CORR Insights(®): development of a mouse model of ischemic osteonecrosis.

Abstract

O steonecrosis is a persistent and confounding orthopaedic pathology that can arise in any bone; common causes include compromised vasculature, exposure to radiation therapy, treatment with corticosteroids, or bisphosphonates treatment [2, 5, 6]. In the appendicular skeleton, osteonecrosis is managed surgically using total joint implants (among other approaches) while osteonecrosis of the jaw is treated with prophylactic antibiotic rinses followed by surgical resection when disease progression leads to substantial pain [1, 3]. Researchers have developed animal models that correspond to the different clinical presentations of osteonecrosis [2]. These models include trauma-induced osteonecrosis, which was modeled through surgical ligation of local blood vessels or femoral dislocation, while corticosteroid-induced osteonecrosis has been modeled through the administration of high doses of methylprednisone or dexamethasone. Other models have tried to replicate the condition by treating animals with ethanol directly injected into the bone marrow, intravenous injections of lipopolysaccharides, or through the injection of horse serum to stimulate a severe immune reaction. Physical methods have also been employed to induce osteonecrosis, including cryogenic or thermal insult. Most of these experimental models result in a high rate of animal mortality, which limits their utility [2]. Additionally, the variability in cell death and the time course of recovery vary across these animal models [1], further complicating our ability to interpret them in the context of the human disease they seek to replicate. In the current study, Kamiya and colleagues cauterized four blood vessels (the popliteal and three genicular vessels) around the distal femur, creating a model of avascular osteonecrosis, and, importantly, doing so without resulting in the premature death of the animals.