Review Article

Radionuclide Imaging in the

Diagnosis and Management of
Orthopaedic Disease

Wellington Hsu, MD
Thomas M. Hearty, MD, DPT
Abstract
Nuclear medicine imaging is often used in the diagnosis and
management of several orthopaedic conditions. Bone scintigraphy
measures gamma ray emission to detect the distribution of an
injected radiolabeled tracer on multiple image projections. In
general, this imaging modality has relatively high sensitivity but low
specificity in the diagnosis of occult fractures, bone tumors,
metabolic bone disease, and infection. Positron emission
tomography measures tissue metabolism and perfusion by
detecting short half-life positron ray emission of an injected
radiopharmaceutical tracer. Historically, positron emission
tomography has been used only to monitor bone metastasis and
aid in the diagnosis of osteomyelitis; however, this technology has
recently been applied to other orthopaedic conditions for which
current imaging modalities are insufficient.

R ecent advances in the accuracy,

From the Department of
Orthopaedic Surgery, Northwestern
University, Chicago, IL.
Dr. Hsu or an immediate family
member is a member of a speakers’
bureau or has made paid
presentations on behalf of Pioneer
Surgical Technology and Stryker and
has received research or institutional
support from Baxter, Medtronic
Sofamor Danek, and Pioneer
Surgical Technology. Neither
Dr. Hearty 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.
J Am Acad Orthop Surg 2012;20:
151-159
http://dx.doi.org/10.5435/
JAAOS-20-03-151
Copyright 2012 by the American
Academy of Orthopaedic Surgeons.
availability, and protocol develop-
ment of nuclear medicine imaging have
led to rapid changes in the indications
and use of these modalities in ortho-
paedics. Unlike conventional diagnos-
tic methods such as plain radiography
and CT, radionuclide imaging can mea-
sure real-time metabolic activity,
thereby providing valuable pathophys-
iologic information that conventional
imaging modalities cannot. Radionu-
clide imaging has a similar amount of
radiation exposure as noncontrast
CT.1,2 As radionuclide imaging tech-
nology continues to advance, its ap-
plications in the diagnosis and man-
agement of orthopaedic disease will
inevitably expand.
Bone Scintigraphy
Bone scintigraphy detects the distri-
bution of an injected radioactive
agent by measuring bodily gamma
ray emission with a specialized cam-
era. Radioactive tracers localize to
tissue with metabolic activity (ie, tis-
sue undergoing acute change and/or
repair). The type of tracer used de-
pends on the tissue of interest. For
example, in bone, a radiopharma-
ceutical such as technetium Tc-99m–
labeled diphosphonate is chosen be-
cause of its affinity for areas with
increased skeletal blood flow and
bone turnover.3,4 Multiple image pro-
jections are used to evaluate either
the whole body or one anatomic
area. Although the specific character-
istics of uptake vary depending on
the particular agent used, each pro-
vides a measure of local cellular met-
abolic activity. Currently accepted
indications for bone scintigraphy in-
clude the diagnosis of occult frac-
tures, bone infection, staging, and
detection of neoplasms3-5 (Table 1).
Bone scintigraphy can be per-

March 2012, Vol 20, No 3 151

Radionuclide Imaging in the Diagnosis and Management of Orthopaedic Disease
Table 1
Diagnostic Accuracy of Bone Scintigraphy for Several Orthopaedic Conditions
FDG-PET
(sensitivity/
Condition specificity)
Bone and joint infection 94.1/87.3
with metallic implants6
Spine infections6 99.9/87.9
Scaphoid fracture7 N/A
Hip occult fracture8 N/A
Charcot foot neuropathy11 100/93.8b
Multiple myeloma9,12 83.8–91.9/83.3–100
Breast cancer metasta- 87/83
sis10
FDG-PET = fluorodeoxyglucose–positron emission tomography, N/A = not applicable, WBC = white blood cell
a
Gallium Ga-67
b
Sensitivity/accuracy
formed as a single scan or in multiple
phases. Single-phase scanning is usually
completed 2 to 4 hours after injection
of the tracer but can be done as late as
36 hours following injection. This scan
produces whole-body planar coronal
images of the skeleton that demon-
strate bone metabolism. This technique
is used chiefly to detect primary or
metastatic bone tumors.
A multiphase scan is performed in
clinical situations in which soft-
tissue perfusion is necessary for diag-
nosis. The first phase, or blood flow
phase, involves imaging done imme-
diately after injection; it shows the
blood flow distribution of the tracer
to the lesion. The second phase, or
blood pool scan, is obtained within 5
minutes after injection and demon-
strates the location of the tracer in
the vascular system and extracellular
space of the surrounding soft tissue.
The third phase measures the bone
uptake of the tracer following excre-
tion from the soft tissues. Multiphase
imaging allows differentiation of
clinical conditions, such as between
cellulitis and osteomyelitis or be-
tween acute and chronic healing
fracture.3-5
Single photon emission CT
(SPECT) provides high-resolution,
152
Bone Scan
(sensitivity/
specificity)
85.4/75.2
86.3/35.8a
100/98
97.8/95
N/A
77/86 86–92/Unknown13
43/98
three-dimensional imaging that can
characterize the precise location and
extent of disease with greater accu-
racy than can be achieved using pla-
nar images. Bone SPECT has proved
to be particularly useful in the detec-
tion of lesions in large and complex
anatomic structures such as the pel-
vis, knees, ankles, and spine (in par-
ticular, the pars interarticularis and
the vertebral body).3-5 The combina-
tion of SPECT and CT (SPECT/CT)
greatly enhances diagnosis and eval-
uation of the disease process.4
Several tracers have been used in
bone scintigraphy because of their
propensity for bony localization (Ta-
ble 2). Technetium Tc-99m–labeled
diphosphonates have a high affinity
for bone osteocytes and osteoblasts
in comparison with other soft tis-
sues, have rapid soft-tissue clearance
(half-life, 6 hours), decay to a stable
element, and provide good image
quality. Tc-99m–labeled tracers have
been used to evaluate fractures, os-
teomyelitis, and bone neoplasms.3-5
Gallium Ga-67 is derived from either
gallium citrate or gallium nitrate.
This tracer is handled in the body in
a manner similar to iron and local-
izes in areas of inflammation. Re-
cently, positron emission tomogra-
Journal of the American Academy of Orthopaedic Surgeons
MRI Labeled WBC
(sensitivity/ (sensitivity/
specificity) specificity)
88.2/84.7 82.8/83.8
81.8/57 83.3/54.9
100/100 N/A
100/100 N/A
76.9/75b N/A
N/A
N/A N/A
phy (PET) has replaced Ga-67 in
many clinical settings; however,
Ga-67 is still used to evaluate
chronic osteomyelitis, septic arthri-
tis, soft-tissue lesions, and response
to therapy.3-5,14
Labeled leukocyte scanning is used
to detect infection. Autologous white
blood cells (WBCs) are tagged with a
radioisotope (ie, indium, Tc-99m)
and reinjected into the circulation.
Localization of these WBCs is
strongly suspicious for infection. For
example, labeled WBCs are useful in
diagnosing infection about metallic
implants and in differentiating be-
tween osteomyelitis and a neuro-
pathic joint.3-5,14 Similarly, leukocyte-
labeled antibodies can be used, as
well. These do not require manipula-
tion of the patient’s blood products.
Exogenous antibodies to granulocyte
surface antigens are labeled with Tc-
99m or indium and injected into the
patient’s circulation. These radiola-
beled antibodies accumulate nonspe-
cifically in infectious and inflamma-
tory processes.6 Although nuclear
medicine imaging is considered to be
a safe procedure with low radiation
exposure, its use is contraindicated
in pregnant patients and breast-
feeding mothers.1
 Wellington Hsu, MD, and Thomas M. Hearty, MD, DPT

Table 2
Common Radiopharmaceuticals (Tracers) Used in Musculoskeletal Nuclear Medicine Imaging
Tracer Indications Physiologic Mechanism

Technetium Tc-99m–labeled Early and occult OM 6 h half-life

diphosphonates Distinguish between soft-tissue infection and 50% localizes to bone
OM Excreted by kidneys
Determine monostotic versus polyostotic bone
lesion
Local recurrence of tumor
Response to chemotherapy and radiotherapy
Gallium Ga-67 Chronic OM Incorporated into calcium hydroxyapatite and
Inflammatory bone processes bone marrow
Measure response to therapy of chronic OM Localizes to areas of inflammation
and septic joints Acts like iron
Differentiate between malignant and benign
soft-tissue lesions
Spinal OM
Labeled WBCs (indium In-111 or Detects acute inflammatory abnormalities Localized to the site by an endogenous inflam-
Tc-99) Recurrent active infection of chronic OM matory pathway
Complex OM (eg, joint arthroplasty, neuropathic Requires colloid subtraction to isolate hot spots
joint, diabetic foot)
Fluorine F-18–fluorodeoxyglu- Staging and monitoring malignancies (lym- Transported into cells through glucose
cose phoma, bone sarcoma) transporters
Diagnosis and monitoring of multiple myeloma Increased uptake with increased cellular metabo-
Detecting breast and lung metastasis lism
Infections in the setting of metallic implants
Detecting primary and secondary spinal
infections
Charcot foot
Fluorine F-18–sodium fluoride Detecting and monitoring metastatic prostate The 18F ion exchanges with hydroxyl groups on
(18F) cancer lesions hydroxyapatite, which incorporates into the
Bone healing/formation (possible future use) formation of bone matrix

OM = osteomyelitis, WBC = white blood cell

Infection
Three-phase Tc-99m bone scanning
is a relatively inexpensive whole-
body imaging modality. Infection can
be detected as increased localized up-
take during all three phases. Differ-
ences between phases can distinguish
the definitive location of infection.
For example, increased activity dur-
ing the late phase is indicative of os-
teomyelitis rather than soft-tissue
infection. Furthermore, bone scintig-
raphy has been used to detect multi-
ple sites of primary and hematoge-
nous osteomyelitis, particularly in
the pediatric population.5,6
Conversely, although three-phase
whole-body imaging has high sensi-
tivity, specificity is relatively poor.
For example, it is difficult to distin-
guish infection from fracture, neuro-
pathic joint, postoperative changes,
and aseptic loosening of a joint pros-
thesis. A meta-analysis of peer-
reviewed articles from 1984 to 2004
on the evaluation of secondary os-
teomyelitis in peripheral bone with
prosthetic joint implants demon-
strated that bone scintigraphy has an
accuracy of 75.5% (sensitivity,
85.4%; specificity, 75.2%), which is
significantly lower than the accuracy
of MRI and aspiration (88.7% and
88.4%, respectively).6 For these rea-
sons, three-phase whole-body imag-
ing has been replaced by other diag-
nostic imaging techniques for
evaluating secondary osteomyelitis
about prosthetic joint implants.
Labeled leukocyte imaging can be
useful in cases of infection that are
complicated by concomitant fractures
or joint prostheses. However, this mo-
dality is limited because leukocytes can
extravasate in the surrounding tissues
after fracture, resulting in inaccurate
uptake and imaging. Techniques in-
volving colloid subtraction improve ac-
curacy by using Tc-99m sulfur colloid
to identify bone marrow but not sites
of infection. This technique has an
overall accuracy of 89.1% (sensitivity,
89.0%; specificity, 89.1% for Tc-99m–
labeled WBCs with colloid subtraction)
for acute and subacute secondary infec-
tions of the peripheral skeleton.4,6
Factors that can affect leukocyte up-
take include steroids, chronic antibi-
otic use, and anatomic differences in
the axial skeleton. Generally, labeled

March 2012, Vol 20, No 3 153

Radionuclide Imaging in the Diagnosis and Management of Orthopaedic Disease

Figure 1

A, Anterior (left) and posterior (right) whole-body

technetium Tc-99m methylene diphosphonate bone
scans. Increased uptake in the thoracic spine is the
result of postoperative changes. There is a suggestion
of decreased activity in both femoral heads. B, Anterior
static rectilinear image of the pelvis clearly
demonstrating decreased uptake surrounded by
increased uptake in both femoral heads. This pattern is
typical of osteonecrosis. (Adapted with permission from
Palestro CJ, Love C, Schneider R: The evolution of
nuclear medicine and the musculoskeletal system.
Radiol Clin North Am 2009;47[3]:505-532. http://www.
sciencedirect.com/science/journal/00338389.)

leukocyte scanning is not effective in
detecting chronic osteomyelitis sec-
ondary to avascularity.6
MRI is the chief diagnostic tool for
primary spinal infections, with
>90% accuracy.15 However, the accu-
racy of MRI decreases with the in-
volvement of spinal infections in the
postoperative setting (78.8%).6 In
bone scintigraphy, gallium scans
have been found to be the most accu-
rate in detecting primary and postop-
erative spinal infections (88.5%),
with a low specificity (35.8%).6
Trauma
In some clinical situations, fractures
cannot be diagnosed with plain radi-
ography alone. Bone scintigraphy
has demonstrated >95% sensitivity
in detecting occult fractures in areas
such as the carpal bones, proximal
femur, ribs, talar dome, pelvis, and
spine.5 For this reason, multiphase
scans have been used in the diagnosis
of scaphoid, stress, and toddlers’
fractures.7,16-18 Bone scan was found
to have equivalent sensitivity but
lesser specificity than MRI in the
evaluation of occult scaphoid frac-
tures (sensitivity, 100% and 100%,
respectively; specificity, 98% and
100%, respectively).7
Alternative imaging modalities (eg,
MRI) have been found to be more
helpful than bone scintigraphy in de-
tecting certain fracture types. For ex-
ample, for occult hip fractures, bone
scans have decreased sensitivity and
specificity compared with MRI (sen-
sitivity, 97.8% and 100%, respec-
tively; specificity, 94.0% to 95.0%
and 100%, respectively).8 In addi-
tion, bone scintigraphy has lower ac-
curacy than do MRI and CT in the
diagnosis of sacral insufficiency frac-
tures.19 However, bone scintigraphy
may be more sensitive for diagnosis of
occult hip fracture and osteonecrosis of
the femoral head within the first 72
hours after insult4 (Figure 1). For
stress fractures of long bones, multi-
phase bone scan has equivalent sensi-
tivity to but less specificity than

154 Journal of the American Academy of Orthopaedic Surgeons


MRI.20 Because MRI provides better
morphologic data and demonstrates re-
covery more accurately, it should be
used in evaluating stress injuries.5,20
One distinct advantage of bone
scintigraphy in the trauma setting is
its ability to distinguish a temporal
relationship. In patients aged <65
years, the sensitivity of multiphase
studies increases from 95% in the
acute setting to 100% 72 hours after
injury.5 In patients aged >65 years,
sensitivity is reportedly 95% by 72
hours after injury. Additionally, cer-
tain fracture patterns are seen at dif-
ferent time points. This information
can be used to classify fractures as
acute (1 to 4 weeks), subacute (6 to
12 weeks) or chronic (12 weeks to 2
years). In the acute stage, blood flow
and blood pool activity are seen. The
subacute stage is marked by a reduc-
tion in blood flow and blood pool
images and localization at the frac-
ture site. In the healing phase, there
is gradual diminution of activity in
the delayed image, with normaliza-
tion of activity 1 to 2 years after the
fracture. Persistent uptake during the
healing phase (ie, >12 weeks after
fracture) raises the suspicion of non-
union and/or infection. Identifying
these patterns can aid in diagnosing
the relative age of the injury.5
Spine
Bone scintigraphy can be used to aid
in the diagnosis of spondylolysis,
that is, a defect of the pars interartic-
ularis of the vertebrae; typically,
spondylolysis is caused by an axial
loading injury to the lumbar spine in
hyperextension.21 Multiphase bone
scan demonstrates low specificity in
the diagnosis of spondylolysis,21 but
SPECT is particularly useful in iden-
tifying the increased metabolic activ-
ity associated with the injury. Ana-
tomic localization of the injury on
CT greatly enhances the diagnostic
capabilities and can be done in con-
March 2012, Vol 20, No 3
Wellington Hsu, MD, and Thomas M. Hearty, MD, DPT
junction with SPECT.21,22 Several case
series demonstrate that SPECT is
also useful in distinguishing between
acute and chronic injury in all
cases.23 There is substantiated con-
cern regarding the long-term ramifi-
cations of radiation exposure from
CT in this patient population; MRI
may be used instead in patient evalu-
ation.24 However, compared with
SPECT/CT, MRI has inferior sensi-
tivity and specificity in the detection
of spondylolysis.21
Bone scintigraphy is also beneficial
in evaluating fragility fractures of the
vertebral body. In situations in which
plain radiographs are equivocal,
bone scans can demonstrate the pres-
ence and acuity of the fracture in ad-
dition to providing whole-spine im-
aging, including of the sacrum and
ribs.5,25 SPECT also has been used to
identify facet joint arthropathy,
which may coincide with vertebral
fracture and may prove to be the
source of pain.25 In a recent study,
bone scintigraphy directly contrib-
uted to a change in management in
18 of 60 osteoporotic patients with
back pain, and it was used to ex-
clude vertebral fracture as the cause
of symptoms in 30 patients.25 Bone
scintigraphy should be considered in
osteoporotic patients with back pain
when clinical findings, plain radio-
graphs, and/or MRI are equivocal.
Positron Emission
Tomography
PET is a nuclear medicine modality
that produces a three-dimensional
image by detecting gamma ray emis-
sion indirectly from a positron-
emitting radioactive tracer. PET
tracers have a propensity for meta-
bolically active cells and provide
valuable information regarding
change and repair. Currently ac-
cepted indications include the diag-
nosis and monitoring of bone neo-
plasms and infections, particularly
those associated with metallic im-
plants.4,6,26 Recent research demon-
strates the utility of PET for measur-
ing bone graft incorporation/fusion
and fracture healing.27-30
Two primary tracers are used to de-
tect orthopaedic conditions. The most
commonly used tracer is fluorine-
18–fluorodeoxyglucose (18F-FDG),
which crosses the plasma membrane
through open glucose transporters of
cells. As a result, 18F-FDG uptake is
directly related to cellular glucose
metabolism. Fluorine-18 sodium flu-
oride (18F) ion is another commonly
used tracer. The 18F isotope typically
exhibits high uptake by bone and has
been shown to deposit on the surface
where the greatest amount of remod-
eling and turnover occurs. This iso-
tope has greater capillary permeabil-
ity than do Tc-99m diphosphonates
and a higher target-to-background
ratio, resulting in improved contrast
and localization during imaging.4
The 18F isotope decays via positron
emission and is captured by detectors
arranged in rings that encircle the pa-
tient, resulting in three-dimensional re-
construction data. PET can be done in
conjunction with CT (ie, PET/CT),
thereby combining functional and
structural imaging for increased ana-
tomic localization26 (Figure 2).
Currently, the availability of PET
and bone scintigraphy is primarily
limited to tertiary hospitals. Both im-
aging technologies require nuclear
medicine technicians and a nuclear
medicine physician for test interpre-
tation. PET costs approximately
three times more than three-phase
bone scintigraphy, four times more
than CT with contrast, and three
times more than MRI with contrast.
Tumor
Bone scintigraphy is inadequate in
detecting and monitoring selected
primary and secondary metastatic
155
Radionuclide Imaging in the Diagnosis and Management of Orthopaedic Disease

Figure 2

Axial views of a patient with metastatic breast carcinoma. Metastatic tumor of the right femoral neck is seen as high
uptake of fluorodeoxyglucose (FDG) on the positron emission tomography (PET) scan (A), as cortical thinning and
sclerosis on CT (B), and with corresponding overlap of findings on the combined FDG PET/CT image (C).
(Reproduced with permission from Palestro CJ, Love C, Schneider R: The evolution of nuclear medicine and the
musculoskeletal system. Radiol Clin North Am 2009;47[3]:505-532. http://www.sciencedirect.com/science/journal/
00338389.)

bone lesions; however, PET can be a
valuable tool in the workup of cer-
tain skeletal tumors.4 PET has partic-
ular uses in the evaluation of skeletal
metastasis, and it can be used to
evaluate for multiple myeloma and
malignant lymphoma, as well. In ad-
dition, PET has been shown to be
useful in evaluating primary bone
sarcomas. In general, 18F-FDG PET
is more sensitive for detecting bone
marrow, soft-tissue, and lytic metas-
tasis, whereas 18F is appropriate for
detecting osteoblastic and osteolytic
lesions.4
It is difficult to differentiate be-
tween inflammatory and neoplastic
disease on PET. Thus, with the ex-
ception of multiple myeloma, PET
has limited use in the initial workup
of a patient with primary bone tu-
mor. For example, 18F-FDG PET
cannot distinguish between malig-
nant and benign bone lesions that
contain histiocytes or giant cells.31,32
Even so, localized uptake on PET
can be used to identify the most met-
abolically active sites for biopsy
planning and can be useful in moni-
toring response to treatment.31,32 Fur-
thermore, PET can assist in staging
primary bone tumors.26,33
18
F-FDG PET is effective in the ini-
tial workup of multiple myeloma
and malignant lymphoma. The sensi-
tivity and specificity of PET for the
diagnosis of multiple myeloma are
high (83.8% to 91.9% and 83.3% to
100%, respectively) and better than
bone scintigraphy.9,12 A greater ex-
tent of disease can be seen on 18F-
FDG PET than on plain radiographs,
and 18F-FDG PET is thought to con-
tribute to the initial staging of soli-
tary plasmacytoma.9 This modality
has high positive predictive value,
sensitivity, and specificity for identi-
fying and following management of
osseous malignant lymphoma le-
sions.34
PET has been shown to be superior
to bone scanning in detecting skeletal
metastasis.4 18F-FDG PET is useful
in detecting soft-tissue and bone me-
tastases in patients with non-small
cell lung cancer.35 Although 18F-FDG
PET is superior to bone scintigraphy
in detecting osteolytic lesions from
breast cancer (sensitivity, 87%; spec-
ificity, 92%), 18F-FDG PET is less
sensitive than bone scintigraphy in
detecting osteoblastic lesions from
breast and prostate cancer.4,32 Be-
cause 18F tracer has a higher propen-
sity to bone cells than does 18F-FDG
tracer, 18F tracer is more sensitive in
the detection of both osteolytic and
osteoblastic metastatic lesions.
In one study, combined 18F
PET/CT was found to be 100% sen-
sitive and specific in detecting pros-
tate cancer metastases, whereas
SPECT alone demonstrated 92%
sensitivity and 82% specificity. 18F
PET alone demonstrated 100% sen-
sitivity and 62% specificity.36 18F has
been shown to be more accurate
than conventional bone scintigraphy
in detecting bone metastasis from
breast cancer, with a direct impact
on clinical management.37 In measur-
ing bone metastasis from prostate
and breast cancer, 18F PET/CT is bet-
ter for detecting sclerotic and mixed
lesions than purely lytic lesions.38
18
F-fluoromethylcholine is a promis-
ing new tracer for use with PET/CT,
and it has the potential to become
the test of choice for evaluating
metastatic prostate cancer.39 Further
research is needed to determine the
optimal imaging modality for detect-
ing bone metastasis.
Infection
18
F-FDG PET can be useful in the
evaluation of soft-tissue and bone in-
fection. For example, 18F-FDG PET
has been shown to have high sensi-
tivity (bone infection, 100%; soft-
tissue infection, 96%) and specificity

156 Journal of the American Academy of Orthopaedic Surgeons

 Wellington Hsu, MD, and Thomas M. Hearty, MD, DPT

(bone infection, 83%; soft-tissue in- Figure 3

fection, 70%)40 compared with MRI
(sensitivity, 82% to 100%; specific-
ity, 75% to 96%).41 For chronic
musculoskeletal infections, PET
yielded 100% sensitivity, 88% speci-
ficity, and 93% accuracy in one
study.42 These results are superior to
those with nonenhanced MRI (sensi-
tivity, 79%; specificity, 53%) but are
similar to those with fat-suppressed
contrast-enhanced imaging (sensitiv-
ity, 88%; specificity, 93%).43 Nota-
bly, PET has higher sensitivity and
specificity in detecting lesions of the
central skeleton than it does lesions
of the peripheral skeleton.40,42
PET demonstrates a significant ad-
vantage over other imaging modali-
ties in the evaluation of infection
with orthopaedic implants (Figure
3). 18FDG PET has a reported Transverse (top row), sagittal (middle row), and coronal (bottom row) positron
emission tomography scans of a 60-year-old woman with a painful
91.9% accuracy in detecting infec- periprosthetic infection about her right knee. Areas of intense uptake can be
tions of peripheral bone in persons seen at the femoral (coronal view) and tibial (sagittal view) implant-bone
with orthopaedic implants (sensitiv- interfaces (arrowheads). (Reproduced with permission from Zhuang H,
ity, 94.1%; specificity, 87.3%), com- Duarte PS, Pourdehnad M, et al: The promising role of 18F-FDG PET in
detecting infected lower limb prosthesis implants. J Nucl Med
pared with 88.7% accuracy with 2001;42[1]:44-48.)
MRI (sensitivity, 88.2%; specificity,
84.7%).6 Zhuang et al44 used 18F-
FDG PET in a prospective study of with 18F-FDG PET than with labeled affect the accuracy of 18F-FDG
74 infected joint arthroplasties. They WBC scintigraphy in the diagnosis of PET.48 FDG-PET is the preferred mo-
reported 90.9% sensitivity and periprosthetic hip infections (sensi- dality for diagnosing secondary ver-
72.0% specificity in detecting infec- tivity, 95.2% and 50%, respectively; tebral column infections in persons
tion associated with knee prostheses specificity, 93% and 95.1%, respec- with metallic implants.6
and 90% sensitivity and 89.3% spec- tively).47 In addition, PET may be a Foot infection in patients with dia-
ificity in detecting infection associ- valuable alternative for patients with betes is a frequent problem that can
ated with hip prostheses. Schiesser a cardiac pacemaker, who are pre- lead to devastating complications;
et al45 reported that in 22 patients, cluded from undergoing MRI. thus, early diagnosis is critical. In
PET was 100% sensitive, 93.3% spe- A recently published meta-analysis such patients, 18F-FDG PET/CT of-
cific, and 97% accurate for the de- demonstrates the superiority of 18F- fers increased localization, thus en-
tection of infection associated with FDG PET compared with MRI and abling differentiation between soft-
metallic implants. These results were bone scintigraphy in evaluating spi- tissue infection and osteomyelitis.11 In
confirmed surgically and on culture. nal infections, including postopera- this study by Basu et al,11 the feet of
In a different study, 18F-FDG PET tively, and with or without implants. 63 patients with diabetes were evalu-
18
demonstrated better results than did F-FDG PET had an accuracy of ated using MRI and 18F-FDG PET.
bone scintigraphy in detecting in- 90% (sensitivity, 99.9%; specificity, Using 18F-FDG PET, the investiga-
fected prosthetic joints (sensitivity, 87.9%), whereas MRI had an accu- tors were able to determine sig-
94% and 68%, respectively; specific- racy of 78.8% (sensitivity, 81.8%; nificant differences between an
ity, 95% and 76%, respectively; ac- specificity, 57%) and CT had an ac- uninfected foot, Charcot neuroar-
curacy, 95% and 74%, respec- curacy of 82.4% (sensitivity, 82.4%; thropathy, and Charcot neuroar-
tively).46 One study demonstrated specificity, 12.8%).6 The presence of thropathy with osteomyelitis. 18F-
greater sensitivity and specificity metallic implants does not seem to FDG PET also had better sensitivity

March 2012, Vol 20, No 3 157

Radionuclide Imaging in the Diagnosis and Management of Orthopaedic Disease
and accuracy than did MRI in diag-
nosing Charcot foot (100.0% versus
76.9%, and 93.8% versus 75.0%,
respectively) and was reliable in dif-
ferentiating Charcot neuropathy
from osteomyelitis. In a series of 14
patients with foot infections, 18F-
FDG PET alone correctly identified
93% of the infected sites, whereas
18
F-FDG PET/CT correctly identified
all of the infected sites.49
Future Directions
The use of PET in the evaluation and
management of orthopaedic disease
is still a new practice, and the appli-
cability of PET to other orthopaedic
diseases is under investigation. In
one such study, Hsu et al27 demon-
strated that 18F-PET correctly pre-
dicted femoral fracture union in a ro-
dent model. An early signal uptake
threshold (ie, signal uptake value
corresponding to fracture region on
PET scan) was established for this
model, above which future bony
healing was seen and below which
nonunion resulted. 18F-PET has also
been used to assess active bone for-
mation throughout healing fusion
mass in a porcine anterior lumbar in-
terbody fusion model.28 Finally, 18F-
PET has been found to be sensitive
and to provide valuable spatial and
temporal information regarding in-
corporation of local bone graft in ac-
etabular defects from osteolysis after
revision total hip arthroplasty.29,30 In-
creasing awareness in the orthopae-
dic community of the strengths of
PET will encourage further research
to better define the indications of
this valuable imaging modality.
Summary
Significant advances have been made
in the technology of nuclear medi-
cine in the past two decades, result-
ing in expanded use of the technol-
ogy in the evaluation of orthopaedic
158
conditions. Conventional imaging
modalities such as MRI, CT, and
plain radiography have disadvan-
tages (eg, availability, radiation ex-
posure, equivocal information); thus,
nuclear medicine technology can be a
valuable adjunctive diagnostic tool.
In orthopaedic conditions such as in-
fection, trauma, and bone tumors,
bone scintigraphy and PET can
greatly enhance the diagnostic capa-
bilities of the orthopaedic surgeon.
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