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      Claudio Marcocci

      Department of Clinical and Experimental Medicine, University of Pisa

      via Paradisa 2

      IT–56124 Pisa (Italy)

      E-Mail [email protected]

      Giustina A, Bilezikian JP (eds): Vitamin D in Clinical Medicine.

      Front Horm Res. Basel, Karger, 2018, vol 50, pp 14–30 (DOI: 10.1159/000486062)

      ______________________

Vitamin D Assays

      Daniel D. Bikle

      VA Medical Center and University of California San Francisco, San Francisco, CA, USA

      ______________________

      Abstract

      The number of requests for vitamin D metabolite measurements has increased dramatically over the past decade leading commercial laboratories to develop rapid high throughput assays. The measurement of 25-hydroxyvitamin D (25[OH]D) and to a lesser extent 1,25-dihydroxyvitamin D (1,25[OH]₂D) dominates these requests, but requests for multiple metabolite measurements in the same sample are also increasing. The most commonly used methods include immunoassays and liquid chromatography/mass spectrometry (LC-MS). Each method has its advantages and disadvantages, but with improvements in technology, especially in LC-MS, this method is gaining ascendance due to its greater precision and flexibility. The use of standards from the National Institutes of Standards and Technology has substantially reduced the variability from laboratory to laboratory, thereby improving the reliability of these measurements. Although the current demand is for measurement of total vitamin D metabolite levels, these metabolites circulate in blood tightly bound to vitamin D binding protein (DBP) and albumin with less than 1% free. The free concentration may be a more accurate indicator of vitamin D status especially in individuals with DBP levels that deviate from the normal population. Thus, methods to measure the free concentration at least of 25(OH)D are becoming available and may supplement if not replace measurements of total levels.

      © 2018 S. Karger AG, Basel

      Introduction

Nearly all, if not all, cells express the vitamin D receptor (VDR) at some stage in their development or activation, and many of these cells are also able to convert vitamin D to its active metabolites. As the appreciation that vitamin D affects numerous physiologic processes other than bone and mineral metabolism, and that these physiologic processes may have different optimal levels of vitamin D [1], interest in the measurement of the levels of vitamin D and its metabolites has soared. Moreover, disorders of vitamin D metabolism can be diagnosed by accurate measurement of these metabolites, and potential differences in ratios of vitamin D metabolites even in otherwise normal individuals can be predictive of differences in responses to dietary intakes of vitamin D in food and/or in supplements due to differences in metabolism [2]. However, the measurement of vitamin D metabolites is not trivial. These are lipophilic materials circulating in low concentrations tightly bound to proteins, vitamin D binding protein (DBP) and albumin in particular, making their measurements difficult. If one considers that only the free (i.e., non-protein bound) metabolite enters cells and is the biologically important concentration to consider [3], the requirements for sensitivity of measurement increase by several orders of magnitude. Moreover, distinguishing between the different metabolites that may differ only modestly chemically but with substantial differences biologically and quantitatively likewise contributes to the difficulties developers of assays have in providing a fast throughput assay at reasonable cost to meet the increasing demand for these measurements. In this review, the most common assays on the market today are described reviewing their advantages and limitations with a discussion of newer technologies including the development of assays intended to measure the free concentrations.

      Vitamin D Production and