Binkley N, Dawson-Hughes B, Durazo-Arvizu R, Thamm M, Tian L, Merkel J M, Jones J C, Carter G D, Sempos C T
Osteoporosis Clinical Research Program and Institute on Aging, University of Wisconsin-Madison, Madison, WI, USA.
Bone Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MI, 02111, USA.
J Steroid Biochem Mol Biol. 2017 Oct;173:117-121. doi: 10.1016/j.jsbmb.2016.12.002. Epub 2016 Dec 12.
Substantial variability is associated with laboratory measurement of serum total 25-hydroxyvitamin D [25(OH)D]. The resulting chaos impedes development of consensus 25(OH)D values to define stages of vitamin D status. As resolving this situation requires standardized measurement of 25(OH)D, the Vitamin D Standardization Program (VDSP) developed methodology to standardize 25(OH)D measurement to the gold standard reference measurement procedures of NIST, Ghent University and CDC. Importantly, VDSP developed protocols for standardizing 25(OH)D values from prior research based on availability of stored serum samples. The effect of such retrospective standardization on prevalence of "low" vitamin D status in national studies reported here for The Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994) and the German Health Interview and Examination Survey for Children and Adolescents (KIGGS, 2003-2006) was such that in NHANES III 25(OH)D values were lower than original values while higher in KIGGS. In NHANES III the percentage with values below 30, 50 and 75 nmol/L increased from 4% to 6%, 22% to 31% and 55% to 71%, respectively. Whereas in KIGGS after standardization the percentage below 30, 50, and 70 nmol/L decreased from 28% to 13%, 64% to 47% and 87% to 85% respectively. Moreover, in a hypothetical example, depending on whether the 25(OH)D assay was positively or negatively biased by 12%, the 25(OH)D concentration which maximally suppressed PTH could vary from 20 to 35ng/mL. These examples underscore the challenges (perhaps impossibility) of developing vitamin D guidelines using unstandardized 25(OH)D data. Retrospective 25(OH)D standardization can be applied to old studies where stored serum samples exist. As a way forward, we suggest an international effort to identify key prior studies with stored samples for re-analysis and standardization initially to define the 25(OH)D level associated with vitamin D deficiency (rickets/osteomalacia). Subsequent work could focus on defining inadequacy. Finally, examples reported here highlight the importance of suspending publication of meta-analyses based on unstandardized 25(OH)D results.
血清总25-羟基维生素D[25(OH)D]的实验室测量存在很大差异。由此产生的混乱局面阻碍了就定义维生素D状态阶段的25(OH)D共识值的形成。由于解决这一情况需要对25(OH)D进行标准化测量，维生素D标准化计划(VDSP)开发了将25(OH)D测量标准化至美国国家标准与技术研究院(NIST)、根特大学和美国疾病控制与预防中心(CDC)的金标准参考测量程序的方法。重要的是，VDSP根据储存血清样本的可用性，制定了对先前研究中的25(OH)D值进行标准化的方案。本文报道了这种回顾性标准化对第三次全国健康和营养检查调查(NHANES III，1988 - 1994年)和德国儿童与青少年健康访谈与检查调查(KIGGS，2003 - 2006年)中全国性研究里“低”维生素D状态患病率的影响，结果是在NHANES III中25(OH)D值低于原始值，而在KIGGS中则更高。在NHANES III中，25(OH)D值低于30、50和75 nmol/L的百分比分别从4%增至6%、22%增至31%和55%增至71%。而在KIGGS中，标准化后低于30、50和70 nmol/L的百分比分别从28%降至13%、64%降至47%和87%降至85%。此外，在一个假设的例子中，根据25(OH)D检测是正向还是负向偏差12%，最大程度抑制甲状旁腺激素(PTH)的25(OH)D浓度可能在20至35 ng/mL之间变化。这些例子强调了使用未标准化的25(OH)D数据制定维生素D指南所面临的挑战(或许是不可能完成的任务)。回顾性25(OH)D标准化可应用于存在储存血清样本的旧研究。作为前进的方向，我们建议开展一项国际努力，以识别有储存样本的关键先前研究，以便首先进行重新分析和标准化，从而确定与维生素D缺乏(佝偻病/骨软化症)相关的25(OH)D水平。后续工作可侧重于定义不足。最后，本文报道的例子凸显了暂停基于未标准化25(OH)D结果的荟萃分析发表的重要性。
