Associations Between Change in Total and Free 25-Hydroxyvitamin D With 24,25-Dihydroxyvitamin D and Parathyroid Hormone

• Published in: The journal of clinical endocrinology and metabolism Vol. 103; no. 9; pp. 3368 - 3375
• Main Authors: Shieh, Albert, Ma, Christina, Chun, Rene F, Wittwer-Schegg, Jonas, Swinkels, Leon, Huijs, Tonnie, Wang, Jeffrey, Donangelo, Ines, Hewison, Martin, Adams, John S
• Format: Journal Article
• Language: English
• Published: United States Copyright Oxford University Press 01-09-2018; Oxford University Press; Endocrine Society
• Subjects: 24,25-Dihydroxyvitamin D 3 - administration & dosage; 25-Hydroxyvitamin D; Adult; Biomarkers; Biomarkers - blood; Calcifediol - blood; Calcium; Calcium - administration & dosage; Clinical s; Dietary Supplements; Female; Humans; Kidney - metabolism; Kidneys; Male; Nutrient deficiency; Parathyroid; Parathyroid Glands - metabolism; Parathyroid hormone; Parathyroid Hormone - blood; Supplements; Time Factors; Vitamin D; Vitamin D - analogs & derivatives; Vitamin D - blood; Vitamin D Deficiency - blood; Vitamin D Deficiency - therapy; Vitamins - administration & dosage
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2018-00515

The physiologic role of free 25-hydroxyvitamin D [25(OH)D] in humans is unclear.
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.
16-week randomized controlled trial.
60 μg (2400 IU)/d of D3 or 20 μg/d of 25(OH)D3.
Academic medical center.
35 adults age ≥18 years with 25(OH)D levels < 20 ng/mL.
24,25(OH)2D, 1,25-dihyroxyvitamin D [1,25(OH)2D] and PTH.
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.
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.