Bisphosphonate Therapeutics in Bone Disease: The Hard and Soft Data on Osteoclast Inhibition

Abstract

Bisphosphonates are chemically stable structural analogs of inorganic pyrophosphate. Owing to their ability to inhibit osteoclast activity, bisphosphonates have become the primary agents to treat conditions marked by excessive osteoclast-mediated bone resorption, such as osteoporosis, Paget’s disease of bone, and cancer-associated bone disease. At the molecular level, bisphosphonates exert their anti-resorptive effects by inhibiting farnesyl pyrophosphate synthase activity within osteoclasts. Bisphosphonates are generally well tolerated, with many patients now having been treated for more than ten years. Widespread bisphosphonate use, however, has revealed both short-term and long-term side effects in some patients. Here, we review our current understanding of the mechanisms by which bisphosphonates inhibit osteoclast function, the current roles for these medications in clinical practice, and areas of concern that have emerged with widespread bisphosphonate use.