Department of Medical Biophysics; Schulich School of Medicine and Dentistry, The University of Western Ontario, 1151 Richmond Street, London, ON, Canada, N6A 3K7.
Arthritis Res Ther. 2012 Feb 3;14(1):R26. doi: 10.1186/ar3727.
Subchondral bone cysts (SBC) have been identified in patients with knee osteoarthritis (OA) as a cause of greater pain, loss of cartilage and increased chance of joint replacement surgery. Few studies monitor SBC longitudinally, and clinical research using three-dimensional imaging techniques, such as magnetic resonance imaging (MRI), is limited to retrospective analyses as SBC are identified within an OA patient cohort. The purpose of this study was to use dual-modality, preclinical imaging to monitor the initiation and progression of SBC occurring within an established rodent model of knee OA.
Eight rodents underwent anterior cruciate ligament transection and partial medial meniscectomy (ACLX) of the right knee. In vivo 9.4 T MRI and micro-computed tomography (micro-CT) scans were performed consecutively prior to ACLX and 4, 8, and 12 weeks post-ACLX. Resultant images were co-registered using anatomical landmarks, which allowed for precise tracking of SBC size and composition throughout the study. The diameter of the SBC was measured, and the volumetric bone mineral density (vBMD) was calculated within the bone adjacent to SBC. At 12 weeks, the ACLX and contralateral knees were processed for histological analysis, immunohistochemistry, and Osteoarthritis Research Society International (OARSI) pathological scoring.
At 4 weeks post-ACLX, 75% of the rodent knees had at least 1 cyst that formed in the medial tibial plateau; by 12 weeks all ACLX knees contained SBC. Imaging data revealed that the SBC originate in the presence of a subchondral bone plate breach, with evolving composition over time. The diameter of the SBC increased significantly over time (P = 0.0033) and the vBMD significantly decreased at 8 weeks post-ACLX (P = 0.033). Histological analysis demonstrated positive staining for bone resorption and formation surrounding the SBC, which were consistently located beneath the joint surface with the greatest cartilage damage. Trabecular bone adjacent the SBC lacked viable osteocytes and, combined with bone marrow changes, indicated osteonecrosis.
This study provides insight into the mechanisms leading to SBC formation in knee OA. The expansion of these lesions is due to stress-induced bone resorption from the incurred mechanical instability. Therefore, we suggest these lesions can be more accurately described as a form of OA-induced osteonecrosis, rather than 'subchondral cysts'.
在膝关节骨关节炎（OA）患者中，已经发现了软骨下骨囊肿（SBC）是引起更大疼痛、软骨丧失和增加关节置换手术机会的原因。很少有研究对 SBC 进行纵向监测，并且使用磁共振成像（MRI）等三维成像技术的临床研究仅限于回顾性分析，因为 SBC 是在 OA 患者队列中确定的。本研究旨在使用双模态、临床前成像技术监测在已建立的膝骨关节炎啮齿动物模型中发生的 SBC 的起始和进展。
8 只动物接受了前交叉韧带横断术和右膝部分内侧半月板切除术（ACLX）。在 ACLX 之前以及之后 4、8 和 12 周连续进行体内 9.4 T MRI 和微计算机断层扫描（micro-CT）扫描。使用解剖学标志对所得图像进行配准，这允许在整个研究过程中精确跟踪 SBC 的大小和组成。测量 SBC 的直径，并计算 SBC 周围骨的体积骨矿物质密度（vBMD）。在 12 周时，对 ACLX 和对侧膝关节进行组织学分析、免疫组织化学和骨关节炎研究协会国际（OARSI）病理评分。
在 ACLX 后 4 周，75%的啮齿动物膝关节至少有 1 个囊肿形成于内侧胫骨平台；到 12 周时，所有 ACLX 膝关节均含有 SBC。成像数据显示，SBC 起源于软骨下骨板破裂处，随着时间的推移其组成不断演变。SBC 的直径随时间显著增加（P=0.0033），并且在 ACLX 后 8 周 vBMD 显著降低（P=0.033）。组织学分析显示 SBC 周围存在骨吸收和形成的阳性染色，这些染色始终位于关节表面下伴有最大软骨损伤的部位。SBC 附近的小梁骨缺乏有活力的成骨细胞，结合骨髓变化，表明骨坏死。
本研究深入了解了导致膝关节 OA 中 SBC 形成的机制。这些病变的扩张是由于所产生的机械不稳定性引起的应力诱导的骨吸收所致。因此，我们建议这些病变可以更准确地描述为一种 OA 诱导的骨坏死形式，而不是“软骨下囊肿”。
