2001糖皮質(zhì)激素誘導(dǎo)的骨質(zhì)疏松癥的預(yù)防和治療指南(英文)美國風(fēng)濕病Glucocorticoid‐InducedOsteoporosis:2001Evidence‐BasedPreventionandTreatmentGuidancefromtheAmericanCollegeofRheumatology1.EpidemiologyandPathophysiologyLong-termexposuretosupraphysiologicglucocorticoid(GC)dosesproducesthemostcommonformofdrug-inducedosteoporosis.Withinthefirst3–6monthsoftherapy,trabecularbonelossacceleratesto6–12%peryear,twicetherateobservedinearlypost-menopause.Vertebralfracturesmayappearafteronly5mgprednisone-equivalentdailyfor3months;hipfracturesriselinearlywithcumulativeexposure.GCsimpairosteoblastdifferentiationviainhibitionofWnt/β-cateninsignaling,increaseosteocyteapoptosis,prolongosteoclastlifespanthroughRANKL/OPGimbalance,andreduceintestinalcalciumabsorptionwhilestimulatingrenalcalciumwasting.Thenetresultisa2-to5-foldincreaseinfractureriskindependentofbonemineraldensity(BMD).2.RiskStratificationAlgorithmStep1:Identifyalladultswhowillreceive≥2.5mgprednisone-equivalentdailyfor≥3months.Step2:AssignbaselinefractureprobabilityusingthemodifiedFRAX?scorewithGCadjustment:multiplymajor-fractureprobabilityby1.15andhip-fractureprobabilityby1.2.Step3:Overlayadditionalclinicalperils:priorfragilityfracture,parentalhipfracture,currentcigaretteuse,dailyalcohol≥3units,rheumatoidarthritis,secondaryosteoporosis(hyperparathyroidism,hypogonadism,malabsorption),andfallrisk≥20%peryear.Step4:Classifypatientsintothreetiers:-Highrisk:FRAXmajorfracture≥20%orhip≥3%orprevalentvertebral/hipfractureorGCdose≥7.5mgdaily.-Moderaterisk:FRAXmajor10–19%orhip1–3%andGCdose5–7.5mgdaily.-Lowrisk:FRAXmajor<10%andhip<1%andGCdose<5mgdaily.3.BaselineEvaluationObtaindetailedGChistory(dose,duration,priorbursts),completefracturehistory,fallassessment(TimedUp&Go,vision,orthostatics),andlaboratoryprofile:serum25-hydroxyvitaminD,calcium,creatinine,alkalinephosphatase,completebloodcount,testosterone(men),follicle-stimulatinghormone(premenopausalwomen),thyroid-stimulatinghormone,and24-hurinecalciumifhypercalciuriasuspected.Orderlateralthoracolumbarradiographsifheightloss≥4cmorkyphosis.PerformcentralDXA(postero-anteriorlumbarspineandtotalhip)within6weeksofGCinitiation;addfemoralneckifhipartifactispresent.Vertebralfractureassessment(VFA)byDXAissubstitutedforradiographswhenavailable.4.Non-PharmacologicMeasures4.1Lifestyle-Smokingcessationprogramwithpharmacologicsupport(varenicline,bupropion,nicotinereplacement).-Limitalcoholto≤1drinkdailyforwomenand≤2formen.-Encourageweight-bearingaerobicexercise≥150minweeklyplusresistancetraining2–3sessionsweekly;avoidflexion-dominantspineexerciseinpatientswithvertebralfractures.-Balancetraining(taichi,yogamodifiedposes)forfallreduction.-Hipprotectorsfornursing-homeresidentsorrecurrentfallers.4.2CalciumandVitaminD-Elementalcalcium1200mgdaily,preferablyindivideddoseswithfood;food-firststrategy(dairy,fortifiedorangejuice,cannedsalmonwithbones).-Ifdietinsufficient,supplementwithcalciumcitrate(betterabsorbedwithproton-pumpinhibitors)orcarbonate.-VitaminD3800–1000IUdaily;repleteif25-OHD<30ng/mLwith50000IUweekly×6–8weeks,thenrecheck.-Formalabsorption(celiac,post-bariatricsurgery),use25-hydroxyvitaminD20–25μgdailyorcalcidiol0.266mgweekly.4.3Fall-PreventionProgram-Annualvisionandhearingscreening;updatelensespromptly.-Reviewpsychoactivedrugs(benzodiazepines,opioids,anticholinergics)anddiscontinueortaper.-Homehazardassessmentbyoccupationaltherapist;installgrabbars,railings,andnight-lights.-Treatorthostatichypotension(midodrine,compressionstockings).-Encouragebedsidecommodefornocturia.5.PharmacologicPrevention5.1BisphosphonatesAlendronate:5mgdailyor35mgweekly(10mgdailyor70mgweeklyforpostmenopausalwomennotonGCs).Risedronate:5mgdailyor35mgweekly.Ibandronate:2.5mgdailyor150mgmonthlyoral,or3mgIVevery3months.Pamidronate:30–60mgIVevery3monthswhenoralintolerance.Initiateinallhigh-riskpatientswithin3monthsofGCstart.ContinueaslongasGCdose≥5mgdaily.AfterGCdiscontinuation,reassess;discontinueifT-score>?1.0andnofractures.5.2Teriparatide(rhPTH1-34)20μgsubcutaneousdailyforupto24months.Reservedforpatientswithveryhighfracturerisk(T-score≤?2.5plusprevalentfractureormultipleGCriskfactors)orintolerance/contraindicationtobisphosphonates.Followwithanti-resorptivetoconsolidategains.5.3CalcitoninIntranasal200IUdailyorsubcutaneous100IUeveryotherday.ProvidesanalgesiaforacutevertebralfracturebutonlymodestBMDbenefit;considerwhenotheragentscontraindicated.5.4HormoneTherapy-Postmenopausalestrogen/progestin:effectiveantiresorptivebutbalanceagainstcardiovascularandbreastrisks;reserveforwomenwithvasomotorsymptoms.-Testosteronereplacementinhypogonadalmen(totaltestosterone<300ng/dL)improvesBMDwhencombinedwithbisphosphonate.5.5ThiazideDiuretics25mghydrochlorothiazidedailyincreasesrenalcalciumretentionandaugmentsBMDinhypercalciuricpatients;monitorpotassiumandcreatinine.6.TreatmentofEstablishedGIOP6.1VertebralFracture-Immediatepaincontrolwithacetaminophen,tramadol,orshort-courseopioids;avoidchronicnarcotics.-Calcitonin200IUintranasaldailyfor4–6weeksreducesacutepain.-Bracingwiththoracolumbarorthosisfor6–12weeks;avoidprolongedimmobilization.-Teriparatide20μgdailyfor18–24months;followwithbisphosphonate.6.2HipFracture-Expeditedsurgicalrepairwithin24–48h;coordinatewithendocrinologyforpre-opoptimization.-StartIVbisphosphonate2weekspost-opwhenrenalfunctionstable.-Fall-preventionrehabilitationwithphysicaltherapy5daysweeklyfor3months.6.3MultipleFractures-Combineanabolicandantiresorptivetherapy:teriparatide18months→zoledronicacid5mgIVannually×3.-Evaluateforunderlyingmalignancy,myeloma,ormastocytosiswithSPEP,skeletalsurvey,andmarrowbiopsyifindicated.7.MonitoringStrategy7.1BMDRepeatspineandhipDXAevery6–12monthswhileGCdose≥7.5mgdaily;annuallyif5–7.5mgdaily;every2yearsif<5mgdaily.7.2BiochemicalMarkersSerumC-telopeptide(CTX)orN-telopeptide(NTX)andosteocalcinatbaselineand3–6monthstoconfirmadherenceandresponse;target≥30%reductionfrombaseline.7.3ImagingLateralspineradiographsorVFAifnewbackpain,heightloss≥2cm,orBMDdecline≥5%atspineor≥7%athip.7.4LaboratorySurveillanceAnnual25-OHvitaminD,calcium,creatinine,andCBC;every2yearstestosterone(men)andFSH(premenopausalwomen).7.5DrugHolidayAfter5yearsoforalbisphosphonateor3yearsofzoledronicacid,considerdiscontinuationifGCstopped,T-score>?1.0,andnofractures;reassessfractureriskevery2years.8.SpecialPopulations8.1ChildrenGC-inducedosteoporosisoccursatcumulativedoses>0.1g/kgprednisone.Monitorheightvelocity;performspineDXA(L1-L4)ifheightZ-scoredeclines≥0.25orbackpain.First-line:optimizecalcium1000mgdaily,vitaminD600–800IUdaily,andencourageweight-bearingsports.IfvertebralfractureorBMDZ-score≤?2.0,giveIVpamidronate1mg/kgmonthly×6;monitorrenalfunctionandgrowthvelocity.8.2PregnancyAvoidbisphosphonatesandteriparatide.Focusoncalcium1500mgdaily,vitaminD1000IUdaily,andphysiotherapy.Ifhigh-doseGCrequired,considercalcitoninnasalsprayforfracturepain.8.3RenalImpairmentForeGFR30–60mL/min,reducezoledronicaciddoseto4mgIVover30min;avoidifeGFR<30.Userisedronateoralendronatewithcaution;monitorcreatinine.8.4TransplantCandidatesInitiatezoledronicacid5mgIVwithin2weeksoftransplant;repeatat1year.Teriparatideissafepre-livertransplantbutcontraindicatedinactivemalignancy.9.AdverseEventManagement9.1Bisphosphonates-Esophagitis:instructpatientstotakewith240mLwater,remainupright30min(60minforibandronate),avoidbedtimedosing.-Acute-phasereaction(fever,myalgia):pre-medicatewithacetaminophen650mg;incidence10%afterfirstzoledronateinfusion.-Osteonecrosisofjaw(ONJ):risk<1/10000forosteoporosisdosing;ensuredentalclearancebeforetherapy;postponeinvasiveproceduresifpossible;ifONJoccurs,discontinuebisphosphonate,prescribechlorhexidinerinses,andrefertooralsurgeon.-Atypicalfemurfracture:counselonprodromalthighpain;obtainfull-femurX-ray;discontinuedrug,considerteriparatide,anduseintramedullarynailingifcompletefracture.9.2Teriparatide-Hypercalcemia:checkserumcalciumat1and3months;if>10.5mg/dL,reducesupplementcalciumto500mgdailyandrecheck;discontinueifpersistent.-Orthostatichypotension:administerfirstdoseinoffice;monitorbloodpressure.9.3Calcitonin-Nasalirritation,rhinitis:switchtosubcutaneousrouteifintolerable.9.4Thiazides-Hypokalemia:supplementwithpotassium-richfoodsor20mEqoralpotassiumdaily;monitormagnesium.10.Drug–DrugInteractions-Proton-pumpinhibitorsdecreaseoralbisphosphonateabsorption;separateby≥30minandprefercalciumcitrate.-Loopdiureticsincreaseurinarycalciumloss;adjustcalciumintakeupward.-Anticonvulsants(phenytoin,carbamazepine)acceleratevitaminDcatabolism;doublevitaminDdose.-Rifampinreducesteriparatideexposureby25%;nodoseadjustmentrequired.-Warfarinplushigh-dosevitaminDmayelevateINR;monitorweeklyfor4weeksaftervitaminDload.11.Cost-EffectivenessAnalysisInaMarkovmodelof60-year-oldwomenstarting10mgprednisonedaily,genericalendronate70mgweeklycosts$42peryearandyieldsanincrementalcost-effectivenessratio(ICER)of$2800perquality-adjustedlife-year(QALY)comparedwithcalcium/vitaminDalone.Zoledronicacid5mgannuallycosts$1100peryearwithICER$11000/QALYinhigh-riskcohorts.Teriparatide$18000per24-monthcourseiscost-effectiveonlywhenfractureriskexceeds45%over2yearsorwhentwoormoreprevalentvertebralfracturesexist.12.PatientEducationToolsProvidepictorialflip-chartillustratingproperbisphosphonateintake,spine-sparingliftingtechniques,and12-minuteosteoporosisworkoutvideo(DVDorstreaming).OfferfractureriskcalculatorsmartphoneappwithreminderalertsforsupplementdosesandDXAappointments.Multilingualhandouts(English,Spanish,Mandarin)listcalciumcontentof200commonfoods.13.QualityIndicatorsforRheumatologyPractices-ProportionofGCusers≥2.5mgdailyfor≥3monthswhoreceivebaselineDXAwithin6weeks:target≥90%.-Proportionofhigh-riskpatientsprescribedbisphosphonatewithin3months:target≥85%.-ProportionwithdocumentedvitaminDrepletion(≥30ng/mL)within6months:target≥80%.-Proportionwithfollow-upDXAwithin12monthswhiledose≥7.5mgdaily:target≥75%.-Proportionwithincidentvertebralfracturewhoreceiveteriparatideorzoledronicacidwithin3months:target≥70%.14.SampleCaseVignetteswithDecisionPathwaysCase1:58-year-oldwomanwithnew-onsetgiant-cellarteritis,treatedwithprednisone60mgdaily,taperedto10mgat3months.BaselineT-scores:spine?1.8,hip?1.4;FRAXmajor18%,hip3.2%.Decision:startalendronate70mgweeklyimmediately;repeatDXAat6months.Case2:34-year-oldmanwithsystemiclupusreceiving15mgprednisonedailyfor18months,prior