Intervention Review

Alendronate 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.CD001155.pub2

How to Cite

Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Welch V, Coyle D, Tugwell P. Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD001155. DOI: 10.1002/14651858.CD001155.pub2.

Author Information

  1. 1

    University of Ottawa, Department of Epidemiology and Community Medicine, 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, CIET, 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

    University of Ottawa, Department of Medicine, Ottawa, Ontario, Canada

*George A Wells, Department of Epidemiology and Community Medicine, University of Ottawa, Room H1-1, 40 Ruskin Street, Ottawa, Ontario, K1Y 4W7, Canada. gawells@ottawaheart.ca.

Publication History

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

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

Osteoporosis is an abnormal reduction in bone mass and bone deterioration leading to increased fracture risk. Alendronate 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 alendronate 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 alendronate, for postmenopausal osteoporosis, were compared to those receiving placebo and/or concurrent calcium/vitamin D. The outcome was fracture incidence.

Data collection and analysis

We undertook study selection and data abstraction in duplicate. We performed meta-analysis of fracture outcomes using relative risks and a > 15% relative change was considered clinically important. We assessed study quality through reporting of allocation concealment, blinding and withdrawals.

Main results

Eleven trials representing 12,068 women were included in the review.

Relative (RRR) and absolute (ARR) risk reductions for the 10 mg dose were as follows. For vertebral fractures, a significant 45% RRR was found (RR 0.55, 95% CI 0.45 to 0.67). This was significant for both primary prevention, with 45% RRR (RR 0.55, 95% CI 0.38 to 0.80) and 2% ARR, and secondary prevention with 45% RRR (RR 0.55, 95% CI 0.43 to 0.69) and 6% ARR. For non-vertebral fractures, a significant 16% RRR was found (RR 0.84, 95% CI 0.74 to 0.94). This was significant for secondary prevention, with 23% RRR (RR 0.77, 95% CI 0.64 to 0.92) and 2% ARR, but not for primary prevention (RR 0.89, 95% CI 0.76 to 1.04). There was a significant 40% RRR in hip fractures (RR 0.60, 95% CI 0.40 to 0.92), but only secondary prevention was significant with 53% RRR (RR 0.47, 95% CI 0.26 to 0.85) and 1% ARR. The only significance found for wrist was in secondary prevention, with a 50% RRR (RR 0.50 95% CI 0.34 to 0.73) and 2% ARR.

For adverse events, we found no statistically significant differences in any included study. However, observational data raise concerns regarding potential risk for upper gastrointestinal injury and, less commonly, osteonecrosis of the jaw.

Authors' conclusions

At 10 mg per day, both clinically important and statistically significant reductions in vertebral, non-vertebral, hip and wrist fractures were observed for secondary prevention ('gold' level evidence, www.cochranemsk.org). We found no statistically significant results for primary prevention, with the exception of vertebral fractures, for which the reduction was clinically important ('gold' level evidence).

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Alendronate 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 alendronate for preventing fractures (broken bones) caused by osteoporosis.

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

- may prevent fractures in the spine, hip or wrist, or in bones other than the spine.

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

- probably prevents fractures in the spine

- probably leads to no difference in fractures of the hip, wrist or bones other than the spine.

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 injury to the throat, esophagus and stomach and, less commonly, reduced blood supply to the jaw bone, which causes the bone tissue to break down.

What is osteoporosis and what is alendronate?
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 are more likely to get osteoporosis after menopause.

Alendronate 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

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

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

Fracture in the hip or wrist

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

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

Fractures in bones other than the spine

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

               - 7 out of 100 women had a fracture when taking alendronate

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

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

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

 Fractures in bones other than the spine:

                 - 1 out of 100 women had a hip fracture when taking a placebo

                 - 1 out of 100 women had a hip fracture when taking alendronate

               - 3 out of 100 women had a wrist fracture when taking a placebo

                 - 4 out of 100 women had a wrist fracture when taking alendronate

 

                - 13 out of 100 women had a fracture somewhere other than the spine when taking a placebo

                 - 12 out of 100 women had a fracture somewhere other than the spine when taking alendronate

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

Alendronate 對於停經後婦女預防骨鬆骨折之原發性和次發性預防(文獻回顧)

骨質疏鬆乃因骨骼質量之不正常下降, 而導致骨折危險性增加。Alendronate 為雙磷酸鹽類之葯物,能耤由干擾蝕骨細胞之活性而抑制骨骼之吸收。

目標

評估 alendronate 在停經後婦女之骨鬆骨折之原發性和次發性預防效應。

搜尋策略

搜索在1966至2007年間所發表之相關隨機對照試驗。

選擇標準

比較女性使用 alendronate 與安慰劑(有或無同時服用鈣片及維生素D) 治療停經後骨質疏鬆至少一年之後,骨折之發生率。

資料收集與分析

本研究乃經由研究報告之選取及資料之摘錄,進行統合分析來評估骨折發生之相對風險,定義大於15%之相對改變為具有臨床上之重要意義。有根據所選報告的分組隱匿、盲法、及撤回等情況來評估該研究之品質。

主要結論

總共有11個臨床試驗,12,068位女性包括在本回溯研究中。使用10 mg之劑量對於相對風險減少率(RRR)和絕對風險減少率(ARR)的結果如下:對椎體骨折而言,有顯著的45%相對風險減少率 (RR 0.55, 95% CI 0.45 to 0.67);且在原發性和次發性預防均有顯著意義;一級預防之相對風險減少率為45% (RR 0.55, 95% CI 0.38 to 0.80),絕對風險減少率為2%。而次發性預防之相對及絕對風險減少率分別為45% (RR 0.55, 95% CI 0.43 to 0.69)及6%。 在非椎體骨折的預防上,則顯著的16%相對風險減少率 (RR 0.84, 95% CI 0.74 to 0.94);次發性預防方面,有顯著的相對及絕對風險減少率,分別為23% (RR 0.77, 95% CI 0.64 to 0.92) 和2%:但是在原發性預防方面卻無顯著的意義(RR 0.89, 95% CI 0.76 to 1.04)。就髖部骨折而言,相對風險減少率為40%,但僅在次發性預防上有顯著的降低,相對及絕對風險減少率分別為53% (RR 0.47, 95% CI 0.26 to 0.85)和1%。同樣地,在腕部骨折方面也僅在次發性預防上在顯著的降低,相對及絕對風險減少率分別50% (RR 0.50 95% CI 0.34 to 0.73)和2%。 而在不良反應方面,在涵蓋的不同研究報告間並無顯著的差異。.但觀察結果仍提高此藥對上腸胃道之傷害,以及雖較少發生的下頷部之骨壞死,這兩種不良反應的注意。

作者結論

每日10毫克之使用劑量,在椎體、非椎體、髖部及腕部骨折之二級預防上,具有臨床上之重要的及統計上之顯著意義的減少效果 (頂級實證,www.cochranemsk.org)。然而,在一級預防方面,除了對椎體骨折有統計上顯著意義的而且是臨床上重要的(頂級實證)減少效果外,對其它骨折並無有意義減少效果。

翻譯人

本摘要由林口長庚醫院陳昭宇翻譯。

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

總結

◆ 1. Alendronate對於停經後婦女骨鬆骨折之預防此一Cochrane文獻回顧之摘要報告指出(Alendronate對於停經後婦女骨鬆骨折之預防此一有關Cochrane文?回溯之摘要報告指出) 2.alendronate有預防椎體、髖部、腕部或其他椎體以外部位骨鬆骨折之效果。(alendronate有預防椎體、髖部、腕部或其是其他椎體以部位骨鬆骨折之效果。) 3.以及較少見的下頷部血流減少而引發之骨骼崩解。(以及較少見的下頷部血流減少而引發之軟組織及骨骼崩解。) ◆ Alendronate對於停經後婦女骨鬆骨折之預防 此一由Cochrane提出的回溯性報告之結論指出,從相關研究結果闡述對已被診斷為低骨密度而具骨折危險性,或是已有椎體骨折之婦女,alendronate有預防椎體、髖部、腕部或其是其他椎體以外部位骨鬆骨折之效果。 在骨密度趨近正常,或尚未有椎體骨折之婦女,alendronate可能僅對椎體骨折有預防效果,而對髖部,腕部或椎體以外之骨折,可能不具預防效果。 在副作用及併發症方面則較少有明確的資訊,特別是不常見但卻嚴重的副作用。可能有的副作用包括消化道的問題,如喉嚨、食道及胃部的傷害,以及較少見的下頷骨血流減少而引發之骨骼組織崩解。 什麼是骨質疏鬆及Alendronate? 骨骼是具活性且持續成長之組織。窮其一生,新舊骨細胞不斷生滅而產生了新的且更強壯的骨骼。而骨質疏鬆,新骨產生來不及更替已崩解之舊骨;並導致骨骼礦物質(如鈣質)之流失。如此一來,骨骼強度變弱,容易因輕微撞擊或跌倒而骨折。 經歷停經期之婦女比起其他人更可能有骨質疏鬆的情況。Alendronate屬於雙磷酸鹽類的葯物,可以減緩舊骨崩解。 對於已被診斷為骨質疏鬆而瀕臨骨折危險,或已經有椎體骨折的婦女,使用Alendronate後之最佳評估為:  椎體骨折減少6%  髖部或腕部骨折減少1%  非椎體之骨折減少2% 而對於骨密度近乎正常,或未有椎體骨折的婦女,使用Alendronate後之最佳評估為:  椎體骨折減少2%  髖部骨折比率無差別  腕部骨折增加1%  非椎體之骨折減少1%,有可能是機會效應。