Developments in the therapeutic applications of bisphosphonates

The authors review the structural, pharmacologic, and clinical aspects of bisphosphonates, a class of drugs currently used to treat several disorders of bone and calcium metabolism. Pertinent literature on the bisphosphonates was reviewed with the help of a MEDLINE search and several bibliographies, including published clinical trials, monographs, and review articles. The bisphosphonates are analogs of pyrophosphate that, when given orally or intravenously, bind avidly to exposed bone mineral and disrupt bone turnover. These agents comprise three groups or generations, based on their potency and chemical structures. All three generations are effective in treating hypercalcemia, Paget's disease of bone, osteoporosis, and other disorders of accelerated bone turnover. The third-generation agents have the greatest potency and offer the promise of a convenient way to suppress or prevent osseous metastasis in patients with certain malignancies. As a group, these agents are well tolerated and, when administered correctly, rarely cause toxicity. The bisphosphonates are safe and effective agents for the treatment of disorders of accelerated bone turnover.