Sleep Disturbance: A Novel Risk Factor for Impaired Bone Remodeling

项目摘要/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 重塑对骨量和强度很重要，一夜之间就会增加，当时数百万人 经验打乱了睡眠。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。这个 该项目的总体目标是建立和量化睡眠中断对骨骼的影响，并 研究骨骼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)通过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，在骨骼脆弱时尤其有害 绝经期在绝经期和更年期之后。具体目标是： 1.研究控制骨骼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损失会影响其他健康男性的骨转换。这一目标将使用 样本来自之前进行的一项操纵睡眠-觉醒周期的临床实验。 2.确定睡眠不足与老年男性骨转换和骨密度之间的关系 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。这 代表了对这些队列的一项新的调查，以证实睡眠和骨骼之间的联系 探索与性行为和性激素状况有关的差异。 3.通过一项小型的临床研究，评估睡眠不足改变骨重建平衡的机制 干预性研究。这些初步数据将支持R01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，这可能会影响临床 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、可修改的危险因素。这位候选人是医学博士克里斯汀·斯旺森，她是一名出色的新手 具有特殊背景的研究员，包括内分泌学、临床和研究培训(专长于 在OHSU完成临床研究硕士学位，并在K23授勋期间完成临床研究硕士学位。穿过 来自Wendy Kohrt博士和Kenneth Wright博士的指导，课程作业，以及成功完成 项目的具体目标，候选人将发展骨骼和睡眠研究的知识库和技能 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。

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.