The effects of methotrexate on the bone mass and turnover in the normal and adjuvant-induced arthritis rats

• Published in: Japanese Journal of Pharmacology Vol. 73; no. suppl.1; p. 91
• Main Authors: Tsuzuiki, Naoki, Segawa, Yoshihide, Omata, Takeshi, Itokazu, Yoshihiko, Oka, Hideki, Inoue, Naonori, Tamaki, Hajime, Aota, Shigeo, Yamaura, Motonori, Nakamura, Toshitaka
• Format: Journal Article
• Language: English
• Published: The Japanese Pharmacological Society 1997
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)44870-1

We examined the effects of methotrexate(MTX) and indomethacin(IND) on bone mass and turnover in normal and adjuvant-induced arthritis male SD rats. Arthritis was induced by a single injection into the right hind paw of 0.5 mg heat killed Mycobacterium butyricum suspended in liquid paraffin. Both normal and arthritic rats were daily given MTX(0.05, 0.1 and 0.2mg/kg) or IND(1.0mg/kg). Rats were sacrificed at the 0, 14 and 28 days. In normal rats, the administration of these agents did not change the lumbar and femoral BMD values, nor did the serum osteocalcin or urinary deoxypyridinoline(D-pyr) levels. Lumbar trabecular osteoclast number(Oc.N/BS) and osteoclast surface(Oc.S/BS) were decreased in the rats given IND. In the arthritic rats. MTX prevented late inflammatory edema in Use hind paw limb, and maintained an age dependent increase in the lumbar and femoral BMD values. While serum osteocalcin levels were decreased and urinary D-pyr values were increased in the arthritic control rats, these bone markers remained at the level of normal rats. Decreases in mineral apposition rate(MAR) and hone formation rate(BFR/BS) and increases in the trabecular Oc.N/BS and Oc.S/BS values were prevented by MTX. IND prevented the inflammatory paw edema, but did not improve the parameters of bone formation. An increase in Oc.N/BS was prevented and the osteopenia was partially prevented by IND. These data suggest that MTX improves bone mass and turnover in the arthritic rats, and in which mechanism of increase in bone resorption may be die to prostaglandins, but bone formation defect due to other cytokines in this model.