RANK, RANKL and OPG in inflammatory arthritis and periprosthetic osteolysis.
Elucidation of the receptor activator of nuclear factor kappa B (RANK), its ligand (RANKL) and osteoprotegerin (OPG) as the final effectors of bone resorption has transformed our understanding of metabolic bone diseases and revealed novel therapeutic targets. Activation of the RANK-RANKL signaling pathway is directly responsible for dramatic focal erosions that are observed in inflammatory arthritis and aseptic loosening of orthopaedic implants. While these conditions share many features common to all metabolic bone disorders (e.g., osteoclastic resorption), they exhibit several unique properties, which are highlighted in this review. Most important is the relative inability of bisphosphonate therapy to inhibit osteolysis in joint inflammation and periprosthetic joint loosening and the unexpected effectiveness of anti-cytokine therapy in both rheumatoid and psoriatic arthritis. Herein, we provide a review of the role of RANK, RANKL and OPG in erosive arthritis and periprosthetic osteolysis and discuss the potential of anti-RANKL therapy for these conditions.
Ritchlin
C T
CT
The Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester 14642, USA.
Schwarz
E M
EM
O'Keefe
R J
RJ
Looney
R J
RJ
D000818:Animals; D001168:Arthritis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010014:Osteolysis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D053244:Osteoprotegerin; D011475:Prosthesis Failure; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor
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