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

Overview

Journal J Clin Endocrinol Metab

Publisher Oxford University Press

Specialty Endocrinology

Date 2018 Jun 23

PMID 29931358

Citations 15

Authors

Albert Shieh

Christina Ma

Rene F Chun

Jonas Wittwer-Schegg

Leon Swinkels

Tonnie Huijs

Jeffrey Wang

Ines Donangelo

Martin Hewison

John S Adams

Affiliations

Soon will be listed here.

Abstract

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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References

Bikle D . Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol. 2014; 21(3):319-29. PMC: 3968073. DOI: 10.1016/j.chembiol.2013.12.016. View

Fraser D, KODICEK E . Unique biosynthesis by kidney of a biological active vitamin D metabolite. Nature. 1970; 228(5273):764-6. DOI: 10.1038/228764a0. View

Aloia J, Dhaliwal R, Mikhail M, Shieh A, Stolberg A, Ragolia L . Free 25(OH)D and Calcium Absorption, PTH, and Markers of Bone Turnover. J Clin Endocrinol Metab. 2015; 100(11):4140-5. PMC: 4702446. DOI: 10.1210/jc.2015-2548. View

Powe C, Ricciardi C, Berg A, Erdenesanaa D, Collerone G, Ankers E . Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. J Bone Miner Res. 2011; 26(7):1609-16. PMC: 3351032. DOI: 10.1002/jbmr.387. View

Bhan I, Powe C, Berg A, Ankers E, Wenger J, Karumanchi S . Bioavailable vitamin D is more tightly linked to mineral metabolism than total vitamin D in incident hemodialysis patients. Kidney Int. 2012; 82(1):84-9. PMC: 3376220. DOI: 10.1038/ki.2012.19. View

Peris P, Filella X, Monegal A, Guanabens N, Foj L, Bonet M . Comparison of total, free and bioavailable 25-OH vitamin D determinations to evaluate its biological activity in healthy adults: the LabOscat study. Osteoporos Int. 2017; 28(8):2457-2464. DOI: 10.1007/s00198-017-4062-8. View

Chun R, Peercy B, Adams J, Hewison M . Vitamin D binding protein and monocyte response to 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D: analysis by mathematical modeling. PLoS One. 2012; 7(1):e30773. PMC: 3265504. DOI: 10.1371/journal.pone.0030773. View

Lundgren S, Carling T, Hjalm G, Juhlin C, Rastad J, Pihlgren U . Tissue distribution of human gp330/megalin, a putative Ca(2+)-sensing protein. J Histochem Cytochem. 1997; 45(3):383-92. DOI: 10.1177/002215549704500306. View

Segersten U, Correa P, Hewison M, Hellman P, Dralle H, Carling T . 25-hydroxyvitamin D(3)-1alpha-hydroxylase expression in normal and pathological parathyroid glands. J Clin Endocrinol Metab. 2002; 87(6):2967-72. DOI: 10.1210/jcem.87.6.8604. View

10.

Bischoff-Ferrari H, Dawson-Hughes B, Stocklin E, Sidelnikov E, Willett W, Edel J . Oral supplementation with 25(OH)D3 versus vitamin D3: effects on 25(OH)D levels, lower extremity function, blood pressure, and markers of innate immunity. J Bone Miner Res. 2011; 27(1):160-9. DOI: 10.1002/jbmr.551. View

11.

Ritter C, Armbrecht H, Slatopolsky E, Brown A . 25-Hydroxyvitamin D(3) suppresses PTH synthesis and secretion by bovine parathyroid cells. Kidney Int. 2006; 70(4):654-9. DOI: 10.1038/sj.ki.5000394. View

12.

Chun R, Lauridsen A, Suon L, Zella L, Pike J, Modlin R . Vitamin D-binding protein directs monocyte responses to 25-hydroxy- and 1,25-dihydroxyvitamin D. J Clin Endocrinol Metab. 2010; 95(7):3368-76. PMC: 2928899. DOI: 10.1210/jc.2010-0195. View

13.

Aloia J, Chen D, Yeh J, Chen H . Serum vitamin D metabolites and intestinal calcium absorption efficiency in women. Am J Clin Nutr. 2010; 92(4):835-40. PMC: 2937584. DOI: 10.3945/ajcn.2010.29553. View

14.

Christensen E, Birn H . Megalin and cubilin: synergistic endocytic receptors in renal proximal tubule. Am J Physiol Renal Physiol. 2001; 280(4):F562-73. DOI: 10.1152/ajprenal.2001.280.4.F562. View

15.

Holick M, Binkley N, Bischoff-Ferrari H, Gordon C, Hanley D, Heaney R . Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011; 96(7):1911-30. DOI: 10.1210/jc.2011-0385. View

16.

Safadi F, Thornton P, Magiera H, Hollis B, Gentile M, Haddad J . Osteopathy and resistance to vitamin D toxicity in mice null for vitamin D binding protein. J Clin Invest. 1999; 103(2):239-51. PMC: 407885. DOI: 10.1172/JCI5244. View

17.

Ritter C, Brown A . Direct suppression of Pth gene expression by the vitamin D prohormones doxercalciferol and calcidiol requires the vitamin D receptor. J Mol Endocrinol. 2010; 46(2):63-6. DOI: 10.1677/JME-10-0128. View

18.

Schwartz J, Kane L, Bikle D . Response of Vitamin D Concentration to Vitamin D3 Administration in Older Adults without Sun Exposure: A Randomized Double-Blind Trial. J Am Geriatr Soc. 2016; 64(1):65-72. PMC: 4724876. DOI: 10.1111/jgs.13774. View

19.

Han J, Alvarez J, Jones J, Tangpricha V, Brown M, Hao L . Impact of high-dose vitamin D on plasma free 25-hydroxyvitamin D concentrations and antimicrobial peptides in critically ill mechanically ventilated adults. Nutrition. 2017; 38:102-108. PMC: 5439302. DOI: 10.1016/j.nut.2017.02.002. View

20.

Bosworth C, Levin G, Robinson-Cohen C, Hoofnagle A, Ruzinski J, Young B . The serum 24,25-dihydroxyvitamin D concentration, a marker of vitamin D catabolism, is reduced in chronic kidney disease. Kidney Int. 2012; 82(6):693-700. PMC: 3434313. DOI: 10.1038/ki.2012.193. View