Assessing vitamin D metabolism – four decades of experience

One hundred years ago, the role of vitamin D for bone mineralization and the prevention of rickets was discovered. Vitamin D comprises a group of over 50 metabolites with multiple functions that go far beyond calcium homeostasis and bone mineralization. Approximately 50 years ago, first methods for the measurement of 25-hydroxyvitamin D (25(OH)D) in human blood were developed. Over the years, different analytical principals were employed including competitive protein binding assays, high-performance liquid chromatography, various immunoassay and mass spectrometric formats. Until the recent standardization of serum 25(OH)D measurement, agreement between methods was unsatisfactory. Since then, comparability has improved, but substantial variability between methods remains. With the advent of liquid chromatography tandem mass spectrometry (LC-MS/MS), the accurate determination of 25(OH)D and other metabolites, such as 24,25(OH)2D, becomes increasingly accessible for clinical laboratories. Easy access to 25(OH)D testing has triggered extensive clinical research showing that large parts of the population are vitamin D deficient. The variable response of vitamin D deficient individuals to supplementation indicates that assessing patients' vitamin D stores by measuring 25(OH)D provides limited insight into the metabolic situation. Meanwhile, first evidence has emerged suggesting that the simultaneous measurement of 25(OH)D, 24,25(OH)2D and other metabolites allows a dynamic evaluation of patients' vitamin D status on metabolic principals. This may help to identify patients with functional vitamin D deficiency from those without. It can be expected that research into the assessment vitamin D status will continue for another 50 years and that this will help rationalizing our approach in clinical practice.