Bone loss in inflammatory arthritis: mechanisms and treatment strategies.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Walsh
Nicole C
NC
Division of Rheumatology and Metabolic Bone Disease, Beth Israel Deaconess Medical Center and New England Baptist Bone and Joint Institute, Harvard Institutes of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
Gravallese
Ellen M
EM
D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D001862:Bone Resorption / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor
D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human