Experimental Study Of Alendronate In The Treatment Of Osteoporosis

Background and Objective:As China entered the aging society and people’s average life expectancy increased,more and more patients with osteoporosis,seriously affecting the quality of life of patients and bring a heavy economic burden to society.Osteoporosis fracture is becoming more and more common in our clinic,but some doctors often ignore the anti-osteoporosis treatment while dealing with the fracture,especially in the basic hospitals of our country.Therefore,this topic takes this as the research direction and the design experiment,explores the alendronate sodium treatment osteoporosis experimental research,provides the reference for the future osteoporosis patients in the clinical treatment.Methods:20 New Zealand adult female rabbits were selected,aged 4~6 months and weighing 2.0~3.0kg.They were randomly divided into two groups,A and B,with 10 rabbits in each group.Bilateral ovaries of 20 adult female rabbits were removed surgically in aseptic condition to establish the animal model of osteoporosis.Ten rabbits in group A were treated with alendronate(1.15 mg·kg-1·week-1)once a week by a stomach tube,whereas the remaining ten in group B were treated with physiological saline.The efficacy of alendronate treatment were evaluated by the sports ability score and the Basso,Beattie,and Bresnahan(BBB)score;the changes in the levels of related cytokines were measured by enzyme-linked immunosorbent assay(ELISA)and immunohistochemical staining.Furthermore,the expression of microRNA-143 in osteoporotic patients was detected by RT-PCR,and the expression of microRNA-143 in osteoporotic patients treated with alendronate sodium was also examined;furthermore,the expression of microRNA-143 in rabbit spinal osteoporosis model was detected after successful establishment,and alendronate sodium and physiological salts were used.In order to further explore the expression level,signal pathway and apoptosis of alendronate sodium in diet-induced osteoporosis in mice,the levels of ALP,the changes of microwave-143/P38 signaling pathway and apoptosis were detected after treatment with alendronate sodium.Results:Treatment improved dyskinesia of the animals in group A than that in group B,with significant improvement occurring in the 4th week of treatment.The BBB score of the group A animals revealed movements similar to normal,but that of the group B animals exhibited significant motor disturbance(P < 0.01).Measurement of the biomechanical properties further showed that alendronate had a positive effect on osteoporosis treatment.The results of ELISA and immunohistochemistry showed that the levels of ALP,BMP-2,bFGF and IGF-1 were elevated in group A,suggesting that alendronate might be able to treat osteoporosis through some cytokine-related mechanisms.After establishing the spinal osteoporosis model of rabbits,the expression of microRNA143 was detected.The results showed that the expression of microRNA143 was significantly increased in the osteoporosis model group.The rabbits in group A and group B were treated with alendronate and saline solution respectively.The results showed that after treatment with alendronate sodium,the mRNA level of microarray-143 in osteoporosis model group decreased significantly(P=0.023).In diet-induced osteoporosis in mice,P38 signaling pathway was activated in bone marrow cells,and ATP production in mitochondria was decreased.Caspase-3 activity assay showed that apoptosis in bone marrow cells was enhanced in diet-induced osteoporosis.Finally,after treatment with alendronate,the signal pathway of microarray-143/P38 in bone marrow cells was inhibited,and the ATP production of mitochondria was increased,Caspase-3 activity assay showed that apoptosis of bone marrow cells decreased in diet-induced osteoporosis.Conclusion:1.Alendronate can treat osteoporosis by regulating the secretion of cytokines such as ALP,BMP-2,bFGF and IGF-1.2.MiR-143 may be a specific biomarker in osteoporosis patients.The level of miR-143 is positively correlated with the severity of osteoporosis.3.Alendronate can treat osteoporosis by inhibiting the expression of miR-143.4.P38 signaling pathway is activated in diet-induced osteoporosis in mice.Inhibition of P38 signaling pathway can alleviate diet-induced osteoporosis.5.Alendronate regulates miR-143/ P38 signaling pathway and inhibits diet induced osteoporosis in mice.