Bone Scan

A bone scan images the metabolic activity of the skeleton. This has traditionally been accomplished by imaging a radionuclide whose physiology closely mimics a metabolic process within bone. Nuclear scintigraphy of the bone commonly utilizes the radionuclides technetium-99m (Tc-99m) or fluoride-18 (F-18). Tc-99m is usually attached to medronic acid (Tc-99m MDP), and F-18 is usually incorporated into sodium fluoride (F-18 NaF). These molecules are injected intravenously, and a nuclear camera that contains a salt crystal captures the decay of photons from the radioisotope. This is achieved through the process of scintillation or fluorescence that occurs when the photon emitted by the radionuclide hits the salt crystal within the nuclear camera. The scintillations are then digitized and converted to images for interpretation by a nuclear medicine physician. Other imaging options in nuclear medicine include F18-FDG PET/CT or radiolabeled white blood cell (WBC) scan using Indium-111 or Tc-99m-HMPAO-labeled WBCs. ^{[1, 2, 3, 4, 5, 6]}

There is an increased risk of radiation effects when a person's cumulative lifetime radiation exposure from diagnostic medical imaging exceeds 100 mSv. In an effort to further understand these potential risks, the International Atomic Energy Agency has launched a global effort to have individuals track their cumulative radiation exposure from medical imaging. ^[7]

Technetium-99m MDP

Tc-99m MDP is used for gamma camera imaging. The standard adult dose is approximately 740 MBq. Tc-99m emits 140 keV gamma rays upon decay, and these gamma rays are detected by nuclear gamma cameras to allow localizing where the Tc-99m travels within the body. For imaging bone metabolism, the radionuclide is usually attached to medronic acid (methylene diphosphonate). Caution is recommended when it is used in pregnant or nursing women. There have been rare reports of allergic reactions to Tc-99m MDP, and medical equipment should be available to treat severe reactions. ^[8] The radiation exposure from a standard adult dose of 740 MBq is approximately 4.2 mSv. ^[9]

(See the image below.)

Tc-99m MDP whole body bone scan showing typical anterior and posterior planar views.

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Fluoride-18 NaF

F-18 NaF is used for bone scans with positron emission tomography (PET). The standard adult dose is approximately 185 MBq. F-18 is a radionuclide that decays by positron emission. A decay positron then annihilates with an electron to form two 512-keV photons that travel in approximately opposite directions, 180° apart. PET cameras (PET scanners) are able to detect these photons and thereby map molecular flow of the F-18 NaF. There are no known adverse reactions to F-18 NaF, ^{[10, 11]} although there is a theoretical small risk from the radiation exposure of approximately 5 mSv. Caution is recommended when it is used in pregnant or nursing women. There is a theoretical risk of an allergic reaction, but these are virtually unheard of because the minuscule amounts administered are thought to be too small to trigger an allergic reaction.

(See the image below.)

18F-NaF PET/CT bone scan. This is the PET-only MIP image seen from the anterior view. It demonstrates degenerative disease in the right lower lumbar spine, which was confirmed by review of the CT images. The scan otherwise shows normal NaF tracer uptake. Note tracer uptake in the ureters, which can be better localized by review of the axial images and by delayed imaging after voiding.

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Drugs that may interfere with bone scans

Drugs that may interfere with bone scintigraphy include aluminum-containing compounds, corticosteroids, iron, methotrexate, nifedipine, hematopoietic growth factors, androgen-deprivation therapy drugs, estrogens, bisphosphonates, drugs that interfere with osteoblastic function, nephrotoxic chemotherapy, and epsilon-aminocaproic acid. If a previous bone scan was thought to be nondiagnostic because of interference from one of these drugs, the scan should be repeated when the patient has stopped taking the medication long enough to minimize interference. ^[6]

Bone scans are useful in a wide range of diseases. ^{[12, 13, 14, 15]} A common reason to obtain a bone scan is in the evaluation of pain, in which a bone scan can help determine whether the source of the pain is from bone pathology or from the soft tissues. For example, a long-distance runner may have foot pain due to a fracture or a sprain. The bone scan can help determine if a bone injury or a tendon sprain is the cause of the pain.

Bone scans can also be useful in the evaluation of systemic diseases such as cancer or nonspecific widespread bone pain.

Society of Nuclear Medicine & Molecular Imaging (SNMMI) Appropriate Use Criteria

The Society of Nuclear Medicine & Molecular Imaging (SNMMI) has released appropriate use criteria for bone scintigrapahy in patients with breast and prostate cancer. ^[16]

Breast Cancer

Bone scintigraphy for breast cancer is appropriate for the following indications ^[16] :

• Initial staging in patients with node-positive disease.
• Patients at any stage or risk who have symptoms referable to the bones.
• Patients who are to undergo bone-directed radionuclide therapy.

Bone scintigraphy is usually appropriate for breast cancer patients who present with a pathologic fracture, require a change in treatment plan, or are suspected of having nonosseous or osseous disease progression. ^[16]

Prostate Cancer

Bone scintigraphy is usually appropriate for the following indications ^[16] :

• Initial staging in patients with intermediate-risk disease (stage T2, PSA level >10 ng/mL, or Gleason score ≥ 7).
• Initial evaluation of patients with high-risk disease (stage T3, PSA level >20 ng/mL, or Gleason score >8).
• Evaluation of patients with symptoms referable to the bones regardless of stage or risk.
• Evaluation of patients in whom a change in treatment is anticipated.
• Evaluation of patients presenting with a pathologic fracture.
• Evaluation of patients who are to undergo radium or other radionuclide bone therapy.

European Association of Nuclear Medicine (EANM) guidelines for bone scintigraphy

The European Association of Nuclear Medicine (EANM) recommends bone scintigraphy when a specific bone disease is present or suspected.

Oncology indications include the following ^[17] :

• Solid tumors with high affinity for bone, including prostate, breast, lung, and renal cancer. 
• Malignant hematologic conditions limited to bone, including Hodgkin disease and non-Hodgkin lymphoma. 
• Bone tumors and bone dysplasia, including osteosarcoma, osteoid osteoma, osteoblastoma, fibrous dysplasia, giant cell tumor, and osteopoikilosis. 
• Soft tissue sarcomas, including rhabdomyosarcoma.
• Paraneoplastic syndromes, including hypertrophic pulmonary osteoarthropathy, algodystrophy, polymyalgia rheumatica, poly(dermato)myositis, and osteomalacia.
• Assessment of bone remodeling before radionuclide therapy (223Ra-Cl2, 89Sr-Cl2, 153Sm-EDTMP, 186Re-HEDP).

Rheumatology indications include the following ^[17] :

• Chronic inflammatory arthritis, including rheumatoid arthritis, spondyloarthropathies and related disorders (ankylosing spondylitis, psoriatic arthritis, Reiter arthritis, SAPHO syndrome [synovitis, acne, pustulosis, hyperostosis, osteitis], chronic recurrent multifocal osteomyelitis), and sacroiliitis.
• Osteoarthritis of the lumbar facet joints and hip, femorotibial and femoropatellar osteoarthritis, rhizarthrosis, and tarsal osteoarthritis. 
• Enthesopathies, including plantar fasciitis, Achilles tendinitis, and bursitis.
• (Avascular) osteonecrosis, which is most frequently located at the femoral head, femoral condyle, and tibial plateau.
• Osteonecrosis of the jaw (ONJ). 
• Complex regional pain syndrome type I of the hand, hip, knee, and foot.
• Tietze syndrome (costochondritis).
• Polymyositis.
• Paget disease.
• Langerhans cell histiocytosis (LCH): single system LCH and multisystem LCH with bone involvement.
• Non-Langerhans cell diseases, such as Erdheim–Chester disease, Schnitzler syndrome, and Rosai Dorfman disease.
• Other rare osteoarticular diseases, such as sarcoidosis with bone involvement, mastocytosis, Behcet disease, and familial Mediterranean fever.

Bone and joint infection indications include the following ^[17] :

• Osteomyelitis (acute, subacute, or chronic; bacterial, mycobacterial, or fungal origin).
• Septic arthritis.
• Spondylodiscitis or spondylitis.
• Septic loosening or mechanical complication of internal fixation (long bones or spine) or arthroplasty (hip, knee, ankle, or shoulder).
• Malignant (necrotizing) external otitis.

Orthopedic indications include the following ^[17] :

• Periostitis, including shin splints and thigh splints. 
• Enthesopathies, including plantar fasciitis, Achilles tendinitis, and bursitis.
• Spondylolisthesis (acute or subacute).
• Radiologic occult stress-related fractures (eg, scaphoid, tarsals) or nonspecific symptoms. 
• Insufficiency fractures, including osteoporotic vertebral or occult fractures, sacral fractures, femoral head or neck fractures, tibial plateau fractures, tarsal and metatarsal fractures.
• Septic loosening, mechanical complication, and synovitis of internal fixation (long bones or spine) or prosthesis (hip, knee, ankle, or shoulder).
• Pseudoarthrosis (delayed union, nonunion).
• Periarticular heterotopic ossification.
• Viability of bone graft.

Metabolic bone disease indications include the following ^[17] :

• Hyperparathyroidism (primary and secondary).
• Osteomalacia.
• Renal osteodystrophy. 
• Rare skeletal manifestations of endocrine disorders, including hyperthyroidism and acromegaly.
• Vitamin D deficiency.

Indications for children and adolescents include the following ^[17] ​:

• Osteochondritis of the hip (Legg-Calve-Perthes disease).
• Transient synovitis of the hip.
• Osteoid osteoma.
• Battered child syndrome.
• Mandibular condylar hyperplasia.
• Bone infarction (sickle cell disease, thalassemia).

According to SNMMI guidelines, bone scintigraphy is usually not appropriate for initial staging in patients with low-risk breast cancer (clinical stage 0 or I) and no other clinical signs or symptoms of disease or for initial staging in patients with a low risk of metastatic prostate disease (PSA level < 10 ng/mL, Gleason score < 6, and no other clinical signs or symptoms of disease). ^[16]

According to the EANM guidelines, bone scintigraphy may not be the preferred imaging modality in the following conditions ^[17] :

• Bone lesions with known inconsistent scintigraphy findings, such as plasmacytoma, multiple myeloma, chordoma, or Ewing sarcoma.
• Benign bone lesions and incidentalomas when properly characterized by radiologic imaging, including bone island, uncomplicated hemangioma, osteitis condensans ilii, nonossifying fibromas, asymptomatic enchondroma of the long bones, ganglion cyst, and asymptomatic Paget disease.
• Symptomatic degenerative joint disease that is well characterized on radiologic imaging and is properly diagnosed based on the pain syndrome and a well-performed clinical examination.

Even though bone scintigraphy may in general not be the preferred imaging modality in the conditions listed above, this recommendation should be assessed within the specific clinical context of the patient.