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Journal of Laboratory Medicine

Official Journal of the German Society of Clinical Chemistry and Laboratory Medicine

Editor-in-Chief: Schuff-Werner, Peter

Ed. by Ahmad-Nejad, Parviz / Bidlingmaier, Martin / Bietenbeck, Andreas / Conrad, Karsten / Findeisen, Peter / Fraunberger, Peter / Ghebremedhin, Beniam / Holdenrieder, Stefan / Kiehntopf, Michael / Klein, Hanns-Georg / Kohse, Klaus P. / Kratzsch, Jürgen / Luppa, Peter B. / Meyer, Alexander von / Nebe, Carl Thomas / Orth, Matthias / Röhrig-Herzog, Gabriele / Sack, Ulrich / Steimer, Werner / Weber, Thomas / Wieland, Eberhard / Winter, Christof / Zettl, Uwe K.


IMPACT FACTOR 2018: 0.389

CiteScore 2018: 0.22

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2567-9449
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Volume 38, Issue 1

Issues

Challenges in describing vitamin D status and activity / Herausforderungen bei der Bestimmung des Vitamin D-Status

Michael Vogeser / Silvia Bächer / Christoph Seger
  • Universitätskliniken/LKH Innsbruck, Zentralinstitut für Medizinische und Chemische Labordiagnostik (ZIMCL), Innsbruck, Austria
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2013-10-16 | DOI: https://doi.org/10.1515/labmed-2012-0034

Abstract

Within a few years, 25-hydroxyvitamin D (25-OHD)1 has emerged as a high volume test in many regions. Several analytical issues have been recognized regarding this analyte, in particular variable co-detection of metabolites (25-hydroxyvitamin D2; 3-epi-25-hydroxyvitamin D; 24,25-dihydroxyvitamin D), variable release of the analyte from its protein bonds and matrix effects in automated ligand binding tests, contributing to an often unsatisfactory correlation of high-throughput assays with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Reference methods based on LC-MS/MS as well as reference materials have been introduced only very recently, achieving a truly significant improvement in the standardization of serum 25-OHD measurement. However, beyond these analytical issues in relation to 25-OHD, it should be scrutinized how biologically appropriate this inactive intermediate metabolite can actually describe vitamin D status as a surrogate marker – individually and at a population level. There is, for example, at present little knowledge regarding individual vitamin D requirement in relation to dietary calcium supply; the impact of genetic variation of vitamin D binding protein on serum concentrations; the impact of genetic variation in downstream metabolism and signaling of vitamin D on individual vitamin demand. Furthermore, there is no accepted approach to assess functional whole year vitamin D status, addressing the fundamental seasonal variation of endogenous generation of vitamin D in many regions. Consequently, additional functional markers should be considered when describing vitamin D status (parathyroid hormone, corrected serum calcium and phosphate, urinary calcium, well selected bone markers, etc.), with season-adapted sampling strategies. In conclusion, it should be recognized that there is substantial uncertainty in the currently used approach to characterize vitamin D status by singular measurement of 25-OHD using mainstream assays. It seems questionable to focus the worldwide debate on a widespread vitamin supplementation merely on cut-off results of this marker.

Zusammenfassung

Innerhalb weniger Jahre hat sich 25-Hydroxy-Vitamin D (25-OHD) in vielen Regionen zu einer massenhaft angeforderten Messgröße entwickelt. Eine Reihe von analytischen Problemen wurden bezüglich dieses Analyten erkannt, insbesondere eine variable Miterfassung von Metaboliten (25-Hydoxyvitamin D2, 3-epi-25-Hydroxyvitamin D3, 24,25-Dihydroxy-Vitamin D), die variable Ablösung des Analyten aus seiner Proteinbindung und Matrixeffekte bei Ligandenbindungs-Tests. All dies trägt zu einer oft unbefriedigenden Korrelation von Hochdurchsatz-Methoden mit der LC-MS/MS bei. Referenzmethoden auf Basis der LC-MS/MS sowie Referenzmaterialien wurden erst vor relativ kurzer Zeit eingeführt; in der Tat hat dies zu einer wesentlichen Verbesserung der Standardisierung der 25-OHD-Messung beigetragen. Über diese analytischen Probleme bezüglich 25-OHD hinaus sollte jedoch eingehend hinterfragt werden, wie biologisch valide dieser inaktive Stoffwechselmetabolit als Surrogat-Marker tatsächlich den Vitamin D-Status zu beschreiben vermag, sowohl individuell als auch auf Populationsebene. So ist zum Beispiel wenig über den Zusammenhang zwischen individuellem Vitamin D-Bedarf und diätetischer Kalzium-Aufnahme bekannt, sowie über den Einfluss genetischer Variablen des Vitamin D-Bindeproteins auf die Serum-Konzentrationen, beziehungsweise über den Einfluss von genetischer Polymorphismen nachgeschalteter Verstoffwechslungs- und Signalwege auf den individuellen Vitamin D-Bedarf. Des Weiteren existiert kein allgemein anerkannter Ansatz zur Erfassung des Ganzjahres-Vitamin D-Status, der die erhebliche jahreszeitliche Variation der endogenen Vitamin D-Bildung – wie in vielen Regionen gegeben – berücksichtigen würde. Entsprechend sollten zusätzliche, funktionelle Marker bezüglich der Beschreibung des Vitamin D-Status geprüft werden (v.a., Parathormon, korrigiertes Serum-Kalzium, Serum-Phosphat, Urin-Kalzium sowie ausgewählte Knochenmarker), jeweils mit einer Jahreszeit-angepassten Strategie der Probengewinnung. Insgesamt sollte berücksichtigt werden, dass eine erhebliche Unschärfe im gegenwärtig überwiegend gewählten Ansatz der Beschreibung des Vitamin D-Status anhand der einmaligen Messung von 25-OHD mittels Standardmethoden besteht. Es erscheint fragwürdig, die weltweite Diskussion über eine flächendeckende Vitamin D-Supplementation ausschließlich auf Entscheidungsgrenzen dieses Markers zu basieren.

Reviewed publication

WallaschofskiH.

Keywords: calcium; cholecalciferol (vitamin D3); hypovitaminosis D; ligand binding assays; liquid chromatography-tandem mass spectrometry (LC-MS/MS); parathyroid hormone (PTH); season; Cholecalciferol (Vitamin D3); Jahreszeit; Kalzium; LC-MS/MS; Liganden-Bindungs-Tests; Parathormon (PTH); Vitamin D-Mangel

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About the article

Correspondence: Prof. Dr. med. Michael Vogeser, Klinikum der Universität München, Institut für Laboratoriumsmedizin, Marchioninistr. 15, 81377 Munich, Germany, Tel.: +49-89-7095-3221, Fax: +49-89-7095-6220, E-Mail:


Received: 2013-07-12

Accepted: 2013-09-11

Published Online: 2013-10-16

Published in Print: 2014-02-01


Conversion of units: 25-hydroxyvitamin D (25-OHD): [ng/mL] × 2.5 > [nmol/L].


Citation Information: LaboratoriumsMedizin, Volume 38, Issue 1, Pages 1–10, ISSN (Online) 1439-0477, ISSN (Print) 0342-3026, DOI: https://doi.org/10.1515/labmed-2012-0034.

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