title: Sustained efficacy and safety of bazedoxifene in preventing fractures in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled study.
abstract: 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.
  
  
  BACKGROUND
  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.affiliation: Cedars-Sinai Medical Center and University of California, Los Angeles, CA, USA. stuarts@slsdss.net
authors.forename: S L
authors.initials: SL
authors.lastname: Silverman
authors.forename: A A
authors.initials: AA
authors.lastname: Chines
authors.forename: D L
authors.initials: DL
authors.lastname: Kendler
authors.forename: A W C
authors.initials: AW
authors.lastname: Kung
authors.forename: C S
authors.initials: CS
authors.lastname: Teglbjærg
authors.forename: D
authors.initials: D
authors.lastname: Felsenberg
authors.forename: N
authors.initials: N
authors.lastname: Mairon
authors.forename: G D
authors.initials: GD
authors.lastname: Constantine
authors.forename: J D
authors.initials: JD
authors.lastname: Adachi
mesh_terms: D000368:Aged; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000188:drug therapy*; D058866:Osteoporotic Fractures / Q000209:etiology / Q000517:prevention & control*; D010919:Placebos; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016103:Spinal Fractures / Q000209:etiology / Q000517:prevention & control; D016896:Treatment Outcome
chemical_list: D050071:Bone Density Conservation Agents; D007211:Indoles; D010919:Placebos; D020845:Selective Estrogen Receptor Modulators; C447119:bazedoxifene