Novel Risk Factors for Vertebral Fractures in Health and Chronic Kidney Disease

健康和慢性肾脏病中椎骨骨折的新危险因素

• 批准号: 8878251
• 负责人: Julie Paik
• 金额: $ 18.52万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-16 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8878251
• 关键词: Acidosis; Adolescent Medicine; Adult; Advisory Committees; Affect; Alcohol consumption; Animals; Bicarbonates; Biocompatible Materials; Biomechanics; Biometry; Bone Density; Bone Matrix; Calcium; Childhood; Chronic Kidney Failure; Clinical; Clinical Investigator; Clinical Research; Cohort Studies; Collagen; Committee Members; Complement; Data; Deformity; Densitometry; Deposition; Development; Diet; Dietary Factors; Doctor of Philosophy; Educational process of instructing; Endocrinologist; Epidemiologist; Epidemiology; Estrogens; Exposure to; Fatty acid glycerol esters; Fracture; Functional disorder; General Hospitals; General Population; Goals; Health; Hip Fractures; Hormone use; Hormones; Hospitals; Hour; Image; Imaging Techniques; Incidence; Individual; Institution; Intake; Intestines; Ionizing radiation; Iron; Israel; Kidney; Laboratories; Lateral; Life Style; Magnetic Resonance Imaging; Massachusetts; Measures; Medical Records; Medical center; Medicine; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Metabolic; Metabolic Bone Diseases; Metabolism; Mid-Career Clinical Scientist Award (K24); Minerals; Morbidity - disease rate; Nurses' Health Study; Osteoblasts; Osteoclasts; Osteoporosis; Osteoporosis prevention; Parathyroid gland; Participant; Pathway interactions; Patients; Pediatric Hospitals; Physical activity; Physiologic calcification; Play; Postmenopause; Prevalence; Property; Protons; Public Health; Public Health Schools; Radiation; Renal function; Research; Research Infrastructure; Research Personnel; Research Proposals; Resources; Risk; Risk Assessment; Risk Factors; Role; Sample Size; Serum; Shapes; Site; Spinal; Spinal Fractures; Techniques; Time; Tissues; Tretinoin; United States National Institutes of Health; Vertebral Bone; Vertebral column; Visual; Vitamin A; Vitamin D; Walking; Water; Woman; Work; Wrist; bioimaging; body density; bone; bone health; bone loss; bone mass; bone metabolism; bone quality; bone strength; bone turnover; calcium absorption; calcium intake; catalyst; cohort; disorder control; experience; follow-up; imaging modality; improved; innovation; lifestyle factors; medical schools; modifiable risk; non-invasive imaging; novel; patient oriented; prevent; professor; programs; prospective; protein intake; skills; solid state; spine bone structure; symposium; therapy development; thiazide; tool; treatment center; vertebra body

DESCRIPTION (provided by applicant): The vertebra is the most common fracture site in adults, making vertebral fractures (VF) a major public health problem. Because of the bone and mineral metabolism derangements associated with declining kidney function, people with chronic kidney disease (CKD) are particularly vulnerable to developing fractures, with elevated fracture rates compared to the general population. However, little is known about modifiable VF risk factors, both in the general population and in individuals with CKD. Also, current non-invasive clinical parameters to assess bone health fail to predict fracture risk in CKD patients accurately. This K23 proposal will investigate novel modifiable risk factors for VF and explore the potential role of non- invasive imaging modalities in VF risk assessment. Taking advantage of the unique strengths of the Nurses' Health Studies I and II including large sample sizes providing high statistical power, long follow-up period, rich, well-validated dietary and lifestyle information, and VF cases confirmed by medical record, we will prospectively study dietary and lifestyle factors and VF risk in women (Aim 1). Vertebral deformities are important predictors of VF, but there are no prospective longitudinal data on vertebral deformities in CKD patients. We will establish a cohort of CKD patients and controls and prospectively follow the development/ progression of vertebral deformities over time (Aim 2). Vertebral deformities will be assessed by vertebral fracture assessment, which images the lateral spine using x-ray absorptiometry, and is a reliable and accurate technique for identifying vertebral deformities and VF with the advantage of low radiation exposure. Amongst our study participants with CKD, we will examine the association between serum bicarbonate level and change in vertebral deformities over time. Current imaging techniques are unable to measure the bone matrix or mineralization, which may play important roles in fracture risk. We will study the bone mineral and matrix content using novel, innovative MR imaging techniques, solid-state (31P) and water- and fat-suppressed proton projection (1H WASPI) MRI in the wrists of patients with CKD and controls (Aim 3). A non-invasive measure of bone matrix and mineral content would provide important information on the intrinsic properties of a patient's bone quality and strength that no current imaging technique is able to provide. Results from this research proposal will have important clinical implications by improving our understanding of VF risk factors and their assessment, thus enabling the development of interventions to prevent fractures and their sequelae. This application is for a K23 award for Julie Paik, MD, MPH, MSc, a nephrologist at Brigham and Women's Hospital (BWH), who is establishing herself as a young investigator in patient-oriented clinical research in bone and mineral metabolism. Her long-term goal is to improve the spinal health of patients with CKD by studying modifiable risk factors and working to optimize their spinal health and prevent fractures. This K23 award will provide Dr. Paik with the support to develop the methodologic tools and research experience necessary to conduct epidemiologic (Aim 1) and patient-oriented (Aims 2 and 3) clinical research, and in the long-term to become an independent clinical investigator. This proposal takes advantage of the rich resources and infrastructure at Harvard Medical School, including the Channing Division of Network Medicine, BWH, the Harvard Catalyst Clinical Research Center at Beth Israel Deaconess Medical Center (BIDMC), and the Martinos Center for Biomedical Imaging at Massachusetts General Hospital (MGH). Dr. Paik's research efforts will be closely guided by her mentor at BWH, Gary Curhan, MD, ScD, Professor of Medicine at Harvard Medical School and Epidemiology at the Harvard School of Public Health, a renowned nephrologist and epidemiologist who has extensive experience conducting innovative research and mentoring investigators such as Dr. Paik. His commitment to mentorship is evidenced by a K24 award from the NIH. Dr. Curhan's expertise and experience will be complemented by an advisory committee comprised of accomplished investigators who are all committed to Dr. Paik's research efforts: Catherine Gordon, MD, MSc, a pediatric endocrinologist, senior clinical research investigator in metabolic bone disease, and Chief of the Division of Adolescent Medicine at Hasbro Children's Hospital; Harold Rosen, MD, an endocrinologist with clinical expertise in osteoporosis, bone health, and clinical densitometry and Director of the Osteoporosis Prevention and Treatment Center at BIDMC; and Jerome Ackerman, PhD, Director of the Biomaterials Laboratory at the MGH Martinos Center, who has been conducting research on solid state MR for over 40 years and has led the solid state MR program at MGH for 28 years. To expand her research skills, Dr. Paik will take advanced coursework in biostatistics and epidemiology at the Harvard School of Public Health. In addition, she will attend conferences and seminars within BWH's Channing Division of Network Medicine and Renal Division, and Harvard-wide seminars and conferences on metabolic bone disease. Through the different components of this K23 proposal, including the research proposal, direct mentorship by Dr. Curhan and the other Advisory Committee members, advanced coursework at the Harvard School of Public Health, and wealth of conferences and seminars within the different divisions of a major research and teaching institution, Dr. Paik will be able to successfully further develop and refine her research skills and work towards her goal of becoming an independent clinical investigator in the field of bone and mineral metabolism.

描述（由申请人提供）：椎骨是成人最常见的骨折部位，使得椎骨骨折（VF）成为一个主要的公共卫生问题。由于与肾功能下降相关的骨和矿物质代谢紊乱，慢性肾病（CKD）患者特别容易发生骨折，与普通人群相比骨折率升高。然而，在一般人群和CKD患者中，对可改变的VF风险因素知之甚少。此外，目前评估骨健康的非侵入性临床参数无法准确预测CKD患者的骨折风险。 本K23提案将调查VF的新的可改变的风险因素，并探索非侵入性成像方式在VF风险评估中的潜在作用。利用护士健康研究I和II的独特优势，包括提供高统计效力的大样本量、长随访期、丰富、经过充分验证的饮食和生活方式 资料，以及经病历证实的VF病例，我们将前瞻性研究饮食和生活方式因素与女性VF风险（目的1）。椎体畸形是VF的重要预测因素，但尚无CKD患者椎体畸形的前瞻性纵向数据。我们将建立一个CKD患者和对照组队列，并前瞻性随访椎体畸形随时间的发展/进展（目标2）。将通过椎体骨折评估评估椎体畸形，该评估使用X线吸收测定法对侧脊柱进行成像，是识别椎体畸形和VF的可靠和准确技术，具有低辐射暴露的优点。在我们的研究参与者中，我们将研究血清碳酸氢盐水平与椎体畸形随时间变化之间的关系。目前的成像技术无法测量骨基质或矿化，这可能在骨折风险中发挥重要作用。我们将使用新型、创新的MR成像技术，固态（31 P）和水和脂肪抑制质子投影（1H WASPI）MRI，研究CKD患者和对照组手腕的骨矿物质和基质含量（目的3）。骨基质和矿物质含量的非侵入性测量将提供关于患者骨质和强度的内在特性的重要信息，这是当前成像技术无法提供的。这项研究提案的结果将通过提高我们对VF风险因素及其评估的理解而具有重要的临床意义，从而能够制定预防骨折及其后遗症的干预措施。 此应用程序是为朱莉白，医学博士，公共卫生硕士，理学硕士，在布里格姆和妇女医院（BWH）的肾病学家，谁是建立自己作为一个年轻的研究者在以病人为导向的临床研究在骨和矿物质代谢的K23奖。她的长期目标是通过研究可改变的风险因素并努力优化其脊柱健康和预防骨折来改善CKD患者的脊柱健康。该K23奖将为白博士提供支持，以开发进行流行病学（目标1）和以患者为导向（目标2和3）的临床研究所需的方法学工具和研究经验，并长期成为独立的临床研究者。该提案利用了哈佛医学院丰富的资源和基础设施，包括BWH网络医学的Channing部门，Beth Israel Deaconess医疗中心（BIDMC）的哈佛催化剂临床研究中心，以及马萨诸塞州总医院（MGH）的Martinos生物医学成像中心。 Paik博士的研究工作将由她在BWH的导师加里·柯汉（Gary Curhan）密切指导，他是哈佛医学院的医学教授和哈佛公共卫生学院的流行病学教授，是一位著名的肾病学家和流行病学家，在开展创新研究和指导Paik博士等研究人员方面拥有丰富的经验。他对导师的承诺得到了NIH颁发的K24奖的证明。Curhan博士的专业知识和经验将得到一个咨询委员会的补充，该委员会由所有致力于Paik博士研究工作的有成就的研究人员组成：Catherine Gordon，医学博士，理学硕士，儿科内分泌学家，代谢性骨病高级临床研究员，Hasbro儿童医院青少年医学部主任; Harold罗森，医学博士，内分泌学家，在骨质疏松症、骨健康和临床密度测定方面具有临床专业知识，BIDMC骨质疏松症预防和治疗中心主任;和MGH Martinos中心生物材料实验室主任杰罗姆阿克曼博士，他从事固态MR研究已有40多年，并在MGH领导固态MR项目已有28年。为了扩展她的研究技能，白博士将在哈佛公共卫生学院学习生物统计学和流行病学的高级课程。此外，她还将参加BWH网络医学和肾脏部的Channing分部的会议和研讨会，以及哈佛大学范围内的代谢性骨病研讨会和会议。 通过这个K23提案的不同组成部分，包括研究提案，Curhan博士和其他咨询委员会成员的直接指导，哈佛公共卫生学院的高级课程，以及主要研究和教学机构不同部门内的丰富会议和研讨会，Paik博士将能够成功地进一步发展和完善她的研究技能，并朝着她成为骨和矿物质代谢领域独立临床研究者的目标努力。