Email updates

Keep up to date with the latest news and content from Arthritis Research & Therapy and BioMed Central.

This article is part of the supplement: 25th European Workshop for Rheumatology Research

Oral presentation

The effects of inflammatory arthritis on bone remodeling

SR Goldring

  • Correspondence: SR Goldring

Author affiliations

Beth Israel Deaconess Medical Center, Division of Rheumatology, and New England Baptist Bone & Joint Institute, Harvard Institutes of Medicine, Boston, Massachusetts, USA

Citation and License

Arthritis Research & Therapy 2005, 7(Suppl 1):S12  doi:10.1186/ar1518

The electronic version of this article is the complete one and can be found online at:


Received:11 January 2005
Published:17 February 2005

© 2005 BioMed Central Ltd

Oral presentation

Rheumatoid arthritis (RA) represents an excellent model for gaining insights into the adverse effects of inflammatory arthritis on skeletal remodeling. Bone erosions at the margins of diarthrodial joints represent the radiographic hallmark of RA. Histopathologic examination of the bone–pannus interface in patients with RA reveals the presence of a heterogeneous population of cells lining the bone surface, including multinucleated cells expressing the full phenotypic repertoire of osteoclasts, the cells that mediate bone resorption in physiologic remodeling. Further evidence implicating osteoclasts in the pathogenesis of marginal joint erosions is derived from animal models of inflammatory arthritis in which animals lacking the capacity to form osteoclasts fail to develop joint erosions. Studies have shown that the RA synovial tissue contains abundant osteoclast precursors and that the RA synovium is a rich source of factors with potent osteoclast differentiation and activation activity. Particular attention has focused on receptor activator of NF-κB ligand (RANKL), a member of the tumor necrosis factor ligand family, because of the requirement of this factor for osteoclastogenesis. RANKL is expressed by synovial fibroblasts and activated T cells in RA synovial tissues and in several different animal models of inflammatory arthritis, treatment with osteoprotegerin (the soluble receptor that inhibits RANKL activity) results in marked suppression of focal bone erosions. In addition, mice possessing the null mutation for RANKL are protected from focal bone destruction in the serum transfer model of inflammatory arthritis. An additional observation in patients with active RA is the absence of radiographic evidence of bone repair. This finding suggests that the processes that regulate coupling of bone resorption and formation under physiologic conditions have been disrupted and that the enhanced focal bone resorption is not matched by a compensatory increase in bone formation. In addition to the disordered focal bone remodeling associated with the synovial lesion, patients with RA also exhibit evidence of generalized axial and appendicular bone loss at sites that are distant from inflamed joints. Assessment of biochemical markers of bone turnover indicates that there is a generalized increase in bone resorption, and that there is a correlation between disease activity and the rate of systemic bone resorption. It is likely that this generalized skeletal bone loss is mediated by synovial cytokines with osteoclastogenic activity that enter the circulation and act as 'endocrine' factors to adversely affect systemic bone remodeling. Recent studies indicate that agents, such as the bisphosphonates, that target osteoclast-mediated bone resorption have the capacity to reduce not only generalized bone osteoporosis but also may have efficacy in retarding the progression of focal joint erosions.