Tibial Mechanoadaptation in Male Mice is Modularised and Retained in Aging
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Background: The murine tibia is a remarkable bone in which to study mechanoadaptive responses. Studies into age-related shifts in these responses do not, however, fully explain sex-specific bone architectural changes related to age. Here, we generate data from male subjects to evaluate whether load-induced skeletal responses are modularised and age-related. Methods: Tibiae in young (12-weeks-old), mature (22-weeks-old), and aged (18-month-old) C57Bl/6 male mice were subjected to pre-calibrated right limb (left, control) loading for 2 weeks. Cortical bone formation was measured in young and mature mice at 3 positions, and new bone formation was evaluated in aged mice at a single location. Micro-computed tomography scans were used to measure trabecular changes. Results: We found that loading increased cortical formation at all tibial positions in young, and all except the most distal position in mature mice. Intriguingly, total cortical formation was also significantly greater in loaded tibiae in aged males. Loading failed to modify trabecular mass/architecture at any age. Conclusions: We conclude that load-induced cortical responses are partially retained, whereas trabecular bone appears resistant to loading in males of all ages. These data indicate modular patterns of mechanoadaptation across bone compartments that align with the emergence of age-related skeletal frailty.
Abstract
Background: The murine tibia is a remarkable bone in which to study mechanoadaptive responses. Studies into age-related shifts in these responses do not, however, fully explain sex-specific bone architectural changes related to age. Here, we generate data from male subjects to evaluate whether load-induced skeletal responses are modularised and age-related. Methods: Tibiae in young (12-weeks-old), mature (22-weeks-old), and aged (18-month-old) C57Bl/6 male mice were subjected to pre-calibrated right limb (left, control) loading for 2 weeks. Cortical bone formation was measured in young and mature mice at 3 positions, and new bone formation was evaluated in aged mice at a single location. Micro-computed tomography scans were used to measure trabecular changes. Results: We found that loading increased cortical formation at all tibial positions in young, and all except the most distal position in mature mice. Intriguingly, total cortical formation was also significantly greater in loaded tibiae in aged males. Loading failed to modify trabecular mass/architecture at any age. Conclusions: We conclude that load-induced cortical responses are partially retained, whereas trabecular bone appears resistant to loading in males of all ages. These data indicate modular patterns of mechanoadaptation across bone compartments that align with the emergence of age-related skeletal frailty.