Idoxifene, a novel selective estrogen receptor modulator, is effective in a rat model of adjuvant-induced arthritis

Idoxifene, a selective estrogen receptor modulator, was evaluated in male a nd female rats with adjuvant-induced arthritis (AA). AA was induced in Lewi s 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 meas urements of paw inflammation, bone mineral content, and bone mineral densit y (BMD) with dual X-ray absorptiometry and by histological evaluation. Seru m interleukin-6 levels were measured as a marker of the anti-inflammatory e ffects of the compound. Estrogen was included for comparison and was admini stered at 5 mg/kg, three times a week s.c. Prophylactic treatment of male A A rats with idoxifene at 10, 3, and 1 mg/kg and estrogen at 5 mg/kg signifi cantly inhibited paw inflammation. There was improved joint integrity measu red by BMD and reduced serum interleukin-6 levels in animals treated with 1 0 mg/kg/day idoxifene. Idoxifene and estrogen were as effective for AA in f emale Lewis rats as in male rats, significantly inhibiting paw inflammation and improving BMD. Histological evaluation of the tibiotarsal joints of fe male rats treated with 10 mg/kg showed protection of bone, cartilage, and s oft tissue. Therapeutic treatment with either idoxifene or estrogen (starti ng on day 10 of disease) of male and female Lewis rats also was effective i n reducing paw inflammation in these animals, although the effect was much less than that observed with the prophylactic dosing protocol.