The correlation between CYP3A activity and the risk of osteonecrosis.

背景：女性头部的骨质疏松症（ONFH）是皮质激素治疗的主要副作用之一。由于皮质激素是由Hepatic cytochrome P450 （CYP） 3A代谢的，这种酶可能对ONFH的病理学的贡献较低。本研究的目的是检验Hepatic CYP 3A活动的可能关联和对患者治疗的ONFH的可能性。方法：在这一前瞻性的受控研究中，我们测量了中等肌兰的清除情况（0.25毫克/千克）估计有类固醇诱导的ONFH患者（n=26）和有酒精相关的ONFH患者（n =29）的Hepatic CYP 3A活动，非ONFH对照患者（n=75）可能导致外科手术。Midazolam清除率比较了各群体之间的关系，以及Hepatic CYP 3A活动水平和ONFH的优越性，通过多变量分析进行了评估。与类固醇诱导的ONFH患者的中唑仑清除率明显低于受控患者和与酒精相关的ONFH患者（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）。中等唑仑清除率低（<9.5毫升·千克^<-1>· min^<-1>）对类固醇诱导的ONFH （调整后的奇数比率）有9折大风险。9.08[95%置信区间， 2.79-29.6]; P <.001）。Midazolam清除率并没有显示与酒精相关的ONFH的显著相关性。结论：低肝炎CYP 3A活动可能对类固醇诱导的ONFH产生重大影响。

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.