Animal models of hematogenous Staphylococcus aureus osteomyelitis in long bones: a review

Abstract

Hematogenous osteomyelitis (HO), especially due to Staphylococcus aureus, is primarily reported in children and occurs when blood-borne bacteria settle in the metaphysis of a long bone and mediate an inflammatory response. The literature contains several reports on animal models aiming to simulate pediatric HO, in order to investigate the pathogenesis and for therapeutic use. In these models, osteomyelitis lesions develop subsequently to bacteremia, which can be induced by either intravenous or intra-arterial inoculation of bacteria. Intravenous inoculation is not optimal because of the ethical aspects of the extensive systemic reaction and the unpredictable identity of bones being infected. Also, intravenous inoculation often has to be combined with the induction of artificial bone necrosis in order to have macroscopic lesions. In contrast, models based on intra-arterial inoculation and subsequent development of local osteomyelitis, are the most accurate and predictable way to extrapolate to pediatric cases of HO. The most commonly used animal species for modeling of HO are rabbits, chickens, and mice, whereas, less frequently, dogs, rats, and pigs have been applied. The use of intra-arterial inoculation, without simultaneous artificial bone necrosis for the development of HO lesions has only been used in porcine models. Because of the similarity of human and porcine physiology, metabolic rate, and size, porcine models of HO are advantageous. Therefore, porcine models based on the intra-arterial induction of osteomyelitis are the most refined HO models.