Effects of load-bearing exercise on skeletal structure and mechanics differ between outbred populations of mice

• Outbred mouse stocks were used to examine whether skeletal benefits of exercise differ between genetically heterogeneous populations.
• In Hsd:ICR outbred mice, treadmill exercise enhanced femoral cortical and trabecular bone structure and diaphyseal mechanical properties.
• In Crl:CD1 outbred mice, treadmill exercise did not alter femoral structure but reduced diaphyseal resistance to fracture.
• Differential effects of exercise were likely due to genetic differences between stocks since most environmental variables were experimentally controlled.
• Just as skeletal benefits of exercise vary between individuals, our results suggest that skeletal adaptability also varies between populations.

Effects of load-bearing exercise on skeletal structure and mechanical properties can vary between inbred strains of mice. Here, we examine whether such variation also exists at the population level. An experiment was performed with two outbred mouse stocks that have been reproductively isolated for > 120 generations (Hsd:ICR, Crl:CD1). Growing females from each stock were either treated with a treadmill-running regimen for 1 month or served as controls. Limb forces were recorded with a force plate and cage activity monitored to verify that they were similar between stocks. After the experiment, femoral cortical and trabecular bone structure were quantified with micro-CT in the mid-diaphysis and distal metaphysis, respectively, and diaphyseal structural strength was determined with mechanical testing. Among Hsd:ICR mice, running led to significant improvements in diaphyseal bone quantity, structural geometry, and mechanical properties, as well as enhanced trabecular morphology. In contrast, among Crl:CD1 mice, the same running regimen had little effect on cortical and trabecular structure and significantly reduced diaphyseal resistance to fracture. In neither stock was body mass, muscle mass, or cage activity level different between runners and controls. Given that most environmental variables were controlled in this study, the differential effects of exercise on Hsd:ICR and Crl:CD1 bones were likely due to genetic differences between stocks. These results suggest that the benefits of loading for bone may vary between human populations (e.g., ethnic groups), in which case exercise programs and technologies designed to promote bone health with mechanical signals may be more advantageous to certain populations than others.