Effect of low dose methotrexate on markers of bone metabolism in patients with rheumatoid arthritis

Objective. To evaluate markers of bone metabolism in patients with active rheumatoid arthritis (RA) and the effect of weekly low dose methotrexate (MTX) on bone turnover. Methods. Forty-two menstruating female patients recently diagnosed to have RA (mean age 35.4 years, mean disease duration 1.03 years) were enrolled in this study. Disease activity was assessed by Ritchie articular index, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP); laboratory tests were done for deoxypyridinoline and bone alkaline phosphatase. Drug therapy was started in the form of a weekly MTX dose (range 10-15 mg). Patients were reassessed after 3 and 9 months for the same variables. No patient received steroids before or during the course of the study. Results. Thirty patients continued the study until 9 months. The mean value for deoxypyridinoline and bone alkaline phosphatase on entry were 8.4 and 12.5; mean values of Ritchie articular index and ESR were initially 10.1 and 59 mm, respectively. In patients with active RA deoxypyridinoline was significantly high (p < 0.01), while bone alkaline phosphatase was negatively correlated (p < 0.01). At 3 months deoxypyridinoline levels had fallen to 6.2, while bone alkaline phosphatase had risen to 18.8. At 9 months there was significantly reduced deoxypyridinoline, to 5.5 (p < 0.001), while bone alkaline phosphatase had risen significantly to 30 (p < 0.001) compared with pre-MTX assessment Conclusion. In patients with RA bone metabolism is affected. In active disease, there was decreased bone formation, while bone resorption was increased. The therapy of weekly low dose MTX had improved bone resorption, suggesting that in patients with RA MTX might have a bone protective effect by controlling disease activity.