur fractures, 789, 790f
Pelvic ring injuries, 267, 785–786Acetabular fractures
classification, 313
clinical evaluation, 314
clinical management, 314–317, 315f–318f
geriatric, 318
prevalence, 313
Pelvic trauma See Pelvic ring injuries
Perilunate injuries, 289
Perioperative surveillance, 68
Peripheral neuropathy, 613–614, 614f
Peripheral vascular disease (PVD), 116, 118
Periprosthetic joint infection (PJI)
clinical presentation, 230–231
diagnosis, 231
etiologic agents of, 231
treatment of, 231
Peritrochanteric space pathology, 521–522
Peroneal tendinopathy, 632
PET-CT See Positron emission tomography-computed tomography
(PET-CT)
Phalangeal fractures, 289–290, 487
Pilon fractures, 302, 303f, 304
PIP joint arthritis See Proximal interphalangeal (PIP) joint arthritis
Plantar fasciitis, 634
Platelet-rich plasma (PRP), 3, 582
osteoarthritis, 199–200
Pleomorphic liposarcoma, 1005, 1005f
Polytrauma care
chest wall injuries, 267, 268f
damage control, 266
early appropriate care, 266–267
early total care, 266
evidence-based care, 268
femoral fractures, 267
nonorthopaedic injuries
abdominal trauma, 265
chest/thoracic trauma, 265
 head trauma, 265–266
open fractures, 267
patient management, 261
pelvic ring injuries, 267
primary survey
airway, 261–262, 262t
breathing, 262
circulation, 262–263, 262t–263t
disability, 263
exposure, 263
resuscitation, 264–265, 264f
secondary survey, 263
shoulder girdle injuries, 267
tertiary survey, 263
Porcine collagen membrane, autologous cultured chondrocytes on,
563–565, 564f
Positron emission tomography-computed tomography (PET-CT),
107, 107f
Postaxial polydactyly, 771–772
Posterior cruciate ligament (PCL), 547–548
Posterior instability, shoulder, 358
Postoperative pain management, 71–72
preemptive analgesia, 71
Postoperative spinal infection
diagnosis, 711
epidemiology, 711
 prevention strategies, 709–711
treatment, 712
PPACA See Patient Protection and Affordable Care Act (PPACA)
Prearthritic hip, imaging of, 509–511
femoroacetabular impingement, 510, 510f
hip dysplasia, 511, 511f
Preaxial polydactyly, 771, 771f
Preclinical research, with clinical disease, 4
Preoperative assessment
acute coronary syndrome, 64–65
American College of Surgeons National Surgical Quality
Improvement Program Surgical Risk Calculator, 65, 66t
cardiac risk, 64–65
Cardiac Risk Index, 64
Modified Frailty Index, 65, 65t
postmyocardial infarction, 64–65
Revised Cardiac Risk Index, 64, 64t
total joint arthroplasty Cardiac Risk Index, 65
Preoperative testing, 65
Primary malignant tumors, 721–724
Progressive collapsing foot deformity (PCFD), 628–629
PROMs See Patient-reported outcome measures (PROMs)
Pronator syndrome, 445
PRO-PMs See Patient-reported outcome-based performance
measures (PRO-PMs)
PROs See Patient-reported outcomes (PROs)
Proximal humerus fractures, 285, 739, 740f
Proximal interphalangeal (PIP) joint arthritis, 446–448, 448f
Proximal tibia physeal fractures, 798–799, 798f
PRP See Platelet-rich plasma (PRP)
Pseudoachondroplasia, 889
Pudendal nerve entrapment, 528
Pulmonary testing, 67
PVD See Peripheral vascular disease (PVD)
Pyomyositis, 231–232

R
Radial head fractures, 286–288, 744–745, 744f
Radial longitudinal deficiency (RLD), 767, 768t, 769f
Radial tear, 574
Radial tunnel syndrome, 398–399, 444–445
Regenerative engineering
autografts, 159
benefits and limitations of, 159, 160t
electrospinning scaffold fabrication
limitations of, 165
postfabrication modification, 165
tendon regeneration, 163–165, 164f
musculoskeletal tissue injury, 160–161
scaffold design, 161–163, 162f
three-dimensional printing scaffold fabrication
 applications, 166
computer-aided design model, 165
with electrospinning, 166–167, 167f
limitations, 167–168
Renal disease, 118
Reverse shoulder arthroplasty (RSA), 370–371
Rhabdomyosarcoma, 1006–1007, 1007f
Rheumatoid arthritis (RA), 446, 116, 117t, 246, 249, 249f, 389–390,
390f
RLD See Radial longitudinal deficiency (RLD)
Rotator cuff arthropathy, 366, 366f
Rotator cuff tear
full-thickness tear, 350
irreparable rotator cuff tear, 351–354, 352f–353f
magnetic resonance imaging, 350, 351f
partial-thickness tear, 350
prevalence, 349–350

S
Scaphoid fractures, 289, 485, 757–758
bone grafting, 486–487
treatment, 486
Scapholunate ligament injury, 455–456
computed tomography, 457
magnetic resonance imaging, 457
physical examination, 456
 treatment, 457–459, 459f
Scapular fractures, 284
SCFE See Slipped capital femoral epiphysis (SCFE)
Scheuermann kyphosis, 869–870, 871f
SCI See Spinal cord injury (SCI)
Secondary arthritis, 534
Scoliosis
casting for, 865
early-onset, 865
congenital, 867–868, 868f
idiopathic, 867, 867f, 867t
treatment strategies, 865, 865f
Septic arthritis, 432
ShoulderShoulder arthritis
anterior shoulder instability, 848–849
clinical evaluation
patient demographics, 340
patient history, 340
physical examination, 340–342, 341f, 343f–344f
computed tomography, 345–346
dislocation, 739
disorders
adhesive capsulitis, 354–355
anterior instability, 356–358, 357f
calcific tendinitis, 354, 354f
 glenohumeral instability, 356
multidirectional instability, 358
muscle rupture, 358–359
posterior instability, 358
prevalence, 349
rotator cuff tear, 349–354, 351f–353f
throwing shoulder, 355–356
girdle injuries, 267
Li le Leaguer’s shoulder, 847–848
magnetic resonance imaging, 344
osseous anatomy
acromioclavicular joint, 339
clavicle, 338
glenohumeral joint, 338–339, 338f–339f
humerus, 337–338, 338f
scapula, 337
scapulothoracic articulation, 339
sternoclavicular joint, 339
plain radiographs, 342–344, 345f
ultrasonography, 344
Shoulder arthritis
acromioclavicular joint
prevalence, 365
surgical intervention, 366
glenohumeral joint
 clinical presentation, 367
complications, 371
computed tomography, 367, 368f
hemiarthroplasty, 368–369
inflammatory arthritis, 366, 366f
joint-preserving treatment, 368
nonsurgical management, 368
osteoarthritis, 366, 366f
osteonecrosis, 366–367, 366f
physical examination, 367
pos raumatic arthritis, 367
radiographic evaluation, 367, 367f
reverse shoulder arthroplasty, 370–371
rotator cuff arthropathy, 366, 366f
total shoulder arthroplasty, 369–370, 369f
Skeletal dysplasias
achondroplasia, 887–889
cleidocranial dysplasia, 890
diastrophic dysplasia, 889–890, 890f
Down syndrome, 890–892, 891f
Ehlers-Danlos syndrome, 886–887, 887t
Marfan syndrome, 881–882, 882t
mucopolysaccharidoses, 892–894, 892t, 893f
multiple epiphyseal dysplasia, 894, 894f
neurofibromatosis type 1, 885–886, 885t, 886f
 osteogenesis imperfecta, 882–885, 884f
pseudoachondroplasia, 889
X-linked hypophosphatemic rickets, 894–896, 895f
Skeletal metastases
abnormal fracture healing, 189
geographic localization of, 155, 155f
lytic lesions, 155–156, 156f
osteoblastic lesions, 155
structural changes in, 154
systemic effect of, 153–154
Slipped capital femoral epiphysis (SCFE), 817–820, 819f
diagnosis, 820
management, 820–821, 822f
SMA See Spinal muscular atrophy (SMA)
Smoking, 114–115
abnormal fracture healing, 187–188
Soft-tissue infections, hand
for antibiotics prophylaxis, 431–432
bite wounds, 433
fight bites, 433
flexor tenosynovitis, 432
hand cellulitis and abscesses, 432
necrotizing fasciitis, 432–433, 433t
septic arthritis, 432
Soft-tissue sarcomas
 angiosarcoma, 1005–1006, 1006f
imaging, 1007–1009, 1008f–1009f
leiomyosarcoma, 1006, 1006f
liposarcoma
atypical lipomatous tumor, 1004, 1004f
dedifferentiated liposarcoma, 1004–1005, 1004f
myxoid liposarcoma, 1005, 1005f
pleomorphic liposarcoma, 1005, 1005f
well-differentiated liposarcoma, 1004, 1004f
prognosis, 1010
rhabdomyosarcoma, 1006–1007, 1007f
synovial sarcoma, 1007, 1008f
treatment, 1009–1010
types, 1003–1004
Spinal column infections
osteomyelitis/osteodiskitis
diagnosis, 706–707
epidemiology, 705, 706f
pathogenesis, 705–706
treatment, 707
postoperative spinal infections
diagnosis, 711
epidemiology, 711
prevention strategies, 709–711
treatment, 712
 spinal epidural abscess, 707
diagnosis, 708–709, 708f
epidemiology, 707–708
pathogenesis, 708
treatment, 709
Spinal cord injury (SCI), 326
Spinal epidural abscess, 707
diagnosis, 708–709, 708f
epidemiology, 707–708
pathogenesis, 708
treatment, 709
Spinal muscular atrophy (SMA), 210–211, 211t
Spinal trauma
computed tomography, 326
magnetic resonance imaging, 326
patient evaluation, 325
spinal cord injury, 326
spinopelvic dissociation, 331
subaxial cervical spine trauma, 327–328, 328f, 328t
thoracolumbar trauma, 328–331, 329f, 329t–330t
upper cervical spine trauma, 326–327
Spinal tumors
anatomic considerations, 720–721
benign primary spinal tumors, 724–726, 725f–726f
imaging, 718–720, 720f
 metastatic spinal disease, 726–727
diagnosis, 727
en bloc surgery, wide margin, 731
mechanical instability, 727–728, 728t
metastasectomy, 731
metastatic epidural cord compression, 729–730
prognosis, 728–729, 729f
radiosensitivity, 727
metastatic tumors, 721
primary malignant tumors, 721–724
Spine
anatomy
cervical, 644–645, 645f
embryology, 641–642, 642f
extrinsic muscles, 651
intrinsic muscles, 647–651, 650f–651f
ligamentous, 646–647, 648f–649f
lumbar, 645–646
muscular control, 647
nerve roots, 642–644
osseous, 644, 645f
sacral, 646
spinal cord, 642–644
thoracic, 645
diagnostic procedures, 666
 history, 659–660, 661f, 662t
imaging modalities, 665–666
physical examination, 660
cervical spine special tests, 663–664
gait, 660
inspection, 660
lumbar spine special tests, 664–665
myelopathic signs, 665
neurologic examination, 662–663
palpation, 662
provocative maneuvers, 663–664, 664–665
range of motion, 661–662, 662t
sacroiliac joint, 665
Spinopelvic dissociation, 331
Spondylolisthesis, 684–685
Sternoclavicular joint injuries, 737–738
Stress test, 67
Subspine impingement, 526–527
Subtrochanteric femoral fractures, 297–298, 789, 790f
Supracondylar humerus fractures, 740–742, 740f
Symbrachydactyly, 766, 767f, 767t
Syndactyly, 772
Syndesmosis injury, 631–632, 631f
Synovial chondromatosis, 997, 997f
Synovial sarcoma, 1007, 1008f
T
Talus, 605–607, 607f
TEA See Total elbow arthroplasty (TEA)
Tendinopathy
de Quervain tenosynovitis, 474–475
distal biceps injuries, 406–408, 406f
distal triceps injuries, 408–409
extensor carpi ulnaris tenosynovitis, 476–477, 477f
intersection syndrome, 475–476, 476f
lateral epicondylitis, 404–406, 405f
medial epicondylitis, 403–404
stenosing flexor tenosynovitis, 477–478
Tendon injuries
extensor tendon injuries
diagnosis, 471–472
pathophysiology, 471, 471f
rehabilitation, 474
tendon reconstruction, 473–474
treatment, 472–473, 472t
flexor tendon injury, 467–471, 468f–469f
Tenosynovial giant cell tumor (TGCT), 996–997
Terrible triad injuries, 286
TESS See Toronto Extremity Severity Score (TESS)
THA See Total hip arthroplasty (THA)
Thoracic trauma, 265
Thoracolumbar compression injury, 876, 876f
Thoracolumbar conditions, degenerative
adult degenerative scoliosis, 688–691, 688f, 689t, 690f–691f
clinical presentations, 680
lumbar disk herniations
clinical presentation/workup, 680–681
nonsurgical management, 681
surgical management, 681–682
lumbar spinal stenosis
clinical presentation and workup, 682–683
nonsurgical management, 683
surgical management, 683
lumbar spondylolisthesis, 683–684
clinical presentation, 685–687, 686f
degenerative spondylolisthesis, 684
isthmic spondylolisthesis, 684
nonsurgical management, 687
spondylolisthesis, classification of, 684–685
surgical management, 687–688
thoracic disk herniation, 682
Transforaminal lumbar interbody fusion (TLIF), 695
minimally invasive surgical techniques
computer-assisted navigation, robotic spine surgery with, 698
contraindications, 695–696
expandable vs. nonexpandable cages, 696–697
 hybrid surgery, 697
indications, 695–696
learning curve, 696
lordosis, 696
navigation, 696
spinal deformity, 697
surgical decision making, 698
surgical planning, 701, 701f
surgical technique, 696
Thoracolumbar trauma, 873
anatomy, 328–329
biomechanics, 328–329
classification, 329, 329f, 329t
treatment, 329–331, 330t
Thrombin inhibitors, direct, 81
Throwing injuries, elbow
etiology, 409
magnetic resonance imaging, 410, 410f
nonsurgical management, 410–411
patient symptoms, 409
physical examination, 409–410
ultrasonography, 410
Throwing shoulder
biceps pathology, 356
glenohumeral internal rotation deficit, 355
 scapular dyskinesis, 356
superior labrum anterior-posterior tears, 355
Tibial plateau fractures, 298, 300
Tibial shaft fractures, 300–302, 801–803, 802f
Tibial tubercle fracture, 799–800, 799f–800f
TKA See Total knee arthroplasty (TKA)
Toddler fracture, 803
Toronto Extremity Severity Score (TESS), 941
Total elbow arthroplasty (TEA), 393–395, 394f–396f
Total hip arthroplasty (THA), 125, 534–537Total knee arthroplasty
(TKA)
adverse local tissue reaction, 538–539
complications, 537–538
computed tomography, 239–240, 240f
fixation methods, 536
instability, 538
medical optimization, 534–535
outpatient, 535
risk stratification, 534–535
spinopelvic relationship, 538, 539t
surgical approaches, 535
Total joint arthroplasty
kinematics, 179, 180f
robotics, 239
Total knee arthroplasty (TKA)
accelerometer-based systems, 129, 130f, 131
 y f
augmented reality, 133–134, 133f
freehand navigated power tools, 131–133, 132f
noncemented tibial component fixation, 127, 127f
preclinical testing, 134
ROBODOC, 126, 127f
surgical robots, 127–129, 128f–129f
virtual reality, 133–134, 133f
Total shoulder arthroplasty (TSA), 369–370, 369f
Tranexamic acid (TXA), 83–84, 84t
Trochanteric bursitis, 522
Turf toe, 627–628

U
Ulnar collateral ligament (UCL) reconstruction, 412f
anatomy, 411
clinical outcomes, 412–413
indications, 411
rehabilitation, 412
surgical intervention, 411
Ultrasonography, 933
elbow, 384–385
hand, 428
hip, 506
shoulder, 344
throwing injuries, elbow, 410
Unicondylar knee arthroplasty (UKA), 582
Upper cervical spine, 870–871, 872f–873f
Upper extremity
embryology of, 765, 766t, 767t
metastatic disease, 984–985, 985f
neuroimaging, 428
neuropathies
carpal tunnel syndrome, 441–443, 442f, 442t
cubital tunnel syndrome, 443–444
Parsonage-Turner syndrome, 445–446
pronator syndrome, 445
radial tunnel syndrome, 444–445
nontraumatic vascular conditions
circulation, 434
diagnosis, 434–435
nonsurgical treatment, 435
occlusive disease, 434
physical examination, 434–435
surgical treatment, 435–436, 436t
vasospastic disease, 434
trauma
acromioclavicular joint injuries, 283–284
clavicular fractures, 284
distal radius fractures, 288–289
forearm fractures, 288
 fracture-dislocations of, elbow, 286, 287f
hand fractures, 289–290
humeral fractures, 285–286
olecranon fractures, 286
radial head fractures, 286–288
scapular fractures, 284
wrist fractures, 289–290

V
Vasculopathy, 613–614, 614f
Venous thromboembolism (VTE) prophylaxis, 80t
American Academy of Orthopaedic Surgeons 2011 guidelines,
82–83, 82t
American College of Chest Physicians 2012 guidelines, 83, 83t
aspirin, 79–80
factor Xa inhibitors, 81
low-molecular-weight heparin, 81
mechanical forms of, 79
risk stratification, 81–82
Surgical Care Improvement Project, 83
thrombin inhibitors, direct, 81
warfarin, 80–81
Vitamin D deficiency, 113–114
osteomalacia, 151, 152f
Volkmann ischemia, 745
Volumetric muscle loss, 212
W
Well-differentiated liposarcoma, 1004, 1004f
Wound care, 615
Wrist, 425
Allen test, 435
carpal instability, 455–463, 456t, 459f, 462f
de Quervain tenosynovitis, 474
distal radius fractures, 483–485
extensor carpi ulnaris tenosynovitis, 476
extensor tendon injuries, 471–474, 471f, 472t
fractures, 289–290
intersection syndrome, 475
septic arthritis, 432
surgical indications, 482, 483t

X
X-linked hypophosphatemic rickets, 894–896, 895f