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Andrew Newberg, MD

Bone ScanS

1. What should a patient know about a bone scan?

A bone scan requires the intravenous injection of a small amount of a radioactive tracer (e.g., technetium [Tc]-99m) that

is absorbed into the bones. The tracer carries a relatively low dose of radioactivity and is extremely unlikely to result in

any allergic or adverse reactions. The patient can eat and take medicines regularly and is able to continue all daily

activities before and after the scan. The scan itself occurs approximately 2 hours after injection of the tracer, and the

scan time is approximately 45 minutes for a whole-body scan. Three-phase bone scans require scanning for

approximately 20 minutes at the time of the injection.

2. What are the normal structures observed on a bone scan? Describe the typical

nonmalignant findings in asymptomatic patients.

Normally, all of the bones should be visible on a bone scan, including individual vertebrae and ribs. The kidneys and

bladder are also seen in most patients. Normal soft tissue uptake can occur in the breasts and sometimes in vascular

structures such as the uterus. Calcified cartilage is also commonly seen in the costochondral and thyroid cartilage.

Common nonmalignant findings in asymptomatic patients include degenerative disease in the spine or joints, dental

or sinus disease, calcification of atherosclerotic disease, and prior fractures (

Fig. 54-1

).

3. Why is a “superscan” associated with a

negative prognosis in the patient with

prostate cancer shown in

Fig. 54-2

?

A “superscan” implies that so much of the methylene

diphosphate (MDP) is taken up by the bones that there is

no significant excretion in the kidneys and bladder or

uptake in the soft tissues. The scan appears almost too

good with high contrast between the bones and other

tissues. The most common causes of a “superscan” are

Figure 54-1.

Anterior and posterior projections of a normal bone scan

using Tc-99m–labeled MDP show uniform activity throughout the bones,

kidney, and bladder, and mild degenerative changes.

Figure 54-2.

Findings on this bone scan (anterior and posterior

projections) are consistent with a “superscan,” in which there is

intense activity throughout virtually all of the bones with no

significant excretion in the kidneys or bladder. Some areas, such as

the proximal humeri and left femur, are particularly intense. This

patient had widespread metastatic prostate cancer.

377

Figure 54-3.

Bone scan shows diffusely increased

activity throughout the entire right (left side of image) arm

and hand on the blood pool images (top) and delayed

images (bottom). These findings are consistent with reflex

sympathetic dystrophy.

renal failure, hyperparathyroidism, metabolic bone disease, Paget disease, or widespread metastatic disease. In a patient

with cancer, a “superscan” implies widespread osseous metastases that cannot be individually distinguished, but rather

occupy almost the entire skeleton.

4. Is there a way to treat successfully a patient with bone pain associated with multiple

osteoblastic metastases?

Patients with bone pain from osteoblastic metastases can be treated primarily with four modalities: cancer-specific

chemotherapy, radiation therapy, narcotic pain management, or beta-emitting radiopharmaceutical agents that target

bone. The last option is often the best when multiple sites are involved that cannot be easily targeted by radiation

therapy or would result in excessive radiation to uninvolved tissues or the whole body. Radiopharmaceutical agents,

such as strontium-89 (Metastron) or samarium-153 (Quadramet), can be injected intravenously in patients with

osteoblastic metastases for relief of pain. Studies suggest that 80% of patients experience some pain relief, and almost

50% have complete relief. Pain relief lasts a mean of 6 to 8 months, and patients can be retreated with similar pain

relief. Although these treatments are not considered a cure, they can substantially improve a patient’s quality of life and

decrease reliance on narcotic medications.

5.

Fig. 54-3

shows a scan of a patient

complaining of swelling and pain in the distal

arm after a recent traumatic event. What is

the diagnosis?

Patients with such symptoms after a traumatic event typically

have either osseous or soft tissue uptake characteristic of focal

injury. In these patients, a three-phase bone scan helps make

that determination. The first two phases—the blood flow, or

vascular, phase and the blood pool, or tissue, phase—help to

show whether there is soft tissue edema. If there is also focal

uptake on the delayed bone images, an osseous injury is

suspected, which may be superimposed on soft tissue injury.

The scan in

Fig. 54-3

shows diffusely increased uptake on all

three phases, however, which is suggestive of reflex

sympathetic dystrophy. Reflex sympathetic dystrophy is a

response to a traumatic event and results from autonomic

dysfunction in the extremity, causing altered regulation of blood

flow. On a bone scan, the typical result is increased flow and

uptake on all three phases. Other patterns have also been

described. Regardless, the findings are almost always diffuse

because they affect the entire extremity, including all of the

fingers and distal arm.

6. What causes a bone scan that does not show

the bones clearly?

Usually a suboptimal bone scan is related to technical factors,

such as not waiting at least 2 hours between the injection and the

scan, poor preparation of the MDP, a significantly infiltrated

injection dose, patient motion, or the camera being set to the

incorrect energy window (e.g., for iodine-123 rather than

Tc-99m). Physiologic reasons for suboptimal scans include large

patient size, resulting in significant photon attenuation, or poor

circulation states, such as congestive heart failure in which the

tracer is not adequately delivered to the bones. Finally, patients

with osteoporosis simply do not have enough bone for good

visualization of osseous structures, and patients with iron

overload have inhibited uptake of the tracer.

7. Is a bone scan an appropriate study for a 65-year-old patient with multiple myeloma?

Bone scans generally are not sensitive for lytic bone lesions, and patients who show multiple myeloma or lytic

abnormalities on computed tomography (CT) or x-ray should not be referred for a bone scan. These patients should

undergo a bone survey with multiple plain film x-rays. Patients with certain cancers that can have mixed lytic and

blastic bone metastases may still benefit from a bone scan. Also, a patient with multiple myeloma with lytic disease in

weight-bearing bones that might be susceptible to pathologic fracture may benefit because the fracture would show up

as a focus of increased uptake. If a nuclear medicine scan is needed to differentiate bone metastases better,

fluorodeoxyglucose positron emission tomography (FDG PET) scan may be the most appropriate choice.

nuclear radiology

378

Bone ScanS

8. Does a bone scan that shows a worsened condition after chemotherapy portend

a bad prognosis?

Although a bone scan that shows apparent worsening abnormalities, characterized by increased activity in known

lesions or the observation of new lesions, can be suggestive of progression of disease, the apparent worsening

abnormalities may also be associated with the “flare” phenomenon. The flare phenomenon results from increased

osteoblastic activity in lesions that is associated with the bone’s healing response after chemotherapy. The flare

response is associated with a good prognosis, suggesting effective therapy. The flare response can occur 2 to 6 months

after chemotherapy. A patient with a bone scan that shows apparent worsening abnormalities in this time period should

be followed up with another bone scan 4 to 6 months later to determine whether the lesions subsequently regress. If

there is improvement on the latter scan, the previous scan can be considered to be related to a flare response

associated with effective treatment.

9. What are the most common findings

on a bone scan that suggest

metastatic disease?

Bone scan findings of metastatic disease most

commonly have intensely increased activity and

may be either a solitary focus or multiple foci (

Fig.

54-4

). Widespread disease may appear as a

“superscan,” in which all of the bones have

diffusely intense uptake (see

question 3

). Cold, or

photopenic, defects can be observed in patients

with lytic bone metastases. Because the

sensitivity of bone scans is not 100%, scans can

have negative results in the face of metastatic

disease. Finally, metastatic disease can be

observed in the soft tissues, including organs such

as the lungs or liver.

10. What are the causes of “cold,” or

photopenic, defects on bone scans?

There are numerous benign and malignant reasons

for photopenic regions on a bone scan. Bones with

avascular necrosis or infarct in the early stage have

photopenia. Lytic bone tumors or metastases can

be cold because there is an absence of osteoblastic

activity. Any metal objects—either external, such as

jewelry, or internal, such as a pacemaker or joint

prosthesis—can attenuate or block photons. Bone

can also be affected by disuse or radiation therapy, in which there is an overall decrease in uptake in a focal area.

Finally, there have been several reports of cold defects in acute osteomyelitis.

11. Are three-phase bone scans alone useful for the diagnosis of osteomyelitis?

Three-phase bone scans can be positive for osteomyelitis if there is a focal area of intense uptake. This is particularly

true when a patient has a superficial area of infection, such as an ulcer or cellulitis. In such a case, the question to be

answered is whether the underlying bone is affected, which can be readily detected on a three-phase bone scan.

Increased uptake on all three phases of a bone scan can also occur in acute fractures, surgical manipulation, metastatic

disease, avascular necrosis, and Paget disease. If any of these other conditions are potentially expected, a three-phase

bone scan by itself is not likely to be useful because of poor specificity.

Figure 54-4.

Anterior and posterior views of a bone scan show a

patient with multiple foci of intense activity throughout the axial skeleton,

consistent with prostate cancer. In particular, there are foci of intense

uptake in multiple ribs, throughout the spine, in the skull, in the right

scapula, and in the pelvis.

Key Points: Common Findings of Metastatic

Disease on Bone Scans

1. Solitary focal lesions

2. Multiple focal lesions

3. “Superscan”

4. Photon-deficient (“cold” defect) lesions

5. Normal findings (false-negative scan)

6. Soft tissue uptake

Bone ScanS

379

nuclear radiology

Figure 54-5.

Anterior and posterior views of a bone scan show a

patient with Paget disease associated with multiple areas of intense

MDP uptake in the mandible, proximal humeri, femurs, right rib, and

spine. The increased activity in the distal femurs can be distinguished

from degenerative changes because Paget disease involves much of the

femur, rather than only the joint area, which would be typical of

osteoarthritis.

12. What other scans can be used to improve diagnostic accuracy?

Studies to consider in addition to three-phase bone scan are an indium-labeled white blood cell scan for the extremities;

a gallium scan for the spine; or a PET scan, which can be used for any site of suspected osteomyelitis. Because these

three studies evaluate infectious or inflammatory processes rather than response of the bone, they have higher

specificity than a bone scan.

13. Is lung uptake normal on a bone scan?

Lung uptake is almost never normal on a bone scan and is usually associated with malignant pleural effusions, large

tumors, inflammatory processes, or metastatic disease. Metastatic osteosarcoma has particularly intense uptake when

involving the lungs. Lung uptake itself is usually detected by comparing the left hemithorax and right hemithorax,

observing for increased uptake in the intercostal spaces.

14. Can Paget disease be distinguished from cancer in the bones?

Paget disease typically is associated with focal areas of intensely increased uptake in the flat bones and the ends of the

long bones. The uptake is usually diffuse, although there can be focal areas of increased uptake. There is no definitive

way to exclude metastatic disease or primary bone tumors from Paget disease on the basis of uptake in the bones. The

pattern of Paget disease in terms of its distribution and appearance may help in the diagnosis, however. It is less likely

that an individual would have an entire hemipelvis as the only site of metastatic disease, but this can commonly be a

presentation of Paget disease.

15. What is the “Mickey Mouse” sign?

In the spine, the “Mickey Mouse” sign refers to foci

in which there is uptake in the entire vertebral

body and the spinous process, which is almost

always Paget disease, rather than metastatic

disease (

Fig. 54-5

).

16. Intense activity on a bone scan in

multiple joints can be the result of

which disorders?

Polyarticular uptake on a bone scan is typically

associated with arthritic conditions, such as

osteoarthritis, rheumatoid arthritis, psoriatic

arthritis, gout, or ankylosing spondylitis. The

diagnosis of these different disorders can be

suggested by the specific joints involved, such as

the knees, acromioclavicular joints, and

interphalangeal joints in osteoarthritis; the

metacarpophalangeal joints in rheumatoid arthritis;

and involvement of the great toe in gout.

17. Can shin splints be differentiated

from stress fractures on a bone

scan?

Shin splints generally show linear increased activity

primarily on the delayed bone images in the

posterior tibia (

Fig. 54-6

). Stress fractures should

be more focally increased with intense uptake on

delayed bone scans and are often more anterior in

their location. Stress fractures commonly show

Key Points: Causes of Cold Defects on a Bone Scan

1. Avascular necrosis

2. Malignant bone tumors

3. Metastases

4. Prosthesis, pacemaker, jewelry, lead shield

5. Barium in colon

6. Disuse atrophy

7. External radiation therapy

8. Early osteomyelitis

380

Bone ScanS

increased activity on the first two phases of the

bone scan, so any patient being referred for stress

fractures should have a three-phase bone scan.

18. Is a prostate-specific antigen (PSA)

level relevant to bone scan findings

in patients with prostate cancer?

Several studies have shown that a low PSA level

(<10 ng/dL) is associated with a very low chance

of having bone metastases. Some authorities

have suggested that for low-risk patients with a

PSA of less than 10 ng/dL, bone scintigraphy

may be unnecessary. PSA levels greater than 20

ng/dL are associated with a significantly

greater chance of bone metastases. Most large

trials have still revealed relatively low

occurrence of abnormalities on bone scans in

the early work-up of patients with prostate

cancer, however. Knowledge of the PSA level is

beneficial because equivocal findings may be

considered less likely to be metastases in a

patient with a very low PSA level.

19. What is the significance of a single

rib lesion in a patient being

evaluated for metastatic disease

from a known primary cancer?

The traditional view is that a single rib lesion has

approximately an 8% to 10% chance of being a

metastasis; this can be modified by the characteristics of the finding. Typically, linear areas of increased activity that

appear to extend along the rib are more suggestive of metastatic disease, whereas small, macular lesions are more

likely the result of trauma. In addition, the patient’s history might reveal a recent fall, which would also more likely

suggest that the finding is the result of trauma.

20. Which benign bone tumors have increased uptake on a bone scan?

Osteoid osteomas have increased uptake on delayed bone scan images and may have an observable photopenic center.

They commonly arise in the femur or spine. Uptake is also very intense for osteochondromas and chondroblastomas.

Enchondromas do not typically have significantly increased uptake on a bone scan.

21. Do bone scans have a role in the evaluation of child abuse?

A bone scan may be an important study in the evaluation of potential child abuse because it enables a ready evaluation

of all of the bones in one scan and can often show old or occult fractures. Even if a child does not complain of pain

in a particular bone, the bone scan can reveal prior trauma. If there are multiple fracture sites that would not occur from

a typical fall or disease process, child abuse might be suspected as the cause.

22. Are planar bone scans sufficient for the evaluation of spondylolysis?

Patients with back pain and suspected spondylolysis can undergo bone scans for the evaluation of abnormalities in the

spine. Planar imaging may be sufficient to show a focus of increased uptake in the region of the posterior elements of

the vertebra. A tomographic image is often necessary for diagnosis, however, if the planar scan has negative or

equivocal results. Studies suggest that single photon emission computed tomography (SPECT) imaging enhances the

sensitivity of planar bone scans. The usual findings are focal increased uptake in the posterior elements of the vertebra,

which can be unilateral or bilateral. Uptake can be seen on the affected side because of the remodeling or on the

contralateral side owing to altered biomechanics.

23. Is increased uptake in the kidneys a clinically relevant finding on a bone scan?

If one or both kidneys have increased uptake on a bone scan, this finding can be clinically relevant because such a

finding can occur in the setting of hydronephrosis and obstruction. Increased uptake on a bone scan may also be the

result of the effects of chemotherapy or from the involvement of tumor, nephrocalcinosis, radiation nephritis, or acute

tubular necrosis. A patient with abnormally increased uptake in one or both kidneys should be followed up with

additional imaging, including anatomic and scintigraphic if clinically indicated.

Figure 54-6.

Bone scan showing linear uptake along the posterior

tibia (arrow) consistent with shin splints. There is no evidence of focal

uptake that would suggest a stress fracture.

Bone ScanS

381

nuclear radiology

Figure 54-7.

Anterior and posterior views of a

bone scan show diffuse, intense uptake throughout

most of the skeletal muscle groups. This finding is

consistent with widespread myositis.

24. What are the causes of liver uptake on a bone

scan?

The most problematic cause of liver uptake on a bone scan is the

presence of hepatic metastases, which most likely are associated

with melanoma or cancers of the colon, breast, or lung. Sometimes

there can be increased activity in the liver associated with overlying

soft tissue activity, in which case the liver is not the actual source of

the increased activity. Diffuse hepatic necrosis, although rare, can

result in increased liver uptake on a bone scan. Finally, a colloid

formation of the tracer because of poor preparation techniques can

result in the equivalent of a sulfur colloid (liver/spleen) scan.

25. What can cause uptake in the muscles on the

scan in

Fig. 54-7

?

Increased uptake in the muscles on a bone scan usually implies some

type of inflammatory process, such as myositis, which was the case in

this patient. Other considerations include rhabdomyolysis,

hypercalcemia, hematomas, and tumors. The latter two conditions are

usually more focal. There are technical factors, such as poor

preparation of the radiopharmaceutical agent, or possibly not waiting

long enough after injection before imaging. The intensity and

diffuseness of the uptake on this scan is indicative of myositis.

B

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[3] B.D. Collier, I. Fogelman, I. Rosenthal (Eds.), Skeletal Nuclear Medicine, Mosby,

St. Louis, 1996.

[4] S. Haukaas, J. Roervik, O.J. Halvorsen, M. Foelling, When is bone scintigraphy

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Br. J. Urol. 79 (1997) 770–776.

[5] I. Sarikaya, A. Sarikaya, L.E. Holder, The role of single photon emission computed

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