title: Bazedoxifene versus oral bisphosphonates for the prevention of nonvertebral fractures in postmenopausal women with osteoporosis at higher risk of fracture: a network meta-analysis.
abstract: OBJECTIVE
  To compare the efficacy of bazedoxifene and oral bisphosphonates for the prevention of nonvertebral fractures (NVFs) in women with higher risk of postmenopausal osteoporosis (i.e., the Fracture Risk Assessment Tool [FRAX] score ≥ 20%), based on currently available evidence from randomized controlled trials.
  
  
  METHODS
  Randomized controlled trials evaluating the NVF relative risk reduction (RRR) with oral bisphosphonates or bazedoxifene were identified by a systematic literature review and combined by means of a network meta-analysis. A subgroup of patients with a FRAX score of 20% or more in the bazedoxifene phase III osteoporosis study was selected as the population of interest on the basis of the bazedoxifene label. In one analysis (analysis 1), the placebo response of the subgroup with a FRAX score of 20% or more was the benchmark to select comparable bisphosphonate trials. Additional analyses incorporated the aggregate data from the bisphosphonate trials with all the FRAX subgroups (analysis 2) or with the individual patient data from the bazedoxifene trial (analysis 3).
  
  
  RESULTS
  Nine identified bisphosphonate trials (alendronate, ibandronate, risedronate; N = 23,440 patients) with a similar placebo response as observed for the subgroup of high risk patients in the bazedoxifene trial were included in analysis 1. The results of the network meta-analysis of this study set suggest that bazedoxifene is expected to have an RRR of 0.43 (95% credible interval [CrI] -0.19 to 0.72) versus alendronate, 0.58 (95% CrI 0.05-0.81) versus ibandronate, and 0.39 (95% CrI -0.29 to 0.70) versus risedronate. Analyses in which treatment effects with bisphosphonates were projected to a population with a FRAX score of 20% or more with meta-regression approaches (analysis 2 and analysis 3) provide similar findings.
  
  
  CONCLUSIONS
  Based on an indirect comparison of randomized trials, bazedoxifene is expected to have at least a comparable RRR of NVF as alendronate, ibandronate, and risedronate in women with higher risk of postmenopausal osteoporosis.
authors: Mapi, Boston, MA, USA.
authors: Alexandra G
authors: AG
authors: Ellis
authors: University of Liège, Belgium.
authors: Jean-Yves
authors: JY
authors: Reginster
authors: Pfizer, Inc., Groton, CT, USA.
authors: Xuemei
authors: X
authors: Luo
authors: Pfizer, Inc., Groton, CT, USA.
authors: Joseph C
authors: JC
authors: Cappelleri
authors: Pfizer Inc., Collegeville, PA, USA.
authors: Arkadi
authors: A
authors: Chines
authors: Pfizer, Inc., New York, NY, USA.
authors: Santosh
authors: S
authors: Sutradhar
authors: Mapi, Boston, MA, USA. Electronic address: jeroen.jansen@tufts.edu.
authors: Jeroen P
authors: JP
authors: Jansen
mesh_terms: D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D050723:Fractures, Bone / Q000517:prevention & control*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use*; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007211:Indoles; C447119:bazedoxifene
keywords: meta-analysis; osteoporosis; systematic review; treatment comparisons