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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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You may find these interesting, they're from Professor Marios Hadjivassiliou, a leading expert on gluten ataxia: http://www.acnr.co.uk/pdfs/volume2issue6/v2i6reviewart2.pdf Best of luck helping your daughter

Yep. The one that is most relevant I think is the post by Backtalk. Backtalk went back on gluten and have to a colostomy done on an emergency basis. Not fun. She regretted ignoring the gluten-free diet.

Welcome Lochella Hopefully you can draw some comfort from finally having an answer and thus starting the path to good health. Healing is going to come from your own body as you progress on the gluten free diet and it stops fighting itself and starts repairing that damage. You're still in the very early days and it's not an instant process sadly. 6 months is the usual figure bandied around for seeing significant improvement, although hopefully you'll get some signs of improvement much quicker than that. The single best thing you can do is to eat good simple whole foods and make sure absolutely no gluten gets into your diet. There's some tips here: With stomach pains peppermint tea is my go to drink. Avoiding caffeine seems to help as well as its rough on digestion at the best of times. This may be a time to ease up on alcohol as well and consider dropping dairy, many find they're lactose intolerant but this can correct itself in time. You will find lots of good info, advice and support here, I hope the community is of help to you as it was to me. Best of luck!

I recently got diagnosed with Celiac disease I must of had it my whole life. I'm 35 I've always had severe stomach problems, in and out of hospitals and misdiagnosed until now. My small intestine is severely damaged I'm now waiting to see a dietitian and my specialist wants to see me again in 2 weeks. How do some of you deal with the pain of the healing process and what helps you? I'm in so much pain?

I recently got diagnosed with Celiac disease I must of had it my whole life, in 35 I've always had severe stomach problems in and out of hospitals and misdiagnosed until now. My small intestine is severely damaged in now waiting to see a dietitian and my specialist wants to see me again in 2 weeks. How do some of you deal with the pain of the healing process and what helps you? I'm in so much pain?