title: Effect of Resveratrol on Preventing Steroid-induced Osteonecrosis in a Rabbit Model.
abstract: BACKGROUND
  Prevention of osteonecrosis (ON) has seldom been addressed. The purpose of this study was to evaluate the effect of resveratrol on preventing steroid-induced ON in rabbits.
  
  
  METHODS
  Seventy-two rabbits were divided into four groups: (1) NEC (ON) group: thirty rabbits were treated with lipopolysaccharide (LPS) once, then with methylprednisolone (MPS) daily for 3 days; (2) PRE (prevention) group: thirty rabbits were given one dose of LPS, then MPS daily for 3 days, and resveratrol on day 0 and daily for 2 weeks; (3) RES (resveratrol) group: six rabbits were given resveratrol for 2 weeks but without LPS/MPS; (4) CON (control) group: six rabbits were given alcohol for 2 weeks but without LPS/MPS. Levels of plasma tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), thrombomodulin (TM), vascular endothelial growth factor (VEGF), maximum enhancement (ME) by magnetic resonance imaging, and ON incidence were evaluated.
  
  
  RESULTS
  The PRE group had a lower ON incidence than the NEC group, but with no significant differences at 2 weeks and 12 weeks. The RES and CON groups did not develop ON. TM and VEGF were significantly higher in the NEC group compared with the PRE group at weeks 1, 2, and 4 (TM: 1 week, P = 0.029; 2 weeks, P = 0.005; and 4 weeks, P = 0.047; VEGF: 1 week, P = 0.039; 2 weeks, P = 0.021; 4 weeks, P = 0.014), but the difference disappeared at 12 weeks. The levels of t-PA and PAI-1 were not significantly different between the NEC and PRE groups. The TM, t-PA, PAI-1, and VEGF concentrations in the RES and CON groups did not change over time. Compared to the baseline, ME in the NEC group decreased significantly (P = 0.025) at week 1, increased significantly (P = 0.021) at week 2, and was decreased at week 12. The variance was insignificant in the PRE group.
  
  
  CONCLUSIONS
  Resveratrol may improve blood supply to bone in a rabbit model of ON of the femoral head via anti-inflammatory effects to protect the vascular endothelium and reduce thrombosis.
authors.forename: Ji-Liang
authors.initials: JL
authors.lastname: Zhai
authors.affiliation: Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China.
authors.forename: Xi-Sheng
authors.initials: XS
authors.lastname: Weng
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Wu
authors.forename: Shi-Gong
authors.initials: SG
authors.lastname: Guo
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005271:Femur Head Necrosis / Q000139:chemically induced / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000633:toxicity; D008279:Magnetic Resonance Imaging; D008775:Methylprednisolone / Q000633:toxicity*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011817:Rabbits; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*; D018180:Thrombomodulin / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D008070:Lipopolysaccharides; D017395:Plasminogen Activator Inhibitor 1; D013267:Stilbenes; D018180:Thrombomodulin; D042461:Vascular Endothelial Growth Factor A; D010959:Tissue Plasminogen Activator; D000077185:Resveratrol; D008775:Methylprednisolone