Interventions for the treatment of decreased bone mineral density associated with HIV infection

  • Review
  • Intervention

Authors


Abstract

Background

Decreased bone mineral density (BMD) occurs more commonly in patients with HIV than in the general population, making this group more susceptible to fragility fractures. However, bone loss is under-treated in patients with HIV.

Objectives

To assess the effects of interventions aimed at increasing bone mineral density in HIV-infected adults.

Search methods

We searched MEDLINE, EMBASE, LILACS, The Cochrane Library, Meeting Abstracts, AIDSTRIALS, ACTIS, Current Controlled Trials, National Institutes of Health Clinical Trials Registry, and CenterWatch (search date July 2006).

Selection criteria

Randomised trials comparing any pharmacological or non-pharmacological therapy with placebo, no treatment, or an alternative therapy, with the goal of increasing bone mineral density in adult (age 18 years or over) patients with HIV.

Data collection and analysis

Two reviewers independently assessed trial eligibility and quality, and extracted data. Where data were incomplete or unclear, conflicts were resolved with discussion and/or trial authors were contacted for further details.

Main results

Three completed randomised-controlled studies examined the role of alendronate in patients with HIV and osteopenia or osteoporosis. When all three studies were combined, much heterogeneity was seen (p<0.0001), most likely due to different populations and interventions. A sensitivity analysis showed that in two studies without heterogeneity (p=0.11), alendronate, calcium and vitamin D improved lumbar BMD after one year when compared with calcium and vitamin D (weighted mean difference +2.65 95% confidence interval (CI) 0.80, 4.51 percent). However the alendronate group did not have less fragility fractures, relative risk (RR) 1.28 (95% CI 0.20, 8.21), or osteoporosis, RR 0.50 (95% CI 0.24, 1.01). Adverse events were not significantly different between groups, RR 1.28 (95% 0.20, 8.21). One randomised-controlled study done in patients with AIDS wasting found that after three months, testosterone enanthane improved lumbar BMD compared to placebo by +3.70 (95% CI 0.48, 6.92) percent, but progressive resistance training did not improve lumbar BMD (+0.40 95% CI -2.81, 3.61 percent). No group in this study had any adverse effects.

Authors' conclusions

The very limited data reviewed showed that bisphosphonate therapy andin those with AIDS wasting syndrome, testosteronemay be safe and possibly effective methods to improve bone mineral density in HIV patients. The available studies are small, of short duration, and not powered to detect changes in WHO categories and fracture rates.

Larger studies using bisphosphonates are currently underway. The role of colecalciferol, androgen replacement in women, and growth hormone are also under investigation.

摘要

背景

人類免疫缺乏病毒感染者骨質密度減少的治療處置

人類免疫缺乏病毒感染的病患,骨質密度(bone mineral density, BMD)較正常人低,使得這群病患更容易發生脆弱性骨折(fragility fracture)。可是對於人類免疫缺乏病毒感染的病患骨質流失的治療是常被忽視的。

目標

評估針對HIV感染的成人這些增加骨質密度的處置是否有效。

搜尋策略

我們搜尋的文獻系統包括:MEDLINE、EMBASE、LILACS、考科藍圖書館(The Cochrane Library)、會議摘要(Meeting Abstracts)、愛滋病臨床試驗(AIDSTRIALS)、ACTIS、當今隨機對照臨床試驗註冊資料庫(Current Controlled Trials)、國家衛生研究院臨床試驗註冊資料庫(National Institutes of Health Clinical Trials Registry)、以及CenterWatch等(搜尋日期:2006年7月)。

選擇標準

我們所收案的必須為隨機臨床試驗,以藥物或非藥物治療法,與安慰劑、不治療、或是替代性療法相比,試驗目標為:使人類免疫缺乏病毒感染的成年病患(成年指的是在18歲以上)的骨密度增加。

資料收集與分析

有2個評論者各自獨立地評估試床試驗的合格性(eligibility)與品質並負責擷取資料。如果原始資料不完整或不清楚,則以討論的方式解決紛爭,或是直接聯絡作者來詢問進一步的細節。

主要結論

有3個完成的隨機對照研究檢驗了alendronate對於人類免疫缺乏病毒病患骨質缺少(osteopenia)或骨質疏鬆(osteoporosis)的角色。當3篇研究整合在一起時,其異質性(heterogeneity)很大(p值<0.0001),最可能是因為不同的研究族群與治療處置所致。進行敏感度分析後發現,其中2個沒有異質性的研究(p值=0.11)顯示,alendronate合併鈣質與維生素D使用1年後,比起使用鈣質與維生素D,可改善腰椎的骨質密度(加權平均差異(weighted mean difference)+2.65%,95%信賴區間0.80~4.51%)。但是alendronate治療組的病患,在脆弱性骨折或骨質疏鬆的發生率都沒有較低,二者的相對風險分別為1.28(95%信賴區間0.20~8.21)與0.50(95%信賴區間0.24~1.01)。副作用的發生率,在治療組和對照組間無顯著差異,相對風險為1.28(95%信賴區間0.20~8.21)。有1個隨機對照研究,研究對象是愛滋病患者併體質耗弱症候群(AIDS wasting),該研究發現,在使用睪固酮(testosterone enanthane) 3個月後,比起安慰劑可以增加腰椎骨質密度達3.70%(95%信賴區間0.48~6.92),而累進式阻抗訓練(progressive resistance training)則不會增進腰椎骨質密度(+0.40%,95%信賴區間−2.81~3.61)。這個研究裡兩組均沒有任何副作用。

作者結論

回顧這些非常有限的資料顯示,雙磷酸鹽類(bisphosphonate)及睪固酮(針對那些愛滋病患者併體質耗弱症候群)對於改善人類免疫缺乏病毒病患的骨質密度,可能是安全而有效果的。但目前已有的都是小型且時程短的研究,不足以偵測到在骨質密度的WHO分類的改變及骨折率。目前已有更大型的研究評估雙磷酸鹽類的效果,而維生素D3 (colecalciferol)、女性使用雄性素替代療法、以及生長激素等治療,都仍在研究中。

翻譯人

本摘要由臺北榮民總醫院鄧仲仁翻譯。

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

總結

骨質的流失和罹患骨質疏鬆的人有較高的骨折機率,因此發展出以藥物或非藥物介入性治療以改善人類免疫缺乏病毒感染者併有骨質疏鬆的骨質密度。量測一個人的骨密度是估量此人發生脆弱骨骨折的一個方法。人類免疫缺乏病毒感染者其骨質密度較正常人要減少,造成他們骨質密度減少的原因仍不明,可能是因為人類免疫缺乏病毒感染本身或是服用抗反轉錄病毒藥物所造成。雖然人類免疫缺乏病毒感染者常發生骨折,但目前證據顯示,他們的骨質流失常無法被有效治療。本篇評論性文章回顧了與人類免疫缺乏病毒感染者骨質流失治療相關的隨機對照臨床試驗。有3個臨床試驗評估以藥物alendronate治療能否改善人類免疫缺乏病毒感染者的骨質密度。這3個臨床試驗在收案的病患及採用的介入性治療都有所差異,但即使相類似的研究都不常有異質性。有另一個臨床試驗評估以睪固酮用於男性人類免疫缺乏病毒感染者或是愛滋病患者併體質耗弱症候群。本篇評論性文章所回顧的4篇研究所提供的資訊有限,主要因為這些研究都是小型且為期短時的研究,因此無法偵測到對骨折的預防效果或是罹患骨質疏鬆病患的減少;在研究設計上,也有一些不足之處。然而這些有限的資料顯示,alendronate做為人類免疫缺乏病毒感染者骨質密度減少的治療,以及睪固酮用於愛滋病患者併體質耗弱症候群,應該安全且可能是有效的。關於這骨質密度減少的治療,已有更大型進一步的研究正在進行中。

Plain language summary

Drug-based and non-drug-based interventions to improve the bone mineral density in patients living with HIV

Osteoporosis is caused by bone loss, and people who have the condition are at higher risk of having a fracture. Measuring a person's bone mass density (BMD) is a way to measure his or her risk of having a fracture due to fragile bones. Decreased BMD is much more common in HIV patients than in the general population. The cause of this decrease is not certain, but it may be because of the HIV infection itself or because of the antiretroviral medications that patients with HIV take. Although patients with HIV often get fractures because of their sometimes more fragile bones, it has been shown that this bone loss is often not effectively treated in this population. This review examines the randomised controlled trials investigating treatments for bone loss in patients with HIV infection.

Three trials examined the use of the drug alendronate to improve BMD in patients with HIV. These three studies were quite different from each other in terms of the populations studied and the interventions used, but even similar studies did not always have heterogeneity. A fourth study examined the use of testosterone in male patients with HIV and AIDS wasting syndrome. The four studies in this review were limited by the fact they were all very small and lasted a short amount of time, and thus they were unable to detect prevention of fractures or changes in number of patients with osteoporosis. There were also further compromises in study design. However, the limited available data show that there may be safe and perhaps effective treatments in the form of alendronate for patients with HIV who have decreased bone mineral density and, in those with AIDS wasting syndrome, testosterone.

Larger studies further examining the issue of decreased BMD are currently underway.

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