Differential Effects of Bone Structural and Material Properties on Bone Competence in C57BL/6 and C3H/He Inbred Strains of Mice

Abstract

The femoral neck is a relevant and sensitive site for studying the degree of osteopenia. Engineering principles predict that bone structural parameters, like cross-sectional geometry, are important determinants of bone mechanical parameters. Mechanical parameters are also directly affected by the material properties of the bone tissue. However, the relative importance of structural and material properties is still unknown. The aim of this study was to compare bone competence and structural parameters between a murine strain showing a low bone mass phenotype, C57BL/6 (B6), and another one showing a high bone mass phenotype, C3H/He (C3H), in order to better determine the role of bone structure and geometry in bone failure behavior. Murine femora of 12- and 16-week-old B6 and 12- and 16-week-old C3H inbred strains were mechanically tested under axial loading of the femoral head. In order to assess the structural properties, we performed three-dimensional morphometric analyses in five different compartments of the mouse femur using micro-computed tomography. The mechanical tests revealed that B6 femora became stiffer, stronger, and tougher at 12-16 weeks, while bone brittleness stayed constant. C3H bone stiffness increased, but strength remained constant, work to failure decreased, and bone became more brittle. These age effects indicated that B6 did not reach peak bone properties at 16 weeks of age and C3H did reach maximal skeletal biomechanical properties before 16 weeks of age. Our investigations showed that 83% of the strength of the femoral neck in the B6 strain was explained by cortical thickness at this location; in contrast, in C3H none of the mechanical properties of the femoral neck was explained by bone structural parameters. The relative contributions of bone structural and material properties on bone strength are different in B6 and C3H. We hypothesize that these different contributions are related to differences at the ultrastructural level of bone that affect bone failure.