Bikle Daniel, Bouillon Roger, Thadhani Ravi, Schoenmakers Inez
VA Medical Center and University of California San Francisco, San Francisco, CA 94158, USA.
Clinical & Experimental Endocrinology, KULeuven, Herestraat 49 ON1 Box 902, 3000 Leuven, Belgium.
J Steroid Biochem Mol Biol. 2017 Oct;173:105-116. doi: 10.1016/j.jsbmb.2017.01.007. Epub 2017 Jan 16.
There is general consensus that serum 25(OH)D is the best biochemical marker for nutritional vitamin D status. Whether free 25(OH)D would be a better marker than total 25(OH)D is so far unclear. Free 25(OH)D can either be calculated based on the measurement of the serum concentrations of total 25(OH)D, vitamin D-binding protein (DBP), albumin, and the affinity between 25(OH)D and its binding proteins in physiological situations. Free 25(OH)D can also be measured directly by equilibrium dialysis, ultrafitration or immunoassays. During the vitamin D workshop held in Boston in March 2016, a debate was organized about the measurements and clinical value of free 25(OH)D, and this debate is summarized in the present manuscript. Overall there is consensus that most cells apart from the renal tubular cells are exposed to free rather than to total 25(OH)D. Therefore free 25(OH)D may be highly relevant for the local production and action of 1,25(OH)D. During the debate it became clear that there is a need for standardization of measurements of serum DBP and of direct measurements of free 25(OH)D. There seems to be very limited genetic or racial differences in DBP concentrations or (probably) in the affinity of DBP for its major ligands. Therefore, free 25(OH)D is strongly correlated to total 25(OH)D in most normal populations. Appropriate studies are needed to define the clinical implications of free rather than total 25(OH)D in normal subjects and in disease states. Special attention is needed for such studies in cases of abnormal DBP concentrations or when one could expect changes in its affinity for its ligands.
普遍共识是，血清25(OH)D是评估营养性维生素D状态的最佳生化标志物。目前尚不清楚游离25(OH)D是否比总25(OH)D是更好的标志物。游离25(OH)D既可以根据血清总25(OH)D、维生素D结合蛋白（DBP）、白蛋白的浓度测量值以及生理情况下25(OH)D与其结合蛋白之间的亲和力来计算。游离25(OH)D也可以通过平衡透析、超滤或免疫测定直接测量。在2016年3月于波士顿举行的维生素D研讨会上，组织了一场关于游离25(OH)D测量及临床价值的辩论，本手稿对此辩论进行了总结。总体而言，人们一致认为，除肾小管细胞外，大多数细胞接触的是游离而非总25(OH)D。因此，游离25(OH)D可能与1,25(OH)D的局部生成和作用高度相关。在辩论中明确的是，血清DBP测量以及游离25(OH)D直接测量需要标准化。DBP浓度或（可能）DBP与其主要配体的亲和力似乎存在非常有限的遗传或种族差异。因此，在大多数正常人群中，游离25(OH)D与总25(OH)D密切相关。需要进行适当研究来确定游离而非总25(OH)D在正常受试者和疾病状态下的临床意义。对于DBP浓度异常或预期其与配体亲和力发生变化的情况，此类研究需要特别关注。
