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

项目总结 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，但 很少有人注意到的副作用是骨代谢受阻。动物和人类数据 睡眠限制和昼夜节律紊乱是夜班工作中固有的，这可能是新的，潜在的 低骨密度(BMD)和增加骨折风险的可改变的危险因素。人类暴露在 反复发作的28岁导致数周的累积睡眠受限和并发的昼夜节律紊乱 小时/天方案显著减少了骨形成，骨没有变化或增加。 再吸收。这些骨骼代谢的变化，如果持续下去，将被预测增加骨折的风险 限制年轻人骨密度峰值的发展和/或加速晚年的骨丢失。事实上， 护士健康研究发现绝经后女性骨折风险增加，报告20 与那些从未上过夜班的人相比，上了几年夜班的人。急、慢性骨骼 人类典型夜班时间表、潜在机制和骨骼恢复或恢复能力的影响 适应是未知的。这个应用程序将通过使用模拟的急性和真实世界来填补这些知识空白 长期上夜班，以评估其对骨骼的影响。科学的目标是确定影响 上夜班的人对骨骼新陈代谢、密度、微结构和强度进行研究，并研究一种可信的 夜班工作损害骨骼代谢的潜在机制(例如，交感神经张力增加) 促进最佳骨骼强度和健康衰老。具体目标是： 1.让健康的成年人享受正常睡眠或模拟夜班工作 (A)确定典型的夜班工作时间表是否会严重分离骨周转标记； (B)研究交感神经张力增加是导致骨骼代谢紊乱的机制之一；及 (C)评估正常睡眠/清醒模式的恢复是否逆转了骨转换标志的解偶联。 2.通过评估骨转换标志物、骨密度、骨微结构和强度的变化 一组医院护士在第一年的夜间工作与白天轮班工作的比较。 这种跨学科、协作的研究将增强个人的健康。它将生成人类数据 将夜班工作确定为骨骼健康受损的一个新的、潜在的可修改的危险因素，并告知 它改变女性和男性骨代谢的机制。这些知识将提供一种 有机会进行干预，预防低骨量、骨质疏松症和骨折，包括功能丧失 它们会导致独立和死亡。此外，这一系列研究提供了新的治疗方案 骨骼健康。这项研究最终将为夜班工作者提供临床建议，并介绍 骨质疏松症预防、评估和治疗的范式转变。

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.