Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, 410008, China.
Arthritis Research Canada, Richmond, V5Y3P2, Canada.
J Clin Endocrinol Metab. 2022 Aug 18;107(9):e3738-e3746. doi: 10.1210/clinem/dgac358.
Previous studies reported proton pump inhibitor (PPI) use may increase the risk of fracture; however, the findings may be susceptible to indication bias because peptic ulcer disease (PUD), 1 major indication for PPIs, may affect skeletal health. Determining whether PUD would increase hip fracture risk may help identify high-risk populations and explore risk factors.
We conducted a cohort study using data from The Health Improvement Network (THIN) in the United Kingdom. THIN contains patient information such as disease diagnosis and medicine prescriptions. Up to 5 non-PUD individuals (n = 138 265) were matched to each case of incident PUD (n = 27 653) by age, sex, and body mass index. We examined the association between PUD and hip fracture by a multivariable Cox proportional hazard model. We repeated the same analysis among individuals with incident PUD and gastroesophageal reflux disease (GERD) (n = 27 160), another disease with similar indication for PPIs, as a positive control exposure.
Over a mean of 5.6 years of follow-up, hip fracture occurred in 589 individuals with PUD and 2015 individuals without PUD (3.8 vs 2.6/1000 person-years), with a multivariable-adjusted hazard ratio (HR) being 1.44 (95% confidence interval [CI], 1.31-1.58). The association persisted among subgroups stratified by sex and age. In positive control exposure analysis, the hip fracture risk was also higher in PUD than GERD (3.8 vs 2.4/1000 person-years; multivariable-adjusted HR = 1.65; 95% CI, 1.45-1.7).
This general population-based cohort study suggests, after controlling for acid-lowering medication and other potential risk factors, PUD is independently associated with an increased risk of hip fracture.
先前的研究报告称质子泵抑制剂 (PPI) 的使用可能会增加骨折的风险；然而，这些发现可能容易受到指示性偏倚的影响，因为消化性溃疡病（PUD）是 PPI 的主要适应证之一，可能会影响骨骼健康。确定 PUD 是否会增加髋部骨折的风险可能有助于确定高危人群并探索风险因素。
我们使用英国的健康改进网络 (THIN) 中的数据进行了一项队列研究。THIN 包含患者信息，如疾病诊断和药物处方。每例新发 PUD（n=27653）匹配多达 5 名非 PUD 个体（n=138265），按年龄、性别和体重指数进行匹配。我们通过多变量 Cox 比例风险模型检查 PUD 与髋部骨折之间的关联。我们在另一项具有相似 PPI 适应证的疾病——胃食管反流病（GERD）（n=27160）的新发 PUD 个体中重复了相同的分析，作为阳性对照暴露。
在平均 5.6 年的随访期间，589 例 PUD 患者和 2015 例无 PUD 患者发生髋部骨折（3.8 比 2.6/1000 人年），多变量调整后的风险比（HR）为 1.44（95%置信区间 [CI]，1.31-1.58）。该关联在按性别和年龄分层的亚组中仍然存在。在阳性对照暴露分析中，PUD 患者的髋部骨折风险也高于 GERD（3.8 比 2.4/1000 人年；多变量调整后的 HR=1.65；95%CI，1.45-1.7）。
这项基于一般人群的队列研究表明，在控制了降低胃酸药物和其他潜在风险因素后，PUD 与髋部骨折风险增加独立相关。
