Effects of arzoxifene on bone, lipid markers, and safety parameters in postmenopausal women with low bone mass

• Published in: Osteoporosis international 2010-07, Vol.21 (7), p.1215-1226
• Main Authors: Downs, R. W. Jr, Moffett, A. M, Ghosh, A, Cox, D. A, Dowsett, S. A, Harper, K
• Format: Article
• Language: English
• Subjects: Aged; Arzoxifene; Biological and medical sciences; Biomarkers - blood; Bone Density - drug effects; Bone Density Conservation Agents - administration & dosage; Bone Density Conservation Agents - adverse effects; Bone Density Conservation Agents - therapeutic use; Bone Remodeling - drug effects; Bone turnover markers; Diseases of the osteoarticular system; Dose-Response Relationship, Drug; Double-Blind Method; Endocrinology; Endometrium - drug effects; Endometrium - pathology; Female; Fundamental and applied biological sciences. Psychology; Humans; Lipids - blood; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Original Article; Orthopedics; osteoporosis; Osteoporosis, Postmenopausal - blood; Osteoporosis, Postmenopausal - drug therapy; Osteoporosis, Postmenopausal - physiopathology; Osteoporosis. Osteomalacia. Paget disease; Piperidines - administration & dosage; Piperidines - adverse effects; Piperidines - therapeutic use; Raloxifene Hydrochloride - therapeutic use; Rheumatology; Safety; Selective estrogen receptor modulator; Selective Estrogen Receptor Modulators - administration & dosage; Selective Estrogen Receptor Modulators - adverse effects; Selective Estrogen Receptor Modulators - therapeutic use; Skeleton and joints; Thiophenes - administration & dosage; Thiophenes - adverse effects; Thiophenes - therapeutic use; Vasomotor System - drug effects; Vasomotor System - physiopathology; Vertebrates: osteoarticular system, musculoskeletal system
• ISSN: 0937-941X; 1433-2965
• DOI: 10.1007/s00198-009-1060-5

Summary In this Phase 2 study of postmenopausal women with low bone, arzoxifene (a selective estrogen receptor modulator (SERM)) significantly reduced bone turnover marker levels and increased bone mineral density (BMD) versus placebo. Arzoxifene generally had greater effects on bone turnover and BMD than raloxifene, a SERM in current clinical use. Arzoxifene's safety profile appeared similar to raloxifene. Introduction This 6-month, Phase 2, double-blind, placebo- and raloxifene-controlled study was designed to assess the effects of arzoxifene on bone turnover and overall safety in postmenopausal women with low bone mass. Methods Postmenopausal women (N = 219; mean age, 59 years) with a T-score between −1 and −2.5 were randomly assigned to daily arzoxifene 5, 10, 20, or 40 mg, raloxifene 60 mg, or placebo. All received daily calcium. Results All arzoxifene doses significantly reduced osteocalcin (primary endpoint), type 1 collagen C-telopeptide, bone specific alkaline phosphatase, and procollagen type I amino-terminal propeptide versus placebo, and increased lumbar spine BMD. Arzoxifene generally had greater effects on bone turnover and BMD than raloxifene. Arzoxifene decreased cholesterol, low-density lipoprotein cholesterol, and fibrinogen versus placebo. Endometrial thickness change with arzoxifene was not significantly different from placebo or raloxifene; no cases of endometrial hyperplasia or adenocarcinoma were observed. Adverse event reporting with arzoxifene was similar to that with raloxifene, as were hot flush and night sweat reporting. Conclusions Arzoxifene suppressed bone turnover and increased BMD. Within the limitations of this study, the endometrial safety profile of arzoxifene appeared similar to that of raloxifene. While no clear dose effect was evident, arzoxifene 20 and 40 mg/day appeared the optimal doses for reducing bone turnover.