The Osteogenic Exerts Of Radial Extracorporeal Shock Wave On Osteoporotic In An Ovariectomized Rat Model

Osteoporosis (OP), a major public health problem, is a chronic skeletal disease characterized by low bone mineral density resulting in fragile bones with increased risk of fracture. The fractures and the subsequent morbidity and mortality caused by OP as enormous public health concern. Pharmaceutical approaches need regular intake of medication and have potential adverse side effects. Exercise programs and biophysical interventions, as the alternative treatments, are the most common and effective strategies for decreasing the risk of developing osteoporosis.Shock waves are acoustical pulses that are characterized by a high peak pressure ranging from5to130Mpa, with a most common energy of50Mpa and a broad frequency of14Hz to20MHz, the most significant aspect of this form of energy is rapid initial rise in pressure amplitude over a short time less than10ns. Extracorporeal shock waves are known to stimilate the differentiation of mesenchymal stem cells toward osteoprogenitors and induce the expression of osteogenic-related growth proteins. Extracorporeal shock wave therapy (ESWT) is effective in the treatment of nonunions and fractures.ESW is a nonsurgical treatment and accompanied by less potential adverse side effects than Pharmaceutical approaches.In this stydy, radial extracorporeal shock wave was applied to the osteoporosis rats model. We investigate if radial extracorporeal shock wave affected new bone formation and bone microarchitecture.Part1Establishment of rat osteoporosis model by ovariectomyObjective:To investigate the feasibility of establish rat soteoporosis model by ovariectomy plus Methylprednisolone injection.Methods:Twenty-four24-week-old female SD rats were divided into three groups randomly.Group A, eight rats were bilaterally ovariectomized; Group B, shame operation (non-osteoporotic); Group C, eight rats were bilaterally ovariectomized and plus Methylprednisolone injection. Before operation and2months after operation, the BMD were measured by double-energy-X-ray absorption meter.2months after operation, the animals were killed with use of an overdose of pentobarbital. The tibiaes were dissected, the soft tissue was removed.The tibiaes were prepared for micro-CT.Results:8weeks after operation, the BMD of lumbar and proximal femur in group C were14.6%and15.4%espectively lower than those in goroup B.8weeks after operation, the BMD of lumbar and proximal femur in group C were8.0%and8.3%espectively lower than those before the operation.8weeks after operation, the micro-CT reconstruction analysis showed that the BMD and BMC of tibiae in group C were11.1%and10.5%espectively lower than those in goroup B. The BV/TV of tibia in group C were23.2%espectively lower than group B. The Tb. N and Tb.Th of tibia in group C were23.2%and28.5%espectively lower than group B, the Tb.Sp of tibia in group C were47.8%higher than group B.Conclusion:The results show that ovariectomy plus Methylprednisolone injection is a effective method to estabish SD rat osteoporosis model.8weeks after ovariectomy, the osteoporosis model were estabished successfully.Part2The effect of radial extracorporeal shock wave on tibie of soteoporosis rat modelObjective:Some recent in vivo study showed that extracorporeal shock wave therapy (ESWT) affected new bone formation and bone microarchitecture in a healthy rat model. The aim of this study was to investigate whether radial ESWT could induce new bone formation in our established osteoporotic rat model. To assess whether radial ESWT might be a potential treatment for osteoporosis.Methods:Twenty four24-week-old female rats were bilaterally ovariectomized plus Methylprednisolone injection to estabish osteoporosis animal model, after8weeks post-ovariectomy, development of osteoporosis was confirmed by double-energy-X-ray absorption meter. All areceived radial extracorporeal shock wave to the right tibia; the contralateral side served as the control. Each shockwave had an exposure consisting of2000pulses at3Hz with an energy density of0.35mJ/mm, At four, eight, and twelve weeks after administration of the shock waves, bone mineral density(BMD), microarchitecture and dynamic histomorphometric index were evaluated respectively. Fourteenth and fifteenth day before euthanasia, subcutaneous injection of tetracycline hydrochloride at25mg/kg. Calcein green were administrated to the rats at5mg/kg at fourth and fifth day, before euthanasia.Results:Four weeks after ESWT, BV/TV was85%of baseline BV/TV in treated legs versus74%in untreated contralateral control legs.77%of baseline BV/TV in treated legs versus66%in untreated contralateral control legs at8weeks after ESWT (p<0.05). At12weeks, the BV/TV of the treated leg was65%of baseline BV/TV, whereas in untreated control legs this was62%. At different time points, Mineral apposition rates of all ESW reated regions were also higher than those of the control (p>0.05).The max load were significantly higher in in treated legs than in untreated control legs8weeks (p<0.05).The rigidity were higher in in treated legs than in untreated control legs8weeks and12weeks (p<0.05).Conclusion:This study shows that bone microarchitecture can be affected by radial shock waves, leading to induce anabolic effects in osteoporotic rats. These findings suggest that radial ESW treatment could enhance local BMD by inducing new bone formation, and indicates that unfocused ESWT might be useful for the treatment of osteopenia and osteoporosis.