Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
Calcif Tissue Int. 2023 Feb;112(2):158-177. doi: 10.1007/s00223-022-00961-5. Epub 2022 Mar 3.
Recent research activities have provided new insights in vitamin D metabolism in various conditions. Furthermore, substantial progress has been made in the analysis of vitamin D metabolites and related biomarkers, such as vitamin D binding protein. Liquid chromatography tandem mass spectrometric (LC-MS/MS) methods are capable of accurately measuring multiple vitamin D metabolites in parallel. Nevertheless, only 25(OH)D and the biologically active form 1,25(OH)2D are routinely measured in clinical practice. While 25(OH)D remains the analyte of choice for the diagnosis of vitamin D deficiency, 1,25(OH)2D is only recommended in a few conditions with a dysregulated D metabolism. 24,25(OH)2D, free and bioavailable 25(OH)D, and the vitamin D metabolite ratio (VMR) have shown promising results, but technical pitfalls in their quantification, limited clinical data and the lack of reference values, impede their use in clinical practice. LC-MS/MS is the preferred method for the measurement of all vitamin D related analytes as it offers high sensitivity and specificity. In particular, 25(OH)D and 24,25(OH)2D can accurately be measured with this technology. When interpreted together, they seem to provide a functional measure of vitamin D metabolism beyond the analysis of 25(OH)D alone. The determination of VDBP, free and bioavailable 25(OH)D is compromised by unresolved analytical issues, lacking reference intervals and insufficient clinical data. Therefore, future research activities should focus on analytical standardization and exploration of their clinical value. This review provides an overview on established and new vitamin D related biomarkers including their pathophysiological role, preanalytical and analytical aspects, expected values, indications and influencing conditions.
近期的研究活动为各种情况下的维生素 D 代谢提供了新的见解。此外，在维生素 D 代谢物及其相关生物标志物（如维生素 D 结合蛋白）的分析方面也取得了实质性进展。液相色谱串联质谱（LC-MS/MS）方法能够准确地同时测量多种维生素 D 代谢物。然而，在临床实践中仅常规测量 25（OH）D 和具有生物活性的 1,25（OH）2D。虽然 25（OH）D 仍然是诊断维生素 D 缺乏症的首选分析物，但只有在 D 代谢失调的少数情况下才推荐使用 1,25（OH）2D。24,25（OH）2D、游离和生物可利用的 25（OH）D、以及维生素 D 代谢物比（VMR）已显示出有希望的结果，但在其定量方面存在技术难题、有限的临床数据以及缺乏参考值，阻碍了它们在临床实践中的应用。LC-MS/MS 是测量所有与维生素 D 相关分析物的首选方法，因为它具有高灵敏度和特异性。特别是，这种技术可以准确地测量 25（OH）D 和 24,25（OH）2D。当一起解释时，它们似乎提供了一种超越单独分析 25（OH）D 的维生素 D 代谢功能衡量标准。VDBP、游离和生物可利用的 25（OH）D 的测定受到未解决的分析问题、缺乏参考区间和有限的临床数据的限制。因此，未来的研究活动应侧重于分析标准化以及探索它们的临床价值。本综述提供了关于已建立和新的维生素 D 相关生物标志物的概述，包括它们的病理生理作用、分析前和分析方面、预期值、适应症和影响条件。
