Zarzour Fatima, Schousboe John T, Binkley Neil, Hans Didier, Leslie William D
Department of Medicine, University of Manitoba, Winnipeg, MB, R2H 2A6, Canada.
Park Nicollet Clinic and HealthPartners Institute, HealthPartners, Minneapolis, MN 55416, United States.
J Bone Miner Res. 2025 Jul 28;40(8):965-972. doi: 10.1093/jbmr/zjaf072.
Proton pump inhibitors (PPI) are widely prescribed medications. Proton pump inhibitors exposure may be associated with lower trabecular bone score (TBS), but has not shown a consistent effect on BMD. We hypothesized that abdominal obesity, which is associated with both gastroesophageal disease and PPI use, could confound the relationship between PPI use and TBS. We assessed the effect of PPI use on TBS (primary measurement) and BMD (secondary measurements) before and after adjustment for sagittal abdominal diameter (SAD), a DXA-derived measure of abdominal soft-tissue thickness. The study population comprised 60 930 individuals (90.3% women, mean age 65.7 yr) that included 11 340 (18.6%) with PPI use in the preceding 12 mo. PPI exposure was categorized from medication persistence ratio (MPR) as non-use (referent), minimal (MPR 0.01-0.25), mild (MPR 0.26-0.5), moderate (MPR 0.51-0.75), and high use (MPR 0.76-1). When logistic regression models were minimally adjusted for age, sex, and scanner, increasing PPI use versus non-use was associated with progressively increasing odds ratios (ORs) for TBS in the lowest tertile (minimal 1.11 [95% CI 1.02-1.22], mild 1.18 [1.04-1.34], moderate 1.34 [1.17-1.53], high 1.41 [1.31-1.52]) but inversely with osteoporotic BMD (minimal 0.97 [0.89-1.06], mild 0.85 [0.75-0.97], moderate 0.82 [0.72-0.94]), and high 0.76 [0.70-0.82]). Sagittal abdominal diameter was greater in PPI users than non-users. After further adjustment for SAD, PPI use was not associated with lower TBS or BMD. Similar patterns were seen in men and women, and for longer durations of PPI use. Among 4742 with a second DXA (mean interval 3.4 yr), PPI use was not associated with more rapid TBS or BMD loss compared to non-users. In conclusion, PPI use is associated with greater SAD, an indicator of abdominal obesity. SAD and other clinical variables have a confounding effect on TBS and BMD measurements. When fully adjusted, PPI exposure did not significantly decrease TBS or BMD.
质子泵抑制剂（PPI）是广泛使用的处方药。使用质子泵抑制剂可能与较低的小梁骨评分（TBS）有关，但对骨密度（BMD）尚未显示出一致的影响。我们推测，与胃食管疾病和PPI使用均相关的腹型肥胖可能会混淆PPI使用与TBS之间的关系。我们评估了在调整矢状腹径（SAD，一种通过双能X线吸收法得出的腹部软组织厚度测量值）前后，PPI使用对TBS（主要测量指标）和BMD（次要测量指标）的影响。研究人群包括60930名个体（90.3%为女性，平均年龄65.7岁），其中11340名（18.6%）在过去12个月内使用过PPI。根据药物持续使用比例（MPR）将PPI暴露分为未使用（参照组）、极少使用（MPR 0.01 - 0.25）、轻度使用（MPR 0.26 - 0.5）、中度使用（MPR 0.51 - 0.75）和高度使用（MPR 0.76 - 1）。当逻辑回归模型对年龄、性别和扫描仪进行最小程度调整后，与未使用PPI相比，PPI使用量增加与最低三分位数的TBS的比值比（OR）逐渐增加相关（极少使用1.11 [95%可信区间1.02 - 1.22]，轻度使用1.18 [1.04 - 1.34]，中度使用1.34 [1.17 - 1.53]，高度使用1.41 [1.31 - 1.52]），但与骨质疏松性BMD呈负相关（极少使用0.97 [0.89 - 1.06]，轻度使用0.85 [0.75 - 0.97]，中度使用0.82 [0.72 - 0.94]，高度使用0.76 [0.70 - 0.82]）。PPI使用者的矢状腹径大于未使用者。在进一步调整SAD后，PPI使用与较低的TBS或BMD无关。在男性和女性中以及PPI使用时间较长的情况下均观察到类似模式。在4742名进行了第二次双能X线吸收法检查（平均间隔3.4年）的患者中，与未使用者相比，PPI使用与TBS或BMD更快丢失无关。总之，PPI使用与更大的SAD相关，SAD是腹型肥胖的一个指标。SAD和其他临床变量对TBS和BMD测量有混杂影响。在进行充分调整后，PPI暴露并未显著降低TBS或BMD。
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