Lin Shu-Man, Lin Jhe-Yi, Tu Yu-Kang, Wu Chih-Hsing, Peng Carol Chiung-Hui, Munir Kashif M, Bukhari Khulood, Jaggon Kory, Fu Yunting, Loh Ching-Hui, Huang Huei-Kai
Department of Physical Medicine and Rehabilitation, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
School of Medicine, Tzu Chi University, Hualien, Taiwan.
Osteoporos Int. 2023 Sep;34(9):1625-1636. doi: 10.1007/s00198-023-06781-z. Epub 2023 May 30.
Previous studies have suggested that bisphosphonates may reduce stroke risk. This meta-analysis, which included 21 studies with 741,274 participants, revealed that bisphosphonates might be associated with lower stroke risk. However, evidence derived from randomized controlled trials identified no statistically significant association. Future high-quality studies are still required to determine causality.
Whether bisphosphonates may reduce the risk of stroke remains inconclusive. We conducted a systematic review and meta-analysis to evaluate the association between bisphosphonate use and the risk of stroke based on up-to-date evidence.
We searched for studies evaluating the effects of bisphosphonate on the risk of stroke from inception until January 3, 2022, on PubMed, Embase, Scopus, and Cochrane libraries and updated our search until August 22, 2022, using PubMed to identify any new potential published studies. Two or more reviewers independently screened articles, extracted data, and assessed the study quality. We retrieved the data to synthesize the pooled relative risk (RR) of stroke associated with bisphosphonate use compared with controls; random-effects models were used for meta-analysis.
A total of 21 studies (7 randomized controlled trials [RCTs] and 14 observational studies) involving 741,274 participants were included in our meta-analysis. Overall, bisphosphonate use was associated with a lower risk of stroke, but the result was only borderline significant (pooled RR = 0.87, 95% confidence interval [CI]: 0.76-0.99, p = 0.048), and high between-study heterogeneity was found (I = 83.7%). Subgroup analyses showed that the evidence derived from RCTs suggested no significant association between bisphosphonate use and stroke risk (pooled RR = 0.93, 95% CI: 0.76-1.13, p = 0.462; I = 13.4%).
Our results suggest that bisphosphonate use is associated with a lower risk of stroke. However, the current evidence does not lead to a definite conclusion due to the borderline statistical significance and high between-study heterogeneity. Future studies, especially RCTs, are necessary to assess causality.
以往研究表明双膦酸盐可能降低中风风险。这项荟萃分析纳入了21项研究，共741274名参与者，结果显示双膦酸盐可能与较低的中风风险相关。然而，来自随机对照试验的证据并未发现有统计学意义的关联。未来仍需要高质量研究来确定因果关系。
双膦酸盐是否可降低中风风险尚无定论。我们进行了一项系统评价和荟萃分析，以根据最新证据评估双膦酸盐使用与中风风险之间的关联。
我们在PubMed、Embase、Scopus和Cochrane图书馆中检索了从研究起始至2022年1月3日评估双膦酸盐对中风风险影响的研究，并使用PubMed更新检索至2022年8月22日，以识别任何新的潜在已发表研究。两名或更多评审员独立筛选文章、提取数据并评估研究质量。我们获取数据以综合双膦酸盐使用与对照组相比的中风合并相对风险（RR）；采用随机效应模型进行荟萃分析。
我们的荟萃分析共纳入21项研究（7项随机对照试验[RCT]和14项观察性研究），涉及741274名参与者。总体而言，使用双膦酸盐与较低的中风风险相关，但结果仅为临界显著（合并RR = 0.87，95%置信区间[CI]：0.76 - 0.99，p = 0.048），且研究间异质性较高（I² = 83.7%）。亚组分析显示，来自RCT的证据表明双膦酸盐使用与中风风险之间无显著关联（合并RR = 0.93，95% CI：0.76 - 1.13，p = 0.462；I² = 13.4%）。
我们的结果表明使用双膦酸盐与较低的中风风险相关。然而，由于统计学意义临界且研究间异质性较高，当前证据并未得出明确结论。未来的研究，尤其是RCT，对于评估因果关系是必要的。
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