Constrained tibial vibration does not produce an anabolic bone response in adult mice

Abstract

Osteoporosis is characterized by low bone mass and increased fracture risk. High frequency, low-amplitude whole-body vibration (WBV) has been proposed as a treatment for osteoporosis because it can stimulate new bone formation and prevent trabecular bone loss. We developed constrained tibial vibration (CTV) as a method for controlled vibrational loading of the lower leg of a mouse. We first subjected mice to five weeks of daily CTV loading (0.5 G maximum acceleration) with loading parameters chosen to independently investigate the effects of strain magnitude, loading frequency, and cyclic acceleration on the adaptive response to vibration. We hypothesized that mice subjected to the highest magnitude of dynamic strain would have the largest bone formation response. We observed a slight, local benefit of CTV loading on trabecular bone, as BV/TV was 5.2% higher in the loaded vs. non-loaded tibia of mice loaded with the highest bone strain magnitude. However, despite these positive differences, we observed significantly lower measures of trabecular structure in both loaded and non-loaded tibias from CTV loaded mice compared to Sham and Baseline Control animals, indicating a negative systemic effect of CTV on trabecular bone. Based on this evidence, we conducted a follow-up study wherein mice were subjected to CTV or sham loading, and tibias were scanned at the beginning and end of the study period using in vivo microCT. Consistent with the findings of the first study, trabecular BV/TV in both tibias of CTV loaded and Sham mice was, on average, 36% and 31% lower on day 36 than day 0, respectively, compared to 20% lower in Age-Matched Controls over the same time period. Contrary to the first study, there were no differences between loaded and non-loaded tibias in CTV loaded mice, providing no evidence for a local benefit of CTV. In summary, 5 weeks of daily CTV loading of mice was, at best, weakly anabolic for trabecular bone in the proximal tibia, while daily handling and exposure to anesthesia was associated with significant loss of trabecular and cortical bone. We conclude that direct vibrational loading of bone in anesthetized, adult mice is not anabolic.