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Review: Etidronate decreases vertebral but not nonvertebral fractures in postmenopausal women

Sophie Jamal, MD
[+] Article and Author Information

Source of funding: Not stated.

For correspondence: Dr. A. Cranney, Ottawa Hospital, Ottawa, Ontario, Canada. E-mail acranney@ottawahospital.on.ca.


Ann Intern Med. 2002;136(3):98. doi:10.7326/ACPJC-2002-136-3-098
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Question: In postmenopausal women, is etidronate effective and safe for treating postmenopausal osteoporosis and preventing fractures?

Data sources: Studies were identified by searching MEDLINE, HealthSTAR, EMBASE/Excerpta Medica, and Current Contents (1966 to 1998) with terms that include etidronate, osteoporosis, postmenopausal, diphosphonates, and bisphosphonates. Conference abstracts were hand searched, references of relevant articles were scanned, and experts were contacted.

Study selection: Published and unpublished studies were selected if they were randomized controlled trials (RCTs) of ≥ 1 year of duration in postmenopausal women; compared etidronate (using the intermittent cyclic method at 400 mg/d for 14 to 20 d, and then using calcium or vitamin D, or both) with placebo, calcium, vitamin D, or calcium plus vitamin D; and evaluated outcomes of fracture reduction, change in bone mineral density (BMD), or toxicity.

Data extraction: Data were extracted on participants, treatment type and duration, outcomes, method of densitometry, and methodologic quality.

Main results: 13 RCTs (1267 women), 9 (1010 women) of which reported vertebral fractures, met the selection criteria. 5 trials included women with established osteoporosis, and 8 trials included early postmenopausal women without osteoporosis. All studies ensured allocation concealment, and 12 used an intention-to-treat analysis. 6 trials were blinded, and 7 were unblinded.At 2 years, etidronate reduced vertebral fractures but had no effect on nonvertebral fractures or hip fractures alone (Table). At 3 years, etidronate was associated with greater percentage changes in BMD than was placebo at the lumbar spine (risk difference [RD] 4.3%, 95% CI 2.7% to 5.9%), at the femoral neck (RD 2.19%, CI 0.4% to 3.95%), and for the total body (RD 0.97%, CI 0.4% to 1.6%) but not at the distal forearm (RD 0.43%, CI −1.6% to 2.5%). Etidronate and placebo did not differ for the number of overall withdrawals.

Conclusion: In postmenopausal women, etidronate safely increases bone mineral density and decreases vertebral fractures but has no effect on nonvertebral or hip fractures.

Etidronate vs placebo in postmenopausal women at 2 years*

OutcomesWeighted event ratesRRR (95% CI)NNT (CI)
EtidronatePlacebo
Vertebral fractures5.9%10%40% (12 to 59)25 (14 to 91)
Nonvertebral fractures11.1%11.3%2% (−42 to 32)Not significant
RRI (CI)NNH
Hip fractures1.7%1.4%20% (−63 to 288)Not significant

*Abbreviations defined in Glossary; RRR, RRI, NNT, NNH, and CI calculated from data in article using a fixed-effects model.

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