title: Epimedium-derived phytoestrogen exert beneficial effect on preventing steroid-associated osteonecrosis in rabbits with inhibition of both thrombosis and lipid-deposition.
abstract: OBJECTIVE
  This study tested the effect of Epimedium-derived phytoestrogen (PE) on preventing steroid-associated osteonecrosis (ON) in rabbit model.
  
  
  METHODS
  Thirty 28-week-old male New-Zealand white rabbits were divided into control group (CON; n=14) and PE group (PE; n=16; 5 mg/kg body weight/day) after receiving an established inductive protocol for inducing steroid-associated ON. Before and after inductive protocol, Dynamic-MRI was employed on bilateral femora for local intra-osseous perfusion, blood samples were examined for coagulation, fibrinolysis and lipid-transportation, and marrow samples were quantified for adipogenesis-gene mRNA expression. Six weeks later, bilateral femora were dissected for Micro-CT-based micro-angiography, and then ON lesion, intravascular thrombosis and extravascular fat-cell-size were examined histopathologically.
  
  
  RESULTS
  The incidence of ON in the PE group (31%) was significantly lower than that in the CON group (93%). Compared to the CON group, local intra-osseous perfusion was maintained in the PE group. Blocked trunk vessels were seldom found in micro-angiography of the PE-treated rabbits. Thrombosis incidence and fat-cell-size were both significantly lower in the PE group than those in the CON group. During the early period after induction, indicator of coagulation, fibrinolysis, lipid-transportation and adipogenesis-gene expression were found with significantly changing pattern in the PE group compared to the CON group.
  
  
  CONCLUSIONS
  PE was able to exert beneficial effect on preventing steroid-associated ON in rabbits with inhibition of both thrombosis and lipid deposition.
authors.affiliation: Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, PR China.
authors.forename: G
authors.initials: G
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Qin
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: W H
authors.initials: WH
authors.lastname: Cheung
authors.forename: J
authors.initials: J
authors.lastname: Griffith
authors.forename: C W
authors.initials: CW
authors.lastname: Chan
authors.forename: K M
authors.initials: KM
authors.lastname: Lee
authors.forename: K S
authors.initials: KS
authors.lastname: Leung
mesh_terms: D000305:Adrenal Cortex Hormones / Q000009:adverse effects; D000818:Animals; D034181:Epimedium / Q000737:chemistry*; D005269:Femur / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D050356:Lipid Metabolism / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D008297:Male; D010020:Osteonecrosis / Q000139:chemically induced / Q000517:prevention & control*; D048789:Phytoestrogens / Q000627:therapeutic use*; D008517:Phytotherapy; D028321:Plant Preparations / Q000627:therapeutic use*; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013927:Thrombosis / Q000517:prevention & control
chemical_list: D000305:Adrenal Cortex Hormones; D048789:Phytoestrogens; D028321:Plant Preparations