The Bone Scan

Arnold I. Brenner, DO, MMM, CPE,*, June Koshy, MD,* Jose Morey, MD,*
Cheryl Lin, MD,* and Jason DiPoce, MD*
Bone imaging continues to be the second greatest-volume nuclear imaging procedure,
offering the advantage of total body examination, low cost, and high sensitivity. Its power
rests in the physiological uptake and pathophysiologic behavior of 99m technetium (99mTc) diphosphonates. The diagnostic utility, sensitivity, specificity, and predictive value of
99m-Tc bone imaging for benign conditions and tumors was established when only planar
imaging was available. Currently, nearly all bone scans are performed as a planar study
(whole-body, 3-phase, or regional), with the radiologist often adding single-photon emission computed tomography (SPECT) imaging. Here we review many current indications for
planar bone imaging, highlighting indications in which the planar data are often diagnostically sufficient, although diagnosis may be enhanced by SPECT. 18F sodium fluoride
positron emission tomography (PET) is also re-emerging as a bone agent, and had been
considered interchangeable with 99m-Tc diphosphonates in the past. In addition to SPECT,
new imaging modalities, including 18F fluorodeoxyglucose, PET/CT, CT, magnetic resonance, and SPECT/CT, have been developed and can aid in evaluating benign and malignant bone disease. Because 18F fluorodeoxyglucose is taken up by tumor cells and Tc
diphosphonates are taken up in osteoblastic activity or osteoblastic healing reaction, both
modalities are complementary. CT and magnetic resonance may supplement, but do not
replace, bone imaging, which often detects pathology before anatomic changes are appreciated. We also stress the importance of dose reduction by reducing the dose of 99m-Tc
diphosphonates and avoiding unnecessary CT acquisitions. In addition, we describe an
approach to image interpretation that emphasizes communication with referring colleagues
and correlation with appropriate history to significantly improve our impact on patient care.
Semin Nucl Med 42:11-26 2012 Elsevier Inc. All rights reserved.

n nuclear medicine, the underlying power of our imaging

techniques is related to the biodistribution, normal physiological uptake, and pathophysiologic behavior of each specific radiopharmaceutical. 99m technetium (99m-Tc) bone
imaging agents were introduced by Subramanian et al1 in the
early 1970s and have proven to be very useful diagnostic
tools.2 Bone scintigraphy still represents the second greatestvolume procedure in nuclear medicine laboratories with
broad diverse applications.3 The clinical utility, sensitivity,
specificity, and predictive value of bone imaging have been
developed on the basis of planar bone imaging data.4
This article reviews the clinical strength of planar bone
imaging, in comparison with single-photon emission computed tomography (SPECT), SPECT/CT, 18F-fluorodeoxyg*Staten Island University Hospital, Staten Island, NY.
Department of Nuclear Medicine, Albert Einstein College of Medicine,
Bronx, NY.
Address reprint requests to: Arnold I. Brenner, DO, Nuclear Medicine and
PET, Staten Island University Hospital, 475 Seaview Avenue, Staten
Island, NY 10305. E-mail: abrenner@siuh.edu

0001-2998/12/$-see front matter 2012 Elsevier Inc. All rights reserved.

doi:10.1053/j.semnuclmed.2011.07.005

lucose (FDG), and positron-emission tomography (PET) imaging and briefly reviews the re-emergence of 18F sodium
fluoride bone PET imaging. We also emphasize how making
use of all available information can enhance our interpretation of planar images, and finally we present an overview of
the role of planar imaging for most common indications for
bone imaging.
Although computed tomography (CT), magnetic resonance imaging (MRI), PET, SPECT, and SPECT/CT have developed into excellent tools for evaluating patients with suspected bony pathology, planar bone imaging has stood the
test of time. More than 3,450,000 bone scans were performed
in the United States in 2005.3 Nearly all bone scans performed still use planar images as their foundation, with
SPECT adding complementary information.

Physiology
The skeleton is a living, active organ that changes during the
normal physiological process of growth and remodeling and
11

A.I. Brenner et al

12
in response to pathologic processes.5 Bone is constantly
changing, with an ongoing level of bone resorption (osteoclastic) and bone formation (osteoblastic). Osteoblasts form
an osteoid matrix that is later mineralized with hydroxyapatite crystals. 99m-Tc diphosphonates chemisorb6 and bind to
the hydroxyapatite crystals in proportion to local blood flow
and osteoblastic activity and are therefore markers of bone
turnover and bone perfusion. They rapidly localize to bone
and clear quickly from background, making them favorable for imaging. Even a 5% change in bone turnover7 can be
detected on bone imaging, whereas on radiographs and CT,
40%-50% of mineral must be lost to detect lucency within
the bone.8-10 Therefore, bone imaging can often detect disease-related dysfunction before anatomic changes are appreciated.11
Bone imaging is sensitive for both primarily osteoblastic
and primarily osteolytic processes. Even a tiny amount of
bony destruction causes an intensely osteoblastic healing
process that surrounds the lytic area. Fractures, osteomyelitis, and lytic metastases are all examples of bony destruction
that can allow early detection of the associated healing process on bone imaging.
Sometimes pathologic bone image findings are characterized by cold areas. This may be caused by very aggressive processes (ie, bone metastasis), indolent processes
that induce little healing reaction (ie, Brodies abscess,
indolent bony metastatic disease, plasmacytoma/neuroblastoma), or disruption of blood flow (ie, cold osteomyelitis, bone infarcts, avascular necrosis, frostbite or gangrene; Fig. 1).12

Planar Bone Imaging

Bone scans have stood the test of time. After myocardial
perfusion studies, they are the second most commonly performed nuclear procedure in the United States. A recent survey showed that the bone scan was the most commonly performed hospital-based procedure, emphasizing its continued
importance.13 Planar imaging is the cornerstone for all indications for bone scans by offering the advantage of total body
examination, low cost, and a high degree of sensitivity. Even
with the availability of ultrasound, CT, MRI, and PET, planar
bone scans remain a popular, useful diagnostic tool, providing an earlier diagnosis and demonstrating more bone lesions.
The power of the bone scan as a diagnostic modality has
lived through many different generations of instrumentation.
Most modern indications for bone scans were proven with
the use of our current radiopharmaceuticals, imaged on rectilinear scanners.14 This was followed by development of analog Anger gamma cameras, initially used for regional images
as a supplement to rectilinear scans. Gamma cameras then
supplanted rectilinear scanning, followed by whole body analog and ultimately digital whole body gamma camera systems.
In microscopy, low-power lenses allow a survey of the
specimen and pattern recognition, whereas high-power
lenses allow a more detailed view of a specific area. Similarly,
SPECT complements planar bone imaging by providing a
detailed view of the area of interest on the basis of symptoms
or planar bone findings. Three-dimensional images of tracer
distribution are acquired from multiplanar acquisitions, im-

Figure 1 (A) Patient with metastatic carcinoma of the lung. Note the multiple areas of increased bone agent uptake in a
pattern consistent with metastasis as well as several photopenic areas in the sternum and left sacroiliac joint. (B) A
64-year-old diabetic woman with cellulitis and ulcer of the right great toe on physical examination. Note the nonvisualization of the distal right great toe consistent with biopsy-proven osteomyelitis.

Bone scanning
proving spatial resolution, and enhancing tissue contrast.15
SPECT may improve sensitivity, specificity, and predictive
value in specific situations and may enhance lesion detection
and characterization. If the bone scan were considered a hotdog, SPECT would be a savory condiment, such as mustard
or sauerkraut, which improves its flavor.
Unlike SPECT imaging of the brain and myocardial perfusion, which are routinely performed as stand-alone studies,
SPECT bone imaging has not emerged as a stand-alone procedure. Almost all bone scans are performed as planar studies, with the addition of SPECT imaging of selected areas.
Recent new approaches to camera design and processing of
SPECT data, such as iterative reconstruction, have great
promise in decreasing time of acquisition, patient absorbed
dose, and perhaps improving the sensitivity and resolution of
SPECT data. These innovations are targeted at nuclear cardiology,16 but soon may represent another improvement in the
diagnostic utility of bone scans.

FDG-PET and 99m-Tc Bone

Imaging as Complementary Examinations
The physiological and pathophysiologic mechanisms of uptake of 18F FDG and 99m-Tc bone agents are different, making these complementary procedures. 99m-Tc diphosphonates are taken up in bone in proportion to blood flow and
osteoblastic activity. Abnormal bone FDG uptake by tumor
cells is in proportion to levels of glucose metabolism. FDG is
transported into tumor cells by glucose transporter proteins
and phosphorylated by hexokinase to FDG-6-phosphate,
which is retained in the malignant cells. Because FDG uptake
is related to metabolic activity of the tumor itself, FDG may
detect metastases before bony destruction or osteoblastic
healing. In osteolytic metastases, FDG is more likely to be
positive, while sclerotic metastases are less likely to be positive.17-20
Because FDG can detect both soft tissue and bony biological tumor activity, it may represent a one-stop shopping
technique for staging, restaging, and evaluating response to
therapy. 99m-Tc diphosphonate bone imaging may be useful
for further evaluation of questionable lesions or painful areas
that are FDG negative. The clinical significance of bone
scanpositive/FDG-negative lesions is unclear, because the
bone scan may represent continued healing in the absence of
biological tumor activity.21 Ben-Haim et al found that 81% of
osteolytic FDG-avid lesions became osteoblastic on CT and
FDG negative after treatment.17,22 Yang et al23 reported equal
sensitivity of FDG imaging and bone scan for detection of
bony metastases, and in another study, FDG sensitivity for
bone metastases from breast cancer was 56%-100%.24
FDG PET/CT has been reported to be useful for evaluating
inflammatory processes in select cases, although the data on
its clinical role in assessment of infection and inflammation
have recently been described as sparse.25 Currently, the Center for Medicare and Medicaid Services will not reimburse
providers for FDG-PET in these situations, severely limiting
its widespread useand reinforcing the important diagnostic place of planar bone imaging in benign bone disease.

13

Fluorine Sodium Fluoride

PET and PET/CT Bone Imaging
In 1962, 18F sodium fluoride was proposed by Blau et al14 as
an excellent radiopharmaceutical for bone imaging and approved for use by the Food and Drug Administration in 1972.
It was widely used for bone imaging using rectilinear scanners.26 Upon the advent of 99m-Tc bone agents and the development of Anger cameras, the 511 keV photon of 18F was
less well suited for imaging and was replaced by 99m-Tc
bone agents. 18F sodium fluoride uptake mechanism in bone
resembles 99m-Tc-diphosphonates and is dependent on regional blood flow as well as new bone formation. 18F sodium
fluoride is substituted for hydroxyl groups in hydroxyapatite,
covalently binding to the surface of new bone. Approximately 50% of the injected dose of 18 F sodium fluoride is
taken up by bone, similar to 99m-Tc-diphosphonates.27,28
Nearly all causes of increased new bone formation result in
increased localization of 18F.29
A Society of Nuclear Medicine practice guideline for use of
18F sodium fluoride PET has recently been published,29 listing the effective dose for 18F sodium fluoride as 0.089 mRem/
mCi (0.024 mSv/M Bq) and the effective dose for 99m Tcmethylene diphosphate (MDP) as 0.021 mRem/mCi (0.0057
mSv/M Bq). When 10 mCi (370 MBq) 18F is used, the effective dose is 890 mRem (8.9 mSv) compared with 25 mCi
(925 MBq) 99m-Tc-MDP effective dose of 530 mRem (5.3
mSv). Thus, radiation dose to the patient is 68% greater when
18F sodium fluoride is used compared with 99m-Tc-MDP.
Exposures may be more comparable using injected dose of 5
mCi (185 MBq) 18F sodium fluoride.
In the United States, the National Outpatient PET Registry
recently began gathering data on the appropriate use of 18F
sodium fluoride, limited only to use in tumor cases. This
program provides coverage with evidence development,
with the goal of assessing the impact of 18F sodium fluoride
PET on intended management, treatment intent, quality of
life, and survival, comparing pre-PET intended management
versus actual management after PET. Because there is no
coverage for benign bone disease, planar 99m-Tc bone imaging still plays a primary role in evaluating bony lesions.

Planar Bone Imaging

Whole-body, regional, and 3-phase bone scans are all planar
procedures. Whole-body imaging provides evaluation of the
entire body with a relatively low cost and high sensitivity.
Regional bone images are greater-resolution images that focus on specific body parts. Three-phase bone imaging is useful for evaluation of relative blood flow and blood pool activity. A radiopharmaceutical is injected as a bolus, and images
are acquired over the area of interest as an angiographic acquisition to evaluate regional arterial flow and venous phase
activity in the bones and soft tissues. Blood pool images are
acquired as regional planar acquisitions to evaluate for soft
tissue and bone hyperemia, followed by delayed (3 hours
after injectionadult; 2 hours after injectionpediatric)
whole body or regional images.30

14

Modern Applications
of Planar Bone Imaging
Detection and Monitoring of Bone Metastases
In the United States, 350,000 patients develop bone metastases each year.31 The overall sensitivity for detecting bony
metastases is 95%, with a false-negative rate of 2%-5%.32
Whole-body planar bone imaging has been a mainstay for
detection of skeletal metastases21 for more than 35 years. The
ability to image the entire skeleton makes planar bone scintigraphy unique compared with other radiographic techniques and MRI, resulting in a rapid, cost-effective survey of
the entire skeletal system for detection of patterns diagnostic
of bone metastases. It is easy for the patient, has no contraindications, and is very sensitive.33 Planar regional and magnified images may be acquired, on the basis of symptoms and
history, to better evaluate suspicious areas on whole body
imaging.
Multiple sites of abnormal bone agent uptake characterized by pattern of distribution, change over time, or definitive
findings on correlative CT, MRI, or radiographic studies, are
consistent with bone metastases. Only 8%-15%34 of patients
with proven metastases have a single lesion.35 A variant
whole-body bone scan pattern of metastatic bone disease is
the superscan diffusely increased activity throughout the
skeleton with decreased renal activity (absent kidney sign).
This usually reflects diffuse metastatic or metabolic bone disease and radiographic correlation is usually diagnostic. Photopenic areas or cold spots represent another variant seen in
very aggressive metastasis or in indolent metastasis, inducing
little healing reaction. Whole-body bone imaging is also useful in patients with malignant primary bone tumors to detect
metastases, evaluate the extent of tumor within bone, and
detect skip lesions.
In multiple myeloma and neuroblastoma, the sensitivity
for sites of bone involvement is approximately 50%,36 because these are often indolent processes that induce little
healing reaction. Therefore, skeletal survey and FDGPET/CT are more informative than whole body bone
scan.
SPECT is complementary to planar bone images and may
help to differentiate benign and suspicious lesions, particularly in the spine, where it improves predictive value.21
SPECT is more sensitive in detecting and localizing vertebral
lesions than planar imaging, with 20%-50% increase in lesion detection.17,37,38 Vertebral findings on planar and SPECT
imaging tend to follow predictable patterns that are likely to
represent benign changes, often degenerative37 and allow interpretation as no definite evidence for metastatic bone disease. For example, bone lesions that extend outward beyond
the extrapolated margin of the vertebra or show bridging of
activity across the posterior arches or vertebral bodies of
more than one vertebra can be attributed to a benign process.
Direct comparison of SPECT slices in transaxial, sagittal, and
coronal planes with matching slices on recent CT, MRI, or
PET/CT studies can often differentiate benign and malignant
lesions.

A.I. Brenner et al
Situations in Which SPECT Is Difficult
to Perform or Precluded for Technical Issues
In certain situations, a 15- to 30-minute SPECT acquisition is
not possible. Examples include nonsedated pediatric patients
or patients for whom prolonged sedation is impractical. Because even small differences in position can cause large
changes in bone images in the pediatric age group, these
patients may be held in position by experienced staff, especially when evaluating the extremities. Some popular gamma
cameras with fixed gantries make it nearly impossible, technically, to acquire SPECT images of the wrists and hands. In
these situations, planar images suffice to yield diagnostic information.
Clinical Situations in
Which the Area of Interest Is Undefined
In these cases, whole-body planar images are performed. If an
abnormality is detected, then SPECT acquisitions targeting
that area may be performed. Whole-body planar imaging can
be useful in patients with known malignancy to detect or
exclude bone metastases or in patients with suspected malignancy because of elevated serum prostatic-specific antigen or
calcium. They can also often detect characteristic findings
and anatomic distribution of Pagets disease in patients with
elevated serum alkaline phosphatase, assess disease activity,
and assess response to therapy.39 In patients with fever, bacteremia, leukocytosis, elevated sedimentation rate/C-reactive
protein (CPR), or subacute endocarditis, whole-body images
may be useful to detect a source of seeding or osteomyelitis.
In pediatric patients presenting with a limp, failure to bear
weight, or lower extremity pain, because the painful site may
represent referred pain, whole-body planar images from sacroiliac joints to feet are usually acquired, often followed by
SPECT.
Reflex Sympathetic Dystrophy (RSD)
or Complex Regional Pain Syndrome
RSD represents an abnormality of the sympathetic nervous
system40 that typically occurs after an inciting event. In these
patients, planar 3-phase bone images often suffice to demonstrate the characteristic findings of RSD diffuse generalized
increased uptake of bone agent throughout all the bones of
one extremity caused by increased generalized blood flow.
Diffusely increased juxtaarticular activity in affected joints of
the symptomatic extremity is also a sensitive indicator of
RSD.9 Planar positive predictive value has been reported as
67%-95%; negative predictive value as 61%-100%,41 sensitivity as 60%-96%, and as specificity 92%.30,42
Evaluation of the Significance of a
Bone Lesion on Radiograph, CT, or MRI
If it is unclear whether a radiographic abnormality represents
a benign or a malignant process, planar whole-body imaging
is of central importance to assess for other involved sites.
Then, regional and SPECT imaging focused on the abnormal
area are usually performed to help characterize the finding as
likely benign, suspicious, or indeterminate by bone scintigraphy. Direct comparison of the bone scan with CT or MRI in
matching coronal, sagittal, and transaxial images is often

Bone scanning
helpful. In general, if the radiographic abnormality corresponds with a normal area on bone scintigraphy, it is very
likely benign. If there is increased bone agent uptake, the
index lesion may be benign or malignant.
Osteomyelitis
Osteomyelitis causes bony destruction that is followed by a
robust osteoblastic healing response; therefore, bone imaging
can detect osteomyelitis before radiographic findings are evident. In the clinical setting of bacteremia, subacute endocarditis, or fever of unknown origin, planar whole-body imaging
represents the principal imaging approach. If the clinical
findings point to a specific location, 3-phase bone imaging is
usually performed, which may include whole-body format
images, complimented by SPECT over the region of interest
or abnormality pinpointed on planar imaging.
MRI is a valuable tool for diagnosis of osteomyelitis when
the site of infection is clinically evident. However, when the
site of infection is unclear, choosing a site for MRI study is
difficult. The authors of recent studies have also demonstrated the usefulness of FDG-PET in the diagnosis of osteomyelitis. Stumpe et al.43,44 reported sensitivity of 100% and
specificity of 83-99%. Nevertheless, because data on the
clinical role of FDG PET in assessment of infection and inflammation are sparse, FDG-PET may have limited value in
diagnosis of uncomplicated cases of acute osteomyelitis compared with the combination of physical examination, evaluation of biochemical markers, and 3-phase 99mTc bone imaging or MRI.25

Pediatric Osteomyelitis
Causes of osteomyelitis include hematogenous spread, direct
inoculation, and local extension from contiguous infection.
Although the hematogenous route of infection is the most
common route of spread in pediatric osteomyelitis, it accounts for only 20% of cases in adult osteomyelitis.45 The
characteristic finding of osteomyelitis on 99m-Tc scintigraphy is increased activity in bone on all 3 phases (Fig. 2).46,47
Although 3-phase imaging is preferred, patient cooperation
and sedation are not always possible for all phases. Delayed
bone images are the most definitive phase, because there is no
osteomyelitis unless the delayed images are abnormal, even
in the setting of increased blood flow and/or blood pool activity.48,49 There is typically a generalized pattern of diffuse
bone agent uptake related to hyperemia noted in the normal
bones of the extremity involved with focal osteomyelitis. This
should be expected and not mistaken for multifocal osteomyelitis or septic arthritis a negative bone scan can often relieve concern for significant pathology.50 In addition to diagnosing or excluding osteomyelitis, bone images can help
detect occult fractures or toddlers fractures,51 which may
represent the true source of the patients symptoms (Fig. 3).
The metaphyses of long bones have rich blood supply and
relatively sluggish flow and can serve as a medium for implantation and proliferation of bacteria.9,52 In infants, metaphyseal vessels penetrate the epiphysis, allowing passage of
infection through the epiphysis into the joint space.53 Thus,
osteomyelitis of the proximal femur is usually associated with

15
septic arthritis in children younger than 1 year of age.54 Pressure from joint fluid can compromise the femoral head
growth center and may represent a surgical emergency.51,55
When children are older than 2, few vessels cross the epiphyseal plate, protecting the epiphysis and joint from infection
and therefore the most common site of osteomyelitis is the
metaphysis. Thus, osteomyelitis usually involves only 1
bone, even in the setting of septic arthritis. Multifocal osteomyelitis rarely occurs, however may be seen in neonates and
immunocompromised patients.
Metabolic Bone Disease,
Such as Hyperparathyroidism
Planar whole-body bone images are necessary, often followed
by regional planar images and perhaps complementary
SPECT imaging. Patients with hyperparathyroidism typically
present with diffusely increased activity throughout the skeleton with faint or no visualization of the kidneys (absent
kidney sign), commonly referred to as a superscan. There is
usually more uptake in the skull and distal extremities in
hyperparathyroidism as compared to diffuse metastatic disease.56 Other findings may also include detection of brown
tumors or metastatic calcifications within the thyroid gland,
lungs or stomach.
Rhabdomyolysis and Other Soft-Tissue Abnormalities
Planar whole body and regional bone images, complemented
by SPECT imaging, are useful for detection and evaluation of
heterotopic ossification or myositis ossificans and help determine if this is an ongoing process (Fig. 4).57
In myoglobinuria, with or without a known history of
significant trauma, detection of soft tissue bony uptake in
sites of rhabdomyolysis may help evaluate the severity and
etiology of the pathologic process.58 Similarly, in electrocution injury, planar bone imaging can often determine the
extent of soft tissue injury.59,60 In dermatomyositis and polymyositis, whole-body imaging may allow detection of many
of the soft-tissue lesions, which are often bone agent avid
(Fig. 5).61,62 Planar imaging can often show evidence of bursitis, which may be the true cause of patient complaints in the
absence of other bony abnormalities.
Bone agents may be taken up in soft-tissue tumors, pleural
effusions, ascites, liver, or stroke. Proposed mechanisms of
uptake include local tissue necrosis; damage causing increased tissue calcium deposition; hyperemia; altered capillary permeability; adsorption onto soft tissue calcium; and
binding to enzyme receptors or denatured proteins.63
Child Abuse
Whole-body planar imaging is often complementary to other
radiographic studies in cases of suspected child abuse. Although older fractures may not be seen on bone scan, the
finding of fractures of different ages older fractures on skeletal survey and more recent fractures on bone scan may be
diagnostic. Bone imaging is particularly useful in diagnosing
rib fractures in infants, which are nearly always related to
abuse.64,65 Planar scintigraphy may detect 25-50% more areas of involvement than radiography, and may allow recognition of periosteal trauma (Fig. 6).51,66

16

A.I. Brenner et al

Figure 2 A 6-year-old boy who presented with painless right-sided limp for 3 days, fever, elevated ESR, and a normal
white blood cell count. The radiograph on the same date as the bone scan was normal. (A) Sequential anterior flow
images show increased flow to the right proximal femur. (B) Blood pool images show increased blood pool activity in
the same area. (C) Delayed images also show increased activity in the right proximal femur consistent with acute
osteomyelitis.

Bone scanning

17

Figure 3 Toddlers fracture in an 18-month-old boy who presented with inability to bear weight, swelling, and point
tenderness over the right tibia. An initial radiograph was interpreted as normal. A bone scan was then performed which
demonstrated uncharacteristic increased activity extending beyond the metaphysis. Because of this finding and the
patients age, a differential, including toddlers fracture was suggested. A repeat radiograph with oblique positioning
demonstrated a toddlers fracture.

Hypertrophic Pulmonary Osteoarthropathy

In patients with carcinoma of the lung, whether symptomatic
or asymptomatic, characteristic findings of hypertrophic pulmonary osteoarthropathy can readily be detected on planar
whole body and regional bone images. Typical findings include linear uptake along the medial and lateral periosteal
surfaces of the long bones of the extremities, more common
in the lower extremities (Fig. 7).67
Avascular Necrosis,
Bone Infarcts, and Femoral Head Viability
Causes of avascular necrosis include sickle cell disease, traumatic interruption of blood supply, as in fracture or slipped
capital femoral epiphysis, interruption of blood supply by
vasculitis, radiation osteonecrosis, steroid use, and LeggCalve-Perthes disease. Although SPECT imaging offers important complementary information, planar images are always performed and typically demonstrate the characteristic
findings of all phases of avascular necrosis and bone infarcts.
Three-phase bone imaging may be helpful as well. Avascular
necrosis generally appears on bone imaging as a photopenic
area for the first 7-10 days after the event. This is followed by
creeping revascularization and reossification leading to a
characteristic combination of increased uptake and a photopenic area (Fig. 8).68 As reossification progresses, there is
increased uptake with no residual photopenic area.
Bone scans may be helpful in determining projected viability of the femoral head following femoral neck fractures
and instrumentation related to traumatic interruption of
blood flow. If avascular necrosis is demonstrated, patients
may be treated with hip arthroplasty rather than internal
fixation.15,69
Legg-Calve-Perthes disease is characterized by avascular
necrosis. Bone scan abnormalities may predate radiographic
changes by 4-6 weeks (photopenic area early with increasing

uptake as repair progresses). The sensitivity and specificity of

bone scintigraphy has been reported to exceed 95%.70
Evaluation of Pain After Orthopedic Prosthesis
Typically, 3-phase planar bone images are performed followed by SPECT imaging. Persistent activity, more than 1
year after surgery (cement) or 2-3 years after surgery (porous
coated) at the trochanter or distal tip of the prosthesis is
characteristic for loosening.56 Prosthetic loosening may be
related to infection, and therefore, patients with clinical loosening may be evaluated to exclude osteomyelitis.71 If there is
no abnormal bone agent uptake related to the prosthesis on
delayed bone images, loosening and osteomyelitis are unlikely.
If 3-phase bone images (often, including SPECT) are abnormal, comparison with 111indium-labeled or 99mTclabeled white blood cell, 67-gallium or 99m-Tc-sulfur
colloid marrow images may help diagnose or exclude infection and better localize soft-tissue infection versus osteomyelitis. Marrow tracers accumulate only in the marrow, but
white blood cells accumulate in both infection and marrow.
When infection is present, there will be white blood cell
uptake but no sulfur colloid uptake in the infected area.72,73
In December 2010, a clinical practice guideline for diagnosis of periprosthetic infections of the hip and knee was
published in the orthopedic literature, which indicates that
testing strategies should be planned according to probability
of periprosthetic infection.71 Greater-probability knee prosthesis patients have either elevated erythocyte sedimentation
rate (ESR) or CRP, whereas greater-probability hip prosthesis
patients have both elevated ESR and CRP. The first diagnostic
test should be joint aspiration. If inconclusive (ie, dry tap;
culture and cell counts disagree), nuclear imaging is useful.
99m-Tc bone imaging, combined bone and radiolabeled

18

A.I. Brenner et al

Figure 4 (A) These images depict a 76-year-old male with a history of bilateral hip replacements 24 years earlier and a
bilateral revision 4 years ago. Note the active bone agent uptake within heterotopic bone superiorlateral to the
prostheses bilaterally consistent with an active process. (B) This image is a plain radiograph depicting the heterotopic
bone formation corresponding to findings on bone scan.

Figure 5 These images depict a 15-year-old boy diagnosed with dermatomyositis at age 6. Note multiple sites of
soft-tissue uptake corresponding to clinically evident abnormalities.

Bone scanning

19
tients, with no plan for reoperation, and elevation of only ESR
or only CRP levels, should be reevaluated clinically within
three months.

Figure 6 A 2-month-old girl who presented with multiple bruises. There

was clinical suspicion of nonaccidental trauma. Rib radiographs were negative for fractures. Note the multiple right-sided rib fractures on bone scan,
always suspicious for child abuse in a child of this age.

white blood cell imaging, gallium imaging, and FDG-PET all

may yield reliable data. However, the clinical value of FDGPET in diagnosis of prosthetic joint infections has recently
been described as being debatable.73 CT or MRI is not recommended by this guideline as a diagnostic test for prosthetic joint infection. Lower-probability hip prosthesis pa-

Evaluation of Suspected Recent

Fracture, Determination of Fracture Age
Examples include occult recent fracture, unexplained pain,
or fractures of indeterminate age on radiography. Typically,
whole-body images are acquired to evaluate for asymmetry,
followed by regional images, complemented with SPECT of
the area of interest. Often, 3-phase planar imaging will be
helpful.74
Because pelvic, sacrococcygeal, and scaphoid fractures are
often difficult to diagnose on radiographs and CT, bone imaging is useful in diagnosing or excluding these fractures as a
cause of the patients pain (Fig. 9).15 Scaphoid fractures are
sometimes difficult to diagnose radiographically and have a
significant incidence of subsequent avascular necrosis. Bone
scans have high sensitivity in detecting these fractures and
may be more sensitive than MRI or CT.75
In patients younger than 65 years of age, 95% of fractures
can be detected by 24 hours after trauma and 99% within 48
hours. In patients of all ages, 95% of fractures are detected by
72 hours post trauma.76 Planar bone imaging is also useful in
determining the age of fractures. Generally, fractures tend to
be positive on bone scan for approximately 1 year; however,
occasionally increased uptake may persist beyond one year.

Figure 7 A 57-year-old woman with a history of lung cancer metastatic to the brain (after left craniotomy). Note the
increased uptake along the periosteal margins of the long bones characteristic for pulmonary hypertrophic osteoarthropathy.

A.I. Brenner et al

20

Figure 8 (A) These images depict a 39-year-man with new-onset right hip pain, pain in the left hip for a few years, pain
in the left shoulder for 3 months, and pain in the right shoulder for 2 years. Note the absence of activity in the right
femoral head consistent with early avascular necrosis. There is a combination of cold and hot areas in both shoulders
and left femoral head consistent with revascularization and reossification phase of avascular necrosis. (B) A 25-year-old
woman with right hip pain for 1 month and the left hip for 3 years. Note the combination of a cold area with increased
uptake in bilateral hips characteristic of avascular necrosis.

Osteoporotic patients are at high risk for osteoporotic insufficiency fractures. Patients with back pain often are found
to have compression fractures on radiographs, CT or MR.
Sometimes these patients present with hip or groin pain and
have radiographic findings consistent with fracture of indeterminate age. Bone scans are helpful in determining if the
fracture is recent and explains the patients symptoms. Therefore, if the bone scan is positive, the fracture is likely recent,
and if negative, it is probably not recent.76
Spondylolysis represents stress related microfractures induced by trauma that may be too subtle to be detected radiographically.77 Bone SPECT is better in detection of spondylolysis
than conventional radiography and often demonstrates abnormalities not evident on planar bone scintigraphy,15,78,79 aiding in
patient management. Bone SPECT may detect abnormalities not
recognizable on other radiographic modalities in 25%-40% of
patients.80
Predicting Growth Arrest
Growth arrest is most commonly related to post-traumatic
premature closure of the physeal plate. Injury involving
the growth plate may disrupt epiphyseal vessels. Planar
images comparing the affected bone to the contralateral

side may show decreased uptake in the epiphyseal plate

(Fig. 10).72
Evaluation of Unexplained
Acute and Chronic Bone Pain
Many patients experience unexplained pain in the extremities, bone pain, or back pain. Bone scans should be part of
the algorithm for evaluating acute and chronic pain syndromes and is useful in identifying the location and the extent of the pathologic process.30 Typically, we begin with
planar images, often as three-phase images followed by
SPECT, of the painful area or any area abnormal on the planar
images.
Evaluation of Benign Bone Lesions
Osteoid osteoma has a characteristic pattern of focal hyperemia on blood pool images and marked intense tracer localization in the nidus on delayed images.9,81 Histiocytosis may
often present as polyostotic disease, and whole-body planar
images followed by SPECT of the area of interest, may be
useful to evaluate extent of disease.

Bone scanning

Figure 9 An 84-year-old man with low back and right hip pain after
left arthroplasty 4 months earlier. (A) Note the increased uptake
across the sacrum in an H pattern consistent with recent sacral
compression fracture with shearing forces on the sacroiliac joints.
(B) CT image shows osteoporosis and did not demonstrate this
recent fracture.

Suspected Sports Injuries and Enthesopathies

Many sports injuries may be associated with fasciitis, tendonitis or enthesopathy, a reactive periostitis in response
to mechanical stress at the attachment of muscles, ligaments or tendons on anchoring bone.15 Accurate diagnosis
of traumatic changes requires knowledge of the site of pain
and mechanism of injury. In traumatic sports injuries,
knowledge of mechanisms of injury related to that particular sport is important.9 Planar images may show focal
increased uptake at sites of tendon or ligament insertion,
usually associated with increased blood flow and blood

21
pool activity.82 Although SPECT imaging is complementary, diagnostic findings are usually evident on planar images.
Avulsion injuries are often not readily apparent on radiography. Planar bone imaging often shows increased
blood pool and delayed bone agent uptake along the superficial cortical bone at the site of avulsion (Fig. 11).9 In
plantar fasciitis and Achilles tendonitis,82 3-phase bone
images often complemented by SPECT imaging may play
an important role in localizing the inflammatory focus.
Stress fractures, microfractures and periosteal trauma
are overuse injuries72 that typically occur in normal bones
in response to abnormal stresses,7 such as unusual or repeated physical activity. This initiates bone remodeling
focally, ultimately leading to pain.82 They are difficult to
diagnose radiographically and at presentation, plain radiographs are often normal. There is a wide spectrum of objective findings on scintigraphy, based on the extent of
injury. Scintigraphic classification of stress fracture has
been graded based on the degree of injury, ranging from
mild increased uptake in the cortex to marked increased
uptake across the width of the bone (complete fracture).
Focal, thicker areas of uptake can usually be interpreted as
a stress fracture, particularly if fusiform or diamond
shaped.83 Some authors maintain that stress fractures are
more likely to have associated hyperemia on three-phase
bone imaging, particularly on blood pool images.56 However, the diagnosis always requires characteristic abnormalities on delayed definitive bone images (Fig. 12).
Linearly increased activity along the periosteal surface
of bone is usually diagnostic of shin splint or significant
periosteal trauma.84,85 Whole-body format imaging is ideally performed, allowing better evaluation of symmetry
and relative intensity of bone agent uptake, followed by
regional images in several positions. If fibular involvement
is suspected, anterior and posterior images in the pigeon
toe position or lateral and medial views will separate the
tibia and fibula. SPECT imaging is particularly helpful
when inspecting three-dimensional reconstructions in
cinematic display, comparing relative intensities in each
extremity and in assessing the thickness and shape of abnormal uptake.

SPECT/CTWhen Is the Extra

Radiation Dose from CT Warranted?
When considering the addition of CT (SPECT/CT) to bone
images, it is important to note that the clinical utility and
effectiveness of bone imaging was proven without CT. In
most cases, bone imaging without coregistered CT yields sufficient information for diagnosis. We need to ask whether the
incremental radiation exposure from CT is justified by the
additional information that it provides, particularly in patients who have had recent CT or MRI of the area. This may
allow for visual fusion of images, yielding the same result.
In other words, is the CT dose really worth it?
CT should probably be performed only in select patient
situations. Before adding CT, we need to decide, in each

A.I. Brenner et al

22

Figure 10 A 14-year-old boy who had a Salter Type II fracture (metaphyseal fracture extending to the physis) of the distal
right femur 1 year before imaging. Note the absence of the normal epiphyseal plate activity in the distal right femur
suggesting growth arrest.

case, if the CT will improve upon the sensitivity, specificity and diagnostic accuracy of bone imaging alone. If so,
then CT acquisition over a limited area (decreasing Dose
Length Product and absorbed dose) may occasionally be
valuable.86

Figure 11 A 13-year-old female dancer with right hip pain. Note the increased uptake in the right ischium consistent with an avulsion fracture.

Dose Modulation and Bone Imaging

Patient and organ specific absorbed doses in Nuclear Medicine are directly related to the injected dose. If one lowers
the injected dose by 50%, the absorbed doses are lowered
by 50%. Typical prescribed doses for 99m-Tc diphosphonate bone scans have increased during the past 35 years.
The widely accepted sensitivity, specificity and diagnostic
accuracy of bone imaging were established long ago using
prescribed doses of 15 mCi (555 MBq). Over the years,
many institutions have gradually increased the injected
doses to 25-30 mCi (925-1110 MBq).87 Greater doses allow faster acquisition times and decrease the imaging time
that patients must endure, improving patient convenience
and satisfaction. They also improve the efficiency of
the department, allowing more studies to be completed.
Dose modulation has also been addressed in pediatrics
with the recent publication of a 2010 pediatric consensus
guideline,88 suggesting 0.25 mCi/kg (9.3 MBq/kg) with a
minimum dose of 1 mCi (37 MBq) for 99 m-Tc MDP bone
imaging as opposed to the current potpourri of approaches
to calculating appropriate dose.
During the past year, we lowered our prescribed doses
for all our nuclear and PET procedures by 12.5%-20%,
with no discernable difference in image quality or diagnostic certainty. This has been publicized throughout our
institution to the delight of our referring physicians and
administration. Even greater reductions in prescribed
doses are contemplated, without using additional dosesparing hardware or software.
There is a great deal of interest throughout the
imaging community in the use of more efficient reconstruction programs that may result in diagnostic quality
images generated from less robust data sets, and lower
doses of ionizing radiation. This approach promises to
allow us to acquire diagnostic bone images using lower
injected and absorbed doses, and imaging for shorter periods.74

Bone scanning

23

Figure 12 A 14-year-old girl with right leg pain. Note the fusiform increased uptake in the distal right tibia consistent
with a stress fracture.

Value-Added Nuclear
Medicine: Nuclear Medicine
Physician/Radiologist as a Physician
Close communication with referring physicians is integral in
nuclear medicine. Planar bone imaging is a useful tool; however, it is most accurate when interpreted with the appropriate history. We need to speak the language of our referring
physicians. Knowing the history and specific clinical question assures that imaging is tailored to the individual patients
clinical need. When the clinical question is not clear, we
should consult with referring physicians to understand the
clinical context. Policies and procedures should assure that
all necessary clinical information is available. Within the
electronic medical record environment, we are revising our
electronic ordering system to better capture history appropriate to the study. Technologists and schedulers should ask
patients pertinent questions before imaging, such as sites of
pain, dates and details of orthopedic surgery or recent trauma
and reports of complementary imaging studies. An anatomic
drawing marking the location of pain, swelling or ulcer is
helpful in correlating bone scan findings to involved sites
(Fig. 13).

We also have a responsibility to patients and their families

to report our impressions in a way that minimizes anxiety.
Our reports affect patient care and well-being. We should
always strive to answer the clinical question as the first statement in our impression. As a result, bone scans can be more
definitively interpreted and reports can be more easily understood, aiding in medical management.
Bone imaging is a very sensitive but nonspecific technique.
In the past, it was common to suggest additional imaging
(radiographs, CT, MRI) to further evaluate abnormalities that
were not clearly diagnostic on planar imaging, which creates
associated anxiety to patients and their families, who must
nervously wait until additional imaging is scheduled, performed, interpreted, and explained to them by their physicians. Now, picture archiving and communication system is
available to most physicians at the time of interpretation.
Nuclear medicine training programs now include basic CT
interpretation, and nuclear physicians routinely interpret hybrid FDG-PET/CT studies. Therefore, many findings that in
the past would have required additional imaging can be directly compared to already existing complementary studies.
Many questionable abnormalities on bone images can be de-

A.I. Brenner et al

24

Figure 13 This anatomic drawing is used by technologists and physicians to mark the location of pain, swelling, or ulcer
and is helpful in correlating bone scan findings to involved sites.

termined to represent either benign (eg, degenerative

change) or pathologic changes. Using visual fusion of existing data and SPECT may yield more clear reports and avoid
the need and associated anxiety, cost and radiation burden
from additional studies.
For example, when bone imaging is performed to detect
metastatic bone disease in a patient who had a recent CT or
MRI, correlation with these studies often yields a more
definitive report. A focal abnormality in the vertebrae,
explainable by degenerative change can be reported as no
definite evidence for metastatic bone disease. This is quite
different from reporting the study as suspicious and suggesting correlative imaging that may be duplicative, expensive, and provide unnecessary radiation exposure. It is
the responsibility of the imaging physician to educate our
referring physicians regarding the appropriate use of imaging studies and their associated radiation exposure, so
they will be more selective when requesting studies.89
Consulting with clinical colleagues is an enriching source
of intellectual stimulation, and allows us to continually
improve the quality of our reports, and their impact on our
patients.

Conclusions
The power of bone imaging lies in the physiological uptake
and pathophysiologic behavior of 99 m-Tc diphosphonates.
Its clinical utility, sensitivity and specificity was established
based on planar imaging data. Planar bone imaging data are
often sufficient for diagnosis and may be enhanced by
SPECT. New imaging modalities, including 18F-FDG-PET,
CT and MR are complementary to 99 -m-Tc bone imaging.
18F-FDG-PET and 99m-Tc bone imaging reflect different biological processes (FDG uptake by tumor cells; MDP uptake
by osteoblastic activity). We can lower radiation doses by
prescribing lower injected doses and minimizing unnecessary additional imaging. We are physicians and should all
adopt a value-added approach to image interpretation.

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