Epimedium-derived phytoestrogen exert beneficial effect on preventing steroid-associated osteonecrosis in rabbits with inhibition of both thrombosis and lipid-deposition.
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.
Zhang
G
G
Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, PR China.
Qin
L
L
Sheng
H
H
Yeung
K W
KW
Yeung
H Y
HY
Cheung
W H
WH
Griffith
J
J
Chan
C W
CW
Lee
K M
KM
Leung
K S
KS
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
D000305:Adrenal Cortex Hormones; D048789:Phytoestrogens; D028321:Plant Preparations