Association of Low Bone Mineral Density with Anti-Citrullinated Protein Antibody Positivity and Disease Activity in Established Rheumatoid Arthritis: Findings from a US Observational Cohort

Abstract

Introduction: To assess the relationship between low bone mineral density (BMD), anti-cyclic citrullinated peptide-2 (anti-CCP2) antibodies, and disease activity in patients with established rheumatoid arthritis (RA).

Methods: Patients enrolled in a single-center, observational cohort registry of patients with RA. Eligible patients had known BMD, as measured by digital X-ray radiogrammetry (DXR-BMD), and anti-CCP2 antibody measurements at the same time point or within 6 months. Anti-CCP2-immunoglobulin (Ig)G-positive (+) patients (≥ 20 U/mL) were distributed into three equal groups (Gp1-3), representing increasing anti-CCP2 antibody concentrations. Associations between BMD and anti-CCP2 antibody status and titer were explored in multivariate regression analyses controlling for covariates (including age, duration of RA, use of steroids, use of osteoporosis medication). Association between disease activity (DAS28 [CRP] < 2.6) and bone loss was also explored.

Results: A total of 149 patients (all women) were included (47 anti-CCP2 antibody negative [-], 102 anti-CCP2+ [34\titer group]). Mean disease duration was greater in the three anti-CCP2+ groups vs. the anti-CCP2- group. DXR-BMD was lower in the anti-CCP2+ vs. the anti-CCP2- groups (Gp1-3 vs. anti-CCP2-: P < 0.0001 for left and right hands). DXR-BMD decreased with increasing anti-CCP2 titer (P < 0.001 for left and right hands). Patients with low DXR-BMD were less likely to have a DAS28 (CRP) < 2.6 (P = 0.0181).

Conclusion: Among patients with established RA, data suggest that anti-CCP2+ patients, particularly those with high anti-CCP2 antibody titers, have lower hand BMD, and patients with lower hand BMD are less likely to have low disease activity.

Funding: Bristol-Myers Squibb.

Trial registration: Clinicaltrials.gov identifier, NCT01793103.

Keywords: Anti-cyclic citrullinated antibodies; Bone density; Osteoporosis; Rheumatoid arthritis.

Fig. 1

Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study (BRASS) design

Fig. 2

Association between DXR–BMD and anti-CCP2 antibody status and titer in a left hand and b right hand. Number of patients in each titer group: anti-CCP2–, n = 47; Gp1, n = 34; GP2, n = 34; Gp3, n = 34. Timeframe between DXR–BMD and anti-CCP2 measurements (months [SD]) were 0.6 (1.4) for anti-CCP2–, 1.8 (2.3) for Gp1, 1.1 (1.8) for GP2, and 1.0 (1.7) for Gp3 (P > 0.05 for comparison between the anti-CCP2+ groups and the anti-CCP2– group). Anti-CCP2 anti-cyclic citrullinated peptide-2 antibodies, anti-CCP2– anti-CCP2 antibody negative, anti-CCP2+ anti-CCP2 antibody positive, DXR–BMD digital X-ray radiogrammetry–bone mineral density, Gp group

Fig. 3

Association between DXR–BMD and DAS28 (CRP) < 2.6. CRP C-reactive protein, DAS28 Disease Activity in 28 joints, DXR–BMD digital X-ray radiogrammetry–bone mineral density