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

虽然人们知道骨骼是一种动态的、活的组织，可以对施加在它身上的力的变化做出反应，但研究人员还没有完全和详细地了解人类的这种反应。该项目将比较一生中超重和健康体重的个体的骨骼，以确定增加负荷和改变行走机制对骨骼微结构的影响。结果将有助于阐明机械力在确定骨骼微结构中所起的作用，并评估骨骼对负荷变化的敏感性。了解骨骼微结构作为负荷的函数的变化可能有助于人类学家根据骨形态重建过去的行为，也可能有助于临床了解骨质疏松和骨关节炎等情况。阐明体重和骨骼微结构之间的关系也可能为法医人类学家提供新的见解，以识别骨骼材料中的死者。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、图像分析和骨骼微结构分析方面接受多样化和高强度的动手研究培训。此外，该项目将促进公共科学宣传，特别是让传统上STEM领域代表性不足的学生参与进来。科学地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将通过添加骨材料来适应，而低应变水平将导致骨吸收或减少。这个项目的目标是测试人类的骨功能适应(沃尔夫定律)，将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)和作用力(动力学)的变化是否以及如何在人类骨骼的骨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堆叠的骨骼，这是一个极其有据可查的人类骨骼收集的一部分。使用新的分析技术并利用成熟的图像分析，该项目将量化肥胖和健康体重个体在人体骨骼中的骨小梁分布模式。结果将促进对人类骨骼中的松质骨结构及其与机械载荷的关系的了解，为数据收集和分析制定指南，并为未来的研究生成数据和软件。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.