THU0067 Association of high titers of anti-carbamylated proteins antibodies with decreased bone mineral density in early arthritis patients
Authors: I. Arias de la Rosa, A.M. Ortiz, M.D. Boveda, S. Castañeda, I. Gonzalez-Alvaro, A. Gonzalez
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) has a negative impact on bone homeostasis, in which multiple inflammatory mediators are involved together with the anti-citrullinated proteins antibodies (ACPA). These antibodies are able to promote osteoclastogenesis and bone loss even before the onset of synovitis. Accordingly, ACPA are associated with the three aspects of bone loss: joint bone erosion, juxta-articular bone loss and, as recently demonstrated<sup>1</sup>, decreased bone mineral density (BMD). Other RA specific autoantibodies, the anti-carbamylated protein antibodies (anti-CarPA), are associated with the presence, severity and progression of erosions with independence of ACPA. However, their implication in the other aspects of bone loss has not been studied. <h3>Objectives</h3> To evaluate the association of anti-CarPA with BMD in a cohort of early arthritis (EA) patients. <h3>Methods</h3> Clinical data and samples were obtained at the first visit of 548 patients from the Princesa Early Arthritis Register Longitudinal (PEARL) study, which recruits patients within one year from arthritis onset. BMD was assessed by dual-energy x-ray absorptiometry (Hologic QDR-4500, Elite, Mass, USA) at the lumbar spine (LS), total hip (TH) and metacarpophalangeal (MCP) joints. BMD was considered as Z-scores, except for MCP due to lack of reference data. Anti-CarPA were determined by ELISA using carbamylated fetal calf serum. The ELISA results were considered as negative, below the 98 percentile of healthy controls, low-positive, below the median of positive patients, and high-positive, otherwise. Data were analysed with linear regression including sex, age, BMI, and menopause as covariates. <h3>Results</h3> Anti-CarPA were positive in 25.9% of the EA patients. The positive patients did not show significant differences in BMD with the negative patients. However, this lack of association was due to the similarity of negative and low-positive patients, because the high-positive patients showed significant decrease of BMD at LS (β=−0.39, p=0.01) and TH (β=−0.30, p=0.02). Nevertheless, we did not found significant association at the juxta-articular bone of the MCP joints. Given the overlap between anti-CarPA and ACPA, we included the two autoantibodies in multivariate analysis. The association with BMD was significant only in the ACPA positive/anti-CarPA high-positive subgroup at LS and TH (p=0.007 and 0.005, respectively). In addition, the coefficients of regression were similar between the ACPA positive/anti-CarPA high-positive and the ACPA negative/anti-CarPA high-positive subgroups (β=−0.50 <i>vs.</i> −0.52 at LS, and β=−0.37 <i>vs.</i> −0.30 at TH). <h3>Conclusions</h3> We found significantly lower BMD at LS and TH in the patients with high anti-CarPA titers. These associations seem to be independent from the presence of ACPA, suggesting that anti-CarPA could contribute to systemic bone loss in EA patients. <h3>Reference</h3> [1] Llorente I, et al. Rheumatol Int2017;37(5):799–806. <h3>Acknowledgements</h3> Supported by grants PI14/01651, PI14/00442, PI12/01578 and RD16/0012/0014 and/0011 of the Instituto de Salud Carlos III (Spain) that were partially financed by the ERDF <h3>Disclosure of Interest</h3> None declared