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P. L. Riches 1, N. Thalayasingam1, S. H. Ralston1
1Rheumatology Department, Institute of Genetics and Molecular Medicine, Edinburgh, United Kingdom

Abstract: Osteoporosis is a recognised complication of autoimmune diseases such as coeliac disease, thyroid disease and rheumatoid arthritis. Until now this osteoporosis has been attributed to multiple mechanisms including malabsorption, over production of pro-inflammatory cytokines, immobility or corticosteroid therapy (1;2) rather than a direct autoimmune process. We have recently described a patient with coeliac disease in whom severe osteoporosis occurred in association with the development of neutralising antibodies to osteoprotegerin (OPG)(3) – an endogenously produced inhibitor of bone resorption. The antibodies blocked the inhibitory effect of OPG on activation of the receptor activator of nuclear factor kappa B signaling pathway.
We have screened 46 patients with coeliac disease for the presence of OPG antibodies using an immunoprecipitation assay and detected antibodies in 33% (15/46) of this cohort. In further pilot studies we have identified OPG antibodies in 20% (2/10) of patients with inflammatory arthritis, 10% (1/10) patients with hypothyroidism and 80% (8/10) of patients with severe osteoporosis (T score <-3.5).
Although we acknowledge that these data are preliminary they provide proof of concept that autoantibodies to OPG occur commonly in a variety of autoimmune diseases as well as a high percentage of unselected patients with severe osteoporosis, raising the possibility that they may contribute more generally to the pathogenesis of osteoporosis. Further work is ongoing to establish the clinical significance of these antibodies.
Reference List
(1) Goldring SR, Gravallese EM. Mechanisms of bone loss in inflammatory arthritis: diagnosis and therapeutic implications. Arthritis Res 2000; 2(1):33-37.
(2) Bianchi ML, Bardella MT. Bone and Celiac Disease. Calcif Tiss Int 2002; 71(6):465-471.
(3) Riches PL, McRorie E, Fraser WD, Determann C, Hof Rv, Ralston SH. Osteoporosis Associated with Neutralizing Autoantibodies against Osteoprotegerin. The New England Journal of Medicine 2009; 361(15):1459-1465.

Disclosure of Interest: None declared

Keywords: osteoporosis, osteoprotegerin antibodies

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