The effect of the steroid-sparing response to low-dose methotrexate on bone metabolism in glucocorticoid-dependent asthmatics

Background: The skeletal effects of low-dose methotrexate (MTX), in glucocorticoid-dependent asthmatics (GCDA), are unknown. Methods: We studied 9 patients from a total of 26 chronic GCDA who completed 28 weeks of MTX (15 mg weekly, intramuscularly). Prednisolone dose was not altered during the first 12 weeks, and was then reduced between 12 and 28 weeks. Mean (S.E.M.) age of the patients was 54 (4.0) years. They had normal bone mineral density (BMD), were not taking medication that affected bone metabolism (except prednisolone and inhaled corticosteroids) and all achieved at least 50% reduction in prednisolone dose at 28 weeks. Blood and urine samples were obtained at baseline, 12, 28 and 40 weeks for measurement of serum osteocalcin (OC) and bone alkaline phosphatase (Bone-ALP) as formation markers and urinary deoxypyridinoline (DPD) and N-terminal cross-linked telopeptide of type I collagen (NTX-I) as resorption markers. Results: Concurrently with the changes in prednisolone dosage serum OC levels increased significantly at 28 weeks (p<0.008) (8.1±1.0 ng/ml) compared to baseline (4.7±0.6 ng/ml) and 12 weeks (5.1±0.6 ng/ml), but trended back by 40 weeks (6.6±0.6 ng/ml). No significant changes were observed for the other bone markers between baseline and the other time points. Conclusions: The beneficial effects of steroid reduction on bone metabolism do not appear to be impaired by concomitant MTX treatment at least over 12 weeks.