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，但 受到关注的不利影响是骨代谢的破坏。动物和人类数据 建议夜班工作固有的睡眠限制和昼夜节律破坏是新颖的，可能是 低骨矿物质密度（BMD）的可修改风险因素和骨折风险增加。人类接触 反复出现的28 小时/天协议显着降低了骨形成，没有变化或骨骼增加 解决。骨骼代谢的这些变化（如果持续存在）将被预计会增加骨折风险 限制年轻人峰值BMD的发展和/或生命后期加速骨质流失。实际上， 护士的健康研究确定了术后妇女的骨折风险增加，这些妇女报告了20多名 与从未在夜班工作的人相比，夜班工作多年。急性和慢性骨骼 人类典型的夜班时间表的影响，基本机制以及骨骼恢复或 适应是未知的。此应用程序将使用模拟的急性和现实世界来填补这些知识空白 慢性夜班工作以评估其对骨骼的影响。科学目标是确定效果 在骨骼代谢，密度，微体系结构和力量上进行夜班工作，并调查合理的 基本机制（例如，同情性语调增加），夜班工作会损害骨骼代谢 促进最佳骨骼强度和健康衰老。具体目的是： 1。将健康的成年人暴露于正常睡眠或模拟夜班工作中 （a）确定典型的夜班工作时间表是否急性化骨转换标记； （b）研究增加的交感神经语调是骨骼代谢破坏的一种机制；和 （c）评估正常睡眠/唤醒模式的恢复是否会逆转骨转换标记物的解偶联。 2。通过评估来表征骨转换标记，BMD，骨微结构和强度的变化 与日班工作相比，一年中的第一年医院护士队列。 这项跨学科的协作研究将增强个人的健康状况。它将生成人类数据 将夜班工作确立为骨骼健康受损的新颖，可能改变的风险因素并告知 它通过改变男女的骨骼代谢的机制。这些知识将为 进行干预以预防低骨质量，骨质疏松和断裂的机会，包括功能丧失 他们造成的独立性和死亡率。此外，这一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 预防，评估和治疗骨质疏松症的范式转移。