Methotrexate in the treatment of rheumatoid arthritis. II. In vivo effects on bone mineral density

OBJECTIVE: To determine the effect of methotrexate (MTX) on bone mineral density (BMD) in rheumatoid arthritis (RA). METHODS: One hundred and sixteen non-steroid-treated RA subjects (90 women) were studied in a prospective, longitudinal, non-randomized study. Subjects started MTX (n=36) or sulphasalazine (n=23) or continued long-term (>5 yr) treatment with MTX (n=28) or other disease-modifying anti-rheumatic drugs (n=29). BMD was estimated at entry and after 1 yr. Markers of bone turnover were measured at entry and at 1 yr, and additionally at 3 and 6 months in those starting treatment. Bone biopsies were taken before and after MTX treatment in four subjects. The primary outcome was change in BMD Z score and secondary outcomes were changes in bone turnover markers and bone formation by histomorphometry. RESULTS: Univariate analysis of covariance found that MTX at baseline was associated with reduced BMD at the femoral neck. However, femoral neck BMD was also associated with radiological damage score for the hand. Multivariate analysis and discriminant analysis of the subset of post-menopausal women showed that reduced bone density associated with MTX was due to confounders such as disease activity. There was no adverse effect of MTX on bone turnover markers or on measures of bone formation in biopsies. CONCLUSIONS: No adverse effect of low-dose MTX (mean 10 mg/week) on bone formation in RA was found.