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Related Experiment Videos

Methotrexate maintains bone mass by preventing both a decrease in bone formation and an increase in bone resorption

Y Segawa1, M Yamaura, S Aota

  • 1Department of Pharmacology, Central Research Laboratory of Zeria Pharmaceutical Co., Ltd., Saitama, Japan.

Bone
|May 1, 1997
PubMed
Summary
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Methotrexate (MTX) improved bone mass and turnover in arthritic rats, while indomethacin (IND) had limited effects. MTX mitigated bone loss and resorption markers, suggesting its therapeutic potential in inflammatory bone conditions.

Area of Science:

  • Pharmacology
  • Rheumatology
  • Bone Biology

Background:

  • Adjuvant-induced arthritis in rats is a model for rheumatoid arthritis.
  • Bone loss and altered bone turnover are common in inflammatory arthritis.
  • Methotrexate (MTX) and indomethacin (IND) are commonly used anti-inflammatory drugs.

Purpose of the Study:

  • To investigate the effects of MTX and IND on bone mass and turnover in normal and arthritic rats.
  • To determine if MTX and IND can prevent or reverse arthritis-induced bone loss.
  • To elucidate the mechanisms by which MTX and IND affect bone metabolism in this model.

Main Methods:

  • Male Sprague-Dawley rats (6 weeks old) were induced with adjuvant arthritis or remained normal.
  • Rats received daily doses of MTX (0.05-0.2 mg/kg) or IND (1.0 mg/kg) for 28 days.

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  • Bone mineral density (BMD), serum osteocalcin, urinary deoxypyridinoline (D-Pyr), mineral apposition rate (MAR), and bone formation rate (BFR/BS) were measured.

    • Main Results:

    • MTX (0.1-0.2 mg/kg) maintained lumbar and femoral BMD in arthritic rats, preventing decreases in MAR and BFR/BS.
    • MTX prevented increases in osteoclast number and surface in arthritic rats.
    • IND partially prevented osteopenia but did not improve bone formation parameters; it did reduce osteoclast activity.

    Conclusions:

    • MTX demonstrates beneficial effects on bone mass and turnover in an adjuvant-induced arthritis rat model.
    • MTX may counteract bone loss by modulating bone resorption and formation pathways.
    • IND showed limited efficacy in preserving bone mass and formation, suggesting different mechanisms of action in inflammatory bone disease.