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Short-term low dose methotrexate ameliorates abnormal bone metabolism and bone loss in adjuvant induced arthritis
Y Suzuki1, M Nakagawa, C Masuda
1Department of Drug Delivery System, St. Marianna University School of Medicine, Kawasaki, Japan.
Objective:
To clarify whether short term weekly methotrexate (MTX) therapy aggravates bone abnormalities in adjuvant induced arthritis (AIA) or improves them through its antiarthritic effect.
Methods:
Bone metabolism and bone mineral density (BMD) were studied in 6 groups of Lewis rats: (1) normal controls, (2) rats given MTX 0.3 mg/kg weekly, (3) rats given MTX 3 mg/kg weekly, (4) AIA rats, (5) AIA rats given MTX 0.3 mg/kg weekly, and (6) AIA rats given MTX 3 mg/kg weekly. Osteogenic activity was determined from serum osteocalcin levels and number of marrow fibroblast colony forming units (osteogenic precursor cells). Bone resorptive activity was assayed by detecting osteoclast-like cells and pit formation in bone marrow cultures.
Results:
In control rats, MTX (3 mg/kg weekly) suppressed osteogenic activity, as shown by low serum osteocalcin levels and decreased growth of marrow fibroblast colony forming units. Osteoclast-like cells and pit formation in bone marrow cultures from control rats were increased by MTX, but BMD was unchanged. In rats with AIA, MTX (3 mg/kg) suppressed arthritis and restored the decreased osteogenic activity of bone marrow cells, and reduced their increased bone resorptive activity. These changes resulted in a significant increase of periarticular BMD in the femur.
Conclusion:
Low dose weekly MTX therapy had a favorable effect on abnormal bone metabolism and osteopenia in rats with AIA.