癌症病人使用雙磷酸鹽類致顎骨壞死之風險評估--統合分析

Risk of Osteonecrosis of Jaw Caused by Bisphosphonates in Cancer Patients: a Meta-Analysis

林小卿(Hsiao-Ching Lin)

指導教授 ： 林双金

高雄醫學大學/藥學院/藥學研究所碩士在職專班/碩士(2014年)

https://doi.org/10.6832/KMU.2014.00014

摘要

【目 的】: 評估癌症病人使用雙磷酸鹽類藥物導致顎骨壞死發生之風險
【研究方法】:
於PubMed 與Cochrane Central Register of Controlled Trials電子資料庫(January 1, 1999- October 2013)進行系統性文獻搜尋。任何探討癌症病人使用雙磷酸鹽類藥物發生顎骨壞死之隨機控制組臨床試驗(randomized controlled trials,RCTs)或世代硏究(Cohort study)皆納入硏究，最終將評讀之研究資料以RevMan 統計軟體 (version 5.0)random-effect模式進行統合分析
【硏究結果】:此研究共收錄23篇RCTs及6篇Cohort studies，符合收納條件有10篇RCTs及4篇世代硏究，共630,355癌症病人，進行統合分析。其中RCTs共7480人使用雙磷酸鹽類，發生顎骨壞死的機率為
0.401% (30/7480)，而非用藥組則只有一人發生顎骨壞死，機率為0.013% (1/7494)。統合分析發現雙磷酸鹽治療組發生顎骨壞死之勝算是無接受治療組的4.32倍(OR，4.32，95% CI:1.65,11.33)。另分析4篇
Cohort studies，發現使用針劑型的雙磷酸鹽類發生顎骨壞死機率為使用口服劑型的雙磷酸鹽之五倍(OR 6.1，95% CI: 3.70∼10.07 vs OR 1.18,95% CI: 0.88∼1.57)。
【結 論】:癌症病人使用雙磷酸鹽類時，會增加顎骨壞死的風險。因此所有的病人，在使用雙磷酸鹽藥物前應先進行完整的口腔評估與告知相關風險，並且要密切追蹤後續不良反應之發生。

關鍵字

雙磷酸鹽類藥物 ； 顎骨壞死 ； 癌症病人

並列摘要

【Objectives】:
This meta-analysis aims to assess the incidence of osteonecrosis of the jaw (ONJ) associated with bisphosphonates in cancer patients .
【Methods】:
The literatures published on PubMed and the Cochrane Central Register of Controlled Trials databases (January 1, 1999- October 2013) were systematically searched. Any randomized controlled trials (RCTs) and cohort studies assessing the risk of ONJ associated with bisphosphonates in cancer patients were eligible for inclusion. Data were pooled using a random-effects model in RevMan statistical software (version 5.0).
【Results】:
Twenty-three RCTs and 6 cohort studies pertaining to the risk of ONJ associated with bisphosphonates in cancer patients were identified, in which 10 RCTs and 4 cohort studies were matched with the inclusion criteria. A total of 630,355 cancer patients were collected in all studies. About 0.401% patients (30/7480) who took bisphosphonates were reported ONJ in RCTs. Only one patient who did not taken bisphosphonates reported the occurrence of ONJ (1/7494, 0.013%). The results of pooled data of odds ratio reported in 10 RCTs indicated that the risk of ONJ associated with bisphosphonates compared with on treatment were 4.32 (95%CI;1.65,11.33). Pooled odds ratio of 4 cohort studies showed that the risk of ONJ associated with intravenous bisphosphonates was five-fold higher than the oral bisphosphonates (OR 6.10, 95% CI: 3.70- 10.07 vs OR 1.18, 95% CI: 0.88-1.57).
【Conclusions】:
The use of bisphosphonates in cancer patients are likely to be associated with increased risk of ONJ. All patients who are going to begin treatment with bisphosphonates should receive a comprehensive dental examination and be informed about the potential adverse effects of bisphosphonates. A recommendation of close monitor on cancer patients who have taken bisphosphonates was suggested.

並列關鍵字

bisphosphonates ； osteonecrosis of the jaw ； cancer patients

參考文獻

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2. Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg. 2003 Sep;61(9):1115-7.

3. Migliorati CA, Epstein JB, Abt E, et al. Osteonecrosis of the jaw and bisphosphonates in cancer: a narrative review. Nat Rev Endocrinol. 2011 Jan; 7(1):34-42.

4. Hoff AO, Toth B, Hu M, et al. Epidemiology and risk factors for osteonecrosis of the jaw in cancer patients. Ann N Y Acad Sci. 2011 Feb;1218(1):47-54.

5. Woo SB, Hellstein JW, Kalmar JR. Systematic Review: Bisphosphonates and Osteonecrosis of the Jaws. Ann Intern Med. 2006 May;144(10):753-61.