Bisphosphonate therapy in rheumatoid arthritis

Focal bone damage and generalized bone loss are features of rheumatoid arthritis (RA). The introduction of TNFalpha antagonists has radically improved the management of RA by providing a means of slowing or preventing the occurrence of focal bone damage. However, some patients with severe RA have contraindications to TNFalpha antagonist therapy and others either fail to respond or fail to tolerate TNFalpha antagonists. In addition, whether TNFalpha antagonists effectively combat generalized bone loss remains unknown. Bisphosphonates can prevent generalized bone loss. Their main target is the osteoclast, which has been identified as the culprit in focal bone damage caused by inflammatory diseases. As a result, the potential effects of bisphosphonates on focal bone damage related to RA are generating strong interest. Although results from the few studies in humans have been disappointing, new insights into the mechanisms of action of amino-bisphosphonates and recent data obtained in animals, most notably with new-generation bisphosphonates, have rekindled the hope that bisphosphonates may be beneficial in RA. We review herein the main studies of the effects of bisphosphonate therapy on focal bone damage and generalized bone loss in patients with RA.