Higher 25(OH)D2 Is Associated With Lower 25(OH)D3 and 1,25(OH)2D3

Context: Despite common use of supplemental vitamin D-2 in clinical practice, the associations of serum vitamin D-2 concentrations with other vitaminDmetabolites and total vitamin D are unclear. Objective: The aim of the study was to measure vitamin D-2 and D-3 levels and examine their associations with each other and with total vitamin D. Design: We performed a cross-sectional analysis of 679 randomly selected participants from the Osteoporotic Fractures in Men Study. 25-Hydroxyvitamin D-2 [ 25(OH)D-2], 25(OH)D-3, 1,25-dihydroxyvitamin D-2 [1,25(OH)(2)D-2], and 1,25(OH)(2)D-3 were measured using liquid chromatography-tandem mass spectrometry and were summed to obtain total 25(OH)D and 1,25(OH)(2)D. Associations between all metabolites (D-2, D-3, and total levels) were examined using Wilcoxon rank-sum tests and Spearman correlations. Results: 25(OH)D-2 and 1,25(OH)(2)D-2 were detectable in 189 (27.8%) and 178 (26.2%) of the men, respectively. Higher 25(OH)D-2 levels did not correlate with higher total 25(OH) D (r = 0.10; P = .17), although median total 25(OH)D was slightly higher in those with detectable vs undetectable 25(OH)D-2 (25.8 vs 24.3 ng/mL; P < .001). 25(OH)D-2 was not positively associated with total 1,25(OH)(2)D levels (r = -0.11; P = .13), and median 1,25(OH)(2)D level was not higher in those with detectable vs undetectable 25(OH)D-2. Higher 25(OH)D-2 was associated with lower 25(OH)D-3 (r = -0.35; P < .001) and 1,25(OH)(2)D-3 (r = -0.32; P < .001), with median levels of both D-3 metabolites 18-35% higher when D-2 metabolites were undetectable. Conclusions: In a cohort of older men, 25(OH)D-2 is associated with lower levels of 25(OH)D-3 and 1,25(OH)(2)D-3, suggesting that vitamin D-2 may decrease the availability of D-3 and may not increase calcitriol levels.