Lin Yang-Chi, Chiang Ping-Hao, Huang Jing-Yang, Wu Wen-Shiann
Department of Medical Education, Chung Shan Medical University Hospital, Taichung, Taiwan.
Department of Medical Education, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.
Osteoporos Int. 2025 Mar;36(3):411-422. doi: 10.1007/s00198-024-07356-2. Epub 2024 Dec 27.
This study examined the impact of thiazide and RAAS antihypertensive medications vs DHP-RAAS medications on fracture risk. The close alignment of such settings with clinical use, combined with the potential bone benefits of ACEis and ARBs, provides enhanced accuracy in bone health evidence.
To determine whether thiazides, combined with either angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB), offer bone-protective benefits compared with dihydropyridine (DHP) drugs combined with ACEi or ARB.
This retrospective cohort study was conducted on the US Collaborative Network from the TriNetX database on March 5th, 2024. It included hypertensive ACEi or ARB users under thiazide or DHP drug treatments spanning from January 1st, 2015, to December 31st, 2022, with exclusion criteria applied. The primary outcome is a composite typical osteoporotic fracture (TOPF). Kaplan Meier analyses were performed after 1:1 propensity-score matching (PSM) with a 5-year follow-up. Besides investigating fracture-related outcomes in thiazide-ACEi/ARB and DHP-ACEi/ARB users, this study explores whether the effects differ between ACEi and ARB users. Subgroup analyses were also performed, and the heterogeneity among the results was assessed using Cochran's Q-tests.
Post-PSM results yield 54,240 patients per cohort in the primary analysis, aging 61.5 ± 12.2 versus 61.4 ± 13.7 (thiazide-ACEi/ARB versus DHP-ACEi/ARB) with predominantly white ethnicity. Thiazide-ACEi/ARB users exhibit lower TOPF risk than DHP-ACEi/ARB users (hazard ratio (HR) = 0.65, 95% confidence interval (CI) 0.61-0.70), and such benefits from thiazides are similar between ACEi and ARB users (ACEi: HR = 0.69; ARB: HR = 0.67, Cochran's Q-test p-value = 0.78). Additionally, the effects of thiazides reveal significant heterogeneity between patients with and without inflammatory polyarthropathy (ICD-10, M05-M14) and benzodiazepine usage (Cochran's Q-test p-value = 0.01, 0.04).
Thiazides are associated with lower risks of typical osteoporotic fractures compared to DHP drugs in patients treated with ACEi or ARB, while such benefits may diminish in those with a diagnosis of inflammatory polyarthropathy and benzodiazepine usage.
本研究考察了噻嗪类和RAAS降压药物与二氢吡啶类RAAS药物对骨折风险的影响。这些研究背景与临床应用紧密相关，再加上ACEI和ARB对骨骼可能有益，提高了骨骼健康证据的准确性。
确定与二氢吡啶类（DHP）药物联合ACEI或ARB相比，噻嗪类药物联合血管紧张素转换酶抑制剂（ACEI）或血管紧张素II受体阻滞剂（ARB）是否具有骨骼保护作用。
2024年3月5日，在TriNetX数据库的美国协作网络上进行了这项回顾性队列研究。纳入2015年1月1日至2022年12月31日期间接受噻嗪类或DHP药物治疗的高血压ACEI或ARB使用者，并应用排除标准。主要结局是典型骨质疏松性骨折（TOPF）的复合结局。在1:1倾向评分匹配（PSM）后进行Kaplan Meier分析，并随访5年。除了调查噻嗪类-ACEI/ARB和DHP-ACEI/ARB使用者的骨折相关结局外，本研究还探讨了ACEI和ARB使用者之间的效果是否存在差异。还进行了亚组分析，并使用Cochran Q检验评估结果之间的异质性。
PSM后的结果在主要分析中每个队列产生54240名患者，年龄分别为61.5±12.2岁和61.4±13.7岁（噻嗪类-ACEI/ARB与DHP-ACEI/ARB），主要为白人种族。噻嗪类-ACEI/ARB使用者的TOPF风险低于DHP-ACEI/ARB使用者（风险比（HR）=0.65，95%置信区间（CI）0.61-0.70），并且噻嗪类药物对ACEI和ARB使用者的益处相似（ACEI：HR=0.69；ARB：HR=0.67，Cochran Q检验p值=0.78）。此外，噻嗪类药物的效果在有和没有炎症性多关节炎（ICD-10，M05-M14）和使用苯二氮䓬类药物的患者之间显示出显著异质性（Cochran Q检验p值=0.01，0.04）。
在接受ACEI或ARB治疗的患者中，与DHP药物相比，噻嗪类药物与典型骨质疏松性骨折风险较低相关，而在诊断为炎症性多关节炎和使用苯二氮䓬类药物的患者中，这种益处可能会减弱。
