| ObjectiveThis study aimed to investigate the effects of liraglutide on bone metabolism markers in rat models with glucocorticoid-induced osteoporosis(GIOP),including the effects on bone mass,bone tissue microstructure,bone biomechanics,and bone turnover markers.Methods(1)Thirty male Sprague–Dawley rats aged 8 weeks were randomly divided into three groups: control,model,and liraglutide intervention.The model and intervention groups were intramuscularly injected with dexamethasone at 1 mg/kg(twice a week)to induce GIOP.Simultaneously,the intervention group was subcutaneously injected with liraglutide at 200 ?g/kg daily.The control group was intramuscularly injected with an equal volume of 0.9% sodium chloride.(2)After 12 weeks of intervention,rats in each group were weighed and their fasting blood glucose(FBG)was measured.We collected peripheral serum,Str ACP,CTX-1,ALP and OC were detected by enzyme-linked immunosorbent assay(Elisa)to evaluate the changes of bone metabolism.(3)Bilateral femur and fifth lumbar spine were collected.Bone mineral density(BMD)and microstructure parameters of bone tissue were measured by micro-CT scanning in the regions of interest.Bone biomechanical parameters were measured by bone biomechanics instrument.Results(1)Compared with blank group in the serum,ALP(40.07±2.45 ng/m Lvs59.86±4.27 ng/m L)and OC(239.97±30.26 pg/m Lvs337.20 ±36.78 pg/m L)significantly decreased((P < 0.05),ACP(51.65±4.93 umol/Lvs43.49 ±4.21 umol/L)and CTX(193.31±43.42pg/mlvs10.35±3.39pg/ml)increased significantly(P < 0.05).Compared with the model group,ALP(57.59 ±1.02 ng/m Lvs 40.07 ±2.45 ng/m L)and OC(311.28 ±17.71 pg/m Lvs239.97±30.26 pg/m L)in the liraglutide group were significantly higher(P < 0.05).ACP(44.48±1.63 umol/Lvs51.65±4.93 umol/L)and CTX(21.52 ±3.41 pg/m Lvs193.31±43.42 pg/m L)in the liraglutide group were significantly lower(P < 0.05).(2)Compared with the blank group,the BMD of femur and lumbar spine in the model group decreased significantly,suggesting that the model was successful.The number of trabeculae decreased,the shape became finer,the continuity decreased,the arrangement was irregular,the spacing widened,and the parameters of bone microstructures in each group had significant statistical significance.Compared with model group,BMD of femur and lumbar spine was significantly increased in liraglutide group.Liraglutide made the trabeculae of glucocorticoid-induced osteoporosis rats thicker and denser,with good bone continuity and regular network structure.It increased the volume fraction of trabeculae and reduced the distance between trabeculae,suggesting that liraglutide could significantly enhance the microstructure of femur.The concentration of PDGF-B in the serum of each group was measured by Elisa,and the content of PDGF-B in the lysate of the vascular tissue was measured by Western blot;(3)Compared with the blank group,the maximal load(102.03 ±12.40Nvs167.24 ±28.25 N)and modulus of elasticity(4262.5±830.86 MPa vs7295.1±835.95MPa)of bone biomechanical indexes in the model group decreased significantly(P < 0.05).Compared with model group,the maximum load(139.41 +1.16 Nvs102.03 +12.40 N)and modulus of elasticity(5789.5 +470.60MPavs4262.5 +830.86MPa)of liraglutide group increased significantly(P < 0.05).ConclusionsLiraglutide can improve bone mineral density,microstructure and strength,and reverse osteoporosis caused by glucocorticoids in many ways.The protective mechanism may be related to reducing bone resorption and promoting bone formation.Liraglutide may become a new drug for osteoporosis. |
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