Bisphosphonates in preclinical bone oncology.

Bisphosphonates, especially nitrogen-containing bisphosphonates, are widely used to block bone destruction in cancer patients with bone metastasis because they are effective inhibitors of osteoclast-mediated bone resorption. In addition to their antiresorptive effects, preclinical evidence strongly suggests that nitrogen-containing bisphosphonates exert direct and indirect anticancer activities through inhibition of tumor cell functions, enhancement of the cytotoxic activity of chemotherapy agents, inhibition of tumor angiogenesis, and stimulation of antitumor immune reactions. This review examines the current evidence and provides insights into ongoing preclinical research on anticancer activities of these bisphosphonates in animal models of tumorigenesis and metastasis.