Simultaneous measurement of 25(OH)-vitamin D and 24,25(OH)2-vitamin D to define cut-offs for CYP24A1 mutation and vitamin D deficiency in a population of 1200 young subjects

Abstract

BackgroundSimultaneous measurement of 25(OH)D and 24,25(OH)2D is a new tool for predicting vitamin D deficiency and allows evaluating CYP24A1 lack of function. Interpretation of 24,25(OH)2D should be performed according to 25(OH)D levels and a ratio, called the vitamin D metabolite ratio (VMR) has been proposed for such a purpose. Unfortunately, the VMR can be expressed in different ways and cannot be used if 24,25(OH)2D concentrations are undetectable. Here, we propose evaluating the enzyme activity taking into consideration the probability that a normal population presents undetectable 24,25(OH)2D concentrations according to 25(OH)D levels. We thus retrospectively measured 25(OH)D and 24,25(OH)2D in a population of 1200 young subjects to evaluate the 25(OH)D threshold above which the enzyme was induced.MethodsSerum samples from 1200 infants, children, adolescent and young adults were used to simultaneously quantify 25(OH)D and 24,25(OH)2D by LCMS/MS.ResultsMedian (interquartile range [IQR]) levels were 20.6 (14.4–27.2) ng/mL for 25(OH)D. 172 subjects (14.3%) presented 24,25(OH)2D values below the LOQ. When 25(OH)D values were <11 ng/mL, 63.1% of subjects presented undetectable 24,25(OH)2D concentrations. Percentage decreased with increasing 25(OH)D values to become 19.7% for 25(OH)D comprised between 12 and 15 ng/mL, 5.1% for 25(OH)D between 16 and 20 and 0.7% for 25(OH)D >21 ng/mL.ConclusionsWe suggest using a statistical approach to evaluate CYP24A1 function according to 25(OH)D concentrations. Our results also show that vitamin D deficiency, as defined biochemically, could be around 20 ng/mL in infants, children, adolescent and young adults and that vitamin D deficiency could be evaluated on a more individual basis.

Renal Phosphate Handling: Independent Effects of Circulating FGF23, PTH, and Calcium

“…There were no changes in the vitamin D metabolite ratios, which are considered as surrogate markers of the hydroxylation enzymes CYP27B1 and CYP24A1. (27,34) FGF23 reduces CYP27B1 activity and increases CYP24A1 activity leading to a reduction in 1,25(OH)2D in favor of increased production of 24,25(OH)2D; whereas PTH increases CYP27B1 activity.…”

Vitamin D Metabolites and Clinical Outcome in Hospitalized COVID-19 Patients

“…Cavalier et al has suggested that the parallel analysis of these two metabolites facilitates an assessment of vitamin D metabolism that is based on dynamic physiologic principles. In particular, the proportion of 25(OH)D and 24,25(OH) 2 D 3 takes the individual set-point for vitamin D sufficiency into account, and may thus detect early functional vitamin deficiencies [ 30 ]. The 25,26(OH) 2 D was recently brought into connection with intestinal calcium transport.…”

How can the orthopedic surgeon ensure optimal vitamin D status in patients operated for an osteoporotic fracture?

“…It also means that when sufficient amounts of biologically active vitamin D are available, CYP24A1 is upregulated, and more 24,25(OH) 2 D is formed [ 28 , 29 ]. This approach could lead to a better personalization of vitamin D supplementation [ 30 ]. Nevertheless, measurement of 24,25(OH) 2 D and VMR (vitamin D metabolite ratio of serum, 24, 25(OH) 2 D to 25(OH)D) values are available only to clinical laboratories equipped with LC-MS capabilities in the absence of available automated immunoassays.…”

“…It also means that when sufficient amounts of biologically active vitamin D are available, CYP24A1 is upregulated, and more 24,25(OH) 2 D is formed [28,29]. This approach could lead to a better personalization of vitamin D supplementation [30]. Nevertheless, measurement of 24,25(OH)…”