title: Osteonecrosis in stroke-prone spontaneously hypertensive rats: effect of glucocorticoid.
abstract: BACKGROUND
  High-dose administration of a steroid hormone has been associated with a major risk of osteonecrosis. In this study we investigated the effects of a steroid hormone on the incidence of osteonecrosis of the femoral head in stroke-prone spontaneously hypertensive rats/Nagasaki (SHRSP/Ngsks).
  
  
  METHODS
  A total of 71 SHRSP/Ngsks were divided into two groups: a control group (C group, n = 40) and a steroid hormone group (S group, n = 31) given 5 mg (about 20 mg/kg) of methylprednisolone acetate during the 17th week of age. We compared the groups' laboratory data, histological appearance, incidence of osteonecrosis, and expression of oxidative stress on immunohistochemical analysis using the monoclonal antibodies anti-4HNE and anti-8OHdG.
  
  
  RESULTS
  The S group showed an increase in total cholesterol, with the amounts of high-density lipoprotein, low-density lipoprotein, and triglycerides all significantly higher than in the C group. Histological examination showed that the frequency of necrosis of the femoral head was significantly higher in the S group (95.2%) than in the C group (51.2%). Most of the histological features of the osteonecrosis demonstrated typical features of a similar sort in the two groups. However, the S group showed bone marrow spaces in the femoral head that were occupied by an increased number of adipocytes and that were swollen, partially degenerative, and necrotic. On immunohistochemical analysis, the stains of anti-4HNE and anti-8OHdG antibody were stronger in the S group than in the C group.
  
  
  CONCLUSIONS
  This study confirmed, to a remarkable degree, the suspicion that the administration of steroid hormone increases the number of adipocytes in marrow. Fat degeneration and necrosis, considered early signs of osteonecrosis, were also observed. It has been hypothesized that osteonecrosis is produced by the ischemic change accompanying compartment pressure load in marrow, where fat degeneration, necrosis, and endothelial cell injury might occur together with oxidative stress.
authors.affiliation: Department of Orthopedic Surgery, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Murata
authors.forename: Kenji
authors.initials: K
authors.lastname: Kumagai
authors.forename: Noriaki
authors.initials: N
authors.lastname: Miyata
authors.forename: Makoto
authors.initials: M
authors.lastname: Osaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shindo
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000447:Aldehydes / Q000276:immunology / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal; D004247:DNA / Q000032:analysis; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005270:Femur Head / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005271:Femur Head Necrosis / Q000139:chemically induced* / Q000150:complications / Q000175:diagnosis; D005938:Glucocorticoids / Q000633:toxicity*; D006973:Hypertension / Q000150:complications*; D007150:Immunohistochemistry; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D000447:Aldehydes; D000911:Antibodies, Monoclonal; D005938:Glucocorticoids; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine; C027576:4-hydroxy-2-nonenal