Bone Scan

Procedures

Skeletal scintigraphy begins with intravenous administration of Tc-99m MDP or Tc-99m HDP, followed by imaging at multiple time points, referred to as "phases." The adult dose of Tc-99m ranges from 10 to 30 millicuries (mCi) or 370 to 1110 megabecquerels (MBq). In children younger than 5 years, the dose is 0.2 to 0.3 mCi/kg or 7 to 11 MBq/kg. Protocols may consist of 1 to 4 phases: flow, blood pool, delayed, and an optional fourth phase. The most frequently used protocols are single-phase studies with a delayed phase or 3-phase studies comprising flow, blood pool, and delayed phases.[6]

The flow phase is a radionuclide angiogram used to assess increased and, less commonly, decreased, arterial flow to the area of concern. Images are acquired every 2 to 5 seconds over 60 to 90 seconds, immediately following injection. The blood pool phase begins immediately after the flow phase and continues for up to 10 minutes postinjection. This phase evaluates the distribution of radiotracer between the blood and the interstitium, allowing assessment of hyperemia, which appears as increased soft-tissue activity due to tracer extravasation. The delayed phase consists of single planar images of the region of interest acquired 2 to 6 hours after injection, reflecting the rate of bone turnover.[7]

A fourth phase, obtained 24 hours after radiotracer administration, is infrequently performed. This phase may provide additional diagnostic information in patients with impaired renal function or peripheral vascular disease, particularly when osteomyelitis is suspected.[8] Three-phase bone scans are most commonly employed to evaluate osteomyelitis, joint prosthesis infection versus loosening, and complex regional pain syndrome. Other indications for bone scintigraphy are typically imaged using a single delayed-phase protocol. This activity focuses primarily on the single-phase bone scan. For detailed information regarding 3-phase studies, refer to the dedicated StatPearls article about triple-phase bone scans.[9]

Delayed-phase images are generally obtained as anterior and posterior whole-body projections, the area of interest, or both, using spot imaging when appropriate. Whole-body imaging is advantageous for nonfocal complaints, such as evaluation of suspected bony metastases, diffuse arthralgia, or elevated alkaline phosphatase of indeterminate origin. Spot imaging is preferred for focal concerns, including exclusion of tibial stress fracture, investigation of unexplained rib pain, or assessment of an indeterminate sclerotic femoral lesion observed on radiographs.

Spot images are smaller field-of-view acquisitions that provide improved spatial resolution and may be obtained in multiple projections, including anterior-posterior, lateral, and anterior-posterior oblique, to enhance anatomic localization of abnormal radiotracer uptake. When anatomic localization remains insufficient on spot images or involves a region of complex anatomy, single-photon emission computed tomography (SPECT) may be performed with or without conventional CT. This technique enables fusion of Tc-99m MDP SPECT images with conventional CT images, thereby allowing precise anatomic localization.[10]

Indications

Skeletal scintigraphy has a broad spectrum of indications, encompassing any process that alters osseous turnover. Certain newer imaging modalities are increasingly replacing traditional bone scans in specific clinical contexts. For instance, routine bone scans are generally not recommended in patients with prostate cancer unless the prostate-specific antigen (PSA) level reaches at least 20 ng/mL.[11][12][13] PET/CT using prostate-specific membrane antigen tracers—68Ga-PSMA-11, 18F-DCFPyL, and 18F-PSMA-1007—has largely supplanted bone scans in this population due to superior sensitivity and specificity.[14][15] PSMA-PET/CT may detect skeletal involvement in patients with PSA levels as low as 0.2 to 0.5 ng/mL, although reliability is highest in individuals with PSA levels exceeding 1 ng/mL.[16][17][18]

The most common indications for bone scans include the detection or follow-up of osseous metastases, the identification of radiographically occult injuries, the evaluation for osteomyelitis, the assessment of osseous stress injuries, and the determination of prosthetic hardware infection or loosening. Less frequently, bone scans are utilized for evaluation of primary bone lesions, assessment of avascular necrosis or bone infarcts, determination of bone graft viability, diagnosis of complex regional pain syndrome, screening for child abuse, mapping the distribution of osteoblastic activity in preparation for radionuclide therapy for bone metastases, evaluation of arthritides, investigation of indeterminate radiographic, laboratory, or clinical findings suggestive of skeletal involvement, and assessment of metabolic bone disease.[19][20][21]

Normal and Critical Findings

An understanding of the normal anatomic distribution of Tc-99m MDP is essential for accurate interpretation of skeletal scintigraphy. Symmetrical radiotracer uptake is expected throughout the osseous structures of a healthy adult. In children, increased uptake is observed in the physes of the long bones, which represent normal growth centers.

Benign areas of increased radiotracer accumulation commonly include the acromioclavicular joints, sternoclavicular joints, sternomanubrial junction, sacroiliac joints, pubic symphysis, and articular surfaces of the shoulders, hips, knees, ankles, and feet. This pattern likely reflects constant bony remodeling at weight-bearing joint surfaces and the predisposition of these areas to degenerative changes. In adult patients, focal increased uptake is frequently observed in the maxillary and mandibular regions due to underlying dental disease, which can induce reactive osteogenesis. Uptake may also be present in the nasopharyngeal region of the facial bones in individuals with chronic sinus disease.

Skeletal scintigraphy is generally not indicated for the evaluation of bone lesions known to yield inconsistent results, including chordomas, Ewing sarcomas, multiple myeloma, and plasmacytomas. The modality is also not recommended for the characterization of bony lesions optimally visualized with standard radiological imaging, such as asymptomatic enchondromas of the long bones, bone islands, ganglion cysts, nonossifying fibromas, osteitis condensans ilii, Paget disease, and uncomplicated hemangiomas. Degenerative joint diseases are best assessed using standard radiological imaging in conjunction with clinical history and focused physical examination.

Normal extraosseous activity is observed faintly in the kidneys and intensely in the bladder, reflecting renal excretion of Tc99m MDP (or Tc-99m HDP). Minimal soft tissue activity may also be physiologic. Absence of renal and bladder activity should raise suspicion for a “superscan.” A superscan represents diffusely increased osseous uptake due to metastatic disease, most commonly from breast or prostate cancer, or metabolic bone disease, resulting in minimal or absent renal excretion of the radiotracer.[22][23] Radiotracer localization to the myocardium may occur in cardiac amyloidosis. Recent studies have explored the potential utility of bone scans for the evaluation of cardiac amyloidosis.[24]

Critical Findings 

Bone scans play a critical role in the detection of osseous metastatic disease, which most commonly involves the axial skeleton and proximal appendicular skeleton, corresponding to regions of red marrow distribution. Evaluation of primary osseous malignancies and extraskeletal metastases, particularly pulmonary metastases, may also be supported by bone scintigraphy, although definitive diagnosis of primary disease typically relies on other imaging modalities. Bone scintigraphy is sensitive for detecting stress fractures, most commonly affecting the lower extremities, including the tibia, metatarsals, and femoral neck. Involvement of the femoral neck is of particular clinical concern due to the risk of progression to a displaced fracture. The modality is also widely used to identify osteomyelitis and to evaluate suspected infection of prosthetic or orthopedic hardware.

In the pediatric population, bone scintigraphy may aid in the detection of occult fractures during evaluation for child abuse when used as an adjunct to a radiographic skeletal survey, particularly in children older than 1 year. Common sites of involvement include the ribs and extremities. However, bone scintigraphy demonstrates low sensitivity for pediatric skull fractures and classic metaphyseal corner fractures.[25] Bone scintigraphy may also aid in detecting nonaccidental trauma when radiographic findings are equivocal.[26]

Bone scans may demonstrate characteristic findings in avascular necrosis, particularly in patients with risk factors such as sickle cell disease or chronic corticosteroid use. Prolonged bisphosphonate therapy may result in atypical femoral fractures, which may also be detected on bone scintigraphy. Incidental soft tissue radiotracer uptake represents a critical finding and may indicate occult malignancy, including breast cancer, malignant pleural effusion, soft tissue sarcoma, or metastatic disease involving the liver.[27] Visualization of the kidneys is expected on every bone scan. Absence of renal activity should prompt concern for a superscan pattern.

Interfering Factors

A major interfering factor in skeletal scintigraphy is impaired renal function. Accurate interpretation of a bone scan depends on renal clearance of the radiotracer from the soft tissues, so that image formation predominantly reflects γ emissions from Tc-99m MDP bound to bone hydroxyapatite. Renal dysfunction limits radiotracer excretion, resulting in persistent extraosseous soft tissue activity that degrades bone visualization and reduces the target-to-background ratio.[28]

The impact of renal insufficiency on skeletal scintigraphy may be partially mitigated by acquiring a 24-hour delayed image, commonly referred to as the fourth phase, which provides additional time for clearance of nonosseous activity. This approach is constrained by the 6-hour physical half-life of Tc-99m, leaving approximately 6.25% of the initial administered activity available for imaging at 24 hours. Similar limitations may arise in the setting of patient dehydration, which can further impair renal clearance of radiotracer from the soft tissues. Oral hydration during the interval between radiotracer administration and delayed-phase image acquisition, typically 2 to 6 hours, improves renal excretion and optimizes image quality.

Additional conditions that may interfere with skeletal scintigraphy include disorders of iron deposition, such as thalassemia major and hemochromatosis. These conditions are associated with increased technetium uptake in the liver and kidneys, which reduces radiotracer availability for skeletal localization. Excess iron directly interferes with the uptake of technetium-based compounds by bone, while concomitant soft tissue accumulation occurs as a result of iron overload. Collectively, these effects hinder the identification of true skeletal abnormalities, including fractures and neoplasms, on skeletal scintigraphy.[29]

Another potential source of interference is suboptimal labeling of Tc 99m with MDP or HDP. Inadequate labeling results in the presence of unbound Tc-99m pertechnetate, commonly referred to as "free technetium." Free technetium localizes physiologically to the salivary glands, thyroid gland, and stomach, which may confound the interpretation of images. This phenomenon applies broadly to Tc-99m–labeled radiotracers and is not unique to skeletal scintigraphy.

The "flare phenomenon" may also confound the interpretation of skeletal scintigraphy. This uptake pattern is characterized by apparent worsening of osseous metastatic disease during the 2 to 6 months following initiation of chemotherapy. New sites of radiotracer uptake may appear, and previously identified lesions may increase in size or intensity.[30] This appearance is thought to reflect increased osteoblastic activity and bone turnover associated with the healing of metastatic involvement, including sclerosis of previously occult lytic lesions. This pseudoprogression resolves on subsequent follow-up bone scans, thereby confirming a therapeutic response.

Complications

Skeletal scintigraphy requires intravenous radiotracer administration. Most complications associated with this examination arise from improper injection technique and primarily affect image quality rather than patient safety.[31] Extravasation of injected Tc-99m MDP into the surrounding soft tissues produces several characteristic effects. Reduced radiotracer delivery to the skeleton markedly degrades visualization of osteoblastic pathology.

Lymphatic uptake of extravasated radiotracer may occur, resulting in lymph node retention that complicates same-day reinjection and may obscure adjacent osseous abnormalities. Intense activity at the injection site further degrades skeletal image quality due to excess photon contribution originating from the site of extravasation. Inadvertent arterial injection may occur in rare cases, producing the so-called "glove phenomenon." This finding is characterized by pronounced asymmetric radiotracer uptake extending distally from the arterial injection site into the hand and fingers.[32]

Patient Safety and Education

Skeletal scintigraphy involves exposure to ionizing radiation from γ rays emitted by the radiotracer Tc-99m. The effective whole-body radiation dose in adults is approximately 0.0057 millisieverts (mSv) per MBq, corresponding to an estimated dose of 4 mSv for the administration of 20 mCi of Tc-99m MDP. In children younger than 5 years, the effective whole-body dose is higher, at approximately 0.025 mSv/MBq. For comparison, the average annual background radiation exposure in adults is approximately 3 mSv.

A small fraction of Tc-99m pertechnetate is excreted in breast milk. However, the estimated fetal radiation dose remains below 1 mSv (100 mrem).[33] Therefore, discontinuation of breastfeeding is not required. Despite this finding, some clinicians recommend temporary cessation of breastfeeding for 12 to 24 hours, reflecting patient concern and adherence to earlier guideline recommendations.[34]

Clinical Significance

Skeletal scintigraphy is a versatile imaging modality that provides a highly sensitive assessment of bone pathology, particularly for the detection of stress injuries and radiographically occult fractures. A negative bone scan at 72 hours effectively excludes fractures of the appendicular skeleton, with reported sensitivities of 95% to 100%. Healing fractures may continue to demonstrate increased uptake long after the initial trauma, with 60% to 80% of fractures returning to normal on bone scan within a year and 95% within 3 years.[35] Detection of osseous stress injury is clinically important because modifying patient activity can prevent progression to complete fracture.

Skeletal scintigraphy also demonstrates high sensitivity for evaluation of osteomyelitis, reaching up to 94%, which confers an excellent negative predictive value.[36] The examination exhibits similar specificity in normal bone. However, the presence of underlying intrinsic lesions, orthopedic hardware, fractures, or recent surgical intervention can reduce specificity to as low as 34%, necessitating additional imaging when positive findings are observed.[37] Complementary nuclear medicine options include F18-fluorodeoxyglucose PET/CT and leukocyte scans with indium-111 or Tc-99m hexamethylpropyleneamine oxime radiolabeling.

The sensitivity of bone scans for metastatic disease varies by primary tumor type. Detailed sensitivity and specificity data for each malignancy are beyond the scope of this activity. However, bone scintigraphy demonstrates the greatest accuracy for osteoblastic metastases and the lowest accuracy for malignancies that predominantly produce osteolytic lesions. Common malignancies with high sensitivity for the detection of bone metastases include breast, prostate, and lung cancer. Malignancies for which bone scintigraphy exhibits low sensitivity include multiple myeloma, renal cell carcinoma, and thyroid carcinoma.