Anti-RANKL therapy for inflammatory bone disorders: Mechanisms and potential clinical applications.
Focal bone loss around inflamed joints in patients with autoimmune disease, such as rheumatoid arthritis, remains a serious clinical problem. The recent elucidation of the RANK/RANK-ligand/OPG pathway and its role as the final effector of osteoclastogenesis and bone resorption has brought a tremendous understanding of the pathophysiology of inflammatory bone loss, and has heightened expectation of a novel intervention. Here, we review the etiology of inflammatory bone loss, the RANK/RANK-ligand/OPG pathway, and the clinical development of anti-RANK-ligand therapy.
Anandarajah
Allen P
AP
Department of Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, New York 14642, USA. Allen.Anandarajah@urmc.rochester.edu
Schwarz
Edward M
EM
D001168:Arthritis / Q000209:etiology / Q000378:metabolism / Q000628:therapy*; D001847:Bone Diseases / Q000209:etiology / Q000628:therapy*; D001862:Bone Resorption / Q000209:etiology* / Q000276:immunology / Q000628:therapy; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D006023:Glycoproteins / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D008954:Models, Biological; D010010:Osteoclasts / Q000502:physiology; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology
D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human