Sien-Yu Ko MD , Jun-Fu Lin MSc , Ching-Heng Lin Ph.D , Yuan-Yang Cheng Ph.D
{"title":"骨质疏松症患者:用唑来膦酸代替阿仑膦酸治疗与缺血性卒中的高风险相关——一项真实世界的全球研究","authors":"Sien-Yu Ko MD , Jun-Fu Lin MSc , Ching-Heng Lin Ph.D , Yuan-Yang Cheng Ph.D","doi":"10.1016/j.jstrokecerebrovasdis.2025.108456","DOIUrl":null,"url":null,"abstract":"<div><h3>Aims</h3><div>We aimed to determine whether prolonged use of bisphosphonates increases the risk of ischemic stroke in the general population and in individuals with pre-existing cardiovascular conditions.</div></div><div><h3>Methods</h3><div>This is a retrospective cohort study adhering to the STROBE checklist. We assessed ischemic stroke incidence following alendronic or zoledronic acid treatment in 1,905,808 patients aged ≥55 years with osteoporosis using TriNetX data from January 1, 2002, to December 31, 2022. Patients were stratified by age and gender, and propensity score matching was used to minimize confounding. Analyses focused on the general population and subgroups with pre-existing atrial fibrillation or atherosclerosis. Hazard ratios were calculated at 5, 10, and 15 years post-index date, using alendronic acid users as the reference (HR = 1). The Kaplan–Meier analysis was used to estimate event-free survival over time.</div></div><div><h3>Results</h3><div>Zoledronic acid was associated with an increased ischemic stroke risk at 5, 10, and 15 years of follow-up compared to alendronic acid in the general population, in women, and in patients without pre-existing atrial fibrillation or aortic atherosclerosis. The Kaplan–Meier analysis of stroke-free survival at 15 years showed 85.9 % in the zoledronic acid group and 89.9 % in the alendronic acid group, with a hazard ratio of 1.22 (95 % confidence interval, 1.11–1.34).</div></div><div><h3>Conclusions</h3><div>Zoledronic acid was associated with an increased ischemic stroke risk compared to alendronic acid in the general population, in women, and in patients without pre-existing atrial fibrillation or aortic atherosclerosis. Therefore, we recommend long-term follow-up and strict management of stroke risk factors in these relatively vulnerable populations.</div></div>","PeriodicalId":54368,"journal":{"name":"Journal of Stroke & Cerebrovascular Diseases","volume":"34 11","pages":"Article 108456"},"PeriodicalIF":1.8000,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Patients with osteoporosis: Treatment with zoledronic acid instead of alendronic acid is associated with a higher risk of ischemic stroke - A real-world global study\",\"authors\":\"Sien-Yu Ko MD , Jun-Fu Lin MSc , Ching-Heng Lin Ph.D , Yuan-Yang Cheng Ph.D\",\"doi\":\"10.1016/j.jstrokecerebrovasdis.2025.108456\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Aims</h3><div>We aimed to determine whether prolonged use of bisphosphonates increases the risk of ischemic stroke in the general population and in individuals with pre-existing cardiovascular conditions.</div></div><div><h3>Methods</h3><div>This is a retrospective cohort study adhering to the STROBE checklist. We assessed ischemic stroke incidence following alendronic or zoledronic acid treatment in 1,905,808 patients aged ≥55 years with osteoporosis using TriNetX data from January 1, 2002, to December 31, 2022. Patients were stratified by age and gender, and propensity score matching was used to minimize confounding. Analyses focused on the general population and subgroups with pre-existing atrial fibrillation or atherosclerosis. Hazard ratios were calculated at 5, 10, and 15 years post-index date, using alendronic acid users as the reference (HR = 1). The Kaplan–Meier analysis was used to estimate event-free survival over time.</div></div><div><h3>Results</h3><div>Zoledronic acid was associated with an increased ischemic stroke risk at 5, 10, and 15 years of follow-up compared to alendronic acid in the general population, in women, and in patients without pre-existing atrial fibrillation or aortic atherosclerosis. The Kaplan–Meier analysis of stroke-free survival at 15 years showed 85.9 % in the zoledronic acid group and 89.9 % in the alendronic acid group, with a hazard ratio of 1.22 (95 % confidence interval, 1.11–1.34).</div></div><div><h3>Conclusions</h3><div>Zoledronic acid was associated with an increased ischemic stroke risk compared to alendronic acid in the general population, in women, and in patients without pre-existing atrial fibrillation or aortic atherosclerosis. Therefore, we recommend long-term follow-up and strict management of stroke risk factors in these relatively vulnerable populations.</div></div>\",\"PeriodicalId\":54368,\"journal\":{\"name\":\"Journal of Stroke & Cerebrovascular Diseases\",\"volume\":\"34 11\",\"pages\":\"Article 108456\"},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2025-09-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Stroke & Cerebrovascular Diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1052305725002332\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Stroke & Cerebrovascular Diseases","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1052305725002332","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Patients with osteoporosis: Treatment with zoledronic acid instead of alendronic acid is associated with a higher risk of ischemic stroke - A real-world global study
Aims
We aimed to determine whether prolonged use of bisphosphonates increases the risk of ischemic stroke in the general population and in individuals with pre-existing cardiovascular conditions.
Methods
This is a retrospective cohort study adhering to the STROBE checklist. We assessed ischemic stroke incidence following alendronic or zoledronic acid treatment in 1,905,808 patients aged ≥55 years with osteoporosis using TriNetX data from January 1, 2002, to December 31, 2022. Patients were stratified by age and gender, and propensity score matching was used to minimize confounding. Analyses focused on the general population and subgroups with pre-existing atrial fibrillation or atherosclerosis. Hazard ratios were calculated at 5, 10, and 15 years post-index date, using alendronic acid users as the reference (HR = 1). The Kaplan–Meier analysis was used to estimate event-free survival over time.
Results
Zoledronic acid was associated with an increased ischemic stroke risk at 5, 10, and 15 years of follow-up compared to alendronic acid in the general population, in women, and in patients without pre-existing atrial fibrillation or aortic atherosclerosis. The Kaplan–Meier analysis of stroke-free survival at 15 years showed 85.9 % in the zoledronic acid group and 89.9 % in the alendronic acid group, with a hazard ratio of 1.22 (95 % confidence interval, 1.11–1.34).
Conclusions
Zoledronic acid was associated with an increased ischemic stroke risk compared to alendronic acid in the general population, in women, and in patients without pre-existing atrial fibrillation or aortic atherosclerosis. Therefore, we recommend long-term follow-up and strict management of stroke risk factors in these relatively vulnerable populations.
期刊介绍:
The Journal of Stroke & Cerebrovascular Diseases publishes original papers on basic and clinical science related to the fields of stroke and cerebrovascular diseases. The Journal also features review articles, controversies, methods and technical notes, selected case reports and other original articles of special nature. Its editorial mission is to focus on prevention and repair of cerebrovascular disease. Clinical papers emphasize medical and surgical aspects of stroke, clinical trials and design, epidemiology, stroke care delivery systems and outcomes, imaging sciences and rehabilitation of stroke. The Journal will be of special interest to specialists involved in caring for patients with cerebrovascular disease, including neurologists, neurosurgeons and cardiologists.