Bisphosphonates and lifespan.

Bisphosphonates are first line agents used to treat osteoporosis and reduce fracture rate. They bind to areas of exposed calcium in the skeleton and cause osteoclast apoptosis, thereby leading to a reduction in remodelling rates. They are also used to decrease skeletal complications of some cancers including a reduction in bone metastases. Following the landmark randomised controlled trial of zoledronate post hip fracture (HORIZON) in which an unexpected survival benefit was found, there has been increasing interest in their potential ability to increase lifespan. This review will consider the clinical evidence for their effect on mortality in both the osteoporosis and non-osteoporosis settings, the latter including studies in intensive care, cancer and cardiovascular disease. Where evidence exists, this review will briefly discuss some of the postulated mechanisms for this survival benefit.