Collaborative Research: Obesity as a Natural Experiment to Investigate Bone Functional Adaptation

合作研究：肥胖作为研究骨功能适应的自然实验

• 批准号: 1923044
• 负责人: Adam Sylvester
• 金额: $ 9.51万
• 依托单位: Johns Hopkins University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1923044&HistoricalAwards=false
• 关键词: Collaborative; Research; Obesity; Natural; Experiment

While it is understood that bone is a dynamic, living tissue that responds to changes in the forces applied to it, researchers do not yet have a complete and detailed understanding of this response in humans. This project will compare the skeletons of individuals who were overweight and healthy-weight during life to determine the effects of increased loading and altered walking mechanics on bone microstructure. Results will help clarify the role mechanical force plays in determining bone microstructure and assess the sensitivity of bone to load alteration. Understanding changes in bone microstructure as a function of loading may help anthropologists reconstruct past behaviors from bone form and may also inform clinical understanding of conditions such as osteoporosis and osteoarthritis. Elucidating the relationship between body weight and bone microstructure may also provide forensic anthropologists new insights for identifying decedents from skeletal material. As part of this project, three female graduate students will receive diverse and intense hands-on research training in high-resolution computed tomography, image analysis, and bone microstructure analysis. In addition, the project will foster public science outreach, specifically engaging students traditionally underrepresented in STEM fields. The theoretical basis behind the scientific understanding of bone functional adaptation is that bone tissue that experiences high levels of mechanical strain will adapt by adding bone material, while low strain levels will lead to bone resorption or reduction. The goal of this project is to test bone functional adaptation ("Wolff's Law") in humans using obesity as a natural experiment in load alteration. Results will establish if and how variation in locomotor motion (kinematics) and applied forces (kinetics) associated with obesity manifest in the trabecular structure of the human skeleton. The researchers will collect high-resolution computed tomography image stacks of bones that are part of an extremely well-documented human skeletal collection. Using novel analytical techniques and leveraging well-established image analysis, this project will quantify the patterns of trabecular bone distribution in obese and healthy-weight individuals across the human skeleton. Results will advance knowledge about trabecular bone structure in the human skeleton and its relationship to mechanical loading, produce guidelines for data collection and analysis, and generate data and software for future research.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

众所周知，骨骼是一种动态的活组织，可以对施加于其上的力的变化做出反应，但研究人员尚未对人类的这种反应有一个完整而详细的了解。该项目将比较生活中超重和健康体重个体的骨骼，以确定增加负荷和改变行走力学对骨骼微观结构的影响。结果将有助于阐明机械力在确定骨微观结构中的作用，并评估骨对载荷变化的敏感性。了解骨骼微观结构的变化作为载荷的功能，可以帮助人类学家从骨骼形态重建过去的行为，也可以为骨质疏松症和骨关节炎等疾病的临床理解提供信息。阐明体重和骨骼微观结构之间的关系也可能为法医人类学家从骨骼材料中识别死者提供新的见解。作为该项目的一部分，三名女研究生将在高分辨率计算机断层扫描、图像分析和骨骼微观结构分析方面接受多样化和高强度的实践研究培训。此外，该项目将促进公共科学推广，特别是吸引传统上在STEM领域代表性不足的学生。科学理解骨功能适应的理论基础是，经历高水平机械应变的骨组织会通过添加骨材料来适应，而低水平应变会导致骨吸收或减少。这个项目的目标是测试骨功能适应（“沃尔夫定律”）在人类使用肥胖作为负荷变化的自然实验。结果将确定与肥胖相关的运动运动（运动学）和施加力（动力学）的变化是否以及如何在人类骨骼的小梁结构中表现出来。研究人员将收集高分辨率的计算机断层扫描图像，这些图像是人类骨骼收藏的一部分。利用新颖的分析技术和完善的图像分析，该项目将量化肥胖和健康体重个体在整个人类骨骼中的小梁骨分布模式。研究结果将促进对人类骨骼小梁骨结构及其与机械载荷关系的了解，为数据收集和分析提供指导，并为未来的研究生成数据和软件。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。