Experimental osteonecrosis induced by a combination of low-dose lipopolysaccharide and high-dose methylprednisolone in rabbits.
OBJECTIVE
The pathogenetic mechanisms involved in steroid-induced osteonecrosis are poorly understood. Appropriate experimental models of the human disease are indispensable to the understanding of successful treatment modalities for osteonecrosis.


METHODS
In the present experiment we devised a novel rabbit model of steroid-induced osteonecrosis by use of two low-dose LPS and three high-dose MPS to investigate the development of osteonecrosis. Thirty eight rabbits were used and tissue assessments were performed on proximal third and distal condyles of femora and humeri obtained 6 weeks after the administration of LPS and MPS. MRI of these regions and intraosseous pressure of proximal femur were obtained at 0 and 6 weeks. Other assessments included serum plasminogen activator/inhibitor ratio, cholesterol level, LDL/HDL ratio, and triglyceride levels at various time points.


RESULTS
The study showed that with this osteonecrosis induction protocol there was low animal mortality (6.2%), high rate of osteonecrosis (90%), induction of thrombotic state, and hypercholesterol/lipidemia.


CONCLUSIONS
On the whole, this is a novel modified animal model of steroid associated osteonecrosis and it would be useful for elucidating the pathogenesis of steroid associated osteonecrosis and developing preventive and therapeutic strategies.
Wu
Xinghuo
X
Department of Orthopaedics, Union Hospital, Tongji Medical College, Science and Technology of Huazhong University, Wuhan 430022, China.
Yang
Shuhua
S
Duan
Deyu
D
Zhang
Yukun
Y
Wang
Jing
J
D017667:Adipocytes / Q000187:drug effects / Q000473:pathology; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005269:Femur / Q000187:drug effects / Q000473:pathology; D005938:Glucocorticoids / Q000633:toxicity; D006811:Humerus / Q000187:drug effects / Q000473:pathology; D008055:Lipids / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity; D008136:Longevity / Q000187:drug effects; 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; D011312:Pressure; D011817:Rabbits; D010959:Tissue Plasminogen Activator / Q000097:blood
D004338:Drug Combinations; D005938:Glucocorticoids; D008055:Lipids; D008070:Lipopolysaccharides; D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator; D008775:Methylprednisolone