Bisphosphonate therapy for osteogenesis imperfecta

  • Review
  • Intervention

Authors


Abstract

Background

In osteogenesis imperfecta (OI) a genetic defect in type I collagen results in multiple fractures with little or no trauma. Bisphosphonates are used to attempt to reduce these fractures.

Objectives

To assess the effectiveness and safety of bisphosphonates in increasing bone mineral density (BMD), reducing fractures and improving clinical function in people with OI.

Search methods

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearches of journals and conference proceedings. We searched PubMed and major conference proceedings.

Register last searched: August 2008.

Selection criteria

Randomised and quasi-randomised controlled trials comparing bisphosphonates to placebo, no treatment, or comparator interventions in all types of OI.

Data collection and analysis

Two authors independently extracted data and assessed trial quality.

Main results

Eight studies (403 participants) were included. Data for oral bisphosphonates versus placebo could not be aggregated. A significant difference favouring bisphosphonates in fracture risk reduction and number of fractures was noted in one trial. No differences were reported in the remaining three trials. Two trials reported data for spine BMD; one found significantly increased lumbar spine density z scores at 12 months and one reported a significant increase in lumbar spine BMD at 12, 24 and 36 months; both favouring bisphosphonates. For intravenous bisphosphonates versus placebo, aggregated data from two trials showed no significant difference for the number of participants with at least one fracture, RR 0.56 (95% CI 0.30 to 1.06). In the remaining trial no significant difference was noted in fracture incidence. For spine BMD, no significant difference was noted in the aggregated data from two trials, MD 9.96 (95%CI -2.51 to 22.43). In the remaining trial a significant difference in mean per cent change in spine BMD z score favoured intravenous bisphosphonates at 6 and 12 months. One trial compared oral versus intravenous bisphosphonates and found no differences in primary outcomes. Data describing growth, bone pain, and functional outcomes after bisphosphonate therapy were incomplete.

Authors' conclusions

Evidence suggests oral or intravenous bisphosphonates increase BMD in children and adults with OI. These were not shown to be different in their ability to increase BMD; it is unclear whether either treatment decreases fractures. Additional studies may determine whether bisphosphonates improve clinical status (reduce fractures and pain; improve growth and functional mobility) in this population. Optimal method, duration of therapy and long-term safety of bisphosphonate therapy requires further investigation.

摘要

背景

以雙磷酸鹽藥物治療成骨不全症

成骨不全症(osteogenesis imperfecta,OI))因先天第一型膠原蛋白缺陷導致在輕微創傷或沒有創傷的情形下產生多發性骨折,使用雙磷酸鹽藥物可以減少這些骨折的發生。

目標

以骨質密度(bone mineral density (BMD))的增加,減少骨折的發生及改善成骨不全症患者的臨床功能,來評估雙磷酸鹽藥物的成效及安全性。

搜尋策略

我們搜尋Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references其包括了由廣泛的電子資料庫找出的參考文獻,並且人工搜尋期刊和研討會資料。我們主要搜尋PubMed和主要的研討會手冊。最後搜尋Register時間為:2008年8月。

選擇標準

以隨機及半隨機對照組之試驗方式,比較所有類型之成骨不全症患者在使用雙磷酸鹽藥物的或使用安慰劑或未治療或比較性治療下之影響

資料收集與分析

2位作者獨立地萃取出試驗數據並評估試驗的品質。

主要結論

收集8個試驗(共403位受試者)的試驗資料,但無法收集到口服雙磷酸鹽比較安慰劑的資料,其中一個試驗表示使用雙磷酸鹽藥物有顯著的減少骨折的發生率及次數,其餘3個試驗結果是沒有差異的,但有2個試驗報告表示在使用雙磷酸鹽藥物治療後脊椎骨質密度,其中1個發現Z分數在第12個月及在第12、24和36個月有顯著的增加,而該2個試驗皆較贊同使用雙磷酸鹽藥物。使用靜脈注射雙磷酸鹽藥物或安慰劑,從2個試驗所收集來的數據顯示無記載顯著的差異,至少有一名受試者骨折,RR 0.56 (95% CI 0.30 to 1.06)。其他的試驗組在骨折發生率上並無顯著的差異。在脊椎骨質密度上這2組試驗收集來的數據也沒有紀錄有顯著差異礦物質密度為9.96(95%CI−2.51−22.43)。但其他試驗組的脊椎骨質密度的z分數之平均百分比改變上,在使用靜脈注射雙磷酸鹽藥物治療後第6個月及第12個月有顯著的差異。其中一個試驗的初步結果顯示口服或靜脈注射雙磷酸鹽類藥物無差異。無完整的數據說明使用雙磷酸鹽藥物治療後的生長情形、骨頭疼痛和功能性結果等。

作者結論

實驗證明在成骨不全症的孩童或成人給於口服的或靜脈注射的磷酸鹽藥物可以增加骨質密度。但在這並沒有說明增加骨質密度能力的差異性,且不清楚治療後是否能降低骨折的發生。未來可以朝著雙磷酸鹽藥物對成骨不全症患者族群之臨床症狀的改善情形(如減少骨折、骨頭疼痛、改善身高和功能性移動)來研究。使用此藥物的最適模式、使用時程以及長期使用的的安全性則需進一步研究。

翻譯人

本摘要由臺灣大學附設醫院簡純青翻譯。

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

總結

雙磷酸鹽藥物治療成骨不全症:成骨不全症是一種遺傳疾病,先天第一型膠原蛋白異常,特性是低骨質密度、骨質脆弱、和因輕微或非外傷性骨折。成骨不全症的治療大多是支持性療法,但現今已有雙磷酸鹽藥物可以用來增加受影響之疾患之骨質密度和可能降低骨折的發生。我們回顧了8個隨機試驗,一些是使用安慰劑的對照組,有些是交叉試驗組,或兩者並行.在4個臨床試驗報告中顯示雙磷酸鹽藥物治療有減少骨折的情形,但另3個臨床試驗無顯著的差異。另一個臨床試驗證明減少了脊椎和上肢的骨折,但下肢的骨折並沒減少。每一個試驗皆證明雙磷酸鹽藥物能有效的改善骨質密度,無論是口服或靜脈注射未來更需進一步研究。骨折的發生率、骨頭疼痛、生長情形和生活品質等雙磷酸鹽藥物治療的指標。未來的研究需要確認雙磷酸鹽藥物是否能改善骨質密度的而減少骨折的發生和功能性的改善,及長期使用的效能及安全性。

Plain language summary

Bisphosphonate therapy for osteogenesis imperfecta

Osteogenesis imperfecta is an inherited disorder of type I collagen characterized by low bone mass, bone fragility, and fractures with minimal or no trauma. Treatment for the disorder is largely supportive, but recently bisphosphonate therapy has been employed in an attempt to increase bone mineral density and potentially reduce fracture incidence in affected individuals. We have included eight randomised trials, some placebo-controlled, some with a cross-over trial design, or both, in our review. Four trials report decreased fractures in some instances in those treated with bisphosphonates; however no significant difference was found in three other trials. Another trial demonstrated decreased vertebral and upper extremity but not lower extremity fractures. Each trial independently demonstrates significant improvements in bone mineral density after treatment with oral or intravenous bisphosphonates. Fracture incidence, bone pain, growth and quality of life indicators influenced by treatment with bisphosphonates warrant further investigation. Further investigation is needed to establish whether the improvements in bone mineral density translate into fracture reduction and functional improvements and to determine the long-term effectiveness and safety of their use.

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