Serum 25-Hydroxyvitamin D Insufficiency in Search of a Bone Disease

Shah, Sonali; Chiang, Cherie; Sikaris, Ken; Lu, Zhong X.; Bui, Minh; Seeman, Ego

doi:10.1210/jc.2016-3189

Cited by 36 publications

(29 citation statements)

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“…Our findings are in line with an earlier animal study which reports similar calcium levels between vitamin D deprived rats as compared to control [33]. A positive association between serum 25-hydroxyvitamin D3 and serum phosphate is reported in blood samples collected from a pathology laboratory in Melbourne [34].…”

Section: Discussionsupporting

confidence: 92%

Maternal vitamin D deficiency increases the thromboxane/prostacyclin ratio through alterations in the one‐carbon cycle in Wistar rats

2019

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This study aims to test the hypothesis that vitamin D deficiency can influence long‐chain polyunsaturated fatty acid metabolism through alterations in the one‐carbon cycle. Wistar rats (n = 8 per group) were given either a control (1,000 IU D3/kg diet) or a vitamin D deficient (VDD) (0 IU D3/kg diet) diet from pre‐pregnancy to delivery. On day 20 of gestation, pregnant female rats were delivered by C‐section to collect placenta and blood. VDD group demonstrated high serum parathyroid hormone, low serum phosphate, low plasma folate, higher plasma homocysteine, and higher plasma malondialdehyde levels (P < 0.05 for all) as compared to control. Lower protein levels of placental cystathionine‐β‐synthase enzyme (P < 0.05) were observed in the VDD group as compared to control. VDD group demonstrated higher placental mRNA levels of the enzymes phospholipase A2 and cyclooxygenase‐2 (P < 0.05 for both) as compared to control. Protein levels of the enzymes phospholipase A2 and cyclooxygenase‐2 were lower (P < 0.05 for both) in the VDD group as compared to the control group. The ratio of thromboxane B2 and 6‐keto prostaglandin F1α in serum was higher (P < 0.05) in the VDD group as compared to control; although the serum levels of 6‐keto prostaglandin F1α and thromboxane B2 were similar in both the groups. Our findings suggest that increased oxidative stress due to maternal vitamin D deficiency results in the imbalance between the vasoconstrictor (thromboxane B2) and vasodilator (6‐keto prostaglandin F1α) eicosanoids, which may lead to endothelial dysfunction and poor pregnancy outcome. © 2019 BioFactors, 45 (4):548–555, 2019

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Section: Discussionsupporting

confidence: 92%

Maternal vitamin D deficiency increases the thromboxane/prostacyclin ratio through alterations in the one‐carbon cycle in Wistar rats

2019

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“…We used cut-off serum 25(OH)D levels of > 20 ng/ml as sufficient, of < 12 ng/ml as deficient, and of 12–20 ng/ml as insufficient to analyze the regression tree values. This cut-off chosen based on previously published data [ 22 , 23 ]. Notably, most subjects in each group were vitamin D deficient, and the proportion of subjects with vitamin D sufficiency did not reach 30%, with exception of the subgroup D in which the majority of individuals (67%) is sufficient.…”

Section: Discussionmentioning

confidence: 99%

Investigation of genetic variation and lifestyle determinants in vitamin D levels in Arab individuals

et al. 2018

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BackgroundDifferences in the concentrations of circulating 25-hydroxyvitamin D [25(OH)D] are associated with a wide range of health outcomes; however, most studies on genetic variants that impact 25(OH)D levels have been conducted in European populations. Here we aimed to identify common genetic variants that affect vitamin D concentrations in individuals of self-reported Arab ethnicity.MethodsThe study included 1151 Arab subjects living in Kuwait. Common variants of single-nucleotide polymorphisms and genes previously associated with vitamin D levels, such as GC, PDE3B, CYP2R1, and NADSYN1, were genotyped. Raw vitamin D level data were corrected for age, body mass index, and sex and then normalized. Regression tree analyses were performed to identify the impact of genetic variants on vitamin D levels.ResultsCompared with other gene variants, the GC gene variants exhibited the greatest impact on vitamin D levels in our study population, of which rs2298850 had the lowest p value (0.003). Individuals homozygous for the derived allele C had lower vitamin D levels. Analyses of the interaction between the number of years for which the subjects had lived in Kuwait and genetic variation in the GC gene showed that those with the CC genotype of rs2298850 who had lived in Kuwait for < 51 years had a mean 25(OH)D level of 10 ng/ml, whereas those who were homozygous for the ancestral allele had a mean 25(OH)D level of 17 ng/ml. Furthermore, subjects who had lived in Kuwait for > 51 years had higher vitamin D levels (mean 28 ng/ml) regardless of the genotype of their GC gene.ConclusionsThe GC gene may play a major role in determining vitamin D levels in Arab populations.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1396-8) contains supplementary material, which is available to authorized users.

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“…There is a wide difference in the recommended intakes of vitamin D in adults, ranging from 200 to 2000 IU daily [13], and the role of vitamin D in health has been under strong debate even in the UK where the relatively low dosage (400 IU daily) was selected by SACN [14][15][16][17][18][19]. Considering the marked seasonal difference in the association between S-25OHD levels and areal BMD [1], it is possible to interpret that the positive relationship between vitamin D status and areal BMD in many observational studies reflects the situation during summer; physical activity outdoors is a key factor, but its adjustment in the analysis would be difficult because only small number of cycles of mechanical loading is enough to maximally stimulate the skeleton [20].…”

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confidence: 99%

Vitamin D and bone health: interpreting observational studies

Sugiyama

2017

J Intern Med

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In a population-based cohort of approximately 5000 women (mean age 68 years), Micha€ elsson et al. [1] recently showed a marked seasonal difference in the association between serum 25-hydroxyvitamin D (S-25OHD) levels and areal bone mineral density (BMD) at the total hip, femoral neck and lumbar spine as well as of the total body. There was positive association between S-25OHD concentrations up to 40 nmol L À1 and areal BMD during summer. By sharp contrast, during winter, areal BMD was not associated with S-25OHD concentrations and similar between even below 20 nmol L À1 and over 80 nmol L À1. I agree with one reasonable explanation of the seasonal difference that a season-related dynamic process influenced the association between S-25OHD levels and areal BMD [1] and would also like to discuss this important evidence from another point of view.Of note, S-25OHD levels were predominantly linked to season-related ultraviolet type B (UV-B) radiation doses, and the difference during summer in areal BMD was relatively greater at the total hip and femoral neck compared with the lumbar spine [1]. The degree of mechanical loading is higher at the former sites than at the latter site, and skeletal loading from activity outdoors can be a major determinant of areal BMD. Consequently, the obvious seasonal discrepancy [1] seems to suggest that the association during summer could result from physical activity, whilst S-25OHD levels might not directly affect areal BMD.In consistent with the above logic, recent evidence is unlikely to support a cause and effect relationships between vitamin D status and musculoskeletal as well as nonmusculoskeletal [2] health in observational studies. For example, a Mendelian randomization study suggested that the association between genetically low vitamin D status and areal BMD was not causal [3], which agrees with the effect of vitamin D supplementation on areal BMD [4] and would be compatible with compensatory adaptation of bone to mechanical strain that is a prominent mechanism in the skeleton [5][6][7]. Furthermore, in the randomized, double-blind, placebo-controlled ViDA trial, monthly high-dose vitamin D supplementation of 100 000 IU colecalciferol for 3-4 years did not change the risk of fractures, and the result was independent of baseline S-25OHD levels including even less than 25 nmol L À1 and over 75 nmol L À1 [8]. The same interpretation can be applied to observational studies showing the association between use of proton pump inhibitors and an increased risk of hip fracture [9,10].As discussed by the authors [1], the effect of vitamin D supplementation on areal BMD appears to be indirect. On the basis of suggestion by the Scientific Advisory Committee on Nutrition (SACN) in adults aged 50 years or older that vitamin D supplementation improves muscle strength/function and increases areal BMD, especially at the femoral neck rather than total hip and notably not at the lumbar spine [11], we suggested that an increase in areal BMD by vitamin D supplementation can result indirectly fro...

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Serum 25-Hydroxyvitamin D Insufficiency in Search of a Bone Disease

Cited by 36 publications

References 17 publications

Maternal vitamin D deficiency increases the thromboxane/prostacyclin ratio through alterations in the one‐carbon cycle in Wistar rats

Maternal vitamin D deficiency increases the thromboxane/prostacyclin ratio through alterations in the one‐carbon cycle in Wistar rats

Investigation of genetic variation and lifestyle determinants in vitamin D levels in Arab individuals

Vitamin D and bone health: interpreting observational studies

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