title: Results of indirect and mixed treatment comparison of fracture efficacy for osteoporosis treatments: a meta-analysis.
abstract: Network meta-analysis techniques (meta-analysis, adjusted indirect comparison, and mixed treatment comparison [MTC]) allow for treatment comparisons in the absence of head-to-head trials. In this study, conditional estimates of relative treatment efficacy derived through these techniques show important differences in the fracture risk reduction profiles of marketed pharmacologic therapies for postmenopausal osteoporosis.
  
  
  BACKGROUND
  This study illustrates how network meta-analysis techniques (meta-analysis, adjusted indirect comparison, and MTC) can provide comparisons of the relative efficacy of postmenopausal osteoporosis therapies in the absence of comprehensive head-to-head trials.
  
  
  METHODS
  Source articles were identified in MEDLINE; EMBASE; Cochrane Central Register of Controlled Trials (CENTRAL) via Wiley Interscience; and Cumulative Index to Nursing and Allied Health Literature (CINAHL) between April 28, 2009 and November 4, 2009. Two reviewers identified English-language articles reporting randomized controlled trials (RCTs) with on-label dosing of marketed osteoporosis agents and fracture endpoints. Trial design, population characteristics, intervention and comparator, fracture outcomes, and adverse events were abstracted for analysis. Primary analyses included data from RCTs with fracture endpoints. Sensitivity analyses also included studies with fractures reported through adverse event reports. Meta-analysis compared fracture outcomes for pharmacological therapies vs. placebo (fixed and random effects models); adjusted indirect comparisons and MTC assessed fracture risk in postmenopausal women treated with denosumab vs. other agents.
  
  
  RESULTS
  Using data from 34 studies, random effects meta-analysis showed that all agents except etidronate significantly reduced the risk of new vertebral fractures compared with placebo; denosumab, risedronate, and zoledronic acid significantly reduced the risk for nonvertebral and hip fracture, while alendronate, strontium ranelate, and teriparatide significantly reduced the risk for nonvertebral fractures. MTC showed denosumab to be more effective than strontium ranelate, raloxifene, alendronate, and risedronate in preventing new vertebral fractures.
  
  
  CONCLUSIONS
  The conditional estimates of relative treatment efficacy indicate that there are important differences in fracture risk reduction profiles for marketed pharmacological therapies for postmenopausal osteoporosis.
authors: Department of Primary Care and Population Health, University College London, London, NW3 2PF, UK. nicholas.freemantle@ucl.ac.uk
authors: N
authors: N
authors: Freemantle
authors: C
authors: C
authors: Cooper
authors: A
authors: A
authors: Diez-Perez
authors: M
authors: M
authors: Gitlin
authors: H
authors: H
authors: Radcliffe
authors: S
authors: S
authors: Shepherd
authors: C
authors: C
authors: Roux
mesh_terms: D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000188:drug therapy*; D058866:Osteoporotic Fractures / Q000209:etiology / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D050071:Bone Density Conservation Agents