Fractured Schedules: Skeletal Effects of Acute and Chronic Night Shift Work

项目摘要 众所周知，夜班工作会增加患心血管疾病、癌症和代谢综合征的风险， 很少受到关注的副作用是骨代谢的破坏。动物和人体数据 暗示睡眠限制和昼夜节律紊乱，这是夜班工作固有的，是新颖的，潜在的， 低骨矿物质密度（BMD）和骨折风险增加的可改变风险因素。人类暴露于 几周的累积睡眠限制和并发的昼夜节律紊乱引起的复发性28 小时/天方案显著降低了骨形成，骨形成没有变化或增加， 再吸收这些骨代谢的变化，如果持续下去，预计会增加骨折的风险， 限制年轻人峰值BMD的发展和/或加速晚年的骨丢失。实际上 护士健康研究发现，绝经后妇女骨折的风险增加， 与从未上过夜班的人相比，急性和慢性骨关节炎 人类典型的夜班时间表的影响，潜在的机制，以及骨骼的恢复能力， 适应未知。此应用程序将填补这些知识空白，通过使用模拟急性和现实世界 长期夜班工作，以评估其对骨骼的影响。科学目标是确定 夜班工作对骨代谢、密度、微结构和强度的影响，并调查一个合理的 基础机制（例如，交感神经张力增加），夜班工作会损害骨代谢， 促进最佳骨骼强度和健康衰老。具体目标是： 1.将健康成年人暴露于正常睡眠或模拟夜班工作， (a)确定一个典型的夜班工作时间表是否会严重影响骨转换指标; (b)研究交感神经张力增加作为骨代谢中断的机制;以及 (c)评价恢复正常睡眠/觉醒模式是否逆转骨转换标志物解偶联。 2.通过评估表征骨转换标志物、BMD、骨微结构和强度的变化 一组医院护士在他们第一年的夜班与白班工作的比较。 这种跨学科的合作研究将提高个人的健康。它将生成人类数据 建立夜班工作作为一种新的，潜在的可改变的骨健康受损的风险因素，并告知 它改变女性和男性骨代谢的机制。这些知识将提供一个 有机会进行干预，以防止低骨量，骨质疏松症和骨折，包括功能丧失 独立性和死亡率。此外，这一系列的研究提供了新的治疗选择， 骨骼健康这项研究最终将为夜班工人提供临床建议，并介绍 骨质疏松症的预防、评估和治疗的模式转变。

PROJECT SUMMARY Night shift work is known to increase risk for cardiovascular disease, cancer, and metabolic syndrome, but an adverse effect that has received little attention is the disruption of bone metabolism. Animal and human data suggest sleep restriction and circadian disruption, which are inherent in night shift work, are novel, potentially modifiable risk factors for low bone mineral density (BMD) and increased fracture risk. Humans exposed to several weeks of cumulative sleep restriction and concurrent circadian disruption induced by a recurring 28 hour/day protocol had significantly decreased bone formation, with no change or an increase in bone resorption. These changes in bone metabolism, if persistent, would be predicted to increase fracture risk by limiting the development of peak BMD in young adults and/or accelerating bone loss later in life. In fact, the Nurses’ Health Study identified an increased risk of fracture in postmenopausal women who reported 20+ years of night shift work compared to those who never worked the night shift. The acute and chronic skeletal effects of typical night shift schedules in humans, underlying mechanisms, and bone’s ability to recover or adapt are unknown. This application will fill these knowledge gaps by using simulated acute and real-world chronic night shift work to evaluate its effects on bone. The scientific objectives are to determine the effects of night shift work on bone metabolism, density, microarchitecture and strength, and investigate a plausible underlying mechanism (e.g., increased sympathetic tone) by which night shift work impairs bone metabolism to promote optimal bone strength and healthy aging. The specific aims are to: 1. Expose healthy adults to normal sleep or simulated night shift work to (a) Determine if a typical night shift work schedule acutely uncouples bone turnover markers; (b) Investigate increased sympathetic tone as a mechanism for the disruption in bone metabolism; and (c) Evaluate whether resumption of a normal sleep/wake pattern reverses bone turnover marker uncoupling. 2. Characterize changes in bone turnover markers, BMD, bone microarchitecture and strength by evaluating a cohort of hospital nurses in their first year of night compared to day shift work. This interdisciplinary, collaborative research will enhance the health of individuals. It will generate human data to establish night shift work as a novel, potentially modifiable risk factor for impaired bone health and inform mechanisms by which it alters bone metabolism in women and men. This knowledge will provide an opportunity to intervene to prevent low bone mass, osteoporosis and fractures, including the loss of functional independence and mortality they cause. Furthermore, this line of research offers new treatment options for bone health. This research will ultimately inform clinical recommendations for night shift workers and introduce a paradigm shift in the prevention, evaluation and treatment of osteoporosis.