Influence of the Vitamin D-binding Protein on the Serum Concentration of 1,25-Dihydroxyvitamin D3

Bouillon, Roger; Assche, F.A. Van; Baelen, Hugo Van; Heyns, Walter; Moor, P. De

doi:10.1172/jci110072

Cited by 501 publications

(294 citation statements)

References 53 publications

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“…Consistent with this, a significant increase in the hourly fractional rate of radiocalcium absorption was found in 27 women with postmenopausal osteoporosis following 3 months of therapy with the anabolic steroid, nandrolone decanoate (92). However, since androgens may affect serum levels of vitamin D-binding protein, thus altering the levels of free 1,25-dihydroxyvitamin D 3 (93), it remains unclear whether androgens might exert their effects on intestinal calcium absorption directly or indirectly through effects on the vitamin D-endocrine system. Some studies also suggest that androgens may affect renal calcium transport.…”

Section: Extraskeletal Effects Of Androgens On Calcium Metabolismmentioning

confidence: 60%

Androgen effects on bone metabolism: recent progress and controversies

Hofbauer

Khosla

1999

European Journal of Endocrinology

122

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Androgens have beneficial effects on skeletal development and maintenance in women and men. The detection and functional characterization of androgen receptors in bone cells has implicated bone tissue as a potential target tissue for androgens. Gonadal and adrenal androgens directly regulate various aspects of osteoblastic lineage cells, including proliferation, differentiation, mineralization, and gene expression. These effects may differ depending on the stage of differentiation, the number of androgen receptors, and other inherent characteristics (species, site, cell biology) of the osteoblastic cell system. In addition, recent studies have suggested that some of the anabolic and anti-resorptive effects of androgens on bone may be mediated by regulation of autocrine and paracrine factors in the bone microenvironment, including transforming growth factor-b, insulin-like growth factors (and their binding proteins), and interleukin-6. This review summarizes the recent progress made in our knowledge of androgen receptor action, local androgen metabolism in bone, and direct and indirect effects of gonadal and adrenal androgens as well as androgen receptor antagonists on bone cells.

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Section: Extraskeletal Effects Of Androgens On Calcium Metabolismmentioning

confidence: 60%

Androgen effects on bone metabolism: recent progress and controversies

Hofbauer

Khosla

1999

European Journal of Endocrinology

122

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“…The majority of 25(OH)D circulates tightly bound to vitamin D-binding protein (VDBP) and more loosely bound to albumin; a much smaller percentage circulates free (31). Bioavailable 25(OH)D (the free plus albumin bound portions) has been proposed as a better indicator of vitamin D activity (32)(33)(34), possibly explaining discrepancies between findings of vitamin D effect on health outcomes in studies relying on total 25(OH)D. Several studies have identified a strong relationship between bioavailable vitamin D and indicators of vitamin D status such as bone mineral density and parathyroid hormone (32,33).…”

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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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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“…Calcidiol (25- [17][18][19]. The free 1,25(OH) 2 D 3 index was calculated as the molar ratio of total 1,25(OH) 2 D 3 to DBP [20]. Serum intact parathyroid hormone (PTH (1-84)) was measured by a two-step immunochemical method, involving an aminoterminal capture and a midregional detecting antibody, as described previously [21].…”

Section: Biochemical Measuresmentioning

confidence: 99%

Factors Associated with Cortical and Trabecular Bone Loss as Quantified by Peripheral Computed Tomography (pQCT) at the Ultradistal Radius in Aging Women

et al. 1997

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Abstract. Peripheral quantitative computed tomography (pQCT) allows the separate determination of cortical and trabecular bone mineral density in the peripheral skeleton. This cross-sectional study was designed to examine the effects of healthy aging on pQCT measurements at the ultradistal radius. In a well-defined sample of 129 community-based women, aged 70-87 years, the differences in cortical and trabecular density over the age range were equivalent to losses of −0.41% and −0.65% per year, respectively. To investigate the mechanism of this agerelated decline, we assessed relationships between both parameters and height, weight, body mass index, dietary calcium intake, grip strength, and serum concentrations of insulin-like growth factor-I (IGF-I), calcidiol (25(OH)D 3 ), calcitriol (1,25(OH) 2 D 3 ), parathyroid hormone (PTH), and sex hormone binding globulin (SHBG). Multiple regression was used to adjust for potential confounders. Age was not significant after controlling for other covariables. Body mass index, grip strength, serum IGF-I, 25(OH)D 3 , and PTH (1-84) were found to be independent predictors of total bone density. Including (total or free) 1,25(OH) 2 D 3 did not improve the model precision. These findings provide evidence that, among other factors, the activity of the growth hormone-IGF-I-axis is of importance for skeletal integrity. Grip strength, serum IGF-I, and PTH (1-84) were discovered to be significantly related to cortical but not to trabecular density, suggesting that different mechanisms may be involved in compact and cancellous bone loss.Key words: Peripheral quantitative computed tomography (pQCT) -Age-related bone loss -Growth hormone -IGF-I.Low bone mass, as estimated by decreased bone mineral density (BMD), is an established predictor of osteoporotic fractures. Although fracture prediction by bone density is partially site-dependent [1], numerous reports have shown that fractures at all skeletal sites are significantly related to low bone mass at the distal forearm [2][3][4][5]. In all of these studies, BMD was assessed with single-photon absorptiometry. Peripheral quantitative computed tomography (pQCT) has been proposed as an adjunct to conventional densitometry [6,7]. BMD determination with pQCT at the site of the distal radius is a method of high precision and low radiation [8]. In addition, pQCT is the only noninvasive assessment of bone mineral to measure a true-dimensional density (as opposed to an areal density by standard methods) and to allow separate determination of cortical and trabecular bone density [9].Studies have indicated that bone loss in elderly women shows no evidence for an age-related leveling off [10][11][12][13]. Even at advanced ages, interventions to preserve or to enhance bone mass may therefore be an effective approach to prevention of fractures. However, the mechanisms leading to age-related bone loss remain poorly defined. Moreover, whether cortical and trabecular bone losses are mediated by differential mechanisms is virtually unknown. In the pres...

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Influence of the Vitamin D-binding Protein on the Serum Concentration of 1,25-Dihydroxyvitamin D3

Cited by 501 publications

References 53 publications

Androgen effects on bone metabolism: recent progress and controversies

Androgen effects on bone metabolism: recent progress and controversies

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

Factors Associated with Cortical and Trabecular Bone Loss as Quantified by Peripheral Computed Tomography (pQCT) at the Ultradistal Radius in Aging Women

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