股骨頭壞死：再生醫(yī)學(xué)的最新研究進展與展望Regenerativemedicineforosteonecrosisofthefemoralhead:presentandfuture.作者：Gun-IlIm作者單位:ResearchInstituteforConvergenceLifeScience,DonggukUniversity,Goyang,SouthKorea.譯者：陶可（北京大學(xué)人民醫(yī)院骨關(guān)節(jié)科）骨質(zhì)自我修復(fù)的顯著例外之一是股骨頭壞死（ONFH）。在股骨頭壞死（ONFH）這種疾病中，股骨頭的血液供應(yīng)受阻和骨內(nèi)壓力增加，隨后導(dǎo)致骨細胞死亡。壞死的股骨頭無法持續(xù)自我修復(fù)，因此，微骨折會累積并發(fā)展到(股骨頭)結(jié)構(gòu)塌陷。尤其是年輕患者（20至40歲）股骨頭壞死（ONFH）的高發(fā)病率，造成了重大的治療負擔(dān)。雖然髖關(guān)節(jié)置換術(shù)的立竿見影的良好效果對于患者和外科醫(yī)生都有吸引力，但在較長的預(yù)期壽命中，髖關(guān)節(jié)置換術(shù)后失敗的可能性很高，因此，嘗試保留股骨頭是合理的。因此，再生醫(yī)學(xué)中的骨再生為股骨頭壞死（ONFH）的治療中找到了良好的應(yīng)用前景?？紤]到股骨頭壞死（ONFH）的發(fā)病機制與細胞死亡有關(guān)，補充可以原位制造骨骼或血管系統(tǒng)的細胞是一個很有前景的概念。髓心減壓手術(shù)去除部分壞死骨以減輕疼痛并可能治愈疾病，為在手術(shù)中添加細胞療法提供了獨特的環(huán)境，同時將額外的發(fā)病率降至最低。除了基于細胞的治療外，包括生長因子、外泌體和基因治療在內(nèi)的非細胞治療也可用于股骨頭壞死（ONFH）的骨再生。用于再生治療的細胞細胞療法在股骨頭壞死（ONFH）中的原型應(yīng)用是在髓心減壓產(chǎn)生的空腔中注射骨髓抽吸濃縮物（BMAC），以期這些細胞可以恢復(fù)壞死股骨頭中的骨小梁。多個研究小組報告了令人鼓舞的結(jié)果。然而，其他研究小組發(fā)現(xiàn)治療患者和對照患者之間沒有顯著差異?？傮w而言，由于患者數(shù)量少且隨訪時間短，大多數(shù)研究的價值相當有限。一項前瞻性雙盲試驗在五年隨訪中為骨髓抽吸濃縮物（BMAC）植入的有效性提供了更高水平的證據(jù)。隨著對干細胞的了解和表征的不斷深入，促進了這些細胞替代骨髓抽吸濃縮物（BMAC）在股骨頭壞死（ONFH）再生醫(yī)學(xué)中的應(yīng)用。在各種細胞類型中，源自骨髓的間充質(zhì)基質(zhì)/干細胞（MSC）被認為是最佳候選細胞。然而，應(yīng)用離體擴增的自體骨間充質(zhì)基質(zhì)/干細胞（MSC）是一個比使用骨髓抽吸濃縮物（BMAC）更復(fù)雜的過程。此外，它們還受到監(jiān)管機構(gòu)的控制。除少數(shù)對照研究外，大多數(shù)報告間充質(zhì)干細胞應(yīng)用的研究都是非對照病例系列。另一方面，干細胞治療股骨頭壞死（ONFH）的薈萃分析顯示，并發(fā)癥都很輕微，發(fā)生率并不顯著（2.8%）。雖然不同的應(yīng)用方法使得直接比較各個研究變得困難，但人們越來越認識到骨髓抽吸濃縮物（BMAC）或骨髓MSC(BMSC)治療在早期（FicatI或II）股骨頭壞死（ONFH）方面具有合理的（即使不是顯著）效果。緩解癥狀并防止股骨頭塌陷的進展。雖然骨髓抽吸濃縮物（BMAC）是股骨頭壞死（ONFH）最常用的干細胞類型，但脂肪干細胞(ASC)作為再生醫(yī)學(xué)的細胞來源具有多種優(yōu)勢。脂肪干細胞(ASC)比骨髓干細胞(BMSC)更容易獲得且痛苦更少。與骨髓干細胞(BMSC)相比，它們不僅在脂肪組織中含量更高，而且具有更大的增殖潛力。脂肪干細胞(ASC)還具有促進血管生成的優(yōu)勢。與自體干細胞MSC相比，同種異體干細胞MSC具有經(jīng)濟優(yōu)勢，因為同種異體細胞可以作為“現(xiàn)成”產(chǎn)品提供，盡管它們存在疾病傳播和免疫排斥的可能性。從這個意義上說，關(guān)于同種異體干細胞MSC是否適用于股骨頭壞死（ONFH）等非致命性疾病存在爭議。另一方面，考慮到來自股骨頭壞死（ONFH）患者的干細胞MSC的增殖和成骨潛力降低，來自健康供體的同種異體干細胞MSC可能對治療這些患者有效。臍帶來源的間充質(zhì)干細胞可能被證明是一個很好的候選者，因為它具有高細胞產(chǎn)量和低免疫原性。細胞的遞送在細胞治療中，出于經(jīng)濟和治療效果的考慮，以及避免因過量而可能出現(xiàn)的并發(fā)癥，需要確定植入細胞的最佳數(shù)量，該數(shù)量與藥物的劑量相當。骨髓抽吸濃縮物（BMAC）和基質(zhì)血管部分是細胞混合物，其中含有少量干細胞。此外，每種成體干細胞預(yù)計具有不同的存活和成骨潛力。根據(jù)目前報道的研究，使用的細胞數(shù)量從10∧6到10∧9個不等，最常用的劑量是10∧8個細胞。盡管如此，每種類型的細胞的最佳數(shù)量仍有待確定。細胞通常已在髓心減壓術(shù)中使用。一些研究還表明，可以通過動脈內(nèi)輸注，有效地輸送治療細胞來治療股骨頭壞死（ONFH）。然而，這些方法的普遍適用性和安全性需要進一步研究?？紤]到再生療法的高成本，只有那些表現(xiàn)出高成功機會的患者才可能適合這種形式的治療。塌陷后股骨頭壞死（ONFH）可能不適合干細胞治療，因為髓心減壓后植入骨髓抽吸濃縮物（BMAC）不能獲得III期股骨頭壞死（ONFH）臨床過程的任何改善。因此，只有早期（I期或II期）患者才可以考慮采用這種治療形式。此外，據(jù)報道，創(chuàng)傷后股骨頭壞死（ONFH）患者的預(yù)后優(yōu)于非創(chuàng)傷性股骨頭壞死（ONFH）患者，這表明，與局部原因相比，患有全身性原因的髖關(guān)節(jié)對再生醫(yī)學(xué)的反應(yīng)較差。此外，研究發(fā)現(xiàn)，病灶尺寸較小的患者可能會取得更好的效果，不進行附加細胞治療的髓心減壓也是如此。因此，塌陷前期、(壞死面積)尺寸較小、可能患有外傷性股骨頭壞死（ONFH）的髖關(guān)節(jié)更適合再生治療。最近一項使用自體骨髓抽吸濃縮物（BMAC）的研究報告稱，植入后三個月，塌陷進展的平均殘留病灶體積為10%（標準差6%）。安全性是細胞療法應(yīng)用中的關(guān)鍵問題之一。干細胞的關(guān)鍵特征，如自我復(fù)制、長壽命和多分化，也是癌細胞所共有的。這意味著干細胞可以發(fā)生惡性轉(zhuǎn)化，這對干細胞植入的安全性構(gòu)成了關(guān)鍵障礙。免疫排斥也會限制同種異體干細胞治療股骨頭壞死（ONFH）的臨床應(yīng)用。然而，目前的文獻表明，干細胞植入治療股骨頭壞死（ONFH）沒有出現(xiàn)嚴重的并發(fā)癥。因此可以提出應(yīng)用干細胞治療股骨頭壞死（ONFH）是相對安全的。盡管如此，仍需要更長時間的隨訪結(jié)果來確保其安全性。由于體外細胞擴增過程是必要的，整個過程必須受到控制和標準化，以便細胞保留其表型和功能潛力，并避免可能的微生物污染。迄今為止，股骨頭壞死（ONFH）干細胞治療中未被注意到和未表征的一個方面是植入細胞的體內(nèi)命運。盡管干細胞被植入的目的是希望它們能移植到受體區(qū)域并分化成成骨細胞，但植入的細胞是否能在該部位存活尚未得到研究。如果沒有足夠的血管供應(yīng)，這些細胞就會缺氧、低血糖、缺乏營養(yǎng)和代謝廢物堆積。在股骨頭壞死（ONFH）中，受體部位的血管供應(yīng)不足可能導(dǎo)致局部微環(huán)境不適合干細胞的生存。這些情況可能是對照研究中干細胞植入結(jié)果不令人滿意的原因。大多數(shù)植入的細胞可能會在短時間內(nèi)經(jīng)歷大量細胞死亡，在死亡前發(fā)揮一定程度的旁分泌作用。因此，如果要促進植入細胞的存活和植入，使這些細胞成為成骨細胞并在植入?yún)^(qū)域內(nèi)再生骨，則需要采取增強措施來增強植入細胞的血管生成潛力。其他方法如基因治療和外泌體也已被探索。治療基因的基因轉(zhuǎn)移可用于增強間充質(zhì)干細胞的治療效率。骨形態(tài)發(fā)生蛋白-2(BMP-2)、血管內(nèi)皮生長因子(VEGF)、堿性成纖維細胞生長因子(bFGF)和血小板衍生生長因子(PDGF)是可轉(zhuǎn)移以促進間充質(zhì)干細胞骨形成和血管生成特性的候選基因。由于主要使用病毒載體的基因轉(zhuǎn)移技術(shù)，使細胞治療的安全性問題進一步復(fù)雜化，基因修飾的間充質(zhì)干細胞尚未應(yīng)用于治療股骨頭壞死（ONFH）患者。由于基因修飾間充質(zhì)干細胞的所有數(shù)據(jù)均來自動物實驗，其在患者中的有效性和安全性目前尚不清楚，有待臨床試驗評估。生長因子可以直接植入病變部位以增強成骨和血管生成。然而，生長因子的直接植入因肽療法的實際問題而變得復(fù)雜，例如半衰期極短以及全身或高劑量給藥的副作用。因此，載體材料的組合使用對于實現(xiàn)生長因子的控制釋放和實際應(yīng)用是必要的。重組骨形態(tài)發(fā)生蛋白BMP和成纖維細胞生長因子2（FGF-2）已與各種載體聯(lián)合應(yīng)用于臨床。已知干細胞MSC的治療益處主要歸因于它們分泌的因子。另外，在生長因子和細胞因子的作用下，細胞通過細胞外囊泡(EV)與鄰近或遠處的細胞進行通訊，其中包括外泌體，外泌體是直徑小于150nm的細胞外囊泡(EV)。從人類干細胞MSC中分離的外泌體通過發(fā)揮增殖和抗凋亡作用以及促進血管生成，在股骨頭壞死（ONFH）大鼠模型中顯示出預(yù)防作用。許多研究報告了積極的結(jié)果。然而，目前尚不清楚再生醫(yī)學(xué)是否可以成為股骨頭壞死（ONFH）治療的規(guī)則改變者，真正改變該疾病的自然史。雖然有必要招募足夠數(shù)量的患者進行良好對照的隨機研究，來確定治療效果，但再生治療的性質(zhì)，包括成本和供體細胞特征的個體差異，使其相當難以進行。就細胞治療而言，由于從一種細胞來源觀察到的結(jié)果無法推演到另一種細胞類型，因此必須對細胞來源和類型進行精確定義。此外，區(qū)分培養(yǎng)擴增細胞和天然細胞以及自體和同種異體來源也是必要的。除了科學(xué)問題之外，監(jiān)管問題也使再生療法變得復(fù)雜。培養(yǎng)擴增細胞的植入需要大多數(shù)發(fā)達國家監(jiān)管機構(gòu)的批準，這對于同種異體或轉(zhuǎn)基因細胞更為嚴格，從而增加了細胞治療的成本。然而，由于壞死骨無法再生，年輕患者不可避免地需要進行關(guān)節(jié)置換術(shù)，因此需要進一步致力于股骨頭壞死（ONFH）再生醫(yī)學(xué)的研究和進步。???Regenerativemedicineforosteonecrosisofthefemoralhead:presentandfuture.Oneofthenotableexceptionstotheparadigmofself-healingboneisosteonecrosisofthefemoralhead(ONFH).Inthisdisease,obstructionofbloodsupplyandincreasedintraosseouspressuretothefemoralheadsubsequentlycausedeathofosteocytes.Necroticbonecannotcontinuallyrepairitself,andconsequentlymicrofracturesaccumulateandprogresstostructuralcollapse.1ThehighincidenceofONFHinyoungpatients(20to40yearsold),inparticular,createsmajortreatmentdilemmas.2Whileimmediategoodresultsofarthroplastyareappealingtobothpatientsandsurgeons,thehighchancesoffailureinthelongremaininglifespanjustifyattemptstopreservethefemoralhead.Therefore,regenerativemedicineforboneregenerationfindsagoodnicheinthetreatmentofONFH.3ConsideringthatthepathogenesisofONFHisrelatedtocelldeath,replenishingcellsthatcanmakeboneorvasculatureinsituisanappealingconcept.Coredecompressionprocedure,inwhichpartofanecroticboneisremovedtoalleviatepainandpossiblycurethedisease,providesuniquecircumstancesforaddingcelltherapytotheprocedurewithminimaladditionalmorbidity.Inadditiontocell-basedtherapy,non-cellulartherapiesincludinggrowthfactor,exosome,andgenetherapymaybeemployedtoregenerateboneinONFH.?CellsusedforregenerativetreatmentTheprototypeapplicationofacelltherapyinONFHistheinjectionofbonemarrowaspirateconcentrate(BMAC)inthecavitycreatedbycoredecompression,withaviewthatthesecellsmayrestorethetrabecularboneinthenecroticfemoralhead.3-5Encouragingresultshavebeenreportedbyseveralgroups.4-8However,othergroupshavefoundnonotabledifferencebetweentreatedpatientsandcontrolpatients.9,10Overall,thevalueofmoststudiesisratherlimitedbecauseoflownumbersofpatientsandbrieffollow-upperiods.Aprospective,double-blindedtrialhasprovidedahigherlevelofevidencefortheeffectivenessofBMACimplantationatafive-yearfollow-up.11?IncreasingknowledgeandcharacterizationofstemcellshavepromotedtheuseofthesecellsinsteadofBMACinregenerativemedicineforONFH.Amongvariouscelltypes,mesenchymalstromal/stemcells(MSCs)derivedfrombonemarrowhavebeenputforwardasthetopcandidate.12However,applicationofexvivoexpandedautologousboneMSCsisamorecomplicatedprocessthanusingBMAC.Inaddition,theyarecontrolledbyregulatoryauthorities.13MoststudiesreportingtheapplicationofMSCsareuncontrolledcaseseriesexceptforafewcontrolledstudies.Ontheotherhand,ameta-analysisofstemcelltherapyinONFHhasshownthatcomplicationsareallminorwithanunremarkablerate(2.8%).14Whileheterogeneousmethodsofapplicationmakeitdifficulttodirectlycompareindividualstudies,thereisanincreasingperceptionthatBMACorbonemarrowMSC(BMSC)treatmenthasreasonable,ifnotremarkable,effectsinearlystage(FicatIorII)ONFHintermsofsymptomaticreliefandpreventingprogressionoffemoralheadcollapse.15-17WhileBMSCisthemostusedstemcelltypeinONFH,adiposestemcells(ASCs)offerseveraladvantagesasacellsourceforregenerativemedicine.ASCsaremoreeasilyandlesspainfullyobtainedthanBMSCs.18Theyarenotonlymoreabundantinfattytissues,butalsohavegreaterproliferativepotentialcomparedwithBMSCs.19ASCsadditionallyhavetheadvantageofpromotingangiogenesis.20?AllogenicMSCshaveeconomicadvantagescomparedwithautologousMSCsbecauseallogeniccellscanbemadeavailableasan‘offtheshelf’product,althoughtheycarrythechanceofdiseasetransmissionandimmunologicalrejection.16Inthissense,thereareargumentsonwhetherallogenicMSCshouldbeappropriatefornon-lethaldiseasessuchasONFH.Ontheotherhand,consideringthattheproliferativeandosteogenicpotentialofMSCsfromONFHpatientsisreduced,21-24allogenicMSCsderivedfromhealthydonorsmightbeeffectiveintreatingthosepatients.Umbilicalcord-derivedMSCsmayprovetobeagoodcandidatebecauseofhighcellyieldandlowimmunogenicity.25?DeliveryofthecellsTheoptimalnumberofimplantedcells,whichiscomparabletothedoseofadrug,needstobedeterminedincelltherapyforthereasonofeconomyandtherapeuticeffects,aswellastoavoidpossiblecomplicationsfromoverdose.BMACandstromalvascularfractionareamixtureofcells,withasmallproportionofstemcells.Also,eachkindofadultstemcellisexpectedtohavedifferentsurvivalandosteogenicpotential.Basedoncurrentreportedstudies,thenumberofusedcellsrangesfrom106to109,andthemostfrequentlyuseddoseis108cells.6-10,26Still,theoptimalnumberremainstobedeterminedforeachtypeofcell.Cellshavemostcommonlybeendeliveredatthetimeofcoredecompression.3,6-11,26Acoupleofstudieshavealsoshownthattherapeuticcellsmaybeeffectivelydeliveredviaintra-arterialinfusiontotreatONFH.27,28However,generalapplicabilityandsafetyofthesemethodsneedfurtherinvestigation.?Giventhehighcostofregenerativetherapy,onlypatientswhowillshowahighchanceofsuccessfulresultsmaybeindicatedforthisformoftreatment.Post-collapseONFHmaynotbeindicatedforstemcelltherapy,29asimplantationofBMACaftercoredecompressioncouldnotleadtoanyimprovementintheclinicalcourseofstageIIIONFH.30Thus,onlyearly-stage(stageIorII)patientsmaybeconsideredforthisformoftreatment.Also,ithasbeenreportedthatpatientswithpost-traumaticONFHhavebetteroutcomesthanpatientswithnon-traumaticONFH,suggestingthathipswithasystemiccauseofthediseasewouldshowlessfavourableresponsetoregenerativemedicinethanthosewithlocalizedcauses.6Furthermore,ithasbeenfoundthatthosewithsmallerlesionsizesmayachievebetterresults,whichisalsothecasewithcoredecompressionwithoutadditivecelltherapy.31Therefore,hipswithpre-collapse,smallersize,probablytraumaticONFHarebettercandidatesforregenerativetherapy.ArecentstudyusingautologousBMSCsreportedthatthemeanthresholdresiduallesionvolumeforprogressionofcollapsewas10%(standarddeviation6%)atthreemonthsafterimplantation.32?Safetyisoneofthecriticalconcernsintheapplicationofcelltherapy.Keyfeaturesofstemcellssuchasself-replication,longlifespan,andmultidifferentiationarealsosharedbycancercells.Thismeansthatstemcellscanundergomalignanttransformation,whichposesakeyobstacleinthesafetyofstemcellimplantation.33ImmunerejectioncanalsolimittheclinicaluseofallogenicstemcellsforONFH.However,currentliteraturesofarshowsnoseverecomplicationsinstemcellimplantationforONFH.14,34,35Therefore,itcanbeproposedthattheapplicationofstemcellsforthetreatmentofONFHisrelativelysafe.Nevertheless,longerfollow-upresultsarestillneededtoensureitssafety.Asinvitrocellexpansionprocessisnecessary,theentireprocessmustbecontrolledandstandardizedsothatcellsmayretaintheirphenotypeandfunctionalpotential,andavoidpossiblemicrobialcontamination.33?OnehithertounheededanduncharacterizedaspectofstemcelltherapyinONFHistheinvivofateofimplantedcells.Althoughstemcellsareimplantedwiththehopethattheywillengrafttotherecipientareaandundergodifferentiationintoosteogeniccells,whetherimplantedcellswillsurviveonthesitehasnotbeeninvestigatedyet.Withoutadequatevascularsupply,thesecellswillsufferfromhypoxia,hypoglycaemia,lackofnutrients,andpilingupofwasteproducts.InONFH,thescantyvascularityattherecipientsitemayrenderthelocalmicroenvironmentunfitforthesurvivalofstemcells.Thesecircumstancesmayaccountforunsatisfactoryresultsofstemcellimplantationincontrolledstudies.Mostimplantedcellsprobablygothroughmassivecelldeathwithinashortperiodoftime,exertingadegreeofparacrineeffectbeforetheydie.Thus,ifthesurvivalandengraftmentofimplantedcellsaretobepromotedsothatthesecellsbecomeosteogeniccellsandregeneratebonewithintheimplantedarea,augmentativemeasurestoenhancetheangiogenicpotentialofimplantedcellswillbenecessary.3?Othermethodssuchasgenetherapyandexosomehavebeenexplored.GenetransferoftherapeuticgenescanbeemployedtoenhancetherapeuticefficiencyofMSCs.Bonemorphogeneticprotein-2(BMP-2),vascularendothelialgrowthfactor(VEGF),basicfibroblastgrowthfactor(bFGF),andplatelet-derivedgrowthfactors(PDGFs)arecandidategenesthatcanbetransferredtopromoteosteogenicandangiogenicpropertiesofMSCs.Asgenetransfertechniqueswhichmostlyuseviralvectorsfurthercomplicatethesafetyissueofcelltherapy,gene-modifiedMSCshavenotyetbeenappliedtotreatONFHpatients.Asalldataongene-modifiedMSCsarefromanimalexperiments,theefficiencyandsafetyinpatientsarenotpresentlyknownandawaitevaluationinclinicaltrials.36-38Growthfactorsmaybedirectlyimplantedinthelesionsitetoenhanceosteogenesisandangiogenesis.However,directimplantationofgrowthfactorsiscomplicatedbypracticalproblemsofpeptidetherapy,suchasanextremelyshorthalf-lifeandsideeffectswithsystemicorhigh-doseadministration.Thecombineduseofcarriermaterialsisthusnecessarytoenablecontrolledreleaseandpracticalapplicationofgrowthfactors.RecombinantBMPsandfibroblastgrowthfactor2(FGF-2)havebeenusedforclinicalapplicationincombinationwithvariouscarriers.39-43ThetherapeuticbenefitofMSCsisknowntobemostlyattributabletofactorstheysecrete.44Inadditiontogrowthfactorsandcytokines,cellscommunicatewithneighbouringordistantcellsviaextracellularvesicles(EVs)includingexosomes,whichareEVssmallerthan150nmindiameter.45ExosomesisolatedfromhumanMSCsshowedpreventiveeffectsinaratmodelofONFHbyexertingproliferativeandantiapoptoticeffects,46andbypromotingangiogenesis.47?Numerousstudieshavereportedpositiveresults.However,itremainsunclearwhetherregenerativemedicinecanbethegame-changerinthetreatmentofONFHthatgenuinelyaltersthenaturalhistoryofthedisease.Whilewell-controlledrandomizedstudiesrecruitingadequatenumbersofpatientsarenecessarytodefinetheplaceoftreatment,thenatureofregenerativetreatment,includingthecostandindividualdifferenceindonorcellcharacteristics,makesitratherdifficulttoperform.Inthecaseofcelltherapy,becauseanoutcomeobservedfromatypeofcellsourcecannotbeprojectedtoanothertypeofcells,precisedefinitionsofcellsourcesandtypesaremandatory.Also,distinguishingbetweenculture-expandedandnativecellsisnecessaryaswellasbetweenautologousandallogenicsources.Inadditiontoscientificconcerns,regulatoryissuescomplicateregenerativetherapies.Theimplantationofculture-expandedcellsneedsapprovalfromregulatoryagenciesinmostdevelopedcountries,whichisevenmorestrictforallogenicorgeneticallymodifiedcells,addingtothecostofcelltherapy.Nevertheless,giventhatfailuretorevitalizenecroticboneinevitablyleadstojointarthroplastyinyoungpatients,furthereffortsneedtobededicatedtotheresearchandadvancementofregenerativemedicineforONFH.?文獻出處：Gun-IlIm.Regenerativemedicineforosteonecrosisofthefemoralhead:presentandfuture.BoneJointRes.2023Jan;12(1):5-8.doi:10.1302/2046-3758.121.BJR-2022-0057.R1.

股骨頭壞死是不是很痛？可能是，也可能不是。這個65歲的老鄉(xiāng)，一瘸一拐地來找我，說左邊腹股溝痛得厲害，抬腿都不行，我一聽，十有八九髖關(guān)節(jié)有問題了。拍個片子，果然左側(cè)股骨頭壞死了。但是讓我沒有料想到的是，右側(cè)髖關(guān)節(jié)發(fā)育不良，目前股骨頭壞死和骨關(guān)節(jié)炎，而且對比左側(cè)嚴重很多，仔細問了一下，老鄉(xiāng)說右側(cè)偶然有不舒服，從來沒有嚴重的痛過。所以說，疼痛是個復(fù)雜的機制，有時候疼痛感和病程并沒有十分直接的聯(lián)系，不痛并不代表沒事，醫(yī)生也不可以掉以輕心。

非手術(shù)治療技術(shù)①保護性負重：減輕患髖負重可有效減輕疼痛，改善功能，并可能在骨壞死修復(fù)期避免股骨頭塌陷。例如使用雙拐輔助行走，不建議長時間使用輪椅；同時應(yīng)注意避免出現(xiàn)對抗性及撞擊性運動。對于病變位于股骨頭內(nèi)側(cè)及面積較?。ǎ?5%）的股骨頭壞死可考慮此方法。一般對于接受保髖手術(shù)治療的患者，建議術(shù)后拄拐3個月，根據(jù)術(shù)后復(fù)查情況逐漸脫拐。②藥物治療：常使用抑制破骨細胞功能和促進成骨細胞功能的藥物，如磷酸鹽類藥物，以及抗凝、降脂、擴張血管、促進纖溶等藥物。藥物治療可單獨應(yīng)用于治療股骨頭壞死，也可與保髖手術(shù)配合應(yīng)用。③中醫(yī)藥治療：中醫(yī)藥治療強調(diào)早期診斷、病證結(jié)合、早期治療。對高危人群及早期股骨頭壞死患者，建議給予活血化瘀、補腎健骨等中藥治療，具有促進壞死修復(fù)、預(yù)防塌陷的作用；配合保髖手術(shù)使用，可提高保髖手術(shù)效果。常用藥物有仙靈骨葆、強骨膠囊等。④物理治療：包括體外震波（亦稱為沖擊波）、電磁場、高壓氧等。手術(shù)治療股骨頭壞死進展迅速，非手術(shù)治療往往效果不佳，常需要手術(shù)治療，包括保留患者自身髖關(guān)節(jié)為主的修復(fù)重建術(shù)和人工髖關(guān)節(jié)置換術(shù)兩大類。手術(shù)的主要目的是減輕疼痛，延緩股骨頭塌陷，改善并維持髖關(guān)節(jié)功能，進而延緩甚至避免髖關(guān)節(jié)置換手術(shù)。保髖手術(shù)方法:髓芯減壓術(shù)、游離骨移植術(shù)、帶或不帶血管蒂骨移植術(shù)、截骨術(shù)等。

股骨頭壞死：基礎(chǔ)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(xué)知識)作者：MichelleJLespasio,NipunSodhi,MichaelAMont.作者單位:DepartmentofOrthopedicSurgery,BostonMedicalCenter,MA.譯者：陶可（北京大學(xué)人民醫(yī)院骨關(guān)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(yīng)暫時或永久中斷造成的。我們將討論髖關(guān)節(jié)股骨頭骨壞死的流行病學(xué)（疾病分布）、發(fā)病機制（發(fā)展機制）、病因（相關(guān)危險因素、原因和疾?。?、臨床表現(xiàn)（報告的癥狀和查體結(jié)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(guān)。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(xué)家Figure1Left,radiographofahealthyhipjoint.Right,radiographofahipjointwheretheosteonecrosishasprogressedtocollapseofthefemoralhead.圖1左圖是健康髖關(guān)節(jié)的X線片；右圖是髖關(guān)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(guān)節(jié)（第一階段）發(fā)展到股骨頭塌陷(并骨關(guān)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(guān)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(guān)節(jié)股骨頭壞死(ON)的流行病學(xué)、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(dǎo)致成熟骨細胞死亡的疾病和危險因素有關(guān)，從而導(dǎo)致骨破壞（例如塌陷）或終末期髖關(guān)節(jié)骨關(guān)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(guān)節(jié)、肩關(guān)節(jié)和腳踝關(guān)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(guān)節(jié)。當最初在髖關(guān)節(jié)以外的區(qū)域進行診斷時，應(yīng)同時對髖關(guān)節(jié)進行臨床評估以及放射線和其他影像學(xué)研究。股骨頭壞死(ON)的原因分為外傷性（與損傷相關(guān)）或非外傷性（與損傷無關(guān)）。準確診斷和分類股骨頭壞死(ON)對于幫助指導(dǎo)治療選擇非常重要。識別相關(guān)風(fēng)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(guān)危險因素、藥物管理和/或手術(shù)，包括關(guān)節(jié)保留手術(shù)和全髖關(guān)節(jié)置換術(shù)(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(guān)節(jié)股骨頭壞死的流行病學(xué)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(guān)合并癥而異。例如，與酒精相關(guān)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(guān)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(guān)節(jié)股骨頭壞死需要住院治療。在許多病例中，雙側(cè)髖關(guān)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(guān)節(jié)股骨頭骨壞死的發(fā)病機制/假說髖關(guān)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(yīng)的局部因素（包括血管損傷、骨內(nèi)壓升高和機械應(yīng)力）綜合作用的結(jié)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(yīng)，導(dǎo)致骨細胞（成熟骨內(nèi)的細胞）和/或間充質(zhì)細胞（形成軟骨、骨和脂肪的干細胞）死亡。結(jié)果是死亡組織脫礦質(zhì)或被新的但較弱的骨組織吸收（小梁變?。?，隨后導(dǎo)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(zhì)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(zhì)激素相關(guān)的股骨頭壞死(ON)涉及循環(huán)脂質(zhì)的變化，可能會在供應(yīng)骨的動脈中引起微栓子。髖關(guān)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(jié)合可直接導(dǎo)致股骨頭骨壞死。在縱向隊列研究和薈萃分析的基礎(chǔ)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(guān)風(fēng)險因素是與股骨頭壞死(ON)最終進展(直接)相關(guān)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(guān)）。股骨頸骨折或脫位的機制是骨外血管受損，導(dǎo)致髖關(guān)節(jié)受影響區(qū)域的血液供應(yīng)中斷。髖關(guān)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(guān)股骨頭壞死(ON)患者。沉箱?。ɡ鐫撍疁p壓）會導(dǎo)致氮氣氣泡的形成，從而阻塞小動脈，導(dǎo)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(guān)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(zhì)類固醇激素與股骨頭壞死(ON)的發(fā)生相關(guān)，可能與藥物的持續(xù)時間和總劑量直接相關(guān)。長期使用高劑量糖皮質(zhì)激素治療的患者似乎處于發(fā)生股骨頭壞死(ON)的最大風(fēng)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(zhì)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(zhì)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(fēng)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(guān)。與股骨頭壞死(ON)相關(guān)的過量飲酒被認為是由于脂質(zhì)形成過多和細胞內(nèi)脂質(zhì)沉積增加導(dǎo)致骨生成減少所致，導(dǎo)致骨細胞死亡和股骨頭壞死(ON)。高劑量皮質(zhì)類固醇激素和過量飲酒共同構(gòu)成了髖關(guān)節(jié)股骨頭壞死(ON)發(fā)展的最高相關(guān)直接危險因素，并且占與創(chuàng)傷無關(guān)的病例的80%以上。一項研究比較了112名患有特發(fā)性髖關(guān)節(jié)股骨頭壞死(ON)患者與168名對照者(沒有全身性皮質(zhì)類固醇激素使用史)，與對照者相比，經(jīng)常飲酒者的風(fēng)險升高，并且與酒精存在明顯的劑量反應(yīng)關(guān)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(fēng)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(dǎo)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(dǎo)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(zhì)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?。ㄒ环N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(yīng)。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(zhì)）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(guān)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(fēng)險。胰腺炎（通常與使用皮質(zhì)類固醇激素有關(guān)）、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(dǎo)致交感神經(jīng)纖維數(shù)量減少的炎癥反應(yīng)（如類風(fēng)濕性關(guān)節(jié)炎、克羅恩?。?、夏科足和炎癥性腸?。?，與股骨頭壞死(ON)相關(guān)。有一些證據(jù)表明股骨頭壞死(ON)可能具有相關(guān)風(fēng)險因素的遺傳基礎(chǔ)。例如，當過度飲酒是相關(guān)風(fēng)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(zhì)類固醇激素的使用成為相關(guān)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(guān)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(fēng)、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(guān)。盡管存在許多可能的關(guān)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(guān)節(jié)股骨頭骨壞死的臨床表現(xiàn)髖關(guān)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(guān)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(guān)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(dǎo)致受影響關(guān)節(jié)的活動范圍減小、行走疼痛、Trendelenburg征和/或骨摩擦音。髖關(guān)節(jié)股骨頭骨壞死的臨床評估髖關(guān)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(xué)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(yīng)針對評估疼痛史、藥物使用（尤其是皮質(zhì)類固醇）、手術(shù)、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?。⑽鼰熀?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(guān)的傷害，因為沉箱病是非創(chuàng)傷性的。髖關(guān)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(guān)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(xué)檢查結(jié)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(shù)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(quán)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(quán)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(dǎo)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(xué)檢查結(jié)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(jié)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(cè)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(guān)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(guān)鍵放射學(xué)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(cè)股骨頭壞死的X線片表現(xiàn)：雙線征，承重區(qū)右側(cè)髖關(guān)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(dān)。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(guān)節(jié)股骨頭骨壞死的鑒別診斷由于有癥狀的髖關(guān)節(jié)股骨頭壞死(ON)患者可能會出現(xiàn)與許多其他髖關(guān)節(jié)病變類似的癥狀，因此在最終診斷之前應(yīng)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(guān)的病因創(chuàng)傷相關(guān)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?。鈮菏д{(diào)）戈謝病輻射非創(chuàng)傷相關(guān)的危險因素皮質(zhì)類固醇激素飲酒系統(tǒng)性紅斑狼瘡庫欣病皮質(zhì)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(fēng)艾滋病病毒感染其他潛在風(fēng)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(zhì)減少，可能單獨發(fā)生或與損傷相關(guān)，特別是那些導(dǎo)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(zhì)減少是復(fù)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(shù)語）的特征。骨髓水腫綜合征可根據(jù)組織學(xué)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(zhì)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(guān)節(jié)股骨頭骨壞死的臨床治療在制定針對癥狀性髖關(guān)節(jié)骨關(guān)節(jié)炎的最佳治療方法時要考慮的因素應(yīng)旨在治療骨關(guān)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(guān)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(zhì)量問題。處理髖關(guān)節(jié)股骨頭壞死(ON)的三種主要治療選擇包括1)非手術(shù)治療、2)關(guān)節(jié)保留手術(shù)和3)全髖關(guān)節(jié)置換術(shù)THA。非創(chuàng)傷性原因引起的髖關(guān)節(jié)股骨頭壞死(ON)的影響引起了特別關(guān)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(guān)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(dǎo)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(guān)節(jié)置換的手術(shù)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(zhì)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(yīng)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(shù)治療；15%至30%之間的病變應(yīng)進行手術(shù)治療；盡管進行了手術(shù)干預(yù)，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(guān)節(jié)置換術(shù)THA。髖關(guān)節(jié)股骨頭骨壞死的非手術(shù)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(guān)節(jié)骨性關(guān)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(guān)節(jié)需要全髖關(guān)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(guān)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(shù)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(shù)選擇髓心減壓髓心減壓是一種微創(chuàng)手術(shù)技術(shù)，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(shù)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(shù)的患者通常會在幾個月后恢復(fù)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(jié)合，幫助再生健康的骨骼并支撐髖關(guān)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(shù)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(shù)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(shù)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(guān)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(guān)節(jié)中有24個（80%）取得了成功的結(jié)果（定義為Harris髖關(guān)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(jié)果。晚期股骨頭壞死(ON)的手術(shù)選擇血管化骨移植血管化腓骨移植是一種更為復(fù)雜的外科手術(shù)，其中從腓骨及其血液供應(yīng)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(shù)髖關(guān)節(jié)截骨術(shù)可以將壞死骨從主要承重區(qū)域去除。盡管該手術(shù)可能會延遲THA手術(shù)，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(shù)的一個結(jié)果是使得未來可能的全髖關(guān)節(jié)置換術(shù)更具挑戰(zhàn)性，并且通常與骨不連的風(fēng)險增加有關(guān)。非血管化骨移植非血管化骨移植手術(shù)有3種類型：1)活板門手術(shù)、2)燈泡技術(shù)和3)Phemister技術(shù)?；畎彘T手術(shù)一種自體松質(zhì)骨和皮質(zhì)骨移植術(shù)，已成功用于Ficat和ArletIII期髖關(guān)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(shù)的結(jié)果顯示，根據(jù)Harris評分系統(tǒng)的判定，結(jié)果均良好或極好。燈泡技術(shù)燈泡技術(shù)使用股骨頸前部的皮質(zhì)窗口。可以使用該窗口去除壞死骨，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(shù)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(guān)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(guān)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(xué)改善。Phemister技術(shù)在Phemister技術(shù)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(zhì)支柱移植物放置在病變處。最近的一項評論報告稱，該手術(shù)的臨床成功率在36%至90%之間。全髖關(guān)節(jié)置換術(shù)（THA）一旦股骨頭發(fā)生嚴重塌陷，置換髖關(guān)節(jié)是唯一實用的手術(shù)選擇，并且可以在晚期股骨頭壞死中提供最可預(yù)測的疼痛緩解。全髖關(guān)節(jié)置換術(shù)（THA）成功地緩解了大多數(shù)患者的疼痛并恢復(fù)了功能。在全髖關(guān)節(jié)置換術(shù)（THA）中，構(gòu)成髖關(guān)節(jié)的患病軟骨和骨骼被由金屬和塑料制成的人工關(guān)節(jié)假體取代。人工髖關(guān)節(jié)置換術(shù)通常可以使用15年，然后就會磨損并需要修復(fù)。對于較年輕的患者，由于可能存在活動限制，全髖關(guān)節(jié)置換術(shù)（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(guān)節(jié)置換術(shù)（THA）翻修。必須仔細考慮全髖關(guān)節(jié)置換術(shù)并與生活質(zhì)量問題進行權(quán)衡，但年輕患者并非絕對禁忌。關(guān)于髖關(guān)節(jié)股骨頭壞死(ON)的患者教育預(yù)防股骨頭壞死(ON)對患者進行有關(guān)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(guān)重要。股骨頭壞死(ON)教育過程涉及識別個人的相關(guān)疾病和與股骨頭壞死(ON)相關(guān)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(yù)防性的，也是必要的，以確保改變危險因素和優(yōu)化護理。預(yù)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(zhì)類固醇激素減少到盡可能低的治療劑量。告知患者皮質(zhì)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(guān)性對于治療這種疾病至關(guān)重要。預(yù)防股骨頭壞死(ON)的進展應(yīng)告知診斷為早期骨關(guān)節(jié)炎的患者采取上述預(yù)防措施，并應(yīng)避免對關(guān)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(guān)節(jié)炎的進展。盡管健康飲食本身并不能直接減少患者關(guān)節(jié)的壓力，但減肥（如果超重/肥胖）會減少髖關(guān)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(jié)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(guān)節(jié)。髖關(guān)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(yīng)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(shù)干預(yù)或采用微創(chuàng)手術(shù)技術(shù)來挽救髖關(guān)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(guān)節(jié)，并考慮患者的生活方式和生活質(zhì)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(guān)節(jié)保留手術(shù)（保髖治療）和全髖關(guān)節(jié)置換術(shù)THA。對患者進行有關(guān)潛在危險因素和股骨頭壞死(ON)發(fā)展的教育，對于預(yù)防該病癥和/或潛在地預(yù)防或阻止早期疾病進展為晚期疾病至關(guān)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.

股骨頭壞死：病因、診斷及治療方式：2019英國醫(yī)學(xué)雜志(BMJ)(醫(yī)學(xué)生及低年資住院醫(yī)師培訓(xùn)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(xué)人民醫(yī)院骨關(guān)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(zhuǎn)診至骨科（保髖治療）團隊。?早期治療可使髖關(guān)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(guān)節(jié)旋轉(zhuǎn)活動(髖關(guān)節(jié)查體之內(nèi)外旋轉(zhuǎn)活動)。Fig2Typicalchangesseenonplainradiograph(top)andMRI(bottom)ofthehipinearlyandlateAVNFH.TheappearanceofearlyAVNFHisnotapparentonplainradiographbutisvisibleonMRI.圖2?早期和晚期股骨頭壞死(AVNFH)髖關(guān)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(gòu)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(cè)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(guān)節(jié)和膝關(guān)節(jié)的平片顯示髖關(guān)節(jié)間隙輕微變窄，沒有其他特征，她被轉(zhuǎn)診到二級骨科診所。髖關(guān)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(dǎo)致軟骨下骨結(jié)構(gòu)完整性喪失。潛在的發(fā)病機制尚不清楚；風(fēng)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(dǎo)致進行性、繼發(fā)性髖關(guān)節(jié)骨關(guān)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(guān)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(guān)節(jié)置換術(shù)的第三大常見適應(yīng)癥。以下因素與股骨頭壞死（AVNFH）風(fēng)險增加相關(guān)：?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??；?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(zhì)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。患有這種疾病的患者可能同時患有慢性風(fēng)濕病和血液病。這可能會導(dǎo)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(jié)構(gòu)，因為髖關(guān)節(jié)疼痛可能源自髖關(guān)節(jié)和非髖關(guān)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(gòu)中準確確定單純由于髖關(guān)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(zhuǎn)診。如果X線片呈陰性并且患者繼續(xù)抱怨髖關(guān)節(jié)疼痛，醫(yī)生可能會診斷為非特異性髖關(guān)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(zhuǎn)診至關(guān)重要，因為骨質(zhì)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(guān)節(jié)的治療干預(yù)(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(xué)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(shù)可降低中短期內(nèi)進一步手術(shù)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(guān)節(jié)骨關(guān)節(jié)炎，關(guān)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(shù)和相關(guān)發(fā)病率的終生風(fēng)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(guān)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(guān)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(guān)節(jié)MRI檢查。股骨頭壞死（AVNFH）通常是雙側(cè)的，雙側(cè)股骨頭壞死（AVNFH）的風(fēng)險通常是在單側(cè)確診后的2年內(nèi)。框1：需要轉(zhuǎn)介或進一步評估的危險信號：?髖關(guān)節(jié)X線檢查正常，髖關(guān)節(jié)疼痛超過6周；?患有髖關(guān)節(jié)疼痛和危險因素的患者，包括：o既往單側(cè)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(guān)節(jié)前側(cè)疼痛的再現(xiàn)并伴有單獨的大腿旋轉(zhuǎn)不能診斷股骨頭壞死（AVNFH），但有助于區(qū)分髖關(guān)節(jié)疼痛與脊柱和膝關(guān)節(jié)疼痛。這可以在患者坐位或仰臥時進行（圖1）。影像學(xué)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(zhuǎn)診。股骨頭壞死（AVNFH）通過髖關(guān)節(jié)MRI進行診斷，當與臨床癥狀密切相關(guān)時，還可以診斷各種可治療的髖關(guān)節(jié)疼痛（例如風(fēng)濕病、肌腱疾病和骨?。▓D2）。僅當有其他原因或高度懷疑風(fēng)濕病或感染時，才應(yīng)考慮進行其他檢查，例如血液檢查。轉(zhuǎn)診如果患者的髖關(guān)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(gòu)就診時，股骨頭壞死（AVNFH）診斷應(yīng)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(shù)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(guān)節(jié)形合度破壞，但其療效目前尚不清楚。手術(shù)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(shù)，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(guān)節(jié)置換術(shù)治療。術(shù)后恢復(fù)包括12個月的非負重康復(fù)鍛煉，并在8周后逐漸恢復(fù)工作和駕駛。通常在術(shù)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(gòu)可以提供新的治療方法，例如骨移植和截骨術(shù)，以分別促進血管再生和減輕受損髖關(guān)節(jié)表面的負荷。一旦發(fā)生塌陷，全髖關(guān)節(jié)置換術(shù)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(guān)節(jié)翻修的風(fēng)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.

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(xué)人民醫(yī)院骨關(guān)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(xué)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(guān)節(jié)置換術(shù)，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(yīng)會導(dǎo)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(guān)，病情進展可能會使人衰弱（殘疾），最終可能需要進行全髖關(guān)節(jié)置換術(shù)(全髖關(guān)節(jié)置換術(shù)(THA))。股骨頭壞死的病因很復(fù)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(guān)于股骨頭壞死的病因?qū)W、病理生理學(xué)、流行病學(xué)和臨床治療的知識，重點介紹了最新進展。流行病學(xué)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(guān)節(jié)置換術(shù)(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(guān)節(jié)置換術(shù)(THA)的比例從9.7%下降到8.3%，可能是因為需要進行全髖關(guān)節(jié)置換術(shù)(THA)的骨關(guān)節(jié)炎迅速增加。病理生理學(xué)和發(fā)病機制一般發(fā)病機制盡管臨床表現(xiàn)是修復(fù)過程的結(jié)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(jié)構(gòu)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(dǎo)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(fēng)險。GardenI（不完全骨折）和GardenII（完全且無移位）被認為是穩(wěn)定且風(fēng)險低的，可以通過內(nèi)固定修復(fù)。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(yīng)考慮髖關(guān)節(jié)置換術(shù)。另外，有文獻報道，股骨轉(zhuǎn)子間骨折導(dǎo)致股骨頭壞死的風(fēng)險較低，一年隨訪時的股骨頭壞死結(jié)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(cè)的，一些估計表明，高達70%的單側(cè)股骨頭壞死患者的對側(cè)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(cè)髖關(guān)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(guān)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(zhì)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(guān)聯(lián)的幾種潛在機制，包括骨基質(zhì)和軟骨變性、誘導(dǎo)干細胞異常、脂質(zhì)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(zhì)類固醇的患者風(fēng)險增加多達10倍；當累積劑量超過10g時，股骨頭壞死的風(fēng)險增加一倍；而使用大劑量皮質(zhì)類固醇患者每日劑量每增加10毫克股骨頭壞死風(fēng)險就會增加3.6%。皮質(zhì)類固醇也與成骨細胞死亡和成骨細胞增殖減少有關(guān)，損害修復(fù)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(zhì)代謝和增加脂肪生成來發(fā)揮（導(dǎo)致股骨頭壞死的）作用。據(jù)推測，脂質(zhì)生成的增加會增加脂肪栓塞導(dǎo)致血管閉塞的風(fēng)險。此外，血脂升高會導(dǎo)致骨髓堵塞、骨內(nèi)壓升高和血流量減少。酒精也可能導(dǎo)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(zhì)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(fēng)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(yīng)。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(guān)。系統(tǒng)性紅斑狼瘡SLE與股骨頭壞死的關(guān)聯(lián)與頻繁的皮質(zhì)類固醇治療有關(guān)；然而，最近的分析顯示，患有SLE的皮質(zhì)類固醇使用者的股骨頭壞死發(fā)生率高于未患SLE的皮質(zhì)類固醇使用者，這表明存在協(xié)同效應(yīng)。SLE研究的薈萃分析已發(fā)現(xiàn)SLE中的許多非皮質(zhì)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(guān)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(guān)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(dǎo)致血管閉塞和骨骼缺血，從而導(dǎo)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(dǎo)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(dǎo)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(guān)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(fēng)險增加，前瞻性研究中影像學(xué)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(jié)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(fēng)險，而甲氨蝶呤和天冬酰胺酶等非激素化療藥物可能會導(dǎo)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(fēng)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(dǎo)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(fēng)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(zhuǎn)錄病毒治療與股骨頭壞死的發(fā)生之間存在密切關(guān)聯(lián)，盡管作者警告說，這種關(guān)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(zhuǎn)錄病毒治療(ART)之間沒有關(guān)聯(lián)，而與酒精、高脂血癥或低最低CD4計數(shù)有關(guān)，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(guān)基因，但尚未確定單一的相關(guān)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(guān)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(guān)，表明凝血功能改變的潛在作用。對選定人群的全基因組關(guān)聯(lián)研究已經(jīng)確定了幾個感興趣的位點，包括ALL、皮質(zhì)類固醇誘導(dǎo)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(guān)，脂質(zhì)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(guān)節(jié)活動范圍有限。股骨頭壞死的診斷主要基于影像學(xué)，盡管查體和病史（采集）對于收集髖關(guān)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(cè)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(quán)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(xué)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(guān)節(jié)發(fā)育不良的兒科患者中，灌注MRI有助于識別閉合復(fù)位/人字形石膏脫外固定后有股骨頭壞死風(fēng)險的患者。此外，全身骨掃描患有多灶性股骨頭壞死風(fēng)險的患者提供了一種選擇，如接受全身性皮質(zhì)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(xué)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(guān)節(jié)置換術(shù)(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(yù)測（效力）。賓夕法尼亞大學(xué)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(xué)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(guān)節(jié)間隙變窄，從而促進各階段之間的區(qū)別僅(V)以及關(guān)節(jié)畸形和關(guān)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(guān)，但將MRI結(jié)果納入I期并根據(jù)關(guān)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(jié)合MRI和X線片的結(jié)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(zhuǎn)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(dǎo)保守治療與髖關(guān)節(jié)置換術(shù)(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(fēng)險評估進展風(fēng)險對于確定適當?shù)闹委熯x擇很重要。盡管對于明確預(yù)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(jié)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(shù)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(zhì)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(guān)于二磷酸鹽使用的研究顯示了不同的結(jié)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(shù)。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(shù)，可以改善股骨頭壞死的臨床和放射學(xué)進展。其他非手術(shù)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(zhì)調(diào)節(jié)劑在試驗中顯示出一些積極的結(jié)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(shù)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(shù)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(fù)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(jié)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(guān)節(jié)置換術(shù)(THA)時間。與許多治療一樣，在疾病早期階段使用時，這些結(jié)果更為積極。高達100%的髖關(guān)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(jié)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(jié)合時，這些結(jié)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(jié)構(gòu)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(yīng)。通過將來自髂骨、脛骨或腓骨的非血管化同種異體皮質(zhì)移植物或來自髂嵴、腓骨或大轉(zhuǎn)子的血管化移植物放置到為手術(shù)或髓心減壓CD手術(shù)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(guān)節(jié)存活率為80%或14年后類似患者中的60%，需要全髖關(guān)節(jié)置換術(shù)(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(zhuǎn)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(xué)進展率較低，全髖關(guān)節(jié)置換術(shù)(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(jié)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(jié)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(shù)截骨術(shù)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(zhuǎn)，以將主要壓力施加在股骨頭非壞死區(qū)域上。股骨頭旋轉(zhuǎn)截骨術(shù)（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(shù)（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(guān)節(jié)置換術(shù)(THA)可能會在截骨術(shù)后變得困難。帳篷植入和改變的解剖結(jié)構(gòu).69髖關(guān)節(jié)置換術(shù)髖關(guān)節(jié)表面置換術(shù)對于晚期股骨頭壞死來說，髖關(guān)節(jié)表面置換是最簡單的選擇，涉及用人造材料替換關(guān)節(jié)表面以保留自然解剖結(jié)構(gòu)。然而，由于材料引起的并發(fā)癥以及可能導(dǎo)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(guān)節(jié)置換術(shù)全髖關(guān)節(jié)置換術(shù)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(guān)節(jié)置換術(shù)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(shù)，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(guān)節(jié)，患者在以后的生活中可能需要再次進行髖關(guān)節(jié)置換術(shù)或翻修術(shù)。髖關(guān)節(jié)置換術(shù)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(guān)節(jié)置換術(shù)(THA)的患者比因骨關(guān)節(jié)炎接受全髖關(guān)節(jié)置換術(shù)(THA)的患者有更多的合并癥和更復(fù)雜的住院時間，但長期隨訪顯示出相似的結(jié)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(guān)節(jié)炎OA患者相比，接受全髖關(guān)節(jié)置換術(shù)(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(jié)果有所改善，超過90%的股骨頭壞死全髖關(guān)節(jié)置換術(shù)(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(shù)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(guān)節(jié)置換術(shù)(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(guān)節(jié)置換術(shù)(THA)治療。需要對側(cè)全髖關(guān)節(jié)置換術(shù)(THA)，特別是如果對側(cè)髖關(guān)節(jié)在第一次全髖關(guān)節(jié)置換術(shù)(THA)時有股骨頭壞死的影像學(xué)證據(jù)，表明需要密切隨訪?？偨Y(jié)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(xué)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(lǐng)域正在取得有希望的發(fā)展，但該領(lǐng)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(zhì)量并延緩他們發(fā)展為衰弱性損傷、股骨頭塌陷或髖關(guān)節(jié)置換術(shù)。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(gòu)登記和大型隊列研究將有助于在這一領(lǐng)域取得進展。在治療領(lǐng)域，有許多潛在的改進途徑。骨修復(fù)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(yù)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(dān)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.

提起股骨頭壞死，必然要談到分期，如Ficat-Arlet分期，Steinberg分期、AssociationResearchCirculationOsseous（ARCO）分期、中日友好CJFH分期等，用來幫助醫(yī)生確定股骨頭壞死的嚴重程度和治療方案的選擇。但是，股骨頭壞死分期聽上去很平常，其實卻容易判斷錯誤——影像檢查的“平面圖”需要在人腦中整合成“立體圖”。如下圖，一位48歲的男性，駕校教練，能看出點什么？影像質(zhì)量對診斷的意義不言而喻，右側(cè)股骨頭壞死局部放大看：很多病人說，磁共振不是最好的檢查嗎？怎么還要常規(guī)做X線片？好吧，如果看磁共振，該病人是這樣的：壞死很明確，但塌陷能看出個錘子來？X光是平面圖，等于天空的月亮是個球體，我們這看到一幅畫，表面的月坑、背面的場景只能靠想象了。CT能夠提供更多信息：但，仍然沒有發(fā)現(xiàn)明顯塌陷區(qū)再看CT橫斷面：終于發(fā)現(xiàn)了蛛絲馬跡，如紅色箭頭所指，即為軟骨開裂區(qū)域。病人半年前行保守治療，未見明顯改善，為了盡快恢復(fù)正常生活，遂決定進行關(guān)節(jié)置換術(shù)。箭頭所示隆起的“軟骨脊”其實就是塌陷以后造成的，猶如地殼劇烈運動形成的山峰。打破砂鍋問到底：箭頭所示區(qū)域即為壞死骨，可見壞死骨和軟骨下骨已經(jīng)整體剝離。小結(jié)典型的股骨頭壞死塌陷診斷非常容易，確定明顯塌陷股骨頭壞死的治療方案也沒什么困難。即將塌陷（高塌陷風(fēng)險）或者剛剛塌陷股骨頭壞死的診斷非常重要，這關(guān)系到治療方案的選擇是否合理。大面積壞死的2期非常容易進展到3期，是否有軟骨下骨的節(jié)裂、是否有頭內(nèi)骨小梁的斷裂，決定著診斷為2期還是3期，決定著治療方案是否為最恰當?shù)倪x項。然后，這一點很容易搞錯，破解方法之一便是依靠CT檢查。這也是X線片和磁共振檢查的不足之處。很多病人不愿意多做檢查，往往認為是醫(yī)生為了檢查而檢查；事實上，各種檢查方法之間各有其優(yōu)缺點，相互驗證才能彌補不足，得到最真實的信息。通過對患者的病史、癥狀及其它相關(guān)臨床因素進行綜合分析，采用合理的影像學(xué)檢查技術(shù)，能快速準確地診斷股骨頭壞死塌陷，從而提高治療的準確性和有效性。