骨软骨损伤：剥脱性骨软骨炎OCD：病因、病理学和影像学，特别关注膝关节：2018年

骨软骨损伤：剥脱性骨软骨炎OCD：病因、病理学和影像学，特别关注膝关节：2018年

作者：Juergen Bruns, Mathias Werner, Christian Habermann.

作者单位: Orthopedic Surgery, Krankenhaus “Gro?-Sand“, Hamburg, Germany.

译者：陶可（北京大学人民医院骨关节科）

摘要

本文回顾了当前对病因、发病机制以及如何诊断和治疗膝关节剥脱性骨软骨炎(OCD)的理解，然后分析了可用的治疗方法和结果。剥脱性骨软骨炎(OCD)见于生长板开放的儿童和青少年（青少年剥脱性骨软骨炎OCD）和生长板闭合的成人（成人剥脱性骨软骨炎OCD）。剥脱性骨软骨炎OCD病变的病因尚不清楚，其特征是软骨下骨区域出现无菌性坏死。机械因素似乎起着重要作用。临床症状不具特异性。因此，影像学技术是最重要的。关于治疗，存在大量文献。除非有不稳定的碎片，否则预计会自然愈合，治疗包括休息和不同程度的固定，直到愈合。骺板开放和低度病变的患者保守治疗效果良好。当需要手术时，手术取决于临床分期和软骨的状态。对于完整的软骨，重新植入手术是有利的。当软骨受损时，可以使用几种技术。虽然钻孔和微骨折等技术产生修复性软骨，但其他技术通过额外的骨软骨移植物或基于细胞的手术（如软骨细胞移植）以重建骨软骨缺损。临床结果的趋势是：采用骨骼和软骨的重建手术会有更好结果，并且在治疗合并症时也会有更好的长期疗效。严重程度的骨关节病很少见。

关键词：病因；总体原则；影像学；膝关节；剥脱性骨软骨炎；病理。

表1. 剥脱性骨软骨炎（OCD）流行病学

峰值（最高发生）发病率：15岁

瑞典的患病率：6/10000

年龄在2至5岁之间的发病率：0

年龄在6至19岁之间的发病率：9.5/100000

男性：15.4/100000

女性：3.3/100000

6至11岁之间的发病率：6.8/100000

男性：11.1/100000

女性：2.3/100000

年龄在12至19岁之间的发病率：11.2/100000

男性：18.1/100000

女性：3.9/1000004

膝关节发生剥脱性骨软骨炎（OCD）的风险

6-11岁与12-19岁比率：1:3.3

膝关节发生剥脱性骨软骨炎（OCD）的风险

男性：3.8

女性：1

表2. 剥脱性骨软骨炎（OCD）的致病因素

病因因素 膝关节

主要位置 股骨内外侧髁

创伤 ++

轻微创伤 +++

遗传学因素 +

感染 +

排除

血管病变 +

行走步态 股骨内侧髁：内翻畸形

股骨外侧髁：外翻畸形

外侧盘状半月板

代谢因素 +++

证据等级：++++ =非常高； +++ =高；++ = 临床观察；+ =假设。

Figure 1. (a) Histology of an advanced osteochondritis dissecans (OCD) lesion (knee joint, toluidine blue) showing a partially loosened “joint mouse” with a broad cleft (arrow) between the partial loose body (top) and the normal subchondral bone (bottom). In the lesion, subchondral bone cysts are visible (C) and necrotic areas (N). (b) Magnification of fig, 1a: The lesion exhibits an area of osteonecrosis (white arrow), subchondral bone cysts (black arrow), and in the “mouse bed,” the sublesional bone a thickened osteoid layer as a sign of enlarged endostal activity (arrowheads).

图1.（a）晚期剥脱性骨软骨炎（OCD）的组织学病变（膝关节，甲苯胺蓝染色），显示部分松散的“关节鼠（游离体）”，在部分游离体（顶部）和正常的软骨下骨（底部）之间具有宽阔的裂缝（箭头）。在病变中，可见软骨下骨囊性变（C）和坏死区域（N）。（b）图1a的放大：病变表现出骨坏死（白箭头），软骨下骨囊性变（黑色箭头）和“游离体骨床”，病变骨质是一层增厚的骨质硬化层，是增强的（骨）内膜活动（短箭头）。

Table 3 presents the OCD classification schemes.

表 3 展示了剥脱性骨软骨炎OCD的分类方案。

表3.分类方案

总体原则（适合多个不同的关节） 膝关节（特定的）

ICRS分类法（关节镜） Arcq：3个放射学阶段

第一阶段(I期)：病变稳定，关节完整，软骨软化 Rodegerdts和Gleissner：5个放射学阶段

第二阶段(II期)：局部不连续性的病变，但病变稳定

第三阶段(III期)：具有完全连续性的病变，尚未游离

第四阶段(IV期)：骨床内软骨下骨裸露或骨软骨碎片脱落或形成游离体

Bruns分类法

X射线 MRI

第一阶段(I期)：没有变化 骨挫伤，骨髓水肿

第二阶段(II期)：局部硬化 骨溶解与骨硬化并存

第三阶段(III期)：部分剥离 部分剥离，软骨下积液

第四阶段(IV期)：完全剥离 完全剥离、缺损，游离体、关节鼠

游离体

骨扫描 骨扫描

CT CT

MRI MRI

骨骺愈合或未愈合 骨骺愈合或未愈合

关节镜检查 关节镜检查

稳定性 稳定或不稳定

CT =计算机断层扫描；ICRS =国际软骨维修协会；MRI =磁共振成像

第三和四阶段可以细分为严重阶段（M）和骨软骨分离形式（D）。

表4. （剥脱性骨软骨炎发生）部位方案

Aichroth-Lindholm划分法：

前后视图：内侧髁：定位“中央”，“中外侧”和“次外侧”

前后视图：外侧髁：“次中央”，“前方”和“次外侧”

Hughston划分法：

前后视图：从内侧到外侧分为5个区域：半月板，非半月板区（内侧髁），髁间，非半月板区，半月板（外侧髁）

外侧视图：在切线位将股骨后髁成2个部分：直接远端或后部

或者

外侧视图：

A = Blumensaat线的前部，

B = Blumensaat线的后部

C =最后1/3部

Figure 2. X-ray of the knee. Anterior-posterior view showing an osteochondritis dissecans lesion at the typical location (medial condyle), black arrows indicate stage IV with an empty lacuna. The loose body is not visible.

图2. 膝关节的X线片。前后视图显示典型位置（内侧髁）的剥脱性骨软骨炎病变，黑色箭头指示IV期带缺损区域，未见游离体。

Figure 3. (a) Magnetic resonance imaging (MRI) (proton density fat saturation) of the same knee joint exhibiting the empty lacuna at the medial condyle (dotted white arrows) and the loose body located at the lateral recessus (white arrows), coronal plane. (b) MRI (proton density fat saturation) of the same knee joint exhibiting the empty lacuna at the medial condyle (dotted white arrows) and the loose body located at the lateral recessus (white arrows), sagittal plane.

图3. （a）同一膝关节的磁共振成像（MRI），该膝关节在内侧髁（白色箭头指示）和位于外侧凹处（白色箭头）的游离体（白色箭头）上表现出空的空隙（白色箭头），冠状位。（b）同一膝关节的MRI在内侧髁出现的空隙（白色箭头指示）和位于外侧凹处（白色箭头）的游离体，矢状位。

表5. （剥脱性骨软骨炎OCD）治疗选项（参考文献请见文中）

总体原则（适合多个不同的关节） 膝关节（特定的）

I期：

青少年剥脱性骨软骨炎OCD 保守 保守

成人剥脱性骨软骨炎OCD 保守 保守

II期：

青少年剥脱性骨软骨炎OCD 保守、钻孔减压 保守、钻孔减压

成人剥脱性骨软骨炎OCD 保守、钻孔减压 保守、钻孔减压

III期：

青少年剥脱性骨软骨炎OCD

+ 成人剥脱性骨软骨炎OCD

(病灶清除术)，REFIX，MFX， (病灶清除术)，REFIX，MFX，

ACI, AMIC, MOPLA, OAT, BMS ACI, AMIC, MOPLA, OAT, BMS

骨组织 +细胞 骨组织 +细胞

IV期：

青少年剥脱性骨软骨炎OCD

+ 成人剥脱性骨软骨炎OCD

(病灶清除术，REFIX，MFX)， (病灶清除术，REFIX，MFX)，

ACI, AMIC, MOPLA, OAT, BMS ACI, AMIC, MOPLA, OAT, BMS

骨组织 +细胞 骨组织 +细胞

同种异体移植

ACI =自体软骨细胞植入；AMIC =自体基质诱导的软骨再生； AOCD =成年剥脱性骨软骨炎；BMS =骨髓刺激； JOCD =青少年剥脱性骨软骨炎；MFX =微骨折术；MOPLA =马赛克镶嵌成形术； OAT =骨软骨自体移植术； REFIX = 重锚定术。

Figure 4. Example of a refixated loose body in the medial condyle of the knee. Prior to the refixation, the subchondral sclerosis had been removed, cancellous bone taken from the iliac crest transplanted into the defect, followed by the refixation using fibrin glue (Tissucol, Baxter, Unterschlei?heim, Germany) and resorbable pins (Ethipin, Ethicon, Hamburg, Germany).

图4. 膝关节内侧髁重新固定的病例。在重新固定之前，已去除软骨下硬化组织，将取自髂嵴的松质骨移植到骨缺损处，然后使用纤维蛋白胶（Tissucol，Baxter，Unterschlei?heim，Germany）和可吸收针固定（Ethipin，Ethicon，Hamburg，德国）。

Figure 5. Adult osteochondritis dissecans (AOCD) stage IV lesion at the medial condyle of the knee with already visible secondary arthritic changes treated with 5 osteochondral plugs implanted as a mosaicplasty with small clefts between the plugs.

图 5. 膝关节内侧髁的成人剥脱性骨软骨炎(AOCD) IV期病变，已经可见的继发性骨关节炎变化，用 5 个骨软骨移植柱行镶嵌成形术植入治疗，在移植柱之间有小裂缝。

Figure 6. Adult osteochondritis dissecans (AOCD) stage-IV lesion at the lateral femoral condyle treated with removal of the subchondral sclerosis, transplantation of cancellous bone taken from the iliac crest and implantation of an autologous chondrocyte implantation (ACI) of the second generation using a gel as carrier for the chondrocytes (CaReS, Arthro Kinetics, Bebenhausen, Germany).

图 6. 通过去除软骨下硬化组织、移植取自髂嵴的松质骨和植入载有第2代自体软骨细胞的凝胶植入物(ACI)治疗股骨外侧髁的成人剥脱性骨软骨炎(AOCD) IV期病变（CaReS，Arthro Kinetics，Bebenhausen，Germany）。

正文介绍

剥脱性骨软骨炎(OCD)是骨骼未成熟和成年患者膝关节疾病的常见原因，当一小块软骨下骨由于局部血液供应障碍而开始与其周围区域分离时，就会发生这种情况。最后，这一小块骨头和覆盖它的软骨可能会开始破裂并（从关节表面上）脱落。正如之前假设的那样，Ambroise Paré（而不是Paget）是第一个（在1870年）描述在关节中发现的这种关节游离体的人。关节游离体形成的3种可能原因：

①急性骨软骨骨折的直接创伤；

②发展成骨坏死和连续碎裂的最小创伤；

③没有自发创伤的证据，K?nig称之为“剥脱性骨软骨炎”（OCD）。

剥脱性骨软骨炎OCD的确切患病率尚不清楚，但据报道，每100000人中有15至29人。Kessler等已经表明，6至19岁患者膝关节剥脱性骨软骨炎OCD的发病率为每100000人中有9.5人，而男性和女性患者分别为每100000人15.4和3.3（表 1）。12至19岁的患者占剥脱性骨软骨炎OCD的大多数，其发病率为每100000人11.2人，而6至11岁的患者为每100000人6.8人。总之，与女性患者相比，男性患者的剥脱性骨软骨炎OCD发生率更高，发生剥脱性骨软骨炎OCD的风险几乎是女性患者的4倍。

本文中的剥脱性骨软骨炎OCD是指受累关节的慢性疾病，不是由急性创伤引起的。急性创伤是由新鲜的骨软骨或软骨损伤(OCL)组成，有或没有脱落的骨软骨碎片。剥脱性骨软骨炎OCD通常被认为是青少年剥脱性骨软骨炎（=JOCD）（发生于未闭合的骨骺板）或成人剥脱性骨软骨炎（=AOCD）（在骨骺闭合后）。这些定义表明，骨骺仍然未闭合的患者比骨骺已经闭合的剥脱性骨软骨炎OCD病变的成人患者，更有可能成功进行非手术治疗。

本文是对剥脱性骨软骨炎OCD已知情况的回顾，特别关注受影响的最大关节：膝关节。在以后的文章中，将讨论肘关节和踝关节。

可以将剥脱性骨软骨炎OCD的病因分为4种不同的可能原因：外伤性、缺血性、遗传性和特发性（表 2）。然而，多因素病因是最可能的原因。

①外伤：可能是由间接外伤引起，是剥脱性骨软骨炎OCD损伤最常见病因，即股骨内侧髁后内侧位置。在胫骨内旋期间，对未成熟膝关节和股骨内侧髁外侧相对应的胫骨的重复压力可能导致剥脱性骨软骨炎OCD。这种软骨下压力刺激反应可能会干扰骨小梁愈合并阻碍骨愈合的能力。由于缺乏软骨的底层（软骨下骨）支撑，后期可导致关节软骨与软骨下骨连接的分离，相关骨软骨区域部分脱落。

②缺血：血管分布不良和诱发的缺血被描述为剥脱性骨软骨炎OCD的潜在原因。一些研究表明，在剥脱性骨软骨炎OCD定位部位观察到的血管模式存在差异。这种关节形态与该部位的局灶性反复创伤以及独特的血管结构相结合，可能引发缺血和随后的剥脱性骨软骨炎OCD。

③遗传学：几位作者已经研究了剥脱性骨软骨炎OCD的潜在遗传联系，但仍然相对未研究剥脱性骨软骨炎OCD发展中的遗传和发育因素。Skagen等提出，OCD病变是由软骨细胞基质合成的改变引起的，导致内质网贮积病表型，这会扰乱或突然的软骨内骨化。此外，具有相似疾病过程的同卵双胞胎病例高度暗示遗传病因。

剥脱性骨软骨炎OCD常见的发病过程

尽管病因尚不完全清楚，但对剥脱性骨软骨炎OCD的发病机制已比较了解。独立于病因，至少可以描述4个阶段。

阶段1（I期）

剥脱性骨软骨炎OCD病变始于软骨下骨，伴有软骨下骨质骨髓减少，这只能通过磁共振成像(MRI)或核素骨扫描检测到。

第二阶段（II期）

病变与软骨下骨的骨髓水肿有关。骨挫伤可能是初始阶段，软骨下骨小梁微骨折可能是与骨髓水肿的形态学相关。

第三阶段（III期）

持续的自然病程以放射学可检测到的硬化环为特征，将病变与周围健康骨质区分开来。病变中心被认为是骨坏死（参见“剥脱性骨软骨炎OCD 组织学”部分）。在这个阶段，在MRI和计算机断层扫描(CT)等成像技术中，软骨似乎仍然完好无损。

第 4 阶段（IV期）

“软骨的软化现象和机械特性的改变”促进了坏死边缘的骨质对周围健康骨骼的反应。仍然存在的机械负荷可能是软骨现在参与并显示出分离迹象的原因。最后，持续的自然过程导致骨软骨碎片脱落，导致单个关节游离体或出现多个碎片（即所谓的“恶意变体”，首先由Wagner描述）。

关于生物力学病因的建议，有几个以生物力学为导向的分析。1950年，Rehbein能够通过人工产生的重复应力，在狗的膝关节中实验性地产生游离体。这些标本在组织学上类似于下面描述的那些发现，这些发现是从人类膝关节的游离体中获得的。

一项使用环氧树脂制成的平面和立体膝关节模型的实验试验，以及股骨远端的有限元分析，揭示了剥脱性骨软骨炎OCD病变发生区域的峰值应力。在膝关节中使用光敏箔来模拟临床上明显的致病因素，例如内翻或外翻畸形（膝关节）与稳定和不稳定的韧带，在剥脱性骨软骨炎OCD病变临床常见的那些区域表现出显着的应力集中。

从临床上看，膝关节骨挫伤被认为是软骨下骨小梁的主要损伤，这可能引发剥脱性骨软骨炎OCD。

剥脱性骨软骨炎OCD组织学

晚期病变的组织学如图1所示。据我们所知，Green和Banks是第一个将软骨下骨坏死描述为仍然具有完整的软骨覆盖的初始病变的人。

由于失去了对软骨的骨骼机械支撑，正在进行的病理过程会导致软骨层继发性损伤。作者建议，只要覆盖的软骨仍然完好无损，就可以通过爬行替代进行愈合。游离体组织学检查显示肥大常见，53%有层状钙化。

Chiroff和Cooke在分离水平和游离体的骨组织部分检测到纤维软骨组织，发现在几乎正常的软骨下成骨细胞和溶骨活性增加。此外，Milgram在一半的游离体中没有发现骨组织。Koch等分析了来自16至44岁患有晚期剥脱性骨软骨炎OCD的患者的30份标本，并观察到软骨中PH 1的甲苯胺染色减少。在软骨下骨板和松质骨中可以看到软骨细胞数量减少以及骨折改变。此外，他们发现骨吸收增强和被脂肪骨髓包围的软骨下骨坏死区域。

Uozumi等描述了3种类型的剥脱性骨软骨炎OCD组织病理学特征：

①伴有软骨下骨小梁坏死的剥脱性骨软骨炎OCD

②具有可存活的软骨下骨小梁的剥脱性骨软骨炎OCD

③没有骨小梁的剥脱性骨软骨炎OCD软骨。

他们总结认为：“软骨下区最初的变化是骨坏死或软骨下骨折；然后骨坏死的骨组织被吸收并被有功能的软骨下骨小梁或没有骨小梁的软骨取代。”相比之下，从股骨内侧髁稳定的青少年剥脱性骨软骨炎JOCD病变中心的8针活检中，没有发现任何退行性变化，未检测到骨坏死。只发现了厚的软骨层和纤维组织，或下面有混合有软骨的薄软骨层，分离区域的软骨下骨小梁和纤维组织和纤维软骨也是如此。

最近，对游离体的分析表明，游离体中的软骨细胞表现出正常的行为，这些细胞被认为可用于自体软骨细胞移植(ACI)。

对已发表的组织学分析数据进行的荟萃分析得出了不一致的结果：在包括软骨下骨在内的10项研究中，有7项报告了骨坏死的迹象；在11篇文献中有2篇提到了退变或不规则的软骨。关于可能的潜在病因，11篇文章中有5篇认为一次主要或多次重复性微创伤是主要病因。总之，组织学结果表明软骨基质的局灶性改变起源于关节软骨的深层，可能是矿化层或软骨下骨。

剥脱性骨软骨炎OCD的诊断

剥脱性骨软骨炎OCD相关症状

症状通常模糊不清，定位不是很准确。可能会出现不同程度的疼痛和僵硬；可能会出现关节肿胀和积液以及关节“打软腿”、“卡住”或“别住”。在任何关节中都没有典型的剥脱性骨软骨炎OCD临床症状。Wilson试验被推荐为膝关节的临床诊断试验，但并不可靠。

剥脱性骨软骨炎OCD定位方案如表4所示。

评估剥脱性骨软骨炎OCD影像学技术

普通X线在开始使用MRI之前，最初的变化只能通过骨扫描检测到，或者在常规X线片上怀疑（出现剥脱性骨软骨炎OCD病变）。随着MRI的引入，可以更轻松地区分阶段。然而，仍然难以可靠地估计软骨层的机械性能。

怀疑剥脱性骨软骨炎OCD病变时的最初诊断计划是从2个X线片检查开始。标准系列包括站立前后位(AP)视图（图 2）、膝关节屈曲35°的侧视图和45°髌骨轴位（sunrise切线位）视图。其他特殊X线视图可能很有用，例如tunnel视图，使病变区域与成像平面更加一致。

磁共振成像MRI是成像检查中第二步的首选方法（图 3a 和 b）。由于MRI系统的可用性在过去10年中有所增加，无辐射、更高场强（1.5和3T）的突然发展、专用线圈设置和高分辨率序列为MRI的发展节省了道路在肌肉骨骼成像中。常规MR方法在所有3个空间方向上使用T1和T2加权图像。最大切片厚度应为3mm，检测距骨骨软骨缺损的灵敏度为96%（特异性0.96）。

Diapola等开发了一个有用的MRI系统，用于评估剥脱性骨软骨炎OCD，有4个等级：

阶段1（I期）：关节软骨增厚和低信号变化。

第 2 阶段（II期）：关节软骨破裂，碎片后面的低信号边缘表明有纤维附着。

第 3 阶段（III期）：关节软骨破裂，碎片后面的高信号变化，表明碎片和下面的骨组织之间有滑液填充

第四阶段（IV期）：游离体。

在评估MR图像上的剥脱性骨软骨炎OCD时，也可以使用关节镜国际软骨修复协会(ICRS)的剥脱性骨软骨炎OCD分类标准和Guhl的分类标准（参见关节镜分类）。

为了改进评估（结果），还可以通过在检查前，将gadolinium钆MR对比材料注入检查关节来进行MRI扫描。这样的dGemeric MRI提供了有关矩阵质量的信息。使用T2加权序列，高信号线或骨软骨病变下方的囊肿的存在表明存在液体并表明存在不稳定的骨软骨缺损，即使该信号可以反映代表愈合反应的血管肉芽组织。质子密度图像和具有脂肪饱和度的三维T1加权序列使用低于1毫米的各向像素（isotropic voxels），具有专用视野（14-20厘米）和静脉造影剂，可提供出色的图像印象，还可以区分细微的变化。使用在这些序列中，MRI在检测甚至不稳定的骨软骨病变方面提供了出色的诊断能力。因此，评估骨软骨病变不需要常规的关节内给药。

使用新实施的高分辨率MRI序列来区分不同类型的骨软骨缺损可提供超过90%的总体准确度。

在日常临床常规中，可以使用1.5- 和3-T系统。比较两个系统上的专用线圈设置，使用更高场强（3-T系统）的图像印象可能更好。然而，尚未证明3-T系统对软骨病变能提供更好的诊断结果。

应用计算机断层扫描CT的两个重要缺点是辐射，特别是在检查患者的年龄方面，以及缺乏软骨的可视化扫描结果。可以通过使用关节内对比材料来克服软骨可视化的缺乏，该材料可以通过直接穿刺关节应用并提供软骨的间接可视化。CT扫描可用于评估剥脱性骨软骨炎OCD剥脱碎片再固定后的骨整合情况。

闪烁骨扫描显像检查

Paletta及其同事发现，定量骨扫描对骨骺未闭合的剥脱性骨软骨炎OCD患者的预后具有100%的预测价值，但对于骨骺闭合的患者，预测价值较低。

Cahill和 Berg开发了一种用于评估青少年剥脱性骨软骨炎OCD患者的闪烁显像结果的分类标准：

① 0期.正常的射线照相和闪烁照相外观。

② 1期. 病灶在平片上可见，但骨扫描显示正常。

③ 2期. 扫描显示病变区域的摄取增加。

④ 3期. 此外，整个股骨髁的同位素摄取增加。

⑤ 4期. 此外，病变对面的胫骨平台有摄取。

膝关节剥脱性骨软骨炎OCD的治疗

膝关节的剥脱性骨软骨炎OCD病变主要位于股骨内侧髁，通常与内翻畸形有关。少数剥脱性骨软骨炎OCD病变位于外侧髁，与外翻畸形有关。

剥脱性骨软骨炎OCD病变位置

股骨外侧髁的病变也可能与盘状半月板相关。外侧髁的病变可以主要与盘状半月板或继发于盘状外侧半月板完全切除后发生。假设膝关节的生物力学改变与盘状半月板或完全外侧半月板切除术后，是导致剥脱性骨软骨炎OCD病变发展的原因。盘状半月板患者的外侧髁突出率明显大于对照组。

只有少数病变位于髌股关节。

剥脱性骨软骨炎OCD病变稳定性

对于青少年剥脱性骨软骨炎JOCD和成人剥脱性骨软骨炎AOCD，采用保守治疗或手术方法的适应症取决于骨软骨碎片的稳定性（表 5）。然而，什么是稳定病变？Wall等指出“稳定的剥脱性骨软骨炎OCD被定义为关节或软骨下骨损伤界面没有破裂。”Trinh 等意识到他们的审查包含对稳定或不稳定病变的不同定义，并将其改编为De Smet 等使用的定义：

如果存在病变不稳定性，

在MRI的T2加权图像上可以看到碎片深处的一条高信号线。

由高信号指示的关节骨折穿过软骨下骨板。

存在局灶性骨软骨缺损。

一个直径5毫米、充满液体的囊肿位于病灶深处。

保守治疗

已经发表了一些文章，区分了提倡保守治疗，但治疗方案不同的青少年剥脱性骨软骨炎JOCD和成人剥脱性骨软骨炎AOCD。

青少年剥脱性骨软骨炎JOCD

大多数患有青少年剥脱性骨软骨炎JOCD的儿童可以通过保守治疗成功。建议限制负重和体育活动，或简单地限制日常活动和固定。一个常见的治疗建议是，患者有6到12周的支具，部分负重，并定期进行物理治疗训练。如果患者在12周时无疼痛并且影像学显示愈合，则患者可以开始跑步活动，但应限制更激进的活动，直到患者在运动和休闲活动（例如跳跃）中进行了几个月的无症状活动，扭曲和冲击载荷。

在最近发表的一项针对42名青少年剥脱性骨软骨炎JOCD患者的回顾性研究中，三分之二 (66%) 的稳定病变在石膏固定初始治疗后愈合，随后进行支撑和活动限制长达6个月。然而，作者在34%的患者中经历了治疗失败。大的病灶比较小的病灶（相对和绝对）明显治疗结果更糟，但所有的外侧病灶都愈合了。

诸如病变大小、股骨髁或非股骨髁定位、患者的年龄和性别等前瞻性因素仍存在争议。

令人感兴趣的是一项欧洲多中心研究，迄今为止患者人数最多（452名患者，509个膝关节）。在最少随访1年的452名患者中，他们将A组276名骺板未闭合患者（例如，14岁以下的男性和13岁以下的女性）与B组所谓的“早熟”患者区分开来，例如男性14岁以上，女性13岁以上。共有154名患者接受了保守治疗，355名患者需要手术。A组患者的结果明显好于B组。情况良好的患者（无肉眼解剖，大小 ＜ 20 cm2）明显优于已经可检测到的患者（所谓的“不利条件”）。与没有石膏的治疗相比，石膏的应用不影响保守治疗的结果（正常和接近正常的膝关节分别为69.2% 和 72%）。相比之下，与手术治疗（33.1% 的膝关节异常）相比，那些状况不佳的患者在保守治疗（44%的膝关节异常）后的结果明显更差。

成人剥脱性骨软骨炎AOCD

关于成人剥脱性骨软骨炎AOCD患者，知之甚少。同时，问题是成人剥脱性骨软骨炎AOCD患者的剥脱性骨软骨炎OCD是从头发生还是在骨骺闭合之前已经存在，但由于治疗失败，骨骺闭合后仍然存在。保守治疗的问题是“那些患有成人剥脱性骨软骨炎AOCD的人如何受到影响？”一般来说，据我们所知，没有明确的答案。只有一项研究将13岁以下（女孩）或14岁（男孩）的患者与早熟期患者（13岁以上的女孩或14岁以上的男孩）进行了比较，并提供了一些可靠的数据。青少年剥脱性骨软骨炎JOCD患者在任何类型的治疗后的结果都好于任何处于早熟期的患者。

对于成人剥脱性骨软骨炎AOCD，保守治疗成功的可能性较小。Lindén指出，无论采用何种保守治疗方案，结果都非常好，并且骺板未闭合的儿童没有表现出退行性变化。Hughston等建议正常活动和加强肌肉而不是固定。非手术治疗后的愈合率范围为50%至94%。

手术治疗

当保守治疗失败时，关节镜评估和治疗被用作下一步治疗策略。接受手术治疗的一般适应症如下：

①已经可见的游离体的不稳定病变；

②预计在6至12个月内发生骨骺闭合时，在观察或非手术治疗期间发生的脱落；

③尽管进行了充分的非手术治疗，但幼年骨软骨损伤仍然有症状时；

④当可检测到已确定的骨软骨碎片不愈合时。

有几种不同的分类系统可用于关节镜下对剥脱性骨软骨炎OCD病变的评估。最著名的是根据Guhl的关节镜分类标准：

第一阶段：稳定病变

第二阶段：病变显示早期分离迹象

第三阶段：部分脱落的病变

第四阶段：有游离体的骨软骨缺损。

国际软骨修复协会ICRS开发了一个评估软骨损伤的系统和一个剥脱性骨软骨炎OCD评估系统。国际软骨修复协会ICRS剥脱性骨软骨炎OCD分类是一种改进的Guhl分类，用于将剥脱性骨软骨炎OCD损伤的软骨评估调整为常见的国际软骨修复协会ICRS评估系统：

国际软骨修复协会ICRS剥脱性骨软骨炎OCD 0期：稳定、正常、完整的覆盖软骨；

国际软骨修复协会ICRS剥脱性骨软骨炎OCD I：稳定，有连续但软化的区域，软骨完整；

国际软骨修复协会ICRS剥脱性骨软骨炎OCD II：稳定但有部分不连续；

国际软骨修复协会ICRS剥脱性骨软骨炎OCD III：完全不连续的原位病变；

国际软骨修复协会ICRS剥脱性骨软骨炎OCD IV：有脱位或游离碎片的骨软骨缺损。

手术治疗的适应症

然而，手术指征是有争议的且不明确。在最近的一篇评论文章中，对783名受试者和862个膝关节的30项研究（仅1项I级）进行了评估。术后平均随访时间为77个月，最少2年。在短期、中期和长期随访中，几乎所有患者在手术治疗的青少年剥脱性骨软骨炎JOCD方面都表现出显着的临床和影像学改善。与其他手术技术相比，切除负重剥脱性骨软骨炎OCD病变导致临床和影像学结果较差。青少年剥脱性骨软骨炎JOCD的结果明显优于成人剥脱性骨软骨炎AOCD。

不同的手术技术，例如逆行或顺行钻孔（单独或与松质骨移植相结合），仅适用于病变较轻者，最好是青少年剥脱性骨软骨炎JOCD。顺行技术比逆行方法容易操作，但为了到达受累的软骨下骨，必须对软骨层进行穿孔。

由于未闭合骨骺，逆行方法更加困难，但它确实使软骨层完好无损。建议使用影像学技术，例如X线透视、MRI、超声或关节镜，以便能够将钻头导向骨软骨缺损处。两种策略的目标都是穿过软骨下骨硬化区或促进血液供应到软骨下骨坏死区。

最重要的预后因素是年龄。影像学观察到，多达100%的青少年剥脱性骨软骨炎JOCD患者的病灶在术后6周至2年内愈合，但仅25%的成人剥脱性骨软骨炎AOCD病例能完全愈合。

大病灶比小病灶需要更长的时间才能愈合。

青少年剥脱性骨软骨炎JOCD

对青少年剥脱性骨软骨炎JOCD有一篇总结25篇文章的最新综述表明，对于稳定病变，最常见的技术是钻孔和使用生物可吸收针固定碎片。主要研究结果是，无论采用何种技术，绝大多数病变均在术后愈合，并且需要高质量的试验来更恰当地比较技术的有效性。在回顾顺行和逆行钻孔后发表了类似的结果。

成人剥脱性骨软骨炎AOCD

关于在成人剥脱性骨软骨炎AOCD中，钻孔治疗稳定病灶几乎一无所知。不稳定的成人剥脱性骨软骨炎AOCD病变大多通过手术治疗。几年来，在软骨层受损的情况下，建议去除脱落的软骨或骨软骨碎片，可能与清创手术相结合。然而，如今，由于结果不佳，已不再这样做，骨关节炎(OA)变化率高达71%。由于这些原因，建议尽可能对部分或完全脱落的游离体进行碎片重新固定（参见图 4 中的示例）。组织学上，这些碎片主要包含有生存活力的软骨。将碎片重新固定与软骨下骨钻孔相结合，建议对软骨下骨硬化区穿孔，或去除硬化骨，然后进行松质骨移植，然后进行碎片重新固定。

骨软骨碎片修复技术

几种方法已用于剥脱性骨软骨炎OCD碎片的再固定，例如骨软骨针、骨软骨柱或钉子、金属螺钉或针，或可吸收螺钉、锚、箭头或针，都可能与纤维蛋白胶结合使用。成功率据报道，这一比例在91.7%和100%之间，具体取决于成像技术或成功的定义。然而，75%的患者在放射学上可检测到退行性关节间隙变窄。最佳碎片再固定技术仍在讨论中。实验观察到，螺钉固定效果最好，但可吸收材料会引发过敏和/或滑膜反应以及软骨损伤。

作者的观点是，成功的碎片再固定取决于碎片上是否存在大量骨骼，以允许与软骨下缺损底部的骨质固定。如果由于游离体过于碎片化或显示出所谓的“恶意形式”而无法进行碎片修复，则需要使用重建技术。

无法进行碎片修复时膝关节剥脱性骨软骨炎OCD治疗的替代技术

关于这些各种手术操作的报道很多，但几乎所有的文章都是病例系列，即IV级报告；虽然具有前瞻性，但没有与其他手术技术进行比较。

只有少数I/II级出版物可用。即使这些文章也并不总是能清楚地区分骨软骨损伤OCL和典型的剥脱性骨软骨炎OCD。青少年剥脱性骨软骨炎JOCD和成人剥脱性骨软骨炎AOCD之间没有明确的区别，评分系统和后续标准也没有得到一致的遵守。

由于文献中描述了不同的手术方法和保守治疗方法的混合，以及所有不同的定义，几乎不可能进行深入的比较。

单独的骨髓刺激技术微骨折(MFX)，或其他骨髓刺激与支持性基质相结合，即所谓的“自体基质诱导软骨形成”(AMIC)是其他可能的替代方案。然而，微骨折MFX术后超过5年可能会面临失败。在比较微骨折MFX和自体基质诱导软骨形成AMIC在治疗小的非剥脱性骨软骨炎OCD病变方面，发现小软骨病变没有显着差异。

自体骨软骨植入物（自体骨软骨移植[OAT]和马赛克成形术）

Wirth等报道了首批自体骨软骨移植OAT的研究之一，在几乎所有12名患有剥脱性骨软骨炎OCD的患者中都取得了良好的结果。Laprell和Petersen发表了第一个长期结果。在他们的病例系列中，他们在6年和12年（平均8.1年）的随访中报告了29名患者中的26名（主要是剥脱性骨软骨炎OCD病变）获得了良好和优异的疗效（ICRS评分）。他们使用内侧髁非负重区作为供体区域，但没有填补剩余的缺损。在随访中，他们在26名患者的取材区观察到囊性病变。

Hangody等报告了76名患者中，89%的患者获得了良好或优秀的结果，这些患者都患有剥脱性骨软骨炎OCD。在另一项使用骨软骨镶嵌成形术的研究中，并非所有病变都是由剥脱性骨软骨炎OCD引起的（33%），作者表示，股骨髁病变患者的结果（92%良好和优异的结果）比胫骨表面重新修复(87%)或髌骨或滑车损伤(79%)患者取得了更好的效果。

对骨软骨移植技术文献的概述表明，尽管存在很大差异，但许多论文并未区分骨软骨移植术OAT和镶嵌成形术。与最初的骨软骨移植术OAT技术相比，在2项研究中，镶嵌成形术填充的缺损仅包含60%至70%的透明软骨（参见图 5 中的示例）。其余 (30%-49%)是纤维软骨组织。命名法的不同使用使得精确比较变得困难。

为数不多的I级文章之一在 18 岁以下的青少年剥脱性骨软骨炎JOCD 患者中比较了微骨折MFX与镶嵌成形术的修复结果。虽然术后长达1年随访，两种技术之间没有显着差异，但在4.2年后的第二次随访中，微骨折MFX患者表现出显着恶化（41%失败），而接受镶嵌成形术治疗的患者保持稳定，91%的结果优秀或良好。

另一项后续研究分析了微骨折MFX或镶嵌成形术后的57名运动员，包括43%的剥脱性骨软骨炎OCD病变。92名镶嵌成形术患者取得了优异或良好的结果，而接受微骨折MFX治疗的患者中有52%的患者在术后最长37.1个月时明显恶化。在10年的长期随访后观察到了类似的结果镶嵌成形术的失败率为25%，而微骨折MFX的失败率为75%。

这两项独立研究表明，微骨折MFX似乎不是治疗剥脱性骨软骨炎OCD病变的手术替代方案。原则上，这是可以预料的，因为病变是骨软骨而不是具有完整软骨下骨板的单独的软骨病变。

两种骨软骨塞技术（OAT，镶嵌成形术）都可以通过关节切开术、小型关节切开术或关节镜来完成。使用这两种技术，开放式术式允许移植物的精确定位，使其能够适应高度和形状以适应周围、健康的关节面。一个缺点是与关节镜检查相比，关节切开术后本体感觉受到干扰和康复期延长。相反，关节镜检查技术需要非常有经验的外科医生。

巨大骨软骨移植Mega-OATS

在病变相当大的情况下，巨大骨软骨移植mega-OAT手术是一种替代方法。该技术使用从股骨髁背侧非负重区外植的大块骨软骨柱，由Imhoff等开创。然而，在此之前，后髁被描述为潜在的供体部位。手术膝关节的第一个结果，平均跟随9.8个月（范围2-26个月）显示93.8%的患者(15/16)有明显的术后改善。作者还治疗了受累膝关节力线异常，但没有观察到对结果的影响。另一篇关于这项技术的文章报道了29名患者中的26名在长达18个月的随访后取得了令人满意的结果。此外，高位胫骨截骨术对结果没有显着影响。29名患者中共有26名（89.7%）主观满意。16名患者(55.2%)能够恢复到术前的体育活动水平。没有观察到供体部位的发病率和移植区域边缘的问题。

巨大骨软骨移植Mega-OAT的优点是移植物是固定的，无需将它们锤入到位。这意味着可以避免移植中的软骨细胞死亡。5年后16名患者（4个外侧病灶，12个内侧病灶）的巨型骨软骨移植OAT结果显示，15名患者（93.8%）有显着改善。未检测到供体部位发病率，但作者提到了移植部位的新形成组织。关于同种异体巨型骨软骨移植OAT移植，仅发表了一份关于5名患者的报告。

自体软骨细胞移植(ACI)

自第一次发表关于自体软骨细胞移植ACI的文章以来，已经发表了几篇大多为IV级质量的文章。今天，这种技术已经有好几代了，主要是将细胞悬浮液播种在骨膜下或播种到支架基质中或支架基质上。

自体软骨细胞移植ACI的科学情况与骨软骨移植OAT/mosaicplasty或碎片修复相同。只有少数I级和II级研究。Peterson等报道了58名剥脱性骨软骨炎OCD患者、35名青少年剥脱性骨软骨炎JOCD患者和23名成人剥脱性骨软骨炎AOCD患者的成功治疗。 平均随访5.6年后，91%的患者总体结果良好或优异；93%的人报告了自我评估的改善。

考虑到剥脱性骨软骨炎OCD不仅是软骨也是骨软骨损伤OCL，一些患者接受了额外的骨移植。然而，不幸的是，没有对那些有骨移植物和没有骨移植物的人进行区分。

另一项IV级研究在40名青少年剥脱性骨软骨炎JOCD患者中报告了类似的结果。经典自体软骨细胞移植ACI治疗后80%的患者随访成功率为85%，失败率为19%。 Ferruzzi 等比较了通过关节切开术(n = 48)与使用细胞种子基质的关节镜手术 (n = 50)进行的自体软骨细胞移植ACI。25名患者患有剥脱性骨软骨炎OCD。他们观察到两组都有显着改善，但开放手术后的失败率为19%，明显高于关节镜技术后的失败率(4%)。此外，他们注意到关节镜介导的治疗后康复更快。

一项对80名患者进行的I级研究比较了自体软骨细胞移植ACI（n = 40）和微骨折MFX（n = 40），包括65%的创伤性病变、28%的OCD病变和7%的未明确诊断的患者，显示两组之间没有显着差异。在2年和5年的随访中，每组报告的成功率为77%，失败率为23%。

Bentley等对自体软骨细胞移植ACI与镶嵌成形术进行了两次比较。第一次在2003年，平均随访时间为1.7年，第二次在2012年，最短随访时间为10年。在第一次随访中，42名镶嵌成形术患者中有9名（21%）表现出优异的结果，而自体软骨细胞移植ACI组58名患者中有23名（40%）表现出优异的结果。此外，镶嵌成形术患者的不良结果率（17%）明显高于自体软骨细胞移植ACI组（0%）。术后1年的关节镜检查显示自体软骨细胞移植ACI后82%的修复良好或良好。在马赛克成形术后，34% 的人有良好的结果，没有“优秀”的结果。在至少10年的随访中，58名自体软骨细胞移植ACI患者中有10名（17%）和镶嵌成形术组42名中的23名（55%）修复失败。

假设无法追踪患者的移植物是完整的（“最佳情况”），失访患者的移植物不完整（“最坏情况”），比较Kaplan-Meier 曲线显示自体软骨细胞移植ACI后的结果明显优于镶嵌成形术后的结果。马赛克成形术后的结果在术后约2年开始恶化。

Basad 等分析了两步手术的结果，该手术使用双层技术在细胞接种支架手术之前植入缺损处的自体骨移植物。他们所有的患者在术后24个月都有明显的平均改善。其他两项研究均使用一步程序和细胞接种的胶原蛋白支架或凝胶中的软骨细胞（CaReS，图 6 中的示例），在长达36个月的随访后显示出显着改善。剥脱性骨软骨炎OCD患者。Steinhagen等显示所有剥脱性骨软骨炎OCD患者从术前到术后3个月和更长（术后长达36个月）的持续改善。在Steinhagen等和Ochs等的研究中，病变的大小分别是12 cm2和9 cm2。

据我们所知，只有1项I级研究比较了2种以上的技术。这些作者描述了一项非常有趣的、前瞻性的、针对青少年剥脱性骨软骨炎JOCD和成人剥脱性骨软骨炎AOCD患者的随机试验。该试验比较了以下程序：

大面积自体骨软骨移植；

自体骨软骨膏移植物；

自体软骨细胞移植（第2代）与骨移植相结合；

仿生骨软骨支架；

骨髓来源的细胞移植。

在总共60名患者中，他们没有发现显着差异，但青少年剥脱性骨软骨炎JOCD患者有更好结果的趋势。总体而言，IKDC（国际膝关节文献委员会）客观评分从术前的37%增加到最后一次随访时的97%向上。然而，随访时间从2.3年（骨髓来源的细胞）到12.2年（大量骨软骨移植物）不等，特定组的患者数量从7人（骨来源细胞植入）到28人（软骨细胞与骨移植物）。不同技术的结果之间的唯一区别是自体软骨细胞移植ACI (0.06)后结果更好的趋势。

同种异体移植物

多年来，新鲜、冷冻或储存的同种异体移植物也被用于晚期膝关节剥脱性骨软骨炎OCD病变。新鲜、冷藏的同种异体移植物是骨软骨同种异体移植物的标准选择，因为冷冻和冻干的软骨没有足够的活软骨细胞。当冷藏的同种异体移植物新鲜时，高达98%的软骨细胞存活7天；到28天，这一比例下降到70%。活力降低伴随着细胞密度降低和代谢活动降低。基质和软骨细胞已在长期恢复研究中显示存活。

然而，在同种异体移植之前，必须对移植物进行广泛的血清学、细菌和病毒检测，直到确保检测结果为阴性。必须筛选供体。必须提供全天候的移植服务。此外，尚未完全消除疾病的免疫原性和计划外转移。然而，据估计，艾滋病毒传播的风险低至大约万分之一，自1980年代后期以来，没有关于这种疾病传播途径的报道。

虽然软骨细胞被基质细胞保护以抵抗免疫反应，但移植物骨性部分的细胞应在很大程度上被去除。与似乎完全整合的软骨相比，骨整合可能是失败的原因。

有2项研究专门报告剥脱性骨软骨炎OCD；其他出版物包括高达45%的剥脱性骨软骨炎OCD患者。一方面，剥脱性骨软骨炎OCD患者的成功率相对较高，7.7年后的存活率为72%，10年后为82%。20年后存活率降至66%（45%的剥脱性骨软骨炎OCD病变）。另一方面，在15%至47%中，失败率和/或进一步手术的必要性很高。Lyon等报道青少年剥脱性骨软骨炎JOCD中的同种异体移植物；手术后，患者（平均年龄15.2岁）在6个月内毫无困难地恢复了日常生活活动，并在第9至第12个月之间恢复了全面的体育活动。

对14名患者的26份标本进行的检索分析显示，存活42个月后，82%的软骨细胞存活。组织学上，所有标本都显示出一些软骨纤维化，但没有移植排斥的迹象。

不同治疗方法后的长期结果

有大量文章的平均随访时间在5到34年之间。这些文章包括至少2项纵向研究，其中对患者进行了两次随访。然而，所有文章都只有IV级，这意味着对长期结果的解释很困难，特别是因为作者可能存在偏见。

关于剥脱性骨软骨炎OCD碎片的切除或去除，结果显示在10到20年后结果明显倾向于较差或一般。Michael等观察到28年后只有35%的结果良好和良好，大部分是在切除后骨关节炎OA率为92%。Twyman等报道了类似的数据。一份关于仅外侧髁剥脱性骨软骨炎OCD的报告描述了大多数患者（22/28膝关节）在关节镜切除和软骨下钻孔后14年的中度骨关节炎OA但更好的临床结果。相比之下，85%到92%的患者在5到15年后碎片再固定后的结果是优秀或良好的。似乎再固定导致骨关节炎OA的发生率明显降低，并且在34年的随访中，35%的中度骨关节炎OA被发现。

就可以进行比较而言，重建疗法倾向于以较低的骨关节炎OA率获得更好的长期结果，如骨软骨移植OAT所述：大多数患者(48%)在8.1年后表现出相同的术后骨关节炎OA等级，当与术前相比，34%的患者受损程度为1级。

Peterson等提到58名患者中有91%的患者在软骨细胞移植术ACI后获得了优异或良好的临床结果，平均随访时间为5.6年，但近50%的患者也提到了骨关节炎OA的迹象。

同种异体移植修复后的长期结果显示成功率相对较高，7.7年后（所有剥脱性骨软骨炎OCD病变）的存活率为72%，10年后为82%。然而，20年后仅为66%（45%剥脱性骨软骨炎OCD)并且在15%到47%之间存在很高的失败率和/或再手术率。

合并症

膝关节力线异常

几位作者报道了膝关节内侧髁剥脱性骨软骨炎OCD病变与内翻畸形以及外侧病变与外翻畸形之间的关系。Jacobi等分析了他们患者的双侧下肢全长X线片，并发现剥脱性骨软骨炎OCD病变和内翻或外翻机械轴的偏差分别与内侧（内翻）和外侧病变（外翻）显着相关。受影响和未受影响的膝关节之间的差异对于外侧而不是内侧病变也很显着。随后，矫正畸形应被视为一个额外的治疗目标，内翻比外翻畸形更重要。Slawski报道了6名成人剥脱性骨软骨炎AOCD患者的7个膝关节内翻畸形，并进行了高位胫骨截骨术，术后Lysholm评分明显改善。

前交叉韧带ACL不稳定和半月板损伤

前交叉韧带ACL不稳定或半月板损伤也应该在治疗上得到解决。Hangody等报道了85%的伴随手术干预率。这些手术中的大多数是前交叉韧带ACL重建、重新排列截骨术、半月板手术或髌股关节重新排列。

有报道称股骨外侧髁的剥脱性骨软骨炎OCD病变与盘状半月板合并，以及在盘状半月板全半月板切除术后发展为剥脱性骨软骨炎OCD病变。随后，我们认为，盘状半月板应通过手术缩小至正常半月板的大小。然而，盘状半月板的全半月板切除术也可能导致同侧剥脱性骨软骨炎OCD病变的发展。

结论

剥脱性骨软骨炎OCD仍然是一个病因学、组织学和治疗学的谜团。关于剥脱性骨软骨炎OCD病变的分类和定义及其与其他病变的区别，以及关于青少年剥脱性骨软骨炎JOCD和成人剥脱性骨软骨炎AOCD的明确定义，存在很多混淆。此外，对于应该使用哪种治疗策略，没有明确且科学依据良好的建议。此外，仍然缺少对临床和影像学成功和/或愈合的明确和统一使用的定义。

尽管有大量关于不同关节剥脱性骨软骨炎OCD的各个方面的文献，但缺乏科学可靠的前瞻性随机研究。

至少对于膝关节的剥脱性骨软骨炎OCD病变仍然存在混淆，并且在“美国骨科医师学会”的一个工作组制定的“剥脱性骨软骨炎的诊断和治疗”出版物中的“建议摘要”中表达了这一点。由Chambers等发表。他们发现，关于16个不同方面的建议强度在10个方面不确定，在2个方面较弱；小组仅在4个方面达成共识。

未来，处理骨关节疾病的机构的国际目标应该是制定一种协议，以提供比从IV级研究中获得的数据更令人满意的数据，这些数据几乎没有科学价值。

Osteochondritis Dissecans: Etiology, Pathology, and Imaging with a Special Focus on the Knee Joint.

Abstract

This article is a review of the current understanding of the etiology, pathogenesis, and how to diagnose and treat knee osteochondritis dissecans (OCD) followed by an analysis of and outcomes of the treatments available. OCD is seen in children and adolescents with open growth plates (juvenile OCD) and adults with closed growth plates (adult OCD). The etiology of OCD lesions remains unclear and is characterized by an aseptic necrosis in the subchondral bone area. Mechanical factors seem to play an important role. Clinical symptoms are unspecific. Thus, imaging techniques are most important. Regarding treatment, a tremendous number of publications exist. Spontaneous healing is expected unless there is an unstable fragment, and treatment involves rest and different degrees of immobilization until healing. Patients with open physes and low-grade lesions have good results with conservative therapy. When surgery is necessary, the procedure depends on the stage and on the state of the cartilage. With intact cartilage, retrograde procedures are favorable. When the cartilage is damaged, several techniques can be used. While techniques such as drilling and microfracturing produce reparative cartilage, other techniques reconstruct the defect with additional osteochondral grafts or cell-based procedures such as chondrocyte transplantation. There is a tendency toward better results when using procedures that reconstruct the bone and the cartilage and there is also a trend toward better long-term results when comorbidities are treated. Severe grades of osteoarthrosis are rare.

Keywords: etiology; general; imaging; knee joint; osteochondritis dissecans; pathology.

文献出处：Juergen Bruns, Mathias Werner, Christian Habermann. Osteochondritis Dissecans: Etiology, Pathology, and Imaging with a Special Focus on the Knee Joint. Review Cartilage. 2018 Oct;9(4):346-362. doi: 10.1177/1947603517715736.

Introduction

Osteochondritis dissecans (OCD) is a common cause of knee disorder among skeletally immature and adult patients and it occurs when a small piece of subchondral bone begins to separate from its surrounding area due to a disturbance of the local blood supply. Finally, a small fragment of bone and the cartilage covering it may begin to crack and get loosened. It was Ambroise Paré and not Paget, as was previously assumed, who was the first (in 1870) to describe such loose bodies found in a joint,1 The term osteochondritis dissecans was initially mentioned in 1888 by K?nig1 who suggested 3 possible causes of the development of loose bodies:

Direct trauma with acute osteochondral fracture

Minimal trauma that develops into osteonecrosis and consecutive fragmentation

No evidence of trauma with a spontaneous development, which K?nig called “osteochondritis dissecans” (OCD).1

The exact prevalence of OCD is unknown but rates of between 15 and 29 per 100,000 have been reported.2,3 Kessler et al.4 have shown that the incidence of OCD of the knee in patients aged 6 to 19 years was 9.5 per 100,000 and 15.4 and 3.3 per 100,000 for male and female patients, respectively (Table 1). Patients aged 12 to 19 years represented the majority of OCD, with an incidence of 11.2 per 100,000 versus 6.8 per 100,000 for those aged 6 to 11 years. In summary, male patients had much greater incidence of OCD and almost 4 times the risk of OCD compared with female patients.4

OCD in this article means a chronic disease of the involved joint that has not resulted from an acute trauma. It is consisting of a fresh osteochondral or chondral lesion (OCL) and with or without a loose osteochondral fragment. OCD is usually regarded as either juvenile OCD (=JOCD) (occurring with an open epiphyseal plate) or adult OCD (=AOCD) (after the physis has closed). These definitions suggest a greater chance of a successful nonsurgical management in patients where the physes are still open than in adult patients with OCD lesions where the physes are already closed.6

This article is a review on what is known about OCD and with a special focus on the largest joint affected; the knee joint. In a future article, the elbow and the ankle joint will be addressed.

Etiology

One may divide the OCD etiology into 4 different possible causes; traumatic, ischemic, hereditary, and idiopathic7,8 (Table 2). However, etiology of multifactorial origin is the most probable cause.

Trauma: Probably caused by indirect trauma as seen on the most common OCD lesion, the posteromedial medial femoral condylar position.7 Repetitive stress to immature knees and on the tibial spine on the lateral aspect of the medial femoral condyle during internal rotation of the tibia may contribute to the development of human OCD. Such a subchondral stress reaction probably interferes with bony trabecular healing and impedes the ability of the bone to heal. Owing to the lack of underlying support of the cartilage, later stages can lead to a separation of the articular cartilage bone connection with partial loosening of the involved osteochondral region.

Ischemia: Poor vascularity and induced ischemia have been described as a potential cause of OCD.8 Some studies have shown difference in vascular pattern that has been seen at the OCD-positioned sites. Such a joint morphology combined with focal repeated trauma on this site with a unique vascular architecture may trigger ischemic events and subsequent OCD.9

Genetics: Several authors have investigated a potential genetic link for OCD but still genetic and developmental factors in the development of OCD remain relatively unstudied. Skagen et al.10 propose that OCD lesions are caused by an alteration in chondrocyte matrix synthesis causing an endoplasmic reticulum storage disease phenotype, which disturbs or abrupt endochondral ossification. Furthermore, cases of identical twins presenting with a similar disease process are highly suggestive of a genetic component.11

General OCD Pathogenesis

Although the etiology is not fully clear, the pathogenesis of OCD is relatively well understood. Independent from the etiology, at least 4 stages can be described.

Stage 1

OCD lesions start in the subchondral bone with intraosseous subchondral osteopenia, which is only detectable with magnetic resonance imaging (MRI) or bone scans.

Stage 2

The lesions are associated with an intraosseous edema of the subchondral bone.12-14 A bone bruise is probably the initial stage and subchondral trabecular microfractures might be the morphological correlate of the bone marrow edema.15-20

Stage 3

The continuing, natural course is characterized by a radiologically detectable sclerotic ring, which demarcates the lesions from the surrounding healthy bone. The center of the lesions is thought to be an osteonecrosis (see section “OCD Histology”). At this stage, the cartilage still seems to appear intact in imaging techniques such as MRI and computed tomography (CT).12

Stage 4

A “softening phenomenon and alteration in the mechanical properties of cartilage”19 promotes a reaction of the bone at the border of the necrosis toward the healthy surrounding bone. Still remaining mechanical loads are probably responsible for the cartilage now being involved and showing signs of separation. Finally, the ongoing natural course leads to a loosening of an osteochondral fragment resulting in a single loose body or the occurrence of multiple fragments (the so-called “malicious variant” first described by Wagner.21,22

There are several biomechanically orientated analyses concerning the suggestion of a biomechanical etiology. Rehbein23 in 1950 was able to experimentally produce loose bodies in knee joints of dogs by artificially produced repetitive stress. The specimens histologically resembled those findings described below, which were obtained from loose bodies in the knee joints of humans.

An experimental trial using plane and stereoscopic knee models made from epoxy resins,24 as well as a finite elements analysis of the distal femur,25 revealed peak stresses in the region where an OCD lesion occurs. Using photosensitive foils in the knee mimicking the clinically obvious factors, such as varus or valgus malalignment (knee) with stable and unstable ligaments, exhibited a significant stress concentration in those areas well-known for the clinical development of OCD lesions.26,27

Seen clinically, bone bruises following a bone contusion of the knee are assumed to be primary lesions of the subchondral trabecular bone, which probably initiates an OCD.17,18

OCD Histology

Histology of an advanced lesion is presented in Figure 1. Green and Banks28,29 were, to our knowledge, the first to describe a subchondral osteonecrosis as the initial lesion with still intact overlying cartilage.

Owing to the loss of the mechanical support of the bone for the cartilage, the ongoing process results in secondary damage to the cartilage layer.30 The authors suggested that healing might be possible by creeping substitution provided that the overlying cartilage is still intact. Histological examinations of loose bodies revealed that hypertrophy was common and laminar calcification was found in 53%.31,32

Chiroff and Cooke33 detected fibrocartilaginous tissue at the level of separation and in the bony part of the loose bodies, an increased osteoblastic and osteolytic activity under the almost normal cartilage was found. Furthermore, Milgram34 found no bone in half of the loose bodies. Koch et al.35 analyzed 30 specimens from patients aged 16 to 44 years who had advanced stages of OCD and observed a decreased toluidine staining of PH 1 in the cartilage. A reduced number of chondrocytes could be seen as well as fractured areas in the subchondral bone plate and in the cancellous bone. Furthermore, they found areas of enhanced bone resorption and necrotic subchondral bone surrounded by fatty bone marrow.

Uozumi et al20 have described 3 types of histopathological features:

OCD with necrotic subchondral trabeculae

OCD with viable subchondral trabeculae

OCD cartilage without bone trabeculae.

They summarized that “the initial change in the subchondral area is bone necrosis or subchondral fracture; the necrotic bone is then absorbed and replaced by viable subchondral trabeculae or cartilage without bone trabeculae.”20 In contrast, osteonecrosis could not be detected in any of 8 needle biopsies from the center of stable JOCD lesions in the medial femoral condyles without any degenerative changes.36 Only a thick cartilage layer and fibrous tissue, or thin cartilage with mixed cartilage underneath were found, as were subchondral trabeculae and fibrous and fibrocartilage at the areas of separation.

Most recently, an analysis of loose bodies showed that the chondrocytes from the loose bodies displayed a normal behavior and the cells were regarded to be usable for autologous chondrocyte implantation (ACI).37

A meta-analysis of the already published data on histological analyses38 resulted in inconsistent findings: In 7 out of 10 studies, which included the subchondral bone, signs of a bony necrosis had been reported; in 2 out of 11 publications, degenerative or irregular cartilage was mentioned. Regarding the possible underlying etiology, 5 out of 11 articles suggested one major or multiple repetitive microtraumata as the etiological factor. In conclusion, the histological results suggest a focal alteration of cartilage matrix originating from the deep layers of the joint cartilage, potentially the mineralized layer or the subchondral bone.37

Diagnosis of OCD

OCD-related Symptoms

Symptoms are often vague and poorly localized. Different degrees of pain and stiffness may be present; swelling and effusion of the joint and “giving way,” “catching,” or “blocking” of the joint might occur. There are no typical clinical signs for an OCD in any joint.12,30,39,40 The Wilson test, recommended as a clinical diagnostic test at the knee joint is not reliable.41-43

OCD localization schemes are presented in Table 4.

Imaging Techniques for OCD Evaluation

Plain X-rays Before the use of MRI started, initial changes could only be detected with bone scans, or suspected on conventional radiographs. With the introduction of MRI, it was possible to differentiate stages more easily. However, it is still difficult to estimate reliably the mechanical properties of the cartilage layer.

The initial diagnostic schedule when an OCD lesion is suspected starts with an X-ray in 2 orthogonal planes. The standard series include a standing anterior-posterior (AP) view (Fig. 2), a lateral view with the knee flexed 35°, and a 45°patella sunrise view. Additional special X-ray views could be useful such as a tunnel view bringing the area with the lesion more in line with the imaging plane up.65

Magnetic Resonance Imaging MRI is the method of choice as the second step in an imaging workup (Fig. 3a and b). Since the availability of MR systems has increased in the past 10 years, the lack of radiation, the sudden development of higher field strengths (1.5 and 3 T), dedicated coil settings, and high-resolution sequences saved the way for the advance of MRI in musculoskeletal imaging. The regular MR approach uses T1- and T2-weighted images in all 3 spatial directions. The maximal slice thickness should be 3 mm, offering a sensitivity of 96% (specificity 0.96) for detecting osteochondral defects at the talus. Diapola et al.50 have developed a useful MRI system for OCD evaluation with 4 gradings:

Stage 1: Thickening of articular cartilage and low signal changes.

Stage 2: Articular cartilage breached, low signal rim behind fragment indicating fibrous attachment.

Stage 3: Articular cartilage breached, high signal changes behind fragment, indicating synovial fluid between fragments and underlying bone

Stage 4: Loose body.

It is also possible to use the arthroscopic International Cartilage Repair Society (ICRS) OCD classification and Guhl’s classsifiaction44,56 when evaluating OCD on MR images (see Arthroscopic Classifications).

To improve the evaluation, MRI can also be performed by injecting gadolinium MR contrast material into the examined joint shortly before the examination. Such a dGemeric MRI gives information about the matrix quality. Using T2-weighted sequences, the presence of a high signal line or a cyst below an osteochondral lesion indicates the presence of fluid and suggests the presence of an unstable osteochondral defect, even though this signal can reflect vascular granulation tissue representing a healing reaction. Proton density images and 3-dimensional T1-weighted sequences with fat saturation using isotropic voxels below 1 mm with a dedicated field of view (14-20 cm) and intravenous contrast material offer a brilliant image impression and can also differentiate subtle changes.65 Using these sequences as well, MRI offers excellent diagnostic capabilities in detecting even unstable osteochondral lesions. Consequently, routinely intra-articular administration is not necessary for evaluating osteochondral lesions.

Using newly implemented high-resolution sequences to differentiate different types of osteochondral defects offers an overall accuracy of more than 90%.66

In the daily clinical routine, 1.5- and 3-T systems are available. Comparing dedicated coil settings on both systems, the image impression might be better using higher field strength (3-T systems). However, 3-T systems have not yet proved to offer better diagnostic results with regard to cartilage lesions.67

Computed Tomography The 2 important shortcomings of CT are the applied radiation, especially with regard to the age of examined patients, and the lack of visualization of the cartilage. The lack of cartilage visualization can be overcome by using intra-articular contrast material, which can be applied by a direct puncture of the joint and offers an indirect visualization of the cartilage. CT scans can be used to assess the osseous integration after refixation of OCD loose fragments.68

Scintigraphic Examination

Paletta and colleagues69 found that quantitative bone scanning had a 100% predictive value for the prognosis in OCD patients with open physes, but for those with closed physes the predictive value was less.

Cahill and Berg47 have developed a classification useful when to evaluate scintigraphic results of juvenile OCD patients:

0.Normal radiographic and scintigraphic appearance.

1.The lesion is visible on plain radiographs, but bone scans reveal normal findings.

2.The scan reveals increased uptake in the area of the lesion.

3.In addition, there is increased isotopic uptake in the entire femoral condyle.

4.In addition, there is uptake in the tibial plateau opposite the lesion.

Treatment of OCD of the Knee Joint

OCD lesions in the knee joint are located predominantly in the medial femoral condyle and are often associated with a varus malalignment. A minority of OCD lesions are located in the lateral condyle and is associated with valgus malalignment.61,70-72

Lesion Location

Lesions at the lateral femoral condyle can also occur in association with discoid menisci. A lesion at the lateral condyle can develop either primarily with a discoid meniscus or secondarily, after a total resection of a discoid lateral meniscus.73-78 It has been assumed that the altered biomechanics of the knee with a discoid meniscus, or after total lateral meniscectomy, are responsible for the development of an OCD lesion.73-78 The prominence ratio of the lateral condyles of patients with a discoid meniscus is significantly larger than that of controls.78

Only a small number of lesions are located in the patellofemoral joint.12,79,80

Lesion Stability

For both JOCD and AOCD, the indication to follow a conservative therapy or go for a surgical approach depends on the stability of the osteochondral fragment (Table 5). However, what is a stable lesion? Wall et al.81 stated, “A stable OCD was defined as one showing no breach in the articular or the subchondral bone-lesion interface.” Trinh et al.82 realized that their review contained varying definitions for a stable or unstable lesion and adapted them to those used by De Smet et al.51

Lesion instability is said to exists if

A line of high-signal deep to the fragment is seen on T2-weighted image on MRI.

An articular fracture, indicated by a high signal, passes through the subchondral bone plate.

A focal, osteochondral defect is present.

A 5-mm diameter, fluid-filled cyst is deep to the lesion.

Conservative Treatment

A few articles have been published that differentiate between JOCD and AOCD advocating conservative treatment but with different treatment regimes

JOCD

Most children suffering from JOCD can be successfully treated conservatively.6,19,48,56,83 Restrictions on weightbearing and sports activities have been suggested or simply limitation of daily activities and immobilisation.5,6,33,48,51,62-64,84,85 A common treatment suggestion is that the patient has a brace for 6 to 12 weeks with partial weightbearing and follows regularly with physiotherapy training. If the patient is pain free at 12 weeks and if the imaging shows healing, the patient could start running activities but more aggressive activities should be restricted until the patient have been followed for more months of symptom free activities in sport and leisure such as jumping, twisting and impact loading.

In a recently published, retrospective study on 42 JOCD patients, two-thirds (66%) of the stable lesions healed after an initial treatment with plaster-cast immobilization followed by bracing and limitation of activity for up to 6 months.81 However, the authors experienced failure of treatment in 34% of the patients. Large lesions did significantly worse than the smaller ones (relatively and absolutely), but all the lateral lesions healed.

Prospective factors such as size of a lesion, condyle or noncondyle localization, age, and gender of the patient are still being controversially discussed.5,6,48,63,84-89

Of interest is a European multicenter study6 with the largest number of patients up to now (452 patients with 509 affected knee joints). In 452 patients with a minimal follow-up of 1 year, they differentiated a group A of 276 patients with open physes, for example, males up to 14 years of age and females up to the age of 13 years, from a group B of so-called “premature” patients, for example, over 14 years of age for males and over 13 years for females. A total of 154 patients received conservative treatment while 355 patients needed surgery. Significantly better results were seen in patients from group A than from group B. Those whose situation was favorable (no gross dissection, size ＜ 20 cm2) did significantly better than those with an already detectable dissection (so-called “unfavorable conditions”). Application of a plaster-cast did not influence the result of the conservative treatment in comparison to treatment without a cast (normal and near-normal knees 69.2% vs 72%, respectively). In contrast, those patients with an unfavorable condition had significantly worse results after conservative treatment (abnormal knees in 44%) when compared with surgical therapy (abnormal knees in 33.1%).6

AOCD Regarding AOCD patients, little knowledge exists. Meanwhile, the question is as to whether OCD in AOCD patients occur de novo or whether it is already present prior to epiphyseal closure but, owing to a failed treatment, is still there after epiphyseal closure. The question as to conservative therapy is “How are those persons with an AOCD affected?” In general, to our knowledge there is no explicit answer. Only 1 study has compared patients up to an age of 13 (girls) or 14 years (boys) with those in a premature stage (girls older than 13 or boys older than 14 years) and presented some reliable data. The results for JOCD patients were better after any type of treatment than for any patient in a premature stage.

For AOCD, successful conservative treatment is less likely.6 Lindén5 noted excellent results, regardless of the conservative therapeutic regime, and that children with open physes display no degenerative changes. Hughston et al.63 recommended normal activity and strengthening of the muscles rather than immobilization. The rate of healing following nonoperative treatment ranged from 50% to 94%.5,6,29,33,48,63,64,81,84,85,90

Surgical Treatment

Arthroscopic evaluation and treatment is used as next step when conservative treatment has failed. Accepted, general indications for surgical treatment are4,47,54,64,91

Unstable lesions with already-visible loose bodies

Detachment that occurs during observation or nonoperative treatment when a physeal closure is predicted to occur within 6 to 12 months

When juvenile lesions remain symptomatic despite adequate nonoperative treatment

When an established nonunion of a fragment is detectable

There exist several different classification systems for the arthroscopic evaluation of an OCD lesion. The most well-known is the arthroscopic classification according to Guhl56:

Stage 1: Stable lesion

Stage 2: Lesions showing signs of early separation

Stage 3: Partially detached lesions

Stage 4: Craters with loose bodies.

ICRS has developed a system for evaluating of cartilage lesions and also a system for OCD evaluations.2 The ICRS OCD classification is a modified Guhl classification to adjust cartilage evaluation of OCD lesions to the common ICRS evaluation system44

ICRS OCD 0: Stable, normal intact overlying cartilage

ICRS OCD I: Stable with continuous but softened area with intact cartilage

ICRS OCD II: Stable with partial discontinuity

ICRS OCD III: In situ lesion with complete discontinuity

ICRS OCD IV: Empty defect with dislocated or loose fragments

General Remarks of Operative Treatment

However, indications for surgery are controversial and unclear.82 In a recent review article,82 30 studies (only 1 level-I) on 783 subjects with 862 knees were evaluated. The mean postoperative follow-up was 77 months, minimum 2 years. Nearly all patients demonstrated significant clinical and radiographic improvements in surgically treated JOCD at short-, mid-, and long-term follow-up. Excision of weightbearing OCD lesions led to poorer clinical and radiographic results than other surgical techniques. Outcomes were significantly better for JOCD versus AOCD.

Different surgical techniques, such as retrograde or anterograde drilling (alone or in combination with cancellous bone grafting),54,57,92-95 should only be indicated for low-grade lesions preferably JOCD.54,96 The anterograde technique is easier than the retrograde approach, but perforation of the cartilage layer is necessary in order to reach the involved subchondral bone.

The retrograde approach is more difficult owing to the open physes but it does leave the cartilage layer intact. Imaging techniques, such as fluoroscopy, MRI, ultrasound, or arthroscopy are recommended in order to be able to navigate the drills toward the defect.95,97-100 The goal of both variants is either to perforate the subchondral sclerosis or to promote blood supply to the subchondral necrotic area.

The most important prognostic factor is age. It was observed radiographically that the lesions had healed within 6 weeks to 2 years postoperatively in up to 100% of the JOCD patients but in only 25% of the AOCD cases.56,57,82,91,101,102

Large lesions need a longer time to heal than small ones.101

JOCD A summary of the most recent review of 25 articles, all on JOCD,103 showed that the most common techniques were transarticular drilling for stable lesions and the use of bioabsorbable pin-fixation for fragment refixation. The key findings were that the vast majority of lesions healed postoperatively, regardless of technique, and that high-quality trials are required to more appropriately compare the effectiveness of techniques.103 A similar résumé was published after reviewing anterograde and retrograde drilling.97

AOCD

Nearly nothing is known about drilling stable lesions in AOCD. Unstable AOCD lesions are mostly treated surgically. For several years, in cases of damage to the cartilage layer, removal of the loose cartilage or osteochondral fragments was recommended, possibly in combination with a debridement procedure. Nowadays, however, this is no longer done owing to poor results, with up to 71% rate of osteoarthritic (OA) changes.2,6,47,55,58,63,83,87,91,104-115 For these reasons, fragment refixation of partially or completely loose bodies—as far as is possible—is recommended (see example in Fig. 4). Histologically, these fragments contain mostly viable cartilage.35,37 Either combining fragment refixation with drilling of the subchondral bone, in order to perforate the subchondral sclerosis, or removal of the sclerosis followed by cancellous bone grafting followed by fragment refixation4,6,64,91,103 is recommended.

Techniques for Fragment Refixation

Several methods have been used for OCD fragment refixation, such as osteochondral pins, plugs or pegs, metallic screws or pins, or resorbable screws, anchors, arrows or pins, all probably in combination with fibrin glue.2,64,82,103,110,112,114,116 The success rate reported has been between 91.7% and 100%, depending on the imaging technique or definition of success.103,116 However, degenerative joint-space narrowing has been radiographically detectable in 75%.110 The optimal fragment refixation technique is still under discussion. It has been observed experimentally that screw-fixation gave the best results117 but that resorbable material can initiate allergic and/or synovial reactions and cartilage damage.118

The authors’ opinion is that successful fragment refixation depends on the existence of a substantial amount of bone on the fragment to allow bony consolidation with the subchondral defect bottom. In cases where fragment refixation is not possible because the loose body is too fragmented, or shows the so-called “malicious form,”21 reconstructive techniques are indicated.

Alternative Techniques for Knee OCD Treatment when Fragment Refixation Is Not Possible

There are numerous reports on these various operative procedures but almost all the articles are case series, that is, level-IV reports; although with a prospective character but without comparison with other procedures.

Only a few level-I/II publications119-126 are available. Even these articles have not always differentiated distinctly between an OCL124 and a typical OCD.119-121 Clear differentiation between JOCD and AOCD has not been made and scoring systems and follow-up criteria have not been consistently adhered to.

With the mixture of different methods of surgery and conservative treatment described in the literature, and with all the different definitions, profound comparisons are nearly impossible.

Bone Marrow Stimulation Techniques Microfracture (MFX) alone, or other bone marrow stimulations combined with a supportive matrix so-called “autologous matrix-induced chondrogenesis” (AMIC) are other possible alternatives.127-129 However, failures can be expected beyond 5 years following MFX.120,130 In a comparison between MFX and AMIC in the treatment of small non-OCD lesions, no significant differences for small cartilage lesions were found.131

Osteochondral Autologous Plug Implants (Osteochondral Autograft Transfer [OAT] and Mosaicplasty) One of the first studies on OAT was reported by Wirth et al.132 with favorable results in almost all of the 12 patients suffering from OCD. First long-term results were published by Laprell and Petersen.133 In their case series, they reported good and excellent results (ICRS score) in 26 out of 29 patients (mostly OCD lesions) at a follow-up of 6 and 12 years (mean 8.1 years). They had used the dorsal medial condyle as the donor region but did not fill up the remaining defect. At the follow-up, they observed cystic lesions in the harvest area in 26 patients.133

Hangody et al.134 reported good or excellent results in 89% of 76 patients, all of whom were suffering from OCD. In another study using the mosaicplasty, in which not all the lesions were caused by OCD (33%), the authors stated that better results were achieved in patients who had a condylar lesion (92% good and excellent results) than in those with a tibial resurfacing (87%) or a patellar or trochlear lesion (79%).135

An overview of the literature on osteochondral transplantation techniques shows that a lot of papers do not differentiate between OAT and mosaicplasty, although there is a substantial difference. In contrast to the original OAT technique, in 2 studies the mosaicplasty filled defects consisted of only 60% to 70% hyaline cartilage (see example in Fig. 5). The rest (30%-49%) were fibrocartilage tissues.135,136 The varying use of the nomenclature makes exact comparison difficult.116,121,122,136-140

One of the very few level-I articles122 compared MFX with mosaicplasty in exclusively JOCD patients up to an age of 18 years. While up to 1 year postoperative, there was no significant difference between the 2 techniques, at the second follow-up after 4.2 years, MFX patients exhibited a significant deterioration (41% failure) while those treated by mosaicplasty remained stable with 91% excellent or good results.

Another follow-up study analyzed 57 athletes after either MFX or mosaicplasty, including 43% OCD lesions. Ninety-two of the mosaicplasty patients had excellent or good results while 52% of the patients who were treated with MFX were significantly worse at a maximum of 37.1 months postoperation.121 Similar results were observed after a long-term follow-up of 10 years where there was a 25% failure rate with mosaicplasty as opposed to 75% with MFX.137

These 2 independent studies showed that MFX does not seem to be a surgical alternative in the treatment of OCD lesions. In principle, this can be expected since the lesion is an osteochondral and not a solely chondral lesion with an intact subchondral bone plate.

Both osteochondral plug techniques (OAT, mosaicplasty) can be applied via an arthrotomy, mini-arthrotomy, or arthroscopically.133-135 With both techniques, the open variant allows a precise positioning of the transplant, enabling it to adapt in height and shape to the surrounding, healthy, articular surface. A disadvantage is the disturbed proprioception and prolonged rehabilitation period after arthrotomy than after arthroscopy.135,141,142 In contrast, arthroscopic techniques require a very experienced surgeon.

Mega-OATS In cases with fairly large lesions, the mega-OAT procedure is an alternative. This technique uses large osteochondral plugs explanted from the dorsal condyles and was inaugurated by Imhoff et al.143 However, well before that, the posterior condyle was described as a potential donor site.21,22,144 First results on operated knee joints with a mean follow-up of 9.8 months (range 2-26 months) showed a distinct postoperative improvement in 93.8% of patients (15/16).143 The authors also treated malalignments of the involved leg but did not observe an influence on the results. Another article on this technique145 reported satisfactory results for 26 out of 29 patients after a follow-up of up to 18 months. Furthermore, a high tibial osteotomy did not significantly influence the results. Altogether 26 out of 29 patients (89.7%) were subjectively satisfied. Sixteen patients (55.2%) were able to return to their preoperative level of sports activities. Neither donor site morbidity nor problems at the rim of the explant region were observed.

Mega-OAT has the advantage that the transplants are fixed without having to hammer them into place. This means that chondrocyte death in the transplants can be avoided. Results of mega-OAT in 16 patients (4 laterals, 12 medial lesions) after 5 years showed a significant improvement in 15 patients (93.8%). No donor site morbidity was detected but the authors mentioned newly-formed tissue in the region from where the transplants had been taken.146 Regarding allogenic mega-OAT transplants, only 1 report on 5 patients has been published.147

Autologous Chondrocyte Implantation (ACI) Since the first publications on ACI,148 several articles of mostly level-IV quality have been published. Today, there are several generations of this technique mostly with cell suspension seeded under a periosteal membrane or seeded into or on scaffolding matrices.

The scientific situation of ACI is the same as for OAT/mosaicplasty or fragment refixation. There are only a few level-I and -II studies. Peterson et al.149 reported successful treatment in 58 patients with OCD, 35 with JOCD, and 23 with AOCD. After a mean follow-up of 5.6 years, 91% of the patients had a good or excellent overall result; 93% reported a self-assessed improvement.

Taking into consideration that OCD is not only a chondral but also an OCL, some of the patients received additional bone grafts. However, unfortunately, no differentiation was made between those with and those without bone grafts.

Another level-IV study150 reported similar results in 40 exclusively JOCD patients. A follow-up in 80% after the classic ACI treated patients a success rate of 85% was found while the failure rate was 19%. Ferruzzi et al.151 compared ACI via an arthrotomy (n = 48) with an arthroscopic procedure (n = 50) using a cell seeded matrix. Twenty-five of the patients were suffering from OCD. They observed a significant improvement in both groups but the failure rate after an open procedure was 19%, distinctly higher than after the arthroscopic technique (4%). In addition, they noted a faster rehabilitation following arthroscopy-mediated treatment.

One level-I study on 80 patients comparing ACI (n = 40) with MFX (n = 40),119,120 including 65% traumatic lesions, 28% OCD lesions and 7% with unspecified diagnoses revealed no significant differences between both groups. At a follow-up of 2 and 5 years, a success rate of 77% and a failure rate of 23% were reported for each group.

Two comparisons of ACI with mosaicplasty were made by Bentley et al. the first in 2003 with a mean follow-up of 1.7 years125 and the second in 2012126 with a minimum follow-up of 10 years. At the first follow-up, 9 out of 42 mosaicplasty patients (21%) exhibited an excellent result in contrast to 23 out of 58 (40%) in the ACI group. Furthermore, the rate of poor results for the mosaicplasty patients was distinctly higher (17%) than in the ACI group (0%). Arthroscopy at 1 year postoperatively demonstrated excellent or good repairs in 82% after ACI. Following mosaicplasty, 34% had good results, no “excellent” outcome. At a minimum of 10 years’ follow-up,126 the repair had failed in 10 out of 58 ACI patients (17%) and 23 out of 42 (55%) from the mosaicplasty group.

Assuming that the grafts of patients who could no longer be traced were intact (“best-case scenario”), grafts of patients lost to follow-up were not intact (“worst-case scenario”), comparison of the Kaplan-Meier curves revealed distinctly better results after ACI than after mosaicplasty. Deterioration of the results after mosaicplasty started at approximately 2 years postoperatively.126

Basad et al.152 analyzed the results of a 2-step procedure using autologous bone grafts implanted into the defect prior to the cell seeded scaffold procedure with a double-layer technique. All their patients had a distinct mean improvement 24 months postoperatively. Two other studies,153,154 both using a 1-step procedure and cell-seeded collagen scaffold or chondrocytes in a gel (CaReS, example in Fig. 6), demonstrated a significant improvement after a follow-up of up to 36 months in all of the OCD patients. Steinhagen et al.153 showed a continual improvement from preoperative to 3 months postoperatively and longer (up to 36 months postoperatively) in all of the OCD patients. The size of the lesions measured up to 12 cm2 and 9 cm2 in the studies by Steinhagen et al.153 and Ochs et al.,154 respectively.

To our knowledge, there is only 1 level-I study comparing more than 2 techniques.123 These authors described a very interesting, prospective, randomized trial on JOCD and AOCD patients. The trial compared the following procedures:

Massive autologous osteochondral transplants

Autologous bone-cartilage-paste grafts,

Autologous chondrocyte transplantation (second generation) in combination with a bone graft

Biomimetic osteochondral scaffolds

Bone marrow–derived cell transplantation.

In a total of 60 patients, they did not find significant differences but there was a tendency toward better results in JOCD patients.123 Overall, the IKDC (International Knee Documentation Committee) objective score increased from 37% preoperatively to 97% at the last follow-up. However, the follow-up time varied from 2.3 years (bone marrow–derived cells) to 12.2 years (massive osteochondral grafts) and the number of patients in a particular group from 7 (bone-derived cell implantation) to 28 (chondrocytes with bone grafts). The only difference among the results of the different techniques was a trend toward better results following ACI (0.06).123

Allografts

For many years fresh, fresh-frozen or stored allografts have also been used in advanced knee OCD lesions.154-161 Fresh, refrigerated allografts are the standard choice for osteochondral allografts since frozen and freeze-dried cartilage has insufficient viable cartilage cells.142,162 When the refrigerated allograft is fresh, up to 98% of the chondrocytes are viable for 7 days; this decreases to 70% by 28 days.65,163 The decreased viability is accompanied by diminished cell density and decreased metabolic activity.65,164 The matrix and chondrocytes have been shown to survive in long-term recovery studies.142

However, extensive serological, bacterial, and viral testing of grafts is necessary prior to allograft transplantation until negative test results have been ensured. Donors must be screened. A round-the-clock transplantation service must be available.142,165 Furthermore, the immunogenicity and unplanned transfer of diseases has not yet been fully eliminated. However, the risk of HIV transmission is estimated to be as low as approximately 1 in 1.6 million, and there have been no reports of this route of disease transmission since the late 1980s.142,165

While chondrocytes are preserved against immunological reactions by the matrix cells, cells in the bony part of the graft should be removed to a great extent. In contrast to the cartilage, which seems to be completely integrated, bony integration can be a cause of failure.142

There are 2 studies reporting exclusively on OCD; other publications include up to 45% OCD patients. On one hand, a relatively high success rate is described for OCD patients with a survival rate of between 72% after 7.7 years159 and, at 10 years, 82%. The survival rate decreases to 66% after 20 years (45% OCD lesions).160 On the other hand, in 15% to 47%, there is a high rate of failure and/or the necessity of further operations.154,158 The use of allografts in JOCD was reported by Lyon et al.161; after surgery, patients (mean age 15.2 years) had returned within 6 months without difficulty to the activities of daily living and, between the 9th and 12th month to full sports activities.

A retrieval analysis of 26 specimens from 14 patients revealed 82% viable chondrocytes after a survival of 42 months. Histologically, all specimens showed some cartilage fibrillation but no signs of transplant rejection.166

Long-term Results after Different Treatments

There are a large number of articles with a mean follow-up of between 5 and 34 years.5,14,59-61,87,107-109,111,133,135,166-170 The articles included at least 2 longitudinal studies in which patients were examined twice.107,109 However, all the articles are only level IV, which means that the interpretation of the long-term results is difficult, particularly since the authors may be biased.107,108,112

Regarding excision or removal of OCD fragments, results revealed a clear tendency toward poor or fair results after a period of 10 to 20 years.166,170 Michael et al.108 observed excellent and good results in only 35% after 28 years mostly following excision with a rate of OA of 92%. Similar data were mentioned by Twyman et al.109 One report on exclusively lateral condylar OCD105 described a moderate OA but better clinical results 14 years after arthroscopic excision and subchondral drilling in most of the patients (22/28 knee joints). In contrast, results after fragment refixation were excellent or good in 85% to 92% of patients after 5 to 15 years.57 It seems that refixation results in a distinctly lower rate of OA and at a follow-up of 34 years, a rate of 35% of moderate OA was seen.111,112

So far as comparison is possible, reconstructive therapies have a tendency to better long-term results with a lower rate of OA, as is described for OAT133: Most of the patients (48%) exhibit the same postoperative grade of OA after 8.1 years when compared with preoperatively, and 34% exhibited an impairment of one grade.

Peterson et al.148 referred to excellent or good clinical results after ACI in 91% of 58 patients with a mean follow-up of 5.6 years but also mentioned signs of OA in nearly 50%.

Long-term results after repair with allografts showed a relatively high rate of success with a survival rate of 72% after 7.7 years (all OCD lesions) and 82% after 10 years.158 However, it was only 66% after 20 years (45% OCD)160 and there was a high failure rate and/or reoperations between 15% up to 47%.155,159,160,171

Comorbidities

Malalignment

Several authors have reported on the relation between medial OCD lesions in the knee joint and varus malalignment as well as between lateral lesions and valgus malalignment.26,96,135,142,172-176 Jacobi et al.173 analyzed the bilateral full-leg radiographs of their patients and found that OCD lesions and deviation of the mechanical axis in the varus or valgus were correlated significantly with medial (varus) and lateral lesions (valgus), respectively. The difference between affected and unaffected legs was also significant for lateral but not medial lesions. Subsequently, correction of the malalignment should be considered as an additional therapeutic goal, more for varus than for valgus malalignment. Slawski176 reported on 6 AOCD patients suffering from a varus malalignment in 7 of their knees with a high-tibial osteomy and achieved a distinct improvement of the postoperative Lysholm score.

ACL Instability and Meniscal Lesions ACL instability or meniscal lesions should also be therapeutically addressed.133,135,142,143 Hangody et al.135 reported a rate of 85% concomitant surgical interventions. The majority of these procedures were ACL reconstructions, realignment osteotomy, meniscal surgery, or patellofemoral realignment.

There are reports on the combination of OCD lesions at the lateral femoral condyle with a discoid meniscus, and the development of an OCD lesion after a total meniscectomy of a discoid meniscus.75 Subsequently, in our opinion, discoid menisci should be surgically reduced to the size of a normal meniscus. However, a total meniscectomy of discoid menisci can also result in the development of an ipsilateral OCD lesion.76

Conclusion

OCD remains an etiological, histological, and therapeutic mystery. There is much confusion regarding the classification and definition of OCD lesions and their differentiation from others, as well as with regard to a clear definition of JOCD and AOCD. Furthermore, there are no clear and scientifically well-based recommendations as to which therapeutic strategy should be used. In addition, a clear and uniformly used definition of the clinical and radiographical success and/or healing is still missing.

Although there are a tremendous number of publications on all aspects regarding OCD in different joints, there is a great lack of scientifically reliable prospective randomized studies.

Confusion still remains, at least for OCD lesions in the knee, and is expressed in the “Summary of Recommendations” in the publication “The Diagnosis and Treatment of Osteochondritis Dissecans” elaborated by a working group of the “American Academy of Orthopaedic Surgeons” and published by Chambers et al.2,177 They found that the strength of recommendations regarding 16 different aspects was inconclusive in 10 and weak in 2. Only in 4 aspects did the group find consensus.

In the future, it should be an international aim of institutions dealing with osteoarticular diseases to develop a protocol for providing more satisfactory data than those obtained from level-IV studies, these being of little scientific worth.