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Associations Between Change in Total and Free 25-Hydroxyvitamin D With 24,25-Dihydroxyvitamin D and Parathyroid
Albert Shieh1, Christina Ma2, Rene F Chun3
1Department of Medicine, University of California, Los Angeles, California.
Context:
The physiologic role of free 25-hydroxyvitamin D [25(OH)D] in humans is unclear.
Objective:
To assess whether rise in total vs free 25(OH)D is associated with change in downstream biomarkers of 25(OH)D entry into target cells in kidney and parathyroid: 24,25-dihyroxyvitamin D [24,25(OH)2D] and PTH, respectively.
Design:
16-week randomized controlled trial.
Intervention:
60 μg (2400 IU)/d of D3 or 20 μg/d of 25(OH)D3.
Setting:
Academic medical center.
Participants:
35 adults age ≥18 years with 25(OH)D levels < 20 ng/mL.
Main Outcome Measures:
24,25(OH)2D, 1,25-dihyroxyvitamin D [1,25(OH)2D] and PTH.
Results:
At baseline, participants [D3 and 25(OH)D3 groups combined] were 35.1 ± 10.6 years. Mean total 25(OH)D, free 25(OH)D, 24,25(OH)2D, and PTH were 16.6 ng/mL, 4.6 pg/mL, 1.3 ng/mL, and 37.2 pg/mL, respectively. From 0 to 4 weeks, rise in only free 25(OH)D was associated with a concurrent 24,25(OH)2D increase [P = 0.03, adjusted for change in 1,25(OH)2D and supplementation regimen] and PTH decrease (P = 0.01, adjusted for change in calcium and supplementation regimen). Between 4 and 8 weeks, and again from 8 to 16 weeks, rises in free and total 25(OH)D were associated with 24,25(OH)2D increase; in contrast, rise in neither total nor free 25(OH)D was associated with PTH decrease during these time periods.
Conclusions:
Early rise in free 25(OH)D during treatment of vitamin D deficiency was more strongly associated with changes in biomarkers of 25(OH)D entry into target kidney and parathyroid cells, suggesting a physiologic role of free 25(OH)D in humans.
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