High-dose methotrexate for chemotherapy is known to cause osteopenia. Dr. Carrasco and colleagues, from Cincinnati Children's Hospital Medical Center in Cincinnati, Ohio, United States, wanted to see whether low-dose methotrexate for JRA carries a risk of osteopathy as well. Case reports and cross-sectional studies on the effects of low-dose methotrexate on bone density have resulted in conflicting data. Measurements in these studies included urinary and serum markers, which reflect bone formation and bone resorption rather than bone density.

The investigators compared JRA patients on low-dose methotrexate to methotrexate-free JRA patients. A total of 177 children aged 6 to 16 years participated in the study. The physiological effects of low-dose methotrexate on bone physiology were followed periodically using biochemical markers of bone turnover. Bone mineral density was measured at months 0, 6, 12, 18, and 24 using dual-energy X-ray absorptiometry. Serum samples were measured at months 0, 12, and 24. Urine samples were taken in months 0, 6, 12, 18, and 24. Results between methotrexate-treated and non-methotrexate-treated groups were then compared.

At 24-month follow-up, total bone mineral density did not differ significantly between the two groups. The methotrexate group had had lower bone alkaline phosphatase and osteocalcin. Correcting for the number of active joints, however, there was no significant difference in bone markers. The methotrexate group continued to have a higher number of joints with active disease and loss of range of motion.

"Low-dose methotrexate does not cause bone mineral density problems. It's the steroids that lower bone mineral density," concluded Dr. Carrasco.

"Corticosteroids are a known risk factor for osteopenia in patients with chronic conditions," he said, pointing out that since half of all arthridites in children are JRA, he and his group think they've clarified an important issue. "Low-dose methotrexate does not affect bone mineral density in adults, as reported in 2004, nor in children."


[Presentation title: Effects of Low-Dose Methotrexate on Bone Density and Markers of Bone Metabolism in Juvenile Rheumatoid Arthritis.]

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