TY - JOUR T1 - Idoxifene, a Novel Selective Estrogen Receptor Modulator, Is Effective in a Rat Model of Adjuvant-Induced Arthritis JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1380 LP - 1386 VL - 291 IS - 3 AU - Alison M. Badger AU - Simon M. Blake AU - Robert A. Dodds AU - Don E. Griswold AU - Barbara A. Swift AU - David J. Rieman AU - George B. Stroup AU - Sandra J. Hoffman AU - Maxine Gowen Y1 - 1999/12/01 UR - http://jpet.aspetjournals.org/content/291/3/1380.abstract N2 - Idoxifene, a selective estrogen receptor modulator, was evaluated in male and female rats with adjuvant-induced arthritis (AA). AA was induced in Lewis rats with Mycobacterium butyricum in paraffin oil injected into the base of the tail, and the animals were treated with idoxifene prophylactically (days 0–21) or therapeutically (days 10–21). Efficacy was determined by measurements of paw inflammation, bone mineral content, and bone mineral density (BMD) with dual X-ray absorptiometry and by histological evaluation. Serum interleukin-6 levels were measured as a marker of the anti-inflammatory effects of the compound. Estrogen was included for comparison and was administered at 5 mg/kg, three times a week s.c. Prophylactic treatment of male AA rats with idoxifene at 10, 3, and 1 mg/kg and estrogen at 5 mg/kg significantly inhibited paw inflammation. There was improved joint integrity measured by BMD and reduced serum interleukin-6 levels in animals treated with 10 mg/kg/day idoxifene. Idoxifene and estrogen were as effective for AA in female Lewis rats as in male rats, significantly inhibiting paw inflammation and improving BMD. Histological evaluation of the tibiotarsal joints of female rats treated with 10 mg/kg showed protection of bone, cartilage, and soft tissue. Therapeutic treatment with either idoxifene or estrogen (starting on day 10 of disease) of male and female Lewis rats also was effective in reducing paw inflammation in these animals, although the effect was much less than that observed with the prophylactic dosing protocol. The American Society for Pharmacology and Experimental Therapeutics ER -