Bone Turnover Responses to Sleep Restriction and Subsequent Sleep Recovery

骨转换对睡眠限制和随后的睡眠恢复的反应

• 批准号: 10117074
• 负责人: Christine M Swanson
• 金额: $ 7.54万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10117074
• 关键词: Address; Adolescence; Adult; Alkaline Phosphatase; Animals; Biological Markers; Bone Density; Bone Resorption; C-telopeptide; Chronic; Circadian Dysregulation; Clinical; Control Groups; Cyclophosphamide; Data; Environment; Evaluation; Exposure to; Fracture; Health; Hip Fractures; Human; Impact evaluation; Impairment; Inpatients; Investigation; Knowledge; Laboratories; Lead; Measures; Menopause; Modeling; N-terminal; Nurses; Nurses' Health Study; Observational Study; Osteocalcin; Osteogenesis; Osteoporosis; Osteoporosis prevention; Participant; Patient Care; Patients; Physical activity; Postmenopause; Procollagen; Prospective Studies; Recovery; Reporting; Research; Risk; Risk Factors; Role; Sampling; Science; Serum; Sleep; Sleep Deprivation; Sleep disturbances; Stress; Terminal Disease; Testing; Time; United States National Institutes of Health; Woman; Work; biological systems; bone; bone health; bone loss; bone mass; bone metabolism; bone turnover; critical period; emerging adult; experience; fracture risk; human old age (65+); improved; innovation; men; modifiable risk; negative affect; novel; older men; physical inactivity; prevention evaluation; prospective; response; shift work; skeletal; wrist fracture

PROJECT SUMMARY Sleep and circadian disruptions negatively impact many biological systems and may represent novel, modifiable risk factors for low bone mass and fracture. We were the first to report that cumulative sleep restriction with concurrent circadian disruption (akin to rotating shift work) suppressed a marker of bone formation but not resorption in healthy men. These data parallel those from sleep restriction studies in animals where lower bone mineral density (BMD) compared to controls was also observed. This uncoupling of bone turnover markers (BTMs) in humans may limit attainment of peak bone mass if sleep and circadian disruption occur in adolescence or early adulthood during bone modeling and consolidation, and may accelerate bone loss when experienced later (e.g. during the menopausal transition, when sleep disturbance is common). My K23 data have demonstrated that combined sleep restriction and circadian disruption induce similar BTM changes in women and that these changes occur within a few days of exposure to the combined sleep and circadian disturbance. The effects of insufficient sleep duration, without extreme circadian disruption, on BTMs, independent of the inpatient laboratory environment and inherent physical inactivity, and the ability to reverse or improve BTM impairments with recovery sleep are unknown. The overall scientific objectives of this R03 application are to evaluate the effects of insufficient sleep duration, without extreme circadian disruption, on BTMs in women and men, independent of physical inactivity, and the role of recovery sleep to stabilize BTMs or compensate for the period of shortened sleep. The central hypothesis is that insufficient sleep duration, independent of relative physical inactivity, will impair a marker of bone formation (P1NP) in women and men with no change in a marker of bone resorption (CTX), and that extending sleep duration will restore P1NP levels to baseline. These novel pilot data will provide a critical extension to my K23 to generate innovative hypotheses with significant clinical impact that I can test in my R01 - a comprehensive investigation of the mechanisms by which sleep and circadian disruption alter bone health in humans. The specific aims are: 1. Investigate if insufficient sleep duration during the work week decreases a marker of bone formation without altering a bone resorption marker. 2. Establish that insufficient sleep induces changes in bone biomarkers independent of physical inactivity inherent in an inpatient lab study, by comparing BTM changes in sleep-restricted participants to controls. 3. Determine if extending sleep for a weekend or 3 weeks can improve or reverse impairments in bone metabolism induced by sleep restriction. This research will have a sustained and powerful influence on science and patient care because it can introduce a paradigm shift in osteoporosis prevention, evaluation, and treatment.

项目摘要 睡眠和昼夜节律破坏对许多生物系统产生负面影响，可能代表新颖的， 低骨骼和骨折的可修改风险因素。我们是第一个报告累积睡眠的人 与并发的昼夜节律限制（类似于旋转的换档工作）抑制了骨头标记 在健康男性中形成但不吸收。这些数据与动物睡眠限制研究的数据平行 还观察到与对照组相比，较低的骨矿物质密度（BMD）。骨头的解偶联 如果睡眠和昼夜节律破坏 发生在骨建模和整合过程中的青春期或成年早期，并可能加速骨骼 稍后经历的损失（例如，在绝经期间，睡眠障碍是常见的）。我的 K23数据表明，综合睡眠限制和昼夜节律造成类似的BTM 妇女的变化，这些变化发生在暴露于综合睡眠的几天之内 昼夜节律。睡眠持续时间不足而没有极端昼夜节律对BTM的影响， 独立于住院实验室环境和固有的身体不活动，以及反向的能力 或改善恢复睡眠的BTM损伤尚不清楚。该R03的总体科学目标 应用是评估睡眠时间不足的影响，而无需极端昼夜节律的影响 男性和男性的BTM，独立于身体不活动的独立性以及恢复睡眠的作用以稳定BTMS 或补偿缩短睡眠期。中心假设是睡眠持续时间不足， 独立于相对身体不活动，会损害男性和男性骨形成的标志（P1NP） 骨吸收标记没有变化（CTX），并且延长睡眠持续时间将恢复P1NP 基线的水平。这些新颖的试点数据将为我的K23提供关键的扩展，以产生创新 我可以在R01中测试具有重大临床影响的假设 - 对 睡眠和昼夜节律破坏的机制改变了人类的骨骼健康。具体目的是： 1。调查工作周期间睡眠时间不足是否会降低骨形成的标记 没有改变骨吸收标记。 2。确定睡眠不足会引起骨生物标志物的变化，而不是身体不活跃 通过将睡眠受限参与者的BTM变化与对照组进行比较，在住院实验室研究中固有。 3.确定延长睡眠是否在周末或3周内可以改善或逆转骨骼 睡眠限制引起的代谢。 这项研究将对科学和患者护理产生持续和强大的影响，因为它可以 引入骨质疏松预防，评估和治疗的范式转移。