Chinese Journal of Tissue Engineering Research ›› 2020, Vol. 24 ›› Issue (15): 2440-2446.doi: 10.3969/j.issn.2095-4344.2629
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Han Guangtao, Li Haohuan, Gao Feng
Received:
2019-10-24
Revised:
2019-11-01
Accepted:
2019-11-25
Online:
2020-05-28
Published:
2020-03-23
About author:
Han Guangtao, Master candidate, Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
Supported by:
CLC Number:
Han Guangtao, Li Haohuan, Gao Feng. Role and significance of anterior cruciate ligament injury in the development of post-traumatic knee osteoarthritis[J]. Chinese Journal of Tissue Engineering Research, 2020, 24(15): 2440-2446.
2.1 创伤后骨关节炎产生的机制 受许多因素影响,前交叉韧带损伤后导致软骨分解和发展为骨关节炎,其机制尚未完全了解。前交叉韧带损伤后骨关节炎的产生可能与软骨下骨和透明软骨损伤的结果有关,在受伤时严重的外力会破坏关节内结构,MRI测量结果显示,隐匿性骨软骨损伤或骨挫伤发生在80%-90%的急性前交叉韧带损伤患者中,最常见于胫骨后外侧平台和股外侧骨[4]。这些损伤提示关节软骨在损伤时会承受相当大的机械冲击。 除了最初的创伤外,缺乏功能正常的前交叉韧带还会导致膝盖的静态和动态负荷发生慢性变化,并增加对软骨和其他关节结构的损伤。因此,随着时间的推移会发生关节内损伤,尤其是软骨和半月板损伤,这些病变在骨关节炎的发展中起着重要作用。许多研究表明,伴随关节内损伤的患者骨关节炎发生率更高。 前交叉韧带重建甚至历史上进行过的前交叉韧带修复,都被认为可以通过恢复膝关节的生物力学稳定性来预防骨关节炎。尽管前交叉韧带重建确实可以改善前交叉韧带损伤患者的膝关节稳定性,但不能恢复正常的膝关节运动。虽然尚未显示前交叉韧带重建能够预防创伤后骨关节炎,但人们对更多的解剖重建技术是否能够恢复膝关节运动学并降低骨关节炎风险抱有浓厚的兴趣。 尽管前交叉韧带重建可以减少膝关节不稳,但创伤后骨关节炎的发生率仍然很高。前交叉韧带损伤可引发一系列致病过程。有研究认为关节受伤后数天和数周内,软骨蛋白聚糖和Ⅱ型胶原蛋白的表达不断增加[5]。在前交叉韧带重建时进行的软骨活检的组织学研究中,有组织学证据表明,前交叉韧带损伤后1年内,变性软骨蛋白聚糖和Ⅱ型胶原蛋白的表达持续增加,这与前交叉韧带损伤的早期增加有关[6];而且蛋白聚糖的总含量与特发性骨关节炎中观察到的相似。 包括前交叉韧带损伤在内的膝关节的任何损伤都可能导致关节变性。关节损伤后,多种炎性细胞因子或生物标志物(例如肿瘤坏死因子α、白细胞介素1β和白细胞介素6)表达上调,尽管这些研究表明这些炎性细胞因子持续升高的时间差异很大,但可以肯定的是,前交叉韧带损伤后细胞因子立即升高并且可能持续较长时间。此外,如果进行前交叉韧带手术,则关节会再次受到创伤,导致关节炎性因子增多,并伴有术后血栓形成。涉及这种炎症的细胞因子与软骨破坏有关,并已被确定为治疗软骨破坏的靶点。 2.2 创伤后骨关节炎产生的危险因素 为了减少创伤后骨关节炎的发生或发展,确定与这种致残过程有关的危险因素将对治疗这种疾病而言是有益的。创伤后骨关节炎的潜在危险因素包括前交叉韧带重建、半月板状态、体质量指数、软骨损伤、年龄、移植物选择、受伤与手术之间的时间间隔等。 2.2.1 前交叉韧带重建 由于前交叉韧带损伤会显著增加骨关节炎风险,所以前交叉韧带重建的手术目标是重新恢复前交叉韧带功能并防止关节不稳,因为关节不稳可能导致关节软骨和其他软组织的重复损伤。但是,没有研究表明前交叉韧带重建可以防止创伤后骨关节炎[7]。 在前交叉韧带重建术出现之前,当前交叉韧带损伤更常以非手术方式治疗时,一项研究显示,在损伤后14年,1/3未经修复或重建的前交叉韧带损伤治疗的患者表现出关节间隙狭窄或明确的骨关节炎[8]。在这项研究中,这些患者中有86%在手术时切除了1个或2个半月板,并且75%的患者恢复了先前的运动。在一项长期随访的回顾性队列临床研究中,研究者评估了19名遭受前交叉韧带损伤且未经治疗的运动员[9],所有运动员都恢复了高水平运动,但在20年的随访中,95%的膝盖表现出严重的骨关节炎和关节不稳症状,并且35年后超过50%的患者接受了全膝关节置换。 有研究指出,前交叉韧带重建患者不能阻止10年后骨关节炎的发生。接受前交叉韧带重建的患者与一组未经手术治疗的患者的影像学结果相比,受伤后17-20年,2组在X射线片上均显示了关节退行性改变[10]。接受前交叉韧带重建治疗的患者中,一半的患者出现了轻度的关节退行性变,而16.5%患有严重的骨关节炎。但是在未经手术治疗的患者中,56%的患者患有严重的骨关节炎。他们认为,前交叉韧带的重建不能预防骨关节炎,但会降低其发病率。有研究认为,在接受了MRI的非手术和重建治疗后,发现与手术治疗的患者相比,非手术患者的胫骨内侧平台和软骨变性的风险增加[11]。此外,还比较了经关节镜确认的前交叉韧带损伤的非手术治疗与重建治疗的比较,观察到前交叉韧带重建患者的膝关节稳定性明显好,但发生骨关节炎的可能性明显要大。但是研究人员排除了2组重要的患者:伴有半月板、软骨或其他韧带损伤的患者和需要在实验时进行翻修手术的患者[12]。与手术治疗的前交叉韧带损伤相比,非手术治疗的前交叉韧带损伤导致需要半月板病变的概率更高。但是,这项研究没有考虑到半月板撕裂继发的膝关节骨关节炎程度,这可能会影响他们关于骨关节炎发病率的结论。 这指出了前交叉韧带损伤中患者治疗和评估的特性,一些具有特征性损伤的患者可能比其他患者更适合进行手术。例如,目前尚不清楚当非手术治疗前交叉韧带损伤时会发生什么继发性损伤。除去半月板损伤的因素,可以使单发前交叉韧带损伤的患者群体更加均一。还有研究发现,与未受伤的对侧膝关节相比,长期而言,单独的前交叉韧带损伤的运动员在前交叉韧带重建后没有增加创伤后骨关节炎发生的风险[12]。上述结论为这一人群的前交叉韧带重建提供了支持,因为手术可以防止继发于半月板的半月板和软骨损伤。此外,前交叉韧带患者一段时间的非手术治疗后重建率增加,这可能被认为是支持原发性前交叉韧带重建的论点[13]。相反,如果患者愿意更改运动方式以避免前交叉韧带损伤的非手术治疗,则可能更可取。还有研究指出,前交叉韧带受伤患者同意适度活动以免再次受伤可以降低骨关节炎发生率[14]。 有研究得出结论,通过X射线和骨扫描评估接受重建的患者发生骨关节炎的概率更高[15]。作者指出,膝关节重建患者退行性关节疾病的发生率增加可以部分解释为膝关节重建患者中半月板手术的发生率较高。但是,对未进行半月板手术的患者进行的骨扫描评分的比较显示,在膝关节重建患者中骨关节炎的发生率较高。 2.2.2 半月板状态 半月板的状态是前交叉韧带损伤后骨关节炎发生的至关重要的因素。多项研究报道,在进行前交叉韧带修复或重建时,半月板损伤、半月板手术或半月板切除术会增加骨关节炎风险。最近的系统评价指出,半月板损伤和半月板切除是创伤后骨关节炎的危险因素[16-20]。无论患者是否接受前交叉韧带手术或非手术治疗,半月板的状况已被确定为前交叉韧带损伤后发生创伤后骨关节炎的最重要因素。有研究对前交叉韧带重建术后10年患者的影像学表现进行比较,将患者分为2组:前交叉韧带重建时半月板完整的患者和前交叉韧带重建时进行半月板切除的患者[21],25例半月板完整的患者中有2例发生骨关节炎,而9例经半月板切除术的患者中全发生骨关节炎。因此,作者指出,应尽可能修复半月板,而不是去除半月板。还有研究发现,在12年前足球比赛中遭受前交叉韧带损伤伴半月板损伤的年轻女性中,膝骨关节炎患病率很高[22]。作者指出,接受了半月板手术的前交叉韧带受伤运动员的膝骨关节炎患病率高于未进行半月板手术的运动员。同样有研究对男性足球运动员进行了评估[23],与单纯的前交叉韧带损伤的患者相比,伴有半月板损伤患者的骨关节炎比例更高。还有研究对前交叉韧带重建并进行半月板切除术的患者进行X射线检查,半月板切除的前交叉韧带重建患者发生骨关节炎的比例大于半月板未切除的前交叉韧带重建患者。作者进一步评估了接受过半月板切除的患者,并指出接受过半月板切除术的19例患者中有16例出现了骨关节炎。有研究发现,在半月板切除的15例患者中有13例发生关节退行性改变,而在半月板完整或修复的46膝中只有12膝出现了这种变化[24]。 在一项有趣的研究中,对265例患有骨关节炎的男女进行了MRI检查,有49例患者发现前交叉韧带完整性受损[25]。值得注意的是,前交叉韧带切除增加了胫骨内侧股室软骨丧失的风险;然而,根据内侧半月板损伤进行调整后,软骨损失的风险没有增加。根据这项研究,在骨关节炎患者中,似乎伴随半月板病理改变介导的软骨损失风险增加。 与半月板损伤相关的骨关节炎升高的发现可能是由于部分或全部半月板切除术后膝关节稳定性降低和膝关节接触力学改变所致[26]。此外,与半月板切除术相关的胫股关节间隙的减少可能会导致软骨变性[27]。 半月板修复或半月板切除而不是完全半月板切除可以解决受伤的半月板。近年来,尽管已经进行了部分而不是全部的半月板切除术,但与前交叉韧带手术相关的骨关节炎的发生率仍然很高,尤其是与无半月板损伤的前交叉韧带手术相比。存在前交叉韧带损伤的半月板修复术也很常见,因为结果显示,与部分半月板切除患者相比,半月板修复的前交叉韧带重建患者的骨关节炎发生率较低[28]。 2.2.3 体质量指数 众所周知,在没有前交叉韧带损伤的患者中,体质量指数与膝关节炎的发作和进展有关[29]。多项研究发现,患者的体质量指数与前交叉韧带损伤后的膝关节间隙变窄或膝关节骨关节炎相关[30-32]。 有研究旨在确定前交叉韧带重建期间观察到的关节内损伤的危险因素,并发现身高、体质量和体质量指数是前交叉韧带重建期间观察到的关节退行性变和半月板损伤的重要危险因素[33]。尽管作者没有将他们的发现与骨关节炎的发生相关联,但其他研究也支持了关节内损伤是骨关节炎发生的危险因素。因此,认为运动员可以通过维持较低的体质量和体质量指数来降低某些关节内病变的风险,从而有可能改善前交叉韧带重建后的长期功能病变。 2.2.4 软骨损伤 前交叉韧带损伤时伴有软骨的损伤是创伤后骨关节炎产生的另一个危险因素。通过对关节镜检查过程中关节软骨的评估研究发现,与“无软骨损伤”组相比,“软骨损伤”组的骨关节炎评分有所提高[34]。在另一项研究中,软骨病变被显示为两个关节腔内骨关节炎发展的危险因素。相反,研究发现外侧隔室的软骨病与膝骨关节炎没有显著相关,但是内侧隔室软骨病与膝骨关节炎显著相关[35]。 关于软骨损伤与骨关节炎的关系存在多种不同的理论。创伤时关节软骨的损伤可能直接导致骨关节炎。同样,前交叉韧带损伤后的软骨不稳以及反复进行的旋转运动可能会增加软骨损伤并导致骨关节炎的发展。与对侧膝关节相比,软骨损伤还产生生化级联反应,软骨破坏性细胞因子浓度升高,而软骨保护性细胞因子浓度降低。 隐匿性骨软骨损伤或骨挫伤与关节软骨损伤之间的关系尚不清楚。急性前交叉韧带损伤患者中80%-90%会发生骨挫伤,最常见于胫骨后外侧平台和股外侧平台。研究指出,从急性前交叉韧带损伤开始到急性前交叉韧带损伤后3年,骨髓水肿的大小与软骨退变有关。但是,其他研究表明骨挫伤与软骨变性或骨关节炎之间无相关性。研究得出结论,在最初受伤时出现骨挫伤并没有显著改变骨关节炎的发生率[36]。 2.2.5 年龄 毫不奇怪,年龄已被确定为创伤后骨关节炎发生的危险因素[37]。有研究发现,年龄在前交叉韧带重建手术时被证明有可能产生髌股骨关节炎,但不产生胫骨股骨骨关节炎[38]。 软骨细胞衰老和先前存在的关节变性在内的因素增加了发生骨关节炎的可能性。换句话说,因为骨关节炎不仅是关节退化的过程,而且是关节机械磨损和重塑的过程,所以合成代谢和分解代谢过程之间的平衡会随着年龄的增长而降低。在前交叉韧带研究中,年龄通常被忽略,因为大多数接受前交叉韧带重建的患者都是年轻人。 2.2.6 移植物选择 随着外科手术技术的改进,前交叉韧带损伤有许多移植物可供选择。而对于移植物选择的意见不同表明缺乏对前交叉韧带重建最佳移植物选择的研究。尽管大多数研究报告了基于优先选择移植物进行前交叉韧带重建的结果,但一些研究已经确定了预防创伤后骨关节炎的较好移植物选择。 2.2.7 受伤与手术干预之间的时间间隔 在选择手术干预的患者中,关于前交叉韧带重建时间的争议依旧存在。由于前交叉韧带重建的目标之一是防止继发性半月板或软骨损伤,因此许多人认为前交叉韧带手术不应推迟。研究表明,与后期重建相比,早期前交叉韧带重建可以减少骨关节炎的发展[39]。 有研究得出结论,受伤和手术之间的时间延迟可能是胫股骨关节炎的预测指标[40]。还有研究证实,在初次受伤后6个月以上进行重建的患者中,有52%出现了骨关节炎[41]。此外,在初次受伤后2年以上进行重建的患者中,80%的患者产生了严重的骨关节炎,这表明更长的损伤和手术间隔时间不仅会增加骨关节炎的风险,还会增加其严重性。特别是对于打算进行旋转运动的人而言,提倡他们尽早进行前交叉韧带重建。在对77例前交叉韧带损伤患者膝部X射线片进行的研究中,研究者发现,与慢性前交叉韧带损伤的患者相比,急性前交叉韧带损伤的患者在手术当天的膝关节退行性变程度较低,但2组的术后膝关节退行性变相同[42]。 2.3 预防措施 预防前交叉韧带损伤是预防创伤后骨关节炎的首要方法。目前正在进行大量研究来这种伤害的风险,从而寻找降低前交叉韧带损伤率并寻找改善损伤后康复的方法。目前,神经肌肉训练是减少前交叉韧带损伤发生率的最有效工具[43]。在一项非随机的前瞻性研究中,参加神经肌肉和本体感受性能计划的女运动员在与年龄和技能匹配的对照组相比,前交叉韧带损伤分别下降了88%和75%[44]。而对所有前交叉韧带预防伤害培训计划的运动员进行系统评估,研究人员发现预防组的运动员相对非预防组而言前交叉韧带损伤风险显著降低[45]。 "
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