Background/Purpose:

Anti- citrullinated protein antibodies (ACPA) are known to be associated with joint destruction and a more severe disease course in rheumatoid arthritis (RA) patients. Recently, ACPA have been identified to directly induce bone loss (1). No study, however, has yet compared ACPA-positive and ACPA-negative RA patients with respect to their periarticular bone structure using high-resolution imaging of bone.

Methods:

Cross-sectional analysis of 234 RA-patients fulfilling the new ACR/EULAR criteria. All patients received micro-computed tomography (2) of the MCP II, II and IV joints of the dominantly affected hand. Age, gender, disease activity (DAS28), disease duration, rheumatoid factor, ACPA (by anti-CCP2 ELISA) and anti-rheumatic therapy were recorded.

Number, width, depth and volume of bone erosion were assessed by 2 independent readers, one of them reading the images twice to test for intrareader-reliability. For calculation of volumes, a semi-ellipsoid formula was used (3).

Results:

137 patients were ACPA positive (RF+: N =108, RF-: N =29), 97 patients ACPA negative (RF+ . N =28, RF-: N =69). All 4 groups were comparable for age, gender, disease activity, disease duration and anti-rheumatic therapy (Tab. 1). 15 patients were excluded from further evaluation due to movement artefacts. RF+/ACPA+ RA patients had significantly more severe erosions (width: 2.00mm; depth: 2.25mm; volume: 13.86mm³) as compared to RF-/ACPA- RA patients (1.25mm; 2.02mm; 4.60mm³; all p<0.0001). Furthermore, when comparing only those patients without RF, we observed that bone erosions in RF-/ACPA+ RA patients were significantly larger in dimension than bone erosions in RF-/ACPA- RA patients (w-+/+-:p=0,0012; w-+/--: p<0.0001; d:-+/+-p=0,0095 and d:-+/--p=0,0347; vol-+/+-:p= 0,0133; vol-+/--:p=0,0055). Intra-observer reproducibility (CH) for erosion counts, width, depth and volumes was high (Spearman's rho between 0.93-0.99; p < 0.001). Interobserver reproducibility (SF; CH) was also very high (cts: 0.99, p < 0.001; w/d: 0.98, p < 0.001; vol.: 0.996, p < 0.001).

Conclusion:

These data show that ACPA-positivity is associated with larger bone erosions in patients with RA. They also support the notion that ACPA essentially contribute to bone loss in RA by enhancing osteoclast activity, which is the key prerequisite for bone erosion. Moreover, ACPA impact bone erosion independent from the presence or absence of RF.

References:

1. Harre et al. Induction of osteoclastogenesis by human antibodies against cittrulinated vimentin. J Clin Investig 2012 May 1; 122(5)
2. Stach CM et al. Periarticular bone structure in rheumatoid arthritis patients and healthy individuals assessed by high-resolution computed tomography. Arthritis Rheum. 2010 Feb;62(2):330-9.
3. Albrecht, A., et al. The structural basis of MRI bone erosions – an assessment by micro-computed tomography [submitted]