Experimental animal models of osteonecrosis

Abstract

Osteonecrosis (ON) or avascular necrosis (AVN) is a common bone metabolic disorder, mostly affecting femoral head. Although many biological, biophysical, and surgical methods have been tested to preserve the femoral head with ON, none has been proven fully satisfactory. It lacks consensus on an optimal approach for treatment. This is due, at least in part, to the lack of ability to systematically compare treatment efficacy using an ideal animal model that mimics full-range osteonecrosis of femoral head (ONFH) in humans with high incidence of joint collapse accompanied by reparative reaction adjacent to the necrotic bone in a reproducible and accessible way. A number of preclinical animal ON models have been established for testing potential efficacy of various modalities developed for prevention and treatment of ON before introduction into clinics for potential applications. This paper describes a number of different methods for creating animal experimental ON models. Advantages and disadvantages of such models are also discussed as reference for future research in battle against this important medical condition.

CORR Insights®: Development of a Mouse Model of Ischemic Osteonecrosis

“…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].…”

“…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.…”

“…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.…”

Development of a Mouse Model of Ischemic Osteonecrosis

“…These models can be categorized broadly as traumatic and nontraumatic osteonecrosis [2,3,11], such as corticosteroid [17,19,46,47], lipopolysaccharide [16], alcohol [45], cryogen [20,40], and immune reaction-induced models of osteonecrosis [32,36]. The site of osteonecrosis in these models, however, is limited to the femoral head except in corticosteroid-induced models which tend to develop multifocal lesions.…”

“…The experimental models also can be divided into large animal models such as canines [31,34,37], porcines [24,41], and sheep [44], and small animal models such as rabbits [5,[15][16][17][19][20][21] and rats [14,29,38]. These models can be further classified into immature and mature animal models that represent pediatric and adult osteonecrotic conditions [11].…”