Hierarchical relationship between bone traits and mechanical properties in inbred mice
Hierarchical relationship between bone traits and mechanical properties in inbred mice
复制标题
DOI：
10.1007/s00335-002-3045-y
复制
发表时间：
2003-02-01
期刊：
影响因子：
2.5
通讯作者：
Nadeau, JH
中科院分区：
文献类型：
--
作者：
Jepsen, KJ;Akkus, O;Nadeau, JH
骨质疏松性骨折的发病率和潜在的危险因素，如低峰值骨量是遗传的，但骨质疏松症的遗传基础仍然知之甚少。基于梁理论，说明结构的力学性能取决于组成材料的数量和质量，我们研究了8个近交系小鼠股骨的全骨力学性能和一组形态和组成特征之间的关系。K-means聚类分析显示，根据骨面积（组织量）、惯性矩（组织分布）和灰分含量（组织质量）的组合，可以根据基因型对个体股骨进行可靠的分类。这一性状组合解释了四个全骨力学特性的66-88%的应变间变异性，这些特性描述了失效过程的各个方面，包括脆性的测量。硬度和最大负荷与皮质区功能相关，而脆性的措施与灰分含量。与此相反，工作失败是不直接相关的一个单一的特征，但取决于一个组合的特征幅度。从这些研究结果，这是完全符合既定的力学理论，我们开发了一个层次的范式，有关的机械性能，定义骨脆性与易于测量的表现出很强的遗传性的表型性状。这一范例将有助于指导寻找骨折易感性和骨质疏松症的基因。此外，由于我们检查的特征是可测量的非侵入性手段，这种方法也可以证明直接适用于骨质疏松症的风险评估。
Osteoporotic fracture incidence and underlying risk factors like low peak bone mass are heritable, but the genetic basis of osteoporosis remains poorly understood. Based on beam theory, stating that mechanical properties of a structure depend on both the amount and quality of the constituent materials, we investigated the relationship between whole bone mechanical properties and a set of morphological and compositional traits in femurs of eight inbred mouse strains. K-means cluster analysis revealed that individual femora could be classified reliably according to genotype based on the combination of bone area (tissue amount), moment of inertia (tissue distribution), and ash content (tissue quality). This trait combination explained 66-88% of the interstrain variability in four whole-bone mechanical properties that describe all aspects of the failure process, including measures of brittleness. Stiffness and maximum load were functionally associated with cortical area, while measures of brittleness were associated with ash content. In contrast, work-to-failure was not directly related to a single trait but depended on a combination of trait magnitudes. From these findings, which were entirely consistent with established mechanical theory, we developed a hierarchical paradigm relating the mechanical properties that define bone fragility with readily measurable phenotypic traits that exhibit strong heritability. This paradigm will help guide the search for genes that underlie fracture susceptibility and osteoporosis. Moreover, because the traits we examined are measurable with non-invasive means, this approach may also prove directly applicable to osteoporosis risk assessment.