Objective. Autoantibodies, such as anti-citrullinated protein antibodies (ACPAs), have been described as inducing bone loss in rheumatoid arthritis (RA), which can also be reflected by bone mineral density (BMD). We therefore examined the association between osteoporosis and autoantibodies in two independent RA cohorts.Methods. Dual x-ray absorptiometry (DXA) of the lumbar spine and left hip was performed in 408 Dutch patients with early RA during 5 years of follow-up and in 198 Swedish patients with early RA during 10 years of follow-up. The longitudinal effect of ACPAs and other autoantibodies on several BMD measures was assessed using generalized estimating equations.Results. In the Dutch cohort, significantly lower BMD at baseline was observed in ACPA-positive patients compared to ACPA-negative patients, with an estimated marginal mean BMD in the left hip of 0.92 g/cm 2 (95% confidence interval [95% CI] 0.91-0.93) versus 0.95 g/cm 2 (95% CI 0.93-0.97) (P = 0.01). In line with this, significantly lower Z scores at baseline were noted in the ACPA-positive group compared to the ACPA-negative group (estimated marginal mean Z score in the left hip of 0.18 [95% CI 0.08-0.29] versus 0.48 [95% CI 0.33-0.63]) (P < 0.01). However, despite clear differences at baseline, ACPA positivity was not associated with greater decrease in absolute BMD or Z scores over time. Furthermore, there was no association between BMD and higher levels of ACPAs or other autoantibodies (rheumatoid factor and anti-carbamylated protein antibodies). In the Swedish cohort, ACPA-positive patients tended to have a higher prevalence of osteopenia at baseline (P = 0.04), but again, ACPA positivity was not associated with an increased prevalence of osteopenia or osteoporosis over time.Conclusion. The presence of ACPAs is associated with significantly lower BMD at baseline, but not with greater BMD loss over time in treated RA patients. These results suggest that ACPAs alone do not appear to contribute to bone loss after disease onset when disease activity is well-managed.

BackgroundAnti-citrullinated protein antibodies (ACPA) are one of the most important serological markers for rheumatoid arthritis (RA) and have been suggested to play a pathophysiologic role by directly binding to osteoclasts. However, the effect of ACPA on systemic bone mineral density (BMD) and in particular their effect on changes in BMD over time is currently unknown.ObjectivesThe aim of this study was to determine whether ACPA associate with changes in BMD over time in patients with RA.MethodsYearly dual X-ray absorptiometry (DXA) scores were performed during 5 years of follow-up in 412 patients with recent-onset RA participating in the IMPROVED study1, a clinical trial in which patients were treated according to a remission- (disease activity score <1.6) steered strategy. The effect of the presence of ACPA on 1) Z-scores of lumbar spine and hip over time, and 2) prevalence of osteopenia/osteoporosis (defined as a T-score ≤−1) over time was analysed using generalised estimating equations. Analyses were adjusted for age, gender, BMI, symptom duration, smoking status, disease activity, prednisone intake, usage of bisphosphonates, calcium intake and serum 25-OH vitamin D levels.ResultsACPA-positive patients had a significantly lower lumbar spine (p=0.04) and hip (p=0.01) Z-score at baseline. There was no difference in prevalence of osteoporosis/osteopenia at baseline between ACPA-positive and ACPA-negative patients (OR (95% CI) 1.02 (0.55 to 1.19)). We hypothesised that ACPA-positive patients would have more BMD loss over time compared to ACPA-negative patients. However, ACPA-positivity did not associate with a stronger decline in Z-score over time at lumbar (p=0.43) or femoral sites (p=0.67). Additionally, no effect of ACPA-positivity was found on the development of osteoporosis/osteopenia over time (p=0.23).ConclusionsACPA-positive patients have a significantly lower baseline BMD compared to ACPA-negative patients. Surprisingly, ACPA do not associate with a decrease in BMD over time in patients who were treated according to a tight control strategy. These results indicate that ACPA alone do not contribute to bone loss after disease onset in the absence of inflammation/disease activity.Reference[1] Wevers-de Boer K, et al. Ann Rheum Dis. 2012Sep;71(9):1472–7.Disclosure of InterestNone declared