Herrmann Markus, Farrell Christopher-John L, Pusceddu Irene, Fabregat-Cabello Neus, Cavalier Etienne
Clin Chem Lab Med. 2017 Jan 1;55(1):3-26. doi: 10.1515/cclm-2016-0264.
In recent years it has been shown that vitamin D deficiency is associated with an increased incidence as well as the progression of a broad range of diseases including osteoporosis, rickets, cardiovascular disease, autoimmune disease, multiple sclerosis and cancer. Consequently, requests for the assessment of vitamin D status have increased dramatically. Despite significant progress in the analysis of vitamin D metabolites and an expansion of our pathophysiological knowledge of vitamin D, the assessment of vitamin D status remains a challenging and partially unresolved issue. Current guidelines from scientific bodies recommend the measurement of 25-hydroxy vitamin D (25-OHD) in blood as the preferred test. However, growing evidence indicates significant limitations of this test, including analytical aspects and interpretation of results. In addition, the relationships between 25-OHD and various clinical indices, such as bone mineral density and fracture risk, are rather weak and not consistent across races. Recent studies have systematically investigated new markers of vitamin D status including the vitamin D metabolite ratio (VMR) (ratio between 25-OHD and 24,25-dihydroxy vitamin D), bioavailable 25-OHD [25-OHD not bound to vitamin D binding protein (DBP)], and free 25-OHD [circulating 25-OHD bound to neither DBP nor albumin (ALB)]. These parameters may potentially change how we will assess vitamin D status in the future. Although these new biomarkers have expanded our knowledge about vitamin D metabolism, a range of unresolved issues regarding their measurement and the interpretation of results prevent their use in daily practice. It can be expected that some of these issues will be overcome in the near future so that they may be considered for routine use (at least in specialized centers). In addition, genetic studies have revealed several polymorphisms in key proteins of vitamin D metabolism that affect the circulating concentrations of vitamin D metabolites. The affected proteins include DBP, 7-dehydrocholesterol synthase and the vitamin D receptor (VDR). Here we aim to review existing knowledge regarding the biochemistry, physiology and measurement of vitamin D. We will also provide an overview of current and emerging biomarkers for the assessment of vitamin D status, with particular attention methodological aspects and their usefulness in clinical practice.
近年来研究表明，维生素D缺乏与多种疾病的发病率增加及病情进展相关，这些疾病包括骨质疏松症、佝偻病、心血管疾病、自身免疫性疾病、多发性硬化症和癌症。因此，对维生素D状态评估的需求急剧增加。尽管在维生素D代谢物分析方面取得了显著进展，且我们对维生素D的病理生理学知识有所扩展，但维生素D状态的评估仍然是一个具有挑战性且部分未解决的问题。科学机构的现行指南推荐测量血液中的25-羟维生素D（25-OHD）作为首选检测方法。然而，越来越多的证据表明该检测存在显著局限性，包括分析方面和结果解读。此外，25-OHD与各种临床指标（如骨密度和骨折风险）之间的关系相当微弱，且在不同种族间并不一致。近期研究系统地调查了维生素D状态的新标志物，包括维生素D代谢物比率（VMR）（25-OHD与24,25-二羟维生素D之间的比率）、生物可利用的25-OHD [未与维生素D结合蛋白（DBP）结合的25-OHD]以及游离25-OHD [既不与DBP也不与白蛋白（ALB）结合的循环25-OHD]。这些参数可能会改变我们未来评估维生素D状态的方式。尽管这些新的生物标志物扩展了我们对维生素D代谢的认识，但关于它们的测量及结果解读仍存在一系列未解决的问题，这阻碍了它们在日常实践中的应用。可以预期，其中一些问题将在不久的将来得到解决，以便它们可被考虑用于常规检测（至少在专业中心）。此外，基因研究揭示了维生素D代谢关键蛋白中的几种多态性，这些多态性会影响维生素D代谢物的循环浓度。受影响的蛋白包括DBP、7-脱氢胆固醇合酶和维生素D受体（VDR）。在此，我们旨在综述关于维生素D生物化学、生理学及测量的现有知识。我们还将概述用于评估维生素D状态的当前及新兴生物标志物，特别关注方法学方面及其在临床实践中的实用性。
