Sleep Disturbance: A Novel Risk Factor for Impaired Bone Remodeling

项目总结/摘要 睡眠障碍会对许多生物系统产生负面影响，并可能对骨骼健康有害。骨 重塑，这是重要的骨量和强度，增加一夜之间，一个时间，数百万 睡眠中断的经历。流行病学数据和动物研究表明睡眠障碍 但是睡眠影响骨骼的方向和机制还没有完全弄清楚。的 该项目的总体目标是建立和量化睡眠中断对骨骼的影响， 研究骨骼重塑和睡眠之间的联系机制。核心假设是， 睡眠障碍（例如，睡眠不足，昼夜节律变化）通过改变平衡对骨骼健康产生负面影响 在骨吸收和骨形成之间，并且在骨脆弱期间特别有害。 例如在绝经过渡期间和之后。具体目标是： 1.检查控制骨重建节律的生理机制，并研究如何 昼夜节律的改变和睡眠的减少会影响健康男性的骨转换。这一目标将使用 来自先前进行的操纵睡眠-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 以及绝经期和绝经后妇女，采用观察性队列研究的横断面分析。这 代表了对这些队列的一种新的调查，以确认睡眠和骨骼之间的联系， 探索与性别和性激素状态相关的差异。 3.通过一个小的临床试验，评估睡眠不足改变骨重建平衡的机制。 干预研究这些初步数据将支持R 01赠款申请的开发。 这项研究填补了睡眠和骨骼研究领域的知识空白，可能会影响临床研究。 骨质疏松症的评估和治疗。如果这一假设被证明是正确的，那么睡眠中断可能是一种 骨质疏松症的新的、可改变的危险因素。候选人克莉丝汀斯旺森，医学博士，是一个优秀的后辈 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和临床研究的硕士学位在K23奖期间完成。通过 导师从博士温迪·柯尔特和肯尼斯·赖特，课程，并成功完成了 项目的具体目标，候选人将开发在骨骼和睡眠研究的知识基础和技能 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

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.