Felson D T, Anderson J J
Lancet. 1987 Apr 18;1(8538):902-6. doi: 10.1016/s0140-6736(87)92870-4.
Studies investigating steroid dose and avascular necrosis of bone (AVN) have found either a weak association or none at all. This quantitative review of published studies has evaluated the effects of steroid dose and bolus steroids on the risk of AVN. 22 papers with sufficient information for analysis were identified. The mean steroid dose for the cohort was plotted against the percentage in whom AVN developed. Total dose was divided into non-bolus (oral) and bolus dose, and doses 1, 3, 6, and 12 months after beginning steroids were tested separately for their association with AVN risk. There was a strong correlation between daily total dose and AVN rate (r = 0.61-0.80). Oral dose was strongly correlated with AVN rate (r = 0.70-0.86), but bolus dose was not associated with AVN risk. This strong association between AVN and steroid dose contrasts with the weak relations found in case-control studies from individual centres in which cases and controls received similar steroid regimens and therefore did not differ greatly in steroid dose. The method of deriving a single exposure level per study and comparing the amount of exposure across studies may be useful in assessing whether a drug's toxicity is dose dependent.
关于类固醇剂量与骨缺血性坏死（AVN）的研究发现，二者之间要么关联较弱，要么毫无关联。这项已发表研究的定量综述评估了类固醇剂量和冲击性类固醇对AVN风险的影响。共识别出22篇有足够信息可供分析的论文。将队列的平均类固醇剂量与发生AVN的百分比进行绘图。总剂量分为非冲击性（口服）剂量和冲击性剂量，并分别测试开始使用类固醇后1、3、6和12个月时的剂量与AVN风险的关联。每日总剂量与AVN发生率之间存在强相关性（r = 0.61 - 0.80）。口服剂量与AVN发生率密切相关（r = 0.70 - 0.86），但冲击性剂量与AVN风险无关。AVN与类固醇剂量之间的这种强关联，与个别中心的病例对照研究中发现的弱关联形成对比，在这些研究中，病例和对照接受相似的类固醇治疗方案，因此在类固醇剂量上差异不大。在每项研究中得出单一暴露水平并比较不同研究间暴露量的方法，可能有助于评估药物毒性是否与剂量相关。
