An Experimental Study On Treatment Of Steroid-Induced Femoral Head Necrosis With Simvastatin And Marrow Stem Cells Transplantation

Objective To approach the possibility of combination of simvastatin and BMSCs transplantation for steroid-induced osteonecrosis of femoral head.Methods The BMSCs harvested from 24 rabbits were prepared for cell suspension at a concentration of 1×107/m L.Seventy New Zealand white rabbits received one intravenous injection of LPS(10μg/kg).After 24 h, three injections of 20 mg/kg of methylprednisolone were given intramuscularly at a time interval of 24h.Forty-eight rabbits diagnosed as having femoral head necrosis by MRI were divided into 4 groups randomly,Group A:no treatment;Group B:only decompression;Group C:decompression with BMSCs transplantation;and Group D:simvastatin drench(10mg/kg/d)and decompression with BMSCs transplantation.The general information of animals were recorded;after 4 and 8 weeks of operation,6 rabbits of each group were chosen randomly to do MRI scan, and femoral heads were harvested to do histopathology and scanning electron microscope(SEM)examination.Results After 8 weeks,rabbits became more active than before treatment,and walking way became normal gradually in groups C and D; 4 weeks after operation,the MRI low signal region of all groups had no obvious changes,but 8 weeks later,the necrosis signal region of group A magnified while it reduced obviously in group D.Histopathological observation:4 weeks after operation,diffuse presence of empty lacunae and pyknotic nuclei of osteocytes were found in the trabeculae,and few newborn micrangium could been seen in group A;lots of empty lacunae and a small quantity of newborn micrangium could been found in group B;and large amounts of osteoblats and newborn micrangium were found around the necrosis regions in groups C and D.The positive ratio of empty lacunae and microvessel density in group D were 19.30±1.52 and 7.08±1.09,showing significant difference(P＜0.05)compared with other groups.After 8 weeks of treatment,the bone trabecula collapsed in many regions in group A;there was fibra callus formation along the decompression channel in group B;few empty lacunae was in the bone trabecular,but the shape of marrow cavity was not normal in group C; and it showed almost normal appearance in group D.The positive ratio of empty lacunae and microvessel density in group D were 11.31±1.28 and 12.37±1.32,showing significant difference(P＜0.05)compared with other groups,meanwhile,showing significant difference(P＜0.05) compared with that of 4 weeks after operation.Scanning electron microscope:8 weeks after operation,in group A the bone trabecula collapsed in many regions,and few osteoblasts could been found on the surface,a great quantity of large size fat cells cumulated in the bone marrow;in group B cracked bone trabecula could been found occasionally;in group C the density of bone trabecula was lower than the normal;and in group D the shape of the marrow cavity and the density of bone trabecula were similar to the normal.Conclusions Simvastatin can promote the differentiation of osteocyte and vascular endothelial cell from MSCs,the combination of simvastatin and marrow stem cells transplantation for the treatment of steroid-induce femoral head necrosis have good application prospects.