Comparative effectiveness of pharmacologic treatments to prevent fractures: an updated systematic review

Ann Intern Med. 2014 Nov 18;161(10):711-23. doi: 10.7326/M14-0317.


Background: Osteoporosis is a major contributor to the propensity to fracture among older adults, and various pharmaceuticals are available to treat it.

Purpose: To update a review about the benefits and harms of pharmacologic treatments used to prevent fractures in adults at risk.

Data sources: Multiple computerized databases were searched between 2 January 2005 and 4 March 2014 for English-language studies.

Study selection: Trials, observational studies, and systematic reviews.

Data extraction: Duplicate extraction and assessment of data about study characteristics, outcomes, and quality.

Data synthesis: From more than 52 000 titles screened, 315 articles were included in this update. There is high-strength evidence that bisphosphonates, denosumab, and teriparatide reduce fractures compared with placebo, with relative risk reductions from 0.40 to 0.60 for vertebral fractures and 0.60 to 0.80 for nonvertebral fractures. Raloxifene has been shown in placebo-controlled trials to reduce only vertebral fractures. Since 2007, there is a newly recognized adverse event of bisphosphonate use: atypical subtrochanteric femur fracture. Gastrointestinal side effects, hot flashes, thromboembolic events, and infections vary among drugs.

Limitations: Few studies have directly compared drugs used to treat osteoporosis. Data in men are very sparse. Costs were not assessed.

Conclusion: Good-quality evidence supports that several medications for bone density in osteoporotic range and/or preexisting hip or vertebral fracture reduce fracture risk. Side effects vary among drugs, and the comparative effectiveness of the drugs is unclear.

Primary funding source: Agency for Healthcare Research and Quality and RAND Corporation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review
  • Systematic Review

MeSH terms

  • Absorptiometry, Photon
  • Adult
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Bisphosphonate-Associated Osteonecrosis of the Jaw / etiology
  • Bone Density
  • Bone Density Conservation Agents / adverse effects
  • Bone Density Conservation Agents / therapeutic use*
  • Comparative Effectiveness Research
  • Denosumab
  • Female
  • Fractures, Bone / prevention & control*
  • Humans
  • Male
  • Neoplasms / chemically induced
  • Osteoporosis / drug therapy*
  • Osteoporotic Fractures / prevention & control*
  • Teriparatide / therapeutic use


  • Antibodies, Monoclonal, Humanized
  • Bone Density Conservation Agents
  • Teriparatide
  • Denosumab