Effects of Gastric Bypass Surgery on Calcium Metabolism and the Skeleton

胃绕道手术对钙代谢和骨骼的影响

• 批准号: 8445148
• 负责人: Anne Louise Schafer
• 金额: --
• 依托单位: VETERANS AFFAIRS MED CTR SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8445148
• 关键词: 25-hydroxyvitamin D; Academic Medical Centers; Adipose tissue; Adult; Affect; Anthropometry; Bariatrics; Biology; Body Composition; Body Weight decreased; Body fat; Body mass index; Bone Density; Calcium; California; Chronic Disease; Clinical Research; Cohort Studies; Commit; Comorbidity; Data; Diabetes Mellitus; Dual-Energy X-Ray Absorptiometry; Eating; Endocrinologist; Endocrinology; Environment; Estrogens; Fatty acid glycerol esters; Fracture; Funding; Future; Gastric Bypass; General Population; Goals; Healthcare; High Prevalence; High Resolution Computed Tomography; Hip region structure; Hormones; Imaging Techniques; Individual; Intestines; Investigation; K-Series Research Career Programs; Knowledge; Malabsorption Syndromes; Master' s Degree; Measurement; Measures; Mediating; Medical Economics; Medical center; Mentors; Mentorship; Metabolic; Methods; Morbidity - disease rate; Obesity; Operative Surgical Procedures; Osteoporosis; Participant; Patients; Peripheral; Population; Porosity; Postoperative Period; Primary Health Care; Procedures; Prospective Studies; Provider; Radial; Radiology Specialty; Recommendation; Research; Research Design; Research Personnel; Resolution; Risk; San Francisco; Serum; Shapes; Signal Transduction; Skeleton; Structure; Surgeon; Testing; Thick; Tracer; Training; Universities; Vertebral column; Veterans; Visceral; Vitamin D; Vitamin D Deficiency; Weight; Weight-Bearing state; Woman; X-Ray Computed Tomography; bariatric surgery; bone; bone health; bone imaging; bone loss; bone mass; bone metabolism; bone turnover; calcium absorption; calcium metabolism; career; clinical care; cohort; design; diet and exercise; economic impact; experience; imaging modality; improved; interest; men; mortality; nutrition; patient oriented; patient population; prospective; public health relevance; screening; skeletal; skills; soft tissue; stable isotope; substantia spongiosa; tibia; tool

DESCRIPTION (provided by applicant): This is a VA Career Development Award-2 (CDA-2) application for Dr. Anne Schafer, an endocrinologist and Clinical Research Fellow at the San Francisco Veterans Affairs Medical Center (SFVAMC). Dr. Schafer is establishing herself as a young investigator in patient-oriented clinical research involving the cross-disciplinary fields of obesity, surgical weight loss, and bone metabolism. Obesity is a chronic disease of staggering proportions. Because weight loss through diet and exercise is difficult to attain and maintain, there is escalating interest in surgical weight loss procedures, including Roux-en-Y gastric bypass. Gastric bypass results in marked and durable weight loss and improvement in comorbidities in the general population and in our veteran patients. However, growing evidence indicates that gastric bypass can have negative effects on the skeleton, increasing bone turnover and decreasing bone mineral density (BMD). This is of critical concern given the tremendous impact of osteoporosis and fracture in both men and women. Vitamin D deficiency due to obesity and post-surgical malabsorption may partially explain the decline in bone mass observed after gastric bypass. Other factors are likely involved as well, such as non-vitamin D-mediated calcium malabsorption, signals related to decreased skeletal loading, and changes in fat-secreted hormones or estrogen (due to changes in fat mass and body composition). Dr. Schafer will characterize the effects of gastric bypass on calcium metabolism and the skeleton in a cohort of 60 men and women whose serum 25- hydroxyvitamin D levels are supplemented and maintained at e30 ng/mL. First, she will test the hypothesis that intestinal calcium absorption is impaired following gastric bypass, even in the setting of vitamin D sufficiency. She will do this by measuring fractional calcium absorption pre-operatively and 6 months post- operatively using dual stable isotopic tracers (Aim 1). Then, she will test the hypothesis that gastric bypass results in decreased BMD and in structural changes associated with impaired skeletal strength. She will do this by performing dual-energy X-ray absorptiometry (DXA), quantitative computed tomography (QCT), and high-resolution peripheral QCT (HR-pQCT) pre-operatively and 6 and 12 months post-operatively (Aim 2). QCT and HR-pQCT are advanced imaging techniques that have distinct advantages over standard methods but have not yet been applied to this population. Finally, she will assess body composition changes by anthropometry, DXA, and QCT, and changes in fat-secreted hormones, and she will evaluate the relationship between changes in skeletal parameters and changes in body composition and hormones (Aim 3). This research is expected to impact the clinical care of gastric bypass patients-veterans and non-veterans alike- by helping to shape recommendations about post-operative nutrition, BMD screening, and potential therapy. The proposed research will provide Dr. Schafer with preliminary data for a larger and longer-term prospective study of the skeletal effects of gastric bypass, which she will propose in a Merit Review application before the end of the CDA-2 period. The CDA-2 will also provide Dr. Schafer with crucial training required for her future career as a VA investigator. Specifically, she will acquire training in (1) design and execution of a prospective cohort study; (2) translational tools of metabolic research (e.g., stable isotope methods); (3) use and interpretation of advanced skeletal imaging modalities; and (4) body composition assessment. To achieve her training goals, Dr. Schafer has assembled a mentorship team comprised of experts in endocrinology, study design, surgery, and radiology. Her training will involve a combination of individual tutorials with her mentors and scientific advisors, hands-on experience, and formal coursework. She will complete a Masters Degree in Clinical Research at the University of California, San Francisco (UCSF) and will take advantage of the rich scientific environment at the SFVAMC and UCSF. Dr. Schafer is committed to improving the health care of veterans through clinical research, and the CDA-2 is critical for the attainment of her career objectives.

描述（由申请人提供）： 这是一个VA职业发展奖-2（CDA-2）的应用程序安妮谢弗博士，内分泌学家和临床研究员在旧金山弗朗西斯科退伍军人事务医疗中心（SFVAMC）。Schafer博士是一名年轻的研究者，从事以患者为导向的临床研究，涉及肥胖、手术减肥和骨代谢等跨学科领域。肥胖是一种比例惊人的慢性疾病。由于通过饮食和运动减肥很难达到和维持，因此对外科减肥手术的兴趣越来越大，包括Roux-en-Y胃旁路手术。胃旁路术在普通人群和我们的退伍军人患者中导致显著和持久的体重减轻和合并症的改善。然而，越来越多的证据表明，胃旁路手术可能对骨骼产生负面影响，增加骨转换和降低骨矿物质密度（BMD）。鉴于骨质疏松症和骨折对男性和女性的巨大影响，这一点至关重要。由于肥胖和术后吸收不良引起的维生素D缺乏可能部分解释胃旁路术后观察到的骨量下降。其他因素也可能涉及，如非维生素D介导的钙吸收不良，与骨骼负荷减少有关的信号，以及脂肪分泌激素或雌激素的变化（由于脂肪量和身体成分的变化）。Schafer博士将描述胃旁路手术对60名男性和女性的钙代谢和骨骼的影响，这些男性和女性的血清25-羟基维生素D水平补充并维持在e30 ng/mL。首先，她将检验胃旁路术后肠道钙吸收受损的假设，即使在维生素D充足的情况下。她将通过使用双稳定同位素示踪剂测量术前和术后6个月的钙吸收分数来完成这一点（目的1）。然后，她将检验胃旁路手术导致骨密度降低和与骨骼强度受损相关的结构变化的假设。她将在术前和术后6个月和12个月（目标2）进行双能X线吸收测定法（DXA）、定量计算机断层扫描（QCT）和高分辨率外周QCT（HR-pQCT）。QCT和HR-pQCT是先进的成像技术，与标准方法相比具有明显优势，但尚未应用于该人群。最后，她将通过人体测量、DXA和QCT评估身体成分的变化，以及脂肪分泌激素的变化，并评估骨骼参数变化与身体成分和激素变化之间的关系（目标3）。这项研究预计将影响胃旁路手术患者的临床护理-退伍军人和非退伍军人一样-通过帮助形成有关术后营养，BMD筛查和潜在治疗的建议。 这项拟议的研究将为Schafer博士提供初步数据，用于对胃旁路术对骨骼影响进行更大规模、更长期的前瞻性研究，她将在CDA-2期结束前的Merit审查申请中提出该研究。CDA-2还将为Schafer博士提供她未来作为VA调查员所需的关键培训。具体而言，她将获得以下方面的培训：（1）前瞻性队列研究的设计和执行;（2）代谢研究的转化工具（例如，稳定同位素方法）;（3）使用和解释先进的骨骼成像模式;（4）身体成分评估。为了实现她的培训目标，Schafer博士组建了一个由内分泌学、研究设计、外科和放射学专家组成的导师团队。她的培训将涉及与她的导师和科学顾问，实践经验和正式课程的个人教程相结合。她将在加州大学旧金山分校弗朗西斯科（UCSF）完成临床研究硕士学位，并将利用SFVAMC和UCSF丰富的科学环境。Schafer博士致力于通过临床研究改善退伍军人的医疗保健，CDA-2对实现她的职业目标至关重要。