Clinical review. Comparative effectiveness of drug treatments to prevent fragility fractures: a systematic review and network meta-analysis

J Clin Endocrinol Metab. 2012 Jun;97(6):1871-80. doi: 10.1210/jc.2011-3060.


Context: 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.

Data sources: We searched multiple databases through 12/9/2011.

Study selection: 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.

Data extraction: Reviewers working independently and in duplicate determined study eligibility and collected descriptive, methodological quality, and outcome data.

Data synthesis: 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.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Bone Density Conservation Agents / therapeutic use*
  • Calcium / therapeutic use
  • Denosumab
  • Fractures, Bone / etiology*
  • Fractures, Bone / prevention & control*
  • Humans
  • Osteoporosis / complications*
  • Osteoporosis / drug therapy*
  • Selective Estrogen Receptor Modulators / therapeutic use
  • Vitamin D / therapeutic use


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Bone Density Conservation Agents
  • Selective Estrogen Receptor Modulators
  • Vitamin D
  • Denosumab
  • Calcium