OP0040 ANTI-CITRULLINATED PROTEIN AUTOANTIBODIES ARE ASSOCIATED WITH ONGOING SYSTEMIC BONE LOSS IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS TREATED ACCORDING TO THE PRINCIPLES OF TREAT-TO-TARGET AND TIGHT-CONTROL

Abstract

Background:Anti-citrullinated protein antibodies (ACPA) are a major risk factor for local and systemic bone loss in patients with rheumatoid arthritis (RA). We previously demonstrated that early RA patients at disease presentation already show reduced systemic bone mineral density (BMD) in association with ACPA-positivity (1). Whether the negative impact of ACPA on bone continues over time despite treatment institution is however unknown.Objectives:To investigate longitudinally the course of systemic bone loss in patients with early RA after institution of treatment with disease modifying anti-rheumatic drugs (DMARDs) according to the principles of treat-to-target and tight-control.Methods:The study population included 100 consecutive early RA patients (<12 months of symptoms) recruited at our Early Arthritis inception cohort and already evaluated for systemic BMD at disease presentation before treatment start (1). After diagnosis, patients were prospectively followed-up at three-months intervals upon initiation of therapy with conventional synthetic DMARDs (methotrexate in 85% of the cases) aimed at the achievement of low disease activity (LDA, 28-joints disease activity score [DAS28] <3.2). BMD was re-assessed after 24 months at the lumbar spine (L1-L4) and hip by the same dual X-ray absorptiometry (DXA) equipment used at baseline. Differences in BMD from baseline were evaluated in relation to demographic and clinical variables (listed in Table 1).Table.Predictors of bone mineral density changes over 24 months% change in BMDlumbar spinetotal hipfemoral neckrprprpAge0.2690.0080.0690.500.2580.01female gender0.0850.42-0.0230.54-0.1210.23menopause0.1370.200.0670.530.0870.41disease duration0.0740.470.0440.670.0160.87cumulative DAS280.0180.860.0020.870.0110.91time to LDA0.1420.16-0.0230.76-0.0440.66time to remission0.0350.74-0.0020.97-0.0110.91ACPA-0.2510.010.1260.22-0.1300.04RF-0.1130.270.1110.280.0010.99months of bisphosphonates0.3680.0030.1710.090.2910.04cumulative steroids-0.1430.16-0.0070.78-0.0090.93months of bDMARDs-0.1630.11-0.0540.48-0.0630.54Results:The study population was mainly composed of females (84%), of whom 64.3% were in post-menopause; the mean (SD) age was 57.4 (13.5) years. Median (IQR) symptoms duration before treatment start was 14 (9-24) weeks. Fourty-three percent of the patients was ACPA positive. After 24 months of treatment, LDA was achieved in 79% of the cases, and remission in 46%; 17.7% of the patients had initiated a biological DMARD. At DXA re-scanning, the BMD at the lumbar spine and total hip remained largely unchanged, whilst at the femoral neck decreased from 0.726 g/cm2 to 0.713 g/cm2 (mean difference [SD] -0.013 [0.056], p=0.02). Predictors of BMD changes at different sites are shown in Table 1. The cumulative dose of prednisone was borderline significant for more BMD loss at the lumbar spine. Cumulative disease activity did not significantly affect BMD changes. Rather, ACPA-positive patients had higher percent changes at both the lumbar spine and the femoral neck. In multivariable analyses, ACPA remained associated with more BMD loss even when adjusting for confounders (age, gender, cumulative steroids, bisphosphonate treatment) (r -0.126, p=0.04 at the lumbar spine; r -0.126, p=0.04 at the femoral neck).Conclusion:Treatment of patients with early RA according to treat-to-target strategies prevents systemic bone loss. However, despite optimal disease control, ACPA positivity continues to be associated with progressive decline in systemic BMD.