THE EFFECT OF LOW-DOSE METHOTREXATE ON BONE METABOLISM AND HISTOMORPHOMETRY IN RATS

Objective. To ascertain the effects of low-dose methotrexate (MTX) on bone metabolism and histomorphometry in rats. Methods. Female Sprague- Dawley rats (6 months old, n = 42) were divided into the following 4 g roups: intraperitoneal (IF) injections of MTX, with and without ovarie ctomy, and IP saline (controls), with and without ovariectomy. Injecti ons were given for 16 weeks. The MTX dose was equivalent to a standard dose for rheumatoid arthritis in humans that would yield similar seru m MTX levels (0.6 +/- 0.1 mu moles). Results, Bone formation (assessed by serum alkaline phosphatase and osteocalcin levels and histomorphom etry) was significantly lower in the MTX groups, and bone resorption ( assessed by urinary hydroxyproline levels and histomorphometry) was in creased in the MTX groups. Bone mass was significantly diminished in t he MTX groups. Conclusion. Prolonged administration of low-dose MTX in rats causes significant osteopenia via suppression of osteoblast acti vity and stimulation of osteoclast recruitment, which results in incre ased bone resorption.