Selection for longer limbs in mice increases bone stiffness and brittleness, but does not alter bending strength

Abstract

The ability of a bone to withstand loads depends on its structural and material properties. These tend to differ among species with different modes of locomotion, reflecting their unique loading patterns. The evolution of derived limb morphologies, such as the long limbs associated with jumping, may compromise overall bone strength. We evaluated bone mechanical properties in the Longshanks mouse, which was selectively bred for increased tibia length relative to body mass. We combined analyses of 3D shape and cross-sectional geometry of the tibia, with mechanical testing and bone composition assays, to compare bone strength, elastic properties and mineral composition in Longshanks mice and randomly bred controls. Our data show that, despite being more slender, cortical geometry and predicted bending strength of the Longshanks tibia were similar to controls. In whole bone bending tests, measures of bone bending strength were similar across groups; however, Longshanks tibiae were significantly more rigid, more brittle, and required less than half the energy to fracture. Tissue-level elastic properties were also altered in Longshanks mice, but the bones did not differ from the control in water content, ash content or density. These results indicate that while Longshanks bones are as strong as control tibiae, selection for increased tibia length has altered its elastic properties, possibly through changes in organic bony matrix composition. We conclude that selection for certain limb morphologies, and/or selection for rapid skeletal growth, can lead to tissue-level changes that can increase the risk of skeletal fracture, which in turn may favor the correlated evolution of compensatory mechanisms to mitigate increased fracture risk, such as delayed skeletal maturity.

Keywords: Artificial selection; Bone cross-sectional geometry; Bone stiffness; Bone strength; Longshanks mouse.