No abstract

This work utilises advances in multi-tissue imaging, and incorporates new metrics which define in situ joint changes and individual tissue changes in osteoarthritis (OA). The aims are to (1) demonstrate a protocol for processing intact animal joints for microCT to visualise relevant joint, bone and cartilage structures for understanding OA in a preclinical rabbit model, and (2) introduce a comprehensive three-dimensional (3D) quantitative morphometric analysis (QMA), including an assessment of reproducibility. Sixteen rabbit joints with and without transection of the anterior cruciate ligament were scanned with microCT and contrast agents, and processed for histology. Semi-quantitative evaluation was performed on matching two-dimensional (2D) histology and microCT images. Subsequently, 3D QMA was performed; including measures of cartilage, subchondral cortical and epiphyseal bone, and novel tibio-femoral joint metrics. Reproducibility of the QMA was tested on seven additional joints. A significant correlation was observed in cartilage thickness from matching histology-microCT pairs. The lateral compartment of operated joints had larger joint space width, thicker femoral cartilage and reduced bone volume, while osteophytes could be detected quantitatively. Measures between the in situ tibia and femur indicated an altered loading scenario. High measurement reproducibility was observed for all new parameters; with ICC ranging from 0.754 to 0.998. In conclusion, this study provides a novel 3D QMA to quantify macro and micro tissue measures in the joint of a rabbit OA model. New metrics were established consisting of: an angle to quantitatively measure osteophytes (σ), an angle to indicate erosion between the lateral and medial femoral condyles (ρ), a vector defining altered angulation (λ, α, β, γ) and a twist angle (τ) measuring instability and tissue degeneration between the femur and tibia, a length measure of joint space width (JSW), and a slope and intercept (m, Χ) of joint contact to demonstrate altered loading with disease progression, as well as traditional bone and cartilage and histo-morphometry measures. We demonstrate correlation of microCT and histology, sensitive discrimination of OA change and robust reproducibility.

Anterior cruciate ligament (ACL) tears are common sports‐related knee injuries that increase the risk of developing post‐traumatic osteoarthritis. ACL tears are rarely an isolated injury but are often associated with traumatic bone marrow lesions (BMLs). While early loss of bone mass following the ACL injury has been previously described, to date, microarchitectural information has not been reported due to the limited resolution of clinical imaging systems. In this study, we provide the first evidence of detailed bone mass and microarchitectural changes in the first 10 months following an acute ACL tear, and localized to traumatic BMLs. Fifteen participants with an acute unilateral ACL tear were assessed at four‐time points using dual‐energy X‐ray absorptiometry and high‐resolution peripheral quantitative computed tomography, and traumatic BMLs were identified with magnetic resonance imaging. Loss of bone mass was localized to the injured knee (−4.6% to −15.8%, depending on bone and depth) and was accelerated immediately following the injury before suggesting a recovery phase. This loss of bone was accelerated even greater in traumatic BMLs (−18.2% to −20.6%, depending on bone). Bone loss was accompanied by microstructural degeneration of trabecular bone. For example, in the lateral femur of the injured knee, the subchondral bone plate decreased in thickness (−9.0%). This study confirmed loss of bone mass in the months following ACL tears and described the underlying bone microstructural changes. The presented bone changes were accelerated in regions of traumatic BMLs. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2325–2336, 2019