Bone and joint destruction in rheumatoid arthritis: what is really happening?
Focal bone erosions occur at the joint margins and in subchondral bone of patients with rheumatoid arthritis (RA). These erosions progress throughout the course of disease and generally correlate with disease severity. Tissue sections from sites of bone erosion in the rheumatoid joint show multinucleated cells with phenotypic characteristics of osteoclasts, the cells responsible for resorbing bone during physiologic remodeling. Factors known to directly or indirectly induce osteoclast differentiation and activation are found in the rheumatoid synovium. These include receptor activator of NF-kappaB ligand (RANKL), which plays a critical role in osteoclast differentiation, as well as a variety of proinflammatory cytokines, including intereukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha), which upregulate RANKL. IL-1 also augments osteoclast activation, and TNF-alpha induces differentiation of early osteoclast precursors. In animal models of RA, RANKL is expressed at sites of bone erosion. Moreover, in a serum transfer model of inflammatory arthritis, animals unable to produce osteoclasts did not show evidence of bone resorption despite the presence of intense inflammation. These observations suggest that osteoclasts mediate focal bone erosions in RA and that targeting of osteoclasts and osteoclast mediated bone resorption represents a rational approach to preventing or reducing focal bone loss in RA.
Goldring
Steven R
SR
Harvard Medical School, New England Baptist Bone and Joint Institute, Boston, Massachusetts 02215, USA. sgoldrin@caregroup.harvard.edu
D001172:Arthritis, Rheumatoid / Q000473:pathology* / Q000503:physiopathology*; D016723:Bone Remodeling / Q000502:physiology; D001862:Bone Resorption / Q000473:pathology*; D002358:Cartilage, Articular / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D010010:Osteoclasts / Q000502:physiology; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013583:Synovial Membrane / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D018836:Inflammation Mediators; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha