Study Of The Inhibition Of Alendronate On The Absorption Of Rat Alveolar Bone After Extration By Local Injection

How to inhibit residual ridge resorption(RRR) has puzzled prostheticdentitions for a long time,which lead to be difficult for the denture's retentionand stabilization because of the loss of bone mass.Many studies hadresearched the pathologic cause of RRR,and tried to find out the way ofprevention and treatment.However ,many studies had not propose a modusoperandi to inhibit alveolar bone resorption were due to the limit of the animalmodel and way of clinic research,inhibited bone resorption drugs for syswhether can use for local,the dosage and the method of local use are still not tomake a conclusion.Now,drugs for inhibit bone resorption include inhibitor of boneresorption,promoter of bone formation and traditional Chinese drug.Amongthe total,inhibitor of bone resorption include estrin,bisphosphonates,calcitionin,estrin antagonist,bean isoflavone et al;promoter of bone formation includefluoride,insulin-like growh factor,androgen,protein anabolichormone,parathormone,statins et al;Chinese drug mainly are drugs forinvigorate the kidney.Alendronate is the triple substitution ofbisphosphonates,which can inhibit bone resorption strongly,depress bonedivert,prevent bone loss,increase bone mass,cut down the incidence rate ofbone fracture,and therapeutic dose can not produce mineralizationdisturbance.Bisphosphonate can prevent various kinds drugs-induced boneresorption and have distinguished effect to calcium metabolism in vivo.Themode of action of alendronate generally is substantivitly inhibit effect toosteoclast,meanwhile,it can effect on osteoblast to excrete inhibited factor ofosteoclast activiation,which can intercept the effect of bone resorption.Underthe effect of alendronate,functional correlation cystoskeleton and shap ofosteocalst are changed,ruffled border which have osteoclast ability isdisappearance,lamellipodia stop activity,recoveried gradually,the flatteningareae of osteoclast is diminished;the volume fract of bone trabecula isincreased,the thickness of bone trabecula is incteased significantly,but the bonetrabecula distance keep constancy;the anisotropism of bone trabecula isbreakdown,rate of bone surface area and volume is cut down significantly,andbone surface density raise up,Young's modulus of bone trabecula isincreased,ultimate stress is accressence,every mechanics characters are allaccentuation.The sequelae of tooth extraction have been investigated in animalssuch as monkeys,dogs,rats and hamsters.These animal studies have shown thathealing of extraction sockets and remodeling changes of the residual ridges aresimilar to those in humans,but the healing period was much shorter in smalllaboratory animals than in humans.In rats ,the histological healing period oftooth extraction sockets was only from two to four weeks.So in this study,weinvestigate inhibit effect of alendronate to alveolar bone resorption by localinjection,at the same time,we detect TRAP positive cell population and IL-1βexpression level in alveolar bone after tooth extraction inrats.Through this study,we want to provid powerful evidence for theclinical studies of inhibit alveolar bone.The 70 healthy 15 weeks male Wister rats were allotted atrandom into three groups,blank group,experiment group and controlgroup.The left and right maxilla first molars were extracted,then,after one week,we inject 35μl alendronate solution in localtooth extraction sockets,and inject sodium chloride in the otherside.Every 3 days inject once till the end of the experiment.60 ratswere perfused and sacrificed at 3 day,14 day,21 day,28 day,35day.All the mesiodistal sections in the first molar region wereprocessed,then proceeded with HE staining,TRAP staining and IL-1βimmumohistochemical staining.Observing the histological changesof tissue,and the result was analyzed by the Computer ImageAnalyzing System and treated by statistics test.The result showed that at 3 day,the number of TRAP positivecells was slight, IL-1β expression level was similar to controlgroup and blank group.At 7 day,14 day,21 day and 28 day,number ofosteoclasts and Howshiop's lacunae were observed on the bonesurface.The number of TRAP positive cells and IL-1β expressionlevel was more higher than the control group and blank group.At 35day,bone resorption get to stabilization,bone tissue structre wassimilar to control group and blank group.The number of the TRAPpositive cells and the IL-1β expression level were lower,noevidence different comparing with the control group and blankgroup.For the experiment group,after local injected,alendronateadsorb to bone,get into osteoclast with cells fuction,and preventcells function by ingibit key enzyme which educe important role onosteoclast function.Besides that,alendronate can effect on cellswhich can secrete cell factor(such as IL-1β,TNF et al.),preventsecretion,decrease osteoclast activiation,intercept the boneabsorption process.At 7 day,14 day,21 day and 28 day of theexperiment,alveolar bone resorption were active after toothextraction,alendronate educe the effect of inhibit bone resorption,the number of the TRAP positive cells and the IL-1β expressionlevel of the experiment were lower than control group.At 35 day,boneresorption get to stabilization,the number of the TRAP positivecells and the IL-1β expression level both depressed obviously.In this study,an animal model about alveolar bone resorptionghas establishment,which can research the pathophysiologic causeand prevention and cure method of alveolar bone resorption.Theresult of the study has suggested that sodium chloride andmechanical stimulation can not prevent alveolar boneresorption,but aldronate can inhibit alveolar bone resorptioneffectually by local injection.In alveolar bone , IL-1β expressionlevel was associate with bone resorption activity,which can use indetect bone resorption.Through the study we can conclude thataldronate can inhibit alveolar bone resorption after toothextraction,and provid powerful experiment evidence on clinicalapplication.