‘One medicine – one pathology’: Assessment and Validation of Animal Models of Orthopaedic Diseases

Abstract

The projects presented here revolve around the utilization of three different animal models of developmental and degenerative orthopaedic diseases, with the work described in order of typical clinical onset in the relevant patient populations. These projects share an integral focus on characterization and validation of the chosen models by histological assessment. The objective of the first phase of this work was to histologically characterize the effects of surgically induced epiphyseal ischemia in a piglet model of Legg-Calvé-Perthes disease on the proximal femoral growth plate, with histomorphometry and immunohistochemical characterization. The objective of the second phase of this work was to determine the sensitivity and specificity of noninvasive quantitative MRI methods in detection of early naturally occurring osteochondrosis lesions ex vivo in the pig, with co-registration and characterization of lesions identified with advanced imaging and identified histologically. The objective of the third phase of this work was to determine the optimal approach for histological assessment of osteoarthritis in murine models, including comparison of two widely recognized murine-specific histological grading schemes and additional microscopic means of evaluation relevant to determination of osteoarthritis severity. Collectively, the results of this work highlight the need for careful evaluation and validation of animal models of orthopaedic diseases, with a focus on repeatability of the model, complete evaluation with reflection on how accurately the model mirrors the human disease, and statistical support for the approach to analysis.