青少年特发性髁突吸收或系发育期异常咬合所致软骨退变相关的病理性改建

Juvenile idiopathic condylar resorption may fundamentally represent condylar cartilage degradation associated with pathological remodeling at growth and developmental stage initiated by aberrant occlusion

摘要

青少年特发性髁突吸收（JICR）是一种发病率较低的颞下颌关节疾病，以髁突组织进行性“吸收”为主要特征，造成患者下颌升支的高度降低、下颌后缩、前牙开𬌗等口颌面畸形。根据笔者研究团队的最新动物实验研究结果，与生长发育完成后出现的髁突吸收不同，JICR可能是发育期异常咬合所致关节软骨退变相关的髁突病理性改建。本文从文献所报道的病因、病理机理、诊断、鉴别诊断和治疗等方面，论证了这一观点：JICR的病因、病理机理尚未明确，损伤性负荷（包括异常咬合）具有一定的致病意义；目前JICR的诊断和治疗均存在很大的挑战性，确诊JICR主要依靠影像特征，但在早期影像特征尚不明显时，确诊该症比较困难，下颌后缩等Ⅱ类错𬌗畸形相关的颌面部畸形常被作为该症的早期表现之一；一些学者反对在JICR病变活跃期进行积极的治疗，认为此时的治疗有导致疾病加重的风险，但如果考虑到创伤性咬合的病因意义，推迟治疗可能导致错失最佳保守治疗时机、加剧髁突病变和口颌面畸形等问题。笔者认为，应尽快诊断和矫正造成该症的异常咬合，防止口颌面畸形的出现或加重。有效诊断和治疗咬合问题，成为解决JICR这一疑难疾病的关键。

Abstract

Juvenile idiopathic condylar resorption (JICR) is a rare temporomandibular joint problem characterized by the progressive resorption of condylar tissues, leading to mandibular ramus height reduction, mandibular retrognathia, and anterior open bite. Emerging evidence from recent animal studies in the laboratory indicated that different from conventional pathological resorption observed in developed condyles, JICR could be condylar cartilage degradation associated with pathological remodeling at growth and developmental stage initiated by aberrant occlusion. At present, however, there is an argument which is evidenced with publications in the etiology, pathogenesis, diagnosis, differential diagnosis and treatment of JICR. The etiology and pathogenesis of JICR remain obscure. Traumatic loading, including that from aberrant occlusion, plays a role in JICR. The diagnosis and differential diagnosis of JICR are challenging. They mostly rely on imaging signs of the condyle deformity, which are not significant at early stages. Making a definite diagnosis of JICR at the early stage is difficult. Retrognathia related maxillofacial deformity is often taken as an early sign of JICR. Many researchers opposed the application of orthodontic and orthognathic treatment during the active phase of JICR because of risks of exacerbating condylar resorption. However, given that traumatic occlusion is etiological to JICR, delayed intervention may compromise conservative management efficacy and progression of the condylar and orofacial deformities. Here, the author advocates for the prompt diagnosis and correction of underlying traumatic occlusion to prevent deformity progression. Effective diagnosis and management of malocclusion constitute the cornerstone for addressing this clinical conundrum.

Graphical abstract

关键词

颞下颌关节 / 髁突 / 咬合 / 特发性髁突吸收 / 开𬌗 / 青少年

Key words

temporomandibular joint / condyle / occlusion / idiopathic condylar resorption / open bite / juvenile

1　 关于JICR的病因及病理机理

JICR的病因病理学说主要有激素紊乱学说和损伤性负荷相关的组织改建学说。

1.1　 激素紊乱学说

JICR病例中女性占比高达60%~90%^[3,12,25-26]，因而雌性激素与JICR的关系受到关注。17β-雌二醇是主要的雌激素之一，与妊娠和哺乳有关，可促进骨保护素表达、降低破骨细胞活性。血清17β-雌二醇减少被认为是发生髁突吸收的重要原因之一^[27]。但雌激素对骨、软骨组织的作用并不是单向的，高水平生理浓度的血清17β-雌二醇对TMJ关节软骨及关节盘有损伤作用^[28-30]。Alsabban等^[12]对88名颌面外科医生经手的100例JICR患者做了调查分析，结果显示：94例女性患者中有42例正在服用避孕药，但有激素不平衡病史者仅占所收集病例的10%。Iwasa等^[31]指出，在其1 735例正畸临床患者中所确诊的12例JICR患者中，仅1例有服用避孕药病史。杨驰团队对JICR患者（94例）和TMJ不可复性盘前移位患者（324例）进行比较后发现：JICR与血清雌激素水平降低并没有明显关联性，而与系统性睾酮水平紊乱有关。采用雌激素β受体敲除的动物进行实验研究^[32]结果表明：咬合异常可引起雌性动物髁突软骨中Ⅱ型胶原表达减少，对雄性动物没有该效应，但这种性别差异与动物血清雌激素水平并不相关。因此，虽然JICR常见于女性患者，但并不一定与雌激素水平有关^[3]。

1.2　 损伤性负荷相关的组织改建学说

损伤性负荷导致髁突吸收的原因，可能是损伤后髁突承载能力下降，这使得其所承受的功能性负荷反射性减弱，髁突出现负荷降低相关的骨丢失。如果损伤造成髁突软骨撕裂，便可出现软骨的局部丧失继而软骨下骨组织吸收^[11,33]，如果组织的适应性改建能力较弱，受损伤的髁突也可出现进行性骨吸收^[11]。Lin等^[34]采用200 g重物从60 cm处砸向实验猪的TMJ，结果发现：实验动物的髁突骨软骨交界区出现了分子水平的退行性改变和炎性改变。另外，损伤性负荷导致髁突后移位或关节盘前移位时，髁突可压迫双板区的血管，导致关节组织缺血性坏死，引起髁突吸收^[9]。

实际上，除直接的外伤因素外，不当的正畸正颌治疗也可损伤TMJ。有文献^[11,35-42]报道，正颌手术，尤其是双颌手术、手术中下颌的顺旋、手术引导的髁突后退、前导下颌超过10 mm，以及矫正Ⅲ类畸形的上颌正颌手术等，都是髁突吸收的危险因素。NiÑo-Sandoval等^[39]报道，5 128 例正颌手术患者中，12.32%出现了髁突吸收，其中70.1%接受的是双颌手术。Scheerlinck等^[43]报道：前导10 mm以上的患者中髁突吸收发生率高达67%。Yoshioka等^[44]认为，正颌手术中如果固定髁突的方式不当，可在髁突内产生扭矩从而导致髁突吸收。Kobayashi等^[45]则强调，对有髁突吸收的患者，其正颌手术应在髁突吸收处于稳定期进行，并应重视TMJ的术后承载问题。然而也有学者指出：正颌手术后髁突吸收比例并不高（0.0%~4.2%）^[46]，正颌术后更多见的是髁突改建^[47]，髁突吸收与固定方法也未见明显关联性^[36]。导致髁突吸收的因素有很多^[39,48]，在生长发育期接受正颌手术的患者中，下颌矢状发育不足和垂直向过生长都可能与正颌手术后髁突吸收有关^[36]。

笔者认为，正颌手术患者以成年人为主，除非存在特殊需求，通常不在生长发育期实施正颌手术。虽然正颌手术后的髁突吸收与JICR的临床表现具有许多相同特征，例如：女性多见、下颌升支后面高较低、下颌平面呈高角、前牙开𬌗及Ⅱ类错𬌗畸形等^{[38,40,49-50]}，但正颌手术后的髁突吸收与JICR具有不同的发病过程（图3）：正颌手术后出现的髁突吸收，是在髁突组织生长发育完成后出现的病理性组织丢失，这种髁突组织丢失可以以缓慢的方式出现，例如，在正颌术后6年才出现^[51]，因此，正颌手术后患者出现的髁突吸收与正颌手术相关的生物力刺激及患者的组织适应性改建能力有关，是组织改建能力与生物力刺激之间不平衡的结果^[37]。而JICR的髁突吸收则出现在生长发育期，生长发育期髁突所承受的最常见的异常生物力刺激，来自于缓慢建立的咬合关系，如Ⅱ类错𬌗。咬合与TMJ之间有密切的生物力关系^[52]，在功能正常的咬合刺激下，髁突的生长发育与下颌骨体在三维方向上的生长相匹配，髁突体积增大，下颌升支向上、向后生长，下颌骨体相对于颅底向前下生长，双髁之间的距离加大^[11]。如果在此过程中存在异常咬合的持续性刺激，髁突的生长发育便可能不均衡，出现髁突的异常发育与改建和下颌升支的生长发育迟缓^[25]，从而表现为JICR。由此可见，咬合创伤相关的TMJ组织异常改建的病理机理学说，可以较好地解释JICR的发生。

2　 JICR的诊断及鉴别诊断

JICR主要依靠病史、临床表现和影像检查结果而做出诊断^[2,9,25]，其中影像检查结果是JICR诊断的金指标，病史和临床表现则主要用于鉴别诊断。

2.1　 影像诊断

典型的JICR影像表现主要是髁突的高度和体积较小，关节面较平，髁颈向后倾斜，与之伴随的异常影像表现主要包括：髁突较小相关的下颌升支高度较低，下齿槽座角（SNB）较小，下颌平面角较小，上颌前突，下颌后缩，前牙开𬌗等颌面畸形 ^{[13, 31]}。Kristensen等^[7]比较了25例JICR和25例正常对照的双侧髁突CBCT特点，发现JICR患者的髁突颈向后倾的比例高达84%，明显高于对照组的22%；与对照组相比，JICR组髁突宽度减小约2 mm，高度降低约4.9 mm，髁突轴角减小约10.6°；70%以上的骨质变形涉及整个髁突头，72%的患者有关节窝与髁突之间的形态不匹配。

但是JICR的影像诊断指标并不完善^[11]，根据晚期JICR髁突体积变小、形态异常等特点，比较容易作出JICR的诊断，尽管晚期髁突前斜面变平的情况已基本稳定，骨皮质变得基本连续^[53]。早期JICR的诊断相对比较困难，尤其是处于生长发育旺盛期的青少年，如果其髁突表面骨皮质的连续性稍差并不一定是JICR，而可能是软骨内成骨的活跃阶段。文献中对髁突生长发育相关的骨表面皮质不连续和早期JICR相关的皮质不连续，尚缺乏明确的分辨标准，在Kristensen等^[7]报道的JICR患者中，仅56%有髁突吸收，40%有骨皮质不连续。Tanaka^[11]认为，JICR患者常因开𬌗及面部畸形问题就诊于正畸科或正颌外科，因此，正畸正颌医生可能是最早发现JICR的医生，如果患者开𬌗，但切牙有磨损，应考虑髁突存在快速吸收问题。由于在生长发育过程中下颌有明显的三维扩容，如果侧位投影测量片显示有下颌骨生长迟缓、下颌顺时针旋转等现象，也应作为是JICR的早期信号予以重视^[11]。可见，咬合问题在JICR早期诊断中具有重要的意义。

2.2　 鉴别诊断

JICR常需要与青少年特发性关节炎（juveni-le idiopathic arthritis，JIA）鉴别：JIA的CT影像表现与JICR很相似^[54]，但JIA属于自身免疫性疾病^[55]，有明显的TMJ区域疼痛、触痛和晨僵等滑膜炎症状^[56]，而JICR则没有明显的炎症表现^[3-4]。Boos-Lima等^[56]对35例受试者的67个JICR标本与8例受试者的15个JIA标本进行了比较，结果显示：JICR的组织病理学表现主要包括不规则的软骨表面严重破坏、纤维软骨变性，其软骨下骨没有炎症浸润，而JIA则更多表现为骨和滑膜的退变与炎症。JICR患者的主要主诉问题通常是颌面畸形，67%的JICR患者有前牙开𬌗，而JIA患者的开𬌗发生率仅11%^[3,54]。基于这些疾病特征鉴别JIA和JICR并不困难。

JICR与TMD的鉴别诊断则比较困难，事实上，JICR患者常有TMD症状。根据Kristensen等^[7]的研究报道，约88%的JICR患者有TMD症状或体征。Iwasa等^[31]所报道的12例JICR中，75%有TMD病史。Shen等^[57]认为关节盘移位可能是JICR的危险因素，因为JICR与病程较长的关节盘前移位密切相关，但是JICR有明显髁突形态变化，而TMD患者中仅一部分（通常为晚期）有髁突骨质改变，TMD患者最常见的主诉症状是颌面部疼痛、TMJ弹响和张口受限。Raman^[58]认为，TMD是一种肌肉收缩所维持的姿势链与生理适应能力之间的不平衡状态。

笔者认为：1）在生长发育旺盛的青少年时期，骨骼肌平衡能力较强，导致其即使已经有明显的髁突变化，患者也常常仅有较轻的TMD症状；2）无论是JICR还是TMD，都涉及咬合、咀嚼肌和TMJ，炎症反应都比较低；3）重症TMD和JICR都有关节的异常改建，许多影像诊断为骨关节炎（TMD的重症）的患者及一些JICR患者均可以没有明显的临床症状，临床上对于伴有TMD症状和体征的、髁突有明显“吸收”样改变的病例，通常以年龄作为区分标准来作出JICR或TMD的诊断。因而，JICR与TMD可能具有相同的异常咬合生物力病因及病理机理，只是JICR出现在青少年生长发育期，神经肌肉症状较轻，关节异常改建活动较重，而TMD好发于成年人，神经肌肉症状乃至精神心理症状较明显，其TMJ骨质变化则主要出现在重症患者。

3　 JICR的治疗

JICR的治疗方法主要有手术和非手术两大类。通常首选非手术治疗，包括非甾体抗炎药、肌肉松弛剂、局部注射透明质酸及皮质类固醇、理疗、咬合板治疗、正畸治疗等^[8]。对晚期严重的JICR则可选择手术治疗，包括关节成形术、自体半关节成形术、髁突切除术与肋软骨移植髁突重建术、自体髁突重建术，以及同种异体全关节重建等，在关节手术（包括关节盘复位或再定位手术）的同时，进行针对改善颌面畸形的正颌手术^[12,25,35]。但正颌治疗的远期疗效并不稳定^[59]，无效率及复发率可高达50%^[3]。有学者^[3,11]指出：文献所报道的这些治疗方法，疗效都不理想，目前并没有哪种治疗方法可以中止JICR。

实际上，JICR患者更多的主诉问题是颌面畸形，而临床上在讨论JICR患者最关心的牙颌问题时，经常关注“髁突吸收”是否处于活跃期。许多学者^[2,10,12,22]认为：处于“髁突吸收”活跃期的JICR，不宜做正畸、正颌手术治疗，否则会加速髁突吸收，甚至建议将正颌手术推迟数年，但这些建议并没有充分的客观依据^[59]，因为并非所有JICR都有进展，据Exposto等^[60]的观察，75%的JICR患者（16例，平均15岁）的髁突及94%的对照组（16例，平均16岁）髁突，在2年随访期内都没有明显的影像学变化。对于处于“髁突吸收”非活跃期的JICR，有学者^[5,61]采用正畸方法改善牙颌畸形，但是正畸正颌治疗是髁突吸收的一个重要风险因素^[59]，前导幅度与JICR患者正颌手术后的复发密切相关^[62]。Wang等^[63]指出：有JICR病史的患者，前导下颌5 mm的正颌手术可刺激处于非活跃期的髁突，导致吸收病变加重。在1 735例正畸患者的12例JICR资料中，有4例曾经做过正畸^[31]。然而JICR的口颌面畸形，确实需要采取正畸、正颌方法加以纠正，笔者曾接诊1例患者，从14岁被确诊为JICR后未能接受尽快正畸治疗的建议，结果在随后的7年内髁突吸收问题不断加重，最近一次复诊时CBCT所能显示的髁突层面已经很少，髁突变形（图4）。合理诊疗JICR对正畸正颌医生是一种挑战^[26,64]。

总之，JICR特征性髁突表面缺损样变可能不是已经形成的髁突骨组织的吸收性改变，而是发育期髁突因异常咬合的刺激而出现的局部骨组织生长发育障碍。因此，笔者建议的JICR治疗策略是尽早治疗咬合，解除咬合干扰，从而阻断髁突软骨退变，促进髁突正常发育，否则，异常咬合刺激可能造成发育期软骨组织因退变而完全丧失，髁突生长发育迟滞，最终呈短小畸形，继而造成下颌后缩、前牙开𬌗等严重的颌面畸形。然而如何进行咬合治疗以中断JICR的进程、促进髁突的生理性生长与改建，尚需要对功能性正常𬌗作深入分析，否则，正如本文引述的文献所报道，正畸、正颌治疗可成为JICR的诱因或促进因素，进而加重JICR的病情。

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基金资助

国家自然科学基金重点国际合作项目(81920108013)