The antitumor potential of bisphosphonates.

Bisphosphonates are primarily known for their ability to inhibit osteoclast-mediated bone resorption and to slow the release of calcium and other bone minerals into the blood stream. However, recent preclinical research has shown that bisphosphonates also exhibit potent antitumor activity. Bisphosphonates reduce proliferation and induce apoptosis of tumor cell lines, and they inhibit tumor cell adhesion and invasion of the extracellular matrix in vitro. In addition, bisphosphonates have been shown to reduce skeletal tumor burden in a variety of animal models. This may reflect either direct antitumor effects or indirect effects via osteoclast inhibition and alteration of the bone microenvironment. The complex mechanisms by which bisphosphonates inhibit bone resorption and interfere with tumor growth and metastasis to bone are beginning to be understood. Research is ongoing to fully elucidate these biochemical mechanisms, and well-designed clinical trials are planned to investigate the antitumor potential of modern nitrogen-containing bisphosphonates in the clinical setting. Copyright 2002, Elsevier Science (USA). All rights reserved.