ECTS Abstracts (2015) 1 OC2.3

Osteoprotegerin autoantibodies are independently associated with reduced bone density in coeliac disease

Philip Riches1, Tamara Gilchrist1, Micaela Rios-Petrakis1, Barbara Hauser1, Nick Kennedy1,2, Helen Gillett2, Peter Gillett2, Clive Goddard2, Alan Shand2, Jack Satsangi1,2 & Stuart Ralston1

1Institute of Genetics and Molecular Medicine, Edinburgh, UK; 2NHS Lothian Gastroenterology Department, Edinburgh, UK.

Background: Autoantibodies neutralising the effect of the bone regulatory cytokine osteoprotegerin (OPG) have been described in a patient with severe osteoporosis and coeliac disease. This study aimed to determine the prevalence of autoantibodies to OPG in patients with coeliac disease, and correlate their presence with bone mineral density.

Methods: A direct enzyme linked immunosorbent assay using recombinant OPG as a capture antigen was developed and used to screen serum from 282 patients with coeliac disease for autoantibodies to OPG. Bone mineral density data was available in 254 patients. A threshold for the presence of OPG antibody was defined as the mean plus three S.D. of values obtained from 102 healthy controls.

Results: OPG autoantibodies were found in 14/282 (5%) patients with coeliac disease. Bone mineral density results are summarised in Table 1. The presence of OPG antibodies was associated with lower spine bone mineral density T and Z-scores on both univariate analysis, and multivariate analysis including age, sex, height and weight as covariates (P<0.05). This association was also seen when analysing the titre of OPG antibody as a continuous trait. A non-significant reduction in mean bone mineral density hip scores was seen in patients with OPG antibodies.

Table 1 Bone mineral density of coeliac patients defined by OPG antibody status.
CharacteristicOPG antibody presentOPG antibody absentP value
Spine BMD T-score−2.00 (±1.2)−1.05 (±1.3)0.02
Spine BMD Z-score−1.12 (±1.39)−0.10 (±1.2)<0.01
Hip BMD T-score −1.36 (±0.99)−1.01 (±1.10)0.29
Hip BMD Z-score −0.38 (±0.84)−0.03 (±0.97)0.24

Conclusion: Raised levels of OPG autoantibodies are found in 5% of patients with coeliac disease and are independently associated with reduced spine bone mineral density. Further work is required to establish the clinical utility of testing for OPG antibodies.

Disclosure: P Riches and S Ralston are co-applicants on a patent application protecting the detection and/or treatment of diseases associated with autoantibodies to osteoprotegerin. This work was supported by the ECTS Amgen Bone Biology Fellowship (2010) and Coeliac UK/CORE charity (2013).