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.

A controlled trial comparing one-year biochemical bone metabolism outcome in postmenopausal frail osteopenic women under weekly alendronate treatment, with or without whole-body vibration intervention

“…Nevertheless, results have been controversial depending on the study design, type of individuals, and treatment, especially concerning the use of BPs 9,10 . To note, WBV proved to increase bone formation in the tibia of growing mice compared to controls 11 while it was shown inactive in adult intact mice 12 .…”

High-frequency loading positively impacts titanium implant osseointegration in impaired bone

“…This makes HF mechanical loading a powerful non-pharmacological intervention not only for the treatment or prevention of osteoporosis but also for fracture healing and beyond [1,19,20]. Numerous in vivo systems employing HF loading have been successfully used, such as whole body vibration (WBV) devices [16][17][18] and individual limb compressive loading setups [21,22]. WBV experiments have evidenced the advantageous effects of HF loading on bone [16][17][18] and on titanium implant osseointegration [23].…”

Adaptation of Tibial Structure and Strength to Axial Compression Depends on Loading History in Both C57BL/6 and BALB/c Mice

“…In particular, our practice is to transport animals to the lab for daily or alternate day loading, whereas others perform loading in their animal facility. Previous data indicated that 5 weeks of daily handling and sedation induced trabecular and cortical loss in the tibia of 6-month, male C57BL/6 mice [18]. …”