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Sleep Disturbance: A Novel Risk Factor for Impaired Bone Remodeling

睡眠障碍：骨重塑受损的新危险因素

基本信息

批准号：
9976325
负责人：
Christine M Swanson
金额：
$ 17.06万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-01 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9976325
关键词：
Adult Affect Animals Applications Grants Area Biological Biology Biometry Bone Density Bone Resorption Bone remodeling Centers for Disease Control and Prevention (U.S.)Circadian Dysregulation Circadian Rhythms Circadian desynchrony Clinical Clinical Endocrinology Clinical Research Clinical Treatment Cohort Studies Cross-Sectional Studies Data Development Disease Doctor of Medicine Epidemic Equilibrium Functional disorder Future Goals Gonadal Steroid Hormones Health Hormones Human Hypoxia Impairment Intervention Studies Investigation Knowledge Link Menopause Mentored Patient-Oriented Research Career Development Award Mentors Mentorship Metabolism Modeling Morbidity - disease rate Osteogenesis Osteoporosis Patient Care Perimenopause Periodicity Physicians Physiological Postmenopause Process Public Health Recording of previous events Research Research Design Research Personnel Research Training Risk Factors Sampling Scientist Sex Differences Skeleton Sleep Sleep Deprivation Sleep Wake Cycle Sleep disturbances Time Training Woman Work age difference aged biological systems bone bone health bone loss bone mass bone metabolism bone strength bone turnover career development circadian cohort epidemiologic data experience experimental study glycemic control human data human old age (65+)innovation knowledge base men modifiable risk mortality novel older men patient population research clinical testing skeletal skills sleep abnormalities young man

项目摘要

PROJECT SUMMARY/ABSTRACT Sleep disturbance negatively impacts many biological systems and may be detrimental to skeletal health. Bone remodeling, which is important for bone mass and strength, increases overnight, a time when millions experience disrupted sleep. Epidemiological data and animal studies suggest a link between sleep disturbance and bone but the direction and the mechanisms by which sleep affects bone are not fully understood. The overall objective of this project is to establish and quantify the skeletal effects of disrupted sleep and to investigate the mechanisms by which bone remodeling and sleep are linked. The central hypothesis is that sleep disturbance (e.g., sleep loss, circadian shifts) negatively impacts bone health by altering the balance between bone resorption and bone formation, and is particularly detrimental during skeletally vulnerable periods such as during and after the menopausal transition. The specific aims are: 1. Examine the physiological mechanisms that control rhythms in bone remodeling and investigate how circadian shifts and accumulating sleep loss affect bone turnover in otherwise healthy men. This aim will use samples from a previously performed clinical experiment that manipulated sleep-wake cycles. 2. Determine the association between sleep loss and bone turnover and bone mineral density in older men and peri- and post-menopausal women using cross-sectional analyses of observational cohort studies. This represents a novel inquiry into these cohorts to confirm the association between sleep and bone while exploring differences related to sex and sex hormone status. 3. Evaluate mechanisms by which sleep loss alters the balance in bone remodeling through a small, clinical intervention study. These preliminary data will support the development of an R01 grant application. This research fills a knowledge gap in the fields of sleep and bone research that could impact the clinical evaluation and treatment of osteoporosis. If the hypothesis is shown to be true, sleep disruption could be a novel, modifiable risk factor for osteoporosis. The candidate, Christine Swanson, M.D., is an outstanding junior investigator with an exceptional background including Endocrinology clinical & research training (specializing in bone) at OHSU and the completion of a Masters of Clinical Research during the K23 award period. Through mentorship from Drs. Wendy Kohrt and Kenneth Wright, coursework, and the successful completion of the project’s specific aims, the candidate will develop a knowledge base and skillset in bone and sleep research that will set her on the path to achieve her overall goal of becoming a successful independent physician scientist.

项目概要/摘要睡眠障碍会对许多生物系统产生负面影响，并可能损害骨骼健康。骨对骨量和强度很重要的重塑在一夜之间就增加了，数百万人经历睡眠中断。流行病学数据和动物研究表明睡眠障碍之间存在联系和骨骼，但睡眠影响骨骼的方向和机制尚不完全清楚。这该项目的总体目标是确定和量化睡眠中断对骨骼的影响，并研究骨重塑和睡眠之间的联系机制。中心假设是睡眠障碍（例如睡眠不足、昼夜节律变化）会改变平衡，对骨骼健康产生负面影响介于骨吸收和骨形成之间，在骨骼脆弱期间尤其有害诸如绝经过渡期间和之后的时期。具体目标是： 1. 检查控制骨重塑节律的生理机制并研究如何昼夜节律的变化和累积的睡眠不足会影响健康男性的骨转换。这个目标将使用来自之前进行的操纵睡眠-觉醒周期的临床实验的样本。 2. 确定老年男性睡眠不足与骨转换和骨矿物质密度之间的关联以及围绝经期和绝经后妇女使用观察性队列研究的横断面分析。这对这些群体进行了一项新颖的调查，以确认睡眠与骨骼之间的关联，同时探索与性别和性激素状态相关的差异。 3. 通过小型临床研究评估睡眠不足改变骨重塑平衡的机制干预研究。这些初步数据将支持 R01 拨款申请的制定。这项研究填补了睡眠和骨骼研究领域的知识空白，可能会影响临床骨质疏松症的评估和治疗。如果这个假设被证明是正确的，睡眠中断可能是一个骨质疏松症的新的、可改变的危险因素。候选人克里斯汀·斯旺森 (Christine Swanson) 医学博士是一名出色的大三学生具有特殊背景的研究者，包括内分泌学临床和研究培训（专门从事骨）在 OHSU 并在 K23 奖励期间完成临床研究硕士学位。通过博士的指导。 Wendy Kohrt 和 Kenneth Wright，课程作业，并成功完成根据项目的具体目标，候选人将开发骨骼和睡眠研究方面的知识库和技能这将使她走上实现成为一名成功的独立医生的总体目标的道路科学家。