Bone loss in inflammatory arthritis: mechanisms and therapeutic approaches with bisphosphonates.
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.
Romas
Evan
E
Department of Medicine, St Vincent's Hospital, The University of Melbourne, 41 Victoria Parade, Fitzroy, Vic. 3065, Australia. romase@svhm.org.au
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology*; D001862:Bone Resorption / Q000517:prevention & control*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D016207:Cytokines / Q000037:antagonists & inhibitors; D004164:Diphosphonates / Q000627:therapeutic use*; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D002352:Carrier Proteins; D016207:Cytokines; D004164:Diphosphonates; D005938:Glucocorticoids; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D014409:Tumor Necrosis Factor-alpha