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曾紀洲主任醫(yī)師 北京潞河醫(yī)院 骨關節(jié)外科 激素使用對股骨頭骨壞死發(fā)生和進展的影響:一項全國性巢式病例對照研究（2024）EffectofCorticosteroidUseontheOccurrenceandProgressionofOsteonecrosisoftheFemoralHead:ANationwideNestedCase-ControlStudy?KwonHM,HanM,LeeTS,JungI,SongJJ,YangHM,LeeJ,LeeSH,LeeYH,ParkKK.EffectofCorticosteroidUseontheOccurrenceandProgressionofOsteonecrosisoftheFemoralHead:ANationwideNestedCase-ControlStudy[J].JArthroplasty,2024轉載文章的原鏈接1：https://pubmed.ncbi.nlm.nih.gov/38830431/轉載文章的原鏈接2：https://www-clinicalkey-com-443.vpnm.ccmu.edu.cn/#!/content/journal/1-s2.0-S0883540324004595?AbstractBackgroundAlthoughitisverywellknownthatcorticosteroidscauseosteonecrosisofthefemoralhead(ONFH),itisunclearastowhichpatientsdevelopONFH.Additionally,therearenostudiesontheassociationbetweencorticosteroiduseandfemoralheadcollapseinONFHpatients.WeaimedtoinvestigatetheassociationbetweencorticosteroiduseandtheriskofONFHamongthegeneralpopulationandwhatfactorsaffectONFHoccurrence.Additionally,weaimedtodemonstratewhichfactorsaffectfemoralheadcollapseandtotalhiparthroplasty(THA)afterONFHoccurrence.雖然眾所周知，皮質類固醇會導致股骨頭骨壞死(ONFH)，但目前尚不清楚哪些患者會發(fā)生ONFH。此外，沒有關于皮質類固醇使用與ONFH患者股骨頭塌陷之間關系的研究。我們的目的是調(diào)查普通人群中皮質類固醇使用與ONFH風險之間的關系，以及影響ONFH發(fā)生的因素。此外，我們旨在證明哪些因素影響ONFH發(fā)生后股骨頭塌陷和全髖關節(jié)置換術(THA)。?MethodsAnationwide,nestedcase-controlstudywasconductedwithdatafromtheNationalHealthInsuranceServicePhysicalHealthExaminationCohort(2002to2019)intheRepublicofKorea.WedefinedONFH(N=3,500)usingdiagnosisandtreatmentcodes.PatientswhohadONFHwerematched1:5toformacontrolgroupbasedonthevariablesofbirthyear,sex,andfollow-upduration.Additionally,inpatientswhohaveONFH,welookedforriskfactorsforprogressiontoTHA.使用韓國國民健康保險服務機構身體健康檢查隊列(2002年至2019年)的數(shù)據(jù)進行了一項全國性的巢式病例對照研究。我們使用診斷和治療代碼定義ONFH(N=3,500)。根據(jù)出生年份、性別、隨訪時間等變量對ONFH患者進行1:5匹配，形成對照組。此外，在患有ONFH的患者中，我們尋找進展為THA的危險因素。?ResultsComparedwiththecontrolgroup,ONFHpatientshadalowhouseholdincomeandhadmorediabetes,hypertension,dyslipidemia,andheavyalcoholuse(drinkingmorethan3to7drinksperweek).Systemiccorticosteroiduse(≥1,800mg)wassignificantlyassociatedwithanincreasedriskofONFHincidence.However,lipidprofiles,corticosteroidprescription,andcumulativedosesofcorticosteroiddidnotaffecttheprogressiontoTHA.與對照組相比，ONFH患者家庭收入較低，糖尿病、高血壓、血脂異常和重度飲酒(每周飲酒超過3至7天)的發(fā)生率更高。全身使用皮質類固醇(≥1800mg)與ONFH發(fā)生率增加顯著相關。然而，脂質譜、皮質類固醇處方和皮質類固醇累積劑量對進展到THA沒有影響。?ConclusionsTheONFHriskincreasedrapidlywhencumulativeprednisoloneusewas≥1,800mg.However,oralorhigh-doseintravenouscorticosteroiduseandcumulativedosedidnotaffecttheprognosisofONFH.SincetheoccurrenceandprognosisofONFHarecomplexandmultifactorialprocesses,furtherstudyisneeded.當累積使用潑尼松龍≥1800mg時，ONFH風險迅速增加。然而，口服或大劑量靜脈注射皮質類固醇和累積劑量不影響股骨頭壞死的預后。由于股骨頭壞死的發(fā)生和預后是一個復雜的多因素過程，需要進一步研究。?Osteonecrosisofthefemoralhead(ONFH)maycauseseverehippain,andcanultimatelyleadtocollapseofthefemoralheadandsubsequentrapiddestructionofthehipjointinrelativelyyoungpatients[1-3].Intractablepaincausedbyfemoralheadcollapseeventuallyleadstototalhiparthroplasty(THA)atayoungage[4,5].Althoughtrauma,theuseofcorticosteroid,andexcessivealcoholintakearewell-knownriskfactorsforONFH,theetiologyofONFHremainsmultifactorial,andnoconsensusexistsonthecommonpathophysiology[6-9].Impairedperfusionofbloodtobone,abnormalcellularreparativeprocesses,andgeneticpointmutationsarepresumedtoaffectONFHoccurrence,butithasnotyetbeenclarified[10-12].股骨頭壞死(Osteonecrosisoffemoralhead,ONFH)可引起嚴重的髖關節(jié)疼痛，在相對年輕的患者中，最終可導致股骨頭塌陷并隨后迅速破壞髖關節(jié)[1-3]。股骨頭塌陷引起的頑固性疼痛最終導致在年輕時進行全髖關節(jié)置換術(THA)[4,5]。雖然創(chuàng)傷、皮質類固醇的使用和過量飲酒是眾所周知的ONFH的危險因素，但ONFH的病因仍然是多因素的，對共同的病理生理尚未達成共識[6-9]。據(jù)推測，骨血流灌注受損、細胞修復過程異常以及基因點突變可能影響ONFH的發(fā)生，但尚未明確[10-12]。AlthoughitisverywellknownthatcorticosteroidscauseONFH,itisunclearastowhichpatientsdevelopONFH.Thereareseveralstudiesreportingthathigh-dosecorticosteroiduseof2grams(g)ormorewithin3monthsisassociatedwithONFHdevelopment[8,13-15].However,thesewerestudieswitharelativelysmallnumberofpatients,andthereareheterogeneitiesinpatientdemographicsandepidemiologicvariabilities.OnceONFHoccurs,theprognosisisknowntobepoor,andtherearestudiesstatingthatfemoralheadcollapseprogressesfromabout24.6to42.8%withnaturalevolutionwithin2years[16,17].Inparticular,whenfemoralheadcollapseoccurs,manypatientsoftenreceiveTHAatayoungage,sopredictingtheprognosisforfemoralheadcollapseisasimportantaspredictingtheoccurrenceofONFH.SeveralstudieshavedemonstratedthatfemoralheadcollapseinONFHpatientsisassociatedwithsize,volume,locationofnecroticlesions,andanatomicalparameters[1,2,18,19].However,therearenostudiesontheassociationbetweencorticosteroiduseandfemoralheadcollapseinONFHpatients.雖然眾所周知，皮質類固醇會引起ONFH，但尚不清楚哪些患者會發(fā)生ONFH。有幾項研究報道，在3個月內(nèi)使用2克或更多的高劑量皮質類固醇與ONFH的發(fā)生有關[8,13-15]。然而，這些研究的患者數(shù)量相對較少，并且在患者人口統(tǒng)計學和流行病學變異方面存在異質性。一旦發(fā)生ONFH，預后很差，有研究表明股骨頭塌陷在2年內(nèi)自然演化，從24.6%發(fā)展到42.8%[16,17]。特別是股骨頭塌陷發(fā)生時，許多患者往往在年輕時接受THA，因此預測股骨頭塌陷的預后與預測ONFH的發(fā)生同樣重要。多項研究表明，ONFH患者股骨頭塌陷與壞死灶的大小、體積、位置和解剖學參數(shù)有關[1,2,18,19]。然而，目前還沒有關于ONFH患者使用皮質類固醇與股骨頭塌陷之間關系的研究。TheNationalHealthInsuranceService(NHIS)ofSouthKoreaisanationalinsurancecoverageservicethatcoversabout97%ofcitizensinSouthKorea,includingdemographicdataandaclaimdatabaseincludingdiagnosesandprescriptions[20].Additionally,theNHISoffershealthscreeningexaminationsforinsuredKoreansaged40yearsorolder,includingbasicbloodtests,smoking,drinking,andphysicalactivitiesusingself-reportedquestionnaires.BecausetheNationalHealthInsuranceService–NationalSampleCohort(NHIS-NSC)isahighlyrepresentativepopulation-basedcohortoftheentireKoreanpopulation,itcanbeusedasapopulation-based,nationwidestudyforepidemiologicresearchonvariousdiseases[20-22].韓國國民健康保險服務(NationalHealthInsuranceService,NHIS)是一項覆蓋韓國約97%公民的國民保險服務，包括人口統(tǒng)計數(shù)據(jù)和包括診斷和處方在內(nèi)的索賠數(shù)據(jù)庫[20]。此外，國民健康保險制度還為40歲或40歲以上的參保韓國人提供健康檢查，包括基本的血液檢查、吸煙、飲酒和使用自我報告問卷的體育活動。由于國民健康保險服務-國民樣本隊列(NationalHealthInsuranceService-NationalSampleCohort,NHIS-NSC)是韓國人口中極具代表性的基于人群的隊列，因此可以作為一項基于人群的全國性研究，用于各種疾病的流行病學研究[20-22]。Therefore,inthepresentstudy,weaimedtoinvestigatetheassociationbetweencorticosteroiduseandtheriskofONFHdevelopmentamongthewholegeneralpopulationandwhatfactorsaffectONFHdevelopmentusinganationwidelargesamplefromlongitudinalnestedcase-controldatainalong-termcohortstudy.Inaddition,weaimedtodemonstratewhichfactorsaffectTHAafterthedevelopmentofONFH.因此，在本研究中，我們旨在通過一項長期隊列研究，在全國范圍內(nèi)采用縱向嵌套病例對照數(shù)據(jù)的大樣本，調(diào)查皮質類固醇使用與整個普通人群中ONFH發(fā)生風險之間的關系，以及影響ONFH發(fā)生的因素。此外，我們旨在證明哪些因素會影響ONFH發(fā)展后的THA。?MaterialsandMethodsStudyPopulationWeuseda2002to2019datasetfromtheNHISPhysicalHealthExaminationCohort(NHIS-NSC)2.0databaseintheRepublicofKorea[23].TheNHIS-NSC2.0databasewascomprisedofatotalof1,137,861participantswhowerestratifiedandrandomlysampledsuchthattheage,sex,region,healthinsurancetype,andhouseholdincomesofthesamplesremainedproportionaltothoseofthe2006Koreanpopulationof50million.Weexcluded223,474participantswhowerealreadyprescribedintravenous(IV)ororalcorticosteroidstoreducethebiasintheanalysisoftheeffectoftheprescribedcorticosteroiddoseonONFH.Fromtheremainingcohort,weexcluded241participantswhowerealreadydiagnosedwithONFHin2002toobtainthenewdevelopmentofONFH(washoutperiod).Therefore,theindexdatewasthedatethatthepatientwasdiagnosedwithONFH.Weincluded914,146participantsinthefinalanalysis.Theinformationinthedatasetincludedallinpatientandoutpatientmedicalclaimsdata,includingprescriptiondruguse,diagnosticandtreatmentcodes,primaryandsecondarydiagnosticcodes,andhealthexaminationdata.AlltheindividualsincludedintheNHIS-NSCwerefolloweduntil2019,unlesstherewasadeathordisqualificationforNationalHealthInsurance,suchasemigration.TheprotocolofthisstudywasapprovedbytheInstitutionalReviewBoardofourinstitution(4-2022-0304)andtheNHIS(NHIS-2022-2-232).我們使用了2002年至2019年的數(shù)據(jù)集，這些數(shù)據(jù)集來自韓國NHIS身體健康檢查隊列(NHIS-nsc)2.0數(shù)據(jù)庫[23]。國民健康保險制度-國家安全保障制度2.0數(shù)據(jù)庫共包括1137861名參與者，這些參與者的年齡、性別、地區(qū)、健康保險類型和家庭收入與2006年韓國5000萬人口的比例保持一致，并進行了分層和隨機抽樣。我們排除了223,474名已經(jīng)靜脈注射或口服皮質類固醇的參與者，以減少處方皮質類固醇劑量對ONFH影響分析的偏倚。從剩余隊列中，我們排除了241名在2002年已經(jīng)診斷為ONFH的參與者，以獲得ONFH的新進展(洗脫期)。因此，索引日期為患者被診斷為ONFH的日期。我們在最終分析中納入了914146名參與者。數(shù)據(jù)集中的信息包括所有住院和門診醫(yī)療索賠數(shù)據(jù)，包括處方藥使用、診斷和治療代碼、初級和二級診斷代碼以及健康檢查數(shù)據(jù)。納入國家健康保險制度-國家安全保障制度的所有個人都被跟蹤到2019年，除非死亡或喪失參加國家健康保險的資格，例如移民。本研究的方案經(jīng)我院機構審查委員會(4-2022-0304)和NHIS(NHIS-2022-2-232)批準。?CaseandControlSelectionWeusedtheInternationalStatisticalClassificationofDiseasesandRelatedHealthProblems,10thRevision(ICD-10)toidentifycasepatients.WedefinedONFH(N=3,500)usingthediagnosticcodeandtreatmentcodeICD-10codesforosteonecrosisofthefemur(SupplementaryTable1).Toavoidlengthbias,anestedcase-controlanalysiswasdesignedtoinvestigatetheeffectoftheprescribedcorticosteroiddoseonONFH.PatientswhohadONFHwerematched1:5toformacontrolgroupbasedonthevariablesofbirthyear,sex,andfollow-upduration.Identicalexclusioncriteriawereappliedtothecontrolgroup(N=12).Finally,casepatients(N=3,488)andcontrolpatients(N=17,440)werematchedbasedonsexandageattheindexdateandcompared(Figure1).我們使用國際疾病和相關健康問題統(tǒng)計分類第十次修訂版(ICD-10)來確定病例患者。我們使用股骨骨壞死的診斷代碼和治療代碼ICD-10來定義ONFH(N=3,500)(補充表1)。為避免長度偏倚，設計了巢式病例對照分析，以調(diào)查處方皮質類固醇劑量對ONFH的影響。根據(jù)出生年份、性別、隨訪時間等變量對ONFH患者進行1:5匹配，形成對照組。對照組(N=12)采用相同的排除標準。最后，根據(jù)索引日期的性別和年齡對病例患者(N=3,488)和對照患者(N=17,440)進行匹配和比較(圖1)。??Fig.1Studyflow:selectionofparticipantsofcasesandmatchedcontrolsONFH,osteonecrosisoffemoralhead.??DefinitionofParametersFromthehealthexaminations,participantswereclassifiedinto4groupsbasedonthebodymassindex(BMI)accordingtotheWorldHealthOrganizationWesternPacificRegionguidelineandtheKoreanpracticalguidelineasfollows:low(<18.5),normal(18.5to23),overweight(23to25),andobese(>25).UnderlyingcomorbiditiesweredefinedbyatleastoneadmissionoroutpatienttreatmentupontheprimaryorfirstsecondarydiagnosisusingtheICD-10codeforthepastyear(hypertension:I10-I15,diabetesmellitus:E10-E14,dyslipidemia:E78).Thefrequencyofdrinkingalcoholwascategorizedas“non-alcoholuse”(drinkinglessthan1drinkperweek),“mildalcoholuse”(drinking1to2drinksperweek),or“heavyalcoholuse”(drinkingmorethan3to7drinksperweek).Smokingstatuswascategorizedasnonsmoker,pastsmoker,orcurrentsmoker.Afterovernightfasting,bloodsampleswereobtained,andserumhigh-densitylipoproteincholesterol,low-densitylipoprotein(LDL)cholesterol,andtriglyceride(TG)resultscouldbeobtained.根據(jù)健康檢查結果，根據(jù)世界衛(wèi)生組織西太平洋地區(qū)指南和韓國實踐指南，將參與者的身體質量指數(shù)(BMI)分為4組:低(<18.5)、正常(18.5~23)、超重(23~25)和肥胖(>25)。潛在的合并癥是在過去一年中使用ICD-10代碼進行原發(fā)性或首次繼發(fā)性診斷時至少進行一次住院或門診治療(高血壓:I10-I15，糖尿病:E10-E14，血脂異常:E78)。飲酒頻率分為“不飲酒”(每周飲酒少于1杯)、“輕度飲酒”(每周飲酒1至2杯)或“重度飲酒”(每周飲酒超過3至7杯)。吸煙狀況分為不吸煙者、過去吸煙者和現(xiàn)在吸煙者。禁食過夜后采集血樣，得到血清高密度脂蛋白膽固醇、低密度脂蛋白膽固醇和甘油三酯(TG)結果。?SystemicCorticosteroidPrescriptionWedefinedsystemiccorticosteroidprescriptionsasoralcorticosteroidprescriptionsandIVcorticosteroidprescription.Systemiccorticosteroidusewasdefinedastheprescriptionofmedicationcodesduringadmissionsandoutpatientvisitsfrom2003totheindexdate(Table1).Bothgroupshadidenticalobservationperiods.Allcorticosteroidformulationswereconvertedintoadailydosebasedonprednisoneequivalentdoses[24](1mgprednisolone=4mghydrocortisone=0.8mgmethylprednisolone=0.8mgtriamcinolone=0.16mgbetamethasone=1.2mgdeflazacort),andwecalculatedcumulativedosesofexposureforcorticosteroidswiththesumofthedosesforalltheprescribeddays,whichwasexpressedasthecumulativedefineddailydose(cDDD)accordingtotheWorldHealthOrganizationdefinition.我們將系統(tǒng)性糖皮質激素處方定義為口服糖皮質激素處方和靜脈糖皮質激素處方。系統(tǒng)性糖皮質激素使用定義為從2003年到基線日期（見表1）的住院和門診就診期間的藥物代碼處方。兩組觀察期相同。將所有糖皮質激素制劑轉換為基于潑尼松等效劑量（1毫克潑尼松龍等于4毫克氫化可的松等于0.8毫克甲基潑尼松龍等于0.8毫克曲安奈德等于0.16毫克倍他米松等于1.2毫克德夫氯喹）的每日劑量，并根據(jù)世界衛(wèi)生組織的定義計算糖皮質激素的累積暴露劑量（累積定義每日劑量，cDDD），即將所有處方天數(shù)的劑量相加。?Table1PrescriptionDrugCodesandDosageofSystemicCorticosteroidBasedontheHealthInsuranceClaimsPaymentCodingSystem.Drug???????Code??????CorticosteroidandDosageOralcorticosteroids116401ATB???betamethasone0.5mg116501ATB???betamethasonesodiumphosphate0.5mg296900ATB???betamethasone0.25mg140801ATB???deflazacort6mg140802ATB???deflazacort30mg141901ATB???dexamethasone0.5mg141903ATB???dexamethasone0.75mg141904ATB???dexamethasone4mg170901ATB???hydrocortisone10mg170905ATB???hydrocortisone20mg170906ATB???hydrocortisone5mg193301ATB???methylprednisolone16mg193302ATB???methylprednisolone4mg193303ATB???methylprednisolone8mg193304ATB???methylprednisolone2mg193305ATB???methylprednisolone1mg217001ATB???prednisolone5mg243201ATB???triamcinolone1mg243202ATB???triamcinolone2mg243203ATB???triamcinolone4mgHigh-doseIVcorticosteroids?171201BIJ???????hydrocortisonesodiumsuccinate100mg171202BIJ?????hydrocortisonesodiumsuccinate250mg171203BIJ?????hydrocortisonesodiumsuccinate40mg193601BIJ?????methylprednisolonesodiumsuccinate125mg193602BIJ?????methylprednisolonesodiumsuccinate250mg193603BIJ?????methylprednisolonesodiumsuccinate40mgmethylprednisolonesodiumsuccinate500mg193604BIJ?????methylprednisolonesodiumsuccinate1000mg193605BIJ?????prednisolonesodiumsuccinate1000mg217301BIJ?????prednisolonesodiumsuccinate250mg217302BIJ???????SubgroupAnalysisATHAafteranONFHdiagnosiswasusedasasurrogateforfemoralheadcollapse.Therefore,wedividedallcasesinto2groups:agroupthatreceivedTHAandanothergroupthatdidnotreceiveTHAusingtreatmentcodes(N0711.N7020).Amongatotalof3,430patients,weexcluded70patientswhohadaTHAtreatmentcodepriortodiagnosis,1,175patientswhoreceivedTHAduringtheobservationperiod,and2,255patientswhodidnot.Wecomparedthe2groupsandanalyzedthemusingtheCoxproportionalhazardsmodel,whichfactorsaffectdiseaseprogressionleadingtoTHA(Figure2).診斷為ONFH后進行THA作為股骨頭塌陷的替代。因此，我們使用治療代碼(N0711)將所有病例分為兩組:接受THA治療的組和未接受THA治療的組。N7020)。在總共3430例患者中，我們排除了70例在診斷前有THA治療代碼的患者，1175例在觀察期間接受THA治療的患者和2255例未接受THA治療的患者。我們對兩組患者進行比較，并使用Cox比例風險模型進行分析，分析影響THA病情進展的因素(圖2)。??Fig.2Studyflow:comparisonofpatientswhoreceivedanddidnotreceivetotalhiparthroplastyafterdiagnosisONFH,osteonecrosisoffemoralhead;THA,totalhiparthroplasty.??DataAnalysisChi-squaredtestsforcategoricalvariableswereperformedtocomparethebaselinecharacteristicsbetweencaseandcontrolpatients.AconditionallogisticregressionanalysiswasperformedtoevaluatetheassociationbetweensystemiccorticosteroiduseandtheriskofONFH.Forsubgroupanalysis,weusedCoxproportionalhazardmodelstoestimateadjustedhazardratios(aHRs)and95%confidenceintervals(CIs).APvalue<.05wasconsideredsignificant.AllstatisticalanalyseswereperformedusingSASEnterpriseGuideversion7.1(SASInstitute,Cary,NorthCarolina).?ResultsDemographicDataforONFHCasesandMatchedControlsTable2showsthebaselinecharacteristicsofcasesandmatchedcontrols.The2groupshadevendistributionsinthematchingvariables,includingsexandbirthyear.Subjectswerepredominantlymen(61.1%),andthemostcommonagegroupwasthoseborninthe1950s(age63to72asof2022).Comparedwiththecontrolgroup,ONFHcasepatientshadlowhouseholdincomeandhadmorediabetes,hypertension,dyslipidemia,andheavyalcoholuse(drinkingmorethan3to7drinksperweek).Inaddition,thecasepatientshadnormalserumLDLlevels(<100mg/dL),butconversely,thereweremanycasesofhypertriglyceridemiawithserumTGlevelsof200mg/dLormore.??Table2BaselineCharacteristicofOsteonecrosisofFemoralHeadCasesandMatchedControls.totalN=20,928(%)?????CasesN=3,488(%)ControlsN=17,440(%)?????PSex????????????????????????Men12,792(61.1)?2,132(61.1)???10,660(61.1)?Women???8,136(38.9)???1,356(38.9)???6,780(38.9)???????Birthyear??????????????????????????????<1930????852(4.1)142(4.1)710(4.1)1930to1939?3,024(14.4)???504(14.4)??????2,520(14.4)?????1940to1949?4,074(19.5)???679(19.5)??????3,395(19.5)?????1950to1959?5,112(24.4)???852(24.4)??????4,260(24.4)?????1960to1969?3,786(18.1)???631(18.1)??????3,155(18.1)?????1970to1979?2,184(10.4)???364(10.4)??????1,820(10.4)?????1980to1989?1,080(5.2)?????180(5.2)900(5.2)1990to1999?558(2.7)93(2.7)??465(2.7)2000to2009?210(1.0)35(1.0)??175(1.0)2010to2019?48(0.2)??8(0.2)????40(0.2)??Age(atindexdate)55.2±16.9????55.2±16.9???????55.2±16.9????Householdincome????????????????????????Low4,535(21.7)???896(25.7)??????3,639(20.9)???????<.001Middle???6,500(31.0)???1,090(31.2)???5,410(31.0)???????High???????9,893(26.5)???1,502(43.1)???8,391(48.1)???????Comorbidities????????????????????????Hypertension?6,631(31.7)???1,301(37.3)???5,330(30.6)?????<.001Diabetesmellitus???4,567(21.8)???908(26.0)???????3,659(21.0)???<.001Dyslipidemia??5,555(26.5)???1,120(32.1)???4,435(25.4)?????<.001Frequencyofdrinkingalcohol??????????????????????????????<1d/wk??10,044(48.0)?1,613(46.2)???8,431(48.3)???????<.0011to2d/wk?????3,987(19.1)???560(16.1)??????3,427(19.7)?????3to7d/wk?????2,794(13.3)???621(17.8)??????2,173(12.5)?????Missing??4,103(19.6)???694(19.9)??????3,409(19.5)???????Smokingstatus?????????????????????????????Non-smoker???9,455(45.2)???1,539(44.1)???7,916(45.4)?????.199Ex-smoker?????2,865(13.7)???462(13.3)??????2,403(13.8)?????Currentsmoker??????4,488(21.4)???790(22.6)???????3,698(21.2)???Missing??4,120(19.7)???697(20.0)??????3,423(19.6)???????BMI,kg/m2??24.0±3.3??????23.9±3.4??????24.0±3.3??.547<18·5?????608(2.9)113(3.2)495(2.8).09018·5to22·9???6,126(29.3)???1,029(29.5)???5,097(29.2)?????23·0to24·9???4,239(20.3)???651(18.7)??????3,588(20.6)?????≥25·0?6,113(29.2)???1,049(30.1)???5,064(29.0)???????Missing??3,842(25.1)???646(18.5)??????3,196(18.3)???????HDL,mg/dL??54.2±20.5????55.2±22.7????54.0±20.0.015<40?2,113(10.1)???339(9.7)1,774(10.2%).03340to59??8,856(42.3)???1,411(40.5)???7,445(42.7%)??≥60???????4,700(22.5)???830(23.8)????3870(22.2%)???????Missing??5,259(25.1)???908(26.0)??????4,351(24.9%)??LDL,mg/dL???114.8±77.2??110.6±56.9??115.7±80.6<.001<100??????5,627(26.9)???1,045(30.0)???4,582(26.3)???????<.001100to159?????8,493(40.6)???1,297(37.2)???7,196(41.3)?????≥160?????1,528(7.3)?????234(6.7)1,294(7.4)?????Missing??5,280(25.2)???912(26.1)??????4,368(25.0)???????TG,mg/dL?????144.5±108.7154.8±125.0142.5±105.1??????<.001<150??????10,395(49.7)?1,651(47.3)???8,744(50.1)???????<.001150to199?????2,447(11.7)???390(11.2)??????2,057(11.8)?????≥200?????2,829(13.5)???540(15.5)??????2,289(13.1)???????Missing??5,257(25.1)???907(26.0)??????4,350(24.9)???????BMI,bodymassindex;HDL,highdensitylipoprotein;LDL,lowdensitylipoprotein;TG,triglyceride.??Table3showsthecomparisonofprescribedsystemiccorticosteroidsincasepatientsandcontrolpatients.Bothgroupshadidenticalobservationperiods(meanobservationperiodwas8.26years).Systemiccorticosteroidwasprescribedatleastoncemoreinthecasegroupthaninthecontrolgroup(71.8versus62.9%,P<.001).EvenwhenoralcorticosteroidsandIVcorticosteroidswerecompared,respectively,thenumberofcasesprescribedcorticosteroidsatleastoncewashigherinthepatientswhohadONFH(oralcorticosteroids:71.2versus62.4%,P<.001/IVcorticosteroids:10.7versus4.9%,P<.001).??Table3DifferenceinCorticosteroidUseBetweenCasesandMatchedControlsFrom2003UntilDiagnosis.TotalN=20,928(%)?????CasesN=3,488(%)ControlsN=17,440(%)?????PCorticosteroid(oralorhigh-doseIV)???????????????????????????Neveruse???????7,453(35.6)???983(28.2)??????6,470(37.1)?????<.001Everuse?13,475(64.4)?2,505(71.8)?10,970(62.9)???????Oralcorticosteroid????????????????????????Neveruse???????7,562(36.1)???1,004(18.8)???6,558(37.6)?????<.001Everuse?13,366(63.9)?2,484(71.2)?10,882(62.4)???????Neveruse???????7,562(36.1)???1,004(18.8)???6,558(37.6)?????<.001<180cDDDs??12,667(60.5)?2,192(62.8)???10,475(60.1)?????180to364cDDDs?397(1.9)146(4.2)251(1.4)365to729cDDDs?179(0.9)84(2.4)??95(0.5)??≥730cDDDs123(0.6)62(1.8)??61(0.4)??High-doseIVcorticosteroid??????????????????????????Neveruse???????19,703(94.2)?3,116(89.3)???16,587(95.1)?????<.001Everuse?1,225(5.8)?????372(10.7)??????853(4.9)Neveruse???????19,703(94.2)?3,116(89.3)???16,587(95.1)?????<.001<180cDDDs??988(4.7)266(7.6)722(4.1)180to364cDDDs?120(0.6)46(1.3)??74(0.4)??365to729cDDDs?77(0.4)??40(1.2)??37(0.2)??≥730cDDDs40(0.2)??20(0.6)??20(0.1)??cDDDs,cumulativedefineddailydoses(prednisolone10mg);IV,intravenous.??CumulativeCorticosteroidDoseandONFHDevelopmentConditionallogisticregressionanalysiswasperformedtoanalyzetheeffectofthecumulativedoseofsystemiccorticosteroidsfor1yearbeforediagnosisontheincidenceofONFH(Table4).SystemiccorticosteroidusewassignificantlyassociatedwithanincreasedriskofONFHincidencecomparedtothatofnonusers.Specifically,higherdosesoforalcorticosteroidwereassociatedwithincreasedriskofONFH(oddsratiosof1.61(95%CI1.47to1.78,P<.001),4.39(95%CI3.47to5.56,P<.001),6.42(95%CI4.65to8.87,P<.001),and5.44(95%CI3.65to8.13,P<.001)forpatientswhohavecorticosteroiduseof<180,180to365,365to720,and>720cDDDs(valuesconvertedtodailyprednisolone10mg),respectively.TheriskofONFHincreasedrapidlywhenthecDDDwas180ormore,thatis,whencumulativeprednisoloneusewas1,800mgormore.Inaddition,atrendtowardriskincreasewithcumulativedosesofIVcorticosteroidusewasshownwithadjustedoddsratio(AOR)of1.63(95%CI1.39to1.90,P<.001),2.34(95%CI1.57to3.49,P<.001),3.77(95%CI2.33to6.10,P<.001),and2.76(95%CI1.41to5.39,P=.003)forpatientswhohavecorticosteroiduseof<180,180to365,365to720,and>720cDDDs(valuesconvertedtodailyprednisolone10mg),respectively.??Table4AdjustedRiskofOsteonecrosisofFemoralHeadOccurrence.ConditionalLogisticRegressionAnalysisforONFHDevelopmentCrudeOR??????95%CI???P?????AdjustedOR??95%CI???????PHouseholdincome????????????????????????????????????????Low1.381.26to1.52???<.001?????1.381.25to1.51???????<.001Middle???1.131.03to1.23???.0071.131.03to1.23???????.008High???????1.00ref.?????????1.00ref.??Comorbidities???????????????????????????????????????Hypertension?1.471.35to1.60???<.001?????1.21???????1.06to1.37???.004Diabetesmellitus???1.381.26to1.51???<.001???????1.070.95to1.20???.289Dyslipidemia??1.471.35to1.60???<.001?????1.18???????1.04to1.34???.012Frequencyofdrinkingalcohol?????????????????????????????????????????????<1d/wk??1.00ref.?????????1.00ref.??1to2d/wk?????0.870.78to0.97???.0150.900.80to1.01.0713to7d/wk?????1.541.38to1.73???<.001?????1.54???????1.36to1.74???<.001Missing??1.080.97to1.20???.1801.120.59to2.14???????.731Smokingstatus?????????????????????????????????????????????Non–smoker??1.00ref.?????????1.00ref.??Ex–smoker?????1.010.89to1.15???.8670.930.82to1.07.314Currentsmoker??????1.131.01to1.26???.0321.01???????0.90to1.14???.855Missing??1.060.95to1.18???.2791.030.55to1.94???????.923BMI,kg/m2?????????????????????????????????????????<18·5?????1.130.91to1.41???.2621.150.92to1.44???????.23218·5to22·9???1.00ref.?????????1.00ref.??23·0to24·9???0.900.81to0.99???.0490.900.80to1.01.062≥25·0?1.020.93to1.13???.6280.990.89to1.09???????.784Missing??1.000.90to1.13???.9450.800.55to1.17???????.254HDL,mg/dL?????????????????????????????????????????<40?1.010.88to1.15???.9250.950.83to1.09???????.44740to59??1.00ref.?????????1.00ref.??≥60???????1.131.03to1.25???.0091.100.99to1.21???????.069Missing??1.121.01to1.23???.0312.910.14to60.46???????.490LDL,mg/dL??????????????????????????????????????????<100??????1.00ref.?????????1.00ref.??100to159?????0.790.72to0.86???<.001?????0.86???????0.78to0.94???.001≥160?????0.790.67to0.92???.0030.84071to0.98???????.031Missing??0.930.83to1.03???.1520.840.28to2.56???????.762TG,mg/dL????????????????????????????????????????????<150??????1.00ref.?????????1.00ref.??150to199?????1.010.89to1.14???.9170.990.88to1.13.970≥200?????1.261.13to1.40???<.001?????1.171.04to1.32.009Missing??1.121.01to1.23???.0250.460.03to7.70???????.585Medication????????????????????????????????????????????Steroid(oralorhigh–doseIV)?????????????????????????????????????????????Neveruse???????1.00ref.?????????1.00ref.??Everuse?1.751.59to1.92???<.001?????1.771.60to1.94<.001POsteroid?????????????????????????????????????????????Neveruse???????1.00ref.?????????1.00ref.??Everuse?1.731.57to1.90???<.001?????1.681.53to1.85<.001Neveruse???????1.00ref.?????????1.00ref.??<180cDDDs??1.631.49to1.79???<.001?????1.61???????1.47to1.78???<.001180to364cDDDs?4.983.96to6.25???<.001???????4.393.47to5.56???<.001365to729cDDDs?7.515.50to10.27?<.001???????6.424.65to8.87???<.001≥730cDDDs8.966.16to13.02?<.001?????5.44???????3.65to8.13???<.001High–doseIVsteroid????????????????????????????????????????????Neveruse???????1.00ref.?????????1.00ref.??Everuse?2.422.12to2.76???<.001?????2.201.92to2.51<.001Neveruse???????1.00ref.?????????1·00?????ref.??<180cDDDs??2.041.76to2.38???<.001?????1.63???????1.39to1.90???<.001180to364cDDDs?3.402.35to4.92???<.001???????2.341.57to3.49???<.001365to729cDDDs?5.863.74to9.18???<.001???????3.772.33to6.10???<.001≥730cDDDs5.232.81to9.73???<.001?????2.76???????1.41to5.39???.003BMI,bodymassindex;cDDDs,cumulativedefineddailydoses(prednisolone10mg);CI,confidenceinterval;HDL,highdensitylipoprotein;IV,intravenous;LDL,lowdensitylipoprotein;ONFH,osteonecrosisoffemoralhead;OR,oddsratio;PO,peroral;TG,triglyceride.??RiskFactorsforTHAinPatientswhoHaveONFHFortheONFHcasepatients,asubgroupanalysiswasperformedon1,175patientsintheTHAgroupand2,255patientsinthenon-THAgroupduringtheobservationperiod.Thefollow-updurationoftheTHAgroup(1,175patients)was1.03±2.25years,andthefollow-updurationofthenon-THAgroup(2,255patients)was7.93±5.15years.Table5showsthebaselinecharacteristicsofTHAcasesandnon-THAcases.IntheTHAgroup,therewasagreaterproportionofmen(63.9versus60.0%,P=.028),higherBMI(24.1versus23.8,P=.027),heavyalcoholuseofthosewhoconsumedalcoholmorethan3to7daysaweek(22.9versus15.2%,P<.001),currentsmokers(26.4versus20.8%,P<.001),andhigherTG(162.3mg/dLversus150.0,P≤.001).However,whentheeffectondiseaseprogressionwasanalyzedusingCoxproportionalhazardsmodelforsurvivalanalysisafterONFHdiagnosis,heavyalcoholuseandlongercorticosteroidusesweretheriskfactorsaffectingdiseaseprogression,anddiabeteswasafactorthatslowedprogression.Moreover,otherlipidprofilesaswellascorticosteroidsusedandcumulativedosesofcorticosteroidsdidnotaffecttheincidenceofTHA(Table6).Inaddition,whenthesurvivalanalysiswasperformedafterthediagnosisofONFHbydividingthepatientgroupintomalesandfemales,heavyalcoholuseinvolvingthosewhoconsumedalcoholmorethan3to7daysaweekincreasedtheriskofdiseaseprogressionafterONFHdiagnosisinmalesonly(aHR:1.38,95%CI1.16to1.65,P<.001),andaBMIof25orhigherinfemalesonlyincreasedtheriskofincidenceofTHAafterONFHdiagnosis(aHR:1.52,95%CI1.18to1.96,P<.001).??Table5Comparisonofthe2GroupsAccordingtoWhetherorNotTotalHipArthroplastywasPerformedDuringtheFollow-UpPeriodAfterOsteonecrosisofFemoralHeadDiagnosis.TotalN=3,430(%)??????THAafterDiagnosisN=1,175(%)?????NoTHAafterDiagnosisN=2,255(%)???????PSex????????????????????????Men2,104(61.3)???751(63.9)??????10,660(61.1)???????.028Women???1,326(38.7)???424(36.1)??????6,780(38.9)???????Birthyear??????????????????????????????<1930????141(4.1)16(1.4)??125(5.5)<.0011930to1939?492(14.3)??????153(13.0)??????339(15.0)?????1940to1949?665(19.4)??????246(20.9)??????419(18.6)?????1950to1959?837(24.4)??????344(29.3)??????493(21.9)?????1960to1969?621(18.1)??????229(19.5)??????392(17.4)?????1970to1979?359(10.5)??????118(10.0)??????241(10.4)?????1980to1989?180(5.3)56(4.8)??124(5.2)1990to1999?92(2.7)??13(1.1)??79(3.5)??2000to2009?35(1.0)??0(0.0)????35(1.6)??2010to2019?8(0.2)????0(0.0)????8(0.3)????Age(atindexdate)55.1±17.0????56.41±13.8???????54.6±18.4????.007Householdincome????????????????????????Low880(25.7)??????283(24.1)??????597(26.5)???????.008Middle???1,077(31.4)???409(34.8)??????668(29.6)???????High???????1,473(42.9)???483(41.1)??????990(43.9)???????Comorbidities????????????????????????Hypertension?1,269(37.0)???445(37.9)??????824(36.5)?????.466Diabetesmellitus???888(25.9)??????285(24.3)???????603(26.7)??????.125Dyslipidemia??1,095(31.9)???383(32.6)??????712(31.6)?????.568Frequencyofdrinkingalcohol??????????????????????????????<1d/wk??1,581(46.1)???504(42.9)??????1,077(47.8)???????<.0011to2d/wk?????549(16.0)??????207(17.6)??????342(15.2)?????3to7d/wk?????613(17.9)??????269(22.9)??????344(15.2)?????Missing??687(20.0)??????195(16.6)??????492(21.8)???????Smokingstatus?????????????????????????????Nonsmoker????1,507(43.9)???491(41.8)??????1,016(45.1)?????.199Ex-smoker?????454(13.2)??????180(15.3)??????274(12.2)?????Currentsmoker??????780(22.7)??????310(26.4)???????470(20.8)??????Missing??689(20.1)??????194(16.5)??????495(21.9)???????BMI,kg/m2???23.9±3.4??????24.1±3.4??????23.8±3.3??.027<18·5?????112(3.3)37(3.2)??75(3.3)??<.00118·5-22·9??????1,014(29.3)???355(30.2)??????659(29.2)?????23·0-24·9??????640(18.7)??????218(18.5)??????422(18.7)?????≥25·0?1,024(29.8)???388(33.0)??????636(28.2)???????Missing??640(18.7)??????177(15.1)??????463(20.5)???????HDL,mg/dL??55.3±22.9????55.7±16.0????55.1±26.1.015<40?331(9.6)110(9.4)221(9.8).03340-59?????1,379(40.2)???494(42.0)??????885(39.2)???????≥60???????822(24.0%)??322(27.4%)??500(22.2%)???????Missing??898(26.2%)??248(21.2%)??649(28.8%)???????LDL,mg/dL???110.6±57.1??111.4±80.9??110.1±37.0.668<100??????1,023(29.8%)378(32.2%)??645(28.6%)???????<.001100-159?1,277(37.2%)464(39.5%)??813(36.1%)???????≥160?????229(6.7%)????81(6.9%)??????148(6.5%)???????Missing??901(26.3%)??252(21.4%)??649(28.8%)???????TG,mg/dL?????154.5±125.1162.3±141.3150.0±114.5??????.024<150??????1,626(47.4%)576(19.0%)??1,050(46.6%)??<.001150-199?378(11.0%)???140(11.9%)???238(10.5%)???????≥200?????530(15.5%)??211(18.0%)???319(14.2%)???????Missing??896(26.1)??????248(21.1)??????648(28.7)???????Systemiccorticosteroid(Oralorhigh-doseIV)???????????????????????????Neveruse???????2,090(60.9)???710(60.4)??????1,380(61.2)?????.687Everuse?1,340(39.1)???465(39.6)??????875(38.8)???????Oralcorticosteroid????????????????????????Neveruse???????2,119(61.8)???718(61.1)??????1,401(62.1)?????.584Everuse?1,311(38.2)???457(38.9)??????854(37.9)???????.690Neveruse???????2,119(61.8)???718(61.1)??????1,401(62.1)?????<180cDDDs??1,240(36.1)???434(36.9)??????806(35.7)?????180-364cDDDs????47(1.4)??15(1.3)??32(1.4)??365-729cDDDs????21(0.6)??8(0.7)????13(0.6)??≥730cDDDs3(0.1)????0(0.0)????3(0.1)????High-doseIVcorticosteroid??????????????????????????Neveruse???????3,322(96.9)???1,142(97.2)???2,180(96.7)?????.471Everuse?108(3.1)33(2.8)??75(3.3)??.858Neveruse???????3,322(96.9)???1,142(97.2)???2,180(96.7)?????<180cDDDs??84(2.4)??26(2.2)??58(2.5)??180-364cDDDs????9(0.3)????2(0.2)????7(0.3)????365-729cDDDs????10(0.3)??4(0.3)????6(0.3)????≥730cDDDs5(0.1)????1(0.1)????4(0.2)????BMI,bodymassindex;cDDDs,cumulativedefineddailydoses(prednisolone10mg);CI,confidenceinterval;HDL,highdensitylipoprotein;IV,intravenous;LDL,lowdensitylipoprotein;ONFH,osteonecrosisoffemoralhead;OR,oddsratio;TG,triglyceride;THA,totalhiparthroplasty.??Table6AdjustedRiskofTotalHipArthroplastyofOsteonecrosisofFemoralHeadPatients.ConditionalLogisticRegressionAnalysisforONFHDevelopmentCrudeOR??????95%CI???P?????AdjustedOR??95%CI???????PSex????????????????????????????????????????Men1.00ref.?????????1.00ref.??Women???0.890.79to1.01???.0601.030.88to1.20???????.731Age?1.011.00to1.01???<.001?????1.011.01to1.02???????<.001Householdincome????????????????????????????????????????Low1.000.86to1.16???.9891.020.88to1.19???????.786Middle???1.201.05to1.37???.0081.211.06to1.38???????.006High???????1.00ref.?????????1.00ref.??Comorbidities???????????????????????????????????????Hypertension?1.120.99to1.26???.0581.100.91to1.32.340Diabetesmellitus???0.950.83to1.09???.4460.80???????0.68to0.96???.013Dyslipidemia??1.090.97to1.23???.1570.980.81to1.19.842Frequencyofdrinkingalcohol?????????????????????????????????????????????<1d/wk??1.00ref.?????????1.00ref.??1to2d/wk?????1.231.05to1.45???.0111.231.02to1.47.0263to7d/wk?????1.501.30to1.74???<.001?????1.38???????1.16to1.65???<.001Missing??0.900.76to1.06???.2043.120.80to12.23???????.103Smokingstatus?????????????????????????????????????????????Nonsmoker????1.00ref.?????????1.00ref.??Ex-smoker?????1.311.11to1.56???.0020.251.03to1.52.027Currentsmoker??????1.261.09to1.45???.0021.17???????0.98to1.41???.085Missing??0.860.73to1.02???.0850.400.10to1.64???????.203BMI,kg/m2?????????????????????????????????????????<18·5?????0.940.67to1.31???.6980.890.63to1.25???????.51018·5to22·9???1.00ref.?????????1.00ref.??23·0to24·9???0.940.80to1.12???.4940.950.80to1.12.519≥25·0?1.090.95to1.26???.2321.110.96to1.29???????.176Missing??0.770.65to0.93???.0051.040.61to1.77???????.880HDL,mg/dL?????????????????????????????????????????<40?0.930.76to1.15???.5170.910.74to1.12???????.37640to59??1.00ref.?????????1.00ref.??≥60???????1.130.98to1.30???.0941.161.01to1.34???????.043Missing??0.770.66to0.90???<.001?????0.320.03to3.11.325LDL,mg/dL??????????????????????????????????????????<100??????1.00ref.?????????1.00ref.??100to159?????0.970.84to1.11???.6140.990.86to1.13.844≥160?????0.930.73to1.18???.5610.960.75to1.23???????.728Missing??0.740.63to0.87???<.001?????5.091.59to16.28??????.006TG,mg/dL????????????????????????????????????????????<150??????1.00ref.?????????1.00ref.??150to199?????1.070.89to1.29???.4471.050.87to1.27.583≥200?????1.191.02to1.39???.0301.110.94to1.31???????.231Missing??0.780.67to0.91???.0010.490.07to3.60???????.485Medication????????????????????????????????????????????Steroid(oralorhigh–doseIV)?????????????????????????????????????????????Neveruse???????1.00ref.?????????1.00ref.??Everuse?1.090.97to1.22???.1721.070.95to1.21???????.268POsteroid?????????????????????????????????????????????Neveruse???????1.00ref.?????????1.00ref.??Everuse?1.090.97to1.23???.1341.070.95to1.21???????.268Neveruse???????1.00ref.?????????1.00ref.??<180cDDDs??1.090.97to1.23???.1421.080.95to1.21.247180to364cDDDs?1.100.66to1.83???.7161.22???????0.73to2.06???.449365to729cDDDs?1.280.64to2.58???.4821.62???????0.79to3.36???.191≥730cDDDs<0.001???<0.001to999.944<0.001???????<0.001to999.943High–doseIVsteroid????????????????????????????????????????????Neveruse???????1.00ref.?????????1.00ref.??Everuse?0.910.64to1.29???.5920.900.63to1.28???????.552Neveruse???????1.00ref.?????????1.00ref.??<180cDDDs??0.950.64to1.39???.7760.870.59to1.30.504180to364cDDDs?0.600.15to2.41???.4740.71???????0.17to2.87???.626365to729cDDDs?1.200.45to3.20???.7191.35???????0.50to3.64???.554≥730cDDDs0.480.07to3.38???.4580.540.07to4.01.545Steroiduseduration?????????????????????????????????????????????Neveruse???????1.00ref.?????????1.00ref.??<3mobeforediagnosis?1.601.45-1.76<.001???????1.621.47-1.78<.0013-6mobeforediagnosis3.863.22-4.63<.001???????3.913.25-4.70<.0016-12mobeforediagnosis??????5.284.16-6.71<.001???????5.234.10-6.67<.001>12mobeforediagnosis7.575.98-9.59<.001???????7.405.82-9.42<.001?查看原圖BMI,bodymassindex;cDDDs,cumulativedefineddailydoses(prednisolone10mg);CI,confidenceinterval;HDL,highdensitylipoprotein;IV,intravenous;LDL,lowdensitylipoprotein;ONFH,osteonecrosisoffemoralhead;OR,oddsratio;PO,peroral;TG,triglyceride;THA,totalhiparthroplasty.??DiscussionWeevaluated3,488ONFHcasesand17,440controlcaseswithmatchingvariablesincludingage,sex,andthetimeofthefollow-upata1:5ratiofromtheNHIS-NSC,includingthefollow-updatafrom2002to2019of1,137,861participantsinanationwidelongitudinalnestedcase-controlstudy.Wedemonstratedthatalowhouseholdincome,diabetes,hypertension,dyslipidemia,heavyalcoholicswhoconsumedalcoholmorethan3daysaweek,andserumTGlevelsof200mg/dLormorewereassociatedwiththedevelopmentofONFH.Inaddition,systemiccorticosteroidusewassignificantlyassociatedwithanincreasedriskofONFHincidencecomparedtothatofnonusers.Specifically,theriskofONFHincreasedrapidlywhenthecDDDswere180ormorecumulativedosesofcorticosteroiduse.WeanalyzedthefactorsaffectingtheprogressionofthediseasebycomparingpatientswhounderwentTHAwiththosewhodidnotundergoTHAduringthefollow-upperiodafterONFHdiagnosis.Men,whohadahigherBMI,heavyalcoholicswhoconsumedalcoholmorethan3daysaweek,currentsmokers,andserumTGlevelsof200mg/dLormorewereassociatedwithTHAafterONFHdiagnosis.However,afteradjustingforcompoundfactors,heavyalcoholicsweretheonlyfactoraffectingtheincidenceofTHAafterONFHdiagnosis,anditmaybeusedtocounselONFHpatients.Otherlipidprofiles,corticosteroidsused,andcumulativedosesofcorticosteroidsdidnotaffecttheincidenceofTHA.我們評估了3488例ONFH病例和17440例對照病例，匹配變量包括年齡、性別和隨訪時間，比例為1:5，來自NHIS-NSC，包括2002年至2019年全國縱向巢式病例對照研究中1137861名參與者的隨訪數(shù)據(jù)。研究表明，家庭收入低、糖尿病、高血壓、血脂異常、每周飲酒超過3天的重度酗酒者以及血清TG水平≥200mg/dL與ONFH的發(fā)生有關。此外，與不使用皮質類固醇的患者相比，全身性使用皮質類固醇與ONFH發(fā)生率增加顯著相關。特別是，當皮質類固醇的累積使用劑量達到180或更高時，ONFH的風險迅速增加。我們通過比較ONFH診斷后隨訪期間接受THA和未接受THA的患者來分析影響疾病進展的因素。BMI較高的男性、每周飲酒超過3天的重度酗酒者、當前吸煙者、血清TG水平≥200mg/dL的男性在ONFH診斷后與THA相關。然而，在調(diào)整復合因素后，重度酗酒者是ONFH診斷后唯一影響THA發(fā)生率的因素，可用于指導ONFH患者。其他脂質特征、使用的皮質類固醇和皮質類固醇的累積劑量對THA的發(fā)生率沒有影響。TherelationshipbetweencorticosteroiduseandONFHdevelopmenthasbeenrevealedinseveralstudies[8,25,26],andtherearealsosomestudiesthathavesuggestedspecificdosesanddurationsofcorticosteroiduse,suchastheassociationwiththedevelopmentofdiseasewhenusingmorethan2gwithin3months[27]orthemeancorticosteroiduseofpatientswhohaveONFHdevelopmentof3,314mg[28].Inthecurrentlargecohortstudyofthegeneralpopulation,weanalyzedvariousfactorsthatcanaffectthedevelopmentofONFH.Asinpreviousstudies,thecaseofcorticosteroiduseatleastonceandadditionalcumulativecorticosteroiddosewereassociatedwiththeincreasedriskofONFHdevelopment,andwhencumulativeprednisoloneusewas1,800mg(180cDDDs)ormore,theriskofONFHdevelopmentincreasedrapidly.Surely,thedevelopmentofONFHrelatedtocorticosteroiduseisthoughttobecausedbyacombinationofnotonlycorticosteroidusebutalsoseveralfactorssuchascomorbidities,alcohol,smoking,andgeneticfactors.Sincecorticosteroidtreatmentisoftenessentialformanydiseases,itisnecessarytobeawareofthecumulativedoseatwhichtheriskofONFHincreasesrapidlywhencontinuouscorticosteroidtreatmentisrequired.?一些研究已經(jīng)揭示了皮質類固醇的使用與ONFH發(fā)展之間的關系[8,25,26]，也有一些研究提出了皮質類固醇使用的特定劑量和持續(xù)時間，如在3個月內(nèi)使用超過2g與疾病發(fā)展的關系[27]，或ONFH發(fā)展患者的平均皮質類固醇使用量為3,314mg[28]。在目前針對普通人群的大型隊列研究中，我們分析了影響ONFH發(fā)展的各種因素。與之前的研究一樣，至少使用一次皮質類固醇和額外的皮質類固醇累積劑量與ONFH發(fā)展的風險增加有關，當潑尼松龍累積使用1800毫克(180cDDDs)或更多時，ONFH發(fā)展的風險迅速增加。當然，與皮質類固醇使用相關的ONFH的發(fā)展被認為不僅是由皮質類固醇使用引起的，還包括合并癥、酒精、吸煙和遺傳因素等多種因素。由于皮質類固醇治療通常對許多疾病至關重要，因此有必要了解在需要持續(xù)皮質類固醇治療時ONFH風險迅速增加的累積劑量。Tothebestofourknowledge,nostudyhascomparedtheincidenceofONFHwithhigh-doseIVandoralcorticosteroidsatthesamecumulativedose.Inthepresentstudy,bothoralcorticosteroidandhigh-doseIVcorticosteroidsincreasedtheriskofdevelopingONFH,andwhencomparingtheoralandhigh-doseIVatthesamecumulativedose,oralcorticosteroidhadahigherrisk;totheAORsoforalcorticosteroidwere1.61(<180cDDDs),4.39(180to365cDDDs),6.42(365to720cDDDs),and5.44(>720cDDDs).TheAORsofhigh-doseIVcorticosteroidwere1.63(<180cDDDs),2.34(180to365cDDDs),3.77(365to720cDDDs),and2.76(>720cDDDs),respectively.Ingeneral,sincetheprednisolonepotencyoforalcorticosteroidsismuchlowerthanthatofhigh-doseIV,thedurationoforalcorticosteroidusewouldhavebeenlongerifthesamecumulativedosewasused.Montetal.reportedthatONFHoccurrencewasassociatedwithmeandailycorticosteroiddose,cumulativedose,andtreatmentduration[8].Ofcourse,ONFHoccurrenceswouldbeaffectedbygeneticsusceptibilityandexposuretovariousriskfactors,butinourstudy,weconfirmedthatmoreONFHoccurredinoralcorticosteroidswitharelativelysmalldailydoseatthesamecumulativedosecomparedtohigh-doseIVcorticosteroid,soitisassumedthatthelongertreatmentperiodofcorticosteroidisalsoassociatedwithdevelopingONFH.據(jù)我們所知，沒有研究比較相同累積劑量的高劑量靜脈注射和口服皮質類固醇對ONFH的發(fā)生率。在本研究中，口服皮質類固醇和高劑量靜脈注射皮質類固醇都增加了發(fā)生ONFH的風險，并且在相同累積劑量下，口服皮質類固醇與高劑量靜脈注射皮質類固醇相比，風險更高;口服皮質類固醇的AORs分別為1.61(<180cDDDs)、4.39(180~365cDDDs)、6.42(365~720cDDDs)和5.44(>720cDDDs)。高劑量靜脈注射皮質類固醇的AORs分別為1.63(<180cDDDs)、2.34(180~365cDDDs)、3.77(365~720cDDDs)和2.76(>720cDDDs)。一般來說，由于口服皮質類固醇的強的松龍效力遠低于高劑量靜脈注射，如果使用相同的累積劑量，口服皮質類固醇的使用時間會更長。Mont等人報道ONFH的發(fā)生與皮質類固醇的平均每日劑量、累積劑量和治療時間有關[8]。當然，ONFH的發(fā)生會受到遺傳易感性和暴露于各種危險因素的影響，但在我們的研究中，我們證實在相同累積劑量下，相對于高劑量靜脈注射皮質類固醇，日劑量相對較小的口服皮質類固醇更易發(fā)生ONFH，因此我們假設皮質類固醇治療時間越長也與ONFH的發(fā)生有關。ItiswellknownthatahigherTGlevel,orLDLcholesterol,isanimportantriskfactorforischemicheartdiseaseandstrokebyinhibitingbloodflow,andONFHispresumedtoberelatedtoinhibitionofbloodflowtothefemoralheadinasimilarmechanism[29].Similartopreviousstudies[7,30],higherTGwasariskfactorforONFHinourstudy.Inaddition,itwasconfirmedthatLDLatlessthan100mg/dLhasaprotectiveeffectontheoccurrenceofONFH.眾所周知，較高的TG或LDL膽固醇水平通過抑制血流是缺血性心臟病和中風的重要危險因素，而ONFH被認為與股骨頭血流的抑制有類似的機制[29]。與以往的研究相似[7,30]，在我們的研究中，高TG是ONFH的危險因素。此外，還證實了低于100mg/dL的LDL對ONFH的發(fā)生有保護作用。SinceONFHoccurspredominantlyinyoungerpatientsandpreservationofthenativejointasmuchaspossibleistheprincipleoftreatment,thediseaseprogressionandprognosisareasimportantastheoccurrenceofthedisease.WeoftenseecasesofbilateralONFHdevelopmentwhereonesidehasfemoralcollapseandtheothersideremainsasymptomaticwithoutfemoralheadcollapse.Alternatively,somecaseswereasymptomaticwithoutfemoralheadcollapse,butreceivedTHA.ItisknownthattheprognosisafterONFHdevelopmentisinfluencedbyvariousfactors,anduntilnow,therehavebeenstudiesshowingthatradiologicfactorssuchasthesizeorlocationofnecrosisoracetabularanatomicalfactorshaveaneffect[1,19,31].Montetal.reportedthattheprevalenceoffemoralheadcollapsewas38%(106of282hips)inameta-analysisandvariedfrom17to73%dependingontheriskfactor[16].Inourstudy,34.3%ofpatientsunderwentTHA,anaverageof1.03±2.25yearsafterdiagnosis,similartothepreviousstudy.Althoughradiologicassessmentcouldnotbeperformed,casesthatmayhaveseengreaterphysicalloads,suchasmen,whohadahigherBMI,excessivedrinking,smoking,andahigherserumTGlevelover200mg/dL,wereassociatedwithdiseaseprogression.Inparticular,thefactorsthatincreasedtheriskofdiseaseprogressionweredifferentinmenandwomen.Wefoundthatcorticosteroidsprescribedornotandcumulativedosesofcorticosteroidswereunlikelytoaffectdiseaseprogression.由于ONFH主要發(fā)生在年輕患者中，治療原則是盡可能保留原有關節(jié)，因此疾病的進展和預后與疾病的發(fā)生同樣重要。我們經(jīng)?？吹诫p側ONFH發(fā)展的病例，其中一側有股骨頭塌陷，另一側無股骨頭塌陷癥狀。另外，一些病例無股骨頭塌陷癥狀，但接受了THA。眾所周知，ONFH發(fā)生后的預后受多種因素影響，迄今已有研究表明，壞死的大小或位置等放射學因素或髖臼解剖因素對ONFH的預后有影響[1,19,31]。Mont等人在一項薈萃分析中報道，股骨頭塌陷的患病率為38%(282髖中的106髖)，根據(jù)危險因素的不同，患病率從17%到73%不等[16]。在我們的研究中，34.3%的患者接受了THA，平均診斷后1.03±2.25年，與之前的研究相似。雖然無法進行放射學評估，但可能出現(xiàn)較大身體負荷的病例，如男性，BMI較高，過度飲酒，吸煙，血清TG水平高于200mg/dL，與疾病進展相關。特別是，增加疾病進展風險的因素在男性和女性中是不同的。我們發(fā)現(xiàn)，開具或不開具皮質類固醇以及皮質類固醇的累積劑量不太可能影響疾病進展。Ourstudyhasseveralpotentiallimitationsthatshouldbeaddressedinfurtherstudies.TheONFHwasassessedbyanoperationaldefinitionusingadiagnosiscode,notbyaradiologicevaluationsuchasanx-rayorMRI.However,theincidenceofONFHinthisstudywassimilartothatinapreviousAsiangeneralpopulationstudythatdefineditusinghipjointx-raysand/orMRI[32].BecauseanaccurateselectionofONFHpatientsmaynothavebeenmade,anestedcase-controlanalysisfromapopulation-basedcohortwasperformedtoincreasetheaccuracyoftheanalysis.Additionally,usingtheNHIS-NSCdatabase,prescriptionrecordsforcorticosteroidscouldbeaccessed.However,theactualintakeofcorticosteroidsinsubjectsmightbedifferentfromtheprescriptionrecords.Fortunately,severalstudieshaveshownagoodcorrelationbetweenprescriptionsandrealexposuretodrugs[33,34].Also,wecouldnotobtaininformationabouttraumaticONFH,whichmayhaveinfluencedtheresultsofthecurrentstudy.Inaddition,wecouldnotassessotherinterventionsthatcouldaffectdyslipidemia,microvascularbloodflow,andosteogenesis,suchastheuseoflipid-loweringmedication,aspirin,antiplatelets,andanticoagulantmedication.Thisshouldbeevaluatedinfuturestudies.Furthermore,ananalysisofmultiplecomorbiditiessuchasrheumaticdisease,sicklecelldisease,humanimmunodeficiencyvirus,organtransplantation,andsoonthatcouldaffecttheoccurrenceandprognosisofONFHwasnotperformed.Inparticular,sincetheprognosisofONFHisdifferentforeachdisease,subgroupanalysisaccordingtocomorbidityisabsolutelynecessaryforfuturestudies.Additionally,weanalyzedtheassociationbetweencumulativedoseofcorticosteroidanddiseaseprogressionafterONFHdiagnosisusingcDDD,andweconfirmedthatcumulativedoseofcorticosteroiddidnotaffectdiseaseprogression.However,sincethenumberofpatientswhohave180cDDDormorewassmall,additionalanalysiswithalargernumberofpatientsmaybeneededtoobtainmoreaccurateresults.我們的研究有幾個潛在的局限性，應該在進一步的研究中加以解決。ONFH通過使用診斷代碼的操作定義進行評估，而不是通過x射線或MRI等放射學評估。然而，本研究中ONFH的發(fā)生率與先前的亞洲普通人群研究相似，該研究使用髖關節(jié)X光片和/或MRI來定義ONFH[32]。由于可能沒有對ONFH患者進行準確的選擇，因此進行了基于人群的隊列嵌套病例對照分析，以提高分析的準確性。此外，使用NHIS-NSC數(shù)據(jù)庫，可以訪問皮質類固醇的處方記錄。然而，受試者的實際皮質類固醇攝入量可能與處方記錄不同。幸運的是，有幾項研究表明，處方與實際接觸藥物之間存在良好的相關性[33,34]。此外，我們無法獲得有關創(chuàng)傷性ONFH的信息，這可能影響了當前研究的結果。此外，我們無法評估其他可能影響血脂異常、微血管血流和成骨的干預措施，如使用降脂藥物、阿司匹林、抗血小板和抗凝藥物。這應該在未來的研究中進行評估。此外，對風濕病、鐮狀細胞病、人類免疫缺陷病毒、器官移植等可能影響ONFH發(fā)生和預后的多重合并癥未進行分析。特別是，由于每種疾病的預后不同，因此根據(jù)合并癥進行亞組分析對于未來的研究是絕對必要的。此外，我們分析了使用cDDD診斷ONFH后皮質類固醇累積劑量與疾病進展之間的關系，我們證實皮質類固醇累積劑量不影響疾病進展。然而，由于cDDD≥180的患者數(shù)量較少，因此可能需要對更多患者進行額外分析，以獲得更準確的結果。?ConclusionLowhouseholdincome,diabetes,hypertension,dyslipidemia,heavyalcoholicswhoconsumedalcoholmorethan3daysaweek,serumTGlevelsof200mg/dLormore,andoralorhigh-doseIVcorticosteroiduseareassociatedwithONFHdevelopment.Specifically,theriskofONFHincreasedrapidlywhencumulativeprednisoloneusewas1,800mgormore.However,oralorhigh-doseIVcorticosteroiduseandcumulativedosedidnotaffecttheprognosisofONFH.SincethedevelopmentandprognosisofONFHarecomplexandmultifactorialprocesses,furtherstudyisneeded.低收入家庭、糖尿病、高血壓、血脂異常、每周飲酒超過3天的重度酗酒者、血清TG水平≥200mg/dL、口服或高劑量靜脈注射皮質類固醇與ONFH的發(fā)生有關。具體來說，當累積使用強的松龍超過1800毫克時，ONFH的風險迅速增加。然而，口服或高劑量靜脈注射皮質類固醇和累積劑量對ONFH的預后沒有影響。由于ONFH的發(fā)展和預后是一個復雜的多因素過程，需要進一步研究。2024年09月27日
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畢春強主任醫(yī)師 中國中醫(yī)科學院廣安門醫(yī)院南區(qū) 骨科 骨質疏松癥在初期通常沒有明顯的臨床表現(xiàn)，但是隨著發(fā)展，可能會出現(xiàn)脊柱變形、疼痛、和輕微外力下的骨折。因此稱它為寂靜的疾病或者靜悄悄的疾病。●?骨質疏松主要有以下4個表現(xiàn)：（1）疼痛。疼痛是原發(fā)性骨質疏松癥最為常見的癥狀?；颊弑憩F(xiàn)為不明原因的腰背疼痛，沿著脊柱兩側彌漫性癥布，平臥休息以后，疼痛可以稍微緩解，直立后仰、久站久坐后疼痛會非常明顯。（2）變矮駝背。許多老年朋友感覺自己身高跟年輕時相比明顯“縮水”了，腰也伸不直了。骨質疏松的脊柱椎體骨量明顯減少、骨強度差，容易壓縮變形，尤其是彎腰等動作容易導致椎體前部分壓縮變扁，這種原因導致的身高短縮通常超過3厘米且有駝背的表現(xiàn)。（3）骨折。骨折是最嚴重的骨質疏松并發(fā)癥，輕則影響機體功能，重則致殘甚至致死。嚴重骨質疏松的患者，輕微受傷甚至日常做家務，如從沙發(fā)上坐地跌倒、彎腰拖地、崴腳就可導致相應部位的骨折，常見的骨折部位是腰背部、髖部和手臂。（4）心肺功能受損。骨質疏松的患者如發(fā)生胸、腰椎壓縮性骨折，可出現(xiàn)脊椎后凸畸形（駝背），胸腔容量變小且胸廓活動范圍受限，導致肺活量和最大換氣量顯著減少，患者往往感覺心慌、憋氣、氣不夠用等，以爬樓、擰重物時較為明顯。為什么會出現(xiàn)骨質疏松？老年人容易得骨質疏松主要是由于性激素的減少、臟器功能的減弱，刺激了破骨細胞，同時也抑制了成骨細胞的增生，造成了骨量減少。在臨床上骨質疏松是非常常見的一種疾病。有研究表明，六十歲以上的老年人得骨質疏松的幾率可以達到百分之三十五以上，并且隨著年齡的增長幾率逐漸增加。隨著老年人年齡的增長，其臟器的功能會下降，吸收營養(yǎng)的效率也會減退。導致維生素D的缺乏、鈣流失等，從而引起骨質疏松。女性由于絕經(jīng)以后，雌激素水平降低，無法有效的抑制破骨細胞，導致破骨細胞過度的增生和活躍，也會導致骨的分解和吸收而形成骨質疏松?？梢酝ㄟ^口服藥物以及在日常生活中增加鈣含量的食物來改善骨質疏松。什么是腰間盤突出？骨質疏松會導致骨頭強度下降，椎間盤承受壓力會過高，椎間盤纖維環(huán)發(fā)生破損的幾率就會變高。纖維環(huán)一旦破損就出現(xiàn)腰間盤突出，骨質疏松跟腰間盤突出是有一定的關系的。骨質疏松跟腰間盤突出是兩種不同的疾病，骨質疏松使骨的強度下降，椎間盤突出是椎間盤破壞以后或椎間盤前塊損傷以后，導致神經(jīng)卡壓的一種表現(xiàn)。骨質疏松如何引起股骨頭壞死？導致股骨頭壞死的常見因素，有長期服用激素類藥物，外傷以及大量飲酒，強制性的脊柱炎，先天性的髖臼發(fā)育不良等。骨質疏松是股骨頭壞死的病因之一。骨質疏松的患者骨骼中，蛋白鈣、磷的比例減少，骨的脆性增加，容易發(fā)生骨折。如果骨折發(fā)生在股骨頭部位，就會引發(fā)股骨頭的血運受到損害，造成股骨頭局部的血液循環(huán)障礙，進而引發(fā)股骨頭壞死。此外，由于骨質疏松造成骨吸收增加，疏松的股骨頭強度會降低，股骨頭局部會出現(xiàn)壓縮塌陷，導致流經(jīng)股骨頭部的骨流量減少，股骨頭的骨細胞和骨髓成分會引發(fā)股骨頭壞死。骨質疏松應該如何進行治療？對于骨質疏松首先要注意是骨質疏松還是骨質疏松癥，因為骨質疏松是一個慢性的蛻變性信號。骨質疏松治療方法：首先要強調(diào)非藥物的治療為主。比如采用平衡的飲食，適當?shù)难a充鈣劑、維生素D，適當?shù)幕顒?，戒煙，預防摔倒，這個是骨質疏松一個基本的治療前提和方案。2024年05月13日251
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唐浩副主任醫(yī)師 北京積水潭醫(yī)院 矯形骨科 股骨頭壞死（Avascularnecrosisofthefemoralhead.AVN）是一種常見的骨科疾病，指的是由于各種原因導致股骨頭的血液供應不足，從而引起骨細胞和骨髓細胞的死亡，進而導致股骨頭的結構破壞和塌陷，最終形成髖關節(jié)炎。股骨頭壞死多發(fā)生在中青年人群，主要表現(xiàn)為髖關節(jié)疼痛和活動受限，嚴重影響生活質量和工作能力，被稱為“不死的癌癥”。股骨頭壞死的原因可以分為原發(fā)性和繼發(fā)性兩大類。原發(fā)性股骨頭壞死又稱為特發(fā)性股骨頭壞死：顧名思義，主要是指股骨頭壞死的原因不明確。對于有明確原因的股骨頭壞死，稱為繼發(fā)性股骨頭壞死，可分為創(chuàng)傷性和非創(chuàng)傷性兩大類。創(chuàng)傷性股骨頭壞死：是指由于髖部外傷，如股骨頸骨折、髖臼骨折、髖關節(jié)脫位等，導致股骨頭的血管受損或中斷，造成股骨頭的缺血壞死。非創(chuàng)傷性股骨頭壞死：是指由于其他原因，如長期使用或濫用糖皮質激素、長期過量飲酒、減壓病、血液病、自身免疫病、感染、放射治療等，導致股骨頭的血管痙攣、狹窄、栓塞或閉塞，造成股骨頭的缺血壞死。我國非創(chuàng)傷性股骨頭壞死最常見的原因是飲酒和糖皮質激素導致的壞死。因此，我們應該避免長期大量飲酒，在醫(yī)生指導下應用糖皮質激素，預防出現(xiàn)股骨頭壞死。股骨頭壞死的癥狀因病變的部位、范圍和程度不同而異。早期，股骨頭壞死可能沒有明顯的癥狀，或者只有輕微的髖關節(jié)不適，難以引起注意。隨著病情的發(fā)展，股骨頭壞死會出現(xiàn)以下的癥狀：?髖關節(jié)疼痛：這是股骨頭壞死的最常見和最主要的癥狀，通常表現(xiàn)為病變側的髖部、臀部或腹股溝部位的疼痛，有時也會放射到大腿內(nèi)側或膝關節(jié)。疼痛的性質可以是鈍痛、隱痛、刺痛或劇痛，疼痛的程度可以是輕微、中等或嚴重，疼痛的時間可以是間歇性、持續(xù)性或加重性。一般來說，疼痛會隨著活動的增加而加重，隨著休息的延長而減輕，但在病變嚴重時，即使在靜止或夜間也會出現(xiàn)疼痛。?髖關節(jié)活動受限：這是股骨頭壞死的另一個常見的癥狀，通常表現(xiàn)為病變側的髖關節(jié)的活動范圍減少，特別是內(nèi)旋、屈曲和外展等方向的活動受限。髖關節(jié)活動受限會影響患者的正常行走、下蹲、上下樓梯等日?；顒樱踔翆е迈诵谢蛐枰褂幂o助器具。?髖關節(jié)畸形：這是股骨頭壞死的晚期癥狀，通常表現(xiàn)為病變側的髖關節(jié)的外形發(fā)生改變，如股骨頭塌陷、髖關節(jié)間隙狹窄、下肢短縮等。髖關節(jié)畸形會進一步加重髖關節(jié)的疼痛和活動受限，甚至導致髖關節(jié)的功能喪失。股骨頭壞死的分型和分期有多種方法，常用的有以下幾種：?根據(jù)病變的程度，分為Ficat分期和ARCO分期。Ficat分期是最常用的分期方法，根據(jù)X線片的表現(xiàn)，分為0期、I期、II期、III期和IV期。0期：無疼痛，X線片正常，MRI或骨掃描出現(xiàn)異常；I期：有疼痛，X線片正常，MRI或骨掃描出現(xiàn)異常；II期：有疼痛，X線片出現(xiàn)囊性變或硬化，沒有軟骨下骨折；III期：有疼痛，X線片出現(xiàn)股骨頭塌陷，有新月征或臺階征；IV期：有疼痛，X線片出現(xiàn)髖臼病變，有關節(jié)間隙狹窄和骨關節(jié)炎。ARCO分型是在FICAT分期的基礎之上，根據(jù)X光片上股骨頭壞死的范圍，將每一期進一步分為ABC三個亞型，并發(fā)現(xiàn)ARCO1/2C型的患者股骨頭塌陷率高達70-90%。這是因為C型患者股骨頭壞死區(qū)域超出了髖臼邊緣以外，整個壞死區(qū)域都在髖臼應力集中區(qū)域，因而更加容易發(fā)生塌陷。?A型：壞死區(qū)位于股骨頭的中心部，占據(jù)股骨頭的1/4至1/2。?B型：壞死區(qū)位于股骨頭的邊緣部，占據(jù)股骨頭的1/4至1/2，但仍在髖臼邊緣外側負重區(qū)以內(nèi)。?C型：壞死區(qū)位于股骨頭的整個部位，占據(jù)股骨頭的1/2以上，超過了髖臼邊緣外側負重區(qū)。ARCO分型的意義在于，由于不同類型患者的塌陷風險不同，該分型可以指導治療方案和預后：A型的患者可以采用保髖治療，如髓心減壓、骨移植等；B型的患者可以采用保髖或置換治療，如髖臼成形術、表面置換術等；C型的患者則需要采用置換治療，如全髖關節(jié)置換術。股骨頭壞死的治療方法主要有非手術治療和手術治療兩種。非手術治療適用于ARCO1/2A型患者，或者已塌陷患者置換前的對癥治療：?藥物治療：目前常用藥物包括降脂藥（如阿托伐他汀）、參與骨代謝藥物（如雙膦酸鹽）、抗凝藥（如阿司匹林）、血管擴張劑（如尼可地爾）、抗炎藥（如非甾體抗炎藥）等，可以改善股骨頭的血液循環(huán)，減輕炎癥反應，促進骨組織修復。?物理治療：包括體外高能震波、高壓氧、電磁場、超聲波等，可以刺激股骨頭的血管生成，增加骨髓血流，抑制骨吸收，增強骨形成。非手術治療的優(yōu)點是無創(chuàng)、安全、經(jīng)濟，但缺點是效果不穩(wěn)定、不可預測，需要長期堅持，且不能根本解決股骨頭的壞死問題，只能延緩病情的進展。因此，非手術治療需要嚴格遵循醫(yī)囑，定期復查，及時評估療效，一旦發(fā)現(xiàn)股骨頭有塌陷的跡象，應及時轉為手術治療。?保髖手術：保髖手術是指通過保留患者自身的股骨頭為主的修復重建術，來延緩或避免行人工髖關節(jié)置換術。保髖手術的種類很多，常用術式包括髓芯減壓術、截骨術、帶或不帶血運的骨移植術、鉭棒植入手術、介入手術、股骨頭自體干細胞移植等。保髖手術適用于股骨頭壞死早期（FICATⅠ期和Ⅱ期），且壞死體積在15%以上者。保髖手術的優(yōu)點是可以最大限度地保留患者自身的骨組織和關節(jié)功能，避免人工關節(jié)置換術的并發(fā)癥和修復術。但缺點是有一定的失敗率和復發(fā)率，需要嚴格掌握適應癥和手術時機。對塌陷前的ARCO1-2A/B型的患者，積水潭醫(yī)院矯形骨科周一新教授領銜研發(fā)了一種新的股骨頭壞死保髖治療術式——多孔AVNCage（3D打印籠形鈦金屬假體）支撐術，可避免既往鉭棒、人工骨、異體骨等植入材料的局限性（如導致后續(xù)治療困難和粗隆區(qū)骨折的并發(fā)癥、不能長時間維持壞死區(qū)減壓、阻礙粗隆區(qū)向壞死區(qū)的修復通道、不能形成長期有效力學支撐等）。自2018年開始，我們采用AVNCAGE這一新型假體，并改良手術工具及手術方式，可避免牽引床手術，可有效避免術中股骨頭穿透等并發(fā)癥。該項創(chuàng)新術式將手術時間從1-2小時縮短為平均0.5小時，使2年股骨頭生存率從平均70-75%(髓心減壓術）提高至88%，使很多中青年病人避免了致殘及人工關節(jié)置換術，降低了醫(yī)療費用，獲批多項專利，獲NMPA3類注冊證1項，目前已經(jīng)在國內(nèi)臨床應用400余例。針對股骨頭壞死已經(jīng)塌陷，但仍未發(fā)生髖關節(jié)骨關節(jié)炎的FICAT3期患者，傳統(tǒng)保髖手術就無能為力了。針對這一部分患者的臨床需求，積水潭醫(yī)院矯形骨科周一新教授領銜研發(fā)了一種新型3D打印個性化定制部分髖關節(jié)假體，采用不損傷旋股動脈的外科脫位入路，進行塌陷區(qū)域股骨頭的部分置換，恢復關節(jié)面平滑度，延緩關節(jié)炎進展，延后或避免全髖置換術。自2021年，我中心已開始以定制化手術開展3D打印定制部分髖關節(jié)置換術，適應證為塌陷早期且壞死面積相對局限的股骨頭壞死病例，采用外科脫位入路，術中不切斷任何髖關節(jié)肌肉，保留髖臼側所有正常結構，可極大保留髖關節(jié)功能，臨床隨訪使得傳統(tǒng)100需要髖關節(jié)置換的FICAT3期患者，有75%病例獲得明顯延緩甚至避免行全髖置換術。該手術填補了FICAT3期股骨頭壞死的手術治療空白，為因股骨頭塌陷致殘的中青年病人帶來了新的治療選擇。當股骨頭壞死進展為髖關節(jié)炎（FICAT4期），就失去了保髖治療機會了，需要進行人工髖關節(jié)置換術。人工髖關節(jié)置換術的種類也很多，常用術式包括全髖關節(jié)置換術、表面置換術、半髖關節(jié)置換術等。人工髖關節(jié)置換術適用于股骨頭壞死晚期（FICAT3-4期）且癥狀嚴重、保髖手術失敗或不適合者。人工髖關節(jié)置換術的優(yōu)點是可以徹底解決股骨頭壞死引起的疼痛和功能障礙，療效顯著、穩(wěn)定，但缺點是有一定的手術風險和并發(fā)癥，如感染、血栓、脫位、松動等，且人工關節(jié)有一定的使用壽命，對于年輕患者，存在可能需要進行二次翻修的風險。2024年02月13日1494
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陶可主治醫(yī)師 北京大學人民醫(yī)院 骨關節(jié)科 股骨頭壞死：基礎知識2019年(致每一位曾經(jīng)或正在遭受股骨頭壞死折磨的病患，都需要了解的科學知識)作者：MichelleJLespasio,NipunSodhi,MichaelAMont.作者單位:DepartmentofOrthopedicSurgery,BostonMedicalCenter,MA.譯者：陶可（北京大學人民醫(yī)院骨關節(jié)科）摘要在本報告中，我們對骨股骨頭壞死進行了簡明且最新的回顧，股骨頭骨壞死是一種病理性、疼痛性且常常致殘的疾病，據(jù)報道是由于受影響的骨骼區(qū)域的血液供應暫時或永久中斷造成的。我們將討論髖關節(jié)股骨頭骨壞死的流行病學（疾病分布）、發(fā)病機制（發(fā)展機制）、病因（相關危險因素、原因和疾病）、臨床表現(xiàn)（報告的癥狀和查體結果）、診斷和分類以及治療方案。ConnectionsEveryactivityofthelivingorganismisconnectedwithaseparatepartofthebodywhenceitarises.Therefore,anactivityisnecessarilydamagedwhenthepartwhichproducesitisaffected.—GalenofPergamon,130AD-210AD,prominentGreekphysician,surgeon,andphilosopherintheRomanEmpire生物體的每項活動都與其產(chǎn)生該活動的身體的一個單獨部分相關。因此，當產(chǎn)生某項活動的部分受到影響時，該活動必然會受到損害?！寮用傻纳w倫，公元130年至公元210年，羅馬帝國著名的希臘內(nèi)科醫(yī)生、外科醫(yī)生和哲學家Figure1Left,radiographofahealthyhipjoint.Right,radiographofahipjointwheretheosteonecrosishasprogressedtocollapseofthefemoralhead.圖1左圖是健康髖關節(jié)的X線片；右圖是髖關節(jié)股骨頭壞死已發(fā)展到塌陷階段的X線片。Figure2ProgressionofosteonecrosisusingtheFicat＆Arletclassificationsystem.Osteonecrosiscanprogressfromanormal,healthyhip(StageI)tothecollapseofthefemoralhead(StageIV).?圖2使用Ficat和Arlet分類系統(tǒng)的股骨頭骨壞死進展情況。股骨頭骨壞死可以從正常、健康的髖關節(jié)（第一階段）發(fā)展到股骨頭塌陷(并骨關節(jié)炎)（第四階段）。介紹本文的目的是介紹影響股骨頭或髖關節(jié)的骨壞死(ON)的最新情況，以及如何在成年人群中最好地治療該病。具體來說，本報告將涵蓋髖關節(jié)股骨頭壞死(ON)的流行病學、發(fā)病機制、病因、臨床表現(xiàn)、診斷和分類以及治療方案。股骨頭壞死(ON)，也稱為缺血性壞死、無菌性壞死或缺血性骨壞死，與許多導致成熟骨細胞死亡的疾病和危險因素有關，從而導致骨破壞（例如塌陷）或終末期髖關節(jié)骨關節(jié)炎。這種情況可能發(fā)生在身體的任何骨骼（例如上肢、膝關節(jié)、肩關節(jié)和腳踝關節(jié)），或者在不同時間發(fā)生在超過1處骨骼，但最常見的是影響髖關節(jié)。當最初在髖關節(jié)以外的區(qū)域進行診斷時，應同時對髖關節(jié)進行臨床評估以及放射線和其他影像學研究。股骨頭壞死(ON)的原因分為外傷性（與損傷相關）或非外傷性（與損傷無關）。準確診斷和分類股骨頭壞死(ON)對于幫助指導治療選擇非常重要。識別相關風險因素和患者教育對于成功治療股骨頭壞死(ON)非常重要。針對相關危險因素、藥物管理和/或手術，包括關節(jié)保留手術和全髖關節(jié)置換術(THA)，在股骨頭壞死(ON)患者的臨床管理中也發(fā)揮著重要作用。髖關節(jié)股骨頭壞死的流行病學盡管股骨頭壞死(ON)的確切患病率尚不清楚，但據(jù)估計，美國每年有20,000至30,000名新診斷患者。在美國，約10%的THA患者的診斷是股骨頭壞死(ON)。股骨頭壞死(ON)影響所有年齡段的人，但最常見于30至65歲之間的患者。診斷時的平均年齡通常小于50歲。男女比例因相關合并癥而異。例如，與酒精相關的股骨頭壞死(ON)是在男性中更常見，而與系統(tǒng)性紅斑狼瘡(SLE)相關的股骨頭壞死(ON)是在女性中更常見。每年有超過20,000人因髖關節(jié)股骨頭壞死需要住院治療。在許多病例中，雙側髖關節(jié)都受到影響。通常，股骨頭壞死(ON)會影響股骨頭及頸部(近端骨骺)。髖關節(jié)股骨頭骨壞死的發(fā)病機制/假說髖關節(jié)股骨頭壞死(ON)發(fā)生的機制仍不清楚。在大多數(shù)情況下，股骨頭壞死(ON)被認為是遺傳傾向、代謝因素和影響血液供應的局部因素（包括血管損傷、骨內(nèi)壓升高和機械應力）綜合作用的結果。大多數(shù)專家都認為產(chǎn)生干細胞和血小板的股骨頭和骨髓缺乏血液供應，導致骨細胞（成熟骨內(nèi)的細胞）和/或間充質細胞（形成軟骨、骨和脂肪的干細胞）死亡。結果是死亡組織脫礦質或被新的但較弱的骨組織吸收（小梁變?。S后導致軟骨下骨折和股骨頭塌陷。其他提出的股骨頭壞死(ON)發(fā)病機制包括由過量糖皮質激素影響骨和靜脈內(nèi)皮細胞的不利影響引起的血管收縮引起的變化，以及過量糖皮質激素相關的股骨頭壞死(ON)涉及循環(huán)脂質的變化，可能會在供應骨的動脈中引起微栓子。髖關節(jié)股骨頭骨壞死的病因創(chuàng)傷性和非創(chuàng)傷性因素的結合可直接導致股骨頭骨壞死。在縱向隊列研究和薈萃分析的基礎上，發(fā)現(xiàn)了在股骨頭壞死(ON)發(fā)展中起明確病因作用的直接危險因素。然而，相關風險因素是與股骨頭壞死(ON)最終進展(直接)相關的大部分因素。股骨頭壞死(ON)的外傷原因股骨頭壞死(ON)的創(chuàng)傷性原因包括股骨頸骨折或脫位以及骨髓成分的直接損傷（例如與放射損傷、氣壓失調(diào)或沉箱病相關）。股骨頸骨折或脫位的機制是骨外血管受損，導致髖關節(jié)受影響區(qū)域的血液供應中斷。髖關節(jié)脫位是另一種類型的創(chuàng)傷性損傷，影響約20%的創(chuàng)傷相關股骨頭壞死(ON)患者。沉箱?。ɡ鐫撍疁p壓）會導致氮氣氣泡的形成，從而阻塞小動脈，導致股骨頭壞死(ON)。出現(xiàn)癥狀的患者可能會在經(jīng)歷此過程數(shù)年后出現(xiàn)髖關節(jié)股骨頭壞死(ON)。壓力的深度和持續(xù)時間以及暴露的次數(shù)是這種疾病進展的重要因素。股骨頭壞死(ON)的非外傷原因許多研究報告稱，長期使用皮質類固醇激素與股骨頭壞死(ON)的發(fā)生相關，可能與藥物的持續(xù)時間和總劑量直接相關。長期使用高劑量糖皮質激素治療的患者似乎處于發(fā)生股骨頭壞死(ON)的最大風險；然而，這些患者通常有多種其他危險因素。接受長期治療的患者中有9%至40%會發(fā)生糖皮質激素誘發(fā)的股骨頭壞死(ON)，而接受短期治療的患者則發(fā)生率要低得多。一項薈萃分析和系統(tǒng)評價發(fā)現(xiàn)，近7%的患者發(fā)生股骨頭壞死(ON)使用＜2g皮質類固醇激素。根據(jù)這項薈萃分析，接受潑尼松劑量低于15mg/d至20mg/d治療的患者發(fā)生股骨頭壞死(ON)的風險較低。一項針對98,390名患者的基于人群的研究表明接受單次短期、低劑量甲強龍逐漸減量治療的患者股骨頭壞死(ON)的發(fā)生率為0.13%，而未接受甲強龍逐漸減量治療的患者的股骨頭壞死(ON)發(fā)生率為0.08%。約31%的股骨頭壞死(ON)患者與飲酒有關。與股骨頭壞死(ON)相關的過量飲酒被認為是由于脂質形成過多和細胞內(nèi)脂質沉積增加導致骨生成減少所致，導致骨細胞死亡和股骨頭壞死(ON)。高劑量皮質類固醇激素和過量飲酒共同構成了髖關節(jié)股骨頭壞死(ON)發(fā)展的最高相關直接危險因素，并且占與創(chuàng)傷無關的病例的80%以上。一項研究比較了112名患有特發(fā)性髖關節(jié)股骨頭壞死(ON)患者與168名對照者(沒有全身性皮質類固醇激素使用史)，與對照者相比，經(jīng)常飲酒者的風險升高，并且與酒精存在明顯的劑量反應關系。對于當前飲酒量低于400毫升/周、400毫升/周至1000毫升/周和超過1000毫升/周的消費者來說，相對風險分別為3.3、9.8和17.9。股骨頭壞死(ON)在鐮狀細胞病患者中很常見，因為它容易導致紅細胞鐮狀化和骨髓增生。大約50%的受影響患者在35歲時出現(xiàn)股骨頭壞死(ON)。鐮狀細胞血紅蛋白病可直接導致血管阻塞和股骨頭壞死(ON)。據(jù)報道，3%至30%的系統(tǒng)性紅斑狼瘡SLE患者會發(fā)生股骨頭壞死(ON)，最危險的是服用糖皮質激素和常規(guī)劑量潑尼松劑量大于20mg/d的患者。據(jù)報道，高達60%的戈謝病（一種遺傳性疾?。┗颊呋加泄晒穷^壞死(ON)，因為它能夠直接阻礙血管供應。戈謝病是一種常染色體隱性遺傳代謝疾病，其中一種脂肪（脂質）稱為葡萄糖腦苷脂不能被充分降解。通常情況下，身體會產(chǎn)生一種稱為葡萄糖腦苷脂酶（細胞膜的正常部分）的酶，它會分解并回收葡萄糖腦苷脂。其他不太常見但與股骨頭壞死(ON)明顯相關的患者包括抗磷脂抗體、庫欣病和系統(tǒng)性紅斑狼瘡SLE患者。急性淋巴細胞白血病、慢性粒細胞白血病和急性粒細胞淋巴瘤的發(fā)展，使患者因使用類固醇激素治療這些疾病而面臨更高的股骨頭壞死(ON)風險。胰腺炎（通常與使用皮質類固醇激素有關）、懷孕、化療、吸煙、血管炎、胸膜炎和中樞神經(jīng)系統(tǒng)因素，例如導致交感神經(jīng)纖維數(shù)量減少的炎癥反應（如類風濕性關節(jié)炎、克羅恩?。⑾目谱愫脱装Y性腸?。?，與股骨頭壞死(ON)相關。有一些證據(jù)表明股骨頭壞死(ON)可能具有相關風險因素的遺傳基礎。例如，當過度飲酒是相關風險因素時，男性受到的影響是女性的3倍。然而，當狼瘡或皮質類固醇激素的使用成為相關危險因素時，女性比男性更容易受到影響。系統(tǒng)性紅斑狼瘡SLE在女性中的發(fā)病率大約是男性的9倍。這種易感性增加是可能的，至少部分原因是與激素和性染色體有關的差異。血液透析、高尿酸患者的慢性腎衰竭或終末期腎病、貧血/痛風、HIV感染、高脂血癥、器官移植和血管內(nèi)凝血也與股骨頭壞死(ON)的發(fā)生有關。盡管存在許多可能的關聯(lián)和聯(lián)系，但估計20%的股骨頭壞死(ON)病例被標記為特發(fā)性或病因不明。髖關節(jié)股骨頭骨壞死的臨床表現(xiàn)髖關節(jié)疼痛是股骨頭壞死(ON)晚期最常見的癥狀，盡管一小部分患者可能沒有癥狀。腹股溝疼痛是最常見的癥狀，其次是大腿和臀部疼痛。疼痛可能因負重或關節(jié)運動而出現(xiàn)。大約三分之二的股骨頭壞死(ON)患者會出現(xiàn)休息時疼痛，大約三分之一的患者會出現(xiàn)夜間疼痛。身體多個部位的疼痛很少見，表明存在多灶性過程。髖關節(jié)股骨頭壞死(ON)的體格表現(xiàn)通常是非特異性的，但可能會導致受影響關節(jié)的活動范圍減小、行走疼痛、Trendelenburg征和/或骨摩擦音。髖關節(jié)股骨頭骨壞死的臨床評估髖關節(jié)股骨頭壞死(ON)通常通過：1)回顧患者病史，2)獲得適當?shù)姆派鋵W評估，3)確定病情階段，以及4)制定治療方案來解決。在評估患者是否患有股骨頭壞死(ON)，問題應針對評估疼痛史、藥物使用（尤其是皮質類固醇）、手術、懷孕、創(chuàng)傷、慢性疾病（尤其是鐮狀細胞病、戈謝病、自身免疫性疾病和白血?。?、吸煙和/或飲酒。當詢問受傷/疾病時，重要的是要仔細探討與髖部骨折、脫位或沉箱病相關的傷害，因為沉箱病是非創(chuàng)傷性的。髖關節(jié)股骨頭骨壞死的診斷和分類在疾病的初始階段診斷髖關節(jié)股骨頭骨壞死對于治療很重要；在初始階段，疾病可能不會進展。大多數(shù)情況下，早期股骨頭壞死(ON)患者一般沒有癥狀，是偶然發(fā)現(xiàn)的；不幸的是，大多數(shù)患者直到股骨頭壞死(ON)發(fā)展到后期才前來接受評估。盡管目前還沒有已知的明確治療方法可以永久阻止股骨頭壞死(ON)進展到后期，但目前有一些治療方法用于此目的，例如降脂劑、抗凝劑和雙磷酸鹽。當患者出現(xiàn)癥狀、影像學檢查結果一致、并且其他引起疼痛和骨異常的原因不太可能或已被排除時，就可以準確地做出股骨頭壞死(ON)的診斷。除了臨床和體檢之外，放射線照片和磁共振成像（MRI）掃描等成像技術也用于診斷。首先，進行普通放射線照相評估，然后進行MRI。據(jù)報道，MRI對于檢測早期股骨頭壞死(ON)的特異性和敏感性＜99%。MRI圖像還可以通過對異常骨占據(jù)的股骨頭區(qū)域進行數(shù)字化，定量評估病變的大小或受影響骨的受累程度。MRI變化包括T1加權圖像上界限分明且均勻的局灶性病變，具有分隔正常骨和缺血骨的單密度線，以及T2加權圖像上的第二條高強度線（特征性雙線征標志）代表血管豐富的肉芽組織。這種級別的成像細節(jié)非常有用，因為受影響骨骼病變的大小和范圍很重要，可以幫助指導治療。然而，對于終末期疾病，股骨頭壞死(ON)患者可能沒有必要使用MRI，因為此階段的治療選擇可能有限。這些發(fā)現(xiàn)通常使用4個階段的Ficat和Arlet系統(tǒng)進行分類，如此處和表1中所述。X線片可以在腹股溝疼痛等癥狀出現(xiàn)后數(shù)月內(nèi)保持正常（第一階段）。最早的放射學檢查結果通常是輕微的骨密度變化，然后是硬化和囊性變（第二階段）。然后，檢查結果會從軟骨下骨塌陷（第III期）發(fā)展到特征性新月征（在股骨頭近端前外側看到軟骨下射線可透性），并隨后出現(xiàn)股骨頭球形度喪失（測量圓度）或股骨頭最終關節(jié)塌陷，可見髖臼空間變窄和退行性變化（第四階段）。要尋找的關鍵放射學特征包括1)階段（塌陷前與塌陷后）、2)病變大小和3)股骨頭凹陷程度。右側股骨頭壞死的X線片表現(xiàn)：雙線征，承重區(qū)右側髖關節(jié)股骨頭壞死X線片（上圖）及MRI表現(xiàn)（下圖）生成骨骼三維圖像的計算機斷層掃描具有中等敏感性，但不具有特異性，可能會給患者帶來顯著的輻射負擔。如果股骨頭已經(jīng)塌陷，計算機斷層掃描可能具有一定的特異性。幸運的是，大多數(shù)臨床醫(yī)生無需計算機斷層掃描即可診斷出股骨頭骨壞死，而計算機斷層掃描通常用于區(qū)分塌陷前和塌陷后疾病。髖關節(jié)股骨頭骨壞死的鑒別診斷由于有癥狀的髖關節(jié)股骨頭壞死(ON)患者可能會出現(xiàn)與許多其他髖關節(jié)病變類似的癥狀，因此在最終診斷之前應充分排除這些癥狀。骨髓水腫綜合征和軟骨下骨折是也需要考慮的許多潛在診斷中的兩個。與骨壞死相關的病因創(chuàng)傷相關的危險因素股骨頸骨折脫位或骨折脫位鐮狀細胞性貧血癥血紅蛋白病沉箱病（氣壓失調(diào)）戈謝病輻射非創(chuàng)傷相關的危險因素皮質類固醇激素飲酒系統(tǒng)性紅斑狼瘡庫欣病皮質醇分泌過多（罕見）慢性腎功能衰竭/血液透析胰腺炎妊娠高脂血癥器官移植血管內(nèi)凝血血栓性靜脈炎吸煙高尿酸血癥/痛風艾滋病病毒感染其他潛在風險因素特發(fā)性原因骨髓水腫綜合征，也稱為髖部暫時性骨質減少，可能單獨發(fā)生或與損傷相關，特別是那些導致神經(jīng)損傷的創(chuàng)傷。在后一種情況下，慢性疼痛和短暫性骨質減少是復雜區(qū)域疼痛綜合征（也稱為反射性交感神經(jīng)營養(yǎng)不良、灼痛等術語）的特征。骨髓水腫綜合征可根據(jù)組織學和MRI與股骨頭壞死(ON)相鑒別。股骨頭軟骨下骨折通常發(fā)生在已有骨質減少的患者中，通常被認為代表不全骨折。這些骨折可能很難通過平片觀察到。早期病變有時會出現(xiàn)輕微的扁平化；股骨頭塌陷是進行性的。髖關節(jié)股骨頭骨壞死的臨床治療在制定針對癥狀性髖關節(jié)骨關節(jié)炎的最佳治療方法時要考慮的因素應旨在治療骨關節(jié)炎的分期和受累程度、骨受累的程度和位置、癥狀的存在（或不存在）以及患者的合并癥。治療的目標是盡可能長時間地保留天然髖關節(jié)，同時考慮患者年齡、活動能力、職業(yè)和生活方式等生活質量問題。處理髖關節(jié)股骨頭壞死(ON)的三種主要治療選擇包括1)非手術治療、2)關節(jié)保留手術和3)全髖關節(jié)置換術THA。非創(chuàng)傷性原因引起的髖關節(jié)股骨頭壞死(ON)的影響引起了特別關注。對于受影響的患者，67%的人報告沒有任何癥狀，但最終可能會出現(xiàn)關節(jié)塌陷。無癥狀的中等、尤其是大面積股骨頭骨壞死的自然病程是病情惡化，最終發(fā)展為終末期疾病，許多患者出現(xiàn)股骨頭塌陷。對于有癥狀的患者，大約80%至85%的病例會在2年內(nèi)導致股骨頭塌陷。因此，早期診斷股骨頭壞死(ON)可能會提供早期治療的機會，這可以防止塌陷，并最終避免股骨頭塌陷而需要進行的全髖關節(jié)置換的手術治療。然而，大多數(shù)患者在病程晚期就診，對于那些已知或可能存在危險因素的患者，特別是使用大劑量皮質類固醇激素的患者，必須高度懷疑（存在股骨頭壞死(ON)）。同樣，對于無癥狀的股骨頭壞死(ON)患者，應考慮影響股骨頭壞死病變的大小、范圍和位置。一般來說，影響股骨頭15%以下的病變最好采用非手術治療；15%至30%之間的病變應進行手術治療；盡管進行了手術干預，但涉及超過30%股骨頭的病變?nèi)钥赡苓M展至塌陷，并最終需要全髖關節(jié)置換術THA。髖關節(jié)股骨頭骨壞死的非手術治療選擇物理治療物理治療可以緩解和減輕一些癥狀，但通常不會阻止進行性髖關節(jié)骨性關節(jié)炎進展到后期。同樣，使用拐杖或手杖等輔助裝置限制負重可能有助于控制疼痛、虛弱和痛性步態(tài)等癥狀。如果治療的目標是防止髖關節(jié)需要全髖關節(jié)置換，那么物理治療是不合適的，并且迄今為止沒有證據(jù)表明負重限制有助于防止進行性骨關節(jié)炎疾病進展為終末期疾病。藥物非甾體類抗炎藥和對乙酰氨基酚可以暫時緩解有癥狀患者的疼痛。當其他藥物無法有效控制中度至重度疼痛時，在考慮手術選擇時，可以明智地短期使用阿片類藥物。目前正在使用但未經(jīng)證實或可靠地用于治療股骨頭壞死(ON)的研究藥物選擇包括1)抗凝劑、2)雙膦酸鹽抗吸收劑、3)降膽固醇他汀類藥物和4)高壓氧。早期股骨頭壞死(ON)的手術選擇髓心減壓髓心減壓是一種微創(chuàng)手術技術，用于控制病情早期（塌陷前）的癥狀（例如Ficat和ArletI期和II期）。該手術包括在股骨頭上鉆孔以緩解壓力并為新血管創(chuàng)造通道以滋養(yǎng)受影響的區(qū)域。已發(fā)表的髓心減壓成功率差異很大，從40%到100%不等，具體取決于患者群體。髓心減壓后的成功率在最早疾病階段的患者中可見。成功進行髓心減壓手術的患者通常會在幾個月后恢復獨立行走，并且可以完全緩解疼痛。骨移植髓心減壓可以與骨移植相結合，幫助再生健康的骨骼并支撐髖關節(jié)的軟骨。骨移植物是移植到壞死或死骨區(qū)域的健康骨組織。一種標準技術使用自體移植，涉及從身體的一個部位取出骨頭并將其移動到身體的另一部位。從捐贈者或尸體上采集的骨移植物稱為同種異體移植物，通常通過骨庫獲取。骨髓抽吸濃縮物髓心減壓配合骨髓抽吸濃縮物注射是使用濃縮骨髓，將其注射到股骨頭壞死的死骨中。這項研究技術從患者的骨髓中采集干細胞并將其注射到股骨頭壞死(ON)區(qū)域。骨髓抽吸濃縮被認為可以防止疾病進一步發(fā)展并刺激新骨生長。經(jīng)皮鉆孔另一種手術選擇是經(jīng)皮鉆孔。在此過程中，通過股骨頸經(jīng)皮鉆一個孔，到達股骨頭的受影響部位。一份對45個髖關節(jié)進行平均隨訪24個月的報告顯示，30個患有Ficat和ArletI期疾病的髖關節(jié)中有24個（80%）取得了成功的結果（定義為Harris髖關節(jié)評分＜70）。一項最近的研究比較了多個鉆探與標準髓心減壓相比，顯示經(jīng)皮鉆探獲得更好的結果。晚期股骨頭壞死(ON)的手術選擇血管化骨移植血管化腓骨移植是一種更為復雜的外科手術，其中從腓骨及其血液供應中取出一段骨。然后將移植物移植到股骨頸和股骨頭上形成的孔道中，并重新連接動脈和靜脈以幫助愈合股骨頭壞死(ON)。截骨術髖關節(jié)截骨術可以將壞死骨從主要承重區(qū)域去除。盡管該手術可能會延遲THA手術，對于股骨頭輕度塌陷前或早期塌陷后的股骨頭壞死患者最有用。然而，截骨術的一個結果是使得未來可能的全髖關節(jié)置換術更具挑戰(zhàn)性，并且通常與骨不連的風險增加有關。非血管化骨移植非血管化骨移植手術有3種類型：1)活板門手術、2)燈泡技術和3)Phemister技術?；畎彘T手術一種自體松質骨和皮質骨移植術，已成功用于Ficat和ArletIII期髖關節(jié)股骨頭壞死(ON)的中小型病變患者。對23名Ficat和ArletIII期或IV期股骨頭壞死(ON)患者進行的30次（在股骨頭上制作的）活板門手術的結果顯示，根據(jù)Harris評分系統(tǒng)的判定，結果均良好或極好。燈泡技術燈泡技術使用股骨頸前部的皮質窗口?？梢允褂迷摯翱谌コ龎乃拦?，隨后可以用非血管化骨移植物填充。Wang等對110名接受燈泡手術的患者（138髖）進行了評估。在平均25個月的隨訪中，平均Harris髖關節(jié)評分從62分提高到79分。在最近的隨訪中，總共94個髖關節(jié)(68%)被認為取得了成功。ARCO分期IIa期患者中100%、IIb期患者中77%、IIc和IIIa期患者中51%出現(xiàn)放射學改善。Phemister技術在Phemister技術中，通過股骨頸插入環(huán)鉆以形成通向病變部位的管道。然后插入第二個環(huán)鉆以形成通往病變部位的另一條管道。然后可以將皮質支柱移植物放置在病變處。最近的一項評論報告稱，該手術的臨床成功率在36%至90%之間。全髖關節(jié)置換術（THA）一旦股骨頭發(fā)生嚴重塌陷，置換髖關節(jié)是唯一實用的手術選擇，并且可以在晚期股骨頭壞死中提供最可預測的疼痛緩解。全髖關節(jié)置換術（THA）成功地緩解了大多數(shù)患者的疼痛并恢復了功能。在全髖關節(jié)置換術（THA）中，構成髖關節(jié)的患病軟骨和骨骼被由金屬和塑料制成的人工關節(jié)假體取代。人工髖關節(jié)置換術通?？梢允褂?5年，然后就會磨損并需要修復。對于較年輕的患者，由于可能存在活動限制，全髖關節(jié)置換術（THA）可能不是最佳解決方案。此外，由于假肢有使用壽命限制（長期使用后部件會磨損），這些患者可能需要在以后的生活中進行全髖關節(jié)置換術（THA）翻修。必須仔細考慮全髖關節(jié)置換術并與生活質量問題進行權衡，但年輕患者并非絕對禁忌。關于髖關節(jié)股骨頭壞死(ON)的患者教育預防股骨頭壞死(ON)對患者進行有關危險因素、治療和管理的教育對于患者對其病情做出更明智的決定至關重要。股骨頭壞死(ON)教育過程涉及識別個人的相關疾病和與股骨頭壞死(ON)相關的危險因素。無癥狀股骨頭壞死的患者進展為有癥狀疾病和股骨頭塌陷的可能性很高。對無癥狀疾病患者的教育是預防性的，也是必要的，以確保改變危險因素和優(yōu)化護理。預防非創(chuàng)傷性股骨頭壞死(ON)需要：1)避免過量飲酒，定義為男性每周＜15杯飲酒，女性每周＜8杯飲酒，2)避免吸煙，以及3)將皮質類固醇激素減少到盡可能低的治療劑量。告知患者皮質類固醇激素的使用與股骨頭壞死(ON)潛在發(fā)展之間的相關性對于治療這種疾病至關重要。預防股骨頭壞死(ON)的進展應告知診斷為早期骨關節(jié)炎的患者采取上述預防措施，并應避免對關節(jié)施加過度壓力，遵循健康飲食，并保持適當?shù)捏w重以減緩骨關節(jié)炎的進展。盡管健康飲食本身并不能直接減少患者關節(jié)的壓力，但減肥（如果超重/肥胖）會減少髖關節(jié)的軸向負荷，從而減少施加到股骨頭/頸（股骨頭和股骨頸）的壓力。結論股骨頭壞死(ON)是一種病理性的、經(jīng)常引起疼痛的病癥，涉及組織壞死區(qū)域，可影響身體的任何骨關節(jié)。髖關節(jié)是最常見的股骨頭壞死(ON)部位，當最初診斷出股骨頭壞死(ON)發(fā)生在身體的其他部位時，應始終利用放射線篩查和MRI掃描進行正確評估。越早診斷股骨頭壞死，無需手術干預或采用微創(chuàng)手術技術來挽救髖關節(jié)的機會就越大。做出股骨頭壞死(ON)診斷后，將考慮病變的大小、范圍和位置以及分類階段，以制定最佳的治療計劃。在此過程中，癥狀的存在或不存在很重要。治療的目標包括嘗試盡可能長時間地保留天然髖關節(jié)，并考慮患者的生活方式和生活質量問題。迄今為止，治療股骨頭壞死(ON)的兩種主要治療選擇包括髖關節(jié)保留手術（保髖治療）和全髖關節(jié)置換術THA。對患者進行有關潛在危險因素和股骨頭壞死(ON)發(fā)展的教育，對于預防該病癥和/或潛在地預防或阻止早期疾病進展為晚期疾病至關重要。OsteonecrosisoftheHip:APrimerAbstractInthisreport,wedeliveraconciseandup-to-datereviewofosteonecrosis,apathologic,painful,andoftendisablingconditionthatisbelievedtoresultfromthetemporaryorpermanentdisruptionofbloodsupplytoanaffectedareaofbone.Wewilldiscusstheepidemiology(diseasedistribution),pathogenesis(mechanismofdevelopment),etiology(associatedriskfactors,causes,anddisorders),clinicalmanifestations(reportedsymptomsandphysicalfindings),diagnosisandclassification,andtreatmentoptionsforhiposteonecrosis.文獻出處：MichelleJLespasio,NipunSodhi,MichaelAMont.OsteonecrosisoftheHip:APrimer.ReviewPermJ.2019;23:18-100.doi:10.7812/TPP/18-100.INTRODUCTIONTheintentofthisarticleistopresentanupdateonosteonecrosis(ON)affectingthefemoralheadorhipjointandhowitcanbestbemanagedintheadultpopulation.Specifically,thisreportwillencompasstheepidemiology,pathogenesis,etiology,clinicalmanifestations,diagnosisandclassification,andtreatmentoptionsforhipON.ON,alsoreferredtoasavascularnecrosis,asepticnecrosis,orischemicbonenecrosis,isassociatedwithmanydisordersandriskfactorsthatcausematurebonecellstodie,leadingtobonedestruction(eg,collapse)orend-stagearthritisofthefemoralhead.Theconditioncanoccurinanyboneinthebody(eg,upperextremity,knees,shoulders,andankles),orinmorethan1boneatdifferenttimes,butitmostcommonlyaffectsthehipjoint.Wheninitiallydiagnosedinanareaotherthanthehip,thehipshouldsimultaneouslybeevaluatedclinicallyandwithradiographicandotherimagingstudies.ThecausesofONareclassifiedaseithertraumatic(relatedtoaninjury)oratraumatic(notrelatedtoaninjury).AccuratelydiagnosingandclassifyingONareimportantinhelpingtodirecttreatmentoptions.IdentificationofassociatedriskfactorsandpatienteducationareimportantinsuccessfulmanagementofON.Targetingassociatedriskfactors,pharmacologicmanagement,and/orsurgery,includingjointpreservingproceduresandtotalhiparthroplasty(THA),alsoplaysignificantrolesintheclinicalcareofpatientswithON.EPIDEMIOLOGYOFHIPOSTEONECROSISAlthoughtheexactprevalenceofONisunknown,theincidenceisestimatedtobebetween20,000to30,000newlydiagnosedpatientseachyearintheUS.1ONistheunderlyingdiagnosisinapproximately10%ofallTHAintheUS.2,3ONaffectspeopleofallages,althoughitismostcommonlyseeninpatientsbetweentheagesof30and65years.4Themeanageatdiagnosisistypicallyyoungerthanage50years.3Themale-to-femaleratiovariesdependingontheassociatedcomorbidities.Forexample,alcohol-associatedONismorecommoninmen,whereasONassociatedwithsystemiclupuserythematosus(SLE)ismorecommoninwomen.3Morethan20,000peopleeachyearrequirehospitaltreatmentforhipON.4Inmanyofthesecases,bothhipsareaffectedbythecondition.Mostcommonly,ONaffectstheproximalend(epiphysis)ofthefemur(hipbone).PATHOGENESISOFHIPOSTEONECROSISThemechanism(s)bywhichhipONdevelopsremainsunclear.Forthemostpart,hipONisbelievedtoresultfromthecombinedeffectsofgeneticpredisposition,metabolicfactors,andlocalfactorsaffectingbloodsupplyincludingvasculardamage,increasedintraosseouspressure,andmechanicalstresses.2,5,6Mostexpertsagreethatalackofbloodsupplytothefemoralheadandbonemarrow,whichproducesstemcellsandplatelets,causesdeathoftheosteocytes(cellswithinmaturebone)and/ormesenchymalcells(stemcellsthatformcartilage,bone,andfat).7Theresultisdemineralizationorresorptionofthedeadtissuebynewbutweakerosseoustissue(trabecularthinning),subsequentlyleadingtosubchondralfractureandcollapseofthefemoralhead.OtherproposedmechanismsforthepathogenesisofONincludevasoconstriction-inducedchangescausedbytheadverseeffectsofexcessglucocorticosteroidsaffectingboneandvenousendothelialcells8,9andexcessglucocorticoid-associatedONinvolvingalterationsincirculatinglipidsbelievedtocausemicroemboliinthearteriesthatsupplybonewithblood.10ETIOLOGYOFHIPOSTEONECROSISAcombinationoftraumaticandatraumaticfactorscandirectlycontributetotheetiologyofON(seeSidebar:EtiologicFactorsAssociatedwithOsteonecrosis).Onthebasisoflongitudinalcohortstudiesandmeta-analyses,directriskfactorshavebeendiscoveredthatplayadefinitiveetiologicroleinthedevelopmentofON.Associatedriskfactors,however,accountformostofthelinkstotheeventualdevelopmentofON.11TraumaticCausesofHipOsteonecrosisTraumaticcausesofONincludefemoralneckfracturesordislocationsaswellasdirectinjuryofboneofmarrowelements(eg,relatedtoradiationinjury,dysbarism,orCaissondisease).Themechanisminvolvedinfemoralneckfracturesordislocationsisdamagetotheextraosseousbloodvessels,whichresultsindisruptedbloodsupplytotheaffectedregionofthehip.Hipdislocationisanothertypeoftraumaticinjury,whichaffectsapproximately20%oftrauma-relatedONpatients.12Caissondisease(eg,decompressioninscubadiving)causestheformationofnitrogenbubblesthatcanoccludearterioles,leadingtoON.PatientswhodevelopsymptomscandevelophipONyearsafterexposuretothisprocess.Thedepthanddurationofpressureandnumberofexposuresareimportantfactorsintheprogressionofthisdisorder.13AtraumaticCausesofHipOsteonecrosisNumerousstudiesreportprolongeduseofcorticosteroidsassociatedwiththedevelopmentofONcanbedirectlyrelatedtodurationandtotaldosageofthemedication.14–16PatientstreatedwithprolongedhighdosesofglucocorticoidsappeartobeatthegreatestriskofdevelopingON;however,thesepatientsoftenhavemultipleotherriskfactors.Glucocorticoid-inducedONdevelopsin9%to40%ofpatientsreceivinglong-termtherapy,anddevelopsmuchlessfrequentlyinpatientsreceivingshort-termtherapy.17Onemeta-analysisandsystematicreviewidentifiedanincidenceofONinnearly7%ofpatientswhoused＜2gofcorticosteroids.18Fromthismeta-analysis,alowerriskwasseeninpatientstreatedwithdosesofprednisonelessthan15mg/dto20mg/d.18Onepopulation-basedstudyof98,390patientsshowedtheincidenceofhipONamongpatientswhohadreceivedasingleshort-term,low-dosemethylprednisolonetaperpackwas0.13%,comparedwith0.08%inpatientswhowerenotprescribedamethylprednisolonetaperpack,thusindicatinganumberneededtoharmof2041patients.19Alcoholusehasbeenassociatedwithapproximately31%ofpatientswhodevelophipON.3,20–22ExcessivealcoholconsumptionrelatedtoONofthehipisbelievedtoresultfromthedecreasedbonegenesiscausedbyexcesslipidformationandincreasedintracellularlipiddeposits,leadingtoosteocytedeathandON.23HighdosesofcorticosteroidsandexcessivealcoholusetogetherpresentthehighestassociateddirectriskfactorsforthedevelopmentofhipON24andaccountformorethan80%ofcasesnotrelatedtotrauma.3,6Onestudycompared112patientswhohadidiopathichipONandnohistoryofsystemiccorticosteroidusewith168controls.3,20Anelevatedriskforregularalcoholdrinkersandacleardose-responserelationshipwithalcoholwerenoted,comparedwithcontrols.Therelativeriskswere3.3,9.8,and17.9forcurrentconsumersoflessthan400mL/wk,400mL/wkto1000mL/wk,andmorethan1000mL/wkofalcohol,respectively.9ONiscommoninpatientswithsicklecelldiseasebecauseofitspropensitytocauseredbloodcellsicklingandbonemarrowhyperplasia.Approximately50%ofaffectedpatientsdevelopONbytheageof35years.25SicklecellhemoglobinopathycandirectlycausevascularobstructionandON.ThedevelopmentofONhasbeenreportedin3%to30%ofpatientswithSLE,andthosemostatriskarepatientswhohavetakenglucocorticoidswithregulardosesofprednisonegreaterthan20mg/d.3,26–28ONhasbeenreportedinasmanyas60%ofpatientswithGaucherdisease(ahereditarydisorder)becauseofitsabilitytodirectlyobstructvascularsupply.3,29,30Gaucherdiseaseisanautosomalrecessiveinheriteddisorderofmetabolismwhereatypeoffat(lipid)calledglucocerebrosidecannotbeadequatelydegraded.Normally,thebodymakesanenzymecalledglucocerebrosidase(anormalpartofthecellmembrane)thatbreaksdownandrecyclesglucocerebroside.31OtherlesscommonbutapparentlinkstohipONincludepatientswithantiphospholipidantibodies,Cushingdisease,29andSLE.Thedevelopmentofacutelymphoblasticleukemia,chronicmyeloidleukemia,andacutemyeloidlymphoma3,32placespatientsatincreasedriskforONrelatedtothetreatmentwithsteroidsfortheseconditions.Pancreatitis(usuallyassociatedwithuseofcorticosteroids),pregnancy,chemotherapy,smoking,vasculitis,pleuritis,andcentralnervoussystemfactorssuchasaninflammatoryresponseresultinginareductioninthenumberofsympatheticnervefibers(asseeninrheumatoidarthritis,Crohndisease,Charcotfoot,andinflammatoryboweldisease),havebeenassociatedwithON.33ThereissomeevidencethathipONmayhaveageneticbasisunderlyingassociatedriskfactors.34Forexample,menareaffectedasmuchas3timesmorethanwomenwhenexcessivealcoholuseistheassociatedriskfactor.However,whenlupusorcorticosteroidusearetheassociatedriskfactors,womenareaffectedmoreoftenthanmen.26,27,32SLEisapproximately9timesmorecommoninwomenthaninmen.35Thisincreasedsusceptibilitymaybemadepossible,atleastinpart,owingtodifferencesrelatedtohormonesandsexchromosomes.35Chronicrenalfailureorend-stagerenaldiseaseinpatientsonhemodialysis,hyperuricemia/gout,HIVinfection,hyperlipidemia,organtransplantation,andintravascularcoagulationarealsolinkedtothedevelopmentofON.31,32,36–39Despitethemanypossibleassociationsandlinks,anestimated20%ofONcasesarelabeledasidiopathicorofunknownetiology.7CLINICALMANIFESTATIONSOFHIPOSTEONECROSISHippainisthemostcommonlyreportedsymptomoflater-stageON,althoughasmallproportionofpatientsmaynothavesymptoms.Paininthegroinisthemostcommonlyreportedsymptom,followedbypainreferredintothethighandbuttock.Paincanpresentwithweightbearingorjointmotion.Painatrestoccursinapproximatelytwo-thirdsofpatientswithON,andpainatnightoccursinapproximatelyone-thirdofpatients.33Paininmultiplelocationsofthebodyisrareandsuggestsamultifocalprocess.PhysicalfindingsofhipONaregenerallynonspecificbutmayentailreducedrangeofmotionoftheaffectedjoint,painfulambulation,Trendelenburgsign,and/orcrepitus.3,40,41ClinicalAssessmentofHipOsteonecrosisONofthehipisgenerallyaddressedby1)reviewofapatient’smedicalhistory,2)obtainingappropriateradiologicevaluation,3)determiningthestageofthecondition,and4)developingaplanfortreatmentoptions.42,43WhenevaluatingapatientforON,questionsshouldbedirectedatassessingahistoryofpain,useofmedications(especiallycorticosteroids),surgery,pregnancy,trauma,chronicmedicalconditions(especiallysicklecelldisease,Gaucherdisease,autoimmunedisease,andleukemia),smoking,and/oralcoholuse.Whenaskingaboutinjuries/illnesses,itisimportanttocarefullyexploreinjuriesrelatedtohipfractures,dislocations,orscubadivingbecauseCaissondiseaseisatraumatic.DIAGNOSISANDCLASSIFICATIONOFHIPOSTEONECROSISDiagnosinghipONintheinitialstagesofthedisorderisimportantformanagement43–46;atinitialstages,thediseasemaynotprogress.Inmostcases,patientswithearly-stageONaregenerallywithoutsymptomsandareidentifiedincidentally;unfortunately,mostpatientsdonotpresentforevaluationuntiltheONhasreachedlaterstages.AlthoughthereispresentlynodefinitivetreatmentknowntopermanentlyhaltONfromprogressingtolaterstages,therearetreatmentmethods,suchaslipidloweringagents,anticoagulants,andbisphosphonates,currentlybeingusedforthispurpose.36–38AdiagnosisofONcanaccuratelybemadewhenapatientissymptomatic,imagingfindingsarecompatible,andothercausesofpainandbonyabnormalitieseitherareunlikelyorhavebeenexcluded.Beyondtheclinicalandphysicalexamination,imagingtechniquessuchasradiographsandmagneticresonanceimaging(MRI)scanningarealsousedfordiagnosis.Plainradiographicevaluationisperformedfirst,followedbyMRI.MRIhasbeenreportedtobe＜99%specificandsensitivefordetectingearlyON.47,48MRIimagescanalsoquantitativelyassessthesizeofthelesionorinvolvementoftheaffectedbonebydigitizingtheareaofthefemoralheadoccupiedbybonewithabnormaltexture.49MRIchangesincludewell-demarcatedandhomogeneousfocallesionsonT1-weightedimageswithasingle-densitylineseparatingnormalandischemicbone,aswellasasecondhigh-intensitylineonT2-weightedimages(thepathognomonicdouble-linesign)representinghypervasculargranulationtissue.3Thislevelofimagingdetailisusefulbecausethesizeandextentofthelesionoftheaffectedboneisimportantandcanhelpdirecttreatment.Forend-stagedisease,however,useofMRIinpatientswithONmaybeunnecessarybecausetreatmentoptionsatthisstagecanbelimited.Thesefindingsareoftenclassifiedusingthe4-stageFicatandArletsystem,whichisdescribedhereandinTable1.Theplainradiographcanremainnormalformonthsaftertheonsetofsymptomssuchasgroinpain(StageI).Theearliestradiographicfindingsareusuallymilddensitychanges,followedbysclerosisandcysts(StageII).Findingsthenprogresstothepathognomoniccrescentsign(subchondralradiolucencyseenintheanterolateralaspectoftheproximalfemoralhead)fromsubchondralcollapse(StageIII),andsubsequentlossofsphericity(measurementoftheroundness)orcollapseofthefemoralheadwitheventualjoint-spacenarrowinganddegenerativechangesintheacetabulumthatarevisible(StageIV).Keyradiographicfeaturestolookforinclude1)stage(precollapsevspostcollapse),2)sizeoflesion,and3)amountofheaddepression.Table1Ficat＆ArletclassificationsystemofthefemoralheadClassificationClinicalRadiographsMRIStage0Nosymptoms;preclinicalNormalNormalStage1PossiblegroinpainNormalormildosteopeniaPossibleedemaStage2Groinpainandstiffness;painwithactivityOsteopeniaand/orsubchondralcysts;diffuseporosis;precollapseofjointspaceOutlinesareaofinvolvementofthefemoralheadStage3Groinpain,stiffness,radiationofpain;painwithactivityCrescentsignand/orsubchondralcollapse(flattening)ofjointwithsecondarydegenerativechanges;lossofsphericityoffemoralheadSameasradiographsStage4Groinpainandlimp;painatrestEnd-stagediseasewithcollapse;extensivedestructionofjoint;reducedjointspaceSameasradiographsOpeninaseparatewindowMRI=magneticresonanceimagingAcomputedtomographyscanproducinga3-dimensionalpictureofthebonehasmoderatesensitivitybutisnonspecificandcanposeasignificantradiationburdentopatients.Computedtomographycanhavesomespecificityifthereisalreadyfemoralheadcollapse.Fortunately,mostcliniciansareassuredwiththeirdiagnosisofONwithoutcomputedtomographyscanning,whichisgenerallyreservedfordistinguishingprecollapseandpostcollapsedisease.DifferentialDiagnosisofHipOsteonecrosisBecausepatientswithsymptomatichipONcanpresentwithsymptomssimilartomanyotherhippathologies,theseshouldbeadequatelyruledoutbeforefinaldiagnosis.Bonemarrowedemasyndromeandsubchondralfracturesaretwoofmanypotentialdiagnosesthatneedtoalsobeconsidered.EtiologicFactorsAssociatedwithOsteonecrosisTraumatic-associatedriskfactorsFemoralneckfractureDislocationorfracture-dislocationSicklecelldiseaseHemoglobinopathiesCaissondisease(dysbarism)GaucherdiseaseRadiationAtraumatic-associatedriskfactorsCorticosteroidadministrationAlcoholuseSystemiclupuserthyematosusCushingdiseaseHypersecretionofcortisol(rare)Chronicrenalfailure/hemodialysisPancreatitisPregnancyHyperlipidemiaOrgantransplantationIntravascularcoagulationThrombophlebitisCigarettesmokingHyperuricemia/goutHIVOtherpotentialriskfactorsIdiopathiccausesBonemarrowedemasyndrome,alsoknownastransientosteopeniaofthehip,mayoccurinisolationorinassociationwithinjuries,particularlythosethatresultinneurologicdamage.Inthelattersituation,chronicpainandtransientosteopeniaarefeaturesofthecomplexregionalpainsyndrome(alsoknownasreflexsympatheticdystrophy,causalgia,andotherterms).3BonemarrowedemasyndromecanbedifferentiatedfromONonthebasisofhistologicandMRIfindings.Subchondralfractureofthefemoralheadtypicallyoccursinpatientswithpreexistingosteopeniaandisgenerallythoughttorepresentaninsufficiencyfracture.50Thesefracturesmaybedifficulttovisualizewithplainradiographs.Subtleflatteningissometimespresentwithearlylesions;collapseofthefemoralheadisprogressive.CLINICALMANAGEMENTOFHIPOSTEONECROSISFactorstoconsiderwhendevelopinganoptimalmanagementapproachforsymptomaticONofthehipshouldbeaimedattreatingthestageanddegreeofinvolvementofON,theextentandlocationofbonyinvolvement,thepresence(orabsence)ofsymptoms,andthepatient’scomorbidities.Thegoaloftherapyistopreservethebiologicalhipjointforaslongaspossiblewhilealsotakingintoconsiderationqualityoflifeissuessuchaspatientage,mobility,occupation,andlifestyle.ThreemaintherapeuticoptionsformanagementofhipONinclude1)nonoperativemanagement,2)joint-preservingprocedures,and3)THA.TheeffectsofatraumaticcausesofhipONposespecialconcerns.Forthoseaffected,67%reportnosymptomsbutmayeventuallygoontohaveacollapsedjoint.51Thenaturalhistoryofasymptomaticmedium-sized,andespeciallylarge,osteonecroticlesionsisprogressiontoworseningoftheconditionandeventuallyend-stagediseaseandcollapseofthehipinasubstantialnumberofpatients.Forthosewithsymptoms,approximately80%to85%ofcaseswillresultincollapseofthefemoralheadwithin2years.6EarlydiagnosisofONmaythereforeprovidetheopportunityforearlytreatment,whichcanpreventcollapseand,ultimately,theneedfortotaljointarthroplasty.However,mostpatientspresentlateinthecourseofthedisease,andahighindexofsuspicionisnecessaryforthosewithknownorprobableriskfactors,particularlypatientswithhigh-dosecorticosteroiduse.3SimilarlyforpatientswithasymptomatichipON,thesize,extent,andlocationofthenecroticlesionaffectingthefemoralheadshouldbeconsidered.Generally,lesionsaffectinglessthan15%ofthefemoralheadarebestmanagednonoperatively;lesionsbetween15%to30%shouldbemanagedsurgically;andlesionsinvolvingmorethan30%ofthefemoralheadarelikelytoprogresstocollapse,despitesurgicalintervention,andeventuallyrequireTHA.3,52,53NonsurgicalTreatmentOptionsinHipOsteonecrosisPhysicalTherapyPhysicaltherapymayprovidereliefandalleviatesomesymptomsbutgenerallywillnotprecludeprogressivehipONfromadvancingtolaterstages.54Similarly,restrictingweight-bearingwiththeuseofassistivedevicessuchascrutchesoracanemaybeusefultocontrolsymptomsofpain,weakness,andantalgicgait.PhysicaltherapyisnotappropriateifthegoaloftreatmentistopreventthehipfromrequiringTHA,andtodatethereisnoevidencethatweight-bearingrestrictionsarehelpfulinpreventingprogressiveONdiseasefromadvancingtoend-stagedisease.MedicationsNonsteroidalanti-inflammatorydrugsandacetaminophenmayprovidetemporaryreliefofpaininsymptomaticpatients.Opioidmedicationsmaybeusedjudiciouslyandforshortperiodsoftimewhenotheragentsareineffectivetomanagemoderate-to-severepainwhilesurgicaloptionsarebeingconsidered.InvestigationalmedicationoptionscurrentlybeingusedbutthatarenotprovenorreliablyusedtotreatONinclude1)anticoagulants,2)bisphosphonateantiresorptiveagents,3)cholesterolloweringstatins,and4)hyperbaricoxygen.SurgicalOptionsinEarly-StageHipOsteonecrosisCoreDecompressionCoredecompressionisaminimallyinvasivesurgicaltechniqueperformedtomanagesymptomsinearlystages(precollapse)ofthecondition(eg,FicatandArletStagesIandII).Theprocedureinvolvesdrillingholesintothefemoralheadtorelievepressureandcreatechannelsfornewbloodvesselstonourishtheaffectedareas.Thepublishedsuccessratesofcoredecompressionvarygreatlyfrom40%to100%,dependingonpatientpopulation.35Highersuccessratesaftercoredecompressionareseeninpatientswiththeearliestdiseasestages.Patientswithsuccessfulcoredecompressionprocedurestypicallyreturntounassistedambulationafterseveralmonthsandcanhavecompletepainrelief.55BoneGraftingCoredecompressioncanbecombinedwithbonegraftingtohelpregeneratehealthyboneandsupportcartilageatthehipjoint.Abonegraftishealthybonetissuethatistransplantedtotheareaofnecroticordeadbone.Astandardtechniqueusesanautograftthatinvolvestakingbonefromonepartofthebodyandmovingittoanotherpartofthebody.Abonegraftthatisharvestedfromadonororcadaveriscalledanallograftandistypicallyacquiredthroughabonebank.BoneMarrowAspirateConcentrationThebonemarrowaspirateconcentrationinjectionprocedurewithcoredecompressioninvolvestheuseofconcentratedbonemarrowthatisinjectedintothedeadboneofthehip.Thisinvestigationaltechniqueharvestsstemcellsfromapatient’sbonemarrowandinjectsthemintotheareaofON.9Thebonemarrowaspirateconcentrationprocedureishypothesizedtopreventfurtherprogressionofthediseaseandtostimulatenewbonegrowth.56PercutaneousDrillingAnothersurgicaloptionispercutaneousdrilling.Inthisprocedure,aholeisdrilledpercutaneouslythroughthefemoralnecktotheaffectedsiteinthefemoralhead.Onereporton45hipswithameanfollow-upof24monthsreported24(80%)of30hipswithFicatandArletStageIdiseasehadsuccessfuloutcomes(definedasHarrisHipScore＜70).57Amorerecentstudycomparingmultipledrillingvsstandardcoredecompressionshowedfavorableresultsinfavorofpercutanteousdrilling.28SurgicalOptionsinAdvanced-StageHipOsteonecrosisVascularizedBoneGraftAvascularizedfibulagraftisamoreinvolvedsurgicalprocedureinwhichasegmentofboneistakenfromthefibulawithitsbloodsupply.Thegraftisthentransplantedintoaholecreatedinthefemoralneckandhead,andthearteryandveinarereattachedtohelphealtheareaofON.55OsteotomyOsteotomyinhipONcanbeperformedtoremovenecroticboneawayfromprimaryweight-bearingareas.AlthoughthisoperationmaydelayTHAsurgery,itismostusefulinpatientswithidiopathicONwhodemonstratesmallprecollapseorearlypostcollapseofthefemoralhead.Aconsequenceofosteotomies,however,isthattheymakesubsequentTHAmorechallengingandareoftenassociatedwithanincreasedriskofnonunionofthebone.NonvascularizedBoneGraftThereare3typesofnonvascularizedbonegraftingsurgeries:1)trapdoorprocedure,2)lightbulbtechnique,and3)Phemistertechnique.ThetrapdoorprocedureisoneinwhichautogenouscancellousandcorticalbonegraftinghavebeensuccessfulinFicatandArletStageIIIhipONinpatientswithsmall-tomedium-sizedlesions.Areviewoftheresultsof30trapdooroperationsperformedon23patientswithFicatandArletStageIIIorStageIVONofthefemoralheadperformedthroughaso-calledtrapdoormadeinthefemoralheadrevealedagoodorexcellentresultasdeterminedbytheHarrisHipScoresystem.11LightbulbTechniqueThelightbulbtechniqueusesacorticalwindowintheanterioraspectofthefemoralneck.Necroticbonecanberemovedusingthiswindow,whichcanbelaterpackedwithnonvascularizedbonegraft.Wangetal55evaluated110patients(138hips)whounderwentthelightbulbprocedure.Atmeanfollow-upof25months,meanHarrisHipScoresimprovedfrom62to79points.Atotalof94hips(68%)wereconsideredtohavesuccessfuloutcomesatlatestfollow-up.Radiographicimprovementswerenotedin100%ofAssociationResearchCirculationOsseousStageIIapatients,77%instageIIbpatients,and51%instageIIcandIIIapatients.55PhemisterTechniqueInthePhemistertechnique,atrephineisinsertedthroughthefemoralnecktocreateatracttothelesion.Asecondtrephineistheninsertedtocreateanothertracttothelesionsite.Acorticalstrutgraftcanthenbeplacedinthelesion.Arecentreviewreportsthisproceduretohaveaclinicalsuccessraterangingfrom36%to90%.25TotalHipArthroplastyOncethefemoralheadhasundergonemajorcollapse,replacingthehipjointistheonlypracticaloperativeoptionandoffersthemostpredictablepainreliefinadvancedON.THAissuccessfulinrelievingpainandrestoringfunctioninthemajorityofpatients.45–47InTHA,thediseasedcartilageandboneconstitutingthehipjointisreplacedwithartificialimplantsmadeofmetalandplastic.Aprosthetichipreplacementgenerallylasts15yearsbeforeitmightwearoutandneedtoberevised.Fortheyoungeragegroup,aTHAmaybeasuboptimalsolutionbecauseofpossibleactivityrestrictions.Additionally,becauseprostheseshavelongevityrestrictions—componentswearafterlong-termuse—thesepatientswilllikelyrequirearevisionTHAlaterinlife.THAmustbecarefullyconsideredandbalancedagainstqualityoflifeissues,butitisnotabsolutelycontraindicatedforyoungerpatients.PATIENTEDUCATIONABOUTHIPOSTEONECROSISPreventionofOsteonecrosisPatienteducationaboutriskfactors,therapies,andmanagementisessentialforpatientstomakebetter-informeddecisionsabouttheircondition.TheprocessofONeducationinvolvesidentificationofanindividual’sassociateddisordersandriskfactorsrelatedtoON.PatientswithasymptomaticONmayhaveahighprevalenceofprogressiontosymptomaticdiseaseandfemoralheadcollapse.Educationforpatientswithasymptomaticdiseaseisprecautionaryandimperativetoensuremodificationofriskfactorsandoptimizationofcare.PreventingatraumaticONrequires1)avoidingexcessiveuseofalcoholdefinedas＜15drinks/wkformenand＜8drinks/wkforwomen,102)avoidingsmoking,and3)reducingcorticosteroidstothelowestpossibletherapeuticdose.InformingpatientsaboutthecorrelationbetweencorticosteroiduseandpotentialdevelopmentofONiscriticalinmanagementofthiscondition.PreventionofProgressionofOsteonecrosisPatientsdiagnosedwithearly-stageONshouldbeadvisedoftheaforementionedprecautionsandshouldavoidplacingexcessivepressureontheirjoints,followahealthydiet,andmaintainanappropriateweighttomitigateprogressionofON.Althoughahealthydietinitselfdoesnotdirectlyreducepressureonapatient’sjoints,weightloss(ifoverweight/obese)willreduceaxialloadsonthehipjoint,whichinturndecreasesthestrainappliedtothefemoralhead/neck(toboththetensionandthecompressionsides).42CONCLUSIONONisapathologicandoftenpainfulconditioninvolvingnecroticareasoftissuethatcanaffectanybonyjointinthebody.ThehipjointisthemostcommonlocationforONandshouldalwaysbeproperlyevaluated,utilizingradiographicscreeningandMRIscanning,whenONisinitiallydiagnosedinanotherbodypart.TheearlieradiagnosisofONismade,thebettertheopportunitytosavethehipjointwithoutsurgicalinterventionorwithminimallyinvasivesurgicaltechniques.AfteradiagnosisofONismade,thesize,extent,andlocationofthelesionandtheclassificationstagesareconsideredtodevelopanoptimalplanofcare.Thepresenceorabsenceofsymptomsisimportantinthisprocess.Thegoalsoftreatmentinvolveattemptingtopreservethebiologicalhipjointforaslongaspossibleandconsiderationofapatient’slifestyleandqualityoflifeissues.Todate,the2maintherapeuticoptionsformanagementofhipONincludejoint-preservingproceduresandTHA.PatienteducationaboutpotentialriskfactorsanddevelopmentofONisessentialtopreventtheconditionand/ortopotentiallypreventorhaltprogressionofearly-stagediseasetolater-stagedisease.2023年07月10日1152
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陶可主治醫(yī)師 北京大學人民醫(yī)院 骨關節(jié)科 股骨頭壞死：病因、診斷及治療方式：2019英國醫(yī)學雜志(BMJ)(醫(yī)學生及低年資住院醫(yī)師培訓之)綜述作者：JonathanNLamb,ColinHolton,PhilipO'Connor,PeterVGiannoudis作者單位:LeedsInstituteofRheumaticandMusculoskeletalMedicine,SchoolofMedicine,UniversityofLeeds,Leeds,UK.譯者：陶可（北京大學人民醫(yī)院骨關節(jié)科）股骨頭壞死你需要了解什么？?股骨頭壞死(AVNFH)的常見危險因素包括：酗酒、使用類固醇激素、化療和免疫抑制劑藥物以及鐮狀細胞性貧血。?如果患者髖部疼痛持續(xù)超過6周且X線片正常，請考慮對髖部進行核磁共振MRI掃描，并轉診至骨科（保髖治療）團隊。?早期治療可使髖關節(jié)7年后存活率提高至88%。Fig1Demonstrationofhiprotationtoelicithippainwiththepatientsitting(A)andsupine(B,C,D).圖1?演示通過患者坐位(A)和仰臥位(B、C、D)引起髖部疼痛的髖關節(jié)旋轉活動(髖關節(jié)查體之內(nèi)外旋轉活動)。Fig2Typicalchangesseenonplainradiograph(top)andMRI(bottom)ofthehipinearlyandlateAVNFH.TheappearanceofearlyAVNFHisnotapparentonplainradiographbutisvisibleonMRI.圖2?早期和晚期股骨頭壞死(AVNFH)髖關節(jié)平片（上）和MRI（下）中看到的典型變化。早期股骨頭壞死(AVNFH)的在平片上表現(xiàn)不明顯，但在MRI上可見明顯信號的改變。Fig3ProposedpathwayformanagingAVNFHinaprimarycaresetting.圖3?在基層醫(yī)療機構中管理股骨頭壞死(AVNFH)的建議診治流程。?典型病例：一名36歲的女性向她的全科醫(yī)生報告，有左側腹股溝疼痛放射到膝蓋的病史。疼痛很嚴重，走路時更嚴重，并伴有跛行。一年后，患者再次去看全科醫(yī)生，盡管進行了鎮(zhèn)痛，但疼痛仍持續(xù)存在。髖關節(jié)和膝關節(jié)的平片顯示髖關節(jié)間隙輕微變窄，沒有其他特征，她被轉診到二級骨科診所。髖關節(jié)磁共振成像(MRI)掃描顯示股骨頭缺血性壞死(AVNFH)伴塌陷的典型特征。什么是股骨頭缺血性壞死？股骨頭壞死（AVNFH）由于微循環(huán)異常而導致軟骨下骨結構完整性喪失。潛在的發(fā)病機制尚不清楚；風險因素可能會以某種方式影響微循環(huán)，但這尚未得到研究證實。共同的終點是微循環(huán)異常和壞死。軟骨下骨隨后塌陷，導致進行性、繼發(fā)性髖關節(jié)骨關節(jié)炎。在英國，平均發(fā)病年齡為58.3歲，每10萬名患者中有2人患病。平均而言，股骨頭壞死（AVNFH）比典型骨關節(jié)炎發(fā)生得更早。它在男性中更為常見，發(fā)病率最高的是25至44歲的男性和55至75.3歲的女性。在英國，它是50.4歲以下人群全髖關節(jié)置換術的第三大常見適應癥。以下因素與股骨頭壞死（AVNFH）風險增加相關：?血液甘油三酯、總膽固醇、低密度脂蛋白膽固醇和非高密度脂蛋白膽固醇水平高；?男性；?城市居民；?股骨頭壞死（AVNFH）家族史；?大量吸煙；?濫用酒精；?超重；?凝血病；?血管病變；?艾滋病病毒；?大量接觸類固醇激素、化療和免疫抑制藥物。類固醇激素已被證明會使骨壞死（非部位特異性）的幾率增加3倍，而免疫抑制劑則增加6倍。Zhao報告稱，服用皮質類固醇激素的患者發(fā)生股骨頭壞死（AVNFH）的幾率高出35倍，患有“酗酒”狀態(tài)的患者則高出6倍。為什么股骨頭壞死（AVNFH）會漏診呢？股骨頭壞死（AVNFH）很少見?；加羞@種疾病的患者可能同時患有慢性風濕病和血液病。這可能會導致診斷的不確定性，特別是考慮到在這些情況下使用化療、免疫調(diào)節(jié)劑和類固醇激素時，這些都是股骨頭壞死（AVNFH）的危險因素。查體可以幫助識別可能引起疼痛的解剖結構，因為髖關節(jié)疼痛可能源自髖關節(jié)和非髖關節(jié)的多個部位。臨床表現(xiàn)可能會被錯過，因為由于時間和空間的限制，在基層醫(yī)療機構中準確確定單純由于髖關節(jié)運動時造成的腹股溝疼痛可能具有挑戰(zhàn)性(比較困難)。股骨頭壞死（AVNFH）早期階段的正常X線片可能會錯誤地讓人放心并延遲適當?shù)霓D診。如果X線片呈陰性并且患者繼續(xù)抱怨髖關節(jié)疼痛，醫(yī)生可能會診斷為非特異性髖關節(jié)疼痛（考慮到肌肉骨骼的原因）并建議患者接受物理治療。在新發(fā)病例中，18.75%只能通過MRI進行診斷，并且在普通X線片上很容易被漏診。只有MRI掃描才具有診斷意義。為什么及早確診股骨頭壞死（AVNFH）很重要？早期診斷和轉診至關重要，因為骨質破壞通常發(fā)生在發(fā)病后2年內(nèi)，因此不可能進行保留髖關節(jié)的治療干預(保髖治療在股骨頭壞死發(fā)病2年內(nèi))。股骨頭壞死（AVNFH）的早期發(fā)現(xiàn)使多學科團隊有時間改變可能引發(fā)股骨頭壞死（AVNFH）發(fā)作的治療方法。股骨頭髓心減壓術可降低中短期內(nèi)進一步手術的需要，但僅適用于疾病的最早階段。一旦患者進展為繼發(fā)性髖關節(jié)骨關節(jié)炎，關節(jié)置換通常是不可避免的。然而，考慮到股骨頭壞死（AVNFH）患者年齡較小，翻修手術和相關發(fā)病率的終生風險很大。如何診斷股骨頭壞死（AVNFH）？股骨頭壞死（AVNFH）診斷從仔細詢問病史和檢查開始，以確定髖關節(jié)疼痛的來源。最終需要MRI來診斷股骨頭壞死（AVNFH），并且還可以診斷髖關節(jié)疼痛的其他原因。仔細的詢問病史病史顯示疼痛持續(xù)超過6周，通常位于腹股溝和大腿，負重和運動時疼痛更嚴重。通常沒有外傷史。詢問危險因素，如果患者有任何“危險信號”，請進行髖關節(jié)MRI檢查。股骨頭壞死（AVNFH）通常是雙側的，雙側股骨頭壞死（AVNFH）的風險通常是在單側確診后的2年內(nèi)?？?：需要轉介或進一步評估的危險信號：?髖關節(jié)X線檢查正常，髖關節(jié)疼痛超過6周；?患有髖關節(jié)疼痛和危險因素的患者，包括：o既往單側股骨頭壞死（AVNFH），o酗酒，o大量接受類固醇激素治療，o免疫治療，?化療，o鐮狀細胞病和其他凝血病，?艾滋病毒，o新近妊娠。查體腹股溝、大腿和膝關節(jié)前側疼痛的再現(xiàn)并伴有單獨的大腿旋轉不能診斷股骨頭壞死（AVNFH），但有助于區(qū)分髖關節(jié)疼痛與脊柱和膝關節(jié)疼痛。這可以在患者坐位或仰臥時進行（圖1）。影像學檢查早期股骨頭壞死（AVNFH）在X線片上并不明顯。如果患者持續(xù)感到疼痛，則需要進一步檢查和轉診。股骨頭壞死（AVNFH）通過髖關節(jié)MRI進行診斷，當與臨床癥狀密切相關時，還可以診斷各種可治療的髖關節(jié)疼痛（例如風濕病、肌腱疾病和骨?。▓D2）。僅當有其他原因或高度懷疑風濕病或感染時，才應考慮進行其他檢查，例如血液檢查。轉診如果患者的髖關節(jié)MRI顯示有股骨頭壞死（AVNFH）改變時，請就診于骨科醫(yī)生（圖3）。在二級醫(yī)療機構就診時，股骨頭壞死（AVNFH）診斷應與開具類固醇激素、化療和免疫治療原發(fā)病的任何治療團隊共享。藥物和手術治療取決于患者的特征和股骨頭壞死（AVNFH）的階段。使用前列環(huán)素類似物和雙膦酸鹽對塌陷前股骨頭壞死（AVNFH），可以減輕癥狀并防止關節(jié)形合度破壞，但其療效目前尚不清楚。手術治療仍存在爭議，但大多數(shù)塌陷前股骨頭壞死（AVNFH）患者均接受髓心減壓手術，并輔以或不輔以藥物治療，以減輕疼痛，并有可能在長達7年的時間里避免88%的患者進行全髖關節(jié)置換術治療。術后恢復包括12個月的非負重康復鍛煉，并在8周后逐漸恢復工作和駕駛。通常在術后12個月即可感受到完全的治療益處。專業(yè)的三級醫(yī)療機構可以提供新的治療方法，例如骨移植和截骨術，以分別促進血管再生和減輕受損髖關節(jié)表面的負荷。一旦發(fā)生塌陷，全髖關節(jié)置換術可以為患者提供快速、可靠的疼痛緩解和功能改善，但與未來有髖關節(jié)翻修的風險，特別是對于年輕患者。?AvascularnecrosisofthehipWhatyouneedtoknow?CommonriskfactorsforAVNFHarealcoholism,useofsteroids,chemotherapyandimmunosuppressantmedication,andsicklecellanaemia.?ConsiderMRIscanofthehipandreferraltoanorthopaedicteamifapatienthasapainfulhipforlongerthansixweekswithnormalradiographs.?Earlytreatmentimprovesthechancesofhipsurvivalbyupto88%atsevenyears.?A36yearoldwomanpresentstoherGPwithahistoryofleftgroinpainradiatingtotheknee.Thepainissevere,worseonwalking,andassociatedwithalimp.ThepatientrevisitstheGPayearlaterwithpersistentpaindespiteanalgesia.Plainradiographsofthehipandkneeshowslightnarrowingofthehipjointspacewithnootherfeaturesandsheisreferredtoasecondarycareorthopaedicclinic.Amagneticresonanceimaging(MRI)scanofthehipshowsclassicfeaturesofavascularnecrosisofthefemoralhead(AVNFH)withcollapse.Whatisavascularnecrosisofthefemoralhead?Osteonecrosisofthefemoralhead(AVNFH)causeslossofintegrityofsubchondralbonestructureduetoabnormalmicrocirculation.Theunderlyingpathogenesisisunclear1;riskfactorsarelikelytoaffectmicrocirculationinsomewaybutthishasnotbeenconfirmedbyresearch.Thecommonendpointisabnormalmicrocirculationandnecrosis.Subchondralbonesubsequentlycollapses,whichleadstoprogressivesecondaryarthritis.MeanageofpresentationintheUKis58.3years,withaprevalenceoftwoper100000patients.2Onaverage,AVNFHoccursearlierinlifethantypicalosteoarthritis.Itismorecommoninmenandthehighestprevalenceisinmenaged25to44andwomenaged55to75.3IntheUKitisthethirdmostcommonindicationfortotalhipreplacementinpeopleunder50.4ThefollowingfactorsareassociatedwithanincreasedriskofAVNFH35:?Highlevelsofbloodtriglycerides,totalcholesterol,lowdensitylipoproteincholesterol,andnon-highdensitylipoproteincholesterol?Malesex?Urbanresidence?FamilyhistoryofAVNFH?Heavysmoking?Alcoholabuse?Overweight?Coagulopathies?Vasculopathies?HIV?Highexposuretosteroids,chemotherapy,andimmunosuppressantmedication.Steroidshavebeenshowntoincreaseoddsofosteonecrosis(non-sitespecific)byafactorofthreeandimmunosuppressantsbyafactorofsix.ZhaoreportedthattheoddsofAVNFHwere35timesgreaterinpatientstakingcorticosteroidsandsixtimesgreaterinpatientswith“alcoholism”status.3Whyisitmissed?AVNFHisrare.Patientswiththeconditioncanhavecoexistingchronicrheumaticandhaematologicalproblems.Thismayleadtodiagnosticuncertainty,particularlygiventheuseofchemotherapy,immunomodulatoryagents,andsteroidsintheseconditions,whichareallriskfactorsforAVNFH.Aphysicalexaminationcanhelpidentifytheanatomicalstructuresthatmightbecausingthepain,sincehippaincanoriginatefrommultiplehipandnon-hipareas.Presentationsmaybemissedbecauseaccuratereproductionofgroinpainonisolatedhipmovementscanbechallengingtoelicitinaprimarycaresettingduetotimeandspaceconstraints.NormalplainradiographsintheearlystagesofAVNFHcanbefalselyreassuringanddelayappropriatereferral.Iftheplainradiographisnegativeandthepatientcontinuestocomplainofhippain,thedoctormaygiveadiagnosisofnon-specifichippain(giventhatmusculoskeletalpresentationsarecommoninprimarycare)andsendthepatientforphysiotherapy.Ofnewpresentations,18.75%arediagnosableonlywithMRIandareeasilymissedonnormalplainradiographs.3OnlytheMRIscanisdiagnostic.Whydoesitmatter?Earlydiagnosisandreferralareessentialsincebonedestructionnormallyoccurswithintwoyearsofdiseaseonset,makingjointpreservinginterventionimpossible.6EarlyidentificationofAVNFHgivesthemultidisciplinaryteamtimetochangemedicaltreatmentswhichmightbeprovokingonsetofAVNFH.Surgicaldecompressionofthefemoralheadreducestheneedforfurthersurgeryintheshorttomediumtermbutisonlysuitablefortheearlieststagesofdisease.5Oncepatientshaveprogressedtosecondaryhiparthritis,jointreplacementisusuallyinevitable.However,giventheyoungerageofpatientswithAVNFH,thelifetimeriskofrevisionsurgeryandassociatedmorbidityisgreat.HowisAVNFHdiagnosed?AVNFHdiagnosisstartswithacarefulhistoryandexaminationtodeterminethatthehipisthesourceofpain.UltimatelyanMRIisrequiredtodiagnoseAVNFHandmayalsodiagnoseothercausesofhippain.AcarefulhistoryAhistoryshowingpainlastinglongerthansixweeks,typicallylocatedinthegroinandthighandwhichisworseonweightbearingandmovementiskey.6Usuallythereisnohistoryoftrauma.AskaboutriskfactorsandreferforMRIofthehipifthepatienthasany“redflags”(box1).AVNFHisoftenbilateralandtheriskofbilateralAVNFHishighestwithintwoyearsofunilateraldiagnosis.6Box1:Redflagsrequiringreferralorfurtherassessment?Hippainformorethansixweekswithnormalhipradiograph?PatientspresentingwithhippainandriskfactorsincludingopreviousunilateralAVNFHoalcoholexcessohighexposuretosteroidtherapyoimmunologictherapyochemotherapyosicklecelldiseaseandothercoagulopathiesoHIVorecentpregnancyExaminationReproductionofpaininthegroin,thigh,andanterioraspectofkneewithisolatedthighrotationwillnotdiagnoseAVNFH,butwillhelptodifferentiatehippainfrompainoriginatingfromthespineandknee.Thiscanbeperformedwiththepatientsittingorsupine(fig1).RadiologicaltestsEarlyAVNFHisnotapparentonplainradiographs.Ifthepatientcontinuestobeinpain,furtherinvestigationandreferraliswarranted.AVNFHisdiagnosedonMRIofthehips,7whichmayalsodiagnoseabreadthoftreatablehippain(suchasrheumatologicaldisease,musculotendinousdisease,andbonydisease)whencarefullycorrelatedwithclinicalsymptoms8(fig2).Otherinvestigations,suchasbloodtests,shouldonlybeconsideredifindicatedforotherreasonsorifthereisahighsuspicionofrheumatologicaldiseaseorinfection.ReferralIfthepatienthassignsofAVNFHonMRIofthehip,refertoanorthopaedicsurgeonforconsultation(fig3).Insecondarycare,AVNFHdiagnosisshouldbesharedwithanycareteamsinvolvedintheadministrationofsteroids,chemotherapy,andimmunologictherapy.MedicalandsurgicaltreatmentdependonthepatientcharacteristicsandstageofAVNFH.Medicaltreatmentofpre-collapsediseasewithprostacyclinanaloguesandbisphosphonatesmayreducesymptomsandpreventlossofjointcongruitybuttheirefficacyisnotcurrentlywelldefined.6Surgically,treatmentremainscontroversial,butmostpatientswithpre-collapseAVNFHareofferedcoredecompressionsurgerywithorwithoutadjunctivepharmacologicaltherapytoreducepainandpotentiallypreventtheneedfortotalhipreplacementin88%ofpatientsforuptosevenyears.910Postoperativerecoveryinvolvesaperiodofnon-weightbearingfor12monthsandgradualreturntoworkanddrivingat8weeks.Fullbenefitisusuallyfeltat12monthsaftersurgery.Specialisttertiarycentresmayoffernoveltreatmentssuchasbonegraftingandosteotomiestoencouragevascularregrowthandunloaddamagedhiparticularsurface,respectively.Oncecollapsehasoccurred,totalhipreplacementcangivepatientsrapid,reliablepainreliefandimprovedfunctionbutisassociatedwiththeriskoffuturerevision,particularlyinyoungerpatients.Afulldescriptionofalltheoptionsisbeyondthescopeofthisarticleandpatientsshoulddiscussallavailableoptionswiththeirsurgeontoenableinformedshareddecisionmaking.文獻出處：JonathanNLamb,ColinHolton,PhilipO'Connor,PeterVGiannoudis.Avascularnecrosisofthehip.BMJ.2019May30;365:l2178.doi:10.1136/bmj.l2178.2023年07月09日531
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陶可主治醫(yī)師 北京大學人民醫(yī)院 骨關節(jié)科 股骨頭壞死治療：2022年最新研究進展作者：GaryGeorge,JosephMLane.作者單位:FromWeillCornellMedicine,NewYork,NewYork(Mr.George),andtheHospitalforSpecialSurgery,NewYork,NewYork(Dr.Lane).譯者：陶可（北京大學人民醫(yī)院骨關節(jié)科）摘要股骨頭壞死是一種進展性、使人致殘的疾病，其病因多種多樣，包括外傷、使用激素(類固醇)和飲酒。診斷和分期基于影像學檢查，包括任何階段的MRI掃描和更晚期病變的X線片檢查。（疾病晚期）唯一確定的治療方法是全髖關節(jié)置換術，盡管，（目前臨床上）采用包括二磷酸鹽和核心減壓在內(nèi)的多種治療方法來延緩病情進展。缺乏令人滿意的保守（治療）措施表明，需要對股骨頭壞死進行進一步研究，包括大型的患者登記，以進一步了解（保守治療的）效果。股骨頭壞死是一種進展性疾病，（股骨頭）缺乏足夠的血液供應會導致受影響區(qū)域的細胞死亡、骨折和塌陷。這種情況通常與股骨頭有關，病情進展可能會使人衰弱（殘疾），最終可能需要進行全髖關節(jié)置換術(全髖關節(jié)置換術(THA))。股骨頭壞死的病因很復雜，有多種致病因素，其中最明顯的是外傷、使用激素和酒精。股骨頭壞死的治療是有爭議的，因為沒有任何一種治療方式是被廣泛接受的，而且很少有研究比較（各種）治療方法（之間的優(yōu)劣）。研究人員估計，美國每年診斷出20,000例新發(fā)的股骨頭壞死病例。股骨頭壞死發(fā)病率的增加和使人致殘的進展表明需要對有效和新穎的治療方法進行深入的研究，以及需要更清楚地了解現(xiàn)有的治療方法。這篇綜述描述了目前關于股骨頭壞死的病因學、病理生理學、流行病學和臨床治療的知識，重點介紹了最新進展。流行病學據(jù)估計，美國每年股骨頭壞死的發(fā)病率約為20000至30000例，主要影響20至40歲之間的年輕人。最近的分析表明，盡管因股骨頭壞死而進行的全髖關節(jié)置換術(THA)數(shù)量有所增加，2001年和2010年（從每100,000名住院患者54.2例到每100,000名住院患者60.6例），因股骨頭壞死而進行全髖關節(jié)置換術(THA)的比例從9.7%下降到8.3%，可能是因為需要進行全髖關節(jié)置換術(THA)的骨關節(jié)炎迅速增加。病理生理學和發(fā)病機制一般發(fā)病機制盡管臨床表現(xiàn)是修復過程的結果，而不是最初的缺血，但股骨頭壞死的發(fā)生是由于骨骼的血流或氧氣輸送受損。在股骨頭壞死中，成骨細胞的骨形成無法與破骨細胞的骨吸收相匹配。這種重塑不平衡并不能充分替代壞死骨，從而留下了結構不健全的骨組織區(qū)域。創(chuàng)傷創(chuàng)傷是股骨頭壞死的最常見原因，會擾亂血流并導致骨細胞死亡。發(fā)生股骨頭外傷性股骨頭壞死的估計因損傷類型而異；然而，在創(chuàng)傷性股骨頭壞死的薈萃分析中，發(fā)現(xiàn)其發(fā)生率高達14.3%。Garden分類對股骨頸骨折進行了分類，可用于估計股股骨頭壞死的風險。GardenI（不完全骨折）和GardenII（完全且無移位）被認為是穩(wěn)定且風險低的，可以通過內(nèi)固定修復。GardenIII（完全骨折和部分移位）和GardenIV（完全骨折和完全移位）內(nèi)固定的股骨頭壞死發(fā)生率要高得多（16%），應考慮髖關節(jié)置換術。另外，有文獻報道，股骨轉子間骨折導致股骨頭壞死的風險較低，一年隨訪時的股骨頭壞死結果為0.95%。非外傷性股骨頭壞死非外傷性股骨頭壞死有多種原因。值得注意的是，在非創(chuàng)傷性股骨頭壞死中，由于系統(tǒng)性危險因素，疾病常常是雙側的，一些估計表明，高達70%的單側股骨頭壞死患者的對側髖部會發(fā)生疾病。在存在系統(tǒng)性危險因素的情況下，一側髖關節(jié)的磨損尚未得到充分研究，可能是由于亞臨床表現(xiàn)、髖關節(jié)之間磨損模式的差異、對癥狀的調(diào)查不足或缺乏協(xié)調(diào)的隨訪。糖皮質激素類固醇的使用是股骨頭壞死的第二個最常見原因。已經(jīng)提出了這種關聯(lián)的幾種潛在機制，包括骨基質和軟骨變性、誘導干細胞異常、脂質代謝的變化、脂肪栓塞的產(chǎn)生、凝血改變。薈萃分析發(fā)現(xiàn)，服用大劑量皮質類固醇的患者風險增加多達10倍；當累積劑量超過10g時，股骨頭壞死的風險增加一倍；而使用大劑量皮質類固醇患者每日劑量每增加10毫克股骨頭壞死風險就會增加3.6%。皮質類固醇也與成骨細胞死亡和成骨細胞增殖減少有關，損害修復和替換骨壞死病變的能力。酒精據(jù)推測，酒精會通過改變脂質代謝和增加脂肪生成來發(fā)揮（導致股骨頭壞死的）作用。據(jù)推測，脂質生成的增加會增加脂肪栓塞導致血管閉塞的風險。此外，血脂升高會導致骨髓堵塞、骨內(nèi)壓升高和血流量減少。酒精也可能導致骨細胞死亡。一項研究還表明，與酒精性股骨頭壞死患者相比，酒精性股骨頭壞死患者的皮質醇水平升高。特發(fā)性股骨頭壞死對照受試者，表明酒精引起的股骨頭壞死可能通過類固醇途徑起作用。之前有研究指出，每天飲酒超過400mL的患者發(fā)生股骨頭壞死的風險高出11倍。高脂血癥高脂血癥被認為會增加骨內(nèi)壓并產(chǎn)生脂肪栓塞，從而減少受影響區(qū)域的血液供應。一項針對老年人低能量股骨頸骨折的研究發(fā)現(xiàn)，發(fā)生股骨頭壞死的患者血脂異常率高于未發(fā)生股骨頭壞死的患者。一項針對急性淋巴細胞白血病(ALL)患者的研究發(fā)現(xiàn)，高脂血癥是發(fā)生股骨頭壞死的危險因素。一項類似的研究發(fā)現(xiàn)，高脂血癥和系統(tǒng)性紅斑狼瘡(SLE)患者與股骨頭壞死的發(fā)生有關。系統(tǒng)性紅斑狼瘡SLE與股骨頭壞死的關聯(lián)與頻繁的皮質類固醇治療有關；然而，最近的分析顯示，患有SLE的皮質類固醇使用者的股骨頭壞死發(fā)生率高于未患SLE的皮質類固醇使用者，這表明存在協(xié)同效應。SLE研究的薈萃分析已發(fā)現(xiàn)SLE中的許多非皮質類固醇危險因素，特別是腎臟受累和中樞神經(jīng)系統(tǒng)（CNS）疾病?；旌蠑?shù)據(jù)表明，抗磷脂抗體的促血栓作用在SLE股骨頭壞死的發(fā)展中發(fā)揮作用。最近對兒童期發(fā)病的SLE的薈萃分析發(fā)現(xiàn)了顯著的股骨頭壞死關聯(lián)，估計6%至8.4%的兒童期發(fā)病的SLE患者會發(fā)生股骨頭壞死，盡管大多數(shù)患者直到青春期后才發(fā)現(xiàn)（并確診）股骨頭壞死。鐮狀細胞性貧血癥對鐮狀細胞病與股骨頭壞死之間關系的研究發(fā)現(xiàn)，每100名鐮狀細胞病患者中就有2至4.5例發(fā)生股骨頭壞死。低氧環(huán)境中血紅蛋白S的沉淀可能會導致血管閉塞和骨骼缺血，從而導致股骨頭壞死。與鐮狀細胞病中其他血管閉塞性損傷的發(fā)展類似。最近的一項研究支持這一理論，指出血紅蛋白水平升高是鐮狀細胞病患者股骨頭壞死的危險因素，并表明血管閉塞、高血液粘度、缺氧和并發(fā)的α地中海貧血會導致股骨頭壞死。戈謝病最近對戈謝登記處的一項評估估計，股骨頭壞死的發(fā)生率為30%。戈謝病可能通過與鐮狀細胞病類似的途徑發(fā)揮作用，受戈謝影響的細胞會阻礙血流或通過增加骨內(nèi)壓，因為它們在體內(nèi)積聚。此外，戈謝細胞可以釋放破骨細胞激活細胞因子，破壞骨形成和吸收的平衡。酶替代可以減輕或延遲股骨頭壞死的癥狀；然而，一項研究表明，骨髓可能是戈謝細胞的“避難所”，導致部分患者盡管接受治療，仍容易發(fā)生股骨頭壞死。減壓病減壓病相關的股骨頭壞死或氣壓異常性股骨頭壞死是由于長時間處于高壓環(huán)境后快速減壓而發(fā)生的?？焖贉p壓會在血液中形成氣泡，因為溶解的氮氣會從溶液中逸出。氮氣在脂肪組織中的高溶解度使得骨髓特別容易受到影響。已經(jīng)提出了多種機制，包括直接阻塞骨髓血流和骨內(nèi)壓升高減少有效血流。最近一項針對患有肌肉骨骼減壓病的潛水員的研究發(fā)現(xiàn)，26%的病例存在氣壓不足性股骨頭壞死的證據(jù)，盡管研究受到這種情況相對罕見的限制。急性淋巴細胞白血病ALL患者發(fā)生股骨頭壞死的風險增加，前瞻性研究中影像學發(fā)生率達到71.8%。ALL患者發(fā)生股骨頭壞死的最大單一因素是青春期，這表明ALL或其治療對骨骼的生長和發(fā)育、重塑有影響。也有可能是代謝和生長時期的變化放大了易感性。老年人占股骨頭壞死診斷患者的一小部分，他們經(jīng)常接受改良的治療方案，與年輕人相比，總體結果更差。最近的一項兒童白血病研究發(fā)現(xiàn)與單純化療相比，接受造血干細胞移植(HSCT)治療的患者股骨頭壞死發(fā)生率更高（6.8%比1.4%），這表明治療方法會影響股骨頭壞死的發(fā)展。此外，對治療方案的審查發(fā)現(xiàn)，患有任何血液系統(tǒng)惡性腫瘤兒童的激素累積劑量的增加發(fā)生股骨頭壞死的危險因素。對治療策略的回顧表明，使用不連續(xù)的激素治療方案可能會降低股骨頭壞死的風險，而甲氨蝶呤和天冬酰胺酶等非激素化療藥物可能會導致股骨頭壞死的發(fā)生。一項隔周地塞米松試驗與持續(xù)治療高危ALL兒童相比，降低了股骨頭壞死的風險。移植最近的一項研究表明，移植患者中的股骨頭壞死是由激素介導的，發(fā)現(xiàn)發(fā)生股骨頭壞死的腎移植患者的累積激素劑量高于未發(fā)生股骨頭壞死的腎移植患者。研究還發(fā)現(xiàn)，隨著環(huán)孢素的引入和激素使用的減少，癥狀性股骨頭壞死的發(fā)生率從20%下降到5%以下。艾滋病病毒多項研究表明，艾滋病毒患者股骨頭壞死的發(fā)病率不斷上升，其風險幾乎是普通人群的三倍。最近的一項研究表明，高活性抗逆轉錄病毒治療與股骨頭壞死的發(fā)生之間存在密切關聯(lián)，盡管作者警告說，這種關聯(lián)并不意味著病理作用。其他研究發(fā)現(xiàn)股骨頭壞死與抗逆轉錄病毒治療(ART)之間沒有關聯(lián)，而與酒精、高脂血癥或低最低CD4計數(shù)有關，盡管其機制尚不清楚。遺傳參與盡管已經(jīng)發(fā)現(xiàn)了股骨頭壞死的家族變異和一些相關基因，但尚未確定單一的相關基因。一個候選基因是II型膠原蛋白的突變，盡管尚未確定明確的因果關系。與健康骨骼相比，壞死區(qū)域中發(fā)現(xiàn)骨保護素水平升高，RANK/RANK配體表達降低，這表明破骨細胞的潛在作用。在多項研究中，因子VLeiden突變和凝血酶原突變與股骨頭壞死患者相關，表明凝血功能改變的潛在作用。對選定人群的全基因組關聯(lián)研究已經(jīng)確定了幾個感興趣的位點，包括ALL、皮質類固醇誘導的股骨頭壞死患者中谷氨酸受體基因附近的變異簇，以及幾個意義不明的位點，這些位點可能與凝血途徑有關，脂質代謝，或飲酒行為。特發(fā)性股骨頭壞死值得注意的是，估計20%至40%的股骨頭壞死病例是特發(fā)性的（無明確病因）。原因不明的高比例可能是由于非特異性早期癥狀和非快速進展的病程，（因而會）妨礙早期診斷，以及缺乏標準化報告和數(shù)據(jù)收集，這可能有助于揭示少見的病因和聯(lián)系。臨床表現(xiàn)和診斷診斷股骨頭壞死的早期階段通常無癥狀，但查體時也可能出現(xiàn)髖部或腹股溝的放射痛以及髖關節(jié)活動范圍有限。股骨頭壞死的診斷主要基于影像學，盡管查體和病史（采集）對于收集髖關節(jié)周圍（其他病變）和潛在病因很重要。X線片是識別股骨頭壞死病例的合適的一線方法，其優(yōu)點包括低成本、高可用性以及對中期和晚期疾病足夠的敏感性。為了準確起見，建議采用正位和“蛙式位”側視圖。在疾病早期的情況下，放射線檢查可能不足以識別早期或微小的變化。MRI是診斷股骨頭壞死的標準，因為它對發(fā)病早期病變具有很高的敏感性。補充成像，包括彌散加權MRI和釓增強灌注MRI可能會進一步提高MRI的診斷能力。灌注MRI可能有助于區(qū)分影像學和癥狀相似的情況，例如骨髓水腫和軟骨下功能不全骨折。在患有髖關節(jié)發(fā)育不良的兒科患者中，灌注MRI有助于識別閉合復位/人字形石膏脫外固定后有股骨頭壞死風險的患者。此外，全身骨掃描患有多灶性股骨頭壞死風險的患者提供了一種選擇，如接受全身性皮質類固醇或免疫抑制劑的患者。鑒別診斷骨髓水腫綜合征骨髓水腫綜合征(BMES)表現(xiàn)為突發(fā)疼痛，沒有明顯的誘發(fā)事件。影像學顯示，與股骨頭壞死的局部區(qū)域相比，BMES顯示彌漫性水腫。一些研究表明BMES可能先于股骨頭壞死發(fā)生。軟骨下不全骨折軟骨下不全骨折的表現(xiàn)（與股骨頭壞死）類似，但發(fā)生在受傷后。盡管這兩種情況都呈現(xiàn)低信號軟骨下帶，但股骨頭壞死成像呈現(xiàn)平滑的凹線，而骨折則呈現(xiàn)鋸齒狀、不連續(xù)的凸面。保守治療不太可能改善骨折癥狀，并且這兩種情況都可能發(fā)展到需要進行全髖關節(jié)置換術(THA)。（股骨頭）腫瘤雖然罕見，但透明細胞軟骨肉瘤和軟骨母細胞瘤可在股骨頭中出現(xiàn)射線可透的病變。這些病癥不伴有股骨頭壞死或其他類似病癥（例如BMES）中出現(xiàn)的水腫。分類系統(tǒng)和分期最流行的股骨頭壞死分期系統(tǒng)是Ficat分期。Ficat系統(tǒng)于1964年開發(fā)，后來進行了修改，包括使用MRI，根據(jù)平片上的表現(xiàn)將股骨頭壞死患者分為0至4期。盡管該系統(tǒng)被廣泛接受并經(jīng)常使用，但批評者認為其局限性在于使用臨床癥狀、觀察者間一致性較低和缺乏預測（效力）。賓夕法尼亞大學開發(fā)該系統(tǒng)的目的是為了更清楚地描述股骨頭壞死的進展，并通過為放射學前疾病添加0期，根據(jù)新月征的不存在(II)或存在(III)將FicatII期分為兩個階段，并將FicatIV期分為兩個階段：扁平化，關節(jié)間隙變窄，從而促進各階段之間的區(qū)別僅(V)以及關節(jié)畸形和關節(jié)間隙閉塞(VI)。骨循環(huán)研究協(xié)會(ARCO)系統(tǒng)與Ficat密切相關，但將MRI結果納入I期并根據(jù)關節(jié)間隙的程度劃分II期。股骨頭變平（如果＜2毫米則為IIIA，如果＞2毫米則為IIIB）。ARCO系統(tǒng)最近根據(jù)國際專家工作組進行了修訂，以更好地結合MRI和X線片的結果。對不同分期系統(tǒng)的系統(tǒng)分析發(fā)現(xiàn)，任何分類系統(tǒng)對于股骨頭壞死分期都是有價值且充分的，只要收集必要的數(shù)據(jù)以允許轉換為另一個指標。為了患者評估和治療的目的，最重要的分類是塌陷前與塌陷前股骨頭碎裂，因為這是指導保守治療與髖關節(jié)置換術(THA)的依據(jù)。出于研究目的（特別是收集注冊數(shù)據(jù)），我們建議使用更新的ARCO指南，因為它們有效地使用多種成像模式并描繪階段之間較小的變化。這可以更詳細地跟蹤疾病進展，并且可能有助于提供更清晰的答案，因為新療法的有效性得到了評估。治療方案進展風險評估進展風險對于確定適當?shù)闹委熯x擇很重要。盡管對于明確預測塌陷的系統(tǒng)尚未達成共識，但對嘗試策略的審查發(fā)現(xiàn)，病變體積增加、壞死＞40%的承重表面以及壞死弧度＞200至250度提示未來的塌陷。觀察最保守的治療方法——觀察——被認為是治療股骨頭壞死的一種可能方法。有一些證據(jù)表明小的早期股骨頭壞死病變可自行消退。與觀察相結合，通常建議限制負重，盡管這尚未顯示出作為主要治療方式的實用性。一項將觀察作為策略的研究發(fā)現(xiàn)，股骨頭壞死四年內(nèi)的失敗率超過80%，不建議作為晚期病變的獨立治療方法。非手術治療藥物一直是股骨頭壞死治療的主要手段，但最近其有效性受到質疑。二磷酸鹽是藥物治療的熱門選擇，通過抑制破骨細胞活性發(fā)揮作用。關于二磷酸鹽使用的研究顯示了不同的結果。盡管一些早期研究表明二磷酸鹽具有積極作用，但最近的一項大型多中心隨機對照試驗發(fā)現(xiàn)阿侖膦酸鈉和安慰劑之間沒有差異。此外，對5項隨機對照試驗的薈萃分析顯示，類似的發(fā)現(xiàn)，幾乎沒有證據(jù)支持二磷酸鹽的功效。二磷酸鹽的主要用途是在疾病的早期階段，隨著股骨頭壞死的進展，二磷酸鹽并不優(yōu)于手術。研究已確定他汀類藥物在延緩股骨頭壞死方面發(fā)揮有益作用的多種潛在機制，包括降脂作用、增加自噬、抑制過氧化物酶體增殖物激活受體γ以及激活Wnt信號通路。他汀類藥物與多種藥物聯(lián)合使用可有效發(fā)揮作用。髓心減壓（CD）手術，可以改善股骨頭壞死的臨床和放射學進展。其他非手術方式已經(jīng)提出了其他幾種治療股骨頭壞死的方式，并取得了不同程度的成功。飲食改變或硫辛酸補充劑等脂質調(diào)節(jié)劑在試驗中顯示出一些積極的結果，但沒有足夠的證據(jù)推薦它們作為主要治療策略。高壓氧治療、脈沖電磁場和體外沖擊波療法已獲得一些積極的成果，但對其有效性的分歧使得它們難以推薦。保髖手術治療髓心減壓CD用于治療股骨頭壞死，以降低骨內(nèi)壓，促進血流增加和骨生成。Ficat在他對股骨頭壞死和髓心減壓CD手術的早期描述中指出，髓內(nèi)壓力增加，髓心減壓CD釋放髓內(nèi)壓力，如果在病變進展早期得到治療，可以緩解疼痛并最終恢復血流。盡管早期的髓心減壓CD研究對其有效性尚不明確，但最近的研究顯示出顯著的益處。對短期和長期結果的研究表明，與更保守的治療方案相比，接受髓心減壓CD治療的患者有所改善，并且延遲了全髖關節(jié)置換術(THA)時間。與許多治療一樣，在疾病早期階段使用時，這些結果更為積極。高達100%的髖關節(jié)存活3年，高達96%的早期疾病存活10年。更準確地說，髓心減壓CD在股骨頭壞死方面顯示出積極的結果，顯示無塌陷、中央病變和小尺寸（合并壞死）角度＜250°。當與移植物和細胞治療相結合時，這些結果可能會更加有益。血管化和非血管化骨移植非血管化骨移植涉及放置骨移植材料以提供結構支撐，目的是降低骨內(nèi)壓力并防止股骨頭壞死早期階段的塌陷。血管化骨移植（VBG）還尋求增加血液供應。通過將來自髂骨、脛骨或腓骨的非血管化同種異體皮質移植物或來自髂嵴、腓骨或大轉子的血管化移植物放置到為手術或髓心減壓CD手術創(chuàng)建的髓心空間中來完成移植。無血管化骨移植已顯示出一定的成功率，特別是對于較小的病變，在多項研究中，經(jīng)過2至9年的隨訪，成功率為55%至87%。血管化骨移植（VBG）顯示（在塌陷前病變中）5年髖關節(jié)存活率為80%或14年后類似患者中的60%，需要全髖關節(jié)置換術(THA)的比例較低。然而，血管化骨移植（VBG）的益處主要在沒有明顯塌陷的較小病變中實現(xiàn)。正在進行的研究評估了使用或不使用生物因子的合成支架增強整合和骨骼生長。盡管尚未找到明確的解決方案，但許多有機、無機和生物材料的開發(fā)前景廣闊。輔助治療由于股骨頭壞死被認為是由骨再生缺陷引起的，因此有人建議使用干細胞治療來阻止或逆轉其發(fā)病機制。研究表明，接受自體干細胞移植治療的患者放射學進展率較低，全髖關節(jié)置換術(THA)需求也較低。在早期研究中，自體干細胞移植與髓心減壓CD相結合顯示，股骨頭塌陷時間平均延遲了10年（最多17年）。此外，細胞療法可以與髓心減壓CD等其他療法相結合。一項研究表明，除了同種異體移植物和/或骨移植物之外，骨形態(tài)發(fā)生蛋白(BMP)在改善骨形成和限制股骨頭壞死進展方面也有益處。保髖截骨術截骨術是通過減輕壞死或壞死前區(qū)域的負重來延緩股骨頭壞死的進展，以防止塌陷。為此，將承重的股骨頭壞死區(qū)域傾斜或旋轉，以將主要壓力施加在股骨頭非壞死區(qū)域上。股骨頭旋轉截骨術（3至15年期間的成功率為82%至100%）和（內(nèi)外翻、前伸后屈）成角截骨術（6至18年期間的成功率為82%至98%）顯示出極高的成功率。然而，如果有必要的話，未來的全髖關節(jié)置換術(THA)可能會在截骨術后變得困難。帳篷植入和改變的解剖結構.69髖關節(jié)置換術髖關節(jié)表面置換術對于晚期股骨頭壞死來說，髖關節(jié)表面置換是最簡單的選擇，涉及用人造材料替換關節(jié)表面以保留自然解剖結構。然而，由于材料引起的并發(fā)癥以及可能導致股骨頭壞死進展，表面置換不再用作股骨頭壞死的治療方法。全髖關節(jié)置換術全髖關節(jié)置換術是目前治療股骨頭壞死的唯一有效方法。然而，潛在的缺點需要仔細考慮。全髖關節(jié)置換術并不是永久的解決方案，盡管它們可能有利于老年患者盡早減少累積手術，但大多數(shù)股骨頭壞死患者相對年輕。鑒于這一人群，如果在診斷時更換關節(jié)，患者在以后的生活中可能需要再次進行髖關節(jié)置換術或翻修術。髖關節(jié)置換術的建議包括晚期疾病、持續(xù)進展和持續(xù)的誘發(fā)因素。盡管因股骨頭壞死而接受全髖關節(jié)置換術(THA)的患者比因骨關節(jié)炎接受全髖關節(jié)置換術(THA)的患者有更多的合并癥和更復雜的住院時間，但長期隨訪顯示出相似的結果：兩組之間的假體存活率、骨長入和無菌性松動等并發(fā)癥無明顯差異。然而，其他研究表明，與髖骨關節(jié)炎OA患者相比，接受全髖關節(jié)置換術(THA)的股骨頭壞死患者敗血癥、輸血需求和再入院率增加。最近的分析顯示，結果有所改善，超過90%的股骨頭壞死全髖關節(jié)置換術(THA)存活4至7年，而1990年之前的存活率為8%至37%，這可能是由于手術中使用的植入物和材料的改進。文獻在檢查病因方面有限。值得注意的是，對需要進行全髖關節(jié)置換術(THA)的股骨頭壞死患者的研究發(fā)現(xiàn)，46.6%的患者將繼續(xù)接受全髖關節(jié)置換術(THA)治療。需要對側全髖關節(jié)置換術(THA)，特別是如果對側髖關節(jié)在第一次全髖關節(jié)置換術(THA)時有股骨頭壞死的影像學證據(jù)，表明需要密切隨訪?？偨Y股骨頭壞死仍然是一種病因、治療和發(fā)育特征存在廣泛差異的疾病。由于發(fā)病率持續(xù)上升，因此有必要加強對病理生理學的了解，以促進新療法和正確治療方案的發(fā)展。盡管骨移植和干細胞治療等領域正在取得有希望的發(fā)展，但該領域仍然缺乏一致意見的治療方案，來為股骨頭壞死患者提供最高的生活質量并延緩他們發(fā)展為衰弱性損傷、股骨頭塌陷或髖關節(jié)置換術。為了更有效地了解這種疾病過程，需要更多數(shù)據(jù)。國家登記處將是確定診斷和治療方向的最完整的系統(tǒng)。在缺乏這種協(xié)調(diào)努力的情況下，機構登記和大型隊列研究將有助于在這一領域取得進展。在治療領域，有許多潛在的改進途徑。骨修復方面的有前景的進步（例如合成代謝藥物）可能在促進愈合中發(fā)揮作用。此外，針對同時發(fā)生的情況進行更有針對性的治療可能會減少類固醇和化療引起的股骨頭壞死的繼發(fā)性發(fā)展。隨著對病因、預防和治療的廣泛研究，我們有理由期望在減輕這種疾病的負擔方面取得進展。OsteonecrosisoftheFemoralHeadAbstractOsteonecrosisofthefemoralheadisaprogressiveanddebilitatingconditionwithawidevarietyofetiologiesincludingtrauma,steroiduse,andalcoholintake.DiagnosisandstagingarebasedonimagingincludingMRIatanystageandplainradiographyinmoreadvancedlesions.Theonlydefinitivetreatmentistotalhiparthroplasty,althoughnumeroustreatmentsincludingdisphosphonatesandcoredecompressionareusedtodelaytheprogression.Lackofsatisfactoryconservativemeasuressuggeststheneedforadditionalresearchofosteonecrosisincludinglargepatientregistriestofurtherunderstandthiscondition.Osteonecrosisisaprogressivedisorderinwhichlackofsufficientbloodsupplyleadstocelldeath,fracture,andcollapseoftheaffectedarea.Theconditionisfrequentlyassociatedwiththefemoralhead,whereprogressioncanbedebilitatingandcanultimatelynecessitatetotalhiparthroplasty(THA).Theetiologyofosteonecrosisiscomplexwithnumerouscontributingagents,mostmarkedlytrauma,steroiduse,andalcohol.Treatmentofosteonecrosisiscontroversialbecausenooptionhasbeenoverwhelminglyembraced,andlittleresearchhascomparedtreatments.Researchersestimatetotalhiparthroplasty(THA)t20,000newcasesofosteonecrosisarediagnosedintheUnitedStateseachyear.1Theincreasingincidenceanddebilitatingprogressionofosteonecrosissuggesttheneedforadditionalinvestigationofeffectiveandnoveltreatments,aswellastheneedforclearerunderstandingofavailabletreatments.Thisreviewcharacterizesthecurrentknowledgeonetiology,pathophysiology,epidemiology,andclinicalmanagementofosteonecrosis,withanemphasisonrecentdevelopments.EpidemiologyTheincidenceofosteonecrosisintheUnitedStateshasbeenestimatedat～20000to30000casesperyear,affectingprimarilyyoungadultsbetweentheagesof20to40years.1Recentanalysishasshowntotalhiparthroplasty(THA)talthoughthenumberoftotalhiparthroplasty(THA)sdoneforosteonecrosishasincreasedbetween2001and2010(from54.2per100,000hospitaladmissionto60.6per100,000hospitaladmission),thepercentageoftotalhiparthroplasty(THA)sdoneforosteonecrosishasdecreasedfrom9.7%to8.3%,likelybecauseoftherapidincreaseinosteoarthritisnecessitatingtotalhiparthroplasty(THA).2PathophysiologyandPathogenesisGeneralPathogenesisOsteonecrosisoccursbecauseofcompromisedbloodfloworoxygendeliverytothebone,althoughtheclinicalpresentationisaresultoftherepairprocess,rathertotalhiparthroplasty(THA)ninitialischemia.Inosteonecrosis,boneformationbyosteoblastsisunabletomatchboneresorptionbyosteoclasts.Thisremodelingimbalancedoesnotadequatelyreplacethenecroticbone,leavingaregionofstructurallyunsoundbonetissues.3TraumaTraumaisthemostcommoncauseofosteonecrosis,4disruptingbloodflowandleadingtoosteocytedeath.Estimatesofoccurrenceoftraumaticosteonecrosisofthefemoralheadvarydependingontheinjurytype5;however,inmeta-analysisoftraumaticosteonecrosis,incidencehasbeenfoundtobeashighas14.3%.6TheGardenclassificationcategorizesfemoralneckfracturesandcanbeusedtoestimatetheriskofosteonecrosis.GardenI(incompletefracture)andGardenII(completeandnondisplaced)areconsideredstableandlowrisk,andcanberepairedwithinternalfixation.GardenIII(completeandpartiallydisplaced)andGardenIV(completeandcompletelydisplaced)havemuchhigherratesofosteonecrosiswithinternalfixation(16%),andarthroplastyshouldbeconsidered.7Intertrochanterichipfracturesresultinalowriskofosteonecrosis,notedat0.95%aftera1-yearfollow-up.8AtraumaticOsteonecrosisAtraumaticosteonecrosisencompassesadiversearrayofcauses.Itisimportanttonotetotalhiparthroplasty(THA)tinatraumaticosteonecrosis,diseaseisfrequentlybilateralowingtosystemicriskfactors,withsomeestimatessuggestingashighas70%ofthepatientswithunilateralosteonecrosisdevelopingdiseaseinthecontralateralhip.9,10Thereasonsforthesparingofonehipinthepresenceofasystemicriskfactorarenotwellstudiedandmaybebecauseofsubclinicalpresentation,differencesinwearpatternsbetweenhips,underinvestigationofsymptoms,orlackofcoordinatedfollow-up.GlucocorticoidsSteroiduseisthesecondmostcommoncauseofosteonecrosis.11,12Severalpotentialmechanismshavebeenproposedforthisassociation,includingbonematrixandcartilagedegeneration,inducedstemcellabnormalities,changesinlipidmetabolism,creationoffatemboli,alteredcoagulation,andchangesinbloodsupply.11,12Meta-analysisfoundupto10timesincreasedriskofpatientsonhigh-dosecorticosteroids,adoublingofriskforosteonecrosiswhenthecumulativedoseexceeds10g,anda0%increaseinriskwitheach10mgincreaseofdailydose.13Corticosteroidshavealsobeenimplicatedinosteoblastdeathanddecreasedosteoblastproliferation,impairingtheabilitytorepairandreplacenecroticlesions.11AlcoholAlcoholishypothesizedtoactthroughalteredlipidmetabolismandincreasedadipogenesis.14Itishypothesizedtotalhiparthroplasty(THA)tincreasedgenerationoflipidsincreasestheriskforfatembolileadingtovascularocclusion.Inaddition,increasedserumlipidscancausepackingofthemarrow,increasingintraosseouspressureanddecreasingbloodflow.5,12Alcoholmayalsocontributetoosteocytedeath.5Astudyhasalsoshownincreasedcortisollevelsinpatientswithalcohol-inducedosteonecrosiscomparedwithidiopathicosteonecrosiscontrolsubjects,suggestingtotalhiparthroplasty(THA)talcohol-inducedosteonecrosismayactthroughthesteroidpathway.15Previousestimatesnotedan11timeshigherriskofosteonecrosisinconsumersof＞400mLofalcoholdaily.16HyperlipidemiaHyperlipidemiaisthoughttodecreasethebloodsupplytoaffectedregionsbyincreasingintraosseouspressureandproducingfatemboli.4Onestudyoflow-energyfemoralneckfracturesintheelderlyfoundhigherbloodlipidabnormalitiesinthosewhodevelopedosteonecrosistotalhiparthroplasty(THA)nthosewhodidnot.17Astudyofpatientswithacutelymphoblasticleukemia(ALL)identifiedhyperlipidemiaasariskfactorfordevelopingosteonecrosis.18Asimilarstudyfoundassociationwithosteonecrosisdevelopmentinpatientswithhyperlipidemiaandsystemiclupuserythematosus(SLE).19SystemicLupusErythematosusTheassociationofSLEwithosteonecrosisisrelatedtofrequentcorticosteroidtreatment;however,recentanalysishasshownhigherincidenceofosteonecrosisincorticosteroiduserswithSLEtotalhiparthroplasty(THA)nincorticosteroiduserswithoutSLE,suggestingsynergisticeffects.20Meta-analysisofSLEstudieshasidentifiednumerousnoncorticosteroidriskfactorsinSLE,notablyrenalinvolvementandcentralnervoussystem(CNS)disease.21,22Mixeddatasuggesttotalhiparthroplasty(THA)ttheprothromboticeffectsofantiphospholipidantibodiesplayaroleinosteonecrosisdevelopmentinSLE.Recentmeta-analysisofchildhood-onsetSLEfoundnotableosteonecrosisassociation,withestimatestotalhiparthroplasty(THA)t6to8.4%ofthepatientswithchildhood-onsetSLEdeveloposteonecrosis,23althoughmostdidnotdeveloposteonecrosisuntilafterpuberty.21SickleCellDiseaseStudiesoftheassociationbetweensicklecelldiseaseandosteonecrosishaveidentified2to4.5casesofosteonecrosisper100patientswithsicklecelldisease.24PrecipitationofhemoglobinSinlow-oxygenenvironmentsmayleadtovaso-occlusionandischemiaofthebone,whichissimilartothedevelopmentofothervaso-occlusiveinjuryinsicklecelldisease.5Arecentstudysupportsthistheory,citingelevatedhemoglobinlevelsasariskfactorforosteonecrosisinpatientswithsicklecelldiseaseandsuggestingtotalhiparthroplasty(THA)tvaso-occlusion,highbloodviscosity,hypoxia,andconcurrentalpha-totalhiparthroplasty(THA)lassemiacontributetoosteonecrosis.25GaucherDiseaseArecentevaluationoftheGaucherRegistryestimatedtheincidenceofosteonecrosisat30%.26Gaucherdiseasemayactthroughasimilarpathtototalhiparthroplasty(THA)tofsicklecelldisease,withGaucher-affectedcellsobstructingthebloodflow27orbyincreasingintraosseouspressurebecausetheyaccumulateinthefattymarrow.3Inaddition,Gauchercellscanreleaseosteoclast-activatingcytokineswhichdisruptthebalanceofboneformationandresorption.26Enzymereplacementcanreduceordelaythesymptomsofosteonecrosis28;however,astudyhassuggestedtotalhiparthroplasty(THA)tthebonemarrowmayserveasa“sanctuarysite”forGauchercells,leavingasubsetofpatientsvulnerabletoosteonecrosisdespitetreatment.29DecompressionSicknessDecompressionsickness–relatedosteonecrosisordysbaricosteonecrosisoccursbecauseofrapiddecompressionafteranextendedperiodinahyperbaricenvironment.Rapiddecompressionformsbubblesinthebloodstreambecausedissolvednitrogencomesoutofthesolution.Thehighsolubilityofnitrogeninfattytissuesmakesthemarrowparticularlysusceptible.Multiplemechanismshavebeenproposed,includingdirectocclusionofbloodflowtothemarrowandtheincreaseinintraosseouspressurereducingeffectivebloodflow.30Arecentstudyofdiverswithmusculoskeletaldecompressionsicknessfoundevidenceofdysbaricosteonecrosisin26%ofthecases,althoughthestudywaslimitedbytherelativerarityofthiscondition.31AcuteLymphoblasticLeukemiaPatientswithALLshowanincreasedriskofosteonecrosis,withradiographicincidencereaching71.8%inprospectivestudies.32ThesinglelargestfactoridentifiedinthedevelopmentofosteonecrosisinpatientswithALLisadolescence,suggestinganeffectofALLoritstreatmentonthegrowthandremodelingofthebone.Itisalsopossibletotalhiparthroplasty(THA)ttheoccurrenceofthistimeofchangingmetabolismandgrowthmagnifiessusceptibilitytoosteonecrosis-causingdamagefromotherfactors.33Olderadults,whomakeupasmallportionofthosediagnosedwithosteonecrosis,oftenundergomodifiedtreatmentregimensandhaveworseoveralloutcomescomparedwiththeiryoungercounterparts.34Arecentstudyofchildhoodleukemiasfoundhigherincidenceofosteonecrosisinpatientstreatedwithhematopoieticstemcelltransplant(HSCT)versuschemotherapyalone(6.8%versus1.4%),suggestingtotalhiparthroplasty(THA)ttreatmentmethodsinfluenceosteonecrosisdevelopment.35Inaddition,areviewoftreatmentregimensidentifiedincreasedcumulativedoseofsteroidsasariskfactorfordevelopingosteonecrosisinchildrenwithanyhematologicmalignancy.36Areviewoftreatmentstrategiessuggestedtotalhiparthroplasty(THA)ttheuseofdiscontinuoussteroidregimensmaydecreasetheriskofosteonecrosisandnonsteroidchemotherapeuticagentssuchasmethotrexateandasparaginasemaycontributetothedevelopmentofosteonecrosis.37Onetrialofalternateweekdexametotalhiparthroplasty(THA)sonereducedtheriskofosteonecrosiscomparedwithcontinuoustreatmentinchildrenwithhigh-riskALL.38TransplantationArecentstudysuggestssteroid-mediateddevelopmentofosteonecrosisintransplantpatients,findingcumulativesteroiddosestobehigherinrenaltransplantpatientswhodevelopedosteonecrosistotalhiparthroplasty(THA)ninthosewhodidnot.Thestudyalsofoundtotalhiparthroplasty(THA)ttheincidenceofsymptomaticosteonecrosisdecreasedfrom20%tolesstotalhiparthroplasty(THA)n5%withtheintroductionofcyclosporineandadecreaseinsteroidusage.39HIVMultiplestudiesshowagrowingincidenceofosteonecrosisinpatientswithHIV,showingnearlythreetimestheriskofthegeneralpopulation.40Onerecentstudyrevealedastrongassociationbetweenhigh-activityantiretroviraltherapyanddevelopmentofosteonecrosis,althoughtheauthorscautiontotalhiparthroplasty(THA)ttheassociationdoesnotimplyapathologicrole.40Otherstudieshavefoundnoassociationbetweenosteonecrosisandantiretroviraltherapy(ART),citinginsteadassociationwithalcohol,hyperlipidemia,41orlownadirCD4counts,42althoughthemechanismisnotwellunderstood.GeneticInvolvementAlthoughfamilialvariantsofosteonecrosisandsomeassociatedgeneshavebeenfound,nosingleresponsiblegenehasbeenidentified.OnegenecandidateisamutationintypeIIcollagen,althoughnodefinitivecausalityhasbeenestablished.43ElevatedlevelsofosteoprotegerinanddecreasedexpressionofRANK/RANKligandhavebeenfoundinnecroticregionscomparedwithhealthybone,suggestingapotentialroleofosteoclast-regulatinggenes.44FactorVLeidenmutationsandprothrombinmutationshavebeenassociatedwithpatientswithosteonecrosisinmultiplestudies,43invokingapotentialroleofalteredcoagulation.Genome-wideassociationstudiesofselectedpopulationshaveidentifiedseverallociofinterest,includingclustersofvariantsnearglutamatereceptorgenesinpatientswithALL,45corticosteroid-inducedosteonecrosis,33andseverallociofunknownsignificance,whichmayberelatedtocoagulationpathways,lipidmetabolism,oralcoholdrinkingbehavior.46IdiopathicOsteonecrosisItisimportanttonotetotalhiparthroplasty(THA)tanestimated20%to40%ofosteonecrosiscasesareidiopathic.47Thishighrateofanunknowncausemaybeduetononspecificearlysymptomsandindolentcourse,whichpreventearlydiagnosis,9aswellaslackofstandardizedreportinganddatacollection,whichmayhelptoreveallittleunderstoodcausesandconnections.ClinicalManifestationsandDiagnosisDiagnosisTheearlystagesofosteonecrosisofthefemoralheadarefrequentlyasymptomaticbutmayalsopresentwithradiatingpainfromthehiporgroinandlimitedrangeofmotionofthejointonphysicalexamination.47Diagnosisofosteonecrosisisprimarilybasedonimaging,althoughexaminationandhistoryareimportanttogathersurroundingcontextandpotentialetiology.5Aplainradiographisanappropriatefirst-linemodalityforidentifyingcasesofosteonecrosis,withbenefitsincludinglowcost,highavailability,andadequatesensitivityformid-stageandlate-stagedisease.48Frontalandlateral“frog-leg”viewsarerecommendedforaccuracy.Inthecaseofearly-stagedisease,radiographymaybeinsufficienttoidentifyearlyorminimalchanges.MRIisthebenchmarkfordiagnosisofosteonecrosisbecauseofitshighsensitivityforearlysignsofonset.Supplementalimaging,includingdiffusion-weightedMRI49andgadolinium-enhancedperfusionMRI,50,51mayfurtheradvancethediagnosticcapabilitiesofMRI.PerfusionMRImayassistindistinguishingbetweenradiographicallyandsymptomaticallysimilarconditionssuchasbonemarrowedemaandsubchondralinsufficiencyfractures.52Inpediatricpatientswithdevelopmentaldysplasiaofthehip,perfusionMRIwashelpfulinidentifyingthoseatriskforosteonecrosisafterclosedreduction/spicacasting.53Inaddition,awhole-bodybonescanprovidesanoptionforpatientsatriskformultifocalosteonecrosis,suchasthosereceivingsystemiccorticosteroidsorimmunosuppressants.54DifferentialDiagnosisBoneMarrowEdemaSyndromeBonemarrowedemasyndrome(BMES)presentsassuddenpainwithoutaclearprecipitatingevent.Onimaging,BMESshowsdiffuseedemacomparedwithmorelocalizedareasinosteonecrosis.Somestudieshavesuggestedtotalhiparthroplasty(THA)tBMESmayprecedeosteonecrosis.5SubchondralInsufficiencyFractureAsubchondralinsufficiencyfracturepresentssimilarlybutoccursafteraninjury.Althoughbothconditionspresentwithlow-signalsubchondralbands,osteonecrosisimagingpresentswithasmooth,concavelinewhilethefracturepresentswithajagged,discontinuous,convexfinding.Conservativetreatmentisunlikelytoimprovefracturesymptoms,andbothconditionscanprogresstotheneedforatotalhiparthroplasty(THA).5NeoplasmAlthoughrare,clearcellchondrosarcomaandchondroblastomacanpresentwithradiolucentlesionsinthefemoralhead.TheseconditionsarenotaccompaniedbytheedemapresentinosteonecrosisorothersimilarconditionssuchasBMES.5ClassificationSystemsandStagingThemostpopularstagingsystemforosteonecrosisofthefemoralheadistheFicatclassification(Table?(Table1).1).Developedin1964andlatermodifiedtoincludetheuseofMRI,theFicatsystemclassifiespatientswithosteonecrosisasstage0to4basedontheappearanceonaplainradiograph.Althoughthissystemiswidelyacceptedandfrequentlyused,detractorscitetheuseofclinicalsymptoms,lowinterobserverconsensus,andlackofprognosticationaslimitations.55TheUniversityofPennsylvaniasystemwasdevelopedinanattempttomoreclearlydelineatetheprogressionofosteonecrosisandtopromotedistinctionsbetweenthestagesbyaddingstage0forpreradiographicdisease,dividingFicatstageIIintotwostagesbasedontheabsence(II)orpresence(III)ofacrescentsign,anddividingFicatIVintotwostages:flatteningwithjointspacenarrowingonly(V)andjointdeformityandjointspaceobliteration(VI).56TheAssociationResearchCirculationOsseous(ARCO)systemcloselyfollowsFicatwiththeexceptionoftheinclusionofMRIfindingsinstageIanddivisionofstageIIbasedontheextentoffemoralheadflattening(IIIAif＜2mmandIIIBif＞2mm).TheARCOsystemwasrecentlyrevisedbasedonaninternationalexperttaskforcetobetterincorporateresultsofbothMRIandplainradiography.57ThesestagingsystemsaresummarizedinTable?Table11.Systematicanalysisofdifferentstagingsystemsfoundtotalhiparthroplasty(THA)tanyclassificationsystemisvaluableandsufficientforthestagingofosteonecrosis,providednecessarydataarecollectedtoallowconversiontoanothermetric.58Forthepurposesofpatientevaluationandtreatment,themostimportantclassificationisprecollapseversuscollapsebecausethisguidesdiscussionofconservativetreatmentversustotalhiparthroplasty(THA).Forresearchpurposes(especiallyforthecollectionofregistrydata),werecommendusingtheupdatedARCOguidelinesbecausetheyeffectivelyusemultipleimagingmodalitiesanddelineatesmallerchangesbetweenstages.Thisallowsforahigherlevelofdetailintrackingdiseaseprogressionandmayhelptoprovidecleareranswersbecausetheeffectivenessofnewtherapiesisevaluated.TreatmentOptionsRiskofProgressionEvaluatingriskofprogressionisimportantindetermininganappropriatetreatmentchoice(Table?(Table2).2).Althoughthereisnoconsensusonasystemtodefinitivelypredictcollapse,areviewofattemptedstrategieshasfoundincreasedlesionvolume,necrosis＞40%oftheweight-bearingsurface,andnecrosisradian＞200to250tobesuggestiveoffuturecollapse.59ObservationThemostconservativemanagement,observation,hasbeenconsideredasapossibleapproachtoosteonecrosis.Therehasbeensomeevidenceforspontaneousresolutionofsmallearly-stageosteonecrosislesions.60Incombinationwithobservation,restrictedweight-bearingisusuallyadvised,althoughthishasnotshownutilityasaprimarytreatmentmodality.61Astudyofobservationasastrategyinosteonecrosisofthehiphasfoundafailurerateofover80%byfouryearsandisnotrecommendedasastandalonetreatmentinadvancedlesions.62NonsurgicalTreatmentPharmacologicAgentsMedicationshavebeenamainstayofosteonecrosistreatment,butrecently,theireffectivenesshasbeenquestioned.Disphosphonatesareapopularchoiceforpharmacologictreatmentandworkbyinhibitingosteoclastactivity.Studiesoftheuseofdisphosphonateshaveshownmixedresults.63Althoughsomeearlystudiesshowedpositiveeffectsofdisphosphonates,arecentlargemulticenterrandomizedcontrolledtrialfoundnodifferencebetweenalendronateandplacebo.64Furthermore,ameta-analysisoffiverandomizedcontrolledtrialshadsimilarfindings,withlittletonoevidencesupportingtheefficacyofdisphosphonatesinthenontraumaticosteonecrosisofthefemoralhead.65Theprimaryutilityofdisphosphonatesisintheearlystagesofdisease,andtheyarenotpreferredtosurgeryasosteonecrosisprogresses.61Studieshaveidentifiedmultiplepotentialmechanismsforbeneficialeffectsofstatinsindelayingosteonecrosisincludinglipid-loweringeffects,47increasedautophagy,66suppressionofPeroxisomeproliferator-activatedreceptorγ,andactivationoftheWntsignalingpathway.67Statinshavebeeneffectiveincombinationwithmultiplecoredecompression(CD)procedures,improvingbothclinicalandradiographicprogressionofosteonecrosis.68OtherNonsurgicalModalitiesSeveralothermodalitieshavebeenproposedforthetreatmentofosteonecrosiswithvaryingsuccess.Lipidmodifierssuchasdietarychangesorlipoicacidsupplementshaveshownsomepositiveresultsintrials,butthereisinsufficientevidencetorecommendthemasprimarytreatmentstrategies.61,63Hyperbaricoxygentreatments,pulsedelectromagneticfields,andextracorporealshockwavetherapyhavebeenproposedshowingsomepositiveoutcomes,butdisagreementabouttheireffectivenessmakesthemdifficulttorecommend.47,61,69JointPreservingProceduresCoreDecompressionCDisdoneforosteonecrosisofthefemoralheadtoreduceintraosseouspressureandpromoteincreasedbloodflowandbonegenesis.Ficat,70inhisearlydescriptionsofosteonecrosisandtheCDprocedure,notedincreasedintramedullarypressures,whicharereleasedwithCDleadingtoareliefofpainandeventualrestorationofbloodflowifthelesionistreatedearlyinitsprogression.AlthougholderstudiesofCDwereequivocalaboutitseffectiveness,studyofmorerecentprocedureshasshownnotablebenefits.Studiesofbothshort-termandlong-termoutcomeshaveshownimprovementinpatientstreatedwithCDanddelayedtimetototalhiparthroplasty(THA)comparedwithmoreconservativetreatmentoptions.71Aswithmanytreatments,theseoutcomesaremorepositivewhenusedintheearlystagesofdisease,withupto100%ofhipssurviving3years69andupto96%surviving10yearsinearly-stagedisease.71Moreprecisely,CDhasshownpositiveresultsinosteonecrosisshowingnocollapse,acentrallesion,andsmallsize(combinednecroticangle＜250°).72Theseoutcomesmayproveevenmorebeneficialwhenpairedwithgraftsandcell-basedtherapy.VascularizedandNonvascularizedBoneGraftingNonvascularizedbonegraftinginvolvestheplacementofbonegraftmaterialtoprovidestructuralsupportwiththeintentofreducingintraosseouspressureandpreventingcollapseinearlystagesofosteonecrosis.Vascularizedbonegrafting(VBG)alsoseekstointroduceincreasedbloodsupply.Thegraftisdonebyplacinganonvascularizedcorticalallograftfromtheilium,tibia,orfibula,73oravascularizedgraftfromtheiliaccrest,fibula,orgreatertrochanter74intoacorespacecreatedfortheprocedureorfromaCDprocedure.Nonvascularizedbonegraftinghasshownmoderatesuccess,especiallywithsmallerlesions,havinga55%to87%successratewitha2-to9-yearfollow-upacrossseveralstudies.69VBGhasshowna5-yearhipsurvivalof80%inprecollapselesionor60%after14yearsinsimilarpatients,69withlowconversiontototalhiparthroplasty(THA).75However,thebenefitsofVBGareprimarilyrealizedinsmallerlesionswithoutnotablecollapse.76Ongoingresearchhasevaluatedsyntheticscaffoldsusedwithorwithoutbiofactorstoenhanceintegrationandbonegrowth.Numerousorganic,inorganic,andbiologicmaterialshavebeendevelopedwithpromise,althoughnodefinitivesolutionhasbeenidentified.77AdjunctiveTherapyBecauseosteonecrosisisthoughttoresultfromadeficiencyofboneregeneration,useofstemcelltreatmentshasbeenproposedtohaltorreverseitspathogenesis.Studieshaveshownlowerratesofradiographicprogressionandlowerneedfortotalhiparthroplasty(THA)inpatientstreatedwithautologousstemcelltransplants.Inearlystudies,thecombinationofautologousstemcelltransplantwithCDshowedanotabledelayofanaverageof10years(upto17years)intimetocollapse.78Inaddition,celltherapycanbecombinedwithothertherapiessuchasCDand/orbonegraftsandcanpotentiallyimproveoutcomes.69Astudyhasshownbenefitsofbonemorphogeneticprotein(BMP)inadditiontoallograftand/orCDinimprovingboneformationandlimitingtheprogressiononosteonecrosis.79OsteotomyOsteotomyattemptstodelaytheprogressofosteonecrosisbyrelievingweight-bearingonnecroticorprenecroticareastopreventcollapse.Todothis,weight-bearingosteonecroticregionisangledorrotatedtoplaceprimarypressureonanon-necroticareaofthebone.Rotational(82%to100%from3to15years)andangular(82%to98%between6and18years)osteotomiesofthefemoralheadhaveshownexcellentsuccessrates.However,futuretotalhiparthroplasty(THA)canbecomedifficultifnecessarybecauseofpersistentimplantandalteredanatomy.69ArthroplastyResurfacingResurfacingofthejointsinquestionisthemostminimaloptionforadvancedosteonecrosisandinvolvesreplacingthearticularsurfacewithartificialmaterialstopreservenaturalanatomy.However,becauseofthecomplicationsfrommaterialsandpossiblecontributiontoosteonecrosisprogression,resurfacingisnolongerusedasosteonecrosistreatmentofthefemoralhead.69TotalJointArthroplastyJointarthroplastyistheonlydefinitivecureforosteonecrosisavailableatthistime;however,potentialdownsidesrequirecarefulconsideration.totalhiparthroplasty(THA)sarenotapermanentsolution,andalthoughtheymaybebeneficialearlyinolderpatientstoreducecumulativeprocedures,mostpatientswithosteonecrosisarerelativelyyoung.Giventhispopulation,ifthejointisreplacedatdiagnosis,thepatientwilllikelyneedanotherarthroplastyorrevisionlaterinlife.Recommendationsforjointarthroplastyincludeadvanceddisease,continuingprogression,andcontinuingprovocativefactors.77Althoughpatientswhohaveatotalhiparthroplasty(THA)forosteonecrosishavemorecomorbiditiesandmorecomplicatedhospitalstaystotalhiparthroplasty(THA)nthosehavingtotalhiparthroplasty(THA)forosteoarthritis,long-termfollow-uphasshownsimilaroutcomebetweenthetwogroupsforimplantsurvival,osseointegration,andcomplicationssuchasasepticloosening.80Otherstudies,however,haveshownincreasedratesofsepsis,81transfusionrequirement,andhospitalreadmissioninpatientswithosteonecrosiswhounderwenttotalhiparthroplasty(THA)comparedwithOApatients.Recentanalysishasshownimprovedoutcomes,with＞90%ofosteonecrosistotalhiparthroplasty(THA)ssurviving4to7yearscomparedwith8to37%survivalratesbefore1990,possiblybecauseofimprovedimplantsandmaterialsusedintheprocedures.69Theliteratureislimitedinexaminingetiology-basedimplantsurvival,butastudyofpatientswithosteonecrosissecondarytoalcoholconsumptionshowedexcellentlong-termoutcomes.82Itisalsoimportanttonotetotalhiparthroplasty(THA)tthestudyofpatientswithosteonecrosisrequiringtotalhiparthroplasty(THA)foundtotalhiparthroplasty(THA)t46.6%ofthepatientswouldgoontorequirecontralateraltotalhiparthroplasty(THA),especiallyifthecontralateralhiphadradiographicevidenceofosteonecrosisatthetimeofthefirsttotalhiparthroplasty(THA),suggestingtheneedforaclosefollow-up.83SummaryOsteonecrosiscontinuestobeaconditionofwidelyvariantetiologies,treatments,anddevelopmentalprofiles.Becauseincidencecontinuestorise,increasedunderstandingofthepathophysiologyisnecessarytopromotedevelopmentsofnewtreatmentsandcorrectiveprocedures.Althoughpromisingdevelopmentsarebeingmadeinareassuchasbonegraftingandstemcelltherapy,thefieldcontinuestolackanagreed-uponregimentoprovidepatientswithosteonecrosisthegreatestqualityoflifeanddelaytheirprogressiontodebilitatinginjury,collapse,orjointarthroplasty.Tomoreeffectivelyunderstandthisdiseaseprocess,moredataareneeded.Anationalregistrywouldbethemostcompletesystemtodeterminediagnosticandtreatmentdirections.Intheabsenceofsuchacoordinatedeffort,institutionalregistriesandlargecohortstudieswouldhelptomakeadvancesinthisrealm.Intheareaoftreatment,therearemanypotentialavenuesforimprovement.Promisingadvancementsinbonerepairsuchasanabolicagentsmayplayaroleinpromotinghealing.Inaddition,moredirectedtherapiesforcoincidentconditionsmayreducethesecondarydevelopmentofosteonecrosisfromsteroidsandchemotherapy.Withanexpandedstudyofetiologies,prevention,andtherapy,thereisareasontohopeforadvancementsinreducingtheburdenofthisdisease.文獻出處：GaryGeorge,JosephMLane.OsteonecrosisoftheFemoralHead.JAmAcadOrthopSurgGlobResRev.2022May1;6(5):e21.00176.doi:10.5435/JAAOSGlobal-D-21-00176.2023年06月18日648
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劉寧主任醫(yī)師 哈醫(yī)大一院 骨科 各位患者朋友們周末好，今天的最后一名手術呢，是一個酒精性股骨頭壞死的患者，那么現(xiàn)在正在等待麻醉，這個患者呢也比較年輕，嗯，只有50幾歲，但是啊股骨頭的壞死啊非常嚴重，那么病人右側股骨頭啊是好的，而左側的股骨頭啊已經(jīng)出現(xiàn)了明顯的塌陷變形，病人呢有長期的飲酒，那么呢，尤其是酒精的慢性的中毒也會導致股骨頭壞死的發(fā)生，而一旦發(fā)生股骨頭壞死呢，隨著你酒精攝入量的增加，那么呢，它的壞死就會逐漸的加重，也有的朋友啊問為什么病人一直在喝酒，右側的股骨頭卻沒有什么事，而左側的股骨頭呢，會出現(xiàn)一個壞死的表現(xiàn)呢？呃，這個呢，在醫(yī)學上現(xiàn)在還沒辦法完全的解釋，只因為呢，酒精啊，可能是對于左側股骨頭的一些血管的問題啊導致。 這個它的缺血的表現(xiàn)呢，更加嚴重，而右側的股骨頭的血管的供應呢，恰巧沒有被這個酒精所完全的破壞，所以右側的股骨頭得以保證了一個正常的一個血液循環(huán)，當然了，隨著科學的進步，那么總有一天也會明確，為什么有些股骨頭壞死呢是單發(fā)，而有些股骨頭壞死呢是多發(fā)。2023年02月17日126
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劉萬軍主任醫(yī)師 上海市第六人民醫(yī)院 骨科-關節(jié)外科 專家介紹：劉萬軍，主任醫(yī)師，醫(yī)學博士，研究生導師；上海交通大學醫(yī)學院附屬第六人民醫(yī)院；骨科-關節(jié)外科主任醫(yī)師，東院關節(jié)外科負責人，擅長疾?。?、髖關節(jié)置換、膝關節(jié)置換手術（股骨頭壞死、嚴重骨折手術后髖關節(jié)炎、嚴重髖關節(jié)發(fā)育不良、嚴重類風濕性髖關節(jié)炎、髖關節(jié)僵直、嚴重老年骨質增生性膝關節(jié)炎引起的關節(jié)痛）；2、髖膝關節(jié)翻劉萬軍+住院后可以立刻做髖關節(jié)手術嗎？修術；3、早期股骨頭壞死的保髖手術；4、早期膝關節(jié)骨性關節(jié)炎的保膝手術；5、關節(jié)置換術后假體感染及術后骨折；6、各類骨關節(jié)疼痛疾病的微創(chuàng)治療。2023年01月25日417
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