This article is part of the supplement: Basic science, rationale, background and future of denosumab: a RANK ligand inhibitor
Department of Internal Medicine 3, University of Erlangen-Nurnberg, Krankenhausstrasse, D-91054 Erlangen, Germany
Arthritis Research & Therapy 2007, 9(Suppl 1):S2 doi:10.1186/ar2166Published: 29 June 2007
Inflammation and degradation of bone are two closely linked processes. Chronic inflammatory arthritis not only leads to inflammatory bone loss but it also involves local erosion of articular bone. This osteo-destructive feature of chronic inflammatory arthritis is a major cause of disability in patients with rheumatoid arthritis. Osteoclasts are essential for the resorption of mineralized cartilage and subchondral bone in chronic arthritis. The observed up-regulation of osteoclast differentiation factors (receptor activator of nuclear factor-κB ligand [RANKL]) in the synovial membrane of chronically inflamed joints indicates that osteoclasts are abundant in this setting, leading to rapid degradation of mineralized tissue. Blockade of osteoclast formation is thus a key strategy in preventing structural damage in arthritis. Denosumab, a humanized antibody that neutralizes RANKL, is an attractive candidate agent to inhibit inflammatory bone loss.