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.
Highlights
Osteogenesis imperfecta (OI or brittle bone disease) is a hereditary disease which results in extreme bone fragility
Whole body vibration (WBV) treatment improved the trabecular and the cortical bone morphology during the growth in very young oim mouse hind limbs. This improvement of the cortical bone morphology correlates with a trend toward an increase of the mechanical properties observed during the three point bending
In the vibrated wild type mice, the osteogenic effect of whole body vibration (WBV) on the cortical bone morphology was apparent when the full lengths of the femur and tibia diaphysis were considered. This “global” improvement was sufficient to obtain a significant positive impact on the femur rigidity and yield limit during the three point bending test. The improvement of both cortical and trabecular bone compartment in the oim mice tibial metaphysis when subjected to WBV is in accordance with the findings of Xie et al in slightly older but still growing BALB mice [39] and suggests that growing bone may be sensitive to WBV
Summary
Osteogenesis imperfecta (OI or brittle bone disease) is a hereditary disease which results in extreme bone fragility. Mutation of the genes coding for collagen type 1 (col-1) is the main cause of OI, resulting in a quantitative or qualitative alteration of col-1 production. This leads to extremely active bone remodelling, disorganized woven bone tissue, reduced trabecular and cortical bone mass and degraded bone mechanical properties [1]. There is currently no direct cure for OI and only symptomatic treatments are available, such as physiotherapy to increase postural strength, surgery to correct bone deformation and
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