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.

Collagen fibril morphology and mechanical properties of the Achilles tendon in two inbred mouse strains

“…Our choice of inbred mouse strains with regard to a structure-function baseline in tendon is rooted in a history of studies investigating bone morphology of different inbred strains to correlate them with their mechanical response (Akhter et al 1998;Turner et al 2000;Jepsen et al 2003;Tommasini et al 2005;Voide et al 2008). B6 and C3H have been identified as a model to study the genetic factors in osteoporosis (Beamer et al 1999).…”

“…This study was reviewed and approved by the local and state authorities for all levels of animal investigation. We used two inbred mouse strains with markedly different skeletal phenotypes, where B6 represents the low bone mass and C3H represents the high bone mass phenotype (Akhter et al 1998;Turner et al 2000;Jepsen et al 2003;Tommasini et al 2005;Voide et al 2008). Ten B6 and 10 C3H female mice were purchased from the Harlan breeding facility (Horst, The Netherlands).…”

Mechanical, biochemical, and dietary determinants of the functional model of bone development of the radius in children and adolescents

“…These parameters of bone geometry, bone volume, CSA and cortical thickness have been shown to be positively related to each other, and can also account for up to 80% of the variance in bone strength (Voide et al 2008). This may explain the larger observed associations between muscle and bone properties using pQCT as opposed to QUS.…”

Preclinical testing of drug delivery systems to bone

“…The speed slows down when using older animals, but still they display a faster healing than humans. Overall, the bones of small animals are more brittle, which makes them inappropriate for some drug delivery systems [137][138][139][140]. Mice, rats, and rabbits do not have a Haversian system [103,141].…”