系统性红斑狼疮的骨质疏松与皮质激素的相关性VIP免费

GCinducedosteoporosis北京协和医院风湿免疫科张烜IntroductionGCsareeffectiveinmanyrheumaticdiseasesButGCinducedOPisacommonsideeffectTrabecularrichsitesegspine&ribsareespeciallyatriskEffectiveRxcanpreventorreverseGCbonelossOPinRAonGCRx多因素–RA•Osteoclast活化(TNFa，RANK)–Physicalinactivity–GCRx–Menopause不同部位骨丢失不同–Hand>Femur>Spine–腰椎骨丢失与GC强相关PathophysiologyMostofthebiologicalactivitiesmediatedvia–Passageacrosscellmembrane–attachmenttocytosolicGCreceptor–bindingtoGCresponseelement–®ulatinggenetranscriptionMayactviaothertranscriptionfactors:–activatedprotein(AP)-1–NFBGCreceptor&bindingEffectsofGConbonemetabolismBoneformation–MostimportantBoneresorbtion–Probablyonlyduring1st6–12monthsofRxOCproduction&postponedapoptosis–Longterm,boneturnoverIntestinalabsorbtionofcalciumUrinaryphosphate&calciumloss–DirecteffectonkidneySecondaryHyperparathyroidismBoneloss–EarlybuttemporaryBoneformationMostimportantDirecteffectsonosteoblastscellreplicationosteocyteapoptosistype1collagengeneexpressionIndirecteffectssynthesis,release,receptorbindingorbindingproteinsofgrowthfactorsegIGFI&II–relatedtosexsteroidproductionEffectsofGConbonemetabolismEpidemiologyCommonFirstrecognisedbyCushingRiskofOPwithGCRxunclear–Reportedinupto50%onlongtermRxFracturerisk–Prospectivedatalacking–Retrospectivecohortstudy•244236ptsonGCRxvs244235controlpts(UKGPregistry)•RRofvertebral#2.6,hip#1.6,nonvertebral#1.3–Estimatedvertebralfractureincidence•13–22%infirstyrofRx•fromcalciumtreatedcontrolarmsofrecentrandomisedcontroltrials–Cumulativeprevalenceofvertebralfractures:•Upto28%(crosssectionalstudies)FactorsassociatedwithfractureriskwithGCRxAgeBMD–Initial&subsequenttoGCRx–Postmenopausalwomen–highestriskGlucorticoiddose–Cumulative&meandailydoseDurationofexposureUnderlyingdiseaseRelativeRiskofFractureRiskfactorsforboneloss&fractureRiskvariesaccordingtoage,dose&underlyingdiseaseThecaseforprimarypreventionisstrongestforpostmenopausalwomen&oldermenwithlowBMDBoneDensity&FractureRiskInpostmenopausalwomen–ain1SDinBMDisassociatedwith–2x#riskInptsonGCRx–riskmaybegreateratlowerBMDDose,duration&formulationofRx&BoneLossdoseGCRx(10mg/yr)vertebralboneloss5-10%/yrdoselowerrateofbonelossBonelossmostrapidin1st6–12monthsofRxGCbonelossappearsreversible–RxofCushing’sInhaledsteroidslesslikelytohavesystemiceffectsexceptathighdosesInvestigationsDEXAscanBiochemicalmarkers–Boneformationegosteocalcin•FallwithinafewhoursofRx–Boneresorption•RiseafteracuteadministrationTreatmentofGCOPPrimaryprevention–Mostrapidbonelosswithin1st6–12monthsofRxSecondarypreventionPreventionofGC-inducedbonelossUselowestdoseGCpossibleMinimiselifestyleriskfactors–smokingIndividualisedexerciseprogrammesDrugRx–Calcium–VitaminD&metabolites–HRT–Bisphosphonates–PTH–CalcitoninDrugRxBeneficialeffectsinspine&hipdemonstratedinspine&hipbyseveralinterventionsPosthoc/safetyanalysisoftrialsofetidronate,alendronate&residronatevertebralfracturesCalciumGCintestinalcalciumabsorbtion&urinarycalciumexcretionConflictingdataonefficacyinprimarypreventionACR:–Calciumintake(diet/suppl)1000–1500mg/dVitaminDactive-metabolitesCalcitriol(1,25dihydroxyvitaminD)Alfacalcidiol(...