Investigational drug significantly increases lumbar spine and total hip BMD
Phase III data, published online in the Journal of Clinical Endocrinology & Metabolism (1) showed that arzoxifene, an investigational selective estrogen receptor modulator (SERM), significantly increased lumbar spine and total hip bone mineral density (BMD) in postmenopausal women with normal or low bone mass, versus placebo. In addition, arzoxifene, dosed at 20 mg/day, decreased biochemical markers of bone turnover, and showed a neutral effect on the uterus and endometrium. These data are from the "FOUNDATION" Study, one of three Phase III trials for arzoxifene. In this Phase III, double-blind, two-year, multi-center trial, 331 postmenopausal women with normal or low bone mass were randomized to receive arzoxifene 20 mg/day or placebo. All subjects received elemental calcium 500 mg/day. The study's primary endpoints were change in lumbar spine and total hip BMD, and endometrial safety measured by endometrial histology. The study included women who were at least two years postmenopausal and between the ages of 45 and 60 with an intact uterus. Subjects' femoral neck or lumbar spine T-scores were between 0 and -2.5, and they did not have pre-existing spine fractures. Arzoxifene significantly increased the lumbar spine BMD by 2.9% vs placebo and total hip BMD by 2.2% vs placebo. Arzoxifene significantly decreased biochemical marker of bone resorption C-terminal cross-linking telopeptide of type I collagen and biochemical marker of bone formation serum N-terminal propeptide of type I collagen. There was no significant difference overall in the number of subjects reporting adverse events in the arzoxifene group compared with the placebo group, with the exception of vaginal yeast infection. New or worsening hot flushes were not significantly different between the arzoxifene and placebo groups. And there were no significant differences in the incidence of endometrial hyperplasia or cancer between the arzoxifene and placebo groups, as assessed by serial endometrial biopsy or in endometrial thickness, as assessed by transvaginal ultrasound. There were no deaths or venous thromboembolic events. 1. Effects of Arzoxifene on Bone Mineral Density and Endometrium in Postmenopausal Women with Normal or Low Bone Mass. M. Bolognese, J. H. Krege, W. H. Utian et al. J Clin Endocrinol Metab published April 7, 2009 as doi:10.1210/jc.2008-2143