Adverse effects of rheumatoid arthritis on bone remodeling

Excerpt

Rheumatoid arthritis (RA) represents an excellent model for gaining insights into the adverse effects of inflammatory arthritis on local articular as well as generalized systemic bone remodeling. Bone loss manifested by focal erosions at the margins of diarthrodial joints represents the radiographic hallmark of RA. These lesions are produced by resorption of cortical bone at the bone–pannus junction. Inflammatory pannus can also extend into the marrow space, with accompanying subcortical and trabecular bone destruction. In animal models of inflammatory arthritis, erosion of subchondral bone contributes significantly to cartilage loss, as the scaffolding bone is destroyed by the inflammatory process. Preservation of subchondral bone integrity would be predicted to have a cartilage sparing effect even in the presence of continued intra-articular joint inflammation. Recent studies employing magnetic resonance imaging have shown that marginal joint erosions occur very early in the course of RA and progress throughout the disease [1, 2]. The propensity of the inflamed pannus tissue in RA to induce bone resorption is probably related to its capacity to produce a variety of factors with potent osteoclast differentiation and activation activity. Particular attention has focused on receptor activator of NF-κB ligand (RANKL), a member of the tumor necrosis factor ligand family, because of the requirement of this factor for osteoclastogenesis. RANKL is expressed by synovial fibroblasts and activated T cells in RA synovial tissues [3]. In three different animal models of inflammatory arthritis, treatment with osteoprotegerin (the soluble receptor that inhibits RANKL activity) results in marked suppression of focal bone erosions [4‐6]. In addition, mice possessing the null mutation for RANKL are protected from focal bone destruction in the serum transfer model of inflammatory arthritis [7]. These observations lend support to the concept that enhanced osteoclast-mediated bone resorption at the pannus–bone interface and in subchondral and trabecular bone play a critical role in the pathogenesis of focal articular bone erosions. …