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Osteoporosis Associated with Neutralizing Autoantibodies against Osteoprotegerin

Celiac.com 12/03/2009 - Clinicians recently described a case of severe osteoporosis with high bone turnover, in which they found neutralizing autoantibodies against osteoprotegerin to be present. They also report finding autoantibodies against osteoprotegerin in three additional patients with celiac disease.

The clinical team reporting the findings was made up of Philip L. Riches, M.R.C.P., Euan McRorie, F.R.C.P., William D. Fraser, Ph.D., F.R.C.Path., Catherine Determann, B.Med.Sci., Rob van’t Hof, Ph.D., and Stuart H. Ralston, M.D. They are associated with the Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh (P.L.R., E.M., C.D., R.H., S.H.R.); and the Unit of Clinical Chemistry, School of Clinical Sciences, University of Liverpool, Liverpool (W.D.F.) — both in the United Kingdom.

The adult patient presented severe, high-turnover osteoporosis associated with subclinical celiac disease and autoimmune hypothyroidism. The clinicians found circulating autoantibodies against osteoprotegerin. 

Autoantibodies against osteoprotegerin block the inhibitory effect of osteoprotegerin on signaling by the receptor activator of nuclear factor (NF)-κB (RANK).

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The patient's osteoporosis did not respond to celiac disease treatment of a gluten-free diet, but completely reversed with bisphosphonate therapy.

Immunoglobulins purified from specimens of the patient’s serum abolished the inhibitory effect of osteoprotegerin on RANKL-induced NF-κB signaling in vitro, while those from the control serum did not, which indicates the presence of neutralizing autoantibodies against osteoprotegerin.

The clinicians used immunoprecipitation assay for osteoprotegerin on non-fasting patient serum samples at several points during the course of his illness, as well as from 10 age-matched healthy male controls, 15 patients with celiac disease, and 14 patients with autoimmune hypothyroidism.  They used bicinchoninic acid assay to measure protein content.

Serum samples from the 10 healthy controls and the 14 patients with autoimmune hypothyroidism showed no evidence of circulating autoantibodies against osteoprotegerin, while the serum samples from 3 of the 15 patients (20%) with celiac disease did show antibodies.

Autoantibodies against osteoprotegerin may be connected to the development of high-turnover osteoporosis, but whether autoantibodies against osteoprotegerin contribute to the pathogenesis of osteoporosis in celiac disease patients remains unknown.

Source:
N Engl J Med 2009;361:1459-65.

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