This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Google Scholar Articles by Bolognese, M. Articles by Omizo, M. PubMed PubMed Citation Articles by Bolognese, M. Articles by Omizo, M. Related Collections Calcium and Bone Metabolism Female Endocrinology

Effects of Arzoxifene on Bone Mineral Density and Endometrium in Postmenopausal Women with Normal or Low Bone Mass

Bethesda Health Research Center (M.B.), Bethesda, Maryland 20892; Lilly Research Laboratories (J.H.K., D.L.M., J.A., M.L.), Indianapolis, Indiana 46285; Rapid Medical Research (W.H.U.), Beachwood, Ohio 44122; Miami Research Associates (R.F.), Miami, Florida 33143; Illinois Bone and Joint Institute (S.B.), Morton Grove, Illinois 60053; and Oregon Osteoporosis Center (M.O.), Portland, Oregon 97225

Address all correspondence to: Dr. Michael Bolognese, Bethesda Health Research Center, Bone Health Center of Bethesda, 10215 Fernwood Road, Suite 40, Bethesda, Maryland 20817. E-mail: mbolognese{at}erols.com. Address requests for reprints to: Dr. John H. Krege, Eli Lilly and Company, Lilly Corporate Center, Drop Code 4109, Indianapolis, Indiana 46285. E-mail: Kregejh{at}lilly.com.

Introduction: Arzoxifene, a benzothiophene estrogen agonist/antagonist, is being developed for prevention and treatment of osteoporosis and for risk reduction of invasive breast cancer in postmenopausal women.

Methods: The effects of arzoxifene 20 mg/d on bone mineral density (BMD), uterine safety, and overall safety were studied in the FOUNDATION study, a 2-yr randomized, placebo-controlled trial including 331 postmenopausal women with normal to low bone mass.

Results: Compared to placebo, arzoxifene significantly increased lumbar spine (+2.9%) and total hip (+2.2%) BMD. Arzoxifene decreased biochemical markers of bone metabolism compared to placebo. Changes in breast density were neutral or slightly decreased in the arzoxifene vs. placebo group. There was no evidence of endometrial hyperplasia or carcinoma in the arzoxifene group as assessed by central review of baseline and follow-up endometrial biopsies. There was no significant change between the groups in endometrial thickness assessed by transvaginal ultrasound. The incidence of uterine polyps and vaginal bleeding was not significantly different between the groups. Vulvovaginal mycotic infection was the only adverse event significantly increased in the arzoxifene vs. placebo group. Hot flushes were not significantly different between the groups.

Conclusion: In postmenopausal women with normal to low bone mass, arzoxifene 20 mg/d increased BMD at the spine and hip and had a neutral effect on the uterus and endometrium.