title: Experimental osteonecrosis induced by a combination of low-dose lipopolysaccharide and high-dose methylprednisolone in rabbits.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Orthopaedics, Union Hospital, Tongji Medical College, Science and Technology of Huazhong University, Wuhan 430022, China.
authors.forename: Xinghuo
authors.initials: X
authors.lastname: Wu
authors.forename: Shuhua
authors.initials: S
authors.lastname: Yang
authors.forename: Deyu
authors.initials: D
authors.lastname: Duan
authors.forename: Yukun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000473:pathology; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005269:Femur / Q000187:drug effects / Q000473:pathology; D005938:Glucocorticoids / Q000633:toxicity; D006811:Humerus / Q000187:drug effects / Q000473:pathology; D008055:Lipids / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity; D008136:Longevity / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D008297:Male; D008775:Methylprednisolone / Q000633:toxicity; D010020:Osteonecrosis / Q000097:blood / Q000139:chemically induced / Q000473:pathology*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011312:Pressure; D011817:Rabbits; D010959:Tissue Plasminogen Activator / Q000097:blood
chemical_list: D004338:Drug Combinations; D005938:Glucocorticoids; D008055:Lipids; D008070:Lipopolysaccharides; D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator; D008775:Methylprednisolone