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.

项目概要 睡眠和昼夜节律紊乱会对许多生物系统产生负面影响，并且可能代表新的、 低骨量和骨折的可改变危险因素。我们是第一个报告累积睡眠的人 同时昼夜节律紊乱的限制（类似于轮班工作）抑制了骨标志物 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相似 与对照组相比，还观察到骨矿物质密度（BMD）较低。这种骨的解耦 如果睡眠和昼夜节律受到干扰，人类的周转标记物 (BTM) 可能会限制骨量峰值的达到 发生在青春期或成年早期的骨建模和巩固过程中，并可能加速骨形成 稍后经历的损失（例如，在更年期过渡期间，睡眠障碍很常见）。我的 K23 数据表明，睡眠限制和昼夜节律紊乱相结合会导致类似的 BTM 女性的变化，并且这些变化发生在暴露于睡眠和睡眠相结合的几天内 昼夜节律紊乱。睡眠时间不足（没有极端的昼夜节律紊乱）对 BTM 的影响， 独立于住院实验室环境和固有的身体不活动，以及逆转的能力 或通过恢复睡眠改善 BTM 损伤尚不清楚。 R03的总体科学目标 应用的目的是评估睡眠持续时间不足（没有极端的昼夜节律紊乱）对 女性和男性的 BTM，与身体不活动无关，以及恢复睡眠对稳定 BTM 的作用 或补偿缩短的睡眠时间。中心假设是睡眠时间不足 与相对缺乏身体活动无关，会损害女性和男性的骨形成标志物 (P1NP) 骨吸收 (CTX) 标志物没有变化，延长睡眠时间将恢复 P1NP 水平至基线。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 睡眠和昼夜节律紊乱改变人类骨骼健康的机制。具体目标是： 1. 研究工作周睡眠时间不足是否会降低骨形成标志 不改变骨吸收标记。 2. 确定睡眠不足会引起骨生物标志物的变化，而与身体不活动无关 这是住院实验室研究中固有的，通过比较睡眠受限的参与者与对照组的 BTM 变化。 3. 确定延长一个周末或三周的睡眠是否可以改善或逆转骨骼损伤 睡眠限制引起的新陈代谢。 这项研究将对科学和患者护理产生持续而强大的影响，因为它可以 引入骨质疏松症预防、评估和治疗的范式转变。