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

慢性质子泵抑制剂治疗对骨矿物质密度和骨的影响

基本信息

批准号：
8527717
负责人：
YU-XIAO YANG
金额：
$ 52.04万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8527717
关键词：
1 year old Acids Address Adherence Adult Adverse effects Age Age-Years Attenuated Barrett Esophagus Binding Body mass index Bone Density Calcium Chronic Clinical Cohort Studies Control Groups Data Development Dimensions Disease Dose Drug Prescriptions Elderly Enzymes Equation Esophagitis Evaluation Food Fracture Frequencies Gastric Acid Gastric Parietal Cells Gastrins Gastroesophageal reflux disease H(+)-K(+)-Exchanging ATPase Health system Hip region structure Homocysteine Homocystine Hormones Hyperhomocysteinemia Least-Squares Analysis Life Long-Term Effects Malabsorption Syndromes Measurement Measures Modality Modeling Monitor Newly Diagnosed Non-Steroidal Anti-Inflammatory Agents Osteoblasts Output Parathyroid gland Patients Pennsylvania Peripheral Pharmaceutical Preparations Physiological Population Prevention Prevention strategy Principal Investigator Production Proton Pump Proton Pump Inhibitors Race Radial Recruitment Activity Regression Analysis Risk Risk Factors Safety Serum Stomach Structure Time Universities Vitamin B 12 Vitamin B 12 Deficiency Vitamins X-Ray Computed Tomography absorption base bisphosphonate bone bone health bone loss bone mass bone metabolism bone strength calcium absorption novel osteoporosis with pathological fracture parathyroid hyperplasia prevent prospective protective effect public health relevance response sex skeletal tool

项目摘要

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.

描述（由主要研究者提供）：质子泵抑制剂（PPI）是最广泛使用的药物之一。越来越多的患者长期持续服用这些强效抑酸剂治疗糜烂性食管炎、Barrett食管和预防非甾体抗炎药相关胃病。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丢失。此外，钙吸收不良和维生素B12缺乏都与骨矿物质密度（BMD）降低和骨质疏松性骨折风险增加有关。与这些数据相一致，最近的研究显示PPI治疗与骨质疏松性骨折风险之间存在正相关性。外周定量计算机断层扫描（pQCT）可以提供骨小梁和皮质体积BMD（vBMD）和尺寸的三维结构分析。这些数据对于有效评估长期PPI治疗对骨强度的影响至关重要。我们假设PPI治疗导致皮质和骨小梁vBMD、皮质尺寸和骨强度降低。我们的主要目标是：1）。比较长期PPI使用者和非使用者之间皮质和骨小梁vBMD、皮质尺寸和骨强度估计值随时间的变化; 2）。在PPI使用者中，确定平均PPI日剂量和PPI依从性程度是否是骨vBMD、尺寸和强度更大损失的预测因子; 3）。比较长期PPI使用者和非使用者PTH水平随时间的变化。拟议的研究将纵向测量在宾夕法尼亚大学卫生系统招募的年龄在55至75岁之间的两组受试者的桡骨和胫骨骨小梁和皮质vBMD和尺寸：1）。开始长期连续PPI治疗新诊断的糜烂性食管炎或Barrett食管的PPI初治患者; 2）。PPI非使用者与PPI使用者在种族、年龄、性别和体重指数方面的频率匹配。将在基线时获得pQCT测量值，然后在未来3年内每年获得一次。将使用广义估计方程或准最小二乘建模进行纵向回归分析，以比较两组之间骨强度pQCT指标的变化。这项研究解决了一个新的和重要的临床问题，有一个直接影响的骨骼健康的巨大人口的老年PPI用户。本研究的结果将有助于确定需要，强度，以及适当的选择模式监测BMD在这一人群中，并指导有效的策略，以防止和/或扭转酸抑制治疗的这种不利影响的发展。公共卫生相关性：质子泵抑制剂（PPI）是最广泛使用的药物之一。这些有效的胃酸抑制剂可能会降低骨密度，增加骨质疏松性骨折的风险。本研究将使用称为外周定量计算机断层扫描的有效放射学工具评估PPI治疗对骨强度的影响。该项目解决了一个新的和重要的临床问题，对数百万PPI使用者的骨骼健康有直接影响。本项目产生的数据将有助于确定慢性PPI使用者监测骨密度和骨结构的需求、强度以及适当的模式选择，并指导制定有效的策略来预防和/或逆转抑酸治疗的不良反应。