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Best Pract Res Clin Rheumatol. 2005 Dec;19(6):1065-79.

Bone loss in inflammatory arthritis: mechanisms and therapeutic approaches with bisphosphonates.

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  • 1Department of Medicine, St Vincent's Hospital, The University of Melbourne, 41 Victoria Parade, Fitzroy, Vic. 3065, Australia.


The inflammatory process in rheumatoid arthritis provokes intense bone resorption, evidenced as bone erosions, juxta-articular osteopenia and generalized osteoporosis. These types of bone loss share a common pathogenesis, and the role of osteoclasts in focal bone erosion was verified in elegant animal studies. The tumour necrosis factor (TNF) family of cytokines and receptors--specifically TNF-alpha, RANKL, RANK and OPG--are dominant regulators of osteoclastic bone resorption in rheumatoid arthritis. The confirmation of the osteoclast mechanism provides new insight into the structural joint protection afforded by disease-modifying drugs and suggests innovative approaches to limit bone destruction. Emerging treatment strategies for bone disease in rheumatoid arthritis are the use of monoclonal antibodies to neutralize RANKL, and powerful bisphosphonates that target pathogenic osteoclasts.

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