Medication Summary
Although patients are generally treated with surgery or radiation therapy, bisphosphonates are playing an increasingly important role in the treatment and prevention of metastatic bone disease. [1] In the future, the modification of RANK ligands is expected to produce additional substances that can further arrest or retard bone destruction by metastatic disease. [26]
Calcium Metabolism Modifiers
Class Summary
Bisphosphonates can be given either orally or intravenously. The intravenous rout is preferred by many oncologists as it is given monthly as a short infusion and does not have the gastrointestinal adverse effects of the oral bisphosphonates. These agents are analogues of inorganic pyrophosphate and act by binding to hydroxyapatite in bone matrix, thereby inhibiting the dissolution of crystals. They prevent osteoclast attachment to the bone matrix and osteoclast recruitment and viability. The newer bisphosphonates are not completely free of the risk of causing a mineralization defect, but their safe therapeutic window is much wider.
Pamidronate (Aredia)
Pamidronate's main action is to inhibit the resorption of bone. The drug is adsorbed onto calcium pyrophosphate crystals and may block the dissolution of these crystals, also known as hydroxyapatite, which are an important mineral component of bone. There is also evidence that pamidronate directly inhibits osteoclasts. No food, indomethacin, or calcium should be ingested within 2 hours before and 2 hours after pamidronate administration. It is administered intravenously.
Zoledronate (Zometa)
Zoledronate inhibits bone resorption. It inhibits osteoclastic activity and induces osteoclastic apoptosis. The drug is adsorbed onto calcium pyrophosphate crystals and may block the dissolution of these crystals, also known as hydroxyapatite, which are an important mineral component of bone. No food, indomethacin, or calcium should be ingested within 2 hours before and 2 hours after zoledronate administration. It is administered intravenously.
Monoclonal Antibodies
Class Summary
Denosumab binds to RANK ligand, a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts, the cells responsible for bone resorption.
Denosumab (Prolia, Xgeva)
Denosumab is a monoclonal antibody that specifically targets RANK ligand, an essential regulator of osteoclasts. Note that two brands exist; they are not interchangeable, and the doses are different. Xgeva is indicated for the prevention of skeleton-related events (SREs) in patients with multiple myeloma or in patients with cancer metastases from solid tumors. SREs include bone fractures from cancer and bone pain requiring radiation. Prolia is indicated in women with breast cancer who have aromatase inhibitor–induced bone loss. Prolia is also indicated for men with prostate cancer who have androgen deprivation–induced bone loss.
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Lateral view of the femur of a 70-year-old man with metastatic prostate carcinoma, the most common cause of osteoblastic metastases in men.
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Radiograph of a patient with severe rest- and activity-related pain at the time of presentation.
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Pathologic fracture. Radiograph shows a displaced fracture through an osteolytic lesion in the distal femur of a 53-year-old woman with lung carcinoma.
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Radiograph shows osteolytic metastasis in the distal femur of a 51-year-old woman with breast carcinoma.
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Lateral radiograph shows sclerotic metastasis of the L2 vertebra in a 54-year-old man with prostatic carcinoma.
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Axial computed tomography scan shows 2 rounded, mixed osteolytic-sclerotic lesions in the thoracic vertebral body of a 44-year-old woman with lung carcinoma.
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Axial computed tomography scan shows a destructive osteolytic lesion in the left acetabulum of a woman with vulval carcinoma. Soft-tissue extension into the pelvic cavity is present.
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Sagittal spin-echo T2-weighted magnetic resonance image shows hypointense lesions in the T10 and L3 vertebrae in a 66-year-old man with lung carcinoma. The tumor involves the T10 pedicle. See also the next image.
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Sagittal short-tau inversion recovery magnetic resonance (MRI) from a 66-year-old man with lung carcinoma. This MRI shows hyperintense lesions in the T10 and L3 vertebrae, with T10 pedicular involvement.
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Sagittal short-tau inversion recovery (STIR) magnetic resonance image (MRI) in a 68-year-old man with thyroid carcinoma. This MRI shows severe compression of the L1 vertebra with retropulsion. Affected T11-L2 vertebrae show signal hyperintensity, posterior vertebral body marginal bulging, and spinal canal narrowing. See also the next image.
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Sagittal gadolinium-enhanced spin-echo T1-weighted magnetic resonance image from a 68-year-old man with thyroid carcinoma. This image shows heterogeneous enhancement of the T11-L2 vertebrae, with prominent epidural component enhancement and spinal canal compromise. See also the next image.
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Axial spin-echo T1-weighted magnetic resonance image (MRI) in a 68-year-old man with thyroid carcinoma. This MRI shows tumor extension from the L1 vertebral body and left pedicle into the left psoas muscle and epidural space, with resultant spinal cord compression. See also the next image.
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Axial gadolinium-enhanced spin-echo T1-weighted magnetic resonance image from a 68-year-old man with thyroid carcinoma. This image shows heterogeneous enhancement of the soft tissue component of the L1 vertebral metastatic tumor.
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Typical scintigraphic pattern of bone metastases in a 60-year-old man with nasopharyngeal carcinoma. This posterior technetium-99m bone scintiscan shows multiple randomly distributed focal lesions scattered throughout the skeleton, particularly the spine, ribs, and pelvis.
