Bone Scan

The bone scan (bone scintigraphy) is a nuclear medicine study of the whole skeleton. It uses a technetium-99m labelled bisphosphonate (methylene diphosphonate or hydroxymethylene diphosphonate) that is taken up by bone in proportion to blood flow and osteoblastic activity. Increased uptake shows areas of bone turnover and repair.

The patient receives 500 to 740 MBq (about 10 MBq for each kg in children, with a minimum dose) of the tracer by intravenous injection. About 50% is taken up by bone in 2 to 4 hours, and the rest is excreted in the urine.

The patient drinks fluids and empties the bladder often. Whole body planar images are taken 2 to 4 hours after injection, and take 15 to 30 minutes.

Single photon emission computed tomography (SPECT), alone or with CT (SPECT-CT), is added for the spine, pelvis, skull base, feet and other complex regions.

A three phase study (a flow phase in the first minute, a blood pool phase at 5 minutes and delayed images at 2 to 4 hours) is used for infection, fracture and complex regional pain.

The effective dose is about 3 to 6 mSv, equal to about 1 to 2 years of natural background radiation. A scan is highly sensitive but not specific, and positive findings are commonly confirmed by radiography, CT or MRI.

Bone metastases occur in about 70% of patients with advanced breast and prostate cancer. The bone scan has a sensitivity of 80 to 95% for bone metastases, detecting them months before radiographs.

For other indications it is sensitive for stress fractures (before radiographs), osteoid osteoma, infection and Paget disease, but is displaced by MRI, PET and CT for many of these uses.

Indications.

• Staging and follow up of bone metastases (prostate, breast, lung, kidney, thyroid and other cancers), in patients with symptoms, high risk disease or raised prostate specific antigen.
• Unexplained bone pain with normal radiographs: stress fracture, occult fracture, and osteoid osteoma.
• Suspected osteomyelitis and septic arthritis (three phase, with other imaging), including diabetic foot.
• Primary bone tumours: extent and skip lesions, and metabolically active lesions.
• Paget disease of bone: extent and activity.
• Fibrous dysplasia and polyostotic disease.
• Avascular necrosis and complex regional pain syndrome (three phase).
• Prosthetic joint loosening and infection (with other agents).
• Metabolic bone disease and its complications (hyperparathyroidism, renal osteodystrophy).
• Non-accidental injury in children (when skeletal survey is not conclusive).
• Heterotopic ossification, and bone viability after trauma or grafting.

Not for myeloma, where lesions are often cold, and not as a screening test.

Contraindications and precautions.

• Pregnancy: avoid unless the benefit is clear. Hydration and frequent voiding reduce foetal dose.
• Breast feeding: pumping is not needed for most patients, though close contact with infants is limited for several hours.
• Allergy to the tracer is very rare.
• Patient needs to stay hydrated and void before imaging. A full bladder hides the pelvis.
• Recent barium, other radionuclide studies or contrast may interfere with the scan.
• Metal, jewellery and clothing with metal should be removed.
• Patients who cannot lie still for 20 to 40 minutes may need sedation, especially children.

Preparation and technique.

No fasting is needed. Patients drink 500 to 1000 mL of fluid between injection and imaging, and empty the bladder just before images. The injection is given intravenously (not through a line that has been used for other drugs). Imaging at 2 to 4 hours (longer in renal failure).

Anterior and posterior whole body images are taken with a gamma camera and a low energy high resolution collimator, with spot views of the skull, chest, pelvis, feet and hands as needed. SPECT-CT of selected areas adds localisation and attenuation correction.

For three phase imaging, the flow phase starts at the time of injection and the blood pool images at 5 minutes. A 24-hour image is added in renal failure, infection assessment and in some cases of suspected osteomyelitis.

Normal appearances.

Tracer uptake is symmetrical and relatively uniform, greatest in the axial skeleton, joints, sacroiliac joints and areas of active growth. The skull sutures, sternum, scapular tips, sternoclavicular joints and costochondral junctions show mild uptake.

The kidneys and bladder are visible, and soft tissue activity is low by 3 to 4 hours.

In children, the growth plates show strong, symmetrical uptake. Uptake in the cervical spine, the knees and the shoulders is increased with age related degenerative change.

Interpretation.

• Metastases: multiple focal areas of increased uptake in a random pattern, mainly in the axial skeleton (spine, ribs, pelvis, proximal femora and skull). Findings are asymmetrical, and elongated or round.
• Diffusely increased uptake in the axial skeleton with absent kidney activity indicates extensive disease, for example prostate cancer, or metabolic bone disease. Look for absent renal and bladder uptake.
• Photopenic (cold) lesions: purely lytic tumours, such as kidney and thyroid metastases, myeloma, and aggressive tumours, and avascular bone. They need radiography, CT or MRI.
• Flare phenomenon: transient increase in uptake after successful treatment, in the first 3 to 6 months, and should not be mistaken for progression.
• Fracture: focal uptake that appears within 24 to 72 hours of injury (up to 1 week in older people), fades over months, and persists up to 12 to 24 months in some. Stress fracture shows a fusiform area of cortical uptake.
• Osteoid osteoma: intense, focal uptake with a surrounding area of lower uptake (double density).
• Paget disease: intense, usually enlarged bone uptake of a whole bone or segment, with a pattern of spread from one end.
• Infection: three phase with focal increase on all three phases in osteomyelitis, and a hyperaemic pattern on blood pool images in cellulitis (soft tissue uptake without bone uptake in delayed images).
• Arthritis: symmetrical periarticular uptake in the hands, wrists, feet and spine, and increased uptake in the joints in degenerative disease.
• Avascular necrosis: a photopenic area early, followed by increased uptake around it (healing response) and focal uptake in the collapsed head.
• Complex regional pain syndrome: increased flow and blood pool, and periarticular delayed uptake in the affected limb.
• Primary bone tumours: intense uptake with extension, and soft tissue involvement.
• Heterotopic ossification: increased uptake in soft tissue next to joints, as it matures it becomes quieter.
• Soft tissue and organ uptake: breast tumours, calcified masses, renal obstruction, ascites, and extravasation at the injection site.
• Non-accidental injury: multiple rib and metaphyseal foci, with a sensitivity better for ribs than skeletal survey.

Critical values and findings needing immediate action.

• Evidence of widespread metastases or pending pathological fracture (intense uptake in a weight bearing long bone, spine): urgent imaging with radiography, CT or MRI and orthopaedic and oncology review.
• Uptake at the vertebra with neurological symptoms: urgent MRI of the spine for cord compression.
• Suspected infection in a patient with fever and focal uptake: antibiotics, cultures and further imaging.
• Occult fracture of the hip or femoral neck: orthopaedic review.
• Unexpected renal obstruction or absent kidney: review of renal function.

Limitations and artefacts.

• Uptake is non-specific. Fracture, infection, arthritis, tumour, Paget disease and surgery all increase uptake. Correlation with radiographs, CT or MRI is essential.
• Lytic metastases, myeloma and early or small lesions can be negative (cold).
• Uniform, diffusely increased uptake can be misread as normal.
• Degenerative disease in the spine and joints often accounts for focal uptake in older people, and SPECT-CT helps separate benign from malignant.
• Urine contamination on the skin or clothing mimics lesions. Bladder activity hides the pelvis and sacrum.
• Extravasation at the injection site, soft tissue uptake, and attenuation from metal or breast tissue cause pitfalls.
• Fractures may be negative for the first 24 to 72 hours, and in the elderly for a week or more.
• Poor technique, too short interval after injection, and renal failure give poor target to background.
• Radiation dose, and scan time of several hours, limit use in children and pregnancy.
• Whole body MRI and PET-based imaging are more sensitive for bone marrow disease and some tumours.

Special groups.

• Children: dose adjusted by weight, with attention to growth plates, and sedation if needed. Used for osteoid osteoma, infection, tumours and non-accidental injury.
• Pregnant patients: avoid when possible.
• Patients with renal failure: delayed images at 24 hours and a lower target to background.
• Patients with prostate cancer on hormone therapy or after treatment: flare, and rising prostate specific antigen with negative scan can prompt PSMA PET.
• Patients with metal implants: SPECT-CT.
• Regions: bone scintigraphy remains a core test where PET and MRI are not available. Bone tuberculosis, osteomyelitis, sickle cell bone disease and metastases are common indications.

Follow up tests.

• Radiographs of areas of uptake, CT for cortical detail, and MRI for marrow and soft tissue.
• SPECT-CT of the area of uptake.
• PET-CT (fluorodeoxyglucose or prostate specific membrane antigen) or fluoride PET for tumour staging.
• Biopsy for an uncertain lesion with suspected malignancy.
• Blood tests: calcium, alkaline phosphatase, prostate specific antigen, full blood count, inflammatory markers, protein electrophoresis.
• Referral to oncology, orthopaedics, rheumatology or endocrinology.