Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, 78227, USA,
Calcif Tissue Int. 2013 Nov;93(5):472-80. doi: 10.1007/s00223-013-9775-x. Epub 2013 Aug 27.
Intracortical microstructure influences crack propagation and arrest within bone cortex. Genetic variation in intracortical remodeling may contribute to mechanical integrity and, therefore, fracture risk. Our aim was to determine the degree to which normal population-level variation in intracortical microstructure is due to genetic variation. We examined right femurs from 101 baboons (74 females, 27 males; aged 7-33 years) from a single, extended pedigree to determine osteon number, osteon area (On.Ar), haversian canal area, osteon population density, percent osteonal bone (%On.B), wall thickness (W.Th), and cortical porosity (Ct.Po). Through evaluation of the covariance in intracortical properties between pairs of relatives, we quantified the contribution of additive genetic effects (heritability [h (2)]) to variation in these traits using a variance decomposition approach. Significant age and sex effects account for 9 % (Ct.Po) to 21 % (W.Th) of intracortical microstructural variation. After accounting for age and sex, significant genetic effects are evident for On.Ar (h (2) = 0.79, p = 0.002), %On.B (h (2) = 0.82, p = 0.003), and W.Th (h (2) = 0.61, p = 0.013), indicating that 61-82 % of the residual variation (after accounting for age and sex effects) is due to additive genetic effects. This corresponds to 48-75 % of the total phenotypic variance. Our results demonstrate that normal, population-level variation in cortical microstructure is significantly influenced by genes. As a critical mediator of crack behavior in bone cortex, intracortical microstructural variation provides another mechanism through which genetic variation may affect fracture risk.
皮质内微观结构影响皮质内裂纹的扩展和停止。皮质内重塑的遗传变异可能有助于机械完整性，从而影响骨折风险。我们的目的是确定皮质内微观结构的正常人群水平变异在多大程度上归因于遗传变异。我们检查了来自一个单一扩展家系的 101 只狒狒（74 只雌性，27 只雄性；年龄 7-33 岁）的右侧股骨，以确定骨单位数量、骨单位面积（On.Ar）、哈弗斯管面积、骨单位密度、骨单位百分比（%On.B）、壁厚度（W.Th）和皮质孔隙率（Ct.Po）。通过评估两对亲属之间皮质内特性的协方差，我们使用方差分解方法来量化这些性状的加性遗传效应（遗传力[h (2)）对变异的贡献。显著的年龄和性别效应占皮质内微观结构变异的 9%（Ct.Po）至 21%（W.Th）。在考虑年龄和性别后，On.Ar（h (2) = 0.79，p = 0.002）、%On.B（h (2) = 0.82，p = 0.003）和 W.Th（h (2) = 0.61，p = 0.013）的遗传效应显著，表明在考虑年龄和性别效应后，残留变异（遗传和环境因素共同作用的结果）的 61-82%归因于加性遗传效应。这相当于总表型方差的 48-75%。我们的研究结果表明，皮质内微观结构的正常人群水平变异受基因的显著影响。作为皮质内裂纹行为的关键介质，皮质内微观结构的变异为遗传变异影响骨折风险提供了另一种机制。
