Bone loss in inflammatory arthritis: mechanisms and treatment strategies
Department of Medicine, Division of Rheumatology
Medical Subject Headings
Arthritis, Rheumatoid; Bone Resorption; Glycoproteins; Humans; Osteoprotegerin; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor
Musculoskeletal Diseases | Rheumatology | Skin and Connective Tissue Diseases
PURPOSE OF REVIEW: Focal bone loss in inflammatory arthritis begins early in the disease process and can contribute to patient morbidity. Current treatment strategies primarily target suppression of the inflammatory cascade with varying success in limiting the progression of focal bone destruction. This review outlines the current understanding of the mechanisms mediating inflammation-induced focal bone loss in rheumatoid arthritis and other inflammatory arthritides and highlights recent studies in animal models of arthritis that have contributed to our knowledge of this process.
RECENT FINDINGS: Bone-resorbing osteoclasts have been identified as important effector cells in inflammation-induced bone loss in both experimental animal models and human rheumatoid arthritis and psoriatic arthritis. The RANK/RANKL (receptor activator of nuclear factor-kappaB and RANK ligand) pathway has been shown to be essential for osteoclast differentiation in inflammatory arthritis. In addition, in vitro and in vivo studies have demonstrated that many cytokines and growth factors elaborated by inflamed synovial tissues may contribute to osteoclast differentiation and activation.
SUMMARY: Elucidation of the mechanisms mediating osteoclast differentiation and function has identified new pathways for potential targeted therapeutic intervention for focal bone loss in inflammatory arthritis. Challenges in the application of this approach are that therapies targeting the osteoclast would need to be used in combination with effective anti-inflammatory agents, and that pathways mediating osteoclast differentiation and function would need to remain at least partially functional to allow for continued skeletal remodeling.
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Citation: Curr Opin Rheumatol. 2004 Jul;16(4):419-27.
Walsh, Nicole C. and Gravallese, Ellen M., "Bone loss in inflammatory arthritis: mechanisms and treatment strategies" (2004). Rheumatology Publications and Presentations. 63.