Serum levels of tissue inhibitor of metalloproteinase-1 and periarticular bone loss in early rheumatoid arthritis

We investigated the relationship between disease activity, serum biological mediators of joint damage, and periarticular bone loss in inflammatory arthritis. Patients with early inflammatory arthritis were recruited from a dedicated early arthritis clinic. At the time of recruitment, all had clinical evidence of synovitis. Patients were assessed at baseline and at 1-year follow-up. Periarticular and axial bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Serum levels of matrix metalloproteinase 1 and tissue inhibitor of metalloproteinases 1 (TIMP-1) were measured by enzyme-linked immunosorbent assay. A total 38 patients were included in the study. Twenty had rheumatoid arthritis (RA) and 18 had a seronegative spondylarthropathy (SpA). At baseline, periarticular hand BMD measurements were similar in RA and SpA. At 1 year, the mean periarticular hand BMD was significantly lower in RA (p<0.05). Significant inverse correlations between both the Ritchie articular index and C-reactive protein levels and the change in periarticular hand BMD at 1 year were observed in RA (r=-0.792, p<0.001 and r=-0.478, p=0.045, respectively). Baseline TIMP-1 levels correlated with the change in periarticular hand BMD at 1 year in RA (r=0.519, p=0.02). At 1 year, radiographic measures of joint damage were highest in RA. Inverse correlations between the change in periarticular hand BMD and the changes in erosion score (r=-0.90, p=0.04) were observed in patients demonstrating significant periarticular bone loss. Persistent disease activity was associated with increased periarticular bone loss in the hands in patients with RA, consistent with synovitis-mediated periarticular bone loss. The correlation between baseline TIMP-1 levels and periarticular bone loss over 1 year suggests that TIMP-1 may have utility as a biomarker of periarticular bone loss in early RA.