Systematic review: comparative effectiveness of treatments to prevent fractures in men and women with low bone density or osteoporosis

Ann Intern Med. 2008 Feb 5;148(3):197-213. doi: 10.7326/0003-4819-148-3-200802050-00198. Epub 2007 Dec 17.


Background: Although several agents are available to treat osteoporosis, the relative efficacy and toxicity of these agents when used to prevent fractures has not been well described.

Purpose: To compare the benefits in fracture reduction and the harms from adverse events of various therapies for osteoporosis.

Data sources: MEDLINE (1966 to November 2007) and other selected databases were searched for English-language studies.

Study selection: For the efficacy analysis, investigators selected studies that reported the rate of or risk for fractures. For the adverse event analysis, they selected studies that reported the relationship between an agent and cardiovascular, thromboembolic, or upper gastrointestinal events; malignant conditions; and osteonecrosis.

Data extraction: Using a standardized protocol, investigators abstracted data on fractures and adverse events, agents and comparators, study design, and variables of methodological quality.

Data synthesis: Good evidence suggests that alendronate, etidronate, ibandronate, risedronate, zoledronic acid, estrogen, parathyroid hormone (1-34), and raloxifene prevent vertebral fractures more than placebo; the evidence for calcitonin was fair. Good evidence suggests that alendronate, risedronate, and estrogen prevent hip fractures more than placebo; the evidence for zoledronic acid was fair. The effects of vitamin D varied with dose, analogue, and study population for both vertebral and hip fractures. Raloxifene, estrogen, and estrogen-progestin increased the risk for thromboembolic events, and etidronate increased the risk for esophageal ulcerations and gastrointestinal perforations, ulcerations, and bleeding.

Limitation: Few studies have directly compared different agents or classes of agents used to treat osteoporosis.

Conclusion: Although good evidence suggests that many agents are effective in preventing osteoporotic fractures, the data are insufficient to determine the relative efficacy or safety of these agents.

Publication types

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

MeSH terms

  • Androgens / adverse effects
  • Androgens / therapeutic use
  • Bone Density Conservation Agents / adverse effects
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Density*
  • Calcium / adverse effects
  • Calcium / therapeutic use
  • Estrogen Replacement Therapy* / adverse effects
  • Estrogens / adverse effects
  • Estrogens / therapeutic use
  • Female
  • Fractures, Bone / etiology
  • Fractures, Bone / prevention & control*
  • Humans
  • Male
  • Osteoporosis / complications*
  • Risk Factors
  • Selective Estrogen Receptor Modulators / adverse effects
  • Selective Estrogen Receptor Modulators / therapeutic use*
  • Testosterone / adverse effects
  • Testosterone / therapeutic use
  • Vitamin D / adverse effects
  • Vitamin D / therapeutic use


  • Androgens
  • Bone Density Conservation Agents
  • Estrogens
  • Selective Estrogen Receptor Modulators
  • Vitamin D
  • Testosterone
  • Calcium