Anti-citrullinated protein antibodies and high levels of rheumatoid factor are associated with systemic bone loss in patients with early untreated rheumatoid arthritis.

Serena Bugatti,Roberto Caporali,Antonio Manzo,Barbara Vitolo,Carlomaurizio Montecucco,Laura Bogliolo

doi:10.1186/s13075-016-1116-9

Abstract

BackgroundAutoantibodies such as anti-citrullinated protein antibodies (ACPA) are major risk factors for articular bone destruction from the earliest phases of rheumatoid arthritis (RA). The aim of the current study was to determine whether RA-associated autoantibodies also impact on systemic bone loss in patients with early disease.MethodsSystemic bone mineral density (BMD) was measured in the lumbar spine and the hip in 155 consecutive treatment-naïve patients with early RA (median symptom duration 13 weeks). Demographic and disease-specific parameters, including clinical disease activity, ultrasonographic (US) examination of the hands and wrists, radiographic scoring of joint damage, ACPA and rheumatoid factor (RF) levels were recorded from all patients. Reduced BMD was defined as Z score ≤ -1 SD and analysed in relation to disease-related characteristics and autoantibody subgroups.ResultsReduced BMD was found in 25.5 % of the patients in the spine and 19.4 % in the hip. Symptom duration, clinical and US disease activity, functional disability and radiographic damage did not significantly impact on spine and hip BMD loss in regression analyses adjusted for possible confounders (age, gender, menopausal status, current smoking, body mass index). In contrast, ACPA positivity (at any level) negatively affected the spine Z-score (adjusted OR (95 % CI) 2.76 (1.19 to 6.42)); the hip Z score was affected by high titres only (adjusted OR (95 % CI) 2.96 (1.15 to 7.66)). The association of ACPA with reduced BMD in the spine was confirmed even at low levels of RF (adjusted OR (95 % CI) 2.65 (1.01 to 7.24)), but was further increased by concomitant high RF (adjusted OR (95 % CI) 3.38 (1.11 to 10.34)). In contrast, Z scores in the hip were significantly reduced only in association with high ACPA and RF (adjusted OR (95 % CI) 4.96 (1.48 to 16.64)).ConclusionsSystemic BMD in patients with early RA is reduced in relation with ACPA positivity and high RF levels. This finding supports the notion that RA-associated autoimmunity may have a direct causative role in bone remodeling.

Highlights

Autoantibodies such as anti-citrullinated protein antibodies (ACPA) are major risk factors for articular bone destruction from the earliest phases of rheumatoid arthritis (RA)
Patients Between 2012 and 2014, all patients newly referred to the Pavia Early Arthritis Clinic with a diagnosis of RA according to the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010 classification criteria [23] were invited to undergo dual-energy x-ray absorptiometry (DXA) at both the hip and the spine
We show here that, overall, systemic bone mineral density (BMD) is preserved in patients with early RA, and classic disease-related risk factors, including disease duration, inflammatory activity and functional ability, have negligible impact on measurable bone remodeling at this stage of the disease

Summary

Introduction

Autoantibodies such as anti-citrullinated protein antibodies (ACPA) are major risk factors for articular bone destruction from the earliest phases of rheumatoid arthritis (RA). Recent experimental evidence indicates that RA-associated autoantibodies, in particular anti-citrullinated protein antibodies (ACPA), can independently stimulate bone remodeling by inducing the differentiation of bone-resorbing osteoclasts [4, 5]. The association between ACPA and further progression in joint damage has been reported in several independent studies, [6,7,8]. Despite having a similar response to steered treatment strategies, ACPA-positive patients with RA have higher rates of joint damage progression over time [9], and serum receptor activator of nuclear factor kappa B ligand (RANKL) is reported to be increased in ACPA-positive patients independent of acute phase reactants and pro-inflammatory cytokines [10]. Elegant imaging studies have recently demonstrated impairment in the bone microstructure in the metacarpophalangeal joints of ACPA-positive healthy individuals despite no signs of arthritis [11]

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