Department of Pharmacy, Taichung Veterans General Hospital, Taichung, Taiwan.
Department of Pharmacy, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Clin Transl Sci. 2023 Nov;16(11):2198-2208. doi: 10.1111/cts.13620. Epub 2023 Sep 5.
Proton pump inhibitors (PPIs) are commonly prescribed medications. The existing data suggest that individuals at a high risk of fractures have been exposed to high doses of PPIs for prolonged durations. CYP2C19 plays a pivotal role in metabolism of PPIs and thereby influences their pharmacokinetic profile. Hence, we hypothesize that CYP2C19 genotypes may be associated with fragility fracture among PPIs users due to PPI exposure. This study aimed to investigate the association between CYP2C19 genotypes, bone mineral density (BMD), and osteoporotic fracture in a hospital-based population. This retrospective cohort study enrolled patients who were prescribed long-term PPIs at Taichung Veterans General Hospital using data extracted from the Taiwan Precision Medicine Initiative between January 2010 and April 2021. Associations between CYP2C19 phenotypes, comorbidities, and fractures in PPI users were analyzed. We enrolled 1518 long-term PPI users; 571 (38%), 727 (48%), and 220 (14%) CYP2C19 normal metabolizers (NMs), intermediate metabolizers (IMs), and poor metabolizers (PMs), respectively. Among them, 49 (3.2%) patients developed fractures within the 1-year follow-up period; 20 (3.5%) fractures in NMs, 24 (3.3%) in IMs, and 5 (2.3%) in PMs, respectively. No significant difference was observed among CYP2C19 genotypes and fracture. Additionally, BMD measurements during the 1-year follow-up period were made available among 75 participants. No significant difference in BMD between CYP2C19 PMs and non-PMs was found. This real-world, hospital-based study concludes that CYP2C19 PMs/IMs are not associated with an increased risk for fractures or reduced BMD in individuals on long-term PPI therapy.
质子泵抑制剂（PPIs）是常用的处方药物。现有数据表明，骨折风险较高的个体长期暴露于高剂量的 PPI 下。CYP2C19 在 PPI 的代谢中起着关键作用，从而影响其药代动力学特征。因此，我们假设 CYP2C19 基因型可能与 PPI 使用者的脆性骨折有关，因为 PPI 的暴露。本研究旨在调查 CYP2C19 基因型、骨密度（BMD）和骨质疏松性骨折之间的关联，研究对象为台中荣民总医院基于医院的人群。这项回顾性队列研究纳入了 2010 年 1 月至 2021 年 4 月期间，使用来自台湾精准医学倡议的数据，从台中荣民总医院开处长期 PPI 的患者。分析了 PPI 使用者中 CYP2C19 表型、合并症和骨折之间的关系。我们纳入了 1518 名长期 PPI 使用者；其中 571 名（38%）、727 名（48%）和 220 名（14%）分别为 CYP2C19 正常代谢者（NMs）、中间代谢者（IMs）和弱代谢者（PMs）。在 1 年的随访期间，有 49 名（3.2%）患者发生骨折；NMs 中 20 例（3.5%）、IMs 中 24 例（3.3%）、PMs 中 5 例（2.3%）。CYP2C19 基因型与骨折之间无显著差异。此外，在 75 名参与者中进行了 1 年随访期间的 BMD 测量。PMs 和非 PMs 之间的 BMD 无显著差异。这项真实世界、基于医院的研究得出结论，CYP2C19 PM/IM 与长期 PPI 治疗个体的骨折风险增加或 BMD 降低无关。
