Positive regulators of osteoclastogenesis and bone resorption in rheumatoid arthritis
1 Department of Medicine 3, University of Erlangen-Nuremberg, Erlangen, 91054 Germany
2 Ludwig Boltzmann Institute of Osteology, Hanusch Hospital of WGKK and AUVA/Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, 1140 Vienna, Austria
Arthritis Research & Therapy 2011, 13:235 doi:10.1186/ar3380
See related review by Zhao and Ivashkiv, http://arthritis-research.com/content/13/4/234Published: 28 July 2011
Bone destruction is a frequent and clinically serious event in patients with rheumatoid arthritis (RA). Local joint destruction can cause joint instability and often necessitates reconstructive or replacement surgery. Moreover, inflammation-induced systemic bone loss is associated with an increased fracture risk. Bone resorption is a well-controlled process that is dependent on the differentiation of monocytes to bone-resorbing osteoclasts. Infiltrating as well as resident synovial cells, such as T cells, monocytes and synovial fibroblasts, have been identified as sources of osteoclast differentiation signals in RA patients. Pro-inflammatory cytokines are amongst the most important mechanisms driving this process. In particular, macrophage colony-stimulating factor, RANKL, TNF, IL-1 and IL-17 may play dominant roles in the pathogenesis of arthritis-associated bone loss. These cytokines activate different intracellular pathways to initiate osteoclast differentiation. Thus, over the past years several promising targets for the treatment of arthritic bone destruction have been defined.