Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA.
Am J Gastroenterol. 2011 Jul;106(7):1209-18; quiz 1219. doi: 10.1038/ajg.2011.113. Epub 2011 Apr 12.
Proton pump inhibitors (PPIs) are widely used in several acid-related gastrointestinal disorders. In vivo studies have suggested that gastric suppression by PPIs could result in decreased intestinal calcium absorption. Subsequently, there have been concerns that the chronic use of a PPI is associated with an increased risk of bone fracture. However, the results of clinical studies are conflicting.
We performed a systematic review and meta-analysis of controlled observational studies to evaluate the risks of PPI use on fracture outcome. All controlled observational studies that compared fracture outcome in patients with PPI therapy with a control group were included. We calculated pooled odds ratios (ORs) using a random-effects model.
Of 1,668 identified studies, 10 (4 cohort and 6 case-control) with 223,210 fracture cases were included in our analysis. In PPI users, compared with non/past users, the OR for hip fracture (n=9) was 1.25 (95% confidence interval (CI)=1.14-1.37). The OR for vertebral fracture (n=4) was 1.50 (95% CI=1.32-1.72) and for wrist/forearm fracture (n=3) was 1.09 (95% CI=0.95-1.24). In subgroup analysis of hip fracture, this association was observed in both high-dose and low-dose PPI exposure. When stratified by duration of exposure, the short duration of PPI use was associated with increased risk of developing hip fracture (OR=1.24; 95% CI=1.19-1.28), whereas there was no significant increase in risk of hip fracture in long-term PPI users (OR=1.30; 95% CI=0.98-1.70). There was significant statistical and clinical heterogeneity among studies for the main analysis and most of the subgroup analyses.
Our results should be interpreted with caution. We found a modest association between PPI use and increased risk of hip and vertebral fractures, but no evidence of duration effect in subgroup analysis. However, observational studies cannot clarify whether the observed epidemiologic association is a causal effect or a result of unmeasured/residual confounding. Thus, randomized controlled studies are required to confirm or refute these results.
质子泵抑制剂 (PPI) 广泛用于多种酸相关胃肠道疾病。体内研究表明，PPI 对胃的抑制作用可能导致肠道钙吸收减少。随后，人们担心长期使用 PPI 会增加骨折风险。然而，临床研究结果存在矛盾。
我们对对照观察性研究进行了系统评价和荟萃分析，以评估 PPI 使用与骨折结局的风险。所有比较 PPI 治疗患者与对照组骨折结局的对照观察性研究均包括在内。我们使用随机效应模型计算汇总比值比 (OR)。
在 1668 项已确定的研究中，有 10 项（4 项队列研究和 6 项病例对照研究）共纳入 223210 例骨折病例。在 PPI 使用者中，与非/既往使用者相比，髋部骨折的 OR（n=9）为 1.25（95%置信区间 (CI)=1.14-1.37）。椎体骨折的 OR（n=4）为 1.50（95%CI=1.32-1.72），腕/前臂骨折的 OR（n=3）为 1.09（95%CI=0.95-1.24）。在髋部骨折的亚组分析中，这种关联在高剂量和低剂量 PPI 暴露中均观察到。按暴露持续时间分层时，短期 PPI 使用与髋部骨折风险增加相关（OR=1.24；95%CI=1.19-1.28），而长期 PPI 使用者髋部骨折风险无显著增加（OR=1.30；95%CI=0.98-1.70）。主要分析和大多数亚组分析中，研究之间存在显著的统计学和临床异质性。
我们的结果应谨慎解读。我们发现 PPI 使用与髋部和椎体骨折风险增加之间存在适度关联，但亚组分析中没有发现持续时间效应的证据。然而，观察性研究无法阐明观察到的流行病学关联是因果关系还是未测量/残留混杂的结果。因此，需要进行随机对照研究来证实或反驳这些结果。
