Abstract
BackgroundThe interest in vitamin D measurement has strongly increased in recent years. The best indicator for circulating vitamin D levels is 25-hydroxy-vitamin D (25(OH)D) which is often measured by different immunoassays. We demonstrate problems in comparability of measures by different immunoassays and the need for standardization in the context of a large population-based cohort study.Methods25(OH)D was measured with the immunoassays Diasorin Liaison in 2006 in 5,386 women and in the context of another project with IDS-iSYS in 4,199 men in 2009–2010 (when the Diasorin Liaison was no longer available in the version utilized in 2006). Standardization was performed by re-measuring of 25(OH)D levels in 97 men and 97 women with liquid chromatography tandem-mass spectrometry (LC-MS/MS) to obtain linear regression conversion equations.ResultsApplying a 30 nmol/L cut-off value for vitamin D deficiency would have resulted in 48.3% of women and 12.1% of men with vitamin D deficiency ahead of standardization. The large gender difference was strongly attenuated after standardization of the assays with only 15.7% of women and 14.3% of men with vitamin D deficiency. Standardization on average increased the 25(OH)D levels by 10.3 nmol/L in women and decreased 25(OH)D levels by 2.9 nmol/L in men.ConclusionThe standardization with LC-MS/MS revealed that much of the observed gender difference was only assay-driven and the extremely high proportion of 48.3% vitamin D deficient women proved to be an exaggeration of the old version of the Diasorin-Liaison immunoassay. Standardization of 25(OH)D immunoassay results by LC-MS/MS is recommended to improve their accuracy and comparability, provided the LC-MS/MS method itself is adequately validated and standardized.
Highlights
The interest in vitamin D measurements is strongly increasing since low vitamin D status is no longer only known to be a risk factor for osteoporotic diseases [1] but has been linked to the occurrence of a variety of other chronic diseases, such as cardiovascular diseases [2], diabetes mellitus [3] and several types of cancer [4]
We report serious problems in comparability of measures by different immunoassays and demonstrate the need for standardization in the context of a large population-based cohort study
Comparison of the immunoassay results In the random sample of 45 women with 25(OH)D measured by both the Diasorin-Liaison and IDS-iSYS immunoassay correlation was found to be high (r = 0.885, p,0.001, R2 = 0.783, Figure 1), but measurements by Diasorin-Liaison were on average 11.5 nmol/L lower than those by IDS-iSYS (p,0.001)
Summary
Ethics Statement Informed consent was obtained by all study participants of the study and all clinical investigations have been conducted according to the principles expressed in the Declaration of Helsinki. 25-OHD measurements In 2006, in the framework of a project on women’s health, the automated Diasorin-Liaison analyzer (Diasorin, Inc., Stillwater, USA) was employed in the central laboratory of the University Clinic of Heidelberg to measure 25(OH)D levels from stored serum samples in 5,386 women. According to the information of the manufacturer, the assay has an intra-assay CV of ,7.3%, an inter-assay CV of ,8.9% and a lower detection limit of 9 nmol/L [6]. Diasorin-Liaison) and men (in whom 25(OH)D was measured with IDS-ISYS) random samples of 100 study participants were drawn and re-measured with isotope-dilution LC-MS/MS (Waters ACQUITY TQ tandem quadrupole mass spectrometer (Waters, Milford, MA, USA)) in the Department of Clinical Chemistry, Canisius Wilhelma Hospital, Nijmegen, The Netherlands. All results and plots were generated with SAS, version 9.2 (Cary, NC, USA)
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