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断裂部位，使椎骨骨折（VF）成为主要的公共卫生问题。由于骨骼和肾脏功能下降有关的骨骼和矿物质代谢危险，患有慢性肾脏疾病（CKD）的人特别容易受到裂缝的影响，与普通人群相比，骨折率升高。但是，对于普通人群和CKD患者，对可修改的VF风险因素知之甚少。同样，当前评估骨骼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。 该K23提案将研究VF的新型可修改风险因素，并探讨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，包括大型样本量，可提供较高的统计能力，较长的随访期，丰富，验证良好的饮食和生活方式 信息以及通过病历确认的VF病例，我们将前瞻性地研究女性的饮食和生活方式因素以及VF风险（AIM 1）。椎骨畸形是VF的重要预测指标，但没有关于CKD患者椎骨畸形的前瞻性纵向数据。我们将建立一组CKD患者和对照组，并前瞻性地遵循椎骨畸形的发展/进展（AIM 2）。椎骨畸形将通过椎骨骨折评估进行评估，该评估使用X射线吸收法对侧面的脊柱进行图像，并且是一种可靠，准确的技术，用于鉴定椎骨畸形和VF，并具有低辐射暴露的优势。在我们的研究参与者中，我们将检查血清碳酸氢盐水平与椎骨畸形随时间变化之间的关联。当前的成像技术无法测量骨基质或矿化，这可能在断裂风险中起重要作用。我们将使用新颖的，创新的MR成像技术，固态（31p）以及在CKD和对照组患者的手腕中研究骨矿物质和基质含量（31p）以及含水和脂肪抑制的质子投影（1H WASPI）MRI（AIM 3）。对骨基质和矿物质含量的非侵入性测量将提供有关患者骨骼质量和强度的内在特性的重要信息，而目前的成像技术无法提供。这项研究建议的结果将通过提高我们对VF风险因素及其评估的理解，从而具有重要的临床意义，从而制定干预措施以防止骨折及其后遗症。 该申请是为Brigham and妇女医院（BWH）的肾脏科医生Julie Paik，MD，MSC颁发的K23奖。她的长期目标是通过研究可修改的危险因素并努力优化其脊柱健康并预防骨折来改善CKD患者的脊柱健康。该K23奖将为Paik博士提供支持，以开发进行流行病学（AIM 1）和以患者为导向（AIMS 2和3）临床研究所必需的方法论工具和研究经验，并长期成为独立的临床研究者。该提案利用了哈佛医学院的丰富资源和基础设施，包括Channing Network Medicine，BWH，Beth Israel Deaconess Medical Center（BIDMC）的哈佛催化剂临床研究中心和马萨诸塞州马萨诸塞州总医院（MGH）的Martinos生物医学成像中心。 Paik博士的研究工作将由BWH，医学博士Gary Curhan，医学博士Gary Curhan，Harvard医学院医学教授和哈佛公共卫生学院的流行病学教授的指导，他拥有一位著名的肾脏医生和流行病学家，他的经验丰富的经验经验，可以进行创新研究和辅导研究人员，例如Paik博士。 NIH的K24奖可以证明他对指导的承诺。 Curhan博士的专业知识和经验将由一个咨询委员会进行补充，该咨询委员会由成熟的研究人员组成，这些研究人员都致力于Paik博士的研究工作：凯瑟琳·戈登（Catherine Gordon），医学博士凯瑟琳·戈登（Catherine Gordon），医学博士，MSC，一名儿科内分泌学家，代谢性骨病高级临床研究者，以及Hasbro儿童医院青少年医学局的首席Harold Rosen，医学博士，具有骨质疏松症，骨骼健康和临床密度法临床专业知识的内分泌学家，BIDMC的骨质疏松预防和治疗中心主任； MGH Martinos中心生物材料实验室主任Jerome Ackerman博士，他已经对Solid State MR进行了研究已有40多年的研究，并领导了MGH的Solid State MR Program 28年。为了扩大她的研究技能，Paik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的网络医学和肾脏分区的Channing部门，以及有关代谢骨骼疾病的范围内的Channing Channing部门，以及哈佛大学范围内的研讨会和会议。 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.