Bone Turnover Responses to Sleep Restriction and Subsequent Sleep Recovery

项目总结 睡眠和昼夜节律紊乱对许多生物系统造成负面影响，可能代表着新的、 低骨量和骨折的可改变的危险因素。我们是第一个报告累积睡眠的人 同时存在昼夜节律紊乱的限制(类似于轮班工作)抑制了一种骨标记 在健康男性中形成而不是吸收。这些数据与动物睡眠限制研究的数据一致。 与对照组相比，也观察到骨密度(BMD)降低。这种脱钩的骨骼 如果睡眠和昼夜节律紊乱，人类体内的周转标志(BTM)可能会限制达到峰值骨量 发生在青春期或成年期早期，在骨骼建模和巩固期间，可能会加速骨骼 后来(例如，在更年期过渡期间，睡眠障碍很常见)时会出现失眠。我的 K23的数据已经证明，睡眠限制和昼夜节律紊乱联合起来会导致类似的BTM 女性的变化，这些变化发生在联合睡眠和睡眠的几天内 昼夜节律紊乱。睡眠时间不足，没有极端的昼夜节律干扰，对BTM的影响， 独立于住院患者的实验室环境和与生俱来的缺乏体力活动，以及逆转的能力 或改善BTM损害与恢复睡眠是未知的。R03的总体科学目标 应用是评估睡眠时间不足在没有极端昼夜节律干扰的情况下对 女性和男性的BTMS，独立于身体缺乏活动，以及恢复睡眠对稳定BTMS的作用 或者弥补睡眠时间缩短的影响。中心假说是睡眠时间不足， 与相对缺乏体力活动无关，会损害女性和男性的骨形成标志(P1NP) 骨吸收指标(CTX)没有变化，延长睡眠时间将恢复P1NP 将标高设置为基线。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 具有重大临床影响的假设，我可以在我的R01中进行测试-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.调查工作日睡眠时间不足是否会降低骨骼形成的一个标志 而不会改变骨吸收标记。 2.确定睡眠不足会导致骨生物标志物的变化，而不依赖于身体缺乏活动 通过比较睡眠受限参与者和对照组的BTM变化，这是住院实验室研究中固有的。 3.确定延长一个周末或3周的睡眠是否可以改善或逆转骨骼损伤 睡眠受限引起的新陈代谢。 这项研究将对科学和病人护理产生持续而强大的影响，因为它可以 在骨质疏松症预防、评估和治疗方面引入范式转变。

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.