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Research ArticleArticle

Idoxifene, a Novel Selective Estrogen Receptor Modulator, Is Effective in a Rat Model of Adjuvant-Induced Arthritis

Alison M. Badger, Simon M. Blake, Robert A. Dodds, Don E. Griswold, Barbara A. Swift, David J. Rieman, George B. Stroup, Sandra J. Hoffman and Maxine Gowen
Journal of Pharmacology and Experimental Therapeutics December 1999, 291 (3) 1380-1386;
Alison M. Badger
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Simon M. Blake
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Robert A. Dodds
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Don E. Griswold
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Barbara A. Swift
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David J. Rieman
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George B. Stroup
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Sandra J. Hoffman
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Maxine Gowen
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Abstract

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.

Footnotes

  • Send reprint requests to: Alison M. Badger, Department of Bone and Cartilage Biology, SmithKline Beecham Pharmaceuticals, 709 Swedeland Rd., King of Prussia, PA 19406. E-mail:Alison_M_Badger{at}SBPHRD.com

  • Abbreviations:
    SERM
    selective estrogen receptor modulator
    BMD
    bone mineral density
    IL
    interleukin
    TNF
    tumor necrosis factor
    AA
    adjuvant arthritis
    BMC
    bone mineral content
    OVX
    ovariectomized
    RA
    rheumatoid arthritis
    • Received July 14, 1999.
    • Accepted September 2, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 291 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 291, Issue 3
1 Dec 1999
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Research ArticleArticle

Idoxifene, a Novel Selective Estrogen Receptor Modulator, Is Effective in a Rat Model of Adjuvant-Induced Arthritis

Alison M. Badger, Simon M. Blake, Robert A. Dodds, Don E. Griswold, Barbara A. Swift, David J. Rieman, George B. Stroup, Sandra J. Hoffman and Maxine Gowen
Journal of Pharmacology and Experimental Therapeutics December 1, 1999, 291 (3) 1380-1386;

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Research ArticleArticle

Idoxifene, a Novel Selective Estrogen Receptor Modulator, Is Effective in a Rat Model of Adjuvant-Induced Arthritis

Alison M. Badger, Simon M. Blake, Robert A. Dodds, Don E. Griswold, Barbara A. Swift, David J. Rieman, George B. Stroup, Sandra J. Hoffman and Maxine Gowen
Journal of Pharmacology and Experimental Therapeutics December 1, 1999, 291 (3) 1380-1386;
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