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: 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
• 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; 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

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.

项目摘要/摘要 睡眠障碍对许多生物系统产生负面影响，可能对骨骼健康有害。骨 重塑对骨骼质量和力量很重要，在一夜之间增加了 经历中断的睡眠。流行病学数据和动物研究表明睡眠障碍之间有联系 和骨头，但是睡眠影响骨骼的方向和机制尚未完全理解。这 该项目的总体目的是建立和量化破坏睡眠的骨骼影响和 研究骨骼重塑和睡眠连接的机制。中心假设是 睡眠障碍（例如睡眠损失，昼夜节律）通过改变平衡对骨骼健康产生负面影响 在骨骼分辨率和骨骼形成之间，在骨骼脆弱时尤其有害 更年期过渡期间和之后的时期。具体目的是： 1。检查控制骨骼重塑中节奏的物理机制，并研究如何 昼夜节律的转移和积累的睡眠损失会影响健康男性的骨骼转换。这个目标将使用 从先前进行的临床实验中的样品操纵睡眠效果周期。 2。确定老年男性睡眠损失与骨骼更新与骨矿物质密度之间的关联 和绝经后妇女使用观察队列研究的横断面分析。这 代表了对这些同类群体的新颖调查，以确认睡眠与骨骼之间的关联 探索与性别和性激素状况有关的差异。 3。评估睡眠损失通过小型临床来改变骨骼重塑的平衡的机制 干预研究。这些初步数据将支持R01赠款应用程序的开发。 这项研究填补了睡眠和骨骼研究领域的知识差距，可能会影响临床 评估和治疗骨质疏松症。如果证明该假设是真实的，则睡眠中断可能是 新型骨质疏松症的新型，可改变的危险因素。候选人克里斯汀·斯旺森（Christine Swanson，M.D。）是一位出色的大三学生 具有特殊背景的研究者包括内分泌临床和研究培训（专门研究 骨）在OHSU，并在K23奖项期间完成了临床研究硕士学位。通过 博士的指导。温迪·科尔特（Wendy Kohrt）和肯尼斯·赖特（Kenneth Wright），课程工作以及成功完成 项目的具体目标，候选人将在骨骼和睡眠研究中发展知识库和技能 这将使她踏上成为成功独立医生的总体目标的道路 科学家。