Treating Glucocorticoid-induced Osteoporosis Rats With Adrenomedullin(27-52)

【Background】Osteoporosis(OP) is a disease characterized by low bone mass anddeterioration of bone microarchitecture, which lead to an increase bonefragility and tendency of fractures. The incidence ofGlucocorticoid-induced osteoporosis(GIOP) takes the first place of theprevalence of secondary osteoporosis. The main cause for GIOP is thedecrease of bone formation, however, the regular drugs for osteoporosismostly belong to antiresorptives. Therefore, the most challenge of theresearch area of osteoporosis is to seek for a bone-forming drugs.Adrenomedullin(ADM) is a potent stimulator which can effectively stimulatethe differentiation of osteoblast. Adrenomedullin (27-52)is a polypeptide thatis a part of adrenomedullin. Comparing with adrenomedullin,Adrenomedullin (27-52) has the same effect on bone but without any effecton lung, platelet, stomach and cardiovascular system. Thus, Adrenomedullin(27-52) have a potential for becoming a effective and selectivebone-forming drug. 【Objective】To investigate the effects of adrenomedullin(27-52) on bone minernaldensity and histology of bone tissue, biomechanical property of the femur,radiography of femur, as well as histomorphometric parameters inglucocorticoid-induced osteoporosis rats.【Material and method】48 adult female Wistar rats were randomly divided into four groups:â‘ normal control;â‘¡DXM,â‘¢DXM+ADM(27-52);â‘£DXM+Vitamin D₃.By intramuscular injection of dexamethasone (DXM) 1mg/kg twice a weekduring the first 8 weeks, the animal model of Glucocorticoid inducedosteopoprosis was established. After DXM, DXM+ADM(27-52) and DXM+Vitamin D₃ were applied normal saline(NS), ADM(27-52) and Vitamin D₃respectively for 8 weeks, bone minemal density and histology of bonetissue, biomechanical property of the femur, radiography of femur, as well ashistomorphometric parameters were measured.【Results】1.bone minernal densityBMD of vertebrae body and femur in ADM(27-52) group wassignificantly higher than those in dexamethasone (DXM) group, while onlyBMD of vertebrae body in Vitamin D₃ group was higher than the DXM group.There were no differences between the BMD of vertebrae body and femur inADM(27-52) group and those in normal control.2. femoral geometrical parameters Comparing with the DXM group, the diameter(P＜0.05) and sectionmodulus under torsion(P＜0.01) were significantly increased inADM(27-52) group, however, these parameters were increased withoutsignificant difference in Vitamin D₃ group.3.Parameters in structural mechanicsComparing with the DXM group, the displacement(P＜0.01) and peakload(P＜0.01) were significantly increased in ADM(27-52) group, however,only peak load (P＜0.05) was significantly increased in Vitamin D₃ group.4. material mechanical parametersComparing with the DXM group, the max-strain(P＜0.01) andmax-stress(P＜0.01) were significantly increased in ADM(27-52) group,however, these parameters were increased without significant difference inVitamin D₃ group.5. histomorphometric parameters of femurComparing with the DXM group, %Tb. Ar and Tb. N significantlyincreased(P＜0.01), while Tb. Sp decreased significantly(P＜0.01) inADM(27-52) group. As to Vitamin D₃ group, %Tb. Ar significantlyincreased(P＜0.05) and Tb. Sp decreased significantly(P＜0.05).6. radiologyAccording to the X-ray film, cortex of femur in ADM(27-52) group ismuch thicker than those in DXM group, and transmittance of Cancellousbone decreased comparing with the DXM group.7.histologyThe trabecular bone was more compact, thicker, less sparse inADM(27-52) group comparing with the DXM group. 【Conclusion】1. ADM(27-52) could significantly increase the bone minernal densityof glucocorticoid-induced osteoporosis rats, and had better effects thanVitamin D₃.2. ADM(27-52) could significantly elevate biomechanical property ofthe femur of glucocorticoid-induced osteoporosis rats. Parameters instructural mechanics, histomorphometry and material mechanics were allimproved, which led to better resistance to fracture.3. ADM(27-52) could improve the microstructure of bone, significantlyincreased %Tb. Ar and Tb. N, moreover, significantly decreased Tb. Sp.Thus,the bone quality was improved.4. ADM(27-52) had a prominent bone-forming effect, and couldinterfere the development of glucocorticoids-induced osteoporosis,ADM(27-52) was a promising bone-forming anti-osteoporosis drug.