Abstract and Introduction
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.
Pathologic changes in bone mass and bone quality can be the manifestation of an intrinsic, often genetically based dysfunction of the skeletal system, which can lead to fragile or otherwise altered bone. Osteogenesis imperfecta or Paget's disease are among the best known examples of primary genetically based bone disease; the former leads to fragile bone and the latter to increased bone mass. More frequently, however, bone becomes the target of extraskeletal processes, and changes in the exogenous or endogenous environment can affect skeletal tissue, accelerate bone loss, and decrease bone quality. Lack of mobility, smoking, and drug therapy are well established exogenous environmental factors that affect bone quality. Endogenous factors include age-induced loss of muscular strength and endocrine changes, such as reduction in sex hormones during the menopause or dysfunction of the thyroid or adrenal hormone axis.
Systemic inflammation is a key example of a condition that profoundly affects the skeleton but is not a primary disorder of bone itself. Recent data suggest that even a minor and subclinical increase in systemic inflammation precipitates bone disease and increases fracture risk. This tight interaction between inflammation and bone is highlighted by the observation that virtually all chronic inflammatory diseases, particularly rheumatic disease and chronic inflammatory bowel disease, are associated with a high prevalence of osteoporosis and increased fracture risk.[2,3,4,5,6] In the case of a more localized inflammatory process, these systemic effects on bone are accompanied by local bone damage at the skeletal sites closest to the inflammatory focus. Similar to destruction mediated by an earthquake, bone damage is most common and most severe in the vicinity of the (inflammatory) epicenter, whereas the effects are less severe at sites distant from the epicenter, although they can still be detected (for instance, bone density measurements in the case of bone loss). Local resorption of alveolar bone in periodontal disease is a good example of local bone loss; another clinically important example is bone erosion in inflammatory arthritis.
Arthritis Res Ther. 2007;9(Supp) © 2007 BioMed Central, Ltd.
Copyright to this article is held by the author(s), licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original citation.
This article is published as part of Arthritis Research & Therapy Volume 9 Supplement 1, 2007: Basic science, rationale, background and future of denosumab: a RANK ligand inhibitor. The full contents of the supplement are available online at https://arthritis-research.com/supplements/9/S1.
Cite this: Erosive Arthritis - Medscape - Jun 29, 2007.