A novel loading method for stimulation of trabecular bone growth in Mice

Vibrational loading has been shown to stimulate trabecular bone growth; therefore it is a promising method for the treatment of osteoporosis. Studies investigating vibrational loading have almost exclusively used whole-body vibration (WBV). In mice, it is difficult to control the amount of skeletal vibration that a particular skeletal site experiences during WBV. In this study we propose constrained tibial vibration (CTV) as a new method to deliver controlled vibrational loading to the skeletons of mice. The CTV device consists of two opposing columns that isolate the lower leg of a mouse and apply a weight that is free to move vertically during vibrational loading. To investigate this new method we analyzed the transmissibility of acceleration through the mouse leg in the CTV system. We found clear peaks in transmissibility at 35 and 65 Hz, with another broad peak at approximately 130 Hz. This demonstrates the strong frequency dependence of the mouse lower leg to CTV. A finite element model was used to find the natural frequencies and mode shapes of a mouse tibia-fibula. In an unconstrained setup (undefined boundary conditions) the first two natural frequencies were at 6,125 and 10,369 Hz. When a mass was added to the distal end of the model to simulate the load bearing setup, the first two natural frequencies were 198 and 5,564 Hz. This suggests that with non-load bearing conditions, vibrational loading is not likely to cause significant bone deformation at frequencies from 20-100 Hz, whereas with load bearing conditions the vibrational loading may cause significant bone strain as the loading frequency approaches the first natural frequency. Finally, in a preliminary experiment we subjected mice to low-level CTV (< 1.0 g maximum acceleration during vibration) with either a load bearing or non-load bearing setup. Bone volume (BV/TV) was increased by 36% in the loaded tibias of mice subjected to load bearing during vibration when compared to non-loaded control limbs. In mice subjected to non-load bearing conditions during vibration, however, the increase was only 7%. This suggests that the osteogenic response due to vibrational loading is dependent on longitudinal bone strain due to weight bearing during loading.