Recommendations on the measurement and the clinical use of vitamin D metabolites and vitamin D binding protein – A position paper from the IFCC Committee on bone metabolism

• Published in: Clinica chimica acta Vol. 517; pp. 171 - 197
• Main Authors: Makris, Konstantinos, Bhattoa, Harjit P, Cavalier, Etienne, Phinney, Karen, Sempos, Christopher T., Ulmer, Candice Z., Vasikaran, Samuel D., Vesper, Hubert, Heijboer, Annemieke C.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-06-2021
• Subjects: 1α,25-dihydroxyvitamin D; 24,25-dihydroxyvitamin D; 25-hydroxyvitamin D; Biomarkers; Bone and Bones - metabolism; Calcifediol; Humans; Immunoassays; Liquid chromatography; Mass spectrometry; Standardization; Vitamin D; Vitamin D binding protein; Vitamin D Standardization Program; CDC; 24,25-dihydroxyvitamin D; PTH; Standardization; PRM; 1α,25(OH)2D3; C3-epi-25(OH)D; VDSCP; JCTLM; CYP27B1; LC-MS/MS; Vitamin D; VDBP; VDDR; EQA; FGF-23; 24,25(OH)2D3; 25(OH)D3; CKD; HPLC; CLIA; AACC; IFCC; Vitamin D Standardization Program; UV; VDSP; 25-hydroxyvitamin D; VDR; Vitamin D binding protein; Liquid chromatography; RIA; CYP24A1; CPBA; CAP; RMP; 7-DHC; 1α,25-dihydroxyvitamin D; VMR; CLD; DEQAS; Mass spectrometry; Immunoassays; SHPT; ELISA
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2021.03.002

•Brief presentation of the metabolism of vitamin D.•Detailed presentation of preanalytical variables affecting the measurement of vitamin D metabolites.•Detailed presentation and recommendations on the analytical measurement and clinical usefulness of vitamin D metabolites.•Current status and future goals for the standardization of analytical methods.
Vitamin D, an important hormone with a central role in calcium and phosphate homeostasis, is required for bone and muscle development as well as preservation of musculoskeletal function. The most abundant vitamin D metabolite is 25-hydroxyvitamin D [25(OH)D], which is currently considered the best marker to evaluate overall vitamin D status. 25(OH)D is therefore the most commonly measured metabolite in clinical practice. However, several other metabolites, although not broadly measured, are useful in certain clinical situations. Vitamin D and all its metabolites are circulating in blood bound to vitamin D binding protein, (VDBP). This highly polymorphic protein is not only the major transport protein which, along with albumin, binds over 99% of the circulating vitamin D metabolites, but also participates in the transport of the 25(OH)D into the cell via a megalin/cubilin complex.
The accurate measurement of 25(OH)D has proved a difficult task. Although a reference method and standardization program are available for 25(OH)D, the other vitamin D metabolites still lack this. Interpretation of results, creation of clinical supplementation, and generation of therapeutic guidelines require not only accurate measurements of vitamin D metabolites, but also the accurate measurements of several other “molecules” related with bone metabolism.
IFCC understood this priority and a committee has been established with the task to support and continue the standardization processes of vitamin D metabolites along with other bone-related biomarkers.
In this review, we present the position of this IFCC Committee on Bone Metabolism on the latest developments concerning the measurement and standardization of vitamin D metabolites and its binding protein, as well as clinical indications for their measurement and interpretation of the results.