Objective: The objective of this study was to describe in life methods by which osteoarthritis can be staged in order to time therapeutic interventions that are relevant to osteoarthritis (OA) clinical trials.
Methods: Twenty-two sheep underwent arthroscopic meniscal destabilization to induce OA. Serial computed tomography (CT) imaging and arthroscopy were used to monitor osteoarthritis progression at 3-month intervals over 9 months. Eleven sheep received 1 intra-articular injection of hyaluronate 3 months after OA induction and another group of 11 received saline. A linear mixed model was used to define the trajectory of shape change in the medial joint compartment. Ordinal logistic regression was used to investigate the association between morphological changes and sclerosis.
Results: Three months after meniscal destabilization there were early bipolar chondral lesions in the medial compartment of the knee, as well as osteophytes and bone remodeling. Superficial fissures and cartilage cracks progressed to discrete areas of cartilage thinning and fibrillation on the medial tibial plateau by 6 months that became cartilage erosions by nine months. A linear mixed effect model demonstrated significant change in medial compartment length and width with over time (P < 0.05) for both groups. A significant association between severity of sclerosis and medial compartment morphology was also observed.
Conclusions: The induction of osteoarthritic lesions with meniscal release model can be followed using noninvasive and minimally invasive procedures allowing for real-time decisions about redosing therapies, or other changes such as extending trial timelines without sacrificing animals to conduct assessments.
Keywords: animal model; intervention; osteoarthritis; trajectory.