Anti-citrullinated protein antibodies are associated with decreased bone mineral density: baseline data from a register of early arthritis patients

Abstract

Since the previous studies showed that anti-citrullinated protein antibodies (ACPA) can induce osteoclasts differentiation and activation, even before arthritis onset, the aim of our study was to determine whether ACPA-positivity is associated with lower bone mineral density (BMD) at baseline visit of a register of early arthritis (EA) patients. The study population comprised 578 patients (80% females) from our EA clinic with a median disease duration, 5.1 months (p25–p75: 6–8); median age, 53.6 years (41.9–66.1), 38% ACPA-positive, and 55% fulfilling 2010 criteria for rheumatoid arthritis. BMD was measured using dual X-ray absorptiometry at lumbar spine, hip, and metacarpophalangeal (MCP) joints of the non-dominant hand to evaluate both systemic and juxta-articular bone mass. ACPA titers were determined through enzyme immunoassay. The effect of ACPA on BMD was analyzed using multivariable analysis based on generalized linear models adjusted for various confounders. ACPA-positive patients showed lower bone mass at lumbar spine and hip, but no differences were observed at MCP joints compared to ACPA-negative patients. However, ACPA-positive patients displayed higher disease activity and disability than ACPA-negative patients. After adjustment for gender, age, body mass index, and other bone-related variables, the presence of ACPA remained significantly associated with lower BMD at the lumbar spine, femoral neck, and hip but not at MCP joints. Disease activity was not associated with baseline bone mass. Our data reinforce the previous preclinical findings suggesting that the systemic bone loss detected at the initial phases of early ACPA-positive arthritis is independent of inflammatory status and, therefore, could be mediated by ACPA.Electronic supplementary materialThe online version of this article (doi:10.1007/s00296-017-3674-9) contains supplementary material, which is available to authorized users.

Anti-CCP-positive patients with RA have a higher 10-year probability of fracture evaluated by FRAX®: a registry study of RA with osteoporosis/fracture

“…Both previous studies [ 17 , 18 ] pertaining to the association of anti-CCP and BMD in patients with early RA revealed a negative effect of anti-CCP+ on BMD at all measured sites, a finding that is inconsistent with those of the present study and other series on established RA [ 13 , 15 ]. There are several possible explanations for the different observations between the studies.…”

“…A recent publication by Wysham et al also demonstrated that a high positive anti-CCP level and appendicular lean muscle mass were associated with FN BMD in established RA [ 16 ]. Llorente et al reported that patients with early RA with anti-CCP+ had lower BMD than the anti-CCP− control subjects at the lumbar spine, FN, and hip [ 17 ]. Bugatti et al also demonstrated that anti-CCP+ patients with early untreated RA had lower BMD than their anti-CCP− counterparts at the lumbar spine and hip [ 18 ].…”

Risk Factors for Systemic Reduced Bone Mineral Density in Premenopausal Female Patients with Early Untreated Rheumatoid Arthritis

“…The presence of reduced systemic BMD in early stages of the RA indicated that while synovial inflammation may take a long time to produce systemic effects such as significant generalized BMD changes [25], reduced BMD in early stages of RA appears to be coupled with autoimmunity. Relevant to this concept, our results had confirmed the recent evidence that link the ACPA and RF to reduced BMD in patients with early RA [21,24].…”

“…The age of the women in the study of Forslind et al ranged from 55 to 61 years which may explain for the higher proportion of the reduced bone mass than in our study. The inclusion of premenopausal females, the short duration of RA symptoms, all patients had an active disease and lack of treatment could exclude the association of traditional osteoporosis risk factors or the disease related factors to the reduced BMD in our patients with early RA in agreement with earlier studies [21] and in contrast to findings of other studies that enrolled patients with early RA but with longer disease duration or variable treatment [22][23][24].…”

Osteoporosis: an Independent Determinant of Bone Erosions in Rheumatoid Arthritis?

“…It is known that low BMD, measured with digital X ray techniques or dual‐energy X‐ray absorptiometry (DXA), is significantly associated with bone erosions in RA patients . Recently, cortical thinning and fenestration have been observed before the clinical onset of arthritis in subjects with anti‐citrullinated protein antibodies (ACPAs), and ACPAs have a negative titer‐dependent effect on BMD . ACPA titer is a well‐known risk factor for bone erosions in RA …”