[Multiple bioimaging modalities in evaluation of an experimental osteonecrosis model induced by a combination of lipopolysaccharide and methylprednisolone].
OBJECTIVE
The present study employed both static and dynamic imaging modalities to study both intra- and extravascular events attributing to steroid-associated osteonecrosis (ON) using an experimental protocol with a single low-dose lippolysaccharide (LPS) injection and subsequently three injections of high-dose methylprednisolone (MPS).


METHODS
Fourteen 28-week-old male New Zealand white rabbits received one intravenous injection of LPS (10 microg/kg). After 24 hours, three injections of 20 mg/kg of MPS were given intramuscularly at a time interval of 24 hours. Additional 6 rabbits were used as controls. Dynamic MRI was performed on bilateral femora for local intraosseous perfusion before and after LPS injection. Blood samples were collected for haematological examinations before and after LPS injection. Bilateral femora were dissected and decalcified for microCT-based microangiography. ON lesion, intravascular thrombus and extravascular marrow fat cell size were examined histopathologically.


RESULTS
Intravascular thrombus was observed in all ON rabbits. Extravascular marrow fat cell size was significantly increased in ON rabbits than that of the controls (P < 0.05). Compared to baseline, a significant decrease in ratio of tissue-type-plasminogen-activator/plasminogen-activator inhibitor 1, activated-partial- thromboplatin-time, and a significant increase in ratio of low-density-lipoprotein/high-density-lipoprotein were only found in ON rabbits (P < 0.05). Dynamic MRI showed a significant decrease in the perfusion index 'maximum enhancement' in the ON rabbits (P < 0.05) and microCT-based microangiography showed blocked stem vessels in ON samples. Overall, 93% of the rabbits (13/14) developed ON and no rabbits died throughout the experiment period.


CONCLUSIONS
Both intra- and extravascular events were found attributing to the steroid-associated ON based on our experimental protocol with a single low-dose LPS injection and subsequent three injections of high-dose MPS. Both high ON incidence and no mortality in rabbits treated with this inductive protocol suggested its effectiveness for future studies on evaluation of therapeutic efficacy of interventions developed for prevention of steroid-associated ON.
Qin
Ling
L
Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, Chinese University of Hong Kong, Hong Kong SAR, P. R. China. Lingqin@cuhk.edu.hk
Zhang
Ge
G
Sheng
Hui
H
Yeung
Kawai
K
Yeung
Hiuyan
H
Chan
Chunwai
C
Cheung
Winghoi
W
Griffith
James
J
Leung
Kwoksui
K
D017667:Adipocytes / Q000187:drug effects / Q000473:pathology; D000818:Animals; D001808:Blood Vessels / Q000473:pathology* / Q000503:physiopathology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005269:Femur / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology; D006728:Hormones / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D008775:Methylprednisolone / Q000633:toxicity*; D010020:Osteonecrosis / Q000097:blood / Q000139:chemically induced / Q000473:pathology*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011817:Rabbits; D010959:Tissue Plasminogen Activator / Q000097:blood; D014057:Tomography, X-Ray Computed / Q000379:methods
D006728:Hormones; D008070:Lipopolysaccharides; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator; D008775:Methylprednisolone