| Project/Area Number |
17591590
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Osaka City University |
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Principal Investigator |
KOBAYASHI Akio Osaka City University, graduate school ofmedicine, visiting vise professor, 大学院医学研究科, 客員助教授 (70285287)
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| Co-Investigator(Kenkyū-buntansha) |
IWAKI Hiroyoshi Osaka City University, graduate school of medicine, instructor, 大学院医学研究科, 講師 (20381981)
TAKAOKA Kunio Osaka City University, graduate school of medicine, professor, 大学院医学研究科, 教授 (30112048)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | osteonecrosis / CYP3A / グルココルチコイド / CYP3A4 / 特発性大腿骨頭壊死症 / midazolam clearance |
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| Research Abstract |
Background: Osteonecrosis of the femoral head (ONFH) is one of the major side effects of corticosteroid therapy. Because corticosteroids are metabolized by hepatic cytochrome P450 (CYP) 3A, a low endogenous activity of this enzyme may contribute to the pathogenesis of ONFH. The purpose of this study was to examine the possible association of hepatic CYP3A activity and the susceptibility to ONFH in patients treated with corticosteroids.
Methods: In this prospective controlled study we measured the clearance of intravenous midazolam (0.25 mg/kg) to estimate hepatic CYP3A activity in patients with steroid-induced ONFH (n=26), patients with alcohol-related ONFH (n=29), and non-ONFH control patients (n=75) undergoing orthopedic surgery. Midazolam clearance was compared between the groups, and the relationship between the level of hepatic CYP3A activity and the prevalence of ONFH was evaluated by multivariate analysis.
Results: Midazolam clearance in patients with steroid-induced ONFH was significantly lower than that in control patients and patients with alcohol-related ONFH (7.7 ± 1.8 mL・kg^<-1>・min^<-1> versus 11.4 ±3.5 mL・kg^<-1>・min^<-1> and 10.5 ± 2.8 mL・kg^<-1>・min^<-1>, respectively; P <.001). Patients with low midazolam clearance (<9.5 mL・kg^<-1>・ min^<-1>) had a 9-fold greater risk for steroid-induced ONFH (adjusted odds ratio. 9.08 [95% confidence interval, 2.79-29.6]; P <.001). Midazolam clearance did not show a significant correlation with the prevalence of alcohol-related ONFH. Conclusions: Low hepatic CYP3A activity may significantly contribute to the risk for steroid-induced ONFH.
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