Genetic variation in femur extrinsic strength in 29 different inbred strains of mice is dependent on variations in femur cross-sectional geometry and bone density

The femurs from groups of mice from 29 different inbred strains were characterized to study the genetic variations in bone parameters. For these analyses, we used peripheral quantitative computed tomography to assess bone size and density in addition to three-point bend testing to assess bone mechanical properties. Highly significant differences between inbred strains were found for all size, density, and mechanical parameters measured (P < 0.0001). Correcting femoral cross-sectional geometry values or bone mechanical properties values for body weight or femur length reduced but did not eliminate the variations in bone geometry or bone mechanical properties. Mice of similar body size had as much as a 40% difference in the midshaft total area of the femur. Regression analysis suggested that 50.9% of the variation in maximum load among strains was related to variations in section modulus, i.e., cross-sectional geometry, 21.5% was related to variations in material bone density, and 27.7% to variations in quality. These components were further analyzed to show that 3.9–27.8% of the variation in maximum load was related to adaptation to mechanical stress. These findings indicate that there is a significant genetic variation in the femur cross-sectional area, density, and mechanical properties between inbred mouse strains. These studies identify inbred mouse strains suitable for future studies identifying genes regulating bone geometry and mechanical properties.