title: Clinical review. Comparative effectiveness of drug treatments to prevent fragility fractures: a systematic review and network meta-analysis.
abstract: BACKGROUND
  Osteoporosis and osteopenia are associated with increased fracture incidence.
  
  
  OBJECTIVE
  The aim of this study was to determine the comparative effectiveness of different pharmacological agents in reducing the risk of fragility fractures.
  
  
  METHODS
  We searched multiple databases through 12/9/2011.
  
  
  METHODS
  Eligible studies were randomized controlled trials enrolling individuals at risk of developing fragility fractures and evaluating the efficacy of bisphosphonates, teriparatide, selective estrogen receptor modulators, denosumab, or calcium and vitamin D.
  
  
  METHODS
  Reviewers working independently and in duplicate determined study eligibility and collected descriptive, methodological quality, and outcome data.
  
  
  RESULTS
  This network meta-analysis included 116 trials (139,647 patients; median age, 64 yr; 86% females and 88% Caucasians; median follow-up, 24 months). Trials were at low to moderate risk of bias. Teriparatide had the highest risk reduction of fractures (odds ratios, 0.42, 0.30, and 0.50 for hip, vertebral, and nonvertebral fractures, respectively) and the highest probability of being ranked first for efficacy (probabilities of 42, 49, and 79% for hip, vertebral, and nonvertebral fractures, respectively). However, differences to denosumab, zoledronate, risedronate, ibandronate, and alendronate were not statistically significant. Raloxifene and bazedoxifene were likely less effective, although these data were limited. Calcium and vitamin D were ineffective given separately but reduced the risk of hip fractures if given in combination (odds ratio, 0.81; 95% confidence interval, 0.68–0.96).
  
  
  CONCLUSIONS
  Teriparatide, bisphosphonates, and denosumab are most effective in reducing the risk of fragility fractures. Differences in efficacy across drugs are small; therefore, patients and clinicians need to consider their associated harms and costs.
authors.affiliation: College of Medicine, Mayo Clinic, The Knowledge and Evaluation Research Unit, Division of Endocrinology, Rochester, Minnesota 55905, USA. Murad.mohammad@mayo.edu
authors.forename: Mohammad Hassan
authors.initials: MH
authors.lastname: Murad
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Drake
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Mullan
authors.forename: Karen F
authors.initials: KF
authors.lastname: Mauck
authors.forename: Louise M
authors.initials: LM
authors.lastname: Stuart
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Lane
authors.forename: Nisrin O
authors.initials: NO
authors.lastname: Abu Elnour
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Erwin
authors.forename: Ahmad
authors.initials: A
authors.lastname: Hazem
authors.forename: Milo A
authors.initials: MA
authors.lastname: Puhan
authors.forename: Tianjing
authors.initials: T
authors.lastname: Li
authors.forename: Victor M
authors.initials: VM
authors.lastname: Montori
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D002118:Calcium / Q000627:therapeutic use; D000069448:Denosumab; D050723:Fractures, Bone / Q000209:etiology* / Q000517:prevention & control*; D006801:Humans; D010024:Osteoporosis / Q000150:complications* / Q000188:drug therapy*; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use; D014807:Vitamin D / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D020845:Selective Estrogen Receptor Modulators; D014807:Vitamin D; D000069448:Denosumab; D002118:Calcium