Sustained efficacy and safety of bazedoxifene in preventing fractures in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled study.

Abstract

UNLABELLED:

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 higher-risk 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 < 0.05). 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.

• Authors: S L Silverman, A A Chines, D L Kendler, A W C Kung, C S Teglbjærg, D Felsenberg, N Mairon, G D Constantine, J D Adachi, Bazedoxifene Study Group
• Journal: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA (Osteoporos Int) Vol. 23 Issue 1 Pg. 351-63 (Jan 2012) ISSN: 1433-2965 [Electronic] England
• PMID: 21779819 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Bone Density Conservation Agents
• Indoles
• Placebos
• Selective Estrogen Receptor Modulators
• bazedoxifene

Topics

• Aged
• Bone Density (drug effects)
• Bone Density Conservation Agents (administration & dosage, adverse effects, therapeutic use)
• Bone Remodeling (drug effects)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Follow-Up Studies
• Humans
• Indoles (administration & dosage, adverse effects, therapeutic use)
• Middle Aged
• Osteoporosis, Postmenopausal (complications, drug therapy)
• Osteoporotic Fractures (etiology, prevention & control)
• Placebos
• Selective Estrogen Receptor Modulators (administration & dosage, adverse effects, therapeutic use)
• Spinal Fractures (etiology, prevention & control)
• Treatment Outcome