Health Management Center, Xiangya Hospital, Central South University, Changsha, Hunan, China; Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Harvard Medical School, Boston, MA, USA.
Bone. 2020 Oct;139:115502. doi: 10.1016/j.bone.2020.115502. Epub 2020 Jun 25.
Previous studies comparing risk of fracture among Proton Pump Inhibitors (PPIs) users with that among non-users were susceptible to confounding by indication. Epidemiologic studies of this association using an active medication as a comparator would appropriately address this bias. We conducted a propensity-score matched cohort study to compare the risk of incident fracture over five years among initiators of PPIs with initiators of histamine 2 receptor antagonist (H2RA) using data collected from The Health Improvement Network (THIN) database in the United Kingdom (2000-2016). The prevalence of PPIs prescription increased 3.8-fold from 2000 (7.9%) to 2012 (30.3%) and remained stable since then. Of the 50,265 propensity-score matched participants in each cohort (mean age was 65 years, and 57% were women), 370 (1.9/1000 person-years) incident hip fracture occurred in the PPIs initiators and 294 (1.5/1000 person-years) in the H2RA initiators during the follow-up period. The rate difference of incident hip fracture for PPIs initiation was 0.4 (95% confidence interval [CI]: 0.2-0.7)/1000 person-years compared with H2RA initiation and the corresponding hazard ratio (HR) was 1.27 (95%CI: 1.09-1.48). Compared with non-PPI use, multivariable-adjusted odds ratios (ORs) of hip fracture were 1.17 (95%CI: 0.94-1.46), 1.55 (95%CI: 1.23-1.96), and 1.67 (95%CI: 1.33-2.10) for 1-2, 3-9 and ≥ 10 prescriptions of PPIs, respectively (P for trend = 0.001). We found that PPIs prescription has been increasing rapidly over the past decade in the United Kingdom, and the initiation of PPIs was associated with a higher risk of hip fracture than initiation of H2RA.
先前比较质子泵抑制剂（PPIs）使用者和非使用者骨折风险的研究容易受到指示性混杂的影响。使用活性药物作为对照剂的此类关联的流行病学研究将适当地解决这种偏差。我们使用来自英国健康改善网络（THIN）数据库的数据进行了一项倾向评分匹配队列研究，以比较在过去五年中 PPI 使用者和组胺 2 受体拮抗剂（H2RA）使用者的骨折发生率（2000-2016 年）。PPIs 的处方率从 2000 年的 7.9%增加到 2012 年的 30.3%，此后一直保持稳定。在每个队列中，50265 名倾向评分匹配的参与者（平均年龄为 65 岁，57%为女性）中，370 名（1.9/1000 人年）发生髋部骨折，294 名（1.5/1000 人年）发生在 H2RA 使用者中在随访期间。与 H2RA 相比，PPIs 起始的髋部骨折发生率差异为 0.4（95%CI：0.2-0.7）/1000 人年，起始的风险比（HR）为 1.27（95%CI：1.09-1.48）。与非 PPI 相比，髋部骨折的多变量调整比值比（OR）分别为 1.17（95%CI：0.94-1.46）、1.55（95%CI：1.23-1.96）和 1.67（95%CI：1.33-2.10），分别为 1-2、3-9 和≥10 个 PPI 处方（P 趋势=0.001）。我们发现，在过去十年中，英国 PPI 的处方量迅速增加，与 H2RA 相比，PPIs 的起始与髋部骨折风险增加相关。
