Fang Fang, Peters Tracy L, Beard John D, Umbach David M, Keller Jean, Mariosa Daniela, Allen Kelli D, Ye Weimin, Sandler Dale P, Schmidt Silke, Kamel Freya
Am J Epidemiol. 2017 Nov 1;186(9):1057-1064. doi: 10.1093/aje/kwx176.
Blood lead and bone turnover may be associated with the risk of amyotrophic lateral sclerosis (ALS). We aimed to assess whether these factors were also associated with time from ALS diagnosis to death through a survival analysis of 145 ALS patients enrolled during 2007 in the National Registry of Veterans with ALS. Associations of survival time with blood lead and plasma biomarkers of bone resorption (C-terminal telopeptides of type I collagen (CTX)) and bone formation (procollagen type I amino-terminal peptide (PINP)) were estimated using Cox models adjusted for age at diagnosis, diagnostic certainty, diagnostic delay, site of onset, and score on the Revised ALS Functional Rating Scale. Hazard ratios were calculated for each doubling of biomarker concentration. Blood lead, plasma CTX, and plasma PINP were mutually adjusted for one another. Increased lead (hazard ratio (HR) = 1.38; 95% confidence interval (CI): 1.03, 1.84) and CTX (HR = 2.03; 95% CI: 1.42, 2.89) were both associated with shorter survival, whereas higher PINP was associated with longer survival (HR = 0.59; 95% CI: 0.42, 0.83), after ALS diagnosis. No interactions were observed between lead or bone turnover and other prognostic indicators. Lead toxicity and bone metabolism may be involved in ALS pathophysiology.
血铅水平和骨转换可能与肌萎缩侧索硬化症（ALS）的风险相关。我们旨在通过对2007年纳入美国退伍军人ALS国家登记处的145例ALS患者进行生存分析，评估这些因素是否也与ALS诊断至死亡的时间相关。使用Cox模型估计生存时间与血铅以及骨吸收（I型胶原C端肽（CTX））和骨形成（I型前胶原氨基端肽（PINP））的血浆生物标志物之间的关联，并对诊断时的年龄、诊断确定性、诊断延迟、发病部位以及修订的ALS功能评定量表评分进行校正。计算生物标志物浓度每增加一倍时的风险比。血铅、血浆CTX和血浆PINP之间相互进行校正。在ALS诊断后，血铅升高（风险比（HR）=1.38；95%置信区间（CI）：1.03，1.84）和CTX升高（HR = 2.03；95% CI：1.42，2.89）均与较短的生存期相关，而较高的PINP与较长的生存期相关（HR = 0.59；95% CI：0.42，0.83）。未观察到铅或骨转换与其他预后指标之间存在相互作用。铅毒性和骨代谢可能参与了ALS的病理生理过程。
