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Rheumatology 2002; 41: 741-749
© 2002 British Society for Rheumatology
Original Papers |
Methotrexate in the treatment of rheumatoid arthritis. II. In vivo effects on bone mineral density
The Royal National Hospital for Rheumatic Diseases, Upper Borough Walls, Bath BA1 1RL,
1 Medical Research Council Environmental Epidemiology Unit, Southampton General Hospital, Southampton SO16 6YD,
2 Department of Medicine, Addenbrooke's Hospital, Cambridge CB2 2QQ and
3 Bone Research Group, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, UK
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.
KEY WORDS: Rheumatoid arthritis, Methotrexate, Osteoporosis, Bone mineral density, Bone turnover.
Correspondence to: N. J. Minaur, 66 Third Avenue, Bath BA2 3NZ, UK.
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