醫(yī)學(xué)專題-類固醇誘發(fā)的骨質(zhì)疏松

Corticosteroid-InducedOsteoporosis2012第一頁，共四十九頁。編輯pptOsteoporosisSystemicskeletaldiseaseLowbonemassMicroarchitecturaldeteriorationofbonetissueIncreaseinbonefragilityandfracturesusceptibility第二頁，共四十九頁。編輯pptClinicalBurdenofCIOMostcommonformofdrug-relatedosteoporosisinmenandwomenOccursatanyage,inbothgenders,acrossracesUpto50%ofpatientsonchronicsteroidtherapysustainosteoporoticfracturesand/ordeveloposteonecrosis第三頁，共四十九頁。編輯pptCorticosteroid-InducedOsteoporosisCommon,iatrogenicformofsecondaryosteoporosisAssociatedwithcorticosteroiduseinchronic,noninfectiousmedicalconditionsAsthma -NephroticsyndromeChroniclungdisease -TransplantationRheumatologicdisorders -etcInflammatoryboweldisease第四頁，共四十九頁。編輯pptClinicalsignificant-Increasebonelossandfracture:6Mo.-Trabecular>corticalbone-7.5mgofprednisolone(equivalent)-Incidenceofosteoporosis~30-50%-Vertebralfracture30-35%,hipfracture50%-Rateofboneloss2-4%peryear-Alternatedayregimen,inhalesteroids第五頁，共四十九頁。編輯pptFractureRiskandDoseofCorticosteroidsRelativeriskoffracturebydosagesofcorticosteroidsofprednisolone.vanStaaTP,etal,1998.

01234562.5mg/d2.5-7.5mg/d>7.5mg/dRelativeriskoffracturecomparedwithcontrolHipfractureVertebralfracture第六頁，共四十九頁。編輯pptCIOinPatientsWithAsthmaRelationshipofpercentagepredictedbonedensitytodurationofcorticosteroidusein44corticosteroid-treatedasthmaticpatients.SchatzM,DudlJ,ZeigerRS,etal.AllergyProc.1993;14:341-345.Reprintedwithpermission.Percentpredictedbonedensityr=-0.39(P=0.009)Durationofcorticosteroiduse(years)12010080604024681012141618202224262830323436第七頁，共四十九頁。編輯pptCIOinPatientsWithRheumatoidArthritisCS=corticosteroid;therapy=7mgprednisoneequivalentperday.DensitychangemeasuredaschangeinabsoluteorZscore(differenceinstandarddeviationcomparedwithhealthyage-matchedcontrolsofthesameraceandsex)comparedtobaseline.VerhoevenAC,etal,1997.第八頁，共四十九頁。編輯ppt*P<0.001;**P=0.002.PercentageofSLEpatients(N=97)withlowBMD,asmeasuredbyDXA.KipenY,etal,1997.CIOandSystemicLupusErythematosus******第九頁，共四十九頁。編輯pptPotentialFactorsCausingBoneLossinInflammatoryBowelDiseaseCorticosteroidsVitaminD/CalciumdeficiencyPoornutritionalstatusInflammationPhysicalinactivityConcurrentmedications(immunosuppressiveagents)第十頁，共四十九頁。編輯pptCIOandChronicObstructivePulmonaryDisease*P<0.05vs.ISUorNSU;**P<0.005vsISU.McEvoyCE,etal,1998.***第十一頁，共四十九頁。編輯pptPathophysiologyofCIO:OverviewBoneremodelingoccursthroughoutadulthoodOsteoporosisresultsfromanimbalancebetweenosteoclastandosteoblastactivityTwometabolicabnormalitiescontributetoincreasedboneresorptionSecondaryhyperparathyroidismduetodecreasedGIabsorptionandurinaryexcretionofcalciumAlteredgonadalfunctionanddecreasedadrenalproductionofandrogens第十二頁，共四十九頁。編輯pptPathophysiologyofCIO

CalciumhomeostasisGonadalhormoneInhibitboneformationIncreaseboneresorptionother第十三頁，共四十九頁。編輯pptCalciumhomeostasis

DecreasecalciumandphosphatefromGItracts unknownmechanismIncreaseurinarycalciumexcretion decreasecalciumreabsorptionatdistaltubulesStimulatiomPTHsecretion第十四頁，共四十九頁。編輯pptGonadalhormoneeffectsDecreasesexhormone:direct&indirectDecreaseLHfrompituitarygland: estrogenandtestosteroneDecreasesynthesisfromadrenalglandsDecreasesexhormonebindingglobulin第十五頁，共四十九頁。編輯pptBoneformationandboneresorptionOsteoblast -inh.Osteoblastproliferation -decreasematrixsynthesis -increaseapoptosis -decreaseproteinsynthesis(type1collagenandnoncollagenousprotein -decreaseosteocalcin,IGF1,IGFBP3,5,insulin-likegrowthfactors,transforminggrowthfactorB,prostaglandinE第十六頁，共四十九頁。編輯pptOsteoclast increaseosteoclastactivity increaseapoptosisofmatureosteoclastBoneformationandboneresorption第十七頁，共四十九頁。編輯pptOsteoblastproliferationApoptosis OBnumberProteinsynthesis BoneformationDifferentiation

BonemassFracture RiskAndrogenOsteoclastapoptosis BoneresorptionOsteoclastformation PTH Calciumandphosphateabsorption(gutandkidney)

Glucocorticoid第十八頁，共四十九頁。編輯pptDiagnosisofCIO:

InitialClinicalWork-UpMedicalhistoryRiskfactorsforbonelossPhysicalexamClinicalsignsandsymptoms第十九頁，共四十九頁。編輯pptPatientEvaluation

HistoryDocumentationofheight,weight,musclestrength, balance,vision

DocumentationofmedicalhistoryDocumentationofmenstrualhistory,infertilityinmenFracturehistoryandFamilyhistoryoffracturesOtherriskfactorsforosteoporosis:-Lifestylesinfluences:calciumandvitaminDintake, smoking,alcoholintake,medications,preventionoffalling-Patienteducation:preventionoffalling,exerciseGeneralhealthandprognosis第二十頁，共四十九頁。編輯pptPatientEvaluationPhysicalexaminationEvidenceofosteoporosis:evidenceoffracture,kyphosis,lossofheight,musclestrengthandsizeGeneralphysicalfindings:assessmentofunderlyingdisorder,othermedicalconditions第二十一頁，共四十九頁。編輯pptPatientEvaluationCompletebloodcountanderythrocyte sedimentationrate(ESR)Serumcalcium,phosphate,creatinine,electrolyte,alkalinephosphatase,25-hydroxyvitaminD,estradiol,testosterone(male)24hr-UrinarycalciumandcreatinineBMDofspineandhipX-raysofappropriateareaslaboratory第二十二頁，共四十九頁。編輯ppt

DiagnosticCriteria* Classification T=0to-1SD Normal T=-1to-2.5SD Osteopenia T

-2.5SD Osteoporosis T

-2.5SD+fragilityfractures Severeosteoporosis*Measuredin“Tscores,”ie,thenumberofstandarddeviationsbeloworabovethepeakbonemassinayoungadultreferencepopulationofthesamesex;SD=standarddeviation.WHOCriteriaforAssessingDiseaseSeverity第二十三頁，共四十九頁。編輯pptGuidelinesforBMDMeasurementBaselineBMDpriorto/within6monthsofinitiatingtherapyAntero-posteriormeasurementoflumbarspineandfemoralneckFollow-upat6and12months,annuallythereafteruntilbonemassstabilizesMeasuringhipalonemaymissmorerapidlossinspine第二十四頁，共四十九頁。編輯pptManagementofCIO:GoalsofTreatmentReducefractureriskMaintaincurrentBMD,preventadditionalbonelossAlleviatepainassociatedwithexistingfracture(s)Maintain/increasemusclestrengthInitiatelifestylechangesasneeded第二十五頁，共四十九頁。編輯pptBMD,VitaminD,andCalciumAdachiJD,etal,1996.-12-10-8-6-4-206months12months18months24months30months36monthsChangeinlumbarspineBMD

frombaseline(%)VitaminD&calcium

Placebo第二十六頁，共四十九頁。編輯pptTreatmentHormonalreplacementtherapyCalcitoninBisphosphonatesActionInhibitboneresorptionPreventapoptosisofosteoblastsPartiallyreversebonelossPreventearlyresorptivephaseofbonelossInhibitboneresorptionMaintainorincreasebonemassPharmacologicTreatmentofCIO:Overview第二十七頁，共四十九頁。編輯pptPharmacologictreatmentofCIOThiazidediuretics increasecalciumabsorptionfromGItract decreaseurinarycalciumexcretionFluorides stimulateosteoblastactivityAnabolicsteroids increaseboneformation第二十八頁，共四十九頁。編輯pptPatientgroupPostmenopausalwomenPremenopausalwomenw/intact ovarianfunctions(ages13-50)MenRecommendationEstrogen+progestinforwomenwithintactuteriBisphosphonateorcalcitoninifHRTcontraindicated

Estrogen-containingOCs(50gestradiol)orequivalentBisphosphonateorcalcitoninif

estrogencontraindicatedTestosterone(ifserumtestosteronelevelslow)BisphosphonateorcalcitoniniftestosteronecontraindicatedHormoneReplacementTherapyintheTreatmentofCIO:ACRGuidelinesAmericanCollegeofRheumatologyTaskForceonOsteoporosisGuidelines,1996.第二十九頁，共四十九頁。編輯ppt-0.06-0.04-0.0200.020.040.06Group1PrednisoneonlyGroup2Prednisone+ERTGroup3Control

Group4ERTonlyChangesinlumbarspineBMD(g/cm2)at1yearEstrogenReplacementTherapy

intheTreatmentofCIO*P=0.008vs.baseline;P=0.027betweengroups1and2.LukertBP,etal,1992.*第三十頁，共四十九頁。編輯pptTestosteroneReplacementTherapy

intheTreatmentofCIO*P=0.005vscontrol;P=0.05between-groupdifference.ReidIR,etal,1996.*-5.0-2.50.02.55.0TestosteronetherapyperiodControlperiodChangesinlumbarspineBMD(%)at1year第三十一頁，共四十九頁。編輯pptCyclicalEtidronateandPreventionofCorticosteroid-InducedBoneLoss*P<0.05between-groupdifference.AdachiJD,etal,1997.RouxC,etal,1998.**-4-3-2-1012LumbarspineFemoralneckTrochanterLumbarspineFemoralneckTrochanterChangesinBMDfrombaseline(%)at1yearEtidronateControl第三十二頁，共四十九頁。編輯ppt0246Lumbarspine*FemoralneckTrochanterChangeinBMDfrombaseline(%)MenPre-menopausalwomenPost-menopausalwomenEtidronate:PooledResultsfrom

ThreeRandomizedTrials*P<0.05between-groupdifference.RouxC,etal,1998.第三十三頁，共四十九頁。編輯pptEfficacyofPamidronateinthe

PreventionofBoneLossBoutsenY,etal,1997.-6-4-202466months12months6months12monthsChangesinBMDfrombaseline(%)Pamidronate+calciumCalciumonly第三十四頁，共四十九頁。編輯pptEfficacyofAlendronateinIncreasingBMD*P<0.001vs.control;**P<0.01vs.control;?P<0.001vs.baseline,?P<0.01vs.baseline;SaagKG,etal,1998.-1.5-0.50.51.52.53.5LumbarspineFemoralneckTrochanterTotalbodyChangeinBMDfrombaseline(%)at48weeksControlAlendronate5mgAlendronate10mg*?*?*?*??**?*?**?第三十五頁，共四十九頁。編輯pptEfficacyofAlendronate:TwoYearsFollow-Up*P<0.001vs.control;**P<0.01vs.control;?P<0.05vs.control.SaagKG,etal,1998.******??-4-3-2-101234LumbarspineFemoralneckTrochanterChangeinBMDfrombaseline(%)ControlAlendronate10mgAlendronate5mgAlendronate2.5mgyear1,10mgyear2第三十六頁，共四十九頁。編輯pptEffectofRisedronateonBMDinPatientsInitiatingCorticosteroidTherapy*P<0.05vscontrol.CohenS,etal,1998.******-4.0-2.00.02.04.0LumbarspineFemoralneckTrochanterChangeinBMDfrombaseline(%)at12monthsControlRisedronate2.5mgRisedronate5mg第三十七頁，共四十九頁。編輯pptEffectofRisedronateonBMDinPatientsonLong-TermCorticosteroidTherapy*P<0.05vs.control.DevogelaerJP,etal,1998.****-3.0-2.0-1.00.01.02.03.0LumbarspineFemoralneckTrochanterChangeinBMDfrombaseline(%)at12monthsControlRisedronate2.5mgRisedronate5mg第三十八頁，共四十九頁。編輯ppt05101520PooledcontrolpatientsPooledrisedronatepatientsPatientswithvertebralfractures(%)EffectofRisedronateonVertebralFractureRatesPooledvertebralfractureratesfrom518patientsonsteroidtherapy.*P=0.016vs.control.ReidD,etal,1998.*第三十九頁，共四十九頁。編輯ppt

Treatment Numberof Changeinlumbar

pooledtrials spineBMD(%)*

VitaminD 18 +1.96Calcitonin 11 +2.11 Bisphosphonates 18 +5.31?BisphosphonatesintheManagementofCIO:AMeta-Analysis*Comparedwithnotreatmentorwithcalciumalone?P=0.0001comparedwithcalcitoninorvitaminD第四十頁，共四十九頁。編輯pptGlucocorticoidtherapyevaluation

Plan-atstartofglucocorticoidtherapy 1.Minimizeglucocorticoiddose

2.Usealternatedaytherapy,topicalsteroidor bonesparingsteroidifpossible

3.Prescribeexercise(weightbaring),physicaltherapy, preventfalling4.Avoidsmokingandexcessalcohol5.Assureadequatecalciumintake6.Addsupplementcalciumupto1000-15000mgcalcium/day7.Addmultivitamincontaining400-800IUvitaminD8.BMDmeasurementofthespineandhip:ifT-scorelower than–1SDstartHRTandifmorethan–1SDstartHRT onlyinpostmenopausalwoman第四十一頁，共四十九頁。編輯pptGlucocorticoidtherapyevaluationReassessmentat2-3mo1.Reviewglucocorticoidtherapy:attempttodecreaseordiscontinue2.Assessexerciseandcalciumintake3.Measureserumcalcium,24hrurinarycalciumifmorethan4mg/kg/dusehydrochlorothiazide25-50mgtwicedaily

Reassessmentat6mo

1.Reviewglucocorticoidtherapyandminimize2.Assessexerciseandcalciumintake3.Repeatserumcalciumand24hrurinarycalciummeasurement4.Altercalcium/vitaminD/thiazidetherapyifnecessary5.Ifpateintistocontinueglucocorticoid,considertorepeatBMD6.ConsiderHRT/bisphosphonate/calcitonin第四十二頁，共四十九頁。編輯pptGlucocorticoidtherapyevaluation

Reassessmentat1yr

1.Reviewglucocorticoidtherapyandminimize2.Assessexerciseandcalciumintake3.Repeatserumcalciumand24hrurinarycalciummeasurement4.BMDmeasurement(spineandhip)5.Altercalcium/vitaminD/thiazidetherapyifnecessary6.Alterfurtherthereapyifbonelossifcontinues

Reassessmentthereafterifglucocorticoidscontinue1.Repeatannualassessmentasabove2.Changetherapyasneeded3.Considernewerdrugsastheybecomeavailable第四十三頁，共四十九頁。編輯pptACRTaskForceonOsteoporosis:

InitiatingLong-TermCorticosteroidTherapyInitialhistory&physical,lab/DXAmeasurementsCalcium/vitaminDsupplementationPatienteducationTscore<-1InitiateHRT;bisphosphonatesorcalcitoninifHRTcontraindicatedTscore>-1MonitorregularlyOnemonthfollow-up:Obtain24hurinetomeasurecalciumIf>300mg/d:addthiazidediureticAdjustdosageofcalciumandvitaminDsupplementation6-12monthsfollow-up:RepeatBMDDecrease>5%:change/addmedicationIncrease,nochange,ordecrease<5%:nochangeintherapyAmericanCollegeofRheumatologyTaskForceonOsteoporosisGuidelines,1996.第四十四頁，共四十九頁。編輯ppt

Anticipatedtherapywithglucocorticoid

Atraumaticfractures

Yes No

Calcium1500mg/dayyesMeasurementofbonemineraldensityVitaminD400-800IU/day Lowerthan2SDbelowthemeanforExercise>5%youngadultsorLowerthan1SDbelowtheScreenforhypogonadismbonelossmeanforaged-matchcontrols NoIfhypogonadismpresent:

Calcium1000mg/dayAddhormonereplacementwith VitaminD400-800IU/dayEstrogeninwomanandtestosteroneinmenExerciseCheckBMDinoneyear:addanti-resorpt