Abstract

Background:Rheumatoid arthritis (RA) is associated with increased systemic bone loss, leading to a high risk for fragility fractures. Especially anti-citrullinated protein antibody (ACPA) positivity is considered a risk factor for local bone erosions and systemic bone loss1.Objectives:The purpose of this study was to compare ACPA positive versus ACPA negative RA patients in terms of the prevalence of osteoporosis and fragility fractures and to identify differences in underlying risk factors that influence bone health.Methods:Rh-GIOP is an ongoing prospective observational study collecting and analyzing disease- and bone-related data from patients with chronic rheumatic diseases or psoriasis treated with glucocorticoids (GC). In this cross-sectional analysis, we performed a matched-pair analysis, matching 114 ACPA positive to 114 ACPA negative RA patients according to age (5-year-steps), sex, and body mass index (BMI, 2-unit-steps). Descriptive analyses were performed, with values displayed as mean ± standard deviation for continuous variables. Non-parametric tests were used at a two-sided significance level of 5% to compare differences in underlying and potential risk factors without adjustment for multiple testing.Results:At same mean age (63.9 ±10.2 years) and BMI (27.9 ±5.6kg/m2), the matched groups had a female proportion of 82.5%. APCA positive patients had a significantly longer mean disease duration (13.9 vs 9.9 years, p<0.001), a higher mean cumulative GC-dose (22.3 vs 13.2g, p<0.01) and mean duration of GC therapy (10.1 vs 6.6 years, p<0.01). There was no significant difference in the prevalence of osteoporosis as defined by dual-energy X-ray absorptiometry (DXA) (18.4 vs 20.2%), nor in the prevalence of vertebral (7.0 vs 5.3%) or non-vertebral fractures (31.6 vs 29.8%). C-reactive protein levels as a marker of disease activity were significantly higher in ACPA positive patients (mean: 8.8 vs 4.3mg/l, p= 0.02), while mean disease activity score (DAS)28 levels were slightly lower in ACPA positive patients (2.4 vs 2.7, p= 0.05). No difference in health assessment questionnaire (HAQ) score was found. RA-specific treatments were similar, especially concerning current mean daily GC-dose (6.7 vs 4.9mg/day), except for Rituximab and targeted synthetic disease modifying anti-rheumatic drugs (DMARDs) which were more commonly used in ACPA positive patients (9.6 vs 2.6%, p=0.05) and (5.3 vs 0%, p=0.029), respectively. ACPA positive patients did not differ significantly from ACPA negative patients in specific anti-osteoporotic treatment, nor in the prevalence of comorbidities or concomitant medication. There were no significant differences in bone-specific laboratory parameters.Conclusion:In a cross-sectional analysis of our cohort, the prevalence of osteoporosis and fragility fractures was similar between ACPA positive and ACPA negative RA patients, despite longer disease duration and GC-treatment in ACPA positive patients. This is remarkable since it implies that ACPA negative patients are at a similar risk for osteoporosis and associated fractures. Optimal management of disease activity with or without GCs may represent a mainstay in preventing disease-related comorbidities such as osteoporosis.

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