Anti-tumor potential of bisphosphonates.

In addition to inhibiting bone resorption, bisphosphonates also exert anti-tumor effects. The most potent compounds are the newer, nitrogen-containing bisphosphonates such as zoledronic acid. In vitro, bisphosphonates inhibit proliferation and induce apoptosis in human tumor cell lines, and interfere with cell adhesion, invasion and growth factor secretion. The combination of bisphosphonates with other anti-cancer drugs such as paclitaxel or tamoxifen markedly enhances these effects. In vivo, zoledronic acid has recently been shown to inhibit angiogenesis. Although bisphosphonates are very effective against bone metastases, their in vivo anti-tumor potential against visceral metastases remains to be explored.