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，导致骨壁厚度减少，但总直径增加。预期习惯性活动引起的局部机械负荷将同时介导矿物质丢失和骨壁改变，这在不同骨骼之间的骨截面图像的比较中应该是可以观察到的。这项博士论文项目旨在确定在40-80岁的活体成年人中，四肢长骨横截面中是否存在与年龄相关的骨密度(BMD)和骨壁几何形状的变化。局部的关系表明，尽管骨量总体减少，但骨骼对负荷的几何适应一直持续到高龄，这对于从考古学背景下解释衰老以及预防与年龄相关的脆性骨折具有重要意义。该项目支持STEM的本科生和研究生培训和研究机会。除了以会议报告和期刊出版物的形式以学术形式传播成果外，这项研究还将提交给项目参与者，以及在公共研究论坛、社区中心和其他无障碍环境中展示。与年龄相关的骨丢失被归因于一系列相互关联的系统因素(如激素下降、肌肉力量丧失)，因此被视为整个身体的一个全球性过程。随着年龄的增长，骨壁直径会随着内表面的去骨和外表面的添加而扩大和变薄。由此产生的骨横截面直径的扩大增强了在机械载荷下的抗弯能力，由于与骨密度下降大致同步，因此被认为是对骨丢失的补偿。在生命的早期，骨壁的几何形状和微结构适应机械载荷。如果这种适应能力持续到成年后期，则与年龄相关的骨壁扩张和骨密度下降可能会根据骨横截面内、沿骨长度和骨元素之间的典型负荷模式而局部不同。如果除局部变异外，结果表明这些过程表现出局部协变性，这项研究可以进一步支持骨壁扩张和BMD下降之间的补偿关系。这一裁决反映了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。

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.