Skeletal impacts of dual in vivo compressive axial tibial and ulnar loading in mice

Abstract

The use of compressive axial tibial loading for evaluation of bone adaptation and mechanotransduction has become a common technique in recent years. Despite its popularity, it only produces a single experimental limb per animal which can escalate sample sizes depending on study endpoints. We hypothesized the combination of compressive axial tibial and ulnar loading in a single animal would induce bone formation in loaded limbs, providing two experimental limbs per animal thereby reducing the animals required per study by half. Male and female C57BL/6J mice were purchased at 9 and 19 weeks (wks). Based on sex and age they were divided into 4 groups of N = 17. From each group, N = 5 were sacrificed at 10 and 20 wks for strain gauge calibration. At 11 wks and 21 wks, the left ulnae and right tibiae of the remaining animals (N = 12/group) were loaded 3 days/week for 4 weeks. Tibiae of all groups experienced significant increases in architectural properties due to loading in both trabecular and cortical compartments while there were no significant improvements in the ulna. Female tibiae showed improvements in mechanical properties, but these were not observed in the male tibiae where detrimental impacts were observed. In the ulna, females showed limited mechanical changes due to loading. Contrastingly, loading in males at 11 wks led to decreased mechanical properties while at 21 wks no impacts were observed. Overall, reported beneficial impacts of loading in tibiae were observed in architectural properties but were not maintained in the males’ mechanical properties. Impacts of ulnar loading on architectural and whole bone mechanical properties that have been reported elsewhere were not observed in any groups. These data suggest when architectural and mechanical properties are end points, combined loading is not optimal for reducing the number of animals required per study.