The Study Of Aspirin And Metformin For The Prevention Of Steroid Induced Osteonecrosis Of The Femoral Head

BackgroundSteroid induced osteonecrosis of the femoral head is a common Orthopaedic disease which is difficult to treat.The progression of the disease is irreversible and the effect of conservative treatment is poor.Abnormal lipids metabolism,coagulation disorders,decreasing in the number and activity of bone mesenchymal stem cells(BMSCs)are considered to be the main reasons leading to steroid-associated osteonecrosis of the femoral head.Currently there is no satisfactory preventive medicine for steroid induced osteonecrosis of the femoral head.Studies have found that aspirin and metformin can enhance osteogenesis,inhibit bone resorption,modulate lipid metabolism and promote osteogenic differentiation of BMSCs.So we hypothesized that aspirin and metformin might prevent steroid induced osteonecrosis of the femoral head.Method1.Lipopolysaccharide(LPS,20?g/kg,intraperitoneal injection twice)and methylprednisolone(MPS,40mg/kg,intramuscular injection 3 times)are used to establish the rat steroid induced osteonecrosis of the femoral head model.The experimental groups are given 10mg/kg/day aspirin or 100mg/kg/day metformin everyday at the time of model establishment.After 1.5/3 months the levels of serum osteocalcin were analyzed and the rats were sacrificed.The incidence of osteonecrosis of the femoral head was evaluated using micro CT and histopathology.2.Two rats of each subgroup of the 1.5 months group were randomly selected for the experiment of BMSCs.The rat femur BMSCs were isolated by whole bone marrow adherence method.The first passage of BMSCs were induced to differentiate into osteoblasts using an osteogenic medium for 14 days,after which the markers relating to osteogenic differentiation were analyzed(alkaline phosphatase,osteocalcin,type ?collagen and calcium deposits).Result1.The incidence of osteonecrosis in the aspirin group was significantly lower than that in the model group,both for 1.5 months and 3 months(p<0.05).The incidence of osteonecrosis in the 1.5months metformin group was lower than that in the 1.5month model group,but not significant(p=0.0995).The incidence of osteonecrosis in the 3months metformin group was significantly lower than that in the 3 months model group(p<0.05).Compared with the model group,the bone volume,trabecular thickness was higher in both the aspirin group and metformin group.2.By using whole bone marrow adherence method,BMSCs can be isolated and cultured.The first generation BMSCs can be induced to osteogenic differentiation.The levels of markers relating to osteogenic differentiation(alkaline phosphatase,osteocalcin,type I collagen and calcium deposits)were significantly higher in the aspirin group compared with model group.The levels of alkaline phosphatase,type I collagen and calcium deposits were significantly higher in the metformin group compared with model group.Conclusion1.Aspirin 10mg/kg/day for 1.5 or 3 months can lead to lower incidence of steroid-associated osteonecrosis of the femoral head,and higher bone volume,trabecular thickness.2.Metformin 100mg/kg/day for 3 months can lead to lower incidence of steroid-associated osteonecrosis of the femoral head,and higher bone volume,trabecular thickness.3.Aspirin 10mg/kg/day or Metformin 100mg/kg/day for 1.5 months can enhance the osteogenic differentiation of BMSCs in steroid-induced osteonecrosis rat model.