Association of high titers of anti-carbamylated protein antibodies with decreased bone mineral density in early arthritis patients.

Cristina Regueiro,Santos Castañeda,Isidoro Gonzalez-Alvaro,Ana M Ortiz,Maria Dolores Boveda,Antonio Gonzalez,Geetha P Bansal

doi:10.1371/journal.pone.0202583

Abstract

Rheumatoid arthritis (RA) has a negative impact on bone that is partly mediated by anti-citrullinated proteins antibodies (ACPA). These antibodies are associated with erosions, and with juxta-articular and systemic bone loss. Other RA autoantibodies, the anti-carbamylated protein antibodies (anti-CarPA), are independently associated with erosions. However, we do not know if they are also associated with juxta-articular and systemic bone loss. Here, we have addressed this question with data from 548 early arthritis (EA) patients. Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry at the lumbar spine (LS), total hip (TH) and metacarpophalangeal joints (MCP). The 25.9% anti-CarPA positive patients did not show significant differences in BMD Z-scores with the negative patients. Nevertheless, this result was due to the similarity between negative and low-positive (below the median of the positive) patients, whereas 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); but not at the juxta-articular bone of MCP. Given the overlap between anti-CarPA and ACPA, we included the two autoantibodies in an analysis that showed significantly lower BMD Z-scores at LS and TH (p< 0.01) only in the ACPA positive/anti-CarPA high-positive subgroup. However, the similar coefficients of regression between the ACPA positive/anti-CarPA high-positive and the ACPA negative/anti-CarPA high-positive subgroups (β = -0.50 vs. -0.52 at LS, and β = -0.37 vs. -0.30 at TH) suggested an independent association. Overall, these results support a contribution of anti-CarPA to systemic bone loss in EA patients.

Highlights

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation of the synovial membrane and joint destruction [1]
We have found significant lower Bone mineral density (BMD) at lumbar spine (LS) and total hip (TH) of patients with high titers of anti-CarPA, suggesting that anti-CarPA at high titers could contribute to systemic bone loss in early arthritis (EA) patients in an independent way
The coexistence of different autoantibodies in patients with RA hampers the determination of their relative contribution to the complications that may appear throughout the disease evolution

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation of the synovial membrane and joint destruction [1]. Two studies in cohorts of early RA (ERA) [12] and early arthritis (EA) [13] patients showed that systemic bone loss correlated with the presence of ACPA. Other RA autoantibodies, the anti-carbamylated protein antibodies (anti-CarPA), are associated with the presence, severity and progression of erosions This association has been observed independently of ACPA, even within ACPA negative patients [16,17,18,19]. The objective of this work has been to analyze whether the presence of antiCarPA was associated with juxta-articular or systemic bone loss in a cohort of EA patients This objective has been pursued by examining the anti-CarPA association with BMD at the MCP joints for juxta-articular bone loss and at the LS and TH for systemic bone loss. Most EA patients show already their definitive anti-CarPA status [18,20] and bone loss is already frequently present at this time [3]

Materials and methods

Results

Discussion