Study On The Mechanism Of Epimedium On Bone Metabolism And Its Application In Metastatic Bone Tumor Treatment

Objective:1 To explore effects of icariin on osteogenic differentiation and bone formation of bone marrow mesenchymal stem cells in osteoporosis rats.2 To investigate the effect of total flavonoids of epimedium combined with radiotherapy chemotherapy or on patients with metastatic bone tumors.Methods:1 Female rats were randomly divided into two groups:one group received ovariectomy?OVX group?and the other group received sham operation?sham operation group?.Bone Marrow Stromal Cells?BMSCs?were isolated from BMSCs and BMSCs were randomly divided into 4groups:OVX group;Icariin(10^-5 mol/L,ICA)treatment group;ICA+5 mg/L Faslodex?ICI182780?treatment group and sham group.Alkaline Phosphatase?ALP?activity,alkaline phosphatase positive cloning,mineralized nodule formation,calcium deposition and the protein and mRNA expressions of estrogen regulatory protein 2?PS-2?,progesterone receptor?PR?,runt-related transcription factor 2?Runx-2?,estrogen ceceptor??ER??,osteoblast specific transcription factor?OSX?in BMSCs were compared between groups.2 138 patients with metastatic bone tumor who received treatment in our hospital from February 2015 to July 2016 were chosen.The patients were divided into radiotherapy group and combination treatment group according to the digital random table method,69 cases/group.The general condition of the two groups was comparable.At the end of the study,22 patients in the radiotherapy group fell off?including death?and 47 patients were included in the study;in the combined treatment group,17 patients fell off?including death?and 52 patients were included in the statistics.Radiotherapy group received radiotherapy alone;combined treatment group received radiotherapy and total flavonoids of epimedium combined therapy.Oral,2 times a day,3 times a day,in 24 weeks.The bone mineral density,bone metabolism,fracture rate,bone pain,bone metastasis,activity,adverse reaction and quality of life were compared between the two groups.3 156 patients with metastatic bone tumor who received treatment in our hospital from February 2015 to July 2016 were chosen.The patients were divided into chemotherapy group and combination treatment group according to the digital random table method,78 cases/group.The general condition of the two groups was comparable.At the end of the study,24 patients in the chemotherapy group fell off?including death?and 54 patients were included in the study;in the combined treatment group,18 patients fell off?including death?and 60 patients were included in the statistics.Chemotherapy group received interventional chemotherapy alone;combined treatment group received chemotherapy and total flavonoids of epimedium combined therapy.Oral,2 times a day,3 times a day,treatment for 24 weeks.The bone mineral density,bone metabolism,fracture rate,bone pain,bone metastasis,activity,adverse reaction and quality of life were compared between the two groups.Results:1 Compared with the model group,the ALP activity,alkaline phosphatase positive clones,mineralized nodule formation,calcium deposition,PS-2,PR,Runx-2,ER?and OSX protein and mRNA expression in BMSCs significantly increased,while the bone formation in BMSCs significantly decreased in ICA group;compared with the ICA group,the ALP activity,alkaline phosphatase positive clones,mineralized nodule formation,calcium deposition,PS-2,PR,Runx-2,ER?and OSX protein and mRNA expression in BMSCs significantly decreased,while the bone formation in BMSCs significantly increased in the ICA+ICI group.2 After treatment,the levels of Estradiol?E₂?,Calcium?Ca?,ALP,bone gla protein?BGP?in serum in the two groups were significantly lower than those before treatment,but the differences between the two groups were not statistically significant;after treatment,the levels of ALP and BGP in serum in the two groups were significantly lower than those before treatment,but the differences between the two groups were not statistically significant;after treatment,the bone mineral density in the radiotherapy group was lower than that before treatment,and the bone mineral density in the combined treatment group was higher than that before treatment,and the difference between two groups was statistically significant;the incidence of fracture in the radiotherapy group was 25.53%,the incidence of fracture in the combined treatment group was9.62%,and the difference was statistically significant??²=4.397,P=0.036?;the total effective rate of bone pain relief was 72.34%in the radiotherapy group,the total effective rate of bone pain relief was 86.54%in the combined treatment group,and the difference was statistically significant??²=6.474,P=0.039?;the total effective rate of bone metastases was 53.19%in the radiotherapy group,the total effective rate of bone metastases was 78.85%in the combined treatment group,the difference was statistically significant??²=7.853,P=0.049?;the total effective rate of activity ability improvement was 76.60%in the radiotherapy group,the total effective rate of activity ability improvement was 90.38%in the combined treatment group,and the difference was statistically significant??²=6.474,P=0.039?;the incidence of adverse reactions in the radiotherapy group was 25%,the incidence of adverse reactions in the combination treatment group was21.15%,and there was no significant difference between the two groups??²=0.844,P=0.932?;after treatment,the scores of physical function,shortness of breath,insomnia,economic difficulty and overall health status in the radiotherapy group were significantly lower than those before treatment,the scores of pain in the combination treatment group were significantly higher than those before treatment,the scores of insomnia,economic difficulties and overall health in the combination treatment group were significantly lower than before treatment,but the differences of body function,pain and overall health status between the two groups was statistically significant.3 After treatment,the level of E₂ in serum in two groups and the level of Ca in the combination treatment group both were significantly lower than those before treatment,the level of E₂ in serum in the combined treatment group was significantly higher than that in the chemotherapy group,the level of Ca in serum in the combined treatment group was significantly lower than that in the chemotherapy group,and the difference was statistically significant?P<0.05?;after treatment,levels of ALP and BGP in serum in chemotherapy group were significantly higher than those before treatment,the levels of ALP and BGP in serum in combination therapy group were significantly lower than those before treatment,the levels of ALP and BGP in serum in the combination group were significantly lower than those in the chemotherapy group;after treatment,the bone mineral density in the chemotherapy group was lower than that before treatment,and the bone mineral density in the combined treatment group was higher than that before treatment,and the difference between two groups was statistically significant;the incidence of fracture in the chemotherapy group was 27.78%,the incidence of fracture in the combined treatment group was 11.67%,and the difference was statistically significant??²=4.737,P=0.030?;the total effective rate of bone pain relief was 53.70%in the chemotherapygroup,the total effective rate of bone pain relief was 73.33%in the combined treatment group,and the difference was statistically significant??²=6.507,P=0.039?;the total effective rate of bone metastases was 50.00%in the chemotherapygroup,the total effective rate of bone metastases was 75.00%in the combined treatment group,the difference was statistically significant??²=8.381,P=0.039?;the total effective rate of activity ability improvement was72.22%in the chemotherapygroup,the total effective rate of activity ability improvement was88.33%in the combined treatment group,and the difference was statistically significant??²=6.044,P=0.049?;the incidence of adverse reactions in the chemotherapygroup was 18.52%,the incidence of adverse reactions in the combination treatment group was 18.33%,and there was no significant difference between the two groups??²=0.001,P=0.908?;after treatment,the scores of physical function,function,mood function,social function,pain,malignant vomiting,insomnia,loss of appetite,diarrhea,economic difficulty and overall health status in chemotherapy group were significantly lower than those before treatment,the scores of nausea and vomiting,insomnia,diarrhea,and economic difficulties in the combination treatment group were significantly lower than those before treatment,but the differences in somatic function,emotional function,social function,pain and overall health status were statistically significant.Conclusions:1 Icariin can promote osteogenic differentiation and bone formation of bone marrow mesenchymal stem cells in ovariectomized rats with osteoporosis.2 The quality of life of patients with metastatic bone tumors decrease with the progression of the disease,but on the basis of radiotherapy taking epimedium total flavonoids can alleviate the deterioration of quality of life may be associated with its ability to reduce osteoporosis and bone pain,inhibit bone metastases and improve patient activity.3 The total flavonoids of epimedium can improve the quality of life of patients with metastatic bone tumors receiving chemotherapy.This may be associated with total flavonoids of Epimedium alleviating osteoporosis,reducing bone pain,improving patient activity,and not significantly increasing the adverse effects.