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The measurement of vitamin D metabolites: part I—metabolism of vitamin D and the measurement of 25-hydroxyvitamin D

Abstract

It has been more than 80 years since the discovery of vitamin D and its ability to cure rickets in children. Vitamin D is a secosteroid and comes in two distinct forms, vitamin D2 and vitamin D3. During the last 40 years, the synthesis and metabolism of vitamin D were elucidated and more than 50 metabolites of vitamin D have been discovered, though commercial measurement procedures have been developed for only a few of them. The clinical significance of vitamin D in calcium and phosphorus homeostasis is well appreciated. However, recent epidemiological data have indicated that it has several extra-skeletal physiologic actions which are still a matter of scientific debate. Both research findings and the debate around the interpretation of the research results have created increased interest in more measurements of vitamin D. With the ever growing family of measurable vitamin D metabolites and the measuring techniques comes a question: What metabolic product will provide the right answers and which is the best way to measure it. The right choice of analytical technique is connected with the question of which metabolite we aim to measure, what is its serum concentration, and the purpose of the measurement. The aim of the first part of this review is to provide a brief overview of vitamin D metabolism and a more detailed analysis of the existing methods and the status of standardization for the measurement of 25-hydroxyvitamin D.

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Abbreviations

7-DHC:

dehydrocholesterol or provitamin D3

24,25(OH)2D3:

24,25-dihydroxyvitamin D3

25(OH)D3:

calcidiol or 25-hydroxyvitamin D3

1α,25(OH)2D3:

calcitriol or 1,25-dihydroxyvitamin D3

C3-epi-25(OH)D:

C3-epimer of the 25(OH)D

CYP27B1:

25(OH)D-1a-hydroxylase

CYP24A1:

24-hydroxylase

PTH:

parathyroid hormone

FGF-23:

fibroblast growth factor-23

VDBP:

vitamin D binding protein

VDDR:

vitamin D-dependent rickets

VDR:

vitamin D receptor

VDSP:

Vitamin D Standardization Program

CLD:

chronic liver disease

CKD:

chronic kidney disease

SHPT:

secondary hyperparathyroidism

UV:

ultraviolet

HPLC:

high-performance liquid chromatography

LC-MS/MS:

liquid chromatography coupled with mass spectrometry

CPBA:

competitive protein binding assays

RIA:

radioimmunoassays

ELISA:

enzyme-linked immunosorbent assays

CLIA:

chemiluminescent assays

RMP:

reference measurement procedure

PRM:

primary reference material

NIST:

National Institute for Standards and Technology

IFCC:

International Federation of Clinical Chemistry

JCTLM:

Joint Committee for Traceability in Laboratory Medicine

AACC:

American Association for Clinical Chemistry

DEQAS:

Vitamin D External Quality Assessment Scheme

CAP:

College of American Pathologists

CDC:

Center for Disease Control

EQA:

External Quality Assessment

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Correspondence to Konstantinos Makris.

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Makris, K., Sempos, C. & Cavalier, E. The measurement of vitamin D metabolites: part I—metabolism of vitamin D and the measurement of 25-hydroxyvitamin D. Hormones (2020) doi:10.1007/s42000-019-00169-7

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Keywords

  • Vitamin D
  • 25-hydroxyvitamin D
  • Liquid chromatography
  • Mass spectrometry
  • Immunoassays
  • Standardization
  • Vitamin D standardization program