Antitumor effects of bisphosphonates

Bisphosphonates are widely used to treat skeletal complications of malignancy. These drugs accumulate in bone where they inhibit osteoclastic bone resorption and reduce the local release of factors that stimulate tumor growth. The mechanism of action of bisphosphonates is dependent on chemical structure: Nonnitrogen‐containing compounds (e.g., etidronate, clodronate) are metabolized into cytotoxic analogues of ATP, whereas the more potent nitrogen‐containing compounds (N‐BPs; e.g., pamidronate, ibandronate, zoledronic acid) inhibit protein prenylation, thus affecting cell function and survival. Because protein prenylation is required by all cells, not just osteoclasts, the possibility arises that N‐BPs could also affect the viability of tumor cells.