Most patients with advanced
malignancy develop bone
metastases during the course of their disease. For the remainder of the patient's life, these bone
metastases lead to skeletal-related events such as
pathologic fractures and
spinal cord compression, as well as bone
pain or lesions requiring palliative
radiation therapy or surgery to prevent or treat fractures. Skeletal-related events result in increased morbidity, mortality and health care costs. For the past decade, intravenous
bisphosphonates (
zoledronic acid,
pamidronate) have been recognized as the primary pharmacologic options in the prevention or treatment of skeletal-related events in patients with bone
metastasis. Recently, the United States Food and Drug Administration approved
denosumab, a fully human
monoclonal antibody, for the prevention of skeletal-related events in patients with bone
metastases from solid
tumors. Three prominent clinical trials were conducted to establish the efficacy of
denosumab. In two of three trials,
denosumab was found to delay the time to first skeletal-related event significantly more than
zoledronic acid in patients with breast or
castration-resistant
prostate cancer with bone
metastasis. The third trial found
denosumab to be noninferior to
zoledronic acid in patients with
metastases from solid
tumors, excluding breast and prostate solid
tumors. Overall survival and progression-free survival were similar between
zoledronic acid and
denosumab. Thus, evidence is insufficient to prove a greater efficacy of one agent over the other. According to the American Society of Clinical Oncology and the National Comprehensive
Cancer Network, patients with bone
metastasis should have
zoledronic acid,
pamidronate, or
denosumab (with
calcium and
vitamin D supplementation) added to their
chemotherapy regimen if they have an expected survival of 3 months or longer and have adequate renal function.