糖皮质激素诱导的骨质疏松研究进展.ppt

Corticosteroid InducedOsteoporosis Osteoporosis SystemicskeletaldiseaseLowbonemassMicroarchitecturaldeteriorationofbonetissueIncreaseinbonefragilityandfracturesusceptibility ClinicalBurdenofCIO Mostcommonformofdrug relatedosteoporosisinmenandwomenOccursatanyage inbothgenders acrossracesUpto50 ofpatientsonchronicsteroidtherapysustainosteoporoticfracturesand ordeveloposteonecrosis Corticosteroid InducedOsteoporosis Common iatrogenicformofsecondaryosteoporosisAssociatedwithcorticosteroiduseinchronic noninfectiousmedicalconditionsAsthma NephroticsyndromeChroniclungdisease TransplantationRheumatologicdisorders etcInflammatoryboweldisease Clinicalsignificant Increasebonelossandfracture 6Mo Trabecular corticalbone 7 5mgofprednisolone equivalent Incidenceofosteoporosis 30 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 P 0 001 P 0 002 PercentageofSLEpatients N 97 withlowBMD asmeasuredbyDXA KipenY etal 1997 CIOandSystemicLupusErythematosus PotentialFactorsCausingBoneLossinInflammatoryBowelDisease CorticosteroidsVitaminD CalciumdeficiencyPoornutritionalstatusInflammationPhysicalinactivityConcurrentmedications immunosuppressiveagents CIOandChronicObstructivePulmonaryDisease P 0 05vs ISUorNSU P 0 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 P 0 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 P 0 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 P 0 001vs control P 0 01vs control P 0 001vs baseline P 0 01vs baseline SaagKG etal 1998 EfficacyofAlendronate TwoYearsFollow Up P 0 001vs control P 0 01vs control P 0 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 P 0 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 P 0 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 Comparedwithnotreatmentorwithcalciumalone P 0 0001comparedwithcalcitoninorvitaminD Glucocorticoidtherapyevaluation Plan atstartofglucocorticoidtherapy1 Minimizeglucocorticoiddose2 Usealternatedaytherapy topicalsteroidorbonesparingsteroidifpossible3 Prescribeexercise weightbaring physicaltherapy preventfalling4 Avoidsmokingandexcessalcohol5 Assureadequatecalciumintake6 Addsupplementcalciumupto1000 15000mgcalcium day7 Addmultivitamincontaining400 800IUvitaminD8 BMDmeasurementofthespineandhip ifT scorelowerthan 1SDstartHRTandifmorethan 1SDstartHRTonlyinpostmenopausalwoman Glucocorticoidtherapyevaluation Reassessmentat2 3mo1 Reviewglucocorticoidtherapy attempttodecreaseordiscontinue2 Assessexerciseandcalciumintake3 Measureserumcalcium 24hrurinarycalciumifmorethan4mg kg dusehydrochlorothiazide25 50mgtwicedailyReassessmentat6mo1 Reviewglucocorticoidtherapyandminimize2 Assessexerciseandcalciumintake3 Repeatserumcalciumand24hrurinarycalciummeasurement4 Altercalcium vitaminD thiazidetherapyifnecessary5 Ifpateintistocontinueglucocorticoid considertorepeatBMD6 ConsiderHRT bisphosphonate calcitonin Glucocorticoidtherapyevaluation Reassessmentat1yr1 Reviewglucocorticoidtherapyandminimize2 Assessexerciseandcalciumintake3 Repeatserumcalciumand24hrurinarycalciummeasurement4 BMDmeasurement spineandhip 5 Altercalcium vitaminD thiazidetherapyifnecessary6 AlterfurtherthereapyifbonelossifcontinuesReassessmentthereafterifglucocorticoidscontinue1 Repeatannualassessmentasabove2 Changetherapyasneeded3 Considernewerdrugsastheybecomeavailable ACRTaskForceonOsteoporosis InitiatingLong TermCorticosteroidTherapy Initialhistory physical lab DXAmeasurementsCalcium vitaminDsupplementationPatienteducation Tscore 1InitiateHRT bisphosphonatesorcalcitoninifHRTcontraindicated Tscore 1Monitorregularly Onemonthfollow up Obtain24hurinetomeasurecalciumIf 300mg d addthiazidediureticAdjustdosageofcalciumandvitaminDsupplementation 6 12monthsfollow up RepeatBMDDecrease 5 change addmedicationIncrease nochange ordecrease 5 nochangeintherapy AmericanCollegeofRheumatologyTaskForceonOsteoporosisGuidelines 1996 AnticipatedtherapywithglucocorticoidAtraumaticfracturesYesNoCalcium1500mg dayyesMeasurementofbonemineraldensityVitaminD400 800IU dayLowerthan2SDbelowthemeanforExercise 5 youngadultsorLowerthan1SDbelowtheScreenforhypogonadismbonelossmeanforaged matchcontrolsNoIfhypogonadismpresent Calcium1000mg dayAddhormonereplacementwit