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The Effects Of ADFR Scheme With Analogue Of C-terminal Pentapeptide Of Osteogenic Growth Peptide And Diphosphonate On Bone Metabolism In Ovariectomized Rats

Posted on:2010-11-19Degree:MasterType:Thesis
Country:ChinaCandidate:W H GuoFull Text:PDF
GTID:2144360275492571Subject:Internal Medicine
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Objective To investigate the effects of ADFR scheme with osteogenic growth peptide C-terminal pentapeptide analogues(11F,110I) and alendronate on biochemical markers of bone turnover,bone histomorphometry,the ratio of ash weight to dry weight (AW/DW),bone mineral density(BMD) and biomechanical parameters in ovariectomized (OVX) rats.The relationships between these parameters were also studied.Methods Forty-nine female SD rats,three months old,were randomly divided into 6 groups.Group 1,11F and alendronate group(11FA);group 2,110I and alendronate group(110IA);group 3,phosphate buffered solution and alendronate group(1/3ALEN); group 4,alendronate group(ALEN);group 5,ovariectomized group(OVX);group 6, sham operated group(SHAM).Ovariectomy was carried out in group 1-5.Above agents were injected subcutaneously in the way of 5days OGP(10(10-14) or PBS solution and 5 days alendronate sodium and 5days free in groupl-3,the concentration of OGP(10-14) and PBS solution were 10nmol/kgweight/day,and alendronate was 100ug/100gweight /day.Group 4 were injected subcutaneously with alendronate everyday,100ug/kgweight /day.Group 5 and 6 were injected subcutaneously with PBS solution everyday,0.1 ml/kgweight/day.The doses were corrected as the change of weight once every week. All rats were sacrificed after 12 weeks.Uterus,kidney,liver,lumb- ar vertebrae,bilateral tibiae and femurs were reserved.The proximal tibial metaphysis was processed undecalcified for quantitive bone histomorphometry.The BMD was measured over the entire femur and lumbar vertebrae by dual energy X-ray absorptiometry(DEXA). Bone strength was measured by compression tests and three-point bending test.The data were analyzed by SPSS11.5.Results 1.Compared with group SHAM,the serum level of ALP and BGP were significantly increased in group OVX,11FA and 110IA.The level of ALP and BGP was higher in group 11FA than that in group 1/3ALEN and ALEN.2.OVX caused a significant decrease in bone mass,the BMD of the medication administration team(MAT) increased,and the BMD of group llFA and ll0IA were higher than other two groups. The BMD of group 1/3ALEN was the lowest in the MAT.3.The ratio of AW/DW was significantly lower in OVX groups than that in other groups.Compared with group SHAM,the ratio of AW/DW was decreased in group 1/3ALEN and ALEN(P<0.05). There was an increased trend of the ratio of AW/DW in group 11FA,the differences were statistical significant comparing with group 1/3ALEN and ALEN(P<0.01).4.(1) morphologic parameter:Compared with group OVX,BV/TV,OV/BV were significantly increased and Tb.sp,OS/BS were significantly decreased in group SHAM;BV/TV, Tb.Th,Tb.N were significantly increased and Tb.sp were significantly decreased in group 11FA and 110IA(P<0.01);Tb.sp,OV/BV,OS/BS were significantly decreased and Tb.N were significantly increased in group 1/3ALEN and ALEN.Tb.N,OV/BV, OS/BS in group 11FA and 110IA were higher than that in group SHAM,1/3ALEN and ALEN.(2) kinesic parameter:Compared with group SHAM,sLS/BS,dLS/BS,MS/ BS were significantly decreased in group OVX.dLS/BS,MS/BS in group 1/3ALEN and ALEN were lower than that in group OVX and SHAM.dLS/BS,MS/BS in group 11FA and 110IA were higher than that in group SHAM,1/3ALEN and ALEN.5.(1) three-point bending test:Elastic loading,modulus of bending elasticity,coefficient of bending stiffness in group 11FA and 110IA were higher than that in group OVX and SHAM.Modulus of bending elasticity,coefficient of bending stiffness in group 1/3ALEN and ALEN were higher than that in group OVX(P<0.01).Maximal loading,elastic loading,bending energy in group 11FA were higher than that in group ALEN.(2) compression test:All of the parameters in compression test in group 11FA and 110IA were higher than that in group OVX.Conclusion:The bone loss in OVX rats could be prevented by combination of the analogues of osteogenic growth peptide C-terminal pentapeptide(11F,110I) and alendronate with different modes.There existed superiorities in bone formation and biomechanical characteristics in ADFR mode of group 11FA and 110IA as compared with the other two groups.
Keywords/Search Tags:osteogenic growth peptide, analogues, osteoporosis, ADFR, bone morphometry, bone mineral density
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