Etidronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women

Cochrane Database Syst Rev. 2008 Jan 23;2008(1):CD003376. doi: 10.1002/14651858.CD003376.pub3.


Background: Osteoporosis is an abnormal reduction in bone mass and bone deterioration leading to increased fracture risk. Etidronate belongs to the bisphosphonate class of drugs which act to inhibit bone resorption by interfering with the activity of osteoclasts.

Objectives: To assess the efficacy of etidronate in the primary and secondary prevention of osteoporotic fractures in postmenopausal women.

Search strategy: We searched CENTRAL, MEDLINE and EMBASE for relevant randomized controlled trials published between 1966 to 2007.

Selection criteria: Women receiving at least one year of etidronate for postmenopausal osteoporosis were compared to those receiving placebo and/or concurrent calcium/vitamin D. The outcome was fracture incidence.

Data collection and analysis: Study selection and data abstraction was done in duplicate. Meta-analysis of fracture outcomes was performed with data presented as relative risks and a relative change greater than 15% was considered clinically important. Study quality was assessed through the reporting of allocation concealment, blinding and withdrawals.

Main results: Eleven studies representing a total of 1248 patients were included in the review.A significant 41% relative risk reduction (RRR) in vertebral fractures across eight studies (RR 0.59, 95% CI 0.36 to 0.96) was found. The six secondary prevention trials demonstrated a significant RRR of 47% in vertebral fractures (RR 0.53, 95% CI 0.32 to 0.87) and a 5% absolute risk reduction (ARR); compared with the pooled result for the two primary prevention trials (RR 3.03, 95% CI 0.32 to 28.44), which was not significant. There were no statistically significant risk reductions for non-vertebral (RR 0.98, 95% CI 0.68 to 1.42), hip (RR 1.20, 95% CI 0.37 to 3.88) or wrist fractures (RR 0.87, 95% CI: 0.32 to 2.36). For adverse events, no statistically significant differences were found in the included studies. However, observational data has led to concerns regarding potential risk for upper gastrointestinal injury.

Authors' conclusions: Etidronate, at 400 mg per day, demonstrated a statistically significant and clinically important benefit in the secondary prevention of vertebral fractures. No statistically significant reductions in vertebral fractures were observed when it was used for primary prevention. In addition, no statistically significant reductions in non-vertebral, hip, or wrist fractures were found, regardless of whether etidronate was used for primary or secondary prevention. The level of evidence for all outcomes is Silver (

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Bone Density / drug effects
  • Bone Density Conservation Agents / adverse effects
  • Bone Density Conservation Agents / therapeutic use*
  • Etidronic Acid / adverse effects
  • Etidronic Acid / therapeutic use*
  • Female
  • Hip Fractures / prevention & control
  • Humans
  • Osteoporosis, Postmenopausal / drug therapy*
  • Osteoporosis, Postmenopausal / prevention & control
  • Spinal Fractures / etiology
  • Spinal Fractures / prevention & control*
  • Wrist Injuries / prevention & control


  • Bone Density Conservation Agents
  • Etidronic Acid