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

基本信息

批准号：
9307806
负责人：
Julie Paik
金额：
$ 19.76万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-16 至 2019-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9307806
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 Fibrinogen Fracture Functional disorder General Hospitals General Population Goals Health Hip Fractures Hormone use 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 Methodology Mid-Career Clinical Scientist Award (K24)Minerals Moderate Exercise Morbidity - disease rate Nurses&apos Health Study Osteoblasts Osteoclasts Osteoporosis Osteoporosis prevention PTH gene Participant Pathway interactions Patients Pediatric Hospitals Physical activity Physiologic calcification Play Postmenopause Prevalence Property Prospective Studies Prospective cohort study Protons Public Health Public Health Schools Radiation exposure Renal function Research Research Infrastructure Research Personnel Research Proposals Resources Risk Risk Assessment Risk Factors Roentgen Rays 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 fracture risk imaging modality improved innovation lifestyle factors medical schools modifiable risk non-invasive imaging novel patient oriented prevent professor programs prospective protein intake public health relevance skills solid state spine bone structure symposium therapy development thiazide tool treatment center vertebra body walking speed

项目摘要

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，使椎骨骨折（VF）成为一个主要的公共卫生问题。由于骨和矿物质代谢紊乱与肾功能下降相关，慢性肾病 (CKD) 患者特别容易发生骨折，与一般人群相比，骨折率较高。然而，对于普通人群和 CKD 患者中可改变的室颤危险因素知之甚少。此外，目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 提案将研究新的可改变的心室颤动风险因素，并探索非侵入性成像方式在心室颤动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，包括提供高统计能力的大样本量、较长的随访期、丰富且经过充分验证的饮食和生活方式信息以及病历证实的心室颤动病例，我们将前瞻性研究女性的饮食和生活方式因素以及心室颤动风险（目标 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 患者和对照队列，并前瞻性地跟踪椎骨畸形随时间的发展/进展（目标 2）。椎骨畸形将通过椎骨骨折评估进行评估，该评估使用 X 射线吸收测量法对脊柱侧方进行成像，是一种可靠、准确的技术，用于识别椎骨畸形和室颤，具有低辐射暴露的优点。在患有 CKD 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系。目前的成像技术无法测量骨基质或矿化情况，而这可能在骨折风险中发挥重要作用。我们将使用新颖、创新的 MR 成像技术、固态 (31P) 和水和脂肪抑制质子投影 (1H WASPI) MRI，研究 CKD 患者和对照患者手腕的骨矿物质和基质含量（目标 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质量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。这项研究计划的结果将通过提高我们对心室颤动危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。本申请旨在为布莱根妇女医院 (BWH) 的肾脏病专家 Julie Paik（医学博士、公共卫生硕士、理学硕士）申请 K23 奖，她正在将自己定位为以患者为导向的骨和矿物质代谢临床研究的年轻研究者。她的长期目标是通过研究可改变的危险因素并努力优化脊柱健康并预防骨折，改善 CKD 患者的脊柱健康。该 K23 奖项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）临床研究所需的方法学工具和研究经验，并从长远来看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，包括网络医学查宁部、BWH、贝斯以色列女执事医疗中心 (BIDMC) 的哈佛催化剂临床研究中心以及马萨诸塞州的马蒂诺斯生物医学成像中心综合医院（MGH）。 Paik 博士的研究工作将得到她在 BWH 的导师 Gary Curhan（医学博士、科学博士、哈佛医学院医学教授和哈佛公共卫生学院流行病学教授）的密切指导，他是一位著名的肾脏病学家和流行病学家，在开展创新研究方面拥有丰富的经验。研究和指导白博士等研究人员。 NIH 颁发的 K24 奖证明了他对指导的承诺。 Curhan 博士的专业知识和经验将得到一个咨询委员会的补充，该委员会由致力于 Paik 博士研究工作的资深研究人员组成：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研究员和首席研究员孩之宝儿童医院青少年医学科； Harold Rosen 医学博士是一位内分泌学家，在骨质疏松症、骨骼健康和临床密度测定方面拥有临床专业知识，也是 BIDMC 骨质疏松症预防和治疗中心主任； Jerome Ackerman 博士是 MGH Martinos 中心生物材料实验室主任，他从事固态 MR 研究已有 40 多年，并领导 MGH 固态 MR 项目 28 年。为了扩展她的研究技能，白南准博士将在哈佛大学公共卫生学院学习生物统计学和流行病学高级课程。此外，她还将参加 BWH 网络医学查宁分部和肾脏分部的会议和研讨会，以及哈佛大学范围内有关代谢性骨病的研讨会和会议。通过该 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、哈佛大学公共卫生学院的高级课程以及专业不同部门内的大量会议和研讨会在研究和教学机构中，白博士将能够成功地进一步发展和完善她的研究技能，并努力实现成为骨和矿物质代谢领域的独立临床研究者的目标。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A Pilot Study Embedding Clinical Pharmacists Within an Interprofessional Nephrology Clinic for the Initiation and Monitoring of Empagliflozin in Diabetic Kidney Disease.

一项将临床药剂师纳入跨专业肾病诊所的试点研究，以启动和监测恩格列净治疗糖尿病肾病的效果。

DOI：
发表时间：
2021-06
期刊：
影响因子：
1.3
作者：
Triantafylidis, Laura K;Hawley, Chelsea E;Fagbote, Christopher;Li, Jiahua;Genovese, Nicole;Paik, Julie M
通讯作者：
Paik, Julie M

Clinical problem solving: Itching for a diagnosis.

临床问题解决：渴望诊断。