Antibodies to cyclic citrullinated protein and erythrocyte sedimentation rate predict hand bone loss in patients with rheumatoid arthritis of short duration: a longitudinal study

Abstract

Introduction: Radiographic progression in rheumatoid arthritis (RA) has in several studies been shown to be predicted by serological markers widely used in daily clinical practice. The objective of this longitudinal study was to examine if these serological markers also predict hand bone mineral density (BMD) loss in patients with RA of short disease duration.

Methods: 163 patients with RA of short disease duration (2.4 years) were included and followed longitudinally. Antibodies to cyclic citrullinated protein (anti-CCP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were analysed from baseline blood-samples. Hand BMD was measured by digital X-ray radiogrammetry (DXR) based on hand and wrist radiographs obtained at baseline and 1, 2 and 5-year follow-up.

Results: During the study period, DXR-BMD decreased by median (inter quartile range) 1.7% (4.1 to 0.4), 2.8% (5.3 to 0.9) and 5.6% (11.7 to 2.3) after 1, 2 and 5 years, respectively. Elevated baseline anti-CCP, RF, ESR and CRP levels were in univariate linear regression analyses consistently associated with DXR-BMD change at all time-points. Anti-CCP and ESR were independently associated with hand DXR-BMD in multivariate linear regression analyses. Elevated anti-CCP levels were consistent and independent predictors of loss in cortical hand bone during the study period, with the odds ratios (95% confidence interval) 2.2 (1.0 to 4.5), 2.6 (1.1 to 6.2) and 4.9 (1.4 to 16.7) for the 1, 2, and 5-year follow-up periods, respectively.

Conclusions: Anti-CCP and ESR were found to be independent predictors of early localised BMD loss. This finding adds to the understanding of anti-CCP and ESR as important predictors of bone involvement in RA.

Figure 1

Cumulative probability plots presenting the individual patients' change in DXR-BMD. (a) Change in digital X-ray radiogrammetry bone mineral density (DXR-BMD) of the entire study group (0 to 1 years, 1 to 2 years, 2 to 5 years). (b-d) Change in DXR-BMD stratified according to antibody to cyclic citrullinated proteins (anti-CCP) positive/negative patients (empty circle: anti-CCP > 25 U/ml, filled circle: anti-CCP ≤ 25 U/ml) for 0 to 1, 1 to 2 and 2 to 5 year change, respectively.