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Abstract
This study has presented the first purely biomechanical surgical model of osteoarthritis (OA) in rats, which could be more representative of the human primary disease than intra-articular techniques published previously. A surgical tibial osteotomy (TO) was used to induce degenerative cartilage changes in the medial knee of Sprague-Dawley rats. The presence of osteoarthritic changes in the medial knee compartment of the operated animals was evaluated histologically and through analysis of serum carboxy-terminal telepeptides of type II collagen (CTX-II). In-vivo biomechanical analyses were carried out using a musculoskeletal model of the rat hindlimb to evaluate the loading conditions in the knee pre and post-surgically. Qualitative and quantitative medial cartilage degeneration consistent with OA was found in the knees of the operated animals alongside elevated CTX-II levels and increased tibial compressive loading. The potential avoidance of joint inflammation post-surgically, the maintenance of internal joint biomechanics and the ability to quantify the alterations in joint loading should make this model of OA a better candidate for modeling primary forms of the disease in humans.
Highlights
Because of the difficulty in recruiting patients during the early, asymptomatic phase of disease pathogenesis, a variety of animal models have been developed to attempt to model the disease
A biomechanical model is used to evaluate the levels of knee joint loading pre and post-surgery to quantify the specific alterations in local joint biomechanics that lead to medial knee OA
Evaluating the exact pathophysiology of OA is difficult for a number of reasons, findings from recent animal work have proposed a dual role for both local joint biomechanics and systemic inflammation type activities[6,26,27]
Summary
Because of the difficulty in recruiting patients during the early, asymptomatic phase of disease pathogenesis, a variety of animal models have been developed to attempt to model the disease. Hartley guinea pig knee joints at 18 months and 3 years old found biochemical changes which reflected reasonably well with those present in human patients[15] The downside of these models, is that the long disease development time alongside relatively low incidence rates of the disease make them unsuitable for any large scale therapeutic studies[16]. One methodology that has received fairly little interest of late is the tibial osteotomy model, whereby the tibia is reset at a varus (or valgus) angle to increase the mechanical loading on the medial (or lateral) side of the knee joint This avoids the need for intra-articular surgery or destabilization of internal joint mechanics, potentially allowing the model to be used as an induced model of primary disease. A biomechanical model is used to evaluate the levels of knee joint loading pre and post-surgery to quantify the specific alterations in local joint biomechanics that lead to medial knee OA
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