Significance of the serum CTX-II level in an osteoarthritis animal model: a 5-month longitudinal study.

OBJECTIVE: The aim of this study was to investigate the clinical value of serum measurement of C-telopeptide of type II collagen (CTX-II). In correlation with late stages of osteoarthritis (OA) evaluated with histological assessment, the evolution of serum CTX-II concentration was followed during a 20-week longitudinal study in rabbit anterior cruciate ligament transection (ACLT) OA model in adult and growing animals. METHODS: OA was induced in five adult and nine growing rabbits. Four adult and four young rabbits were unoperated. Serum sampling was made at week 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16 and 20 after the surgery in all rabbits. Animals were euthanized 20 weeks after the surgery. Serum CTX-II levels were analyzed with a recently available enzyme-linked immunosorbent assay (ELISA) kit, the protocol of which has been modified to increase the sensitivity of the test. RESULTS: Significant differences for the CTX-II levels at W3, W6, W8, W10, W12, W14, W16 and W20 were observed between the adult ACLT and the control groups. A negative correlation between CTX-II levels and cartilage thickness of the medial compartment of the knee at W8, W10, W12 and a positive correlation between the CTX-II levels and the histomorphological score of the medial compartment of the knee at W3, W6, W8, W10, W12 were noted in adult animals. In young animals, operated or not, we observed high CTX-II levels at the beginning of the study, which decreased until the end. CONCLUSION: Our results suggest the interest of the serum CTX-II monitoring for the OA progression and the relevance of the multiple time point analysis of this biomarker. Moreover, they address the question of the importance of correctly choosing the age of the animals used in the pre-clinical studies of OA.

Knee joint ultrasonography of the ACLT rabbit experimental model of osteoarthritis: relevance and effectiveness in detecting meniscal lesions.

OBJECTIVES: To develop a protocol for rabbit knee joint ultrasonography (US); to grade ultrasonographically the meniscal injuries of the anterior cruciate ligament transection (ACLT) rabbit model of osteoarthritis (OA); to assess with US the effectiveness of the ACLT; to compare final US with macroscopy for the evaluation of medial and lateral meniscal injuries depending on the age and weight when ACLT is performed. METHODS: Twenty-two skeletally mature and adolescent New Zealand white rabbits were housed during the same period at the Institut Claude-Bourgelat, Lyon, France. Surgical ACLT was performed in the left knee of nine adolescent and five adult rabbits. Final US and macroscopic semi-quantitative grading of the meniscal injuries were compared 5 months after ACLT. RESULTS: A standardised protocol was developed to evaluate the rabbit knee joint. US was performed in both control and ACLT knees. Normal and abnormal meniscal US appearances were described. A semi-quantitative scale to grade US meniscal injuries was created. Macroscopic and US total meniscal scores were significantly positively correlated (P<0.001, r=0.70). US detection of meniscal injuries was 92% sensitive and 87.5% specific compared to macroscopy. Positive and negative predictive values of US were, respectively, 92% and 87.5%. US detection of the ACLT effectiveness was 100% specific and 78.5% sensitive. CONCLUSION: A significant relationship was found between ultrasonographic and macroscopic grading of meniscal injuries. US was both specific and sensitive in detecting meniscal lesions. We propose US as a non-invasive, non-expensive, in vivo imaging technique for preclinical studies in the ACLT rabbit OA model.

Non-invasive in vivo quantification of the medial tibial cartilage thickness progression in an osteoarthritis rabbit model with quantitative 3D high resolution micro-MRI.

OBJECTIVE: To develop a quantitative non-invasive in vivo three-dimensional (3D) high resolution (HR) micro-magnetic resonance imaging (microMRI) protocol to measure the medial tibial cartilage thickness (MT.ThC) in the normal rabbit and in the anterior cruciate ligament transection (ACLT) rabbit model of osteoarthritis and quantify the progression of MT.ThC. METHODS: The left knee of 10 control and 40 operated rabbits was imaged in vivo with a 7T microMRI system at 3 and 5 months after ACLT. A 3D fast low angle short (FLASH) fat-suppressed MRI protocol was implemented leading to 44x176 microm(3) spatial resolution and to 44 microm(3) isotropic voxel after cubic interpolation. Semi-automatic MT.ThC measurements were made in 3D, in four different locations, in vivo and longitudinally in both groups. At 5 months, gross macroscopy, visual analogical evaluation of the cartilage and histology were compared to the MR-based MT.ThC. RESULTS: At 3 and 5 months, the MT.ThC measured in the minimum interbone distance area was the thinnest MR-based MT.ThC. It was significantly lower in the operated group and among the four evaluated MT.ThC, it was the most discriminative between the normal and the operated groups (P<0.05). The MT.ThC measured in the minimum interbone distance area was also the most sensitive to change in the operated group (66.4% MT.ThC loss, P=0.003) while no significant changes were observed in the control group. CONCLUSION: Quantitative 3D HR microMRI allowed for non-invasive longitudinal MT.ThC measurements in four different locations in both the normal and the operated rabbits. We concluded the MT.ThC measured in the minimum interbone distance area reflected the severity of the disease and was the most effective to measure the progression of the medial tibial cartilage destruction.