Abstract
The assay of vitamin D that began in the 1970s with the quantification of one or two metabolites, 25-OH-D or 1,25-(OH)(2)D, continues to evolve with the emergence of liquid chromatography tandem mass spectrometry (LC-MS/MS) as the technique of choice. This highly accurate, specific, and sensitive technique has been adopted by many fields of endocrinology for the measurement of multiple other components of the metabolome, and its advantage is that it not only makes it feasible to assay 25-OH-D or 1,25-(OH)(2)D but also other circulating vitamin D metabolites in the vitamin D metabolome. In the process, this broadens the spectrum of vitamin D metabolites, which the clinician can use to evaluate the many complex genetic and acquired diseases of calcium and phosphate homeostasis involving vitamin D. Several examples are provided in this review that additional metabolites (eg, 24,25-(OH)(2)D(3), 25-OH-D(3)-26,23-lactone, and 1,24,25-(OH)(3)D(3)) or their ratios with the main forms offer valuable additional diagnostic information. This approach illustrates that biomarkers of disease can also include metabolites devoid of biological activity. Herein, a case is presented that the decision to switch to a LC-MS/MS technology permits the measurement of a larger number of vitamin D metabolites simultaneously and does not need to lead to a dramatic increase in cost or complexity because the technique uses a highly versatile tandem mass spectrometer with plenty of reserve analytical capacity. Physicians are encouraged to consider adding this rapidly evolving technique aimed at evaluating the wider vitamin D metabolome toward streamlining their approach to calcium- and phosphate-related disease states. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.