Morphologic and Histologic Assessment of Porcine Model of Legg-Calvé-Perthes Disease at a Clinically Relevant Time Point.

Abstract

Previous studies using the porcine model of Legg-Calvé-Perthes Disease (LCPD) focused on treatments initiated 1 week following osteonecrosis (ON) induction, which represents the early avascular necrosis (AVN) stage (Stage Ia). Most patients, however, present to the clinic during later stages, like the late AVN (Stage Ib) or the early fragmentation stage (Stage IIa), when development of deformity and revascularization is initiated. This study's purpose was to determine the histologic and morphologic changes in the porcine model at 3 weeks after the ON induction. We hypothesized that the 3-week time point better represents a clinically relevant stage of LCPD when patients present to clinic. Eighteen piglets underwent ON induction surgery. Femoral heads were assessed using X-ray, histology, and micro-CT at 3 weeks post-ON. X-ray and histologic assessments revealed subchondral fracture, mild femoral head deformity, variable degree of revascularization (33 ± 30%, range 0%-88%), and early necrotic bone remodeling changes with significantly decreased osteoblast (p < 0.0001) and osteoclast numbers (p < 0.0001) compared to the normal side. Taken together, the results of this study provide comprehensive morphologic and histologic evidence of the late AVN stage (Stage 1b) in the porcine model, which is a clinically relevant time point to develop and test new treatment strategies. A wide variability of revascularization was seen at the 3-week time point, which stresses the importance of evaluating femoral head perfusion and individualizing treatment even in the early stage of AVN.