Experimental osteonecrosis induced by a combination of low-dose lipopolysaccharide and high-dose methylprednisolone in rabbits

Objectives: The pathogenetic mechanisms involved in steroid-induced osteonecrosis are poorly understood. Appropriate experimental models of the human disease are indispensable to the understanding of successful treatment modalities for osteonecrosis. Methods: In the present experiment we devised a novel rabbit model of steroid-induced osteonecrosis by use of two low-dose LPS and three high-dose MPS to investigate the development of osteonecrosis. Thirty eight rabbits were used and tissue assessments were performed on proximal third and distal condyles of femora and humeri obtained 6 weeks after the administration of LPS and MPS. MRI of these regions and intraosscous pressure of proximal femur were obtained at 0 and 6 weeks. Other assessments included serum plasminogen activator/inhibitor ratio, cholesterol level, LDL/HDL ratio, and triglyceride levels at various time points. Results: The study showed that with this osteonecrosis induction protocol there was low animal mortality (6.2%), high rate of osteonecrosis (90%), induction of thrombotic state, and hypercholesterol/lipidemia. Discussion: On the whole, this is a novel modified animal model of steroid associated osteonecrosis and it would be useful for elucidating the pathogenesis of steroid associated osteonecrosis and developing preventive and therapeutic strategies. (C) 2008 Elsevier Masson SAS. All rights reserved.