Predictors of Early Bone Erosion in Patients With Synovitis of Recent Onset

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To identify risk factors for the development of radiographic erosions early in the course of inflammatory arthropathies, an inception cohort of 238 patients with peripheral joint synovitis of less than one year duration was evaluated. Of these patients, 70 (28%) had early RF+RA, 36 (15%) had RF-RA, 43 (18%) had spondylarthropathy, and 89 (37%) had undifferentiated arthritis. Patients underwent clinical, serological and radiographic evaluation, HLA typing, and closed synovial biopsy of an affected joint. A total of 23% of patients had multiple radiographic erosions, with RA patients having the highest frequency (37%). The presence of multiple erosions was associated with the presence of the shared epitope only in the RF-RA patients (OR 9.9, P < 0.01). Anti-Sa antibodies were associated with the presence of multiple erosions in both RF+ and RF- patients (odds ratios 2.0 and 6.3 respectively), but numbers were too small to reach statistical significance. The presence of either SE or anti-Sa was highly associated with erosions in the RF-RA patients (odds ratio of 25.7, P < 0.05).

As elevated tissue and serum levels of the gelatinases (MMP-2 and MMP-9) have been associated with enhanced invasiveness in cancer, we tested the hypothesis that elevated levels and activity of the gelatinases were associated with the presence erosions. Serum levels of active MMP-2 and -9 were measured in a subset of 45 RA, 21 non-RA patients, and 4 normal volunteers. Tissue expression of MMP-2,-9,-14 and TIMP-1, 2 were assessed using immunohistology and synovial activity of MMP-2 and -9 were measured using gel zymography.

Serum levels of total and active MMP-2 and -9 did not predict erosions. Patients with erosions had higher synovial tissue levels of active MMP-2 than patients with no erosions (3.5 ± 2.1 ng/mg vs 1.9 ± 2.5 ng/mg, P = 0.04). MMP-9 levels tended to be higher in the patients with erosive disease, although the range of expression was very wide. No other immunohistologic parameter correlated with the presence of early erosions.

In this cohort of patients with early synovitis, the presence of either shared epitope or anti-Sa antibodies was associated with early erosion formation, particularly in patients with RF-RA. In the synovial tissues of these patients, high levels of MMP-2 activity are the most closely associated with erosive disease.