Dosing Schedule for a Bone-Modifying Agent

Bony involvement develops in approximately 73% of patients with metastatic breast carcinoma, 68% in patients with prostate cancer, and in nearly all patients with multiple myeloma. Before the introduction of bone-modifying agents (BMA), patients with metastatic carcinoma to bones were often hospitalized for skeletal-related events (SRE), such as pain, hypercalcemia, spinal cord compromise, and pathologic fractures, that lead to significant morbidity and mortality, reduced quality of life, and high costs. Randomized trials showed that bisphosphonates, including pamidronate and zoledronic acid, and the receptor activator of nuclear factor kappa-B ligand (RANKL) monoclonal antibody denosumab significantly decrease the incidence of SRE in patients with bone metastases. In the United States, the US Food and Drug Administration approved these compounds for treating metastatic bone disease, and these agents were quickly adopted in clinical practice. Two other bisphosphonates—clodronate and ibandronate—have been licensed for use in bone metastases outside the United States.

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