Serum cysteine proteases and their inhibitors in rheumatoid arthritis: relation to disease activity and radiographic progression.

This study aims to investigate the serum levels of cysteine proteases cathepsins B and H and their inhibitors stefin A, stefin B, and cystatin C, as well as traditional inflammatory markers such as C-reactive protein in patients with rheumatoid arthritis and to correlate these markers with scores of disease activity and radiographic progression. Seventy-two patients with rheumatoid arthritis were included from two previously described cohorts of patients with chronic polyarthritis. At inclusion, disease activity was assessed by a 28-joint count, patient global assessment, and serum C-reactive protein. Erosive status of hands and wrists was expressed by the Larsen score and recorded at inclusion and after 1 year. Serum levels of cathepsin B, cathepsin H, stefin A, stefin B, and cystatin C were determined by enzyme-linked immunosorbent assay. Neither cathepsin B nor cathepsin H serum levels were associated with disease activity, presence or progression of erosive disease. Number of swollen joints correlated with serum levels of stefin A and B and correlated negatively with cystatin C serum levels. Erosive disease was associated with high serum levels of C-reactive protein and stefin A and low serum levels of cystatin C. Progression of radiographic destruction was associated with high serum levels of C-reactive protein, stefin A and B, whereas serum levels of cystatin C were not associated with radiographic progression. The findings in this study support further investigation in the regulation of the activity of cathepsins and their inhibitors in erosive rheumatoid arthritis.

Low bone mineral density is associated with reduced hip joint space width in women: results from the Copenhagen Osteoarthritis Study.

OBJECTIVE: Since estrogen receptors (ER-alpha/ER-beta) were identified in human chondrocytes, animal and experimental studies have demonstrated the importance of continued estrogen production for the integrity of articular cartilage. However, human epidemiological support of the hypothesis has been inconclusive. The present cross-sectional study investigated the relationship between reduced bone mineral density (BMD), as a surrogate parameter of endogenous estrogen status assessed by digital x-ray radiogrammetry, and reduced minimum hip joint space width (JSW). DESIGN: Standardized hand radiographs of the Copenhagen Osteoarthritis Study cohort of 3,913 adults (1,470 male/2,443 female) with a mean age of 60 years (range, 18-92) were analyzed using X-Posure digital software, version 2.0 (Sectra-Pronosco). The system is operator independent. From 1,200 individual measurements per radiograph, mean BMD was calculated. Minimum hip JSW was assessed on standardized pelvic radiographs. RESULTS: Digital x-ray radiogrammetry BMD decreased in both men and women after the age of 45 years, progressively more so in women. Although minimum hip JSW in men remained relatively unaltered throughout life, a marked decline in female minimum hip JSW after age 45 years was observed. We found moderate but highly significant relationships between reduced BMD and reduced hip JSW in women (P < 0.0001), adjusted for age and dysplastic joint incongruity. CONCLUSION: We believe that the present study supports the hypothetical relationship between reduced estrogen levels and hip JSW reduction in women.