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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）：椎体是成人中最常见的骨折部位，使椎体骨折（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骼和矿物质代谢紊乱，慢性肾脏疾病（CKD）患者特别容易发生骨折，与一般人群相比，其骨折率较高。然而，对于普通人群和CKD患者中可改变的VF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。本K23提案将研究新的可改变的VF危险因素，并探讨无创成像模式在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，包括提供高统计能力的大样本量，长随访期，丰富的，经过验证的饮食和生活方式