Therapeutic impact of low amplitude high frequency whole body vibrations on the osteogenesis imperfecta mouse bone

Abstract

Osteogenesis imperfecta (OI) is characterized by extremely brittle bone. Currently, bisphosphonate drugs allow a decrease of fracture by inhibiting bone resorption and increasing bone mass but with possible long term side effects. Whole body mechanical vibrations (WBV) treatment may offer a promising route to stimulate bone formation in OI patients as it has exhibited health benefits on both muscle and bone mass in human and animal models. The present study has investigated the effects of WBV (45Hz, 0.3g, 15minutes/days, 5days/week) in young OI (oim) and wild type female mice from 3 to 8weeks of age. Vibration therapy resulted in a significant increase in the cortical bone area and cortical thickness in the femur and tibia diaphysis of both vibrated oim and wild type mice compared to sham controls. Trabecular bone was not affected by vibration in the wild type mice; vibrated oim mice, however, exhibited significantly higher trabecular bone volume fraction in the proximal tibia. Femoral stiffness and yield load in three point bending were greater in the vibrated wild type mice than in sham controls, most likely attributed to the increase in femur cortical cross sectional area observed in the μCT morphology analyses. The vibrated oim mice showed a trend toward improved mechanical properties, but bending data had large standard deviations and there was no significant difference between vibrated and non-vibrated oim mice. No significant difference of the bone apposition was observed in the tibial metaphyseal trabecular bone for both the oim and wild type vibrated mice by histomorphometry analyses of calcein labels. At the mid diaphysis, the cortical bone apposition was not significantly influenced by the WBV treatment in both the endosteum and periosteum of the oim vibrated mice while a significant change is observed in the endosteum of the vibrated wild type mice. As only a weak impact in bone apposition between the vibrated and sham groups is observed in the histological sections, it is possible that WBV reduced bone resorption, resulting in a relative increase in cortical thickness. Whole body vibration appears as a potential effective and innocuous means for increasing bone formation and strength, which is particularly attractive for treating the growing skeleton of children suffering from brittle bone disease or low bone density pathologies without the long term disadvantages of current pharmacological therapies.

Fig. 1

Illustration of the regions of cortical and trabecular bone investigated for the morphology analyses on the micro computed tomography images obtained from the mice femur and tibia.

Fig. 2

Calcein labels observed by FITC fluorescence light microscopy (10 ×) in the tibia mid-diaphysis cross-section of a wild type vibrated mouse (left) and in the frontal slices of the proximal tibia of a wild type (middle) and oim (right) vibrated mice. The red box represent the trabecular bone region of interest (between 200 and 1200 μm under the growth plate) analysed from the proximal tibia.

Fig. 3

Cortical bone cross section area and mean thickness (mean and standard deviation) measured along the diaphysis of the tibia (A, C) and femur (B, D) of the wild type and oim mice (* p < 0.05, ** p < 0.01). Cortical mean thickness was significantly greater in the Oim vibrated mice in the proximal tibia and the femur mid-diaphysis. Cross section area was also found significantly greater in the proximal tibia of the oim vibrated mice. Wild vibrated mice exhibited also greater cortical thickness in the tibia mid-diaphysis. In the femur only a tendency is observed but not significant. A tendency toward greater value of cross-section area was also observed in the tibia and femur of the wild type vibrated mice but only significant at 60% of the femur total length.

Fig. 4

Trabecular bone surface (mm²) and bone volume fraction measured in the tibia proximal metaphysis (A, C) and femur distal metaphysis (B, D) of the wild type and oim mice. (* p < 0.05, ** p < 0.01). In the tibia, bone volume fraction was significantly greater in the vibrated group for the oim mice but not for the wild type mice. In the femur, no significant difference was found between vibrated and sham groups for both parameters. Oim vibrated mice exhibited a significantly higher bone volume fraction while wild type mice showed only a non-significant trend. In the femur, no significant difference were found.