Intervention Review

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

  1. George A Wells1,*,
  2. Ann Cranney2,
  3. Joan Peterson3,
  4. Michel Boucher4,
  5. Beverley Shea5,
  6. Vivian Welch6,
  7. Doug Coyle7,
  8. Peter Tugwell8

Editorial Group: Cochrane Musculoskeletal Group

Published Online: 23 JAN 2008

Assessed as up-to-date: 13 NOV 2007

DOI: 10.1002/14651858.CD003376.pub3


How to Cite

Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Welch V, Coyle D, Tugwell P. Etidronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD003376. DOI: 10.1002/14651858.CD003376.pub3.

Author Information

  1. 1

    University of Ottawa Heart Institute, Cardiovascular Research Reference Centre, Ottawa, Ontario, Canada

  2. 2

    Ottawa Hospital, Division of Rheumatology, Ottawa, Ontario, Canada

  3. 3

    Ottawa Civic Hospital / Loeb Research Institute, Clinical Epidemiology Unit, Ottawa, Ontario, Canada

  4. 4

    HTA Development Canadian Agency for Drugs and Technologies in Health (CADTH), Ottawa, Ontario, Canada

  5. 5

    University of Ottawa, Institute of Population Health, Ottawa, Ontario, Canada

  6. 6

    University of Ottawa, Centre for Global Health, Institute of Population Health, Ottawa, Ontario, Canada

  7. 7

    Ottawa Health Research Institute, Epidemiology and Community Medicine, Ottawa, Ontario, Canada

  8. 8

    Ottawa Hospital, Centre for Global Health, Institute of Population Health, Department of Medicine, Ottawa, Ontario, Canada

*George A Wells, Cardiovascular Research Reference Centre, University of Ottawa Heart Institute, Room H1-1, 40 Ruskin Street, Ottawa, Ontario, K1Y 4W7, Canada. gawells@ottawaheart.ca.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 23 JAN 2008

SEARCH

 

Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. アブストラクト
  5. 摘要

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 methods

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.)

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. アブストラクト
  5. 摘要

Etidronate for preventing fractures caused by osteoporosis in postmenopausal women

This summary of a Cochrane review presents what we know from research about the effect of etidronate for preventing fractures (broken bones) caused by osteoporosis.

In women who have already been diagnosed with low bone density, putting them at risk of a fracture or have already had a fracture in the bones of their spine, etidronate:

-may prevent fractures in the bones of the spine.

- may lead to no difference in hip or wrist fractures or fractures in the bones other than in the spine.

In women whose bone density is closer to normal or who may not have had a fracture in the bones of their spine yet, etidronate:

- may lead to no difference in fractures in the bones of the spine, or in bones other than those of the spine.

- it is not known whether etidronate prevents hip or wrist fractures since no evidence was found that looked at the effect of etidronate in these women.

 

We often do not have precise information about side effects and complications. This is particularly true for rare but serious side effects. Possible side effects may include digestive problems such as heartburn, nausea and upset stomach.

What is osteoporosis and what is etidronate?
Bone is a living, growing part of your body. Throughout your lifetime, new bone cells grow and old bone cells break down to make room for the new, stronger bone. When you have osteoporosis, the old bone breaks down faster than the new bone can replace it. As this happens, the bones lose minerals (such as calcium). This makes bones weaker and more likely to break even after a minor injury, like a little bump or fall.

Women who have gone through menopause are more likely to get osteoporosis than other people. Etidronate belongs to the class of drugs called bisphosphonates. It is a type of medication that slows down the cells that break down the old bone.

The best estimate of what happens to women that have already been diagnosed with low bone density or have already had a fracture in the bones of their spine:

Fracture of the spine:

                 - 11 out of 100 women had a fracture when taking a placebo

                 - 6 out of 100 women had a fracture when taking etidronate

 

Fractures in bones other than the spine:

                 - 13 out of 100 women had a fracture when taking a placebo

                 - 14 out of 100 women had a fracture when taking etidronate

 

Fractures in the hip or wrist:

                 - there was no difference in the number of women who had hip or wrist fractures which may be the result of chance

 

 

The best estimate of what happens to women whose bone density is closer to normal or who may not yet have had a fracture in the bones of their spine:

 

Fracture of the spine

                 - 0 out of 100 women had a fracture when taking a placebo

                 - 1 out of 100 women had a fracture when taking etidronate

 

Fractures in bones other than the spine

                 - 11 out of 100 women had a fracture when taking a placebo

                 - 6 out of 100 women had a fracture when taking etidronate

 

For these women, fractures in the hip or wrist were not measured in the studies.

 

アブストラクト

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. アブストラクト
  5. 摘要

閉経後女性における骨粗鬆症性骨折の一次および二次予防のためのエチドロネート

背景

骨粗鬆症は骨量の異常減少と骨の劣化であり、骨折リスク増加につながる。エチドロネートはビスホスホネート系の医薬品クラスに属し、破骨細胞の活動を妨げることにより、骨吸収の抑制作用を示す。

目的

閉経後女性を対象に骨粗鬆症性骨折に対するエチドロネートの一次および二次予防の有効性を評価する。

検索戦略

1966年~2007年に発表された関連性のあるランダム化比較試験について、CENTRAL、MEDLINEおよびEMBASEを検索した。

選択基準

閉経後骨粗鬆症のためにエチドロネートを1年間以上投与した女性を、プラセボおよび/またはカルシウム/ビタミンDを同時投与した女性と比較した。アウトカムは骨折の罹患率とした。

データ収集と分析

研究の選択とデータ抽出は二重に行った。相対リスクとして表したデータを用いて骨折アウトカムのメタアナリシスを行い、15%を超える相対的変化を臨床的に重要であるとみなした。割付けの隠蔽化、盲検化、中止の報告を通して研究の質を評価した。

主な結果

計1248例の患者を対象とした11件の研究を本レビューに含めた。研究8件での脊椎骨折の相対リスク減少(RRR)は41%で、有意であった(RR 0.59、95%CI 0.36~0.96)。二次予防に関する6件の試験から、脊椎骨折のRRRは47%で有意であり(RR 0.53、95%CI 0.32~0.87)、絶対リスク減少(ARR)は5%であった。これに対して一次予防に関する2件の試験をプールした結果(RR 3.03、95%CI 0.32~28.44)は有意でなかった。非脊椎骨折(RR 0.98、95%CI 0.68~1.42)、大腿骨近位部骨折(RR 1.20、95%CI 0.37~3.88)、手首関節骨折(RR 0.87、95%CI 0.32~2.36)のそれぞれのリスクに、統計学的に有意な減少はみられなかった。有害事象について、選択した研究で統計学的な有意差はなかった。しかし、観察データから上部消化管損傷リスクの可能性が懸念された。

著者の結論

エチドロネートは1日400mgで、脊椎骨折の二次予防に統計学的に有意で臨床的にも重要な利益を示した。一次予防に使用した場合は、脊椎骨折に統計学的に有意な減少は認められなかった。さらに、エチドロネートを一次、二次予防のいずれかの目的で使用したにもかかわらず、非脊椎骨折、大腿骨近位部骨折、手首関節骨折に統計学的に有意な減少を認めなかった。すべてのアウトカムに対するエビデンスのレベルは「シルバー」である(www.cochranemsk.org)。

訳注

監  訳: 林 啓一,2008.4.1

実施組織: 厚生労働省委託事業によりMindsが実施した。

ご注意 : この日本語訳は、臨床医、疫学研究者などによる翻訳のチェックを受けて公開していますが、訳語の間違いなどお気づきの点がございましたら、Minds事務局までご連絡ください。Mindsでは最新版の日本語訳を掲載するよう努めておりますが、編集作業に伴うタイム・ラグが生じている場合もあります。ご利用に際しては、最新版(英語版)の内容をご確認ください。

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. アブストラクト
  5. 摘要

背景

Etidronate在初級預防及次級預防停經後婦女骨質疏鬆症引起的骨折

骨質疏鬆症因骨質密度降低而增加骨折的危險性。Etidronate是干擾噬骨細胞,而抑制骨骼吸收的雙磷酸鹽類藥物。

目標

研究Etidronate在初級預防及次級預防停經後婦女骨質疏鬆症引起的骨折效果。

搜尋策略

搜尋包括CENTRAL, MEDLINE and EMBASE之隨機對照控制臨床研究 (1966年到2007年)。

選擇標準

至少使用Etidronate一年,比較安慰劑或同時鈣/維生素D治療預防停經後婦女骨質疏鬆症。結果指標為骨折發生率。

資料收集與分析

兩位作者獨立進行資料摘錄。骨折發生率資料以相對風險﹝RR﹞及相對改變超過15% 為顯著。並以報告之分配隱密性、盲法、及退出率為方法的品質評估。

主要結論

11個研究包含1248例病患於分析中。8個研究顯示脊椎骨折相對減少風險(RRR) 41% (RR 0.59, 95% CI 0.36 to 0.96)。6個研究顯示次級預防脊椎骨折相對減少風險47% (RR 0.53, 95% CI 0.32 to 0.87)及5% 絕對減少風險(ARR, absolute risk reduction);比上2個初級預防研究(R .03, 95% CI 0.32 to 28.44)並未顯著差異。在減少非脊椎骨折方面,並未有顯著差異(RR 0.98, 95% CI 0.68 to 1.42),髖(R .20, 95% CI 0.37 to 3.88)或腕骨骨折(RR 0.87, 95% CI: 0.32 to 2.36)。副作用並未顯著差異。但觀察性研究顯示上消化道傷害之潛在風險。

作者結論

Etidronate每日400毫克口服次級預防脊椎骨折減少風險有顯著差異。初級預防脊椎骨折則並無顯著差異。此外,在非椎骨折,髖或腕骨骨折,無論次級初級預防上並無顯著差異。所有結果證據等級為銀(www.cochranemsk.org.)。

翻譯人

本摘要由林口長庚醫院余光輝翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

Etidronate預防停經後婦女骨質疏鬆症引起的骨折。 該Cochrane review概要介紹了我們所知道的etidronate來預防骨質疏鬆症引起的骨折。被診斷為骨質密度低的女性,常會陷入骨折的危險或已經發生脊椎骨折,Etidronate:可能預防脊椎骨骨折但在髖部骨折或手腕骨折或脊椎骨以外的骨折是沒有差異的。在骨骼密度接近正常或還沒有脊椎骨骨折的婦女,etidronate:對預防脊椎骨骨折或脊椎之外的其他骨頭沒有差異。目前還不知道是否etidronate可預防髖關節或手腕骨折。這是因為沒有證據表明etidronate在這些婦女的作用。我們往往沒有確切的資訊有關於etidronate的副作用和併發症。尤其是罕見但嚴重的副作用。可能的副作用包括消化系統的問題,如胃灼熱,噁心,胃部不適。什麼是骨質疏鬆症和etidronate是什麼?骨頭是活的,你的身體成長的一部分。在你整個一生中,新的骨細胞生長和舊的骨骼細胞分解留出空間給新的、更強的骨頭。當你有骨質疏鬆症時,舊骨質分解速度快於新骨可以代替它。當這種情況發生時,骨骼會失去礦物質(如鈣)。這使得骨頭較弱,更容易折斷,即使是輕微的損傷,像一個小的碰撞或跌倒。婦女在經歷更年期時比其他人更容易患骨質疏鬆症。Etidronate屬於所謂的雙膦酸鹽類藥物。這是一種藥物,可減慢細胞分解舊的骨頭。已經被確診為骨密度低婦女常陷入骨折的危險或已經發生脊椎骨折的風險, 使用Etidronate會發生什麼情況的最佳估計為:減少 5例脊椎骨折。在髖關節或手腕骨折則沒有區別。每100個會多出1個人有脊椎以外的骨頭骨折。這可能是偶然的結果。在骨骼密度接近正常或可能還沒有發生脊椎骨折的婦女上使用etidronate最樂觀估計會發生什麼變化:每100個會多出1個人有脊椎骨骨折,少5個婦女有脊椎骨以外的骨折。這可能是偶然的結果。對這些婦女而言,髖關節骨折或手腕骨折沒有在該試驗被測量。