Dataset Information

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

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.

SUBMITTER: Shieh A

PROVIDER: S-EPMC6126886 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Shieh Albert A Ma Christina C Chun Rene F RF Wittwer-Schegg Jonas J Swinkels Leon L Huijs Tonnie T Wang Jeffrey J Donangelo Ines I Hewison Martin M Adams John S JS

The Journal of clinical endocrinology and metabolism 20180901 9

<h4>Context</h4>The physiologic role of free 25-hydroxyvitamin D [25(OH)D] in humans is unclear.<h4>Objective</h4>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.<h4>Design</h4>16-week randomized controlled trial.<h4>Intervention</h4>60 μg (2400 IU)/d of D3 or 20 μg/d of 25(OH)D3.<h4>Setting</h4>Academic medical center.<h4>Pa ...[more]

PMID: 29931358

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Project description:Background and objectivesElevated concentrations of fibroblast growth factor 23 (FGF23) are postulated to promote 25-hydroxyvitamin D (25[OH]D) insufficiency in CKD by stimulating 24-hydroxylation of this metabolite, leading to its subsequent degradation; however, prospective human studies testing this relationship are lacking.Design, setting, participants, & measurementsAn open-label prospective study was conducted from October 2010 through July 2012 to compare the effect of 8 weeks of oral cholecalciferol therapy (50,000 IU twice weekly) on the production of 24,25(OH)2D3 in vitamin D-insufficient patients with CKD (n=15) and controls with normal kidney function (n=15). Vitamin D metabolites were comprehensively profiled at baseline and after treatment, along with FGF23 and other mineral metabolism parameters.ResultsVitamin D3 and 25(OH)D3 concentrations increased equivalently in the CKD and control groups following cholecalciferol treatment (median D3 change, 8.6 ng/ml [interquartile range, 3.9-25.6 ng/ml] for controls versus 12.6 ng/ml [6.9-41.2 ng/ml] for CKD [P=0.15]; 25(OH)D3 change, 39.2 ng/ml [30.9-47.2 ng/ml] for controls versus 39.9 ng/ml [31.5-44.1 ng/ml] for CKD [P=0.58]). Likewise, the absolute increase in 1α,25(OH)2D3 was similar between CKD participants and controls (change, 111.2 pg/ml [64.3-141.6 pg/ml] for controls versus 101.1 pg/ml [74.2-123.1 pg/ml] for CKD; P=0.38). Baseline and post-treatment 24,25(OH)2D3 concentrations were lower in the CKD group; moreover, the absolute increase in 24,25(OH)2D3 after therapy was markedly smaller in patients with CKD (change, 2.8 ng/ml [2.3-3.5 ng/ml] for controls versus 1.2 ng/ml [0.6-1.9 ng/ml] for patients with CKD; P<0.001). Furthermore, higher baseline FGF23 concentrations were associated with smaller increments in 24,25(OH)2D3 for individuals with CKD; this association was negated after adjustment for eGFR by multivariate analysis.ConclusionsPatients with CKD exhibit an altered ability to increase serum 24,25(OH)2D3 after cholecalciferol therapy, suggesting decreased 24-hydroxylase activity in CKD. The observed relationship between baseline FGF23 and increments in 24,25(OH)2D3 further refutes the idea that FGF23 directly contributes to 25(OH)D insufficiency in CKD through stimulation of 24-hydroxylase activity.

Project description:Background:Interpretation of serum vitamin D biomarkers across pregnancy is complex due to limited understanding of pregnancy adaptations in vitamin D metabolism. During pregnancy, both gestational age and serum 25-hydroxyvitamin D [25(OH)D] concentrations may influence the concentrations of 1,25-dihydroxyvitamin D [1,25(OH)2D], 24,25-dihydroxyvitamin D [24,25(OH)2D], and parathyroid hormone (PTH). Objective:We aimed to identify predictors of change in serum 25(OH)D across gestation in pregnant adolescents and to assess the contribution made by cholecalciferol (vitamin D3) supplementation. We sought to determine whether gestational age and 25(OH)D concentration interacted to affect serum 1,25(OH)2D, 24,25(OH)2D, or PTH. Methods:Pregnant adolescents (n = 78, 59% African American, mean ± SD age: 17 ± 1 y) living in Rochester, NY (latitude 43°N) were supplemented with 200 IU or 2000 IU vitamin D3/d and allowed to continue their daily prenatal supplement that contained 400 IU vitamin D3. Serum was collected at study entry (18 ± 5 wk of gestation), halfway through study participation, and at delivery (40 ± 2 wk). Serum concentrations of the biochemical markers were modeled with linear mixed-effects regression models. Results:Vitamin D3 supplement intake and season of delivery determined change in 25(OH)D across pregnancy. Fall-winter delivery was associated with a decline in 25(OH)D unless vitamin D3 supplement intake was >872 IU/d. The interaction of gestational age and 25(OH)D affected 24,25(OH)2D concentrations. For a given 25(OH)D concentration, model-predicted serum 24,25(OH)2D increased across gestation except when 25(OH)D was <13 ng/mL. Below this threshold, 24,25(OH)2D was predicted to decline over time. Mean serum 1,25(OH)2D was elevated (>100 pg/mL) throughout the study. Conclusion:Our results suggest that when maternal serum 25(OH)D was low, its catabolism into 24,25(OH)2D decreased or remained stable as pregnancy progressed in order to maintain persistently elevated serum 1,25(OH)2D. Furthermore, in adolescents living at latitude 43°N, standard prenatal supplementation did not prevent a seasonal decline in 25(OH)D during pregnancy. This study was registered at clinicaltrials.gov as NCT01815047.

Project description:BackgroundConcentrations of 25-hydroxyvitamin D [25(OH)D] tend to be lower in African Americans than in non-Hispanic whites, but whether adding information on parathyroid hormone (PTH) can help explain the higher cardiometabolic risk among African Americans is unknown.ObjectivesThis study examined race (black/white)-specific independent and joint associations of 25(OH)D and PTH with cardiometabolic biomarkers including high-sensitivity C-reactive protein (hs-CRP), estimated glomerular filtration rate (eGFR), and homeostasis model assessment of insulin resistance (HOMA-IR) and β-cell function (HOMA-B).MethodsAmong 1500 white and 1300 black postmenopausal women without cardiovascular disease from the Women's Health Initiative Observational Study, a weighted linear regression analysis and a novel penalized spline-based semiparametric model with contour plots, accounting for possible nonlinear relations and interactions simultaneously, were used to investigate the race-specific independent and joint associations of 25(OH)D and PTH with each biomarker.ResultsBlack women had lower concentrations of 25(OH)D and higher PTH, HOMA-IR, HOMA-B, hs-CRP, and eGFR than white women (all P values < 0.0001). Lower 25(OH)D and higher PTH were each independently and jointly associated with higher HOMA-IR in both white and black women, whereas a similar joint relation with HOMA-B was observed in white women only. In contrast, PTH was nonlinearly associated with HOMA-B in black women and positively associated with hs-CRP in white women, independently of 25(OH)D. Whereas there was an inverse linear relation between PTH and eGFR in white women after accounting for 25(OH)D, PTH and 25(OH)D were jointly and nonlinearly associated with eGFR in black women.ConclusionsWe found that the joint association of 25(OH)D and PTH with β-cell function, systemic inflammation, and kidney function apparently differed between white and black women. Further studies are needed to determine whether differences in the vitamin D-PTH endocrine system contribute to racial disparities in cardiovascular health.

Dataset Information

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

Context

Objective

Design

Intervention

Setting

Participants

Main outcome measures

Results

Conclusions

Publications

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

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