Effects of acute femoral head ischemia on the growth plate and metaphysis in a piglet model of Legg-Calvé-Perthes disease

Abstract

To determine the effects of acute (≤7 days) femoral head ischemia on the proximal femoral growth plate and metaphysis in a piglet model of Legg-Calvé-Perthes disease (LCPD). We hypothesized that qualitative and quantitative histological assessment would identify effects of ischemia on endochondral ossification. Unilateral femoral head ischemia was surgically induced in piglets, and femurs were collected for histological assessment at 2 (n=7) or 7 (n=5) days post-ischemia. Samples were assessed qualitatively, and histomorphometry of the growth plate zones and primary spongiosa was performed. In a subset of samples at 7 days, hypertrophic chondrocytes were quantitatively assessed and immunohistochemistry for TGFβ1 and Indian hedgehog was performed. By 2 days post-ischemia, there was significant thinning of the proliferative and hypertrophic zones, by 63μm (95% CI-103,-22) and-19 μm (95% CI-33,-5), respectively. This thinning persisted at 7 days post-ischemia. Likewise, at 7 days post-ischemia, the primary spongiosa was thinned to absent by an average of 311μm (95% CI-542,-82) in all ischemic samples. TGFβ1 expression was increased in the hypertrophic zone at 7 days post-ischemia. Alterations to the growth plate zones and metaphysis occurred by 2 days post-ischemia and persisted at 7 days post-ischemia. Our findings suggest that endochondral ossification may be disrupted at an earlier time point than previously reported and that growth disruption may occur in the piglet model as occurs in some children with LCPD.