Aged mice have enhanced endocortical response and normal periosteal response compared to young-adult mice following 1 week of axial tibial compression


Brodt, M.D. and Silva, M.J.


With aging, the skeleton may lose its ability to respond to positive mechanical stimuli. We hypothesized that aged mice are less responsive to loading compared to young-adult mice. We subjected aged (22 mo) and young-adult (7 mo) BALB/c male mice to daily bouts of axial tibial compression for one week, and evaluated cortical and trabecular responses using microCT and dynamic histomorphometry. The right legs of 95 mice were loaded for 60 rest-inserted cycles/day to 8, 10 or 12 N peak force (generating mid-diaphyseal strains of 900-1900 µ endocortically and 1400-3100 µ periosteally). At the mid-diaphysis, mice from both age groups showed a strong anabolic response on the endocortex (Ec) and periosteum (Ps) (Ec.MS/BS and Ps.MS/BS: loaded [right] vs. control [left], p < 0.05). Generally, bone formation increased with increasing peak force. At the endocortical surface, contrary to our hypothesis, aged mice had a significantly greater response to loading than young-adult mice (Ec.MS/BS and Ec.BFR/BS: 22-mo vs. 7-mo, p < 0.001). Responses at the periosteal surface did not differ between age groups (p < 0.05). The loading-induced increase in bone formation resulted in increased cortical area in both age groups (loaded vs. control, p < 0.05). In contrast to the strong cortical response, loading only weakly stimulated trabecular bone formation. Serial (in vivo) microCT at the proximal metaphysis revealed that loading caused a loss of trabecular bone in 7-mo mice whereas it appeared to prevent bone loss in 22-mo mice. In summary, one week of daily tibial compression stimulated a robust endocortical and periosteal bone formation response at the mid-diaphysis in both young-adult and aged male BALB/c mice. We conclude that aging does not limit the short-term anabolic response of cortical bone to mechanical stimulation in our animal model.

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