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

Joint Bone Spine. 2008 Oct;75(5):573-8. doi: 10.1016/j.jbspin.2007.11.004. Epub 2008 May 9.

Abstract

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 intraosseous 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / drug effects
  • Adipocytes / pathology
  • Animals
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / pathology
  • Disease Models, Animal*
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Femur / drug effects
  • Femur / pathology
  • Glucocorticoids / toxicity
  • Humerus / drug effects
  • Humerus / pathology
  • Lipids / blood
  • Lipopolysaccharides / toxicity
  • Longevity / drug effects
  • Magnetic Resonance Imaging
  • Male
  • Methylprednisolone / toxicity
  • Osteonecrosis / blood
  • Osteonecrosis / chemically induced
  • Osteonecrosis / pathology*
  • Plasminogen Activator Inhibitor 1 / blood
  • Pressure
  • Rabbits
  • Tissue Plasminogen Activator / blood

Substances

  • Drug Combinations
  • Glucocorticoids
  • Lipids
  • Lipopolysaccharides
  • Plasminogen Activator Inhibitor 1
  • Tissue Plasminogen Activator
  • Methylprednisolone