Mechanical Loading, Sex, Age, and Cortical Location Influence Bone Tissue Composition in Mice
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The application of non-invasive mechanical loads to rodent limbs induces geometric and material changes in the skeleton11. Geometric adaptation has been characterized extensively, but the material changes are less well understood. Raman microspectroscopy measures chemical composition at the tissue level and was used to detennine the effects of in vivo mechanical loading, sex, age, and cortical location on periosteal composition in mouse tibiae. The degree of mineralization (mineral-to-matrix) and carbonate substitution (CO32-:PO43-) ratios were used to assess tissue composition. The degree of mineralization at the periosteum was lower with loading in all mouse groups. Sex and age-based differences in mineralization were present in the control limbs. Males had greater mineralization but lower carbonate substitution than females. Mature females were more mineralized than but had similar carbonate substitution to younger growing females. Variation in tissue composition by cortical location occurred in mature females but not in growing females and males. To understand the implications of these findings on functional performance, the material changes reported here need to be combined with geometric and morphological analyses to form a more complete view of structural adaptation of the tibia.