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Meta-Analysis
. 2008 Jan 23;2008(1):CD003376.
doi: 10.1002/14651858.CD003376.pub3.

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

G A Wells  1 , A Cranney, J Peterson, M Boucher, B Shea, V Robinson, D Coyle, P Tugwell
Affiliations
Meta-Analysis

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

G A Wells et al. Cochrane Database Syst Rev. .

Update in

Abstract

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 (www.cochranemsk.org.).

PubMed Disclaimer

Conflict of interest statement

None at present.

The Cochrane Funding Arbitration Panel recommended withdrawal of the original review from The Cochrane Library. The original review was externally supported by Merck and Proctor & Gamble to support research staff.

This current review was updated without the support of any industry sponsor.

Figures

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1
FRACTURE Index (based on Black et al 2001)
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2
Five year risk of fracture by Quintiles of the FRACTURE Index: Assessment with bone mineral density
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3
Five year risk of fracture by Quintiles of the FRACTURE Index: Assessment without bone mineral density
4
4
Estimated five year age‐specific risks of first and subsequent osteoporotic fractures (from Doherty et al 2001)
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Summary of Findings Primary Prevention
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Summary of Findings Secondary Prevention
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Summary of Literature Search for Etidronate
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8
Weighted relative risk (RR) of fracture after etidronate (400 mg)
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9
Five year FRACTURE Index specific risk of fracture after etidronate (400mg)
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10
Five year age‐specific risk of first and subsequent fracture after etidronate (400 mg)
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Weighted relative risk (RR) of fracture with etidronate (400 mg): Person years
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Weighted relative risk of fracture after etidronate (400 mg) by years of treatment
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Weighted relative risk of fracture after etidronate (400 mg): Follow‐up denominators
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14
Weighted relative risk of fracture after etidronate (400 mg) by years of treatment: Follow‐up denominators
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Weighted relative risk (RR) of fracture after etidronate (400 mg): sensitivity analysis by baseline prevalent vertebral fracture site
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Summary of adverse drug events reported in randomized placebo‐controlled trials of etidronate (part 1)
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Summary of adverse drug events reported in randomized placebo‐controlled trials of etidronate (part 2)
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Summary of adverse drug events reported in randomized placebo‐controlled trials of etidronate (Part 3)
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19
Adverse drug reactions reported to CADRMP for etidronate, alendronate and risedronate
1.1
1.1. Analysis
Comparison 1 Etidronate 400 mg vs Control ‐ all years baseline denominators, Outcome 1 Vertebral Fractures.
2.1
2.1. Analysis
Comparison 2 Etidronate 400 mg vs Control ‐ all years baseline denominators, Outcome 1 Non Vertebral Fractures.
3.1
3.1. Analysis
Comparison 3 Etidronate 400 mg vs Control ‐ all years baseline denominators, Outcome 1 Hip Fractures.
4.1
4.1. Analysis
Comparison 4 Etidronate 400 mg vs Control ‐ all years baseline denominators, Outcome 1 Wrist Fractures.
5.1
5.1. Analysis
Comparison 5 Etidronate 400 mg vs Control ‐ 1 year baseline denominators, Outcome 1 Fractures.
6.1
6.1. Analysis
Comparison 6 Etidronate 400 mg vs Control ‐ 2 years baseline denominators, Outcome 1 Fractures.
7.1
7.1. Analysis
Comparison 7 Etidronate 400 mg vs Control ‐ 2 years baseline denominators, Outcome 1 Fractures.
8.1
8.1. Analysis
Comparison 8 Etidronate 400 mg vs Control ‐ 3 years baseline denominators, Outcome 1 Fractures.
9.1
9.1. Analysis
Comparison 9 Etidronate 400 mg vs Control ‐ 4 years baseline denominators, Outcome 1 Fractures.
10.1
10.1. Analysis
Comparison 10 Etidronate 400 mg vs Control ‐ all years baseline denominators, Outcome 1 Withdrawals due to side effects.
10.2
10.2. Analysis
Comparison 10 Etidronate 400 mg vs Control ‐ all years baseline denominators, Outcome 2 Withdrawals overall.
11.1
11.1. Analysis
Comparison 11 Etidronate 200 mg vs Control ‐ 2 years baseline denominators, Outcome 1 Sites.
See this image and copyright information in PMC

Update of

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