Risk factors for developing osteonecrosis after prophylaxis in steroid-treated rabbits.
OBJECTIVE
Both abnormal lipid metabolisms and coagulopathy have been suggested to be associated with the development of steroid-induced osteonecrosis (ON). We examined plasma risk factors for development of steroid-induced ON in rabbits after prophylaxis with a lipid-lowering agent and/or an anticoagulant.


METHODS
Seventy adult male rabbits were injected intramuscularly once with 20 mg/kg methylprednisolone acetate. Fifty-five rabbits received prophylaxis with probucol (a lipid-lowering agent; n = 20) or warfarin (an anticoagulant; n = 14) or both (n = 21). Probucol and warfarin were administered beginning 1 to 2 weeks prior to steroid injection. Two weeks after steroid injection, the bilateral femora and humeri were examined histopathologically for the presence of ON. Based on a logistic regression model, laboratory variables before steroid injection were assessed to determine whether they demonstrated any association with the risk of ON.


RESULTS
Twenty-one rabbits developed ON. In the univariate analyses, significant positive associations were observed between plasma concentrations of triglyceride and low-density lipoprotein and the risk of development of ON. In the multivariate model, only the plasma triglyceride level suggested a positive association. Even after adjusting for probucol and warfarin use, the plasma triglyceride level was still suggested to be a predictor for development of ON. Rabbits with higher baseline triglyceride levels had a more pronounced triglyceride increase in their response to steroids.


CONCLUSIONS
Our study suggests that, after prophylaxis with probucol and/or warfarin, plasma triglyceride level is associated with the development of steroid-induced ON in rabbits.
Motomura
Goro
G
Department of Orthopaedic Surgery, Kyushu University, Fukuoka, Japan.
Yamamoto
Takuaki
T
Miyanishi
Keita
K
Kondo
Kyoko
K
Hirota
Yoshio
Y
Iwamoto
Yukihide
Y
D000305:Adrenal Cortex Hormones / Q000009:adverse effects; D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000925:Anticoagulants / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D018890:Chemoprevention; D004195:Disease Models, Animal; D005230:Fatty Acids, Nonesterified / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008775:Methylprednisolone / Q000009:adverse effects / Q000031:analogs & derivatives; D000077555:Methylprednisolone Acetate; D016017:Odds Ratio; D010020:Osteonecrosis / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D011341:Probucol / Q000627:therapeutic use*; D011817:Rabbits; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood; D014859:Warfarin / Q000627:therapeutic use*
D000305:Adrenal Cortex Hormones; D000924:Anticholesteremic Agents; D000925:Anticoagulants; D015415:Biomarkers; D005230:Fatty Acids, Nonesterified; D008077:Lipoproteins, LDL; D014280:Triglycerides; D000077555:Methylprednisolone Acetate; D014859:Warfarin; D011341:Probucol; D008775:Methylprednisolone