The effect of methotrexate on the urinary pyridinium crosslink level in adjuvant induced arthritis in rats.

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The effect of methotrexate on bone metabolism was investigated in adjuvant arthritis in rats (AA rats) . Methotrexate was orally administered to rats for 28 days from the next day after adjuvant inoculation. Twenty four-hour urine samples were obtained before sacrifice, pyridinoline (PY) and deoxypyridinoline (DPY), and creatinine concentrations in urine were measured by HPLC and the alkaline picronate method, respectively. Urinary PY and DPY in AA rats were increased 3.8 and 2.7 times that of age-matched controls, respectively. Doses of 0.05, 0.1 and 0.2 mg/kg caused a dose-dependent inhibition of the inflammatory parameters (fibrinogen, A/G) and the excretion of urinary PY and DPY in AA rats. Indomethacin (1 mg/kg, p. o.) had a significant inhibitory effect on both inflammatory parameters and urinary PY, but not on DPY. Moreover, the fourth lumbar of vertebra was used for determination of morphological changes. The trabecular number in the vertebra in the AA rats significantly decreased in comparison with that of age-matched normal. Methotrexate (0.05, 0.1 and 0.2 mg/kg) dose- dependently and completely inhibited severe changes observed in the vertebra of AA rats, while indomethacin only partly inhibited these changes. The present study indicates that MTX can prevent bone destruction in AA rats and measurement of urinary DPY is a useful marker for examination the effect of drugs on bone destruction.
日本炎症・再生医学会の論文