title: Multiple bioimaging modalities in evaluation of an experimental osteonecrosis induced by a combination of lipopolysaccharide and methylprednisolone.
abstract: OBJECTIVE
  The present study employed both static and dynamic imaging modalities to study both intra- and extravascular events attributing to steroid-associated osteonecrosis (ON) using an experimental protocol with a single low-dose lipopolysaccharide (LPS) injection and subsequently three injections of high-dose methylprednisolone (MPS).
  
  
  METHODS
  Fourteen 28-week-old male New Zealand white rabbits received one intravenous injection of LPS (10 microg/kg). 24 h later, three injections of 20 mg/kg of MPS were given intramuscularly at a time interval of 24 h. Additional 6 rabbits were used as controls. Dynamic MRI was performed on bilateral femora for local intraosseous perfusion before and after LPS injection. Blood samples were collected for hematological examinations before and after LPS injection. Bilateral femora were dissected and decalcified for microCT-based microangiography. ON lesion, intravascular thrombus and extravascular marrow fat cell size were examined histopathologically.
  
  
  RESULTS
  Intravascular thrombus was observed in all ON rabbits. Extravascular marrow fat cell size was significantly increased in ON rabbits than that of the controls (P<0.05). Compared to baseline, a significant decrease in ratio of tissue-type plasminogen activator/plasminogen activator inhibitor 1, activated partial thromboplatin time and a significant increase in ratio of low-density lipoprotein/high-density lipoprotein were only found in ON rabbits (P<0.05). Dynamic MRI showed a significant decrease in the perfusion index 'maximum enhancement' in the ON rabbits (P<0.05), and microCT-based microangiography showed blocked stem vessels in ON samples. Overall, 93% of the rabbits (13/14) developed ON, and no rabbits died throughout the experiment period.
  
  
  CONCLUSIONS
  Both intra- and extravascular events were found attributing to the steroid-associated ON based on our experimental protocol with a single low-dose LPS injection and subsequent three injections of high-dose MPS. Both high ON incidence and no mortality in rabbits treated with this inductive protocol suggested its effectiveness for future studies on evaluation of therapeutic efficacy of interventions developed for prevention of steroid-associated ON.
authors.affiliation: Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, PR China. Lingqin@cuhk.edu.hk <Lingqin@cuhk.edu.hk>
authors.forename: L
authors.initials: L
authors.lastname: Qin
authors.forename: G
authors.initials: G
authors.lastname: Zhang
authors.forename: H
authors.initials: H
authors.lastname: Sheng
authors.forename: K W
authors.initials: KW
authors.lastname: Yeung
authors.forename: H Y
authors.initials: HY
authors.lastname: Yeung
authors.forename: C W
authors.initials: CW
authors.lastname: Chan
authors.forename: W H
authors.initials: WH
authors.lastname: Cheung
authors.forename: J
authors.initials: J
authors.lastname: Griffith
authors.forename: K H
authors.initials: KH
authors.lastname: Chiu
authors.forename: K S
authors.initials: KS
authors.lastname: Leung
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000633:toxicity*; D015999:Multivariate Analysis; D010020:Osteonecrosis / Q000139:chemically induced / Q000473:pathology*; D010314:Partial Thromboplastin Time; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011817:Rabbits; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000097:blood; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D008070:Lipopolysaccharides; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator; D008775:Methylprednisolone