Vertebral Compression Fractures and Antibodies to Citrullinated Vimentin in Established Rheumatoid Arthritis

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Background/Purpose:

Patients with RA have high rates of osteoporosis and fractures and RA induces articular and extra-articular bone loss. Seropositivity for any CCP antibody is associated with risk of erosions and osteoporosis. In vitro, human antibodies against citrullinated vimentin bind osteoclast cell surfaces, activate their bone resorptive activity and in an animal model, induce bone loss. In humans, it is not known whether these antibodies are a specific risk factor for osteoporosis. The aim of this study was to assess the prevalence of radiographic vertebral compression fractures (VCF), as a marker of skeletal fragility, in an established RA cohort and whether the presence of antibodies to citrullinated vimentin were associated with this.

Methods:

Data was obtained from a prospective established RA cohort (ACR/EULAR 2010 or ACR 1987 criteria) undergoing elective arthroplasty. VCF were identified on the lateral pre-operative chest radiograph by two independent readers utilizing the Genant semi-quantitative method. Antibodies to citrullinated vimentin epitopes were measured by mean fluorescence intensity utilizing a custom, bead-based, antigen array comprising CCP and RA-associated citrullinated antigens. To identify risk factors predictive of vertebral compression, univariate logistic regression analysis was performed including known potential risk factors for bone loss in RA.

Results:

181 participants had an available chest radiograph. Median age was 65 years [IQR 56, 71] and median disease duration 11 years [IQR 3, 20]. 80% were female, 37% were on current glucocorticoid therapy and 21% had prior exposure. Only 3% self-reported a diagnosis of osteoporosis or use of osteoporosis medications. Despite these numbers, almost half, 76/181 (42%) [58 female] had radiographic VCF (Table 1). Participants with VCF were older [median age 68 years vs. 64 years, p=0.03]. In univariate analysis of potential risk factors, only age was associated with VCF (Table 2). No significant differences were seen in antibody levels, including antibody isotypes to citrullinated vimentin.

Conclusion:

Vertebral compression fractures were prevalent in patients in this established RA cohort. The strongest risk factor for VCF was age. Antibodies to citrullinated vimentin, implicated in early RA models, were not associated with VCF. Our results highlight the profound detrimental skeletal effects of RA. Further studies are needed to investigate the mechanisms of focal versus generalized bone loss, as well as skeletal changes that occur with RA progression.

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