GCinducedosteoporosis英文版风湿免疫科.ppt

GCinducedosteoporosis英文版风湿免疫科

IntroductionGCsareeffectiveinmanyrheumaticdiseasesButGCinducedOPisacommonsideeffectTrabecularrichsitesegspineribsareespeciallyatriskEffectiveRxcanpreventorreverseGCboneloss

OPinRAonGCRx多原因RAOsteoclast活化(TNFa，RANK)PhysicalinactivityGCRxMenopause不同部位骨丢失不同HandFemurSpine腰椎骨丢失与GC强有关

PathophysiologyMostofthebiologicalactivitiesmediatedviaPassageacrosscellmembraneattachmenttocytosolicGCreceptorbindingtoGCresponseelementregulatinggenetranscriptionMayactviaothertranscriptionfactors:activatedprotein(AP)-1NF?B

GCreceptorbinding

EffectsofGConbonemetabolism?BoneformationMostimportant?BoneresorbtionProbablyonlyduring1st6–12monthsofRx?OCproductionpostponedapoptosisLongterm,?boneturnover?Intestinalabsorbtionofcalcium?UrinaryphosphatecalciumlossDirecteffectonkidneySecondaryHyperparathyroidism?BonelossEarlybuttemporary

?BoneformationMostimportantDirecteffectsonosteoblasts?cellreplication?osteocyteapoptosis?type1collagengeneexpressionIndirecteffects?synthesis,release,receptorbindingorbindingproteinsofgrowthfactorsegIGFIIIrelatedtosexsteroidproduction

EffectsofGConbonemetabolism

EpidemiologyCommonFirstrecognisedbyCushingRiskofOPwithGCRxunclearReportedinupto50%onlongtermRxFractureriskProspectivedatalackingRetrospectivecohortstudy244236ptsonGCRxvs244235controlpts(UKGPregistry)RRofvertebral#2.6,hip#1.6,nonvertebral#1.3Estimatedvertebralfractureincidence13–22%infirstyrofRxfromcalciumtreatedcontrolarmsofrecentrandomisedcontroltrialsCumulativeprevalenceofvertebralfractures:Upto28%(crosssectionalstudies)

FactorsassociatedwithfractureriskwithGCRxAgeBMDInitialsubsequenttoGCRxPostmenopausalwomen–highestriskGlucorticoiddoseCumulativemeandailydoseDurationofexposureUnderlyingdisease

Re