title: A rat model of early stage osteonecrosis induced by glucocorticoids.
abstract: BACKGROUND
  Glucocorticoid (GC)-induced osteonecrosis (ON) is an important complication of medical therapy. The exact pathomechanisms of ON has not been clearly elucidated. There is a need for a reproducible animal model that better approximates the clinical scenario.
  
  
  METHODS
  To determine the genetic susceptibility of rats to develop GC-induced femoral head ON, we evaluated 5 different inbred strains of rats (Spontaneous Hypertensive Rat, Wistar Kyoto, Wistar Furth, SASCO Fisher and Lewis). Prednisone pellets (dosage of 1.82-2.56 mg/kg/day) were implanted subcutaneously for 90. After 90 days, the femurs were resected and examined histologically and radiographically. Pathological and histological examination was performed. Hematoxylin and eosin (H & E) staining was used to delineate the femoral head osteonecrosis lesions as well as abnormalities of articular cartilage and growth plate.
  
  
  RESULTS
  The greatest differences in H & E staining were seen in the Wistar Kyoto and Wistar Furth groups. In these groups 4 out of 5 and 3 out of 5, respectively, steroid-induced rats revealed growth plate disruption with acellular areas. The TUNEL apoptosis staining assay for apoptosis revealed that 4 out of 5 of Wistar Kyoto rats, 5 out of 5 of Wistar Furth, 2 out of 4 of surviving Lewis and 2 out of 2 of the surviving spontaneous hypertensive rats had apoptotic osteocytes in trabeculae, whereas none of the Fisher rats showed apoptotic osteocytes.
  
  
  CONCLUSIONS
  We postulate that Wistar Kyoto, Wistar Furth and spontaneous hypertensive rats may be strains of rats more susceptible to develop ON of the femoral head while Fisher rats were the most resistant.
authors.affiliation: Department of Human Genetics, McGill University Health Center (MUHC), 1650 Cedar Avenue, Montreal, QC H3G 1A4, Canada.
authors.forename: Mohammad Amin
authors.initials: MA
authors.lastname: Kerachian
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Harvey
authors.forename: Denis
authors.initials: D
authors.lastname: Cournoyer
authors.forename: Terry Y
authors.initials: TY
authors.lastname: Chow
authors.forename: Ayoub
authors.initials: A
authors.lastname: Nahal
authors.forename: Chantal
authors.initials: C
authors.lastname: Séguin
mesh_terms: D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D004343:Drug Implants; D005260:Female; D005271:Femur Head Necrosis / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D020022:Genetic Predisposition to Disease; D005938:Glucocorticoids / Q000008:administration & dosage / Q000633:toxicity*; D006132:Growth Plate / Q000187:drug effects / Q000473:pathology; D010011:Osteocytes / Q000473:pathology; D010865:Pilot Projects; D011241:Prednisone / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D013045:Species Specificity
chemical_list: D004343:Drug Implants; D005938:Glucocorticoids; D011241:Prednisone