TY - JOUR

T1 - Sustained efficacy and safety of bazedoxifene in preventing fractures in postmenopausal women with osteoporosis

T2 - Results of a 5-year, randomized, placebo-controlled study

AU - Silverman, S. L.

AU - Chines, A. A.

AU - Kendler, D. L.

AU - Kung, A. W.C.

AU - Teglbjærg, C. S.

AU - Felsenberg, D.

AU - Mairon, N.

AU - Constantine, G. D.

AU - Adachi, J. D.

AU - Мазуренко, Сергей Олегович

N1 - Funding Information: This study was sponsored by Wyeth Research, which was acquired by Pfizer Inc in October 2009. The authors thank Monika Ciesielska for statistical analysis. Medical writing assistance for this manuscript was provided by Bo Choi, Ph.D., of MedErgy and was funded by Pfizer Inc. Funding Information: Dr. Silverman has served on advisory boards for Wyeth and Lilly and on the speakers bureau for Lilly. Dr. Kendler has served as a consultant/speaker for and has received research grants from Amgen, Biosante, Eli Lilly, GSK, Merck, Novartis, Nycomed, Pfizer, Procter & Gamble, Roche, Servier, Wyeth, and Zelos. Dr. Kung has served as an advisory board member/consultant/speaker for Eli Lilly, GSK, Merck, MSD (Asia Ltd), Procter & Gamble, Roche, sanofi-aventis, and Servier. Dr. Felsenberg has served as a consultant/speaker for Amgen, Bayer/Schering, Chugai, Eli Lilly, GSK, Merck/MSD, Novartis, Nycomed, Procter & Gamble, Roche, Servier, TEVA, and Wyeth. Dr. Adachi has served as a consultant/speaker for Amgen, Astra Zeneca, Eli Lilly, GSK, Merck, Novartis, Nycomed, Pfizer, Procter & Gamble, Roche, sanofi-aventis, Servier, Wyeth, and Bristol-Myers Squibb. Drs. Constantine, Mairon, and Chines were employees of Wyeth Research, which was acquired by Pfizer Inc in October 2009. All other authors report no conflicts of interest.

PY - 2012/1

Y1 - 2012/1

N2 - Summary In this 2-year extension of a 3-year study, bazedoxifene showed sustained efficacy in preventing new vertebral fractures in postmenopausal women with osteoporosis and in preventing non-vertebral fractures in higherrisk women. Bazedoxifene significantly increased bone mineral density and reduced bone turnover versus placebo and was generally safe and well tolerated. Introduction This study evaluated the efficacy and safety of bazedoxifene for the treatment of postmenopausal osteoporosis over 5 years. Methods A total of 4,216 postmenopausal women with osteoporosis were enrolled in this 2-year extension of a 3-year, randomized, double-blind, placebo-controlled, phase 3 trial. In the core study (N=7,492), subjects received bazedoxifene 20 or 40 mg/day, raloxifene 60 mg/day, or placebo. The raloxifene arm was discontinued after 3 years; subjects receiving bazedoxifene 40 mg were transitioned to bazedoxifene 20 mg after 4 years. Five-year findings are reported for bazedoxifene 20 and 40/20 mg and placebo. Endpoints included incidence of new vertebral fractures (primary) and non-vertebral fractures, and changes in bone mineral density (BMD) and bone turnover markers. Results At 5 years, the incidence of new vertebral fractures in the intent-to-treat population was significantly lower with bazedoxifene 20 mg (4.5%) and 40/20 mg (3.9%) versus placebo (6.8%; P<0.05), with relative risk reductions of 35% and 40%, respectively. Non-vertebral fracture incidence was similar among groups. In a subgroup of higher-risk women (n=1,324; femoral neck T-score ≤-3.0 and/or ≥1 moderate or severe or ≥2 mild vertebral fracture[s]), bazedoxifene 20 mg reduced non-vertebral fracture risk versus placebo (37%; P=0.06); combined data for bazedoxifene 20 and 40/20 mg reached statistical significance (34% reduction; P≤.05). Bazedoxifene significantly increased BMD and reduced bone turnover versus placebo (P≤0.05) and was generally safe and well tolerated. Conclusions The findings support a sustained anti-fracture effect of bazedoxifene on new vertebral fractures in postmenopausal osteoporotic women and on non-vertebral fractures in the higher-risk subgroup of women.

AB - Summary In this 2-year extension of a 3-year study, bazedoxifene showed sustained efficacy in preventing new vertebral fractures in postmenopausal women with osteoporosis and in preventing non-vertebral fractures in higherrisk women. Bazedoxifene significantly increased bone mineral density and reduced bone turnover versus placebo and was generally safe and well tolerated. Introduction This study evaluated the efficacy and safety of bazedoxifene for the treatment of postmenopausal osteoporosis over 5 years. Methods A total of 4,216 postmenopausal women with osteoporosis were enrolled in this 2-year extension of a 3-year, randomized, double-blind, placebo-controlled, phase 3 trial. In the core study (N=7,492), subjects received bazedoxifene 20 or 40 mg/day, raloxifene 60 mg/day, or placebo. The raloxifene arm was discontinued after 3 years; subjects receiving bazedoxifene 40 mg were transitioned to bazedoxifene 20 mg after 4 years. Five-year findings are reported for bazedoxifene 20 and 40/20 mg and placebo. Endpoints included incidence of new vertebral fractures (primary) and non-vertebral fractures, and changes in bone mineral density (BMD) and bone turnover markers. Results At 5 years, the incidence of new vertebral fractures in the intent-to-treat population was significantly lower with bazedoxifene 20 mg (4.5%) and 40/20 mg (3.9%) versus placebo (6.8%; P<0.05), with relative risk reductions of 35% and 40%, respectively. Non-vertebral fracture incidence was similar among groups. In a subgroup of higher-risk women (n=1,324; femoral neck T-score ≤-3.0 and/or ≥1 moderate or severe or ≥2 mild vertebral fracture[s]), bazedoxifene 20 mg reduced non-vertebral fracture risk versus placebo (37%; P=0.06); combined data for bazedoxifene 20 and 40/20 mg reached statistical significance (34% reduction; P≤.05). Bazedoxifene significantly increased BMD and reduced bone turnover versus placebo (P≤0.05) and was generally safe and well tolerated. Conclusions The findings support a sustained anti-fracture effect of bazedoxifene on new vertebral fractures in postmenopausal osteoporotic women and on non-vertebral fractures in the higher-risk subgroup of women.

KW - Bazedoxifene

KW - Fracture

KW - Osteoporosis

KW - Postmenopausal

KW - SERMs

UR - http://www.scopus.com/inward/record.url?scp=84857366519&partnerID=8YFLogxK

UR - http://www.ncbi.nlm.nih.gov/pubmed/?term=Mazurenko+S

U2 - 10.1007/s00198-011-1691-1

DO - 10.1007/s00198-011-1691-1

M3 - Article

C2 - 21779819

AN - SCOPUS:84857366519

VL - 23

SP - 351

EP - 363

JO - Osteoporosis International

JF - Osteoporosis International

SN - 0937-941X

IS - 1

ER -