A Comparison of Measured and Calculated Free 25(OH) Vitamin D Levels in Clinical Populations

Schwartz, Janice B.; Lai, Jennifer C.; Lizaola, Blanca; Kane, Lynn; Markova, Sardana; Weyland, P.; Terrault, Norah A.; Stotland, Nada L.

doi:10.1210/jc.2013-3874

Cited by 168 publications

(198 citation statements)

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“…Although this limits the generalizability of the results, we did not have sufficient numbers of African-American patients to perform accurate genotype analysis and calculate bioavailable 25(OH)D levels. Calculated free 25(OH)D has been shown to overestimate measured levels, although those calculations did not incorporate VDBP binding affinity by haplotype (35). To the best of our knowledge, we believe that, despite these limitations, this is the first study to report factors that influence VDBP levels in a relatively large cohort of critically ill children and to attempt to address the issue of 25(OH)D bioavailability in critical illness with some rigor.…”

Section: Original Researchmentioning

confidence: 96%

“…Bioavailable 25(OH)D can be calculated using several equations and a mathematical model, which incorporate 25(OH)D, VDBP, albumin levels, and VDBP binding affinity by haplotype to varying degrees (32)(33)(34). Recently, an assay of free 25(OH)D has become commercially available, and a comparison of the calculated to measured free 25(OH)D showed that a calculation that does not incorporate VDBP binding affinity overestimates the measured levels (35).…”

Section: Low Serum Concentrations Of Total 25-hydroxyvitamin D (25[oh]d)mentioning

confidence: 99%

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Critically Ill Children Have Low Vitamin D Binding Protein, Influencing Bioavailability of Vitamin D

Madden¹,

Feldman²,

Chun³

et al. 2015

Annals ATS

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Rationale: Vitamin D deficiency, often defined by total serum 25-hydroxyvitamin D (25[OH]D) ,20 ng/ml, is common in critically ill patients, with associations with increased mortality and morbidity in the intensive care unit. Correction of vitamin D deficiency in critical illness has been recommended, and ongoing clinical trials are investigating the effect of repletion on patient outcome. The biologically active amount of 25(OH)D depends on the concentration and protein isoform of vitamin D-binding protein (VDBP), which is also an acutephase reactant affected by inflammation and injury.Objectives: We performed a secondary analysis of a cohort of critically ill children in which we reported a high rate of vitamin D deficiency, to examine how VDBP level and genotype would impact vitamin D status. Methods:We prospectively enrolled 511 children admitted to the pediatric intensive care unit over a 12-month period. Measurements and Main Results:We measured serum VDBP in 479 children. We genotyped single nucleotide polymorphisms rs7041 and rs4588 in the VDBP gene (GC) to determine haplotypes GC1F, GC1S, and GC2 in 178 subjects who consented, then calculated bioavailable 25(OH)D from serum 25(OH)D, VDBP, albumin, and GC haplotype. The median serum VDBP level was 159 mg/ml (interquartile range, 108-221), lower than has been reported in healthy children. Factors predicting lower levels in multivariate analysis included age ,1 year, nonwhite race, being previously healthy, 25(OH)D ,20 ng/ml and greater illness severity. In the subgroup that was genotyped, GC haplotype had the strongest association with VDBP level; carriage of one additional copy of GC1S was associated with a 37.5% higher level (95% confidence interval, 31.9-44.8; P , 0.001). Bioavailable 25(OH)D was also inversely associated with illness severity (r = 20.24, P , 0.001), and ratio to measured total 25(OH)D was variable and related to haplotype.Conclusions: Physiologic deficiency of 25(OH)D in critical illness may be more difficult to diagnose, given that lower VDBP levels increase bioavailability. Treatment studies conducted on the basis of total 25(OH)D level, without consideration of VDBP concentration and genotype, may increase the risk of falsely negative results.

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Section: Original Researchmentioning

confidence: 96%

Section: Low Serum Concentrations Of Total 25-hydroxyvitamin D (25[oh]d)mentioning

confidence: 99%

Critically Ill Children Have Low Vitamin D Binding Protein, Influencing Bioavailability of Vitamin D

Madden¹,

Feldman²,

Chun³

et al. 2015

Annals ATS

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“…However, in some conditions such parameter may not represent a reliable marker of vitamin D activity due to modifications of free hormone levels independently of total hormone storage and amount [8][9][10]. Consistently with the free hormone hypothesis, only hormone not bound to protein vectors can exert biological actions [11].…”

mentioning

confidence: 88%

“…More than 80 % of circulating vitamin D (i.e., both 25(OH)-vitamin D and 1,25-dihydroxy-vitamin D3) is bound to vitamin D-binding protein (VDBP) which acts as regulator of hormone bio-availability to target tissue [12]. Indeed, VDBP could be either a reservoir of vitamin D prolonging its half-life or a modulator of hormone biological activity [9,10,13]. In clinical conditions, the inhibitory effects of VDBP on vitamin D activity seem to be predominant and some individuals may be misclassified as vitamin D sufficient or insufficient by measurement of serum 25(OH)vitamin D alone in the presence of modifications in VDBP production.…”

mentioning

confidence: 99%

“…In clinical conditions, the inhibitory effects of VDBP on vitamin D activity seem to be predominant and some individuals may be misclassified as vitamin D sufficient or insufficient by measurement of serum 25(OH)vitamin D alone in the presence of modifications in VDBP production. In fact, bio-available vitamin D is sufficient, despite low total 25(OH) vitamin D levels, in subjects with low levels of VDBP (e.g., patients with liver cirrhosis) [9,10]. Conversely, an increase in serum VDBP may cause a functional vitamin D deficiency even in the presence of normal 25(OH) vitamin D values [14].…”

mentioning

confidence: 99%

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Vitamin D-binding protein: one more piece in the puzzle of acromegalic osteopathy?

2016

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In only 5 years, more than 20,000 papers (more than 300 in the last month) dealing with vitamin D have been published, reflecting the deep interest of the scientific community for the role of this hormone in health and disease. There is an agreement that adequate vitamin D status should be defined by concentrations of serum that is the immediate precursor of the active hormone 1,25 dihydroxy-vitamin D3 [7]. However, in some conditions such parameter may not represent a reliable marker of vitamin D activity due to modifications of free hormone levels independently of total hormone storage and amount [8][9][10]. Consistently with the free hormone hypothesis, only hormone not bound to protein vectors can exert biological actions [11]. More than 80 % of circulating vitamin D (i.e., both 25(OH)-vitamin D and 1,25-dihydroxy-vitamin

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PTH and Vitamin D

Khundmiri

Murray

Lederer

2016

Comprehensive Physiology

234

158

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PTH and Vitamin D are two major regulators of mineral metabolism. They play critical roles in the maintenance of calcium and phosphate homeostasis as well as the development and maintenance of bone health. PTH and Vitamin D form a tightly controlled feedback cycle, PTH being a major stimulator of vitamin D synthesis in the kidney while vitamin D exerts negative feedback on PTH secretion. The major function of PTH and major physiologic regulator is circulating ionized calcium. The effects of PTH on gut, kidney, and bone serve to maintain serum calcium within a tight range. PTH has a reciprocal effect on phosphate metabolism. In contrast, vitamin D has a stimulatory effect on both calcium and phosphate homeostasis, playing a key role in providing adequate mineral for normal bone formation. Both hormones act in concert with the more recently discovered FGF23 and klotho, hormones involved predominantly in phosphate metabolism, which also participate in this closely knit feedback circuit. Of great interest are recent studies demonstrating effects of both PTH and vitamin D on the cardiovascular system. Hyperparathyroidism and vitamin D deficiency have been implicated in a variety of cardiovascular disorders including hypertension, atherosclerosis, vascular calcification, and kidney failure. Both hormones have direct effects on the endothelium, heart, and other vascular structures. How these effects of PTH and vitamin D interface with the regulation of bone formation are the subject of intense investigation.

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A Comparison of Measured and Calculated Free 25(OH) Vitamin D Levels in Clinical Populations

Cited by 168 publications

References 28 publications

Critically Ill Children Have Low Vitamin D Binding Protein, Influencing Bioavailability of Vitamin D

Critically Ill Children Have Low Vitamin D Binding Protein, Influencing Bioavailability of Vitamin D

Vitamin D-binding protein: one more piece in the puzzle of acromegalic osteopathy?

PTH and Vitamin D

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