2019 ISAKOS Biennial Congress ePoster #1302
Comparison of Post-Traumatic Osteoarthritis Injury Initiation Methods in an Ovine Model
Timothy A. Burkhart, PhD, London, ON CANADA
Alexander El Warrak, DVM, MSc, PhD, Etobicoke, ON CANADA
Omar Turk, BSc, London, ON CANADA
Kyla Huebner, MD, London, ON CANADA
Rob Longstaffe, MD, London, ON CANADA
Philip P. Roessler, MD, MHBA, Bonn GERMANY
Alexandra M. Blokker, MESc, London, ON CANADA
Mark B. Hurtig, DVM, MVSc, Guelph, ON CANADA
Alan Getgood, MD, FRCS(Tr&Orth), DipSEM, London, ON CANADA
Western University, London, ON, CANADA
FDA Status Not Applicable
An impact with a concommitant meniscal lesion results in greater, whole joint, symptoms of post-traumatic osteoarthritis
Post-traumatic osteoarthritis (PTOA) is a significant complication of sports trauma. There is a significant need for a clinically translatable animal model to further investigate the pathogenesis of PTOA, as well as investigate the development of disease modifying molecules.
To develop and validate a large animal ovine model that can mimic the impaction injury seen at the time of anterior cruciate ligament injury to investigate the development and propagation of PTOA.
Twelve skeletally mature female sheep were used for this study and all protocols were approved by the institutions Animal Use Committee. A medial para-patellar arthrotomy was implemented to gain access to the medial femoral condyle and the medial meniscus of both stifle joints. Sheep were randomized into two groups: i) uni-lateral impact (n=6) – the medial femoral condyle of one, randomly assigned, stifle joint was subjected to a 30MPa impact load using a custom designed impactor to the proximal, mid, and distal weight bearing surfaces while the contra-lateral limb received only an arthrotomy; and ii) uni-lateral impact plus medial meniscus transection (n=6) – one, randomly assigned, stifle joint was subjected to the previously described impact protocol and an anterior medial meniscus destabilising root transection; the contra-lateral limb receive only an arthrotomy. At four days post-surgery the animals were returned to pasture for three months at which time they were euthanized and the hind limbs were disarticulated from the hip to allow for micro-CT scanning, gross morphological assessment, and analysis of the tibial femoral joint surfaces using India ink. Two-way mixed ANOVA was used to determine the effect of each injury mechanism on the initiation of OA (a=0.05).
Both injury models resulted in a significantly greater affected surface area when compared to the arthrotomy only condition on both the MFC (11% vs. 7% of total joint surface) and the tibial plateau (17% vs. 10%) of total joint surface. However, there were no differences between injury models. With respect to the macroscopic scoring, the injury models resulted in greater scores, indicating more severe OA compared to the arthrotomy only. The addition of a meniscal injury produced greater OA compared to the impact only (21 vs 8 [total macroscopic score], respectively). Micro CT demonstrated a greater mean [SD] trabecular number in the medial tibial plateau in the arthrotomy only joints (1.5 [0.1] mm-1) compared to the injury model joints (1.3 [0.1] mm-1). No significant differences were observed between the two types of injury model.
The results presented here suggest that both injury types were successful in initiating PTOA in an ovine model. However, the impact with a concomitant meniscal lesion resulted in greater damage and propagation of PTOA through the joint. The inconclusive imaging results imply that this was early stage OA and suggests that cartilage and soft tissue damage may precede damage to the underlying bone tissue. These methods of PTOA initiation may therefore act as a suitable model for the development of drugs to modulate PTOA in the ACL injured population.