Osteoporosis International

, Volume 24, Issue 1, pp 209–217 | Cite as

Results of indirect and mixed treatment comparison of fracture efficacy for osteoporosis treatments: a meta-analysis

  • N. FreemantleEmail author
  • C. Cooper
  • A. Diez-Perez
  • M. Gitlin
  • H. Radcliffe
  • S. Shepherd
  • C. Roux
Original Article



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.


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.


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.


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.


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.


Meta-analysis Mixed treatment comparison Osteoporosis Postmenopausal women Treatment efficacy 



The authors would like to acknowledge James Matcham for the technical statistical support and Sally Wade and Mandy Suggitt, on behalf of Amgen Inc., for the writing and editorial support.

Conflicts of interest

This study was funded by Amgen Inc. NF has received research grants from Amgen Inc. and has served as a consultant for Amgen Inc., Sanofi-Aventis, Pfizer, Wyeth, and Eli Lilly. CC has received consulting and lecture fees from Amgen Inc., GSK, Eli Lilly, Novartis, Servier, and Alliance for Bone Health. AD-P has received honoraria from or consulted for Amgen Inc., Novartis, Eli Lilly, and MSD and received research grants from the Alliance of Bone Health and Amgen Inc. CR has received research grants and/or honoraria from Amgen, MSD, Servier, Novartis, and Lilly. MG, HR, and SS are employees of and have stock ownership in Amgen Inc.

Supplementary material

198_2012_2068_MOESM1_ESM.doc (664 kb)
ESM 1 (DOC 663 kb)


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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2012

Authors and Affiliations

  • N. Freemantle
    • 1
    Email author
  • C. Cooper
    • 2
  • A. Diez-Perez
    • 3
  • M. Gitlin
    • 4
  • H. Radcliffe
    • 5
  • S. Shepherd
    • 6
  • C. Roux
    • 7
  1. 1.Department of Primary Care and Population HealthUniversity College LondonLondonUK
  2. 2.University of SouthamptonSouthamptonUK
  3. 3.Autonomous University of BarcelonaBarcelonaSpain
  4. 4.Amgen Inc.Thousand OaksUSA
  5. 5.Amgen Ltd.CambridgeUK
  6. 6.Amgen Ltd.UxbridgeUK
  7. 7.Paris Descartes UniversityParisFrance

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