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Open Access Research article

An in vivo investigation of the initiation and progression of subchondral cysts in a rodent model of secondary osteoarthritis

David D McErlain12, Veronica Ulici3, Mark Darling4, Joseph S Gati2, Vasek Pitelka3, Frank Beier3 and David W Holdsworth125*

Author Affiliations

1 Department of Medical Biophysics; Schulich School of Medicine and Dentistry, The University of Western Ontario, 1151 Richmond Street, London, ON, Canada. N6A 3K7

2 Imaging Research Laboratories, Robarts Research Institute; Schulich School of Medicine and Dentistry, The University of Western Ontario, 100 Perth Drive, London, ON, Canada. N6A 5K8

3 Department of Physiology & Pharmacology; Schulich School of Medicine and Dentistry, The University of Western Ontario, 1151 Richmond Street, London, ON, Canada. N6A 3K7

4 Department of Pathology; Schulich School of Medicine and Dentistry, The University of Western Ontario, 1151 Richmond Street, London, ON, Canada. N6A 3K7

5 Department of Surgery; Schulich School of Medicine and Dentistry, The University of Western Ontario, 1151 Richmond Street, London, ON, Canada. N6A 3K7

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Arthritis Research & Therapy 2012, 14:R26  doi:10.1186/ar3727

Published: 3 February 2012

Abstract

Introduction

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.

Methods

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.

Results

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.

Conclusions

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'.