[An experimental osteonecrosis of femoral head induced by a combination of a single low-dose lipopolysaccharide and methylprednisone].
OBJECTIVE
To investigate both incidence and mechanism attributing to steroid-associated osteonecrosis of femoral head (ONFH) using an experimental protocol with a single low-dose lipopolysaccharide (LPS) injection and subsequently three injections of high-dose methylprednisolone (MPS).


METHODS
Twenty-five New Zealand white rabbits with body weight of (3.0 +/- 0.3) kg were divided randomly into 2 groups. In treatment group, 19 rabbits received one intravenous injection of LPS (10 microg/kg); 24 hours later, three injections of 20 mg/kg of MPS were given intramuscularly at an interval of 24 hours. Additional 6 rabbits which received normal saline injection at the same time point were used as controls (control group). The blood samples were collected for hematological examinations before and after LPS injection, MRI was performed on bilateral hip six weeks after last MPS injection, meanwhile, bone marrow was aspirated from femoral head region to evaluate stem cell's activity. Bilateral femoral heads were harvested to make histopathology examination.


RESULTS
All animals survived throughout the experiment period except one death on the second day after LPS injection. In the histopathological examination for the femoral head, ONFH+ was observed in 16 rabbits (88.9%), and the lesions were mainly in the metaphysis. In ONFH+ rabbits, micro vessels fibrous thrombosis and extravascular marrow fat cell size increasing were found around necrotic bone; The femoral heads of control group had no changes. MRI accurate ratio was 93.8% (15/16). Compared to baseline, a significant decrease in ratio of tissue plasminogen activator/plasminogen activator inhibitor 1 and activated partial thromboplatin time, and a significant increase in ratio of low-density lipoprotein/high-density lipoprotein were only found in ONFH+ rabbits (P < 0.05). Meanwhile there was a significant decrease in the number of CFU-F (8.50 +/-9.63) compared with the control (70.17 +/- 7.78, P < 0.05).


CONCLUSIONS
A single low-dose LPS injection and subsequent three injections of high-dose MPS is effective on building steroid-associated ONFH model, coagulation and lipometabolism abnormality, activity degeneration of stem cell may be the key factors of ONFH.
Yang
Jianping
J
Department of Orthopeadics, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing Jiangsu, 210006, P. R.China.
Wang
Liming
L
Xu
Yan
Y
Fan
Kewu
K
Wang
Jinsong
J
D017667:Adipocytes / Q000473:pathology; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005270:Femur Head / Q000000981:diagnostic imaging / Q000473:pathology*; D005271:Femur Head Necrosis / Q000097:blood / Q000139:chemically induced / 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*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011817:Rabbits; D011859:Radiography; D011897:Random Allocation; D010959:Tissue Plasminogen Activator / Q000097:blood
D006728:Hormones; D008070:Lipopolysaccharides; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator; D008775:Methylprednisolone