系统性红斑狼疮的骨质疏松与皮质激素的相关性.ppt
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1、GC induced osteoporosis北京协和医院风湿免疫科张烜IntroductionnGCsareeffectiveinmanyrheumaticdiseasesnButGCinducedOPisacommonsideeffectnTrabecularrichsitesegspine&ribsareespeciallyatrisknEffectiveRxcanpreventorreverseGCbonelossOP in RA on GC Rxn多因素RAOsteoclast活化(TNFa,RANK)PhysicalinactivityGCRxMenopausen不同部位骨丢失不同
2、HandFemurSpine腰椎骨丢失与GC强相关PathophysiologynMostofthebiologicalactivitiesmediatedviaPassageacrosscellmembraneattachmenttocytosolicGCreceptorbindingtoGCresponseelement®ulatinggenetranscriptionnMayactviaothertranscriptionfactors:activatedprotein(AP)-1NFBGC receptor&bindingEffects of GC on bone metabol
3、ismnBoneformationMostimportantnBoneresorbtionProbablyonlyduring1st612monthsofRxOCproduction&postponedapoptosisLongterm,boneturnovernIntestinalabsorbtionofcalciumnUrinaryphosphate&calciumlossDirecteffectonkidneynSecondaryHyperparathyroidismBonelossEarlybuttemporary Bone formationnMostimportantnDirect
4、effectsonosteoblastscellreplicationosteocyteapoptosistype1collagengeneexpressionnIndirecteffectssynthesis,release,receptorbindingorbindingproteinsofgrowthfactorsegIGFI&IIrelatedtosexsteroidproductionEffects of GC on bone metabolismEpidemiologynCommonnFirstrecognisedbyCushingnRiskofOPwithGCRxunclearR
5、eportedinupto50%onlongtermRxnFractureriskProspectivedatalackingRetrospectivecohortstudy244236ptsonGCRxvs244235controlpts(UKGPregistry)RRofvertebral#2.6,hip#1.6,nonvertebral#1.3Estimatedvertebralfractureincidence1322%infirstyrofRxfromcalciumtreatedcontrolarmsofrecentrandomisedcontroltrialsCumulativep
6、revalenceofvertebralfractures:Upto28%(crosssectionalstudies)Factors associated with fracture risk with GC RxnAgenBMDInitial&subsequenttoGCRxPostmenopausalwomenhighestrisknGlucorticoiddoseCumulative&meandailydosenDurationofexposurenUnderlyingdiseaseRelative Risk of FractureRisk factors for bone loss&
7、fracturenRiskvariesaccordingtoage,dose&underlyingdiseasenThecaseforprimarypreventionisstrongestforpostmenopausalwomen&oldermenwithlowBMDBone Density&Fracture RisknInpostmenopausalwomenain1SDinBMDisassociatedwith2x#risknInptsonGCRxriskmaybegreateratlowerBMDDose,duration&formulation of Rx&Bone Lossndo
8、seGCRx(10mg/yr)vertebralboneloss5-10%/yrndoselowerrateofbonelossnBonelossmostrapidin1st612monthsofRxnGCbonelossappearsreversibleRxofCushingsnInhaledsteroidslesslikelytohavesystemiceffectsexceptathighdosesInvestigationsnDEXAscannBiochemicalmarkersBoneformationegosteocalcinFallwithinafewhoursofRxBoner
9、esorptionRiseafteracuteadministrationTreatment of GC OPnPrimarypreventionMostrapidbonelosswithin1st612monthsofRxnSecondarypreventionPrevention of GC-induced bone lossnUselowestdoseGCpossiblenMinimiselifestyleriskfactorssmokingnIndividualisedexerciseprogrammesnDrugRxCalciumVitaminD&metabolitesHRTBisp
10、hosphonatesPTHCalcitoninDrug RxnBeneficialeffectsinspine&hipdemonstratedinspine&hipbyseveralinterventionsnPosthoc/safetyanalysisoftrialsofetidronate,alendronate&residronatevertebralfracturesCalciumnGCintestinalcalciumabsorbtion&urinarycalciumexcretionnConflictingdataonefficacyinprimarypreventionnACR
11、:Calciumintake(diet/suppl)10001500mg/dVitamin D active-metabolitesnCalcitriol(1,25dihydroxyvitaminD)nAlfacalcidiol(1vitaminD)n1oprevention:BMDvsplacebon2oprevention:activevitDmetabolitesbetterthansimplevitDBMD/fracture/painRisk:hypercalcaemia&hypercalcuriaHRTn1controlledtrialinmenBMDwithtestosterone
12、vscalciumn1randomisedcontroltrialinpostmenopausalwomenBMDwithoestrogenvscalciumnNotrialsinpremenopausalwomennNofracturedatanReservedforptswithhormonedeficiencyBisphosphonatesnboneresorbtionnMayGCinducedapoptosisofosteoblastsAlendronatenCombinedanalysisoftrials(477pts)vertebral/femoralneck/trochanter
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- 系统性红斑狼疮 骨质 疏松 皮质激素 相关性
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