Impact of Anti-Citrullinated Protein Antibodies on Progressive Systemic Bone Mineral Density Loss in Patients With Early Rheumatoid Arthritis After Two Years of Treat-to-Target.

Serena Bugatti,Carlomaurizio Montecucco,Francesca Motta,Paolo Delvino,Ludovico De Stefano,Antonio Manzo,Laura Bogliolo

doi:10.3389/fimmu.2021.701922

Abstract

ObjectivesTo investigate the association of anti-citrullinated protein antibodies (ACPA) with changes in systemic bone mineral density (BMD) in patients with early rheumatoid arthritis (RA) after two years of treat-to-target.MethodsBMD was measured at the lumbar spine (LS) and femoral neck (FN) in 100 patients with recent onset RA at baseline and after 24 months of treatment aimed at low disease activity (LDA) according to the 28-joints disease activity score (DAS28 <3.2). Multivariable regression analyses were performed to determine independent associations between autoantibodies and other disease and treatment-related parameters with BMD loss.ResultsAfter 24 months, the majority of the patients were at least in LDA (78%), with slightly more ACPA-positive subjects achieving the target. The BMD had significantly decreased at both the LS (mean [SD] percent loss -1.8 [6.2], p=0.03) and the FN (-2.4 [7.3], p=0.03) in ACPA-positive but not in ACPA-negative patients. Consequently, the proportion of patients with reduced BMD (Z score ≤-1) after 24 months was significantly higher among ACPA-positive patients at both the spine (39.5% vs 19.3%, p=0.05) and the hip (37.2% vs 12.2%, p=0.007). The association between ACPA and BMD loss was independent of other variables including age, gender, disease activity, cumulative dose of glucocorticoids and duration of therapy with bisphosphonates at the LS but not the FN.ConclusionsACPA are associated with ongoing BMD loss at the spine despite suppression of inflammation and adoption of prophylactic measures. ACPA-positive RA patients should be therefore strictly monitored for the development of osteoporosis.

Highlights

Rheumatoid arthritis (RA) is a chronic immune-inflammatory disease characterized by destructive synovitis and pathologic bone remodeling, ranging from localized joint erosions to systemic osteoporosis (OP) [1, 2]
Median symptom duration at study inclusion was of approximatively 21 weeks in both anti-citrullinated protein autoantibodies (ACPA)-positive and –negative patients
Results from our analysis indicate that, despite suppression of inflammation and adoption of prophylactic measures, ACPApositive early RA patients are exposed to increased risk of systemic bone loss, especially at the spine, in the first two years after treatment start

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic immune-inflammatory disease characterized by destructive synovitis and pathologic bone remodeling, ranging from localized joint erosions to systemic osteoporosis (OP) [1, 2]. Several lines of experimental and clinical evidence have consistently established the key contribution of autoantibodies in osteoclast-induced bone loss [5,6,7]. ACPA-positive RA patients exhibit higher degrees of local and systemic bone damage [11,12,13,14] as well as reduced bone strength [15], and ACPApositive individuals start showing periarticular bone loss in the absence of clinically evident synovitis [16]. We previously reported that ACPA-positive, treatment-naïve early RA patients already display reduced systemic bone mineral density (BMD) at presentation [17]. We evaluated longitudinally the changes in BMD in relation to the autoantibody status in our inception cohort of early RA patients during the first two years of tightly controlled treatment according to standardized protocols

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Conclusion