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Randomized Controlled Trial
. 2015 Nov;100(11):4140-5.
doi: 10.1210/jc.2015-2548. Epub 2015 Aug 27.

Free 25(OH)D and Calcium Absorption, PTH, and Markers of Bone Turnover

Affiliations
Randomized Controlled Trial

Free 25(OH)D and Calcium Absorption, PTH, and Markers of Bone Turnover

John Aloia et al. J Clin Endocrinol Metab. 2015 Nov.

Abstract

Context: It has been proposed that serum free 25-hydroxyvitamin D [25(OH)D] may better reflect vitamin D action than total 25(OH)D. An ELISA for serum free 25(OH)D has recently become available, permitting direct assay.

Objective: To determine whether serum free 25(OH)D provides additional information in relation to calcium absorption and other biomarkers of vitamin D action compared to total serum 25(OH)D.

Setting: Ambulatory research setting in a teaching hospital.

Outcome: Serum free 25(OH)D measured in a previously performed study of varied doses of vitamin D3 (placebo and 800, 2000, and 4000 IU) on calcium absorption, PTH, procollagen type 1 N-terminal propeptide, and C-terminal telopeptides of type I collagen. Free 25(OH)D was measured by ELISA. Calcium absorption was measured at baseline and at 10 weeks using stable dual calcium isotopes.

Results: Seventy-one subjects completed this randomized, placebo-controlled trial. Baseline group mean free and total 25(OH)D varied from 4.7 ± 1.8 to 5.4 ± 1.5 pg/mL, and from 23.7 ± 5.9 to 25.9 ± 6.1 ng/mL, respectively. Participants assigned to the 4000-IU dose arm achieved free 25(OH)D levels of 10.4 pg/mL and total 25(OH)D levels of 40.4 ng/mL. Total and free 25(OH)D were highly correlated at baseline and after increasing vitamin D dosing (r = 0.80 and 0.85, respectively). Free 25(OH)D closely reflected changes in total 25(OH)D. PTH was similarly correlated at baseline and follow-up with total and free 25(OH)D. Serum C-terminal telopeptides of type I collagen had a moderate positive correlation with total and free 25(OH)D at follow-up. The serum 1,25-dihydroxyvitamin D change increased significantly with the change in 25(OH)D but not with the change in free 25(OH)D.

Conclusion: There was no advantage from measuring free over total 25(OH)D in assessing the response of calcium absorption, PTH, and markers of bone turnover to vitamin D. Free 25(OH)D responded to increasing doses of vitamin D in a similar fashion to total 25(OH)D.

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Figures

Figure 1.
Figure 1.
Total 25(OH)D (ng/mL) vs free 25(OH)D (pg/mL).
Figure 2.
Figure 2.
Total 25(OH)D (ng/mL) vs free 25(OH)D (pg/mL) 10-week changes with estimated regression.
Figure 3.
Figure 3.
Ten-week free 25(OH)D (pg/mL) by dose group with estimated regression.

References

    1. Bikle DD, Gee E, Halloran B, Kowalski MA, Ryzen E, Haddad JG. Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein. J Clin Endocrinol Metab. 1986;63(4):954–959. - PubMed
    1. Chun RF, Peercy BE, Orwoll ES, Nielson CM, Adams JS, Hewison M. Vitamin D and DBP: the free hormone hypothesis revisited. J Steroid Biochem Mol Biol. 2014;144:132–137. - PMC - PubMed
    1. Powe CE, Evans MK, Wenger J, et al. Vitamin D-binding protein and vitamin D status of black Americans and white Americans. N Engl J Med. 2013;369(21):1991–2000. - PMC - PubMed
    1. Aloia JF. African Americans, 25-hydroxyvitamin D, and osteoporosis: a paradox. Am J Clin Nutr. 2008;88(2):545S–550S. - PMC - PubMed
    1. Ponda MP, McGee D, Breslow JL. Vitamin D-binding protein levels do not influence the effect of vitamin D repletion on serum PTH and calcium: data from a randomized, controlled trial. J Clin Endocrinol Metab. 2014;99(7):2494–2499. - PMC - PubMed

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