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陶可主治醫(yī)師 北京大學(xué)人民醫(yī)院 骨關(guān)節(jié)科 股骨頭壞死：再生醫(yī)學(xué)的最新研究進(jìn)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(xì)胞死亡。壞死的股骨頭無(wú)法持續(xù)自我修復(fù)，因此，微骨折會(huì)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(fù)擔(dān)。雖然髖關(guān)節(jié)置換術(shù)的立竿見影的良好效果對(duì)于患者和外科醫(yī)生都有吸引力，但在較長(zhǎng)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。考慮到股骨頭壞死（ONFH）的發(fā)病機(jī)制與細(xì)胞死亡有關(guān)，補(bǔ)充可以原位制造骨骼或血管系統(tǒng)的細(xì)胞是一個(gè)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(xì)胞療法提供了獨(dú)特的環(huán)境，同時(shí)將額外的發(fā)病率降至最低。除了基于細(xì)胞的治療外，包括生長(zhǎng)因子、外泌體和基因治療在內(nèi)的非細(xì)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(xì)胞細(xì)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(xì)胞可以恢復(fù)壞死股骨頭中的骨小梁。多個(gè)研究小組報(bào)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(duì)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(shí)間短，大多數(shù)研究的價(jià)值相當(dāng)有限。一項(xiàng)前瞻性雙盲試驗(yàn)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(duì)干細(xì)胞的了解和表征的不斷深入，促進(jìn)了這些細(xì)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(xì)胞類型中，源自骨髓的間充質(zhì)基質(zhì)/干細(xì)胞（MSC）被認(rèn)為是最佳候選細(xì)胞。然而，應(yīng)用離體擴(kuò)增的自體骨間充質(zhì)基質(zhì)/干細(xì)胞（MSC）是一個(gè)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(jī)構(gòu)的控制。除少數(shù)對(duì)照研究外，大多數(shù)報(bào)告間充質(zhì)干細(xì)胞應(yīng)用的研究都是非對(duì)照病例系列。另一方面，干細(xì)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(gè)研究變得困難，但人們?cè)絹碓秸J(rèn)識(shí)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(jìn)展。雖然骨髓抽吸濃縮物（BMAC）是股骨頭壞死（ONFH）最常用的干細(xì)胞類型，但脂肪干細(xì)胞(ASC)作為再生醫(yī)學(xué)的細(xì)胞來源具有多種優(yōu)勢(shì)。脂肪干細(xì)胞(ASC)比骨髓干細(xì)胞(BMSC)更容易獲得且痛苦更少。與骨髓干細(xì)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(xì)胞(ASC)還具有促進(jìn)血管生成的優(yōu)勢(shì)。與自體干細(xì)胞MSC相比，同種異體干細(xì)胞MSC具有經(jīng)濟(jì)優(yōu)勢(shì)，因?yàn)橥N異體細(xì)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(gè)意義上說，關(guān)于同種異體干細(xì)胞MSC是否適用于股骨頭壞死（ONFH）等非致命性疾病存在爭(zhēng)議。另一方面，考慮到來自股骨頭壞死（ONFH）患者的干細(xì)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(xì)胞MSC可能對(duì)治療這些患者有效。臍帶來源的間充質(zhì)干細(xì)胞可能被證明是一個(gè)很好的候選者，因?yàn)樗哂懈呒?xì)胞產(chǎn)量和低免疫原性。細(xì)胞的遞送在細(xì)胞治療中，出于經(jīng)濟(jì)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(xì)胞的最佳數(shù)量，該數(shù)量與藥物的劑量相當(dāng)。骨髓抽吸濃縮物（BMAC）和基質(zhì)血管部分是細(xì)胞混合物，其中含有少量干細(xì)胞。此外，每種成體干細(xì)胞預(yù)計(jì)具有不同的存活和成骨潛力。根據(jù)目前報(bào)道的研究，使用的細(xì)胞數(shù)量從10∧6到10∧9個(gè)不等，最常用的劑量是10∧8個(gè)細(xì)胞。盡管如此，每種類型的細(xì)胞的最佳數(shù)量仍有待確定。細(xì)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(dòng)脈內(nèi)輸注，有效地輸送治療細(xì)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(jìn)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(jī)會(huì)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(xì)胞治療，因?yàn)樗栊臏p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(bào)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(duì)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(huì)取得更好的效果，不進(jìn)行附加細(xì)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(xiàng)使用自體骨髓抽吸濃縮物（BMAC）的研究報(bào)告稱，植入后三個(gè)月，塌陷進(jìn)展的平均殘留病灶體積為10%（標(biāo)準(zhǔn)差6%）。安全性是細(xì)胞療法應(yīng)用中的關(guān)鍵問題之一。干細(xì)胞的關(guān)鍵特征，如自我復(fù)制、長(zhǎng)壽命和多分化，也是癌細(xì)胞所共有的。這意味著干細(xì)胞可以發(fā)生惡性轉(zhuǎn)化，這對(duì)干細(xì)胞植入的安全性構(gòu)成了關(guān)鍵障礙。免疫排斥也會(huì)限制同種異體干細(xì)胞治療股骨頭壞死（ONFH）的臨床應(yīng)用。然而，目前的文獻(xiàn)表明，干細(xì)胞植入治療股骨頭壞死（ONFH）沒有出現(xiàn)嚴(yán)重的并發(fā)癥。因此可以提出應(yīng)用干細(xì)胞治療股骨頭壞死（ONFH）是相對(duì)安全的。盡管如此，仍需要更長(zhǎng)時(shí)間的隨訪結(jié)果來確保其安全性。由于體外細(xì)胞擴(kuò)增過程是必要的，整個(gè)過程必須受到控制和標(biāo)準(zhǔn)化，以便細(xì)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(xì)胞治療中未被注意到和未表征的一個(gè)方面是植入細(xì)胞的體內(nèi)命運(yùn)。盡管干細(xì)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(xì)胞，但植入的細(xì)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(xì)胞就會(huì)缺氧、低血糖、缺乏營(yíng)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(xì)胞的生存。這些情況可能是對(duì)照研究中干細(xì)胞植入結(jié)果不令人滿意的原因。大多數(shù)植入的細(xì)胞可能會(huì)在短時(shí)間內(nèi)經(jīng)歷大量細(xì)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(jìn)植入細(xì)胞的存活和植入，使這些細(xì)胞成為成骨細(xì)胞并在植入?yún)^(qū)域內(nèi)再生骨，則需要采取增強(qiáng)措施來增強(qiáng)植入細(xì)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(qiáng)間充質(zhì)干細(xì)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(zhǎng)因子(VEGF)、堿性成纖維細(xì)胞生長(zhǎng)因子(bFGF)和血小板衍生生長(zhǎng)因子(PDGF)是可轉(zhuǎn)移以促進(jìn)間充質(zhì)干細(xì)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(xì)胞治療的安全性問題進(jìn)一步復(fù)雜化，基因修飾的間充質(zhì)干細(xì)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(xì)胞的所有數(shù)據(jù)均來自動(dòng)物實(shí)驗(yàn)，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(yàn)評(píng)估。生長(zhǎng)因子可以直接植入病變部位以增強(qiáng)成骨和血管生成。然而，生長(zhǎng)因子的直接植入因肽療法的實(shí)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(duì)于實(shí)現(xiàn)生長(zhǎng)因子的控制釋放和實(shí)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(xì)胞生長(zhǎng)因子2（FGF-2）已與各種載體聯(lián)合應(yīng)用于臨床。已知干細(xì)胞MSC的治療益處主要?dú)w因于它們分泌的因子。另外，在生長(zhǎng)因子和細(xì)胞因子的作用下，細(xì)胞通過細(xì)胞外囊泡(EV)與鄰近或遠(yuǎn)處的細(xì)胞進(jìn)行通訊，其中包括外泌體，外泌體是直徑小于150nm的細(xì)胞外囊泡(EV)。從人類干細(xì)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(jìn)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(bào)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?cè)摷膊〉淖匀皇?。雖然有必要招募足夠數(shù)量的患者進(jìn)行良好對(duì)照的隨機(jī)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(xì)胞特征的個(gè)體差異，使其相當(dāng)難以進(jìn)行。就細(xì)胞治療而言，由于從一種細(xì)胞來源觀察到的結(jié)果無(wú)法推演到另一種細(xì)胞類型，因此必須對(duì)細(xì)胞來源和類型進(jìn)行精確定義。此外，區(qū)分培養(yǎng)擴(kuò)增細(xì)胞和天然細(xì)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(kuò)增細(xì)胞的植入需要大多數(shù)發(fā)達(dá)國(guó)家監(jiān)管機(jī)構(gòu)的批準(zhǔn)，這對(duì)于同種異體或轉(zhuǎn)基因細(xì)胞更為嚴(yán)格，從而增加了細(xì)胞治療的成本。然而，由于壞死骨無(wú)法再生，年輕患者不可避免地需要進(jìn)行關(guān)節(jié)置換術(shù)，因此需要進(jìn)一步致力于股骨頭壞死（ONFH）再生醫(yī)學(xué)的研究和進(jìn)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(xiàn)出處：Gun-IlIm.Regenerativemedicineforosteonecrosisofthefemoralhead:presentandfuture.BoneJointRes.2023Jan;12(1):5-8.doi:10.1302/2046-3758.121.BJR-2022-0057.R1.2023年08月06日452
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張會(huì)文副主任醫(yī)師 唐山市第二醫(yī)院 手外科 非手術(shù)治療技術(shù)①保護(hù)性負(fù)重：減輕患髖負(fù)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(zhǎng)時(shí)間使用輪椅；同時(shí)應(yīng)注意避免出現(xiàn)對(duì)抗性及撞擊性運(yùn)動(dòng)。對(duì)于病變位于股骨頭內(nèi)側(cè)及面積較小（＜15%）的股骨頭壞死可考慮此方法。一般對(duì)于接受保髖手術(shù)治療的患者，建議術(shù)后拄拐3個(gè)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(xì)胞功能和促進(jìn)成骨細(xì)胞功能的藥物，如磷酸鹽類藥物，以及抗凝、降脂、擴(kuò)張血管、促進(jìn)纖溶等藥物。藥物治療可單獨(dú)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(qiáng)調(diào)早期診斷、病證結(jié)合、早期治療。對(duì)高危人群及早期股骨頭壞死患者，建議給予活血化瘀、補(bǔ)腎健骨等中藥治療，具有促進(jìn)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(qiáng)骨膠囊等。④物理治療：包括體外震波（亦稱為沖擊波）、電磁場(chǎng)、高壓氧等。手術(shù)治療股骨頭壞死進(jìn)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(jìn)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。2023年07月28日433
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陶可主治醫(yī)師 北京大學(xué)人民醫(yī)院 骨關(guān)節(jié)科 股骨頭壞死：基礎(chǔ)知識(shí)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(shí))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(bào)告中，我們對(duì)骨股骨頭壞死進(jìn)行了簡(jiǎn)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(bào)道是由于受影響的骨骼區(qū)域的血液供應(yīng)暫時(shí)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(jī)制（發(fā)展機(jī)制）、病因（相關(guān)危險(xiǎn)因素、原因和疾病）、臨床表現(xiàn)（報(bào)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(xiàng)活動(dòng)都與其產(chǎn)生該活動(dòng)的身體的一個(gè)單獨(dú)部分相關(guān)。因此，當(dāng)產(chǎn)生某項(xiàng)活動(dòng)的部分受到影響時(shí)，該活動(dòng)必然會(huì)受到損害。—佩加蒙的蓋倫，公元130年至公元210年，羅馬帝國(guó)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(jìn)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(bào)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(jī)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(wú)菌性壞死或缺血性骨壞死，與許多導(dǎo)致成熟骨細(xì)胞死亡的疾病和危險(xiǎn)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(shí)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(dāng)最初在髖關(guān)節(jié)以外的區(qū)域進(jìn)行診斷時(shí)，應(yīng)同時(shí)對(duì)髖關(guān)節(jié)進(jìn)行臨床評(píng)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(wú)關(guān)）。準(zhǔn)確診斷和分類股骨頭壞死(ON)對(duì)于幫助指導(dǎo)治療選擇非常重要。識(shí)別相關(guān)風(fēng)險(xiǎn)因素和患者教育對(duì)于成功治療股骨頭壞死(ON)非常重要。針對(duì)相關(guān)危險(xiǎn)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(jì)，美國(guó)每年有20,000至30,000名新診斷患者。在美國(guó)，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(shí)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(huì)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(jī)制/假說髖關(guān)節(jié)股骨頭壞死(ON)發(fā)生的機(jī)制仍不清楚。在大多數(shù)情況下，股骨頭壞死(ON)被認(rèn)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(jī)械應(yīng)力）綜合作用的結(jié)果。大多數(shù)專家都認(rèn)為產(chǎn)生干細(xì)胞和血小板的股骨頭和骨髓缺乏血液供應(yīng)，導(dǎo)致骨細(xì)胞（成熟骨內(nèi)的細(xì)胞）和/或間充質(zhì)細(xì)胞（形成軟骨、骨和脂肪的干細(xì)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?。S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(jī)制包括由過量糖皮質(zhì)激素影響骨和靜脈內(nèi)皮細(xì)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(huì)在供應(yīng)骨的動(dòng)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(duì)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(xiǎn)因素。然而，相關(guān)風(fēng)險(xiǎn)因素是與股骨頭壞死(ON)最終進(jìn)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(jī)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。沉箱病（例如潛水減壓）會(huì)導(dǎo)致氮?dú)鈿馀莸男纬?，從而阻塞小?dòng)脈，導(dǎo)致股骨頭壞死(ON)。出現(xiàn)癥狀的患者可能會(huì)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(shí)間以及暴露的次數(shù)是這種疾病進(jìn)展的重要因素。股骨頭壞死(ON)的非外傷原因許多研究報(bào)告稱，長(zhǎng)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(shí)間和總劑量直接相關(guān)。長(zhǎng)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(xiǎn)；然而，這些患者通常有多種其他危險(xiǎn)因素。接受長(zhǎng)期治療的患者中有9%至40%會(huì)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(xiàng)薈萃分析和系統(tǒng)評(píng)價(jià)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(xiàng)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(xiǎn)較低。一項(xiàng)針對(duì)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(qiáng)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(qiáng)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(rèn)為是由于脂質(zhì)形成過多和細(xì)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(xì)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(xiǎn)因素，并且占與創(chuàng)傷無(wú)關(guān)的病例的80%以上。一項(xiàng)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(duì)照者(沒有全身性皮質(zhì)類固醇激素使用史)，與對(duì)照者相比，經(jīng)常飲酒者的風(fēng)險(xiǎn)升高，并且與酒精存在明顯的劑量反應(yīng)關(guān)系。對(duì)于當(dāng)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(fèi)者來說，相對(duì)風(fēng)險(xiǎn)分別為3.3、9.8和17.9。股骨頭壞死(ON)在鐮狀細(xì)胞病患者中很常見，因?yàn)樗菀讓?dǎo)致紅細(xì)胞鐮狀化和骨髓增生。大約50%的受影響患者在35歲時(shí)出現(xiàn)股骨頭壞死(ON)。鐮狀細(xì)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(bào)道，3%至30%的系統(tǒng)性紅斑狼瘡SLE患者會(huì)發(fā)生股骨頭壞死(ON)，最危險(xiǎn)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(bào)道，高達(dá)60%的戈謝?。ㄒ环N遺傳性疾?。┗颊呋加泄晒穷^壞死(ON)，因?yàn)樗軌蛑苯幼璧K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(huì)產(chǎn)生一種稱為葡萄糖腦苷脂酶（細(xì)胞膜的正常部分）的酶，它會(huì)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(kù)欣病和系統(tǒng)性紅斑狼瘡SLE患者。急性淋巴細(xì)胞白血病、慢性粒細(xì)胞白血病和急性粒細(xì)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(xiǎn)。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、克羅恩病）、夏科足和炎癥性腸病），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(xiǎn)因素的遺傳基礎(chǔ)。例如，當(dāng)過度飲酒是相關(guān)風(fēng)險(xiǎn)因素時(shí)，男性受到的影響是女性的3倍。然而，當(dāng)狼瘡或皮質(zhì)類固醇激素的使用成為相關(guān)危險(xiǎn)因素時(shí)，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(jì)20%的股骨頭壞死(ON)病例被標(biāo)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(fù)重或關(guān)節(jié)運(yùn)動(dòng)而出現(xiàn)。大約三分之二的股骨頭壞死(ON)患者會(huì)出現(xiàn)休息時(shí)疼痛，大約三分之一的患者會(huì)出現(xiàn)夜間疼痛。身體多個(gè)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(huì)導(dǎo)致受影響關(guān)節(jié)的活動(dòng)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(píng)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(dāng)?shù)姆派鋵W(xué)評(píng)估，3)確定病情階段，以及4)制定治療方案來解決。在評(píng)估患者是否患有股骨頭壞死(ON)，問題應(yīng)針對(duì)評(píng)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(xì)胞病、戈謝病、自身免疫性疾病和白血病）、吸煙和/或飲酒。當(dāng)詢問受傷/疾病時(shí)，重要的是要仔細(xì)探討與髖部骨折、脫位或沉箱病相關(guān)的傷害，因?yàn)槌料洳∈欠莿?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(duì)于治療很重要；在初始階段，疾病可能不會(huì)進(jìn)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(píng)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(jìn)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(dāng)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(shí)，就可以準(zhǔn)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(jìn)行普通放射線照相評(píng)估，然后進(jìn)行MRI。據(jù)報(bào)道，MRI對(duì)于檢測(cè)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(duì)異常骨占據(jù)的股骨頭區(qū)域進(jìn)行數(shù)字化，定量評(píng)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(qiáng)度線（特征性雙線征標(biāo)志）代表血管豐富的肉芽組織。這種級(jí)別的成像細(xì)節(jié)非常有用，因?yàn)槭苡绊懝趋啦∽兊拇笮『头秶苤匾?，可以幫助指?dǎo)治療。然而，對(duì)于終末期疾病，股骨頭壞死(ON)患者可能沒有必要使用MRI，因?yàn)榇穗A段的治療選擇可能有限。這些發(fā)現(xiàn)通常使用4個(gè)階段的Ficat和Arlet系統(tǒng)進(jìn)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(huì)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(cè)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(jì)算機(jī)斷層掃描具有中等敏感性，但不具有特異性，可能會(huì)給患者帶來顯著的輻射負(fù)擔(dān)。如果股骨頭已經(jīng)塌陷，計(jì)算機(jī)斷層掃描可能具有一定的特異性。幸運(yùn)的是，大多數(shù)臨床醫(yī)生無(wú)需計(jì)算機(jī)斷層掃描即可診斷出股骨頭骨壞死，而計(jì)算機(jī)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(huì)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(gè)。與骨壞死相關(guān)的病因創(chuàng)傷相關(guān)的危險(xiǎn)因素股骨頸骨折脫位或骨折脫位鐮狀細(xì)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(xiǎn)因素皮質(zhì)類固醇激素飲酒系統(tǒng)性紅斑狼瘡庫(kù)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(xiǎn)因素特發(fā)性原因骨髓水腫綜合征，也稱為髖部暫時(shí)性骨質(zhì)減少，可能單獨(dú)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(yíng)養(yǎng)不良、灼痛等術(shù)語(yǔ)）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(rèn)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(shí)會(huì)出現(xiàn)輕微的扁平化；股骨頭塌陷是進(jìn)行性的。髖關(guān)節(jié)股骨頭骨壞死的臨床治療在制定針對(duì)癥狀性髖關(guān)節(jié)骨關(guān)節(jié)炎的最佳治療方法時(shí)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(biāo)是盡可能長(zhǎng)時(shí)間地保留天然髖關(guān)節(jié)，同時(shí)考慮患者年齡、活動(dòng)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(duì)于受影響的患者，67%的人報(bào)告沒有任何癥狀，但最終可能會(huì)出現(xiàn)關(guān)節(jié)塌陷。無(wú)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(duì)于有癥狀的患者，大約80%至85%的病例會(huì)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(huì)提供早期治療的機(jī)會(huì)，這可以防止塌陷，并最終避免股骨頭塌陷而需要進(jìn)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(duì)于那些已知或可能存在危險(xiǎn)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(duì)于無(wú)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(jìn)行手術(shù)治療；盡管進(jìn)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(jìn)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(huì)阻止進(jìn)行性髖關(guān)節(jié)骨性關(guān)節(jié)炎進(jìn)展到后期。同樣，使用拐杖或手杖等輔助裝置限制負(fù)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(biāo)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(fù)重限制有助于防止進(jìn)行性骨關(guān)節(jié)炎疾病進(jìn)展為終末期疾病。藥物非甾體類抗炎藥和對(duì)乙酰氨基酚可以暫時(shí)緩解有癥狀患者的疼痛。當(dāng)其他藥物無(wú)法有效控制中度至重度疼痛時(shí)，在考慮手術(shù)選擇時(shí)，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(shí)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(jìn)行髓心減壓手術(shù)的患者通常會(huì)在幾個(gè)月后恢復(fù)獨(dú)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(biāo)準(zhǔn)技術(shù)使用自體移植，涉及從身體的一個(gè)部位取出骨頭并將其移動(dòng)到身體的另一部位。從捐贈(zèng)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(kù)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(xiàng)研究技術(shù)從患者的骨髓中采集干細(xì)胞并將其注射到股骨頭壞死(ON)區(qū)域。骨髓抽吸濃縮被認(rèn)為可以防止疾病進(jìn)一步發(fā)展并刺激新骨生長(zhǎng)。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(gè)孔，到達(dá)股骨頭的受影響部位。一份對(duì)45個(gè)髖關(guān)節(jié)進(jìn)行平均隨訪24個(gè)月的報(bào)告顯示，30個(gè)患有Ficat和ArletI期疾病的髖關(guān)節(jié)中有24個(gè)（80%）取得了成功的結(jié)果（定義為Harris髖關(guān)節(jié)評(píng)分＜70）。一項(xiàng)最近的研究比較了多個(gè)鉆探與標(biāo)準(zhǔn)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(dòng)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(huì)延遲THA手術(shù)，對(duì)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(gè)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(xiǎn)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(duì)23名Ficat和ArletIII期或IV期股骨頭壞死(ON)患者進(jìn)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(píng)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(duì)110名接受燈泡手術(shù)的患者（138髖）進(jìn)行了評(píng)估。在平均25個(gè)月的隨訪中，平均Harris髖關(guān)節(jié)評(píng)分從62分提高到79分。在最近的隨訪中，總共94個(gè)髖關(guān)節(jié)(68%)被認(rèn)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(gè)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(xiàng)評(píng)論報(bào)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(yán)重塌陷，置換髖關(guān)節(jié)是唯一實(shí)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(cè)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?？梢允褂?5年，然后就會(huì)磨損并需要修復(fù)。對(duì)于較年輕的患者，由于可能存在活動(dòng)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(zhǎng)期使用后部件會(huì)磨損），這些患者可能需要在以后的生活中進(jìn)行全髖關(guān)節(jié)置換術(shù)（THA）翻修。必須仔細(xì)考慮全髖關(guān)節(jié)置換術(shù)并與生活質(zhì)量問題進(jìn)行權(quán)衡，但年輕患者并非絕對(duì)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(duì)患者進(jìn)行有關(guān)危險(xiǎn)因素、治療和管理的教育對(duì)于患者對(duì)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(shí)別個(gè)人的相關(guān)疾病和與股骨頭壞死(ON)相關(guān)的危險(xiǎn)因素。無(wú)癥狀股骨頭壞死的患者進(jìn)展為有癥狀疾病和股骨頭塌陷的可能性很高。對(duì)無(wú)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(xiǎn)因素和優(yōu)化護(hù)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(duì)于治療這種疾病至關(guān)重要。預(yù)防股骨頭壞死(ON)的進(jìn)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(duì)關(guān)節(jié)施加過度壓力，遵循健康飲食，并保持適當(dāng)?shù)捏w重以減緩骨關(guān)節(jié)炎的進(jìn)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(huì)減少髖關(guān)節(jié)的軸向負(fù)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(dāng)最初診斷出股骨頭壞死(ON)發(fā)生在身體的其他部位時(shí)，應(yīng)始終利用放射線篩查和MRI掃描進(jìn)行正確評(píng)估。越早診斷股骨頭壞死，無(wú)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(jī)會(huì)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(jì)劃。在此過程中，癥狀的存在或不存在很重要。治療的目標(biāo)包括嘗試盡可能長(zhǎng)時(shí)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(duì)患者進(jìn)行有關(guān)潛在危險(xiǎn)因素和股骨頭壞死(ON)發(fā)展的教育，對(duì)于預(yù)防該病癥和/或潛在地預(yù)防或阻止早期疾病進(jìn)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(xiàn)出處：MichelleJLespasio,NipunSodhi,MichaelAMont.OsteonecrosisoftheHip:APrimer.ReviewPermJ.2019;23:18-100.doi:10.7812/TPP/18-100.INTRODUCTIONTheintentofthisarticleistopresentanupdateonosteonecrosis(ON)affectingthefemoralheadorhipjointandhowitcanbestbemanagedintheadultpopulation.Specifically,thisreportwillencompasstheepidemiology,pathogenesis,etiology,clinicalmanifestations,diagnosisandclassification,andtreatmentoptionsforhipON.ON,alsoreferredtoasavascularnecrosis,asepticnecrosis,orischemicbonenecrosis,isassociatedwithmanydisordersandriskfactorsthatcausematurebonecellstodie,leadingtobonedestruction(eg,collapse)orend-stagearthritisofthefemoralhead.Theconditioncanoccurinanyboneinthebody(eg,upperextremity,knees,shoulders,andankles),orinmorethan1boneatdifferenttimes,butitmostcommonlyaffectsthehipjoint.Wheninitiallydiagnosedinanareaotherthanthehip,thehipshouldsimultaneouslybeevaluatedclinicallyandwithradiographicandotherimagingstudies.ThecausesofONareclassifiedaseithertraumatic(relatedtoaninjury)oratraumatic(notrelatedtoaninjury).AccuratelydiagnosingandclassifyingONareimportantinhelpingtodirecttreatmentoptions.IdentificationofassociatedriskfactorsandpatienteducationareimportantinsuccessfulmanagementofON.Targetingassociatedriskfactors,pharmacologicmanagement,and/orsurgery,includingjointpreservingproceduresandtotalhiparthroplasty(THA),alsoplaysignificantrolesintheclinicalcareofpatientswithON.EPIDEMIOLOGYOFHIPOSTEONECROSISAlthoughtheexactprevalenceofONisunknown,theincidenceisestimatedtobebetween20,000to30,000newlydiagnosedpatientseachyearintheUS.1ONistheunderlyingdiagnosisinapproximately10%ofallTHAintheUS.2,3ONaffectspeopleofallages,althoughitismostcommonlyseeninpatientsbetweentheagesof30and65years.4Themeanageatdiagnosisistypicallyyoungerthanage50years.3Themale-to-femaleratiovariesdependingontheassociatedcomorbidities.Forexample,alcohol-associatedONismorecommoninmen,whereasONassociatedwithsystemiclupuserythematosus(SLE)ismorecommoninwomen.3Morethan20,000peopleeachyearrequirehospitaltreatmentforhipON.4Inmanyofthesecases,bothhipsareaffectedbythecondition.Mostcommonly,ONaffectstheproximalend(epiphysis)ofthefemur(hipbone).PATHOGENESISOFHIPOSTEONECROSISThemechanism(s)bywhichhipONdevelopsremainsunclear.Forthemostpart,hipONisbelievedtoresultfromthecombinedeffectsofgeneticpredisposition,metabolicfactors,andlocalfactorsaffectingbloodsupplyincludingvasculardamage,increasedintraosseouspressure,andmechanicalstresses.2,5,6Mostexpertsagreethatalackofbloodsupplytothefemoralheadandbonemarrow,whichproducesstemcellsandplatelets,causesdeathoftheosteocytes(cellswithinmaturebone)and/ormesenchymalcells(stemcellsthatformcartilage,bone,andfat).7Theresultisdemineralizationorresorptionofthedeadtissuebynewbutweakerosseoustissue(trabecularthinning),subsequentlyleadingtosubchondralfractureandcollapseofthefemoralhead.OtherproposedmechanismsforthepathogenesisofONincludevasoconstriction-inducedchangescausedbytheadverseeffectsofexcessglucocorticosteroidsaffectingboneandvenousendothelialcells8,9andexcessglucocorticoid-associatedONinvolvingalterationsincirculatinglipidsbelievedtocausemicroemboliinthearteriesthatsupplybonewithblood.10ETIOLOGYOFHIPOSTEONECROSISAcombinationoftraumaticandatraumaticfactorscandirectlycontributetotheetiologyofON(seeSidebar:EtiologicFactorsAssociatedwithOsteonecrosis).Onthebasisoflongitudinalcohortstudiesandmeta-analyses,directriskfactorshavebeendiscoveredthatplayadefinitiveetiologicroleinthedevelopmentofON.Associatedriskfactors,however,accountformostofthelinkstotheeventualdevelopmentofON.11TraumaticCausesofHipOsteonecrosisTraumaticcausesofONincludefemoralneckfracturesordislocationsaswellasdirectinjuryofboneofmarrowelements(eg,relatedtoradiationinjury,dysbarism,orCaissondisease).Themechanisminvolvedinfemoralneckfracturesordislocationsisdamagetotheextraosseousbloodvessels,whichresultsindisruptedbloodsupplytotheaffectedregionofthehip.Hipdislocationisanothertypeoftraumaticinjury,whichaffectsapproximately20%oftrauma-relatedONpatients.12Caissondisease(eg,decompressioninscubadiving)causestheformationofnitrogenbubblesthatcanoccludearterioles,leadingtoON.PatientswhodevelopsymptomscandevelophipONyearsafterexposuretothisprocess.Thedepthanddurationofpressureandnumberofexposuresareimportantfactorsintheprogressionofthisdisorder.13AtraumaticCausesofHipOsteonecrosisNumerousstudiesreportprolongeduseofcorticosteroidsassociatedwiththedevelopmentofONcanbedirectlyrelatedtodurationandtotaldosageofthemedication.14–16PatientstreatedwithprolongedhighdosesofglucocorticoidsappeartobeatthegreatestriskofdevelopingON;however,thesepatientsoftenhavemultipleotherriskfactors.Glucocorticoid-inducedONdevelopsin9%to40%ofpatientsreceivinglong-termtherapy,anddevelopsmuchlessfrequentlyinpatientsreceivingshort-termtherapy.17Onemeta-analysisandsystematicreviewidentifiedanincidenceofONinnearly7%ofpatientswhoused＜2gofcorticosteroids.18Fromthismeta-analysis,alowerriskwasseeninpatientstreatedwithdosesofprednisonelessthan15mg/dto20mg/d.18Onepopulation-basedstudyof98,390patientsshowedtheincidenceofhipONamongpatientswhohadreceivedasingleshort-term,low-dosemethylprednisolonetaperpackwas0.13%,comparedwith0.08%inpatientswhowerenotprescribedamethylprednisolonetaperpack,thusindicatinganumberneededtoharmof2041patients.19Alcoholusehasbeenassociatedwithapproximately31%ofpatientswhodevelophipON.3,20–22ExcessivealcoholconsumptionrelatedtoONofthehipisbelievedtoresultfromthedecreasedbonegenesiscausedbyexcesslipidformationandincreasedintracellularlipiddeposits,leadingtoosteocytedeathandON.23HighdosesofcorticosteroidsandexcessivealcoholusetogetherpresentthehighestassociateddirectriskfactorsforthedevelopmentofhipON24andaccountformorethan80%ofcasesnotrelatedtotrauma.3,6Onestudycompared112patientswhohadidiopathichipONandnohistoryofsystemiccorticosteroidusewith168controls.3,20Anelevatedriskforregularalcoholdrinkersandacleardose-responserelationshipwithalcoholwerenoted,comparedwithcontrols.Therelativeriskswere3.3,9.8,and17.9forcurrentconsumersoflessthan400mL/wk,400mL/wkto1000mL/wk,andmorethan1000mL/wkofalcohol,respectively.9ONiscommoninpatientswithsicklecelldiseasebecauseofitspropensitytocauseredbloodcellsicklingandbonemarrowhyperplasia.Approximately50%ofaffectedpatientsdevelopONbytheageof35years.25SicklecellhemoglobinopathycandirectlycausevascularobstructionandON.ThedevelopmentofONhasbeenreportedin3%to30%ofpatientswithSLE,andthosemostatriskarepatientswhohavetakenglucocorticoidswithregulardosesofprednisonegreaterthan20mg/d.3,26–28ONhasbeenreportedinasmanyas60%ofpatientswithGaucherdisease(ahereditarydisorder)becauseofitsabilitytodirectlyobstructvascularsupply.3,29,30Gaucherdiseaseisanautosomalrecessiveinheriteddisorderofmetabolismwhereatypeoffat(lipid)calledglucocerebrosidecannotbeadequatelydegraded.Normally,thebodymakesanenzymecalledglucocerebrosidase(anormalpartofthecellmembrane)thatbreaksdownandrecyclesglucocerebroside.31OtherlesscommonbutapparentlinkstohipONincludepatientswithantiphospholipidantibodies,Cushingdisease,29andSLE.Thedevelopmentofacutelymphoblasticleukemia,chronicmyeloidleukemia,andacutemyeloidlymphoma3,32placespatientsatincreasedriskforONrelatedtothetreatmentwithsteroidsfortheseconditions.Pancreatitis(usuallyassociatedwithuseofcorticosteroids),pregnancy,chemotherapy,smoking,vasculitis,pleuritis,andcentralnervoussystemfactorssuchasaninflammatoryresponseresultinginareductioninthenumberofsympatheticnervefibers(asseeninrheumatoidarthritis,Crohndisease,Charcotfoot,andinflammatoryboweldisease),havebeenassociatedwithON.33ThereissomeevidencethathipONmayhaveageneticbasisunderlyingassociatedriskfactors.34Forexample,menareaffectedasmuchas3timesmorethanwomenwhenexcessivealcoholuseistheassociatedriskfactor.However,whenlupusorcorticosteroidusearetheassociatedriskfactors,womenareaffectedmoreoftenthanmen.26,27,32SLEisapproximately9timesmorecommoninwomenthaninmen.35Thisincreasedsusceptibilitymaybemadepossible,atleastinpart,owingtodifferencesrelatedtohormonesandsexchromosomes.35Chronicrenalfailureorend-stagerenaldiseaseinpatientsonhemodialysis,hyperuricemia/gout,HIVinfection,hyperlipidemia,organtransplantation,andintravascularcoagulationarealsolinkedtothedevelopmentofON.31,32,36–39Despitethemanypossibleassociationsandlinks,anestimated20%ofONcasesarelabeledasidiopathicorofunknownetiology.7CLINICALMANIFESTATIONSOFHIPOSTEONECROSISHippainisthemostcommonlyreportedsymptomoflater-stageON,althoughasmallproportionofpatientsmaynothavesymptoms.Paininthegroinisthemostcommonlyreportedsymptom,followedbypainreferredintothethighandbuttock.Paincanpresentwithweightbearingorjointmotion.Painatrestoccursinapproximatelytwo-thirdsofpatientswithON,andpainatnightoccursinapproximatelyone-thirdofpatients.33Paininmultiplelocationsofthebodyisrareandsuggestsamultifocalprocess.PhysicalfindingsofhipONaregenerallynonspecificbutmayentailreducedrangeofmotionoftheaffectedjoint,painfulambulation,Trendelenburgsign,and/orcrepitus.3,40,41ClinicalAssessmentofHipOsteonecrosisONofthehipisgenerallyaddressedby1)reviewofapatient’smedicalhistory,2)obtainingappropriateradiologicevaluation,3)determiningthestageofthecondition,and4)developingaplanfortreatmentoptions.42,43WhenevaluatingapatientforON,questionsshouldbedirectedatassessingahistoryofpain,useofmedications(especiallycorticosteroids),surgery,pregnancy,trauma,chronicmedicalconditions(especiallysicklecelldisease,Gaucherdisease,autoimmunedisease,andleukemia),smoking,and/oralcoholuse.Whenaskingaboutinjuries/illnesses,itisimportanttocarefullyexploreinjuriesrelatedtohipfractures,dislocations,orscubadivingbecauseCaissondiseaseisatraumatic.DIAGNOSISANDCLASSIFICATIONOFHIPOSTEONECROSISDiagnosinghipONintheinitialstagesofthedisorderisimportantformanagement43–46;atinitialstages,thediseasemaynotprogress.Inmostcases,patientswithearly-stageONaregenerallywithoutsymptomsandareidentifiedincidentally;unfortunately,mostpatientsdonotpresentforevaluationuntiltheONhasreachedlaterstages.AlthoughthereispresentlynodefinitivetreatmentknowntopermanentlyhaltONfromprogressingtolaterstages,therearetreatmentmethods,suchaslipidloweringagents,anticoagulants,andbisphosphonates,currentlybeingusedforthispurpose.36–38AdiagnosisofONcanaccuratelybemadewhenapatientissymptomatic,imagingfindingsarecompatible,andothercausesofpainandbonyabnormalitieseitherareunlikelyorhavebeenexcluded.Beyondtheclinicalandphysicalexamination,imagingtechniquessuchasradiographsandmagneticresonanceimaging(MRI)scanningarealsousedfordiagnosis.Plainradiographicevaluationisperformedfirst,followedbyMRI.MRIhasbeenreportedtobe＜99%specificandsensitivefordetectingearlyON.47,48MRIimagescanalsoquantitativelyassessthesizeofthelesionorinvolvementoftheaffectedbonebydigitizingtheareaofthefemoralheadoccupiedbybonewithabnormaltexture.49MRIchangesincludewell-demarcatedandhomogeneousfocallesionsonT1-weightedimageswithasingle-densitylineseparatingnormalandischemicbone,aswellasasecondhigh-intensitylineonT2-weightedimages(thepathognomonicdouble-linesign)representinghypervasculargranulationtissue.3Thislevelofimagingdetailisusefulbecausethesizeandextentofthelesionoftheaffectedboneisimportantandcanhelpdirecttreatment.Forend-stagedisease,however,useofMRIinpatientswithONmaybeunnecessarybecausetreatmentoptionsatthisstagecanbelimited.Thesefindingsareoftenclassifiedusingthe4-stageFicatandArletsystem,whichisdescribedhereandinTable1.Theplainradiographcanremainnormalformonthsaftertheonsetofsymptomssuchasgroinpain(StageI).Theearliestradiographicfindingsareusuallymilddensitychanges,followedbysclerosisandcysts(StageII).Findingsthenprogresstothepathognomoniccrescentsign(subchondralradiolucencyseenintheanterolateralaspectoftheproximalfemoralhead)fromsubchondralcollapse(StageIII),andsubsequentlossofsphericity(measurementoftheroundness)orcollapseofthefemoralheadwitheventualjoint-spacenarrowinganddegenerativechangesintheacetabulumthatarevisible(StageIV).Keyradiographicfeaturestolookforinclude1)stage(precollapsevspostcollapse),2)sizeoflesion,and3)amountofheaddepression.Table1Ficat＆ArletclassificationsystemofthefemoralheadClassificationClinicalRadiographsMRIStage0Nosymptoms;preclinicalNormalNormalStage1PossiblegroinpainNormalormildosteopeniaPossibleedemaStage2Groinpainandstiffness;painwithactivityOsteopeniaand/orsubchondralcysts;diffuseporosis;precollapseofjointspaceOutlinesareaofinvolvementofthefemoralheadStage3Groinpain,stiffness,radiationofpain;painwithactivityCrescentsignand/orsubchondralcollapse(flattening)ofjointwithsecondarydegenerativechanges;lossofsphericityoffemoralheadSameasradiographsStage4Groinpainandlimp;painatrestEnd-stagediseasewithcollapse;extensivedestructionofjoint;reducedjointspaceSameasradiographsOpeninaseparatewindowMRI=magneticresonanceimagingAcomputedtomographyscanproducinga3-dimensionalpictureofthebonehasmoderatesensitivitybutisnonspecificandcanposeasignificantradiationburdentopatients.Computedtomographycanhavesomespecificityifthereisalreadyfemoralheadcollapse.Fortunately,mostcliniciansareassuredwiththeirdiagnosisofONwithoutcomputedtomographyscanning,whichisgenerallyreservedfordistinguishingprecollapseandpostcollapsedisease.DifferentialDiagnosisofHipOsteonecrosisBecausepatientswithsymptomatichipONcanpresentwithsymptomssimilartomanyotherhippathologies,theseshouldbeadequatelyruledoutbeforefinaldiagnosis.Bonemarrowedemasyndromeandsubchondralfracturesaretwoofmanypotentialdiagnosesthatneedtoalsobeconsidered.EtiologicFactorsAssociatedwithOsteonecrosisTraumatic-associatedriskfactorsFemoralneckfractureDislocationorfracture-dislocationSicklecelldiseaseHemoglobinopathiesCaissondisease(dysbarism)GaucherdiseaseRadiationAtraumatic-associatedriskfactorsCorticosteroidadministrationAlcoholuseSystemiclupuserthyematosusCushingdiseaseHypersecretionofcortisol(rare)Chronicrenalfailure/hemodialysisPancreatitisPregnancyHyperlipidemiaOrgantransplantationIntravascularcoagulationThrombophlebitisCigarettesmokingHyperuricemia/goutHIVOtherpotentialriskfactorsIdiopathiccausesBonemarrowedemasyndrome,alsoknownastransientosteopeniaofthehip,mayoccurinisolationorinassociationwithinjuries,particularlythosethatresultinneurologicdamage.Inthelattersituation,chronicpainandtransientosteopeniaarefeaturesofthecomplexregionalpainsyndrome(alsoknownasreflexsympatheticdystrophy,causalgia,andotherterms).3BonemarrowedemasyndromecanbedifferentiatedfromONonthebasisofhistologicandMRIfindings.Subchondralfractureofthefemoralheadtypicallyoccursinpatientswithpreexistingosteopeniaandisgenerallythoughttorepresentaninsufficiencyfracture.50Thesefracturesmaybedifficulttovisualizewithplainradiographs.Subtleflatteningissometimespresentwithearlylesions;collapseofthefemoralheadisprogressive.CLINICALMANAGEMENTOFHIPOSTEONECROSISFactorstoconsiderwhendevelopinganoptimalmanagementapproachforsymptomaticONofthehipshouldbeaimedattreatingthestageanddegreeofinvolvementofON,theextentandlocationofbonyinvolvement,thepresence(orabsence)ofsymptoms,andthepatient’scomorbidities.Thegoaloftherapyistopreservethebiologicalhipjointforaslongaspossiblewhilealsotakingintoconsiderationqualityoflifeissuessuchaspatientage,mobility,occupation,andlifestyle.ThreemaintherapeuticoptionsformanagementofhipONinclude1)nonoperativemanagement,2)joint-preservingprocedures,and3)THA.TheeffectsofatraumaticcausesofhipONposespecialconcerns.Forthoseaffected,67%reportnosymptomsbutmayeventuallygoontohaveacollapsedjoint.51Thenaturalhistoryofasymptomaticmedium-sized,andespeciallylarge,osteonecroticlesionsisprogressiontoworseningoftheconditionandeventuallyend-stagediseaseandcollapseofthehipinasubstantialnumberofpatients.Forthosewithsymptoms,approximately80%to85%ofcaseswillresultincollapseofthefemoralheadwithin2years.6EarlydiagnosisofONmaythereforeprovidetheopportunityforearlytreatment,whichcanpreventcollapseand,ultimately,theneedfortotaljointarthroplasty.However,mostpatientspresentlateinthecourseofthedisease,andahighindexofsuspicionisnecessaryforthosewithknownorprobableriskfactors,particularlypatientswithhigh-dosecorticosteroiduse.3SimilarlyforpatientswithasymptomatichipON,thesize,extent,andlocationofthenecroticlesionaffectingthefemoralheadshouldbeconsidered.Generally,lesionsaffectinglessthan15%ofthefemoralheadarebestmanagednonoperatively;lesionsbetween15%to30%shouldbemanagedsurgically;andlesionsinvolvingmorethan30%ofthefemoralheadarelikelytoprogresstocollapse,despitesurgicalintervention,andeventuallyrequireTHA.3,52,53NonsurgicalTreatmentOptionsinHipOsteonecrosisPhysicalTherapyPhysicaltherapymayprovidereliefandalleviatesomesymptomsbutgenerallywillnotprecludeprogressivehipONfromadvancingtolaterstages.54Similarly,restrictingweight-bearingwiththeuseofassistivedevicessuchascrutchesoracanemaybeusefultocontrolsymptomsofpain,weakness,andantalgicgait.PhysicaltherapyisnotappropriateifthegoaloftreatmentistopreventthehipfromrequiringTHA,andtodatethereisnoevidencethatweight-bearingrestrictionsarehelpfulinpreventingprogressiveONdiseasefromadvancingtoend-stagedisease.MedicationsNonsteroidalanti-inflammatorydrugsandacetaminophenmayprovidetemporaryreliefofpaininsymptomaticpatients.Opioidmedicationsmaybeusedjudiciouslyandforshortperiodsoftimewhenotheragentsareineffectivetomanagemoderate-to-severepainwhilesurgicaloptionsarebeingconsidered.InvestigationalmedicationoptionscurrentlybeingusedbutthatarenotprovenorreliablyusedtotreatONinclude1)anticoagulants,2)bisphosphonateantiresorptiveagents,3)cholesterolloweringstatins,and4)hyperbaricoxygen.SurgicalOptionsinEarly-StageHipOsteonecrosisCoreDecompressionCoredecompressionisaminimallyinvasivesurgicaltechniqueperformedtomanagesymptomsinearlystages(precollapse)ofthecondition(eg,FicatandArletStagesIandII).Theprocedureinvolvesdrillingholesintothefemoralheadtorelievepressureandcreatechannelsfornewbloodvesselstonourishtheaffectedareas.Thepublishedsuccessratesofcoredecompressionvarygreatlyfrom40%to100%,dependingonpatientpopulation.35Highersuccessratesaftercoredecompressionareseeninpatientswiththeearliestdiseasestages.Patientswithsuccessfulcoredecompressionprocedurestypicallyreturntounassistedambulationafterseveralmonthsandcanhavecompletepainrelief.55BoneGraftingCoredecompressioncanbecombinedwithbonegraftingtohelpregeneratehealthyboneandsupportcartilageatthehipjoint.Abonegraftishealthybonetissuethatistransplantedtotheareaofnecroticordeadbone.Astandardtechniqueusesanautograftthatinvolvestakingbonefromonepartofthebodyandmovingittoanotherpartofthebody.Abonegraftthatisharvestedfromadonororcadaveriscalledanallograftandistypicallyacquiredthroughabonebank.BoneMarrowAspirateConcentrationThebonemarrowaspirateconcentrationinjectionprocedurewithcoredecompressioninvolvestheuseofconcentratedbonemarrowthatisinjectedintothedeadboneofthehip.Thisinvestigationaltechniqueharvestsstemcellsfromapatient’sbonemarrowandinjectsthemintotheareaofON.9Thebonemarrowaspirateconcentrationprocedureishypothesizedtopreventfurtherprogressionofthediseaseandtostimulatenewbonegrowth.56PercutaneousDrillingAnothersurgicaloptionispercutaneousdrilling.Inthisprocedure,aholeisdrilledpercutaneouslythroughthefemoralnecktotheaffectedsiteinthefemoralhead.Onereporton45hipswithameanfollow-upof24monthsreported24(80%)of30hipswithFicatandArletStageIdiseasehadsuccessfuloutcomes(definedasHarrisHipScore＜70).57Amorerecentstudycomparingmultipledrillingvsstandardcoredecompressionshowedfavorableresultsinfavorofpercutanteousdrilling.28SurgicalOptionsinAdvanced-StageHipOsteonecrosisVascularizedBoneGraftAvascularizedfibulagraftisamoreinvolvedsurgicalprocedureinwhichasegmentofboneistakenfromthefibulawithitsbloodsupply.Thegraftisthentransplantedintoaholecreatedinthefemoralneckandhead,andthearteryandveinarereattachedtohelphealtheareaofON.55OsteotomyOsteotomyinhipONcanbeperformedtoremovenecroticboneawayfromprimaryweight-bearingareas.AlthoughthisoperationmaydelayTHAsurgery,itismostusefulinpatientswithidiopathicONwhodemonstratesmallprecollapseorearlypostcollapseofthefemoralhead.Aconsequenceofosteotomies,however,isthattheymakesubsequentTHAmorechallengingandareoftenassociatedwithanincreasedriskofnonunionofthebone.NonvascularizedBoneGraftThereare3typesofnonvascularizedbonegraftingsurgeries:1)trapdoorprocedure,2)lightbulbtechnique,and3)Phemistertechnique.ThetrapdoorprocedureisoneinwhichautogenouscancellousandcorticalbonegraftinghavebeensuccessfulinFicatandArletStageIIIhipONinpatientswithsmall-tomedium-sizedlesions.Areviewoftheresultsof30trapdooroperationsperformedon23patientswithFicatandArletStageIIIorStageIVONofthefemoralheadperformedthroughaso-calledtrapdoormadeinthefemoralheadrevealedagoodorexcellentresultasdeterminedbytheHarrisHipScoresystem.11LightbulbTechniqueThelightbulbtechniqueusesacorticalwindowintheanterioraspectofthefemoralneck.Necroticbonecanberemovedusingthiswindow,whichcanbelaterpackedwithnonvascularizedbonegraft.Wangetal55evaluated110patients(138hips)whounderwentthelightbulbprocedure.Atmeanfollow-upof25months,meanHarrisHipScoresimprovedfrom62to79points.Atotalof94hips(68%)wereconsideredtohavesuccessfuloutcomesatlatestfollow-up.Radiographicimprovementswerenotedin100%ofAssociationResearchCirculationOsseousStageIIapatients,77%instageIIbpatients,and51%instageIIcandIIIapatients.55PhemisterTechniqueInthePhemistertechnique,atrephineisinsertedthroughthefemoralnecktocreateatracttothelesion.Asecondtrephineistheninsertedtocreateanothertracttothelesionsite.Acorticalstrutgraftcanthenbeplacedinthelesion.Arecentreviewreportsthisproceduretohaveaclinicalsuccessraterangingfrom36%to90%.25TotalHipArthroplastyOncethefemoralheadhasundergonemajorcollapse,replacingthehipjointistheonlypracticaloperativeoptionandoffersthemostpredictablepainreliefinadvancedON.THAissuccessfulinrelievingpainandrestoringfunctioninthemajorityofpatients.45–47InTHA,thediseasedcartilageandboneconstitutingthehipjointisreplacedwithartificialimplantsmadeofmetalandplastic.Aprosthetichipreplacementgenerallylasts15yearsbeforeitmightwearoutandneedtoberevised.Fortheyoungeragegroup,aTHAmaybeasuboptimalsolutionbecauseofpossibleactivityrestrictions.Additionally,becauseprostheseshavelongevityrestrictions—componentswearafterlong-termuse—thesepatientswilllikelyrequirearevisionTHAlaterinlife.THAmustbecarefullyconsideredandbalancedagainstqualityoflifeissues,butitisnotabsolutelycontraindicatedforyoungerpatients.PATIENTEDUCATIONABOUTHIPOSTEONECROSISPreventionofOsteonecrosisPatienteducationaboutriskfactors,therapies,andmanagementisessentialforpatientstomakebetter-informeddecisionsabouttheircondition.TheprocessofONeducationinvolvesidentificationofanindividual’sassociateddisordersandriskfactorsrelatedtoON.PatientswithasymptomaticONmayhaveahighprevalenceofprogressiontosymptomaticdiseaseandfemoralheadcollapse.Educationforpatientswithasymptomaticdiseaseisprecautionaryandimperativetoensuremodificationofriskfactorsandoptimizationofcare.PreventingatraumaticONrequires1)avoidingexcessiveuseofalcoholdefinedas＜15drinks/wkformenand＜8drinks/wkforwomen,102)avoidingsmoking,and3)reducingcorticosteroidstothelowestpossibletherapeuticdose.InformingpatientsaboutthecorrelationbetweencorticosteroiduseandpotentialdevelopmentofONiscriticalinmanagementofthiscondition.PreventionofProgressionofOsteonecrosisPatientsdiagnosedwithearly-stageONshouldbeadvisedoftheaforementionedprecautionsandshouldavoidplacingexcessivepressureontheirjoints,followahealthydiet,andmaintainanappropriateweighttomitigateprogressionofON.Althoughahealthydietinitselfdoesnotdirectlyreducepressureonapatient’sjoints,weightloss(ifoverweight/obese)willreduceaxialloadsonthehipjoint,whichinturndecreasesthestrainappliedtothefemoralhead/neck(toboththetensionandthecompressionsides).42CONCLUSIONONisapathologicandoftenpainfulconditioninvolvingnecroticareasoftissuethatcanaffectanybonyjointinthebody.ThehipjointisthemostcommonlocationforONandshouldalwaysbeproperlyevaluated,utilizingradiographicscreeningandMRIscanning,whenONisinitiallydiagnosedinanotherbodypart.TheearlieradiagnosisofONismade,thebettertheopportunitytosavethehipjointwithoutsurgicalinterventionorwithminimallyinvasivesurgicaltechniques.AfteradiagnosisofONismade,thesize,extent,andlocationofthelesionandtheclassificationstagesareconsideredtodevelopanoptimalplanofcare.Thepresenceorabsenceofsymptomsisimportantinthisprocess.Thegoalsoftreatmentinvolveattemptingtopreservethebiologicalhipjointforaslongaspossibleandconsiderationofapatient’slifestyleandqualityoflifeissues.Todate,the2maintherapeuticoptionsformanagementofhipONincludejoint-preservingproceduresandTHA.PatienteducationaboutpotentialriskfactorsanddevelopmentofONisessentialtopreventtheconditionand/ortopotentiallypreventorhaltprogressionofearly-stagediseasetolater-stagedisease.2023年07月10日1134
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陶可主治醫(yī)師 北京大學(xué)人民醫(yī)院 骨關(guān)節(jié)科 股骨頭壞死：病因、診斷及治療方式：2019英國(guó)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(xiǎn)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(xì)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(qǐng)考慮對(duì)髖部進(jìn)行核磁共振MRI掃描，并轉(zhuǎn)診至骨科（保髖治療）團(tuán)隊(duì)。?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(dòng)(髖關(guān)節(jié)查體之內(nèi)外旋轉(zhuǎn)活動(dòng))。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(hào)的改變。Fig3ProposedpathwayformanagingAVNFHinaprimarycaresetting.圖3?在基層醫(yī)療機(jī)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(bào)告，有左側(cè)腹股溝疼痛放射到膝蓋的病史。疼痛很嚴(yán)重，走路時(shí)更嚴(yán)重，并伴有跛行。一年后，患者再次去看全科醫(yī)生，盡管進(jìn)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(jí)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(jī)制尚不清楚；風(fēng)險(xiǎn)因素可能會(huì)以某種方式影響微循環(huán)，但這尚未得到研究證實(shí)。共同的終點(diǎn)是微循環(huán)異常和壞死。軟骨下骨隨后塌陷，導(dǎo)致進(jìn)行性、繼發(fā)性髖關(guān)節(jié)骨關(guān)節(jié)炎。在英國(guó)，平均發(fā)病年齡為58.3歲，每10萬(wàn)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(guó)，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(xiǎn)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(huì)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(bào)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(huì)漏診呢？股骨頭壞死（AVNFH）很少見?；加羞@種疾病的患者可能同時(shí)患有慢性風(fēng)濕病和血液病。這可能會(huì)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(shí)，這些都是股骨頭壞死（AVNFH）的危險(xiǎn)因素。查體可以幫助識(shí)別可能引起疼痛的解剖結(jié)構(gòu)，因?yàn)轶y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(gè)部位。臨床表現(xiàn)可能會(huì)被錯(cuò)過，因?yàn)橛捎跁r(shí)間和空間的限制，在基層醫(yī)療機(jī)構(gòu)中準(zhǔn)確確定單純由于髖關(guān)節(jié)運(yùn)動(dòng)時(shí)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(huì)錯(cuò)誤地讓人放心并延遲適當(dāng)?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(huì)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(jìn)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?yàn)楣琴|(zhì)破壞通常發(fā)生在發(fā)病后2年內(nèi)，因此不可能進(jìn)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(tuán)隊(duì)有時(shí)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(jìn)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(jìn)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(xiǎn)很大。如何診斷股骨頭壞死（AVNFH）？股骨頭壞死（AVNFH）診斷從仔細(xì)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(xì)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(fù)重和運(yùn)動(dòng)時(shí)疼痛更嚴(yán)重。通常沒有外傷史。詢問危險(xiǎn)因素，如果患者有任何“危險(xiǎn)信號(hào)”，請(qǐng)進(jìn)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(xiǎn)通常是在單側(cè)確診后的2年內(nèi)。框1：需要轉(zhuǎn)介或進(jìn)一步評(píng)估的危險(xiǎn)信號(hào)：?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(xiǎn)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(xì)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(dú)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(shí)進(jìn)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(jìn)一步檢查和轉(zhuǎn)診。股骨頭壞死（AVNFH）通過髖關(guān)節(jié)MRI進(jìn)行診斷，當(dāng)與臨床癥狀密切相關(guān)時(shí)，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(dāng)有其他原因或高度懷疑風(fēng)濕病或感染時(shí)，才應(yīng)考慮進(jìn)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(shí)，請(qǐng)就診于骨科醫(yī)生（圖3）。在二級(jí)醫(yī)療機(jī)構(gòu)就診時(shí)，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(tuán)隊(duì)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(duì)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(zhēng)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(zhǎng)達(dá)7年的時(shí)間里避免88%的患者進(jìn)行全髖關(guān)節(jié)置換術(shù)治療。術(shù)后恢復(fù)包括12個(gè)月的非負(fù)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(gè)月即可感受到完全的治療益處。專業(yè)的三級(jí)醫(yī)療機(jī)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(jìn)血管再生和減輕受損髖關(guān)節(jié)表面的負(fù)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(xiǎn)，特別是對(duì)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(xiàn)出處：JonathanNLamb,ColinHolton,PhilipO'Connor,PeterVGiannoudis.Avascularnecrosisofthehip.BMJ.2019May30;365:l2178.doi:10.1136/bmj.l2178.2023年07月09日527
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美國(guó)股骨頭壞死手術(shù)方法有什么特點(diǎn)？＃美國(guó)＃美國(guó)股骨頭壞死＃美國(guó)髖關(guān)節(jié)置換＃美國(guó)骨科＃美國(guó)骨科專家
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高緒仁主任醫(yī)師 徐州醫(yī)科大學(xué)附屬醫(yī)院 骨科 美國(guó)202年的這個(gè)美國(guó)髖關(guān)節(jié)學(xué)會(huì)上，他們有一個(gè)報(bào)道，就是說統(tǒng)計(jì)了美國(guó)2010年到2020年這十年間，美國(guó)治療股骨頭壞死的這個(gè)手術(shù)的情況一個(gè)統(tǒng)計(jì)，哎，我們從這個(gè)總體的統(tǒng)計(jì)比例上，你可以看到，就是這個(gè)美國(guó)的，哎，將近90%的是治療股骨頭壞死的手術(shù)方法是什么？ 這個(gè)患者是選用了人工全髖關(guān)節(jié)置換手術(shù)啊，其他呀，你像這個(gè)半髖置換啊，隨心減壓呃，骨移植啊，還有節(jié)骨啊，還有這個(gè)髖關(guān)節(jié)關(guān)節(jié)鏡，這些手術(shù)方法占的比例，腫起來合起來。 也就是10%，雖然說你看從這個(gè)圖上看啊，雖然說是這個(gè)這個(gè)保守治療不患髖關(guān)節(jié)的方法，雖然略微在這十十年間，從2010年到2022年略微有所增加，但是人工全髖關(guān)節(jié)置換手術(shù)仍然是在美國(guó)治療股骨頭壞死的一個(gè)最主流的手術(shù)，它的手術(shù)率是90%左右。2023年06月12日69
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張超主任醫(yī)師 云南省第一人民醫(yī)院 骨科 周未一位中年患者來復(fù)查，患者3月前因?yàn)榧に叵嚓P(guān)性左髖疼痛股骨頭壞死到我院就診，診斷為2期股骨頭壞死。患者因?yàn)槠渌膊?，需要長(zhǎng)期口服激素治療。曾經(jīng)到多家醫(yī)院就診，均建議行人工關(guān)節(jié)置換手術(shù)。到我院就診，考慮患者年齡及工作，建議保關(guān)節(jié)手術(shù)治療，微創(chuàng)手術(shù)死骨刮除植骨修復(fù)手術(shù)。術(shù)后3月，患者來復(fù)查，髖關(guān)節(jié)基本不痛?；颊咝g(shù)后扶雙拐保護(hù)3個(gè)月，建議患者再扶拐保守3個(gè)月。保住原生股骨頭，讓患者能夠復(fù)返工作崗位及正常生活。股骨頭壞死后，建議全部的患者禁止喝酒及抽煙。2023年04月09日423
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