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

破碎的时间表：急性和慢性夜班工作对骨骼的影响

• 批准号: 10172736
• 负责人: Christine M Swanson
• 金额: $ 35.58万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10172736
• 关键词: Acute; Address; Adrenergic Receptor; Adult; Adverse effects; Animals; Attention; Biochemical; Bone Density; Bone Resorption; Cells; Cessation of life; Chronic; Circadian Dysregulation; Clinical; Coupled; Data; Development; Evaluation; Exposure to; Fracture; Health; Hospital Nursing; Hour; Human; Impairment; Individual; Jet Lag Syndrome; Knowledge; Lead; Life; Light; Malignant Neoplasms; Measures; Metabolic syndrome; Morbidity - disease rate; Nurses; Nurses' Health Study; Osteoblasts; Osteogenesis; Osteoporosis; Osteoporosis prevention; Participant; Pattern; Periodicity; Postmenopause; Protocols documentation; Recommendation; Recovery; Reporting; Research; Research Design; Risk Factors; Schedule; Sleep; Sleep Wake Cycle; Sleep disturbances; Structure; Sympathetic Nervous System; System; Time; Woman; Work; animal data; bone; bone health; bone loss; bone mass; bone metabolism; bone strength; bone turnover; cardiovascular disorder risk; cohort; density; experience; exposed human population; follow-up; fracture risk; functional independence; functional loss; healthy aging; human data; indexing; men; modifiable risk; mortality; novel; prevent; prevention evaluation; research clinical testing; response; screening guidelines; shift work; skeletal; sleep pattern; young adult

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.

项目概要 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，但 很少受到关注的不良影响是骨代谢的破坏。 表明夜班工作固有的睡眠限制和昼夜节律紊乱是新颖的，可能是 骨矿物质密度 (BMD) 低和骨折风险增加的可改变风险因素。 数周的累积睡眠限制和由反复出现的 28 引起的并发昼夜节律紊乱 每小时/每天的方案显着减少了骨形成，但骨量没有变化或增加 骨代谢的这些变化如果持续存在，预计会增加骨折风险。 限制年轻人骨密度峰值的发展和/或加速晚年骨质流失。 护士健康研究发现，报告 20 岁以上的绝经后女性骨折风险增加 与从未上过夜班的人相比，从事夜班工作多年的急性和慢性骨骼疾病。 典型夜班时间表对人类的影响、潜在机制以及骨骼恢复或恢复的能力 该应用程序将通过使用模拟急性和现实世界来填补这些知识空白。 长期夜班工作来评估其对骨骼的影响科学的目标是确定其影响。 夜班工作对骨代谢、密度、微结构和强度的影响，并研究了一个合理的模型 夜班工作损害骨代谢的潜在机制（例如，交感神经张力增加） 促进骨骼最佳强度和健康老龄化，具体目标是： 1. 让健康成年人正常睡眠或模拟夜班工作 (a) 确定典型的夜班工作安排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破坏的机制； (c) 评估恢复正常睡眠/觉醒模式是否会逆转骨转换标记物解偶联。 2. 通过评估来表征骨转换标志物、BMD、骨微结构和强度的变化 一组医院护士在第一年的夜间工作与白班工作的比较。 这项跨学科的合作研究将增强个人的健康，并将产生人类数据。 将夜班工作确定为骨骼健康受损的一种新的、潜在可改变的风险因素，并告知 这些知识将提供改变女性和男性骨代谢的机制。 有机会进行干预以预防低骨量、骨质疏松症和骨折，包括功能丧失 此外，这一系列研究还为这些疾病提供了新的治疗选择。 这项研究最终将为夜班工人提供临床建议并介绍。 骨质疏松症预防、评估和治疗的范式转变。