Wright Ellen, Schofield Peter T, Molokhia Mariam
Department of Primary Care and Public Health Sciences, King's College London, London, UK.
BMJ Open. 2015 Dec 7;5(12):e007133. doi: 10.1136/bmjopen-2014-007133.
Concerns have been raised about a possible link between bisphosphonate use, and in particular alendronate, and upper gastrointestinal (UGI) cancer. A number of epidemiological studies have been published with conflicting results. We conducted a systematic review and meta-analysis of observational studies, to determine the risk of esophageal and gastric cancer in users of bisphosphonates compared with non-users.
We searched PubMed, MEDLINE, EMBASE, Web of Knowledge and Cochrane Database of Systematic Reviews for studies investigating bisphosphonates and esophageal or gastric cancer. We calculated pooled ORs and 95% CIs for the risk of esophageal or gastric cancer in bisphosphonate users compared with non-users. We performed a sensitivity analysis of alendronate as this was the most common single drug studied and is also the most widely used in clinical practice.
11 studies (from 10 papers) examining bisphosphonate exposure and UGI cancer (gastric and esophageal), met our inclusion criteria. All studies were retrospective, 6/11 (55%) case-control and 5/11(45%) cohort, and carried out using data from 5 longitudinal clinical databases. Combining 5 studies (1 from each database), we found no increased risk, OR 1.11 (95% CI 0.97 to 1.27) of esophageal cancer in bisphosphonate users compared with non-users and no increased risk of gastric cancer in bisphosphonate users, OR 0.96 (95% CI 0.82 to 1.12).
This is the fourth and most detailed meta-analysis on this topic. We have not identified any compelling evidence for a significantly raised risk of esophageal cancer or gastric cancer in male and female patients prescribed bisphosphonates.
人们对双膦酸盐类药物（尤其是阿仑膦酸盐）的使用与上消化道（UGI）癌症之间可能存在的联系表示担忧。已经发表了一些流行病学研究，但结果相互矛盾。我们对观察性研究进行了系统评价和荟萃分析，以确定双膦酸盐使用者与非使用者相比患食管癌和胃癌的风险。
我们在PubMed、MEDLINE、EMBASE、Web of Knowledge和Cochrane系统评价数据库中搜索了调查双膦酸盐与食管癌或胃癌的研究。我们计算了双膦酸盐使用者与非使用者相比患食管癌或胃癌风险的合并比值比（OR）和95%可信区间（CI）。由于阿仑膦酸盐是研究最常见的单一药物，也是临床实践中使用最广泛的药物，因此我们对其进行了敏感性分析。
11项研究（来自10篇论文）探讨了双膦酸盐暴露与UGI癌症（胃癌和食管癌），符合我们的纳入标准。所有研究均为回顾性研究，6/11（55%）为病例对照研究，5/11（45%）为队列研究，使用了5个纵向临床数据库的数据。综合5项研究（每个数据库1项），我们发现双膦酸盐使用者与非使用者相比患食管癌的风险没有增加，OR为1.11（95%CI为0.97至1.27），双膦酸盐使用者患胃癌的风险也没有增加，OR为0.96（95%CI为0.82至1.12）。
这是关于该主题的第四项也是最详细的荟萃分析。我们没有发现任何令人信服的证据表明，服用双膦酸盐的男性和女性患者患食管癌或胃癌的风险显著增加。
