Osteopetrosis (Marble Bones, Albers-Schönberg Disease)

Definition:

● Failed osteoclastic resorption of the calcified cartilage in the metaphysis which results in persistence of
primitive chondro-ostoid instead of the normal cancellous bone. (Brashear, 1986)
● Result of an imbalance between bone formation and bone resorption which results in failed bone
resorption due to a defect in osteoclast production and/or function. (Solomon et. al., 2010)
● Characterized by abnormally dense bone with poor medullary canal formations which results in
alterations in the material properties, resulting in bone fragility and abnormalities of haemopoiesis.
(Blom et. al., 2018)

Epidemiology

● Incidence: 1:100,000-500,000
● Age of onset can be as early as infantile (congenita) or as late as adolescence up to adulthood (tarda)
● Tarda > congenita
● No sex predilection
● In 1977, there was an increased incidence of 3.4:100,000 live births on Costa Rican children affected
with osteopetrosis congenita. (Loria-Cortes et. al.)

Etiology

Unknown cause in 30% of all total cases, however 70% can be factored to genetic mutation in at least one of
the following genes which is responsible for the development and/or function of the osteoclasts:

● TCIRG1 – 50% of autosomal recessive (congenita)

● CLCN7 – 75% of autosomal dominant (tarda), 10-15% autosomal recessive (congenita)
● OSTM1
● RANKL
● RANK
● PLEKHM1
● CAII
● IKBKG (NEMO) – x-linked osteopetrosis*
● Kindlin-3
● CalDAG-GEF1
● CTSK
● LEMD3

*gene mutation in the X chromosome

Pertinent Anatomy

The Skeletal System: Bone Tissue

Composition of a Bone:

● Collagen – for the tensile strength of a bone

● Mineral or inorganic salts – for the hardness
o Tricalcium phosphate (hydroxyapatite crystals)
o Calcium carbonate
● Bone Matrix – a.k.a. organic matter of the bone, combination of the collagenous fibers and the
amorphous ground substance found in bone
 ● Intercellular Substance – combination of bone matrix and inorganic salts

Classification of Bones According to Form:

● Long – humerus, femur, tibia, metacarpals, phalanges

● Flat – scapula, sternum, skull bones
● Short – carpals, tarsals
● Irregular bones – vertebrae, pelvis, maxilla sphenoid
● Wormian or Sutural – small clusters of bone seen between joints of certain cranial bones
● Sesamoid - patella

Parts of a long bone:

● Diaphysis: shaft or body of a bone

● Epiphysis (Epiphyses): proximal and distal shafts of a bone
● Metaphysis(Metaphyses): region between the diaphysis and epiphyses
o Contains epiphyseal plates on a growing bone which becomes the epiphyseal line after the
growing years stop
● Articular Cartilage: part of epiphyses where a bone to bone connection is made to form a joint
● Periosteum: surrounds the rest of the bone’s surface not covered by the articular cartilage
● Medullary Cavity(Marrow Cavity): inside the diaphysis, contains yellow blood marrow and blood vessels
on adults, helps minimize the weight of the bones
● Endosteum: lines the medullary cavity, contains bone forming cells and connective tissues

Structure of a Bone:
 ● Cancellous or Spongy
o Found within the layer of a compact bone
o Poor in mineral salt content
o Contains cavities that are filled with red marrow which can be found in the interconnecting
spaces of a lone bone called trabeculae or spicules
o Osteocytes in spongy bones obtain nutrients and oxygen from the marrow
o Short bones, flat bones, irregular bones, and the epiphyses are primarily made up of cancellous
material.
● Compact or Cortical
o Found in the surface of a bone
o Hard and dense due to the richness of mineral salts
o No interconnecting spaces are seen
o Primarily structured to provide protection and support, and help release stress
o Contains the Haversian Canal which is responsible for the delivery of nutrients and oxygen to
bone cells in a compact bone

Cells Found in a Bone:

● Osteoprogenitor cells
o Unspecialized bone stem cells derived from the mesenchyme
o Found in the inner portion of the periosteum, in the endosteum, and the canals within bones that
contain blood vessels
o Can undergo cell division and result to osteoblasts
● Osteoblasts
o Bone building cells
o Synthesize and secrete collagen fibers and other organic components needed to build the
extracellular matrix of bone tissue
o Initiate calcification
o Can become osteocytes when trapped within the extracellular matrix
● Osteocytes
o Mature bone cells
o Main cells in bone tissue and maintain its daily metabolism, such as the exchange of oxygen
and wastes in the blood
● Osteoclasts
o Derived from the fusion of as many as 50 monocytes
o Concentrated in the endosteum
o Ruffled Border – where the lysosomal enzymes and acids digest bone protein and mineral
components of the underlying extracellular matrix (resorption)

The Microscopic Structure of Bone and the Haversian Canal

● The intercellular substance of a bone is arranged in concentric layers or in LAMELLAR fashion. Each
layer is called LAMELLA.
● Between the bony lamella are very small concavities called LACUNAE which contain OSTEOCYTES
● From each lacunae radiate several small canals called CANALICULI which get its nutrients through the
HAVERSIAN CANAL
● The haversian canal get its nutrients from the VOLKMANN’S CANALS which communicate with the
periosteum
 ● In SPONGY BONES, the canaliculi can directly be in contact with the marrow cavity in order to obtain
oxygen and nutrients for the osteocytes.
● In COMPACT BONES, the canaliculi get its nutrients from the haversian canals
● The HAVERSIAN SYSTEM is made up of the haversian canal, lamellae,canaliculi, and osteocytes.

Bone Formation:

● Intramembranous Ossification
o Bones formed by this process is sometimes called membrane bones
o Example: flat bones of the skull, most facial bones, mandible, medial part of clavicle
o Process of development
▪ Development of the ossification center
▪ Calcification
▪ Formation of the trabeculae
▪ Development of the periosteum
● Endochondral or Intercartilaginous Ossification
o Replacement of a hyaline cartilage by a bone
o Most bones in the body undergo this process, but can mostly be observed in long bones
o Process of development:
▪ Development of the cartilage model
▪ Growth of the cartilage model
▪ Development of the primary ossification center
▪ Development of the medullary (marrow) cavity
▪ Development of the secondary ossification centers
▪ Formation of the articular cartilage and epiphyseal plate

Functions of Bone and the Skeletal System:

● Support – structural framework which acts as the site for attachment of skeletal muscles
● Protection – protects internal organs from injuries
● Assistance in movement – skeletal muscles
● Mineral homeostasis – calcium and phosphorus
● Blood cell production – red bone marrow, hemopoiesis
● Triglyceride storage – yellow bone marrow

S/S

Osteopetrosis Tarda

● F
● airly benign, seldom causes symptoms
● May only be discovered after a pathological fracture (transverse) or an x-ray
 ● Unimpaired appearance and function, unless there are complications: pathological fractures or cranial
nerve compression due to bone encroachment on foramina

Osteopetrosis Congenita

● Malignant, causes severe disability

● (+) growth retardation with genu valgum
● Bone encroachment on marrow can result on the following:
o Pancytopenia
o Haemolysis
o Anemia
o Hepatosplenomegaly
o Osteitis of the mandible
● Early death in childhood due to repeated hemorrhage or infection
DDx

Osteopetrosis Pyknodysostosis Osteopathia striata Osteopoikilosis

● Widespread, ● Sclerotic bones ● (+) coarse ● Small, scattered

commonly on which persists on longitudinal condensation
pelvis, vertebrae, cranial sutures, striations on ● Metaphyseal and
skull, and limbs dental anomalies, cancellous bones epiphyseal region
● Metaphyseal and short distal ● Some cases show ● Autosomal
region phalanges autosomal dominant
● Autosomal ● Autosomal dominant ● Thickened
recessive or recessive with ● A.K.A. Striped trabeculae in
dominant bone fragility Bones cancellous bones
● Celery like ● Cathepsin K gene ● A.K.A Spotted
appearance with Bones
dense longitudinal
striations on long
bones
● A.K.A. Marble
Bones

Medical, Surgical, and Pharmacological Mx

Osteopetrosis Tarda

● Treatment is required if complication occurs, symptomatic treatment

Osteopetrosis Congenita

● Regular administration of vitamin D

● Erythropoietin for anemia
● Corticosteroids
● Marrow transplant
● Long term treatment of gamma interferon (IFN-γ-1b or Actimmune)

PT Management

Osteopetrosis Tarda

If patient suffered from a fracture:

● Acute Phase
o PRICE to manage inflammation, icing for 10 mins x 2 times after 2-5 mins rest
o AROM exercises to the joints above and below the immobilized region, 7 reps x 1 set or as
tolerated by the patient
o Muscle setting exercises to the muscles affected above and below the immobilized region, 8
s.h. x 3 reps x 1 set
o Training for the use of Assistive Device as needed
● Subacute Phase
 o Progress from PROM to AAROM exercises on the affected joint, 7 reps x 1 set or within pain
limits of the patient
o Isometric exercises with progression to level of resistance of the muscles on the affected area, 8
s.h. x 3 reps x 1 set
o Maintain strength of muscles and integrity of joints above and below area of affectation
o TENS on area to relieve pain after exercises, 30 mins
o Decrease the number of ADs needed if possible
● Chronic Phase
o Heating modalities (HMP, SWD, US) to relieve pain and improve circulation before exercises,
20 mins
o Massage to improve skin condition and promote skin healing
o CKC or OKC to improve joint mobility and increase muscle strength
o TENS on area after exercise to relieve pain if present, 30 mins
o Gait training if applicable

Osteopetrosis Congenita

● Pain management with the use of TENS; 15-20 mins*

● ES or FES depending on patient’s MMT; 15-20 mins*
● PROM on all major joints, all planes and axes to maintain joint integrity
● Gait training
● Play exercises for strengthening and readying muscles for motor movements
● Education of family members, especially primary caregiver on correct positioning to prevent
development of pressure sores

*Observe absolute precaution, ask primary physician if allowed

Pathophysiology

Abnormality in the genes that form the osteoblast

Abnormal osteoclasts attach to the bone surface and cannot breakdown bone
Osteoblasts attach to the bone and bone thickens

Marble bone prone to fracture

References:

Blom, A. W., Warwick, D., Whitehouse, M. R. & Bristol, N. (2018). Apley’s and Solomon’s System of
Orthopaedics and Trauma 10th Edition. Florida: CRC Press.

Solomon, L., Warwick, D. & Nayagam, S. (2010). Apley’s System of Orthopaedics and Fracture 9th Edition.
London: Hodder Education.

Brashear Jr., H. R. & Raney Sr., R. B. & Shands Jr., A. R. (1986). Handbook of Orthopedic Surgery 10th
Edition. St. Louis: Mosby.

Brunton, L., Chabner, B. & Knollman, B. (2011). Goodman and Gilman’s The Pharmacological Basis of
Therapeutics 12th Edition. USA: The McGraw-Hill Companies, INC.

Tortora, G. J. & Derrickson, B. (2014). Principles of Anatomy and Physiology 14th Edition. USA: Wiley.

Stark, Z. & Savarirayan, R. (2009). Osteopetrosis. Orphanet Journal of Rare Diseases, 4 (5). Doi:
10.1186/1750-1172-4-5.