Rheumatology 2002; 41: 1232-1239
© 2002 British Society for Rheumatology
Original Papers |
Osteoclast formation and activity in the pathogenesis of osteoporosis in rheumatoid arthritis
Nuffield Department of Orthopaedic Surgery and
1 Department of Pathology, University of Oxford, Nuffield Orthopaedic Centre, Oxford OX3 7LD, UK
Objective. Rheumatoid arthritis (RA) is often complicated by generalized osteopenia due to increased bone resorption by osteoclasts. We analysed a number of cellular and humoral factors that influence osteoclast formation from circulating precursors in RA patients.
Methods. Monocytes isolated from RA patients and normal controls were cultured with macrophage colony-stimulating factor (M-CSF) and nuclear factor-
B ligand (RANKL), or with RANKL-expressing UMR106 cells and 1,25 dihydroxyvitamin D3 [1,25(OH)2D3]. Osteoclast differentiation was assessed by expression of tartrate-resistant acid phosphatase (TRAP) and vitronectin receptors (VNR) and lacunar resorption.
Results. Osteoclasts formed from RA patients exhibited increased resorptive activity but there was no difference in the relative proportion of circulating osteoclast precursors between RA patients and normal controls. Osteoclast precursors in RA patients were not more sensitive to the osteoclastogenic effects of 1,25(OH)2D3, M-CSF or RANKL. Dexamethasone, but not interleukin (IL) 1ß, tumour necrosis factor 
and IL-6, increased osteoclast formation and lacunar resorption.
Conclusion. There is an increase in the extent of lacunar resorption carried out by osteoclasts formed from circulating precursors in RA patients. This is not due to an increase in the number of circulating precursors or increased sensitivity to the osteoclastogenic effects of 1,25(OH)2D3, M-CSF, RANKL or inflammatory cytokines. Our findings suggest that increased osteoclast functional activity rather than osteoclast formation is more likely to play a role in the generalized bone loss that occurs in RA, and that corticosteroids stimulate osteoclast formation and resorption.
KEY WORDS: Rheumatoid arthritis, Osteoarthritis, Osteoclast, Bone resorption.
Correspondence to: N. A. Athanasou.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. Morimoto, S. Kuroda, T. Kizawa, K. Nomura, C. Higuchi, H. Yoshikawa, and T. Tomita Equivalent osteoblastic differentiation function of human mesenchymal stem cells from rheumatoid arthritis in comparison with osteoarthritis Rheumatology, June 1, 2009; 48(6): 643 - 649. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. F. Shead, C. S. Haworth, E. Gunn, D. Bilton, M. A. Scott, and J. E. Compston Osteoclastogenesis during Infective Exacerbations in Patients with Cystic Fibrosis Am. J. Respir. Crit. Care Med., August 1, 2006; 174(3): 306 - 311. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F R Byrne, S Morony, K Warmington, Z Geng, H L Brown, S A Flores, M Fiorino, S L Yin, D Hill, V Porkess, et al. CD4+CD45RBHi T cell transfer induced colitis in mice is accompanied by osteopenia which is treatable with recombinant human osteoprotegerin Gut, January 1, 2005; 54(1): 78 - 86. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. O'Gradaigh, S. Bord, D. Ireland, and J. E. Compston Osteoclastic bone resorption in rheumatoid arthritis and the acute-phase response Rheumatology, November 1, 2003; 42(11): 1429 - 1430. [Full Text] [PDF]
|
|