Doctoral Dissertation Research: Exploring Localized Relationships Between Age-related Bone Loss and Cortical Expansion in Diaphyseal Bone

随着人类年龄的增长，长骨的矿物质含量密度下降，骨骼几何形状发生变化，骨壁厚度减少，但总直径增加。预期来自习惯性活动的局部机械负荷将介导矿物质损失和骨壁变化，这应该在不同骨之间的骨横截面图像的比较中观察到。本博士论文项目旨在确定年龄相关的骨矿物质密度（BMD）和骨壁几何形状的变化是否在40-80岁之间的成年人的四肢长骨横截面中局部共同发生。一个本地化的关系将表明，骨负荷的几何适应持续到老年，尽管整体损失的骨量，这对解释老化的考古背景，以及预防与年龄相关的脆性骨折的影响。该项目支持本科生和研究生在STEM的培训和研究机会。除了以会议演讲和期刊出版物的形式进行学术传播之外，这项研究还将向项目参与者以及公共研究论坛，社区中心和其他可访问的环境进行介绍。骨质疏松相关的骨丢失归因于许多相互关联的全身因素（例如，激素下降，肌肉力量丧失），从而被视为全身的整体过程。随着年龄的增长，骨壁直径扩大，并通过从内表面去除骨和在外表面上添加骨而变得更薄。由此产生的骨横截面直径的扩张增强了在机械载荷下的抗弯曲性，并且由于与BMD下降大致同时发生，其特征在于对骨丢失的补偿。在生命早期，骨壁几何形状和微观结构适应机械载荷。如果这种适应能力延伸到成年后期，则年龄相关的壁扩张和BMD下降可能根据骨横截面内、沿着骨长度和骨元素之间的典型载荷模式而局部变化。如果，除了局部变化，结果表明，这些过程表现出局部协变，这项研究可以提供进一步的支持骨壁的扩张和BMD下降之间的补偿关系。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

As humans age, the density of the mineral content of long bones declines, and bone geometry changes so that thickness of the bone wall decreases but overall diameter increases. It is expected that local mechanical loading from habitual activity will mediate both mineral loss and bone wall changes, which should be observable in comparisons of bone cross-sectional images between different bones. This doctoral dissertation project seeks to establish whether age-related changes in bone mineral density (BMD) and bone wall geometry co-occur locally within limb long bone cross-sections among living adults between 40-80 years of age. A localized relationship would suggest that geometric adaptation of bone to loading persists into advanced age despite overall loss of bone mass, which has implications for the interpretation of aging from archaeological contexts as well as for prevention of age-related fragility fractures. The project supports undergraduate and graduate training and research opportunities in STEM. In addition to scholarly dissemination of results in the form of conference presentations and journal publications, this research will be presented to project participants, as well as at public research forums, community centers, and other accessible settings. Age-related bone loss has been attributed to a host of interrelated systemic factors (e.g., hormone decline, loss of muscle strength) and is thereby treated as a global process throughout the body. With age, bone wall diameters expand and become thinner through the removal of bone from the internal surface and addition on the external surface. The resulting expansion of bone cross-sectional diameter bolsters resistance to bending under mechanical loads and, due to roughly concurrent timing with BMD decline, has been characterized as compensatory to bone loss. Earlier in life, bone wall geometry and microstructure adapt to mechanical loading. If this ability to adapt extends into late adulthood, it is possible that age-related wall expansion and BMD decline vary locally according to typical loading patterns within a bone cross-section, along the length of a bone, and between bone elements. If, in addition to local variation, results indicate that these processes exhibit local covariation, this research can provide further support to the compensatory relationship between the expansion of bone walls and BMD decline.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.