Vitamin D-binding protein as it is understood in 2016: is it a critical key with which to help to solve the calcitriol conundrum?

Abstract

Background: The misnamed ‘vitamin’ D is actually the hormone calcitriol (1,25 dihydroxyhydroxyvitamin D). It has a central regulatory role in calcium metabolism, and more widely in the immune system. The prohormone calcifediol (25 hydroxyvitamin D) is more easily measured in the laboratory and is the analyte used in reference interval formulation. Being highly lipid soluble, both calcifediol and calcitriol travel in the bloodstream on carriage proteins, principally on vitamin D-binding protein. Summary: This review reports our current understanding of vitamin D-binding protein. Its genetic determinants and their effect on it and secondarily on calcifediol concentrations and assays are described. Its complex interplay with parathyroid hormone is considered. The analytical state of the art is translated into the challenge it imposes clinically, in the formulation of reference intervals and in their use in advising and managing patients. Several recent challenges thrown up to laboratories by percipient clinicians highlight the dilemma vitamin D-binding protein poses. A way forward is suggested.