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

• 批准号: 9156445
• 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
• 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/9156445
• 关键词: Adult; Affect; Age; Applications Grants; Area; Biological; Biology; Biometry; Bone Density; Bone Resorption; Bone remodeling; Centers for Disease Control and Prevention (U.S.); Circadian Rhythms; Clinical; Clinical Research; Clinical Treatment; Cohort Studies; Cross-Sectional Studies; Data; Development; Disease; Doctor of Medicine; Endocrinology; Epidemic; Epidemiology; Equilibrium; Functional disorder; Future; Goals; Gonadal Steroid Hormones; Health; Hormones; Human; Hypoxia; 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 Characteristics; Skeleton; Sleep; Sleep Wake Cycle; Sleep disturbances; Time; Training; Woman; Work; aged; animal data; biological systems; bone; bone health; bone loss; bone mass; bone metabolism; bone strength; bone turnover; career development; cohort; experience; glycemic control; human data; human old age (65+); innovation; knowledge base; men; modifiable risk; mortality; novel; older men; patient population; research clinical testing; research study; sex; skeletal; skills; young man

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。 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 流行病学数据和动物研究表明睡眠障碍之间存在联系。 但睡眠影响骨骼的方向和机制尚不完全清楚。 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，并且在骨骼脆弱期间尤其受损 更年期过渡期间和之后等时期的具体目标是： 1. 检查控制骨重塑节律的生理机制并研究如何 昼夜节律变化和累积的睡眠不足会影响健康男性的骨转换。 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系 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。 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 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，可能影响临床 骨质疏松症的评估和治疗如果该假设被证明是正确的，那么睡眠中断可能是一个问题。 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）医学博士是一位杰出的大三学生。 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。 Wendy Kohrt 博士和 Kenneth Wright 博士的指导、课程作业以及成功完成 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。