An update on bisphosphonates.

Over the past 15 years, bisphosphonates have been demonstrated as effective therapy for the treatment of osteoporosis based on their ability to suppress bone turnover resulting in increased bone mineral content and increased bone strength. The mechanism of action at the cellular level has been identified, and the more potent nitrogen-containing bisphosphonates clearly have reduced the risk of vertebral and nonvertebral fractures in patients with osteoporosis. Future use of these therapies is evolving to less frequent administration, and the interaction with anabolic therapies is presently being defined. Data to date support long-term safety with bisphosphonates in small numbers of patients treated for 5 to 10 years, and continued vigilant follow-up of the post-marketing experience will be necessary to determine if sustained bone turnover suppression is associated with rare musculoskeletal adverse events. Further development of bisphosphonates as adjunctive therapy to reduce bone metastases is in progress, and trials evaluating bisphosphonates as a structure modifying agent in osteoarthritis are nearing completion.