Review Article

Multiple Myeloma: Diagnosis and

Orthopaedic Implications

Thomas J. Scharschmidt, MD
Joshua D. Lindsey, MD
Pamela S. Becker, MD, PhD
Ernest U. Conrad, MD
Abstract
Multiple myeloma is a hematologic malignancy that commonly
affects the skeletal system. The disease is primarily managed
medically with chemotherapeutic agents. Pathologic fractures are
common in patients with diagnosed and undiagnosed disease. The
number of patients diagnosed with multiple myeloma is increasing,
as is the incidence of associated pathologic fractures. Novel
chemotherapeutic agents and radiation therapy protocols have
been used to extend the average life span of patients with this
disease. Various methods that allow for restoration of function and
pain reduction can be used to stabilize and manage fractures
associated with multiple myeloma. The orthopaedic surgeon and
oncology team must work together to develop an individualized
treatment plan to improve patient quality of life and provide pain
relief.

M ultiple myeloma is a hematog-

From the Department of
Orthopaedics, Ohio State University
College of Medicine, Columbus, OH
(Dr. Scharschmidt), the Department
of Orthopaedics and Sports
Medicine (Dr. Lindsey and
Dr. Conrad), and the Division of
Hematology (Dr. Becker), University
of Washington Medical Center,
Seattle, WA.
J Am Acad Orthop Surg 2011;19:
410-419
Copyright 2011 by the American
Academy of Orthopaedic Surgeons.
enous malignancy of mono-
clonal plasma cells that typically
presents with pain, pathologic frac-
ture, recurrent infection, and/or fa-
tigue. The annual incidence of newly
diagnosed cases in the United States
is 3 to 4 per 100,000 people.1 The
median age at diagnosis is 65 years,
with a slight male predilection. Mul-
tiple myeloma accounts for approxi-
mately 1% of all malignant diseases,
and median survival is approxi-
mately 50 months after diagnosis.2,3
Spectrum of Disease
Plasma cells are of B-lymphocyte lin-
eage. These cells are responsible for
producing antibodies after exposure
to an antigen. Several mutations
have been identified in association
with multiple myeloma; the most
common are mutation of chromo-
some 14q32 and deletion of chromo-
some 13.4-6 These cytogenetic find-
ings are associated with poor
outcome.6 However, the specific
mechanism of the transition of a
plasma cell to a population of malig-
nant monoclonal plasma cells is
largely unknown (Figure 1).
Several diagnoses associated with
multiple myeloma are considered in
the spectrum of disease. These in-
clude symptomatic myeloma, asymp-
tomatic or smoldering myeloma,
monoclonal gammopathy of unde-
termined significance, nonsecretory
myeloma, and solitary plasmacy-
toma2,3,7,8 (Table 1).
Symptomatic myeloma represents
the classic definition of multiple my-
eloma. The diagnosis is typically
made after the patient presents with
symptoms such as unexplained ane-
mia, renal failure, bone pain, infec-
tion, and hypercalcemia.1,3 Serum
and/or urine electrophoresis results
demonstrate a monoclonal protein
level (ie, M spike) that represents the
antibody produced by the tumor
cells. Immunoglobulin (Ig) G is the

410 Journal of the American Academy of Orthopaedic Surgeons

 Thomas J. Scharschmidt, MD, et al

Figure 1 detected on serum and/or urine elec-
trophoresis, and evidence of end-
organ damage (eg, hypercalcemia,
renal insufficiency, anemia, bone le-
sions, more than two severe infec-
tions per year, amyloidosis, hypervis-
cosity syndrome).2,3,7,8
mediator of myeloma bone disease.
Knowledge of this pathologic pro-
cess has led to increased use of
diphosphonates to treat patients
with multiple myeloma.
Clinical Presentation

Clinical presentation of multiple my-

Photomicrograph demonstrating
typical multiple myeloma histology,
with monoclonal proliferation of
plasma cells (hematoxylin-eosin,
magnification ×200).
most common antibody detected, but
any of the subtypes (ie, IgM, IgE,
IgA) may be present. The abnormal
proteins found in urine (ie, Bence
Jones) are composed of the free light
chains that are excreted through the
kidney.3
A skeletal survey is performed to
evaluate for the presence of bony le-
sions. The serum calcium level is
evaluated; it is often elevated. Bone
marrow aspirate is evaluated to mea-
sure the percentage of plasma cells.
Quantitative Ig assay should be ob-
tained to determine the extent of im-
munoparesis. Kidney function tests
should be performed; the results may
be altered as the result of protein de-
position. The β-2 microglobulin
(β2M) level, which has been linked
to overall prognosis, should be mea-
sured, as well. The diagnostic criteria
for symptomatic myeloma include
the presence of all of the following:
clonal plasma cells >10% on bone
marrow biopsy, monoclonal protein
Myeloma Bone Disease
Lytic bone disease is a hallmark of mul-
tiple myeloma, and a substantial per-
centage of patients develop pathologic
fractures.9 Bone resorption occurs as
the result of osteoclastic stimulation
and activity. Osteoblastic activity de-
creases, as evidenced by low levels of
alkaline phosphatase and osteocal-
cin.10 The uncoupling of osteoclastic
and osteoblastic activity leads to
overall bone loss.
The pathophysiology of myeloma
bone disease is primarily driven by
osteoclastic stimulation by malignant
cells. The osteoclast, not the my-
eloma cell itself, is responsible for
bone destruction. Myeloma cells ad-
here to bone marrow stromal cells
and stimulate the production of re-
ceptor activator of nuclear factor-κ B
ligand (RANKL) and other pro-
osteoclastic mediators (eg, macro-
phage colony-stimulating factor,
interleukin-6, interleukin-11, tumor
necrosis factor).11 The production of
osteoprotegerin, which competes
with receptor activator of nuclear
factor-κ to bind to RANKL as a
decoy receptor, is also suppressed, re-
sulting in further osteoclast activa-
tion. Thus, the RANKL/osteo-
protegerin pathway is the primary
eloma ranges from asymptomatic,
with incidental discovery, to symp-
tomatic, with severe life-threatening
anemia, infection, or disabling bone
pain. Fatigue, bone pain, and recur-
rent infections are the most common
presenting complaints. Multiple end
organs can be affected by myeloma,
which explains the wide spectrum of
presenting symptoms; these symp-
toms (ie, hypercalcemia, renal insuf-
ficiency, anemia, and bone lesions)
are often referred to by the abbrevia-
tion “CRAB.”1,3
Staging
The Durie-Salmon system has tradi-
tionally been used to stage multiple
myeloma. This complex classifica-
tion takes into account the quantity
of monoclonal proteins in the blood
or urine, hemoglobin level, serum
calcium level, findings on skeletal
survey, and renal function as deter-
mined by serum creatinine level.12
Although the Durie-Salmon classi-
fication is still used, it is being super-
seded by the much simpler Interna-
tional Staging System (ISS), which
was published in 2005 by the Inter-
national Myeloma Working Group.13
The ISS is based on β2M and albu-

Dr. Becker or an immediate family member serves as a board member, owner, officer, or committee member of the National
Comprehensive Cancer Network; serves as a paid consultant to or is an employee of Alder Biopharmaceuticals; has received
research or institutional support from Amgen, Genzyme, Millenium: The Takeda Oncology Company, and Celgene; and has stock or
stock options held in Forest Laboratories. Dr. Conrad or an immediate family member serves as a paid consultant to or is an
employee of Zimmer; serves as an unpaid consultant to Stryker; has received research or institutional support from Zimmer; and has
received nonincome support (such as equipment or services), commercially derived honoraria, or other non-research–related funding
(such as paid travel) from Northwest Tissue Services/Puget Sound Blood Center. Neither of the following authors nor any immediate
family member has received anything of value from or owns stock in a commercial company or institution related directly or indirectly
to the subject of this article: Dr. Scharschmidt and Dr. Lindsey.

July 2011, Vol 19, No 7 411

Multiple Myeloma: Diagnosis and Orthopaedic Implications

Table 1
Diagnosis and Management of Multiple Myeloma2,3,7,8
Diagnosis Diagnostic Criteria Management Prognosis

Symptomatic >10% clonal plasma cells present
myeloma on bone marrow biopsy
Monoclonal protein detected on
serum and/or urine
electrophoresis
Evidence of end-organ damage
(eg, hypercalcemia, renal insuffi-
ciency, anemia, bone lesions,
>2 severe infections per year,
amyloidosis, hyperviscosity syn-
drome)
Asymptomatic (ie, Same as symptomatic myeloma,
smoldering) but without evidence of end-
myeloma organ involvement
Monoclonal gammop- Asymptomatic, often discovered
athy of undeter- incidentally
mined significance Monoclonal band <30 g/L, plasma
cells <10%
Nonsecretory Same as symptomatic myeloma,
myeloma except that plasma cells do not
produce protein, so electrophore- duction chemotherapy
sis is negative for protein
Plasmacytoma Solid tumor composed of plasma
cells in bone or soft tissue
Transplant candidates: autologous ISS stage I, 62 mo; stage II, 44 mo;
stem cell transplantation with stage III, 29 mo
induction chemotherapy
Nontransplant candidates: chemo-
therapy
Routine surveillance (every 2-3 mo Once the patient progresses to
by an oncologist) symptomatic myeloma, the prog-
nosis is the same as that of
symptomatic myeloma
Annual electrophoresis for surveil- Prognosis is determined after pro-
lance gression to symptomatic my-
eloma. Approximately 10% pro-
gress to symptomatic myeloma.
Transplant candidates: autologous ISS stage I, 62 mo; stage II, 44 mo;
stem cell transplantation with in- stage III, 29 mo
Nontransplant candidates: chemo-
therapy
Radiation, surveillance Prognosis is determined after pro-
gression to symptomatic my-
eloma. Approximately10%–15%
progress to symptomatic my-
eloma.

ISS = International Staging System

min levels. β2M is part of the major
histocompatibility complex protein
class that is present in all nucleated
cells. β2M levels can be elevated in
patients with renal disease, lym-
phoma, and other disease processes;
therefore, the ISS should be applied
only to patients who match the crite-
ria for the diagnosis of multiple my-
eloma.
ISS stage I disease is defined by a
β2M level <3.5 mg/L and serum al-
bumin level ≥3.5 g/dL. Patients with
stage II disease have β2M levels be-
tween 3.5 and 5.4 mg/L. Stage III
disease is characterized by β2M level
≥5.5 mg/L. The ISS correlates well
with average reported survival rates:
stage I, 62 months; stage II, 44
months; and stage III, 29 months.13
Imaging
In the patient with suspected multi-
ple myeloma, a radiographic skeletal
survey should be performed concur-
rently with bone marrow aspiration
and either serum or urine electropho-
resis. The survey should be scruti-
nized for multiple lytic lesions. The
number of lytic bone lesions is one
criterion in the Durie-Salmon staging
system. In 2003, the original system
was updated to incorporate MRI
findings and was renamed Durie-
Salmon PLUS.14 In the updated sys-
tem, stage I disease is characterized
by the presence of zero to four focal
bone lesions and/or mild diffuse
spine disease on MRI. Stage II dis-
ease is characterized by the presence
of 5 to 20 focal bone lesions and/or
moderate diffuse spine disease visible
on MRI. In stage III disease, >20 fo-
cal bone lesions and/or severe diffuse
spine disease is visible on MRI.
Radiography
Plain radiographs are the standard of
care for evaluation of persons with
myeloma. A survey of the appendicu-
lar skeleton, spine, pelvis, and skull
should be performed in persons with
suspected myeloma. However, le-
sions are not evident on plain radio-
graphs until approximately 50%
bone destruction has occurred.2 Even
so, approximately 80% of patients
with multiple myeloma have positive
radiographic findings at presenta-

412 Journal of the American Academy of Orthopaedic Surgeons


Figure 2
AP radiograph of a hip
demonstrating multiple lytic
punched-out lesions in a patient
with multiple myeloma. These
lesions typically measure <2 cm
and lack reactive bone around the
defect.
tion.15 Typical myeloma lesions are
small (average, 20 mm) and lytic,
with a sharp zone of transition and
lack of reactive bone15 (Figure 2).
Four distinct forms of myeloma have
been identified radiographically: soli-
tary plasmacytoma, diffuse disease,
diffuse osteopenia, and sclerosing
myeloma.2 Plain radiographs are the
most widely used standardized test
for the evaluation of impending and
pathologic fractures associated with
multiple myeloma.
CT
CT is helpful in defining the extent
of lytic bone lesions that are poorly
visualized radiographically. Common
findings include punched-out lytic le-
sions, expansile lesions with soft-
tissue masses, pathologic fractures,
and osteosclerosis.2 CT also allows
July 2011, Vol 19, No 7
evaluation of the cross-sectional
anatomy of the lesion, which is im-
portant for gauging the integrity of
the cortical bone and predicting the
risk of pathologic fracture. Although
mechanical pain may be the best in-
dicator of an impending fracture, in-
volvement of >50% of the cortical
bone visible on CT has traditionally
been one of the criteria used for rec-
ommending prophylactic fixation
versus radiation therapy.16 Any pa-
tient who may have an impending
fracture that is not obvious on plain
radiographs should be evaluated
with CT through the lesion. CT-
guided biopsy is used for tissue diag-
nosis in the setting of inconclusive
results on serum or urine electropho-
resis.
Nuclear Medicine Studies
Technetium-based bone scans rely on
an osteoblastic response for uptake
of the radiopharmaceutical agent.
Because multiple myeloma is primar-
ily driven by osteoclastic activity and
is a disease of bone resorption, bone
scan tends to be unreliable, and the
extent of disease can be underesti-
mated. Hubner et al17 compared
bone scans with plain radiographs
for the evaluation of bone lesions.
Uptake occurred on the bone scan in
only 44% of radiographically abnor-
mal areas, and findings were normal
in 48% of these lesions.2,17 In gen-
eral, lesions with uptake on bone
scan are the result of a complication
of myeloma, such as insufficiency or
pathologic fracture. Therefore, a
bone scan is not recommended as
part of routine staging in persons
with multiple myeloma.
The use of fludeoxyglucose F 18
positron emission tomography (FDG
PET) is gaining in popularity in
many areas of oncology for early de-
tection, staging, and monitoring of
diseases such as multiple myeloma.18
In a recent series of 43 patients,
Thomas J. Scharschmidt, MD, et al
Schirrmeister et al19 reported that
FDG PET had a sensitivity of 92.7%
in identifying radiographically os-
teolytic lesions in 23 patients. In 14
patients, lesions that were not appar-
ent radiographically were detected
on FDG PET.
PET has been demonstrated to be
more sensitive than radiographs in
screening and diagnosing myeloma.
In fact, Lütje et al20 suggested that
FDG PET used in combination with
low-dose CT can replace conven-
tional radiographs as the standard of
care. Most large centers now use
FDG PET as part of the initial stag-
ing and in assessing patient response
to treatment.18,21 FDG PET also
should be considered in patients with
a diagnosis of solitary plasmacytoma
because it may uncover additional
sites of disease. In a study of 15 pa-
tients with known plasmacytoma
who underwent FDG PET for stag-
ing, additional lesions were found in
5 patients, which resulted in treat-
ment modification for 4 patients.22
MRI
Indications for MRI in patients with
multiple myeloma are expanding.
MRI appears to be more sensitive
and specific than radiography in
identifying bone marrow lesions, es-
pecially in the pelvis and spine.23 On
T1-weighted spin-echo images, a le-
sion appears as a hypointense area
on a background of hyperintense
marrow. T2-weighted spin-echo se-
quences reveal hyperintense focal im-
ages relative to the hypointense mar-
row (Figure 3). Diffuse involvement
presents as general hyperintensity
compared with the surrounding mus-
culature.15
Several authors have recommended
MRI of the entire appendicular skel-
eton, pelvis, and spine at the time a
patient is diagnosed with multiple
myeloma.8,21,23 Some authors suggest
that initially obtaining an MRI may
413
Multiple Myeloma: Diagnosis and Orthopaedic Implications

Figure 3 Figure 4

Sagittal T2-weighted spin-echo

magnetic resonance image
demonstrating a large sacral lesion
in a patient with multiple myeloma.
In this image, all lesions have
hyperintense signal characteristics.

obviate the need for additional stud-

ies in patients in whom stage III
disease is apparent on that MRI sur-
vey.21 Findings suggestive of my-
eloma include an expansile focal
mass, multiple focal masses in the
appendicular skeleton, diffuse mar-
row involvement, and multiple com-
pression fractures in the patient with
no known malignancy.
MRI or FDG PET should also be
obtained in the patient with sus-
pected solitary plasmacytoma. Addi-
tional lesions have been reported in
up to one third of cases evaluated us-
ing whole-body MRI.23 Patient treat-
ment is affected by the number of le-
sions present.
MRI also may be used to monitor
response to treatment because it can
show reduction in or resolution of le-
sions identified on initial imaging.
Resolution of the bone marrow to a
normal pattern is associated with a
better prognosis and longer remis-
sion.21,24 Most centers now favor
PET-CT to MRI for evaluating pa-
tients with multiple myeloma.
Treatment algorithm for newly diagnosed myeloma. * ≥12 months of therapy
and stable disease for ≥2 months. (Adapted with permission from Kyle RA,
Rajkumar SV: Multiple myeloma. N Engl J Med 2004;351[18]:1860-1873.)
Initial Therapy
Medical Management
Nontransplant Candidate
Management of myeloma addresses Patients with medical comorbidities,
plasma cell proliferation and symp- of advanced age, or in poor physical
toms secondary to it. Treatment of condition are not candidates for
patients with monoclonal gammop- transplantation. These patients are
athy of undetermined significance or treated with oral melphalan and
asymptomatic myeloma consists of prednisone in combination with ei-
annual surveillance to monitor for ther thalidomide or bortezomib1,26
transformation to symptomatic my- (Figure 4). The cycles of melphalan
eloma. There is no evidence that plus prednisone reduce the collection
early management of asymptomatic of peripheral blood stem cells, but in
myeloma improves survival.25 Initial older patients (ie, >65 years), they
therapy for symptomatic myeloma is also reduce the severity of toxic side
determined by whether the patient is effects. Better response rates are seen
a candidate for autologous stem cell with more aggressive regimens (ie,
transplantation1,3 (Figure 4). lenalidomide-dexamethsone or tha-

414 Journal of the American Academy of Orthopaedic Surgeons


lidomide-dexamethasone); however,
no survival benefit has been shown.1
Transplant Candidate
Transplant candidates undergo in-
duction therapy consisting of dexa-
methasone combined with thalido-
mide, lenalidomide, or bortezomib.1,3
Combinations include lenalidomide
and dexamethasone; bortezomib and
dexamethasone; bortezomib, thalid-
omide, and dexamethasone; and
bortezomib, lenalidomide, and dex-
amethasone. Approximately 70% to
90% of patients respond to initial
therapy.1 Side effects include myelo-
suppression, thrombosis, gastrointes-
tinal effects (eg, infection, diarrhea),
and neuropathy. Most of these side
effects are reversible.
Autologous and Allogeneic
Stem Cell Transplantation
Autologous stem cell transplantation
involves transplantation of the pa-
tient’s own stem cells after chemo-
therapy. This procedure is not cura-
tive. However, it has been shown to
increase disease-free survival by 2 to
3 years.3 Candidates are selected
based on age, performance status (ie,
measure of disease burden on overall
patient activities), and evidence of
preserved organ function. In younger
transplant candidates (ie, aged <65
years), combinations of induction
chemotherapeutic drugs are recom-
mended. These drugs are not toxic to
the hematopoietic cells and do not
impair the ability to collect adequate
numbers of peripheral blood stem
cells. Given the multiple treatments
available and the lack of consensus
regarding which is most effective, pa-
tients are encouraged to enroll in
clinical trials in an effort to deter-
mine best practices.
In general, patients are treated
with a chemotherapy regimen for
several months until maximal re-
sponse is achieved, after which they
undergo mobilization and collection
July 2011, Vol 19, No 7
of autologous stem cells, followed by
high-dose melphalan chemotherapy
and infusion of stem cells.1 Tandem
sequential autologous (ie, double-
auto) transplants have demonstrated
an advantage in patients with resid-
ual myeloma following the first
transplant.3,27
Minimal myeloablative (ie, mini-
allo) regimens were developed in re-
sponse to substantial mortality fol-
lowing high-dose melphalan and
high-dose total body irradiation with
allogeneic stem cell transplantation.
A combination of autologous trans-
plant followed by mini-allo trans-
plant has been shown to be success-
ful.28 In one study, 6 of 13 patients
who showed response to initial che-
motherapy and who achieved partial
or complete remission following the
combined procedure were event-free
at 2-year follow-up.29 Maintenance
therapy with interferon alpha or
prednisone can be considered after
autologous or allogeneic stem cell
transplant in an effort to prolong the
time to progression; however, con-
troversy persists regarding the bene-
fit of this therapy.1
Salvage Therapy
Eventual relapse after treatment is
the natural history of multiple my-
eloma. With relapse that occurs >6
months after prior therapy, the
potential exists for a therapeutic re-
sponse to the initial therapy regi-
men.30 Regimens for relapsed my-
eloma that have been studied and
approved by the US FDA include
lenalidomide and dexamethasone,
bortezomib and dexamethasone, and
bortezomib and liposomal doxoru-
bicin.
Additional Adjuvant Agents
Patients with multiple myeloma may
suffer from conditions related to the
complexity of the disease process
and to complications associated with
Thomas J. Scharschmidt, MD, et al
therapy, such as anemia and neurop-
athy. Adjuvant agents and processes,
including diphosphonates, growth
factors, transfusion, and vitamin
supplements, can be used to manage
these complications (Table 2).
Orthopaedic
Considerations
The orthopaedic surgeon may be
consulted to perform a biopsy for
initial diagnosis, provide recommen-
dations for nonsurgical care, per-
form prophylactic fixation of im-
pending fractures, or stabilize
pathologic fractures in the patient
with myeloma bone disease. Typi-
cally, a patient presents with an im-
pending or pathologic fracture with
no prior diagnosis of myeloma. In
the patient with a bone lesion and
unknown primary malignancy, the
workup includes radiographs of the
entire bone; bone scan; MRI of the
extremity; CT of the chest, abdomen,
and pelvis; complete blood count; se-
rum and/or urine electrophoresis;
prostate-specific antigen in men; and,
in women, a breast examination or
mammogram. In a prospective study
of 40 patients with skeletal metasta-
ses of unknown origin who were
evaluated using this strategy, the pri-
mary site of the malignant tumor
was identified in 34 patients
(85%).31
When the electrophoresis is posi-
tive, radiographic bone survey and
bone marrow biopsy are performed
for staging. However, no further bi-
opsy of the lesion is required for di-
agnosis. Biopsy is required in some
cases, such as in the patient with sus-
pected plasmacytoma and when elec-
trophoresis is not obtained. Biopsy
must be done carefully because my-
eloma lesions can be very vascular,
and there is a risk of substantial
blood loss. This should also be taken
into account during preplanning for
415
Multiple Myeloma: Diagnosis and Orthopaedic Implications
Table 2
Adjuvant Agents for Managing Complications Associated With Multiple
Myeloma Therapy
Category Agent Indications
Diphosphonate Pamidronate, zoledronic Evidence of bone loss
acid
Growth factor Granulocyte colony–stimu- Neutropenia associated with
lating factor agents such as bortezomib,
lenalidomide, or combination
therapies
Epoetin α, darbepoietin Patients with renal insufficiency
with subsequent erythropoietin
production may benefit from
supplementation.
Transfusion — Treatment-acquired anemia and
thrombocytopenia may require
red cell and/or platelet transfu-
sion.
Vitamin supplement Pyridoxine Vitamin supplements may be
and other medica- helpful in preventing drug-
tions related peripheral neuropathy.
Thalidomide and bortezomib in
particular are associated with
neuropathy.
Gabapentin, pregabalin Painful neuropathy
intramedullary or open procedures. who is being considered for bone
Blood type and crossmatch should be marrow transplant. In this scenario,
obtained prior to either type of sur- an aggressive surgical approach pre-
gery. transplant may be considered. If such
The orthopaedic surgeon may be a lesion were to progress and result
asked to evaluate a painful bone in a fracture during the transplant,
lesion in a patient with known my- the patient would be at risk of a long
eloma to determine whether prophy- delay prior to surgical fixation. Were
lactic surgical stabilization is war- such a fracture to occur in a weight-
ranted. Not all bone lesions are bearing bone, requiring a long period
prone to fracture, and several factors of bed rest, the immunocompro-
should be considered when deciding mised patient would be at risk of
on appropriate treatment. pneumonia, pressure sores, and gen-
Pain can be produced by the tumor eral deconditioning.
itself or by mechanical weakening of In the patient with myeloma, sev-
the bone. When the tumor is the eral medical factors must be consid-
cause of pain, the lesion frequently ered before proceeding with surgery.
responds to radiation therapy. Non- Many newly diagnosed patients are
surgical management also should be hypercalcemic, and this condition
considered for lesions in non–weight must be managed prior to surgical
bearing areas (eg, upper extremity, il- intervention. Consultation with the
iac wing) in which surgical manage- medical oncologist is essential be-
ment could delay systemic care. cause many chemotherapeutic agents
Another important consideration is cause myelosuppression and may
a lesion that does not meet criteria cause a nadir at various times after
for surgical stabilization but is lo- administration of the drug; this
cated in a high-risk area in a patient could affect optimal surgical timing.
416 Journal of the American Academy of Orthopaedic Surgeons
Dexamethasone is used in many regi-
mens, and a stress dose of steroids
may be warranted at the time of sur-
gery.
Patients with a malignant diagnosis
are at increased risk of thromboem-
bolic disease, and chemotherapy in-
creases this risk further, to sevenfold
that of the general population.32 As
such, these patients are considered to
be at highest risk of deep vein throm-
bosis and pulmonary embolism, and
they are typically treated in accor-
dance with the American College of
Chest Physicians guidelines on thera-
peutic heparin (international normal-
ized ratio, 2 to 3) or low-molecular-
weight heparin.33 Anticoagulation
therapy may need to be stopped and
coagulopathies corrected preopera-
tively, with resumption of anticoagu-
lation immediately postoperatively.
In patients with multiple myeloma,
surgical indications are typically lim-
ited to management of impending or
pathologic fracture. A substantial
percentage of patients with multiple
myeloma develop pathologic frac-
tures.9 Basic principles of surgery for
patients with metastatic disease
should be followed, including preop-
erative imaging of the entire involved
bone, achieving an immediately sta-
ble and durable construct, and post-
operative radiation therapy.16,34,35
Overall patient prognosis and life ex-
pectancy should be considered prior
to any surgical intervention.
For impending fracture or a pain-
ful lesion that is unresponsive to ra-
diation therapy, stabilization surgery
is typically recommended when life
expectancy is >3 months. This allows
ample time for postoperative recov-
ery and achievement of beneficial
pain relief. For the patient whose life
expectancy is <3 months, palliative
treatment should be discussed with
the patient and family. When surgery
is chosen, as much of the involved
bone as possible is stabilized, typi-
cally with intramedullary fixation, to

Figure 5
AP radiograph demonstrating
humeral stabilization with an
intramedullary implant in a patient
with a myeloma lesion in the
humerus.
avoid creating new stress risers in
pathologic bone (Figure 5). For a
large defect, curettage can be per-
formed, and the bone can be stabi-
lized with polymethylmethacrylate
cement around the intramedullary
device.
For a periarticular lesion, a custom
or megaprosthesis can be used, with
the goal of achieving an immediately
durable construct that allows early
mobilization36 (Figure 6). Good func-
tional results and pain relief can be
expected.36,37 The surgeon should
avoid using press-fit implants and
constructs that rely on bony in-
growth.
The periacetabular region is a com-
mon site of myeloma lesions. Periac-
etabular lesions often present with
large cavities and are painful as a re-
sult of their presence in a weight-
bearing area. Few appealing surgical
interventions exist, given the com-
plex anatomy of the bony pelvis. If
the acetabular subchondral plate is
July 2011, Vol 19, No 7
Figure 6
A, Preoperative AP radiograph of the hip demonstrating pathologic fracture
through a myeloma lesion. B, Postoperative AP radiograph demonstrating a
stable, durable construct achieved with a modular proximal femoral
prosthesis.
intact, we prefer to perform curet-
tage of the lesion and stabilize it with
polymethylmethacrylate cement and
modified Harrington pin fixation. If
the subchondral plate is violated by
tumor extension, complex total hip
reconstruction with an acetabular
cage is performed. Internal or exter-
nal hemipelvectomy can be consid-
ered in the patient with intractable
pain.
Spinal compression fractures have
been identified in >40% of patients
with newly diagnosed myeloma.2 In
painful lesions, percutaneous verte-
broplasty has proved to be effective
in alleviating pain.38 In that study, all
10 patients with multiple myeloma
reported mild or moderate pain re-
lief. These interventions allow imme-
diate improvement in quality of life
following an outpatient procedure or
a short hospital stay (80% reported
pain relief within 7 days of the pro-
cedure).38 In most patients, pain re-
lief can be expected to last up to 2
Thomas J. Scharschmidt, MD, et al
years after the procedure.39 MRI
should be done preoperatively to as-
sess for extraosseous disease. In the
patient with considerable soft-tissue
involvement, radiation therapy to
the area before stabilization may be
helpful.
Neural compression or more ex-
tensive spinal bony involvement that
is not amenable to a percutaneous
procedure is relatively rare, given the
sensitivity of the disease to radiation
therapy. In patients who present with
either neural compression or exten-
sive bony involvement, effective
management typically consists of spi-
nal cord decompression and stabili-
zation of the vertebral column
through an anterior, a posterior, or a
combined approach. Although these
procedures are extensive, they result
in significant improvement in patient
quality of life and pain reduction,
along with stabilization or improved
neurologic function.39
417
Multiple Myeloma: Diagnosis and Orthopaedic Implications
Radiation Therapy
External beam radiation therapy is a
mainstay of treatment in the patient
with myeloma bone disease.40 It is
used as an antimyeloma therapy as
well as a palliative treatment method
in patients with incurable disease.
Radiation therapy alone has the po-
tential to be curative in patients with
solitary plasmacytoma.41 However, it
is typically used for palliative pain
relief in patients with symptomatic
lesions. Pain relief is typically
achieved with a dose of approxi-
mately 3,000 cGy administered in 10
to 15 fractions.42
Other indications for radiation
therapy include impending or patho-
logic fracture, spinal cord compres-
sion, and other local neurologic
problems caused by tumor. Patients
who undergo surgical fixation or sta-
bilization of an active lesion should
be treated with adjuvant radiation to
the surgical field to decrease local re-
currence of the disease. Adjuvant ra-
diation is not used in persons with
mechanical failure of the bone, as is
seen in those who have responded
well to chemotherapy and who have
residual lytic cavities.
Radiotherapeutic agents (eg, stron-
tium 89) have been described as a
palliative treatment in the patient
with intractable bone pain.2 Re-
sponse to these adjuvants is depen-
dent on an osteoblastic response and
may not be effective in a purely os-
teoclastic scenario. Thus, technetium
bone scan should be obtained prior
to radiation therapy to identify the
magnitude of osteoblast involvement
in order to determine whether the
patient is a good candidate for this
treatment.2
Summary
Multiple myeloma is a primary ma-
lignancy of plasma cells that mani-
418
fests in various ways. Bony pain and
pathologic fracture are among the
most common presentations. In the
past decade, advances in treatment
have led to improved outcomes in
patients with multiple myeloma, in-
cluding event-free and overall sur-
vival. As a result, more patients are
presenting with orthopaedic manifes-
tations of the disease. Thus, ortho-
paedic surgeons need to understand
the basic pathophysiology of the dis-
ease and the appropriate manage-
ment of impending and pathologic
fractures.
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