Effect of Chronic Proton Pump Inhibitor Therapy on Bone Mineral Density and Bone

描述（由主要研究者提供）：质子泵抑制剂（PPIs）是最广泛使用的药物之一。对于糜烂性食管炎、巴雷特食管和非甾体抗炎药相关胃病的患者来说，长期持续服用这些强效抑酸药变得越来越普遍。PPI治疗导致血清胃泌素水平升高，并可能损害钙和食物结合的维生素B12的吸收。ppi诱导的高胃泌素血症对甲状旁腺有直接的营养作用，导致甲状旁腺增生、甲状旁腺激素分泌增加和骨质流失。此外，钙吸收不良和维生素B12缺乏与骨密度（BMD）降低和骨质疏松性骨折风险增加有关。与这些数据一致，最近的研究显示PPI治疗与骨质疏松性骨折的风险呈正相关。外周定量计算机断层扫描（pQCT）可以提供小梁和皮质体积骨密度（vBMD）和尺寸的三维结构分析。这些数据对于有效评估慢性PPI治疗对骨强度的影响是必要的。我们假设PPI治疗导致皮质和小梁vBMD、皮质尺寸和骨强度下降。我们的主要目标是：1)。比较长期PPI使用者和非PPI使用者的皮质和小梁vBMD、皮质尺寸和骨强度随时间的变化；2）. 在PPI使用者中，确定平均每日PPI剂量和PPI依从程度是否预测骨vBMD、尺寸和强度的更大损失；3）. 比较长期PPI使用者和非PPI使用者之间PTH水平随时间的变化。本研究将纵向测量宾夕法尼亚大学健康系统招募的两组年龄在55 - 75岁之间的受试者的桡骨、胫骨小梁和皮质vBMD和尺寸：1)。新诊断为糜烂性食管炎或巴雷特食管开始长期持续PPI治疗的患者；2）. 非PPI使用者的频率与PPI使用者的种族、年龄、性别和体重指数相匹配。pQCT测量将在基线时进行，然后在未来3年内每年进行一次。纵向回归分析将使用广义估计方程或准最小二乘模型来比较两组之间pQCT测量骨强度的变化。这项研究解决了一个新的和重要的临床问题，它对大量老年PPI使用者的骨骼健康有直接影响。当前研究的结果将有助于确定在这一人群中监测骨密度的必要性、强度以及适当选择的模式，并指导制定有效的策略来预防和/或逆转酸抑制治疗的这种不良影响。

DESCRIPTION (provided by principal investigator): Proton pump inhibitors (PPIs) are among the most widely used medications. It is becoming increasingly common for patients to take these potent acid suppressants on a long-term and continuous basis for erosive esophagitis, Barrett's esophagus and protection against nonsteroidal anti-inflammatory drug-related gastropathy. PPI therapy leads to elevated serum gastrin levels and may impair the absorption of calcium and food-bound vitamin B12. PPI-induced hypergastrinemia has a direct trophic effect on the parathyroid glands, leading to parathyroid hyperplasia, increased parathyroid hormone secretion and bone loss. Furthermore, both calcium malabsorption and vitamin B12 deficiency are associated with reduced bone mineral density (BMD) and increased osteoporotic fracture risk. Consistent with these data, recent studies revealed a positive association between PPI therapy and the risk of osteoporotic fractures. Peripheral quantitative computed tomography (pQCT) can provide a three-dimensional structural analysis of trabecular and cortical volumetric BMD (vBMD) and dimensions. These data are imperative for a valid assessment of the effect of chronic PPI therapy on bone strength. We hypothesize that PPI therapy leads to decreased cortical and trabecular vBMD, cortical dimensions and bone strength. Our primary aims are: 1). To compare the changes over time in cortical and trabecular vBMD, cortical dimensions and estimates of bone strength between long-term PPI users and non-users; 2). Among PPI users, to determine whether average PPI daily dose and extent of PPI adherence are predictors of greater loss in bone vBMD, dimensions and strength; 3). To compare the changes over time in PTH levels between long-term PPI users and non-users. The proposed study will longitudinally measure radial and tibial trabecular and cortical vBMD and dimensions in two groups of subjects between 55 to 75 years of age recruited at the University of Pennsylvania Health System:1). PPI-na¿ve patients who are starting long-term continuous PPI therapy for newly diagnosed erosive esophagitis or Barrett's esophagus; 2). PPI-non users frequency matched with the PPI users on race, age, sex and body mass index. The pQCT measurements will be obtained at baseline and then yearly over the next 3 years. Longitudinal regression analyses will be conducted using generalized estimating equations or quasi-least squares modeling to compare the changes in pQCT measures of bone strength between the two groups. This study addresses a novel and important clinical question that has a direct impact on the bone health of the enormous population of elderly PPI users. The results of the current study will help determine the need, the intensity, as well the appropriate choice of modality for monitoring BMD in this population and guide the development of effective strategies to prevent and/or reverse this adverse effect of acid suppressive therapy. PUBLIC HEALTH RELEVANCE: Proton pump inhibitors (PPIs) are among the most widely used medications. These potent stomach acid suppressants may reduce bone density and increase the risk of osteoporotic fractures. This study will assess the effect of PPI therapy on bone strength using a valid radiographic tool called peripheral quantitative computed tomography. This project addresses a novel and important clinical question that has a direct impact on the bone health of the millions of PPI users. The data generated by the current project will help determine the need, the intensity, as well the appropriate choice of modality for monitoring bone mineral density and bone structure among chronic PPI users and guide the development of effective strategies to prevent and/or reverse this adverse effect of acid suppressive therapy.