Higher 25(OH)D2 Is Associated With Lower 25(OH)D3 and 1,25(OH)2D3

Swanson, Christine M.; Nielson, Carrie M.; Shrestha, Smriti; Lee, Christine G.; Barrett‐Connor, Elizabeth; Jans, Ivo; Cauley, Jane A.; Boonen, Steven; Bouillon, Roger; Vanderschueren, Dirk; Orwoll, Eric S.

doi:10.1210/jc.2014-1069

Cited by 33 publications

(32 citation statements)

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“…Variables most likely to affect the above associations were used in base and multivariable models and parallel those used in previous MrOS analyses for 25OHD and skeletal outcomes . We previously evaluated the relationships between vitamin D metabolites in this cohort and found that the amount of supplementation was minimal and did not significantly affect the associations of vitamin D metabolites . Therefore, these analyses were not adjusted for vitamin D supplement use.…”

Section: Methodssupporting

confidence: 82%

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Associations of 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D With Bone Mineral Density, Bone Mineral Density Change, and Incident Nonvertebral Fracture

Swanson

Srikanth

Lee

et al. 2015

Journal of Bone and Mineral Research

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Relationships between 1,25-dihydroxyvitamin D (1,25(OH)2D) and skeletal outcomes are uncertain. We examined the associations of 1,25(OH)2D with bone mineral density (BMD), BMD change, and incident fractures in a cohort of older men and compared them with those of 25-hydroxyvitamin D (25OHD). The study population included 1000 men (aged 74.6 ± 6.2 years) in the Osteoporotic Fractures in Men (MrOS) study, of which 537 men had longitudinal dual-energy X-ray absorptiometry (DXA) data (4.5 years of follow-up). A case-cohort design and Cox proportional hazards models were used to test the association between vitamin D metabolite levels and incident nonvertebral and hip fractures. Linear regression models were used to estimate the association between vitamin D measures and baseline BMD and BMD change. Interactions between 25OHD and 1,25(OH)2D were tested for each outcome. Over an average follow-up of 5.1 years, 432 men experienced incident nonvertebral fractures, including 81 hip fractures. Higher 25OHD was associated with higher baseline BMD, slower BMD loss, and lower hip fracture risk. Conversely, men with higher 1,25(OH)2D had lower baseline BMD. 1,25(OH)2D was not associated with BMD loss or nonvertebral fracture. Compared with higher levels of calcitriol, the risk of hip fracture was higher in men with the lowest 1,25(OH)2D levels (8.70 to 51.60 pg/mL) after adjustment for baseline hip BMD (hazard ratio [HR] = 1.99, 95% confidence interval [CI] 1.19–3.33). Adjustment of 1,25(OH)2D data for 25OHD (and vice versa) had little effect on the associations observed but did attenuate the hip fracture association of both vitamin D metabolites. In older men, higher 1,25(OH)2D was associated with lower baseline BMD but was not related to the rate of bone loss or nonvertebral fracture risk. However, with BMD adjustment, a protective association for hip fracture was found with higher 1,25(OH)2D. The associations of 25OHD with skeletal outcomes were generally stronger than those for 1,25(OH)2D. These results do not support the hypothesis that measures of 1,25(OH)2D improve the ability to predict adverse skeletal outcomes when 25OHD measures are available.

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Section: Methodssupporting

confidence: 82%

“…Aliquots of a single‐serum pool were included in alternate assay runs. Using the pooled serum, the interassay coefficients of variation (CVs) for 25OHD 2 and 25OHD 3 were both 4.4%, and the intra‐assay CVs were 6.4% and 4.9%, respectively . This assay does not cross‐react with 24‐hydroxy‐ or 26‐hydroxy‐derivatives.…”

Section: Methodsmentioning

confidence: 98%

Associations of 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D With Bone Mineral Density, Bone Mineral Density Change, and Incident Nonvertebral Fracture

Swanson

Srikanth

Lee

et al. 2015

Journal of Bone and Mineral Research

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“…It might also reflect our finding that supplementation with vitamin D 2 led to a decrease in 25(OH)D 3 concentrations, as also observed in non‐trial settings by others , while supplementation with vitamin D 3 did not affect 25(OH)D 2 concentrations in the present trial. The decrease in 25(OH)D 3 concentrations in the D 2 group may suggest different bioavailability , possible more rapid metabolism or clearance of circulating 25(OH)D 3 following D 2 supplementation, or competition for enzymatic activity by CYP2R1 for 25‐hydroxylation of vitamin D 2 and D 3 . It has been suggested that an upregulation in mechanisms required to metabolize D 2 and its metabolites may increase the degradation of circulating 25(OH)D 3 concentrations but the biological significance of these changes is currently unclear.…”

Section: Discussionsupporting

confidence: 91%

“…This may be partially attributable to the shorter half‐life of 25(OH)D 2 versus 25(OH)D 3 in the circulation, which is related to the lower affinity of the D 2 metabolite for the vitamin D‐binding protein . It might also reflect our finding that supplementation with vitamin D 2 led to a decrease in 25(OH)D 3 concentrations, as also observed in non‐trial settings by others , while supplementation with vitamin D 3 did not affect 25(OH)D 2 concentrations in the present trial. The decrease in 25(OH)D 3 concentrations in the D 2 group may suggest different bioavailability , possible more rapid metabolism or clearance of circulating 25(OH)D 3 following D 2 supplementation, or competition for enzymatic activity by CYP2R1 for 25‐hydroxylation of vitamin D 2 and D 3 .…”

Section: Discussionsupporting

confidence: 77%

Effects of vitamin D₂ or D₃ supplementation on glycaemic control and cardiometabolic risk among people at risk of type 2 diabetes: results of a randomized double‐blind placebo‐controlled trial

Forouhi

Menon

Sharp

et al. 2016

Diabetes Obesity Metabolism

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AimsTo investigate the effect of short‐term vitamin D supplementation on cardiometabolic outcomes among individuals with an elevated risk of diabetes.MethodsIn a double‐blind placebo‐controlled randomized trial, 340 adults who had an elevated risk of type 2 diabetes (non‐diabetic hyperglycaemia or positive diabetes risk score) were randomized to either placebo, 100 000 IU vitamin D2 (ergocalciferol) or 100 000 IU vitamin D3 (cholecalciferol), orally administered monthly for 4 months. The primary outcome was change in glycated haemoglobin (HbA1c) between baseline and 4 months, adjusted for baseline. Secondary outcomes included: blood pressure; lipid levels; apolipoprotein levels; C‐reactive protein levels; pulse wave velocity (PWV); anthropometric measures; and safety of the supplementation.ResultsThe mean [standard deviation (s.d.)] 25‐hydroxyvitamin D [25(OH)D]2 concentration increased from 5.2 (4.1) to 53.9 (18.5) nmol/l in the D2 group, and the mean (s.d.) 25(OH)D3 concentration increased from 45.8 (22.6) to 83.8 (22.7) nmol/l in the D3 group. There was no effect of vitamin D supplementation on HbA1c: D2 versus placebo: −0.05% [95% confidence interval (CI) −0.11, 0.02] or −0.51 mmol/mol (95% CI −1.16, 0.14; p = 0.13); D3 versus placebo: 0.02% (95% CI −0.04, 0.08) or 0.19 mmol/mol (95% CI −0.46, 0.83; p = 0.57). There were no clinically meaningful effects on secondary outcomes, except PWV [D2 versus placebo: −0.68 m/s (95% CI −1.31, −0.05); D3 versus placebo −0.73 m/s (95% CI −1.42, −0.03)]. No important safety issues were identified.ConclusionsShort‐term supplementation with vitamin D2 or D3 had no effect on HbA1c. The modest reduction in PWV with both D2 and D3 relative to placebo suggests that vitamin D supplementation has a beneficial effect on arterial stiffness.

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“…25‐OH D3 and 1,25‐(OH)2 D3 correlate in patients without PHPT . However, elevated levels of iPTH increase the metabolism of 25‐OH D3‐1,25‐(OH)2 D3 by directly activating 1α‐hydroxylase.…”

Section: Discussionmentioning

confidence: 99%

Factors influencing pre‐operative urinary calcium excretion in primary hyperparathyroidism

Kaderli

Riss

Geroldinger

et al. 2017

Clinical Endocrinology

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Higher 25(OH)D2 Is Associated With Lower 25(OH)D3 and 1,25(OH)2D3

Abstract: In a cohort of older men, 25(OH)D2 is associated with lower levels of 25(OH)D3 and 1,25(OH)2D3, suggesting that vitamin D2 may decrease the availability of D3 and may not increase calcitriol levels.

Cited by 33 publications

References 30 publications

Associations of 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D With Bone Mineral Density, Bone Mineral Density Change, and Incident Nonvertebral Fracture

Associations of 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D With Bone Mineral Density, Bone Mineral Density Change, and Incident Nonvertebral Fracture

Effects of vitamin D₂ or D₃ supplementation on glycaemic control and cardiometabolic risk among people at risk of type 2 diabetes: results of a randomized double‐blind placebo‐controlled trial

Factors influencing pre‐operative urinary calcium excretion in primary hyperparathyroidism

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Higher 25(OH)D2 Is Associated With Lower 25(OH)D3 and 1,25(OH)2D3

Abstract: In a cohort of older men, 25(OH)D2 is associated with lower levels of 25(OH)D3 and 1,25(OH)2D3, suggesting that vitamin D2 may decrease the availability of D3 and may not increase calcitriol levels.

Cited by 33 publications

References 30 publications

Associations of 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D With Bone Mineral Density, Bone Mineral Density Change, and Incident Nonvertebral Fracture

Associations of 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D With Bone Mineral Density, Bone Mineral Density Change, and Incident Nonvertebral Fracture

Effects of vitamin D2 or D3 supplementation on glycaemic control and cardiometabolic risk among people at risk of type 2 diabetes: results of a randomized double‐blind placebo‐controlled trial

Factors influencing pre‐operative urinary calcium excretion in primary hyperparathyroidism

Contact Info

Product

Resources

About

Effects of vitamin D₂ or D₃ supplementation on glycaemic control and cardiometabolic risk among people at risk of type 2 diabetes: results of a randomized double‐blind placebo‐controlled trial