类固醇诱发的骨质疏松.ppt
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类固醇诱发的骨质疏松.ppt
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Corticosteroid-InducedOsteoporosis,2012,Osteoporosis,SystemicskeletaldiseaseLowbonemassMicroarchitecturaldeteriorationofbonetissueIncreaseinbonefragilityandfracturesusceptibility,ClinicalBurdenofCIO,Mostcommonformofdrug-relatedosteoporosisinmenandwomenOccursatanyage,inbothgenders,acrossracesUpto50%ofpatientsonchronicsteroidtherapysustainosteoporoticfracturesand/ordeveloposteonecrosis,Corticosteroid-InducedOsteoporosis,Common,iatrogenicformofsecondaryosteoporosisAssociatedwithcorticosteroiduseinchronic,noninfectiousmedicalconditionsAsthma-NephroticsyndromeChroniclungdisease-TransplantationRheumatologicdisorders-etcInflammatoryboweldisease,Clinicalsignificant,-Increasebonelossandfracture:
6Mo.-Trabecularcorticalbone-7.5mgofprednisolone(equivalent)-Incidenceofosteoporosis30-50%-Vertebralfracture30-35%,hipfracture50%-Rateofboneloss2-4%peryear-Alternatedayregimen,inhalesteroids,FractureRiskandDoseofCorticosteroids,Relativeriskoffracturebydosagesofcorticosteroidsofprednisolone.vanStaaTP,etal,1998.,0,1,2,3,4,5,6,2.5mg/d,2.5-7.5mg/d,7.5mg/d,Relativeriskoffracture,comparedwithcontrol,Hipfracture,Vertebralfracture,CIOinPatientsWithAsthma,Relationshipofpercentagepredictedbonedensitytodurationofcorticosteroidusein44corticosteroid-treatedasthmaticpatients.SchatzM,DudlJ,ZeigerRS,etal.AllergyProc.1993;14:
341-345.Reprintedwithpermission.,CIOinPatientsWithRheumatoidArthritis,CS=corticosteroid;therapy=7mgprednisoneequivalentperday.DensitychangemeasuredaschangeinabsoluteorZscore(differenceinstandarddeviationcomparedwithhealthyage-matchedcontrolsofthesameraceandsex)comparedtobaseline.VerhoevenAC,etal,1997.,*P0.001;*P=0.002.PercentageofSLEpatients(N=97)withlowBMD,asmeasuredbyDXA.KipenY,etal,1997.,CIOandSystemicLupusErythematosus,*,*,*,*,PotentialFactorsCausingBoneLossinInflammatoryBowelDisease,CorticosteroidsVitaminD/CalciumdeficiencyPoornutritionalstatusInflammationPhysicalinactivityConcurrentmedications(immunosuppressiveagents),CIOandChronicObstructivePulmonaryDisease,*P0.05vs.ISUorNSU;*P0.005vsISU.McEvoyCE,etal,1998.,*,*,PathophysiologyofCIO:
Overview,BoneremodelingoccursthroughoutadulthoodOsteoporosisresultsfromanimbalancebetweenosteoclastandosteoblastactivityTwometabolicabnormalitiescontributetoincreasedboneresorptionSecondaryhyperparathyroidismduetodecreasedGIabsorptionandurinaryexcretionofcalciumAlteredgonadalfunctionanddecreasedadrenalproductionofandrogens,PathophysiologyofCIO,CalciumhomeostasisGonadalhormoneInhibitboneformationIncreaseboneresorptionother,Calciumhomeostasis,DecreasecalciumandphosphatefromGItractsunknownmechanismIncreaseurinarycalciumexcretiondecreasecalciumreabsorptionatdistaltubulesStimulatiomPTHsecretion,Gonadalhormoneeffects,Decreasesexhormone:
direct&indirectDecreaseLHfrompituitarygland:
estrogenandtestosteroneDecreasesynthesisfromadrenalglandsDecreasesexhormonebindingglobulin,Boneformationandboneresorption,Osteoblast-inh.Osteoblastproliferation-decreasematrixsynthesis-increaseapoptosis-decreaseproteinsynthesis(type1collagenandnoncollagenousprotein-decreaseosteocalcin,IGF1,IGFBP3,5,insulin-likegrowthfactors,transforminggrowthfactorB,prostaglandinE,Osteoclastincreaseosteoclastactivityincreaseapoptosisofmatureosteoclast,Boneformationandboneresorption,OsteoblastproliferationApoptosisOBnumberProteinsynthesisBoneformationDifferentiationBonemassFractureRiskAndrogenOsteoclastapoptosisBoneresorptionOsteoclastformationPTHCalciumandphosphateabsorption(gutandkidney),Glucocorticoid,DiagnosisofCIO:
InitialClinicalWork-Up,MedicalhistoryRiskfactorsforbonelossPhysicalexamClinicalsignsandsymptoms,PatientEvaluation,HistoryDocumentationofheight,weight,musclestrength,balance,visionDocumentationofmedicalhistoryDocumentationofmenstrualhistory,infertilityinmenFracturehistoryandFamilyhistoryoffracturesOtherriskfactorsforosteoporosis:
-Lifestylesinfluences:
calciumandvitaminDintake,smoking,alcoholintake,medications,preventionoffalling-Patienteducation:
preventionoffalling,exerciseGeneralhealthandprognosis,PatientEvaluation,PhysicalexaminationEvidenceofosteoporosis:
evidenceoffracture,kyphosis,lossofheight,musclestrengthandsizeGeneralphysicalfindings:
assessmentofunderlyingdisorder,othermedicalconditions,PatientEvaluation,Completebloodcountanderythrocytesedimentationrate(ESR)Serumcalcium,phosphate,creatinine,electrolyte,alkalinephosphatase,25-hydroxyvitaminD,estradiol,testosterone(male)24hr-UrinarycalciumandcreatinineBMDofspineandhipX-raysofappropriateareas,laboratory,DiagnosticCriteria*ClassificationT=0to-1SDNormalT=-1to-2.5SDOsteopeniaT-2.5SDOsteoporosisT-2.5SD+fragilityfracturesSevereosteoporosis*Measuredin“Tscores,”ie,thenumberofstandarddeviationsbeloworabovethepeakbonemassinayoungadultreferencepopulationofthesamesex;SD=standarddeviation.,WHOCriteriaforAssessingDiseaseSeverity,GuidelinesforBMDMeasurement,BaselineBMDpriorto/within6monthsofinitiatingtherapyAntero-posteriormeasurementoflumbarspineandfemoralneckFollow-upat6and12months,annuallythereafteruntilbonemassstabilizesMeasuringhipalonemaymissmorerapidlossinspine,ManagementofCIO:
GoalsofTreatment,ReducefractureriskMaintaincurrentBMD,preventadditionalbonelossAlleviatepainassociatedwithexistingfracture(s)Maintain/increasemusclestrengthInitiatelifestylechangesasneeded,BMD,VitaminD,andCalcium,AdachiJD,etal,1996.,-12,-10,-8,-6,-4,-2,0,6,months,12,months,18,months,24,months,30,months,36,months,ChangeinlumbarspineBMD,frombaseline(%),VitaminD&calcium,Placebo,PharmacologicTreatmentofCIO:
Overview,PharmacologictreatmentofCIO,ThiazidediureticsincreasecalciumabsorptionfromGItractdecreaseurinarycalciumexcretionFluoridesstimulateosteoblastactivityAnabolicsteroidsincreaseboneformation,PatientgroupPostmenopausalwomenPremenopausalwomenw/intactovarianfunctions(ages13-50)Men,RecommendationEstrogen+progestinforwomenwithintactuteriBisphosphonateorcalcitoninifHRTcontraindicatedEstrogen-containingOCs(50gestradiol)orequivalentBisphosphonateorcalcitoninifestrogencontraindicatedTestosterone(ifserumtestosteronelevelslow)Bisphosphonateorcalcitoniniftestosteronecontraindicated,HormoneReplacementTherapyintheTreatmentofCIO:
ACRGuidelines,AmericanCollegeofRheumatologyTaskForceonOsteoporosisGuidelines,1996.,-0.06,-0.04,-0.02,0,0.02,0.04,0.06,Group1,Prednisone,only,Group2,Prednisone,+ERT,Group3,Control,Group4,ERTonly,ChangesinlumbarspineBMD(g/cm,2,),at1year,EstrogenReplacementTherapyintheTreatmentofCIO,*P=0.008vs.baseline;P=0.027betweengroups1and2.LukertBP,etal,1992.,*,TestosteroneReplacementTherapyintheTreatmentofCIO,*P=0.005vscontrol;P=0.05between-groupdifference.ReidIR,etal,1996.,*,-5.0,-2.5,0.0,2.5,5.0,Testosteronetherapy,period,Controlperiod,ChangesinlumbarspineBMD(%),at1year,CyclicalEtidronateandPreventionofCorticosteroid-InducedBoneLoss,*P0.05between-groupdifference.AdachiJD,etal,1997.RouxC,etal,1998.,*,*,-4,-3,-2,-1,0,1,2,Lumbar,spine,Femoral,neck,Trochanter,Lumbar,spine,Femoral,neck,Trochanter,ChangesinBMDfrombaseline(%)at1year,Etidronate,Control,0,2,4,6,Lumbarspine*,Femoralneck,Trochanter,ChangeinBMDfrombaseline(%),Men,Pre-menopausalwomen,Post-menopausalwomen,Etidronate:
PooledResultsfromThreeRandomizedTrials,*P0.05between-groupdifference.RouxC,etal,1998.,EfficacyofPamidronateinthePreventionofBoneLoss,BoutsenY,etal,1997.,-6,-4,-2,0,2,4,6,6months,12months,6months,12months,ChangesinBMDfrombaseline(%),Pamidronate+calcium,Calciumonly,EfficacyofAlendronateinIncreasingBMD,*P0.001vs.control;*P0.01vs.control;P0.001vs.baseline,P0.01vs.baseline;SaagKG,etal,1998.,*,*,*,*,*,*,*,EfficacyofAlendronate:
TwoYearsFollow-Up,*P0.001vs.control;*P0.01vs.control;P0.05vs.control.SaagKG,etal,1998.,*,*,*,*,-4,-3,-2,-1,0,1,2,3,4,Lumbarspine,Femoralneck,Trochanter,ChangeinBMDfrombaseline(%),Control,Alendronate10mg,Alendronate5mg,Alendronate2.5mgyear1,10mgyear2,EffectofRisedronateonBMDinPatientsInitiatingCorticosteroidTherapy,*P0.05vscontrol.CohenS,etal,1998.,*,*,*,*,*,*,-4.0,-2.0,0.0,2.0,4.0,Lumbarspine,Femoralneck,Trochanter,ChangeinBMDfrombaseline(%),at12months,Control,Risedronate2.5mg,Risedronate5mg,EffectofRisedronateonBMDinPatientsonLong-TermCorticosteroidTherapy,*P0.05vs.control.DevogelaerJP,etal,1998.,*,*,*,*,-3.0,-2.0,-1.0,0.0,1.0,2.0,3.0,Lumbarspine,Femoralneck,Trochanter,ChangeinBMDfrombaseline(%),at12months,Control,Risedronate2.5mg,Risedronate5mg,0,5,10,15,20,Pooledcontrolpatients,Pooledrisedronate,patients,Patientswithvertebralfractures(%),EffectofRisedronateonVertebralFractureRates,Pooledvertebralfractureratesfrom518patientsonsteroidtherapy.*P=0.016vs.control.ReidD,etal,1998.,*,TreatmentNumberofChangeinlumbarpooledtrialsspineBMD(%)*VitaminD18+1.96Calcitonin11+2.11Bisphosphonates18+5.31,BisphosphonatesintheManagementofCIO:
AMeta-Analysis,*ComparedwithnotreatmentorwithcalciumaloneP=0.0001comparedwithcalcitoninorvitaminD,Glucocorticoidtherapyevaluation,Plan-atstartofglucocorticoidtherapy1.Minimizeglucocorticoiddose2.Usealternatedaytherapy,topicalsteroidorbonesparingsteroidifpossible3.Prescribeexercise(weightbaring),physicaltherapy,preventfalling4.Avoidsmokingandexcessalcohol5.Assureadequatecalciumintake6.Addsupplementcalciumupto1000-15000mgcalcium/day7.Addmultivitamincontaining400-800IUvitaminD8.BMDmeasurementof
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- 关 键 词:
- 类固醇 诱发 骨质 疏松
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