Bisphosphonates were the first bone-directed therapies used to treat skeletal complications resulting from malignant bone disease. Reducing the incidence of skeletal complications has significantly improved patient quality of life. Intravenous bisphosphonates also have been evaluated as an adjunct treatment to minimize bone loss from cancer therapy. In these settings, there is a suggested improvement in cancer-associated outcomes, in addition to their bone-protective benefits. Denosumab is a fully human antibody to the receptor activator of nuclear factor-kappaB ligand. Recently reported data suggest that denosumab is efficacious in decreasing skeletal-related events, but the long-term safety of denosumab remains to be determined. The available data for the approved intravenous bisphosphonates, including zoledronic acid, as well as for other investigational bone-directed therapies is reviewed, with a focus on the incidence and management of treatment-associated side effects.
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