Vitamin D Binding Protein special Issue – June 2014

Editorial: Vitamin D Binding Protein and Vitamin D Levels

International Journal of Endocrinology. Volume 2014 (2014), Article ID 638263, 2 pages
http://dx.doi.org/10.1155/2014/638263
Zhongjian Xie,1 Arthur C. Santora,2 Sue A. Shapses,3 and Xiangbing Wang4
1Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
2 Clinical Research, Diabetes and Endocrinology, Merck Research Laboratories, 126 East Lincoln Avenue, RY34B-148, Rahway, NJ 07065-0900, USA
3Department of Nutritional Science, Rutgers University, New Brunswick, NJ 08901, USA
4Division of Endocrinology, Metabolism and Nutrition, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08093, USA

Received 21 May 2014; Accepted 21 May 2014; Published 25 June 2014

Copyright © 2014 Zhongjian Xie et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Over the past few decades, there has been a growing interest in understanding the multifunctional characteristics and clinical importance of vitamin D binding protein (DBP). Multiple studies have shed light on DBP, giving rise to hopes of identifying novel mechanisms as well as utilizing DBP as a potential therapeutic agent. The current issue is comprised of 6 manuscripts, two of which are review articles. The areas covered in this special issue mostly highlight the potential role of DBP in several conditions including periodontitis and frailty, implying that measurement of DBP may provide useful information in addition to total 25-hydroxy vitamin D concentration.

In this issue, the review by P. Yousefzadeh et al. titled “Vitamin D binding protein impact on 25-hydroxyvitamin D levels under different physiologic and pathologic conditions” calls for the implementation of DBP testing during the interpretation of 25-hydroxyvitamin D [25(OH)D] results under different clinical situations. I. Bhan reviews the recent findings regarding the association between the differences in vitamin D binding protein levels and bone density in his paper titled “Vitamin D binding protein and bone health.” The author has compiled studies concerned with DBP, including DBP polymorphisms in relation to bone health and its association with vitamin D bioavailability. These findings may impact not only strategies for designing novel therapeutic agents that influence DBP or its binding, but also our understanding of the mechanism of vitamin D in the context of bone health. Evidence is emerging that the DBP polymorphisms are associated with race and ethnicity, resulting in differences in DBP levels and binding affinity that affect the transport and metabolism of vitamin D and its metabolites.

Using serum samples from various populations with varying DBP levels, J. Freeman et al., in their paper titled “Influence of vitamin D binding protein on accuracy of 25-hydroxyvitamin D measurement using the ADVIA Centaur vitamin D total assay,” assessed the agreement between the ADVIA Centaur vitamin D total assay for 25(OH)D testing and the liquid chromatography mass spectrometry (LS-MS/MS) method and concluded that the ADVIA Centaur vitamin D total assay demonstrated good performance compared to the LS-MS/MS method across the normal range of DBP concentrations. This is one example of methods development in the field to ensure accurate and simpler protocols for measuring circulating 25(OH)D in future study.

X. Zhang et al., in their paper titled “Vitamin D-binding protein levels in plasma and gingival crevicular fluid (GCF) of patients with generalized aggressive periodontitis,” examined the association of DBP with generalized aggressive periodontitis (GAgP). The authors found that GAgP patients had higher plasma DBP concentrations but lower GCF DBP concentrations than healthy controls, suggesting that decreased GCF-DBP level and increased plasma DBP level are associated with periodontitis. This study adds to the growing evidence of the potential role of DBP in the pathogenesis of periodontitis.

Existing evidence shows an association of high circulating 25(OH)D levels with low TSH levels in younger individuals, but there is insufficient information on whether it is the same in the elderly and middle-aged. Q. Zhang et al., in their paper titled “Association of high vitamin D status with low circulating thyroid-stimulating hormone independent of thyroid hormone levels in middle-aged and elderly males,” report that such an association does exist in middle-aged and elderly males, independent of thyroid hormone levels. The authors also demonstrated the link between vitamin D insufficiency and serum thyroid antibody levels.

Y. Wang et al., in their paper entitled “Vitamin D binding protein affects the correlation of 25(OH)D and frailty in the older men,” assessed the frailty status in elderly men of Changsha city, China, and concluded that serum DBP levels should be measured when evaluating the 25(OH)D- frailty relationship.

We hope that these articles convey new insights to readers and researchers into the current renewed interest in vitamin D and DBP research.

Zhongjian Xie, Arthur C. Santora, Sue A. Shapses, Xiangbing Wang


Testing

Influence of Vitamin D Binding Protein on Accuracy of 25-Hydroxyvitamin D Measurement Using the ADVIA Centaur Vitamin D Total Assay
International Journal of Endocrinology, Volume 2014 (2014), Article ID 691679, 12 pages
http://dx.doi.org/10.1155/2014/691679
Research Article
James Freeman, Kimberly Wilson, Ryan Spears, Victoria Shalhoub, and Paul Sibley
Siemens Healthcare Diagnostics, 511 Benedict Avenue, Tarrytown, NY 10591, USA

Received 13 December 2013; Revised 7 April 2014; Accepted 28 April 2014; Published 19 June 2014

Academic Editor: Arthur Santora

Copyright © 2014 James Freeman et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Vitamin D status in different populations relies on accurate measurement of total serum 25-hydroxyvitamin D [25(OH)D] concentrations [i.e., 25(OH)D3 and 25(OH)D2]. This study evaluated agreement between the ADVIA Centaur Vitamin D Total assay for 25(OH)D testing (traceable to the NIST-Ghent reference method procedure) and a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for various populations with different levels of vitamin D binding protein (DBP). Total serum 25(OH)D concentrations were measured for 36 pregnant women, 40 hemodialysis patients, and 30 samples (DBP-spiked or not) from healthy subjects. ELISA measured DBP levels. The mean serum DBP concentrations were higher for pregnancy (415 μg/mL) and lower for hemodialysis subjects (198 μg/mL) than for healthy subjects and were highest for spiked serum (545 μg/mL). The average bias between the ADVIA Centaur assay and the LC-MS/MS method was −1.4% (healthy), −6.1% (pregnancy), and 4.4% (hemodialysis). The slightly greater bias for samples from some pregnancy and hemodialysis subjects with serum DBP levels outside of the normal healthy range fell within a clinically acceptable range—reflected by analysis of their low-range (≤136 μg/mL), medium-range (137–559 μg/mL), and high-range (≥560 μg/mL) DBP groups. Thus, the ADVIA Centaur Vitamin D Total assay demonstrates acceptable performance compared with an LC-MS/MS method for populations containing different amounts of DBP.
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Different Conditions

Vitamin D Binding Protein Impact on 25-Hydroxyvitamin D Levels under Different Physiologic and Pathologic Conditions
International Journal of Endocrinology; Volume 2014 (2014), Article ID 981581, 6 pages
http://dx.doi.org/10.1155/2014/981581
Review Article
Pegah Yousefzadeh,1 Sue A. Shapses,2 and Xiangbing Wang1
1Division of Endocrinology, Metabolism & Nutrition, Department of Medicine, Rutgers University-Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA
2Department of Nutritional Sciences, Rutgers University, New Brunswick, NJ 08901, USA

Received 18 January 2014; Revised 3 April 2014; Accepted 10 April 2014; Published 28 April 2014

Academic Editor: Zhongjian Xie

Copyright © 2014 Pegah Yousefzadeh et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

There is a high prevalence of vitamin D deficiency worldwide, but how to define vitamin D deficiency is controversial. Currently, the plasma concentration of total 25-hydroxyvitamin D [25(OH)D] is considered an indicator of vitamin D status. The free hormone hypothesis states that protein-bound hormones are inactive while unbound hormones are free to exert biological activity. The majority of circulating 25(OH)D and 1,25(OH)2D is tightly bound to vitamin D binding protein (DBP), 10–15% is bound to albumin, and less than 1% of circulating vitamin D exists in an unbound form. While DBP is relatively stable in most healthy populations, a recent study showed that there are gene polymorphisms associated with race and ethnicity that could alter DBP levels and binding affinity. Furthermore, in some clinical situations, total vitamin D levels are altered and knowing whether DBP is also altered may have treatment implications. The aim of this review is to assess DBP concentration in different physiological and pathophysiological conditions. We suggest that DBP should be considered in the interpretation of 25(OH)D levels.
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Vitamin D Binding Protein and Bone Health

International Journal of Endocrinology; Volume 2014 (2014), Article ID 561214, 5 pages
http://dx.doi.org/10.1155/2014/561214
Ishir Bhan
Massachusetts General Hospital, Harvard Medical School, 5 Suite 750, 50 Staniford Street, Boston, MA 02114, USA

Received 24 February 2014; Accepted 4 May 2014; Published 1 June 2014

Vitamin D binding protein (DBP) is the major carrier protein of 25-hydroxyvitamin D (25(OH) D) in the circulation, where it may serve roles in maintaining stable levels during times of decreased 25(OH) availability and in regulating delivery of 25(OH) D to target tissues. Several genetic polymorphisms of DBP have been described that lead to phenotypic changes in the protein that may affect affinity, activity, and concentration. These polymorphisms have been linked with alterations in bone density in several populations. One of the mechanisms by which DBP may alter bone health involves regulating vitamin D bioavailability. DBP-bound vitamin is thought to be relatively unavailable to target tissues, and thus alterations in DBP levels or affinity could lead to changes in vitamin D bioactivity. As a result, functional vitamin D status may differ greatly between individuals with similar total 25(OH) D levels. Additionally, DBP may have independent roles on macrophage and osteoclast activation. This review will summarize recent findings about DBP with respect to measures of bone density and health.

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Other Special Issue articles ( full free text on-line)

  • Vitamin D-Binding Protein Levels in Plasma and Gingival Crevicular Fluid of Patients with Generalized Aggressive Periodontitis,
    Xin Zhang, Huanxin Meng, Li Xu, Li Zhang, Dong Shi, Xianghui Feng, Ruifang Lu, and Zhibin Chen, Volume 2014 (2014), Article ID 783575, 6 pages
  • Vitamin D Binding Protein Impact on 25-Hydroxyvitamin D Levels under Different Physiologic and Pathologic Conditions,
    Pegah Yousefzadeh, Sue A. Shapses, and Xiangbing Wang, Volume 2014 (2014), Article ID 981581, 6 pages
  • Vitamin D Binding Protein Affects the Correlation of 25(OH)D and Frailty in the Older Men,
    Yi Wang, Yan-Jiao Wang, Jun-Kun Zhan, Zhi-Yong Tang, Wu Huang, Pan Tan, Shan Gao, Cai-Li Ma, Zai-Jin Jian, and You-Shuo Liu, Volume 2014 (2014), Article ID 543783, 6 pages
  • Association of High Vitamin D Status with Low Circulating Thyroid-Stimulating Hormone Independent of Thyroid Hormone Levels in Middle-Aged and Elderly Males,
    Qingqing Zhang, Zhixiao Wang, Min Sun, Mengdie Cao, Zhenxin Zhu, Qi Fu, Yuan Gao, Jia Mao, Yanyun Li, Yun Shi, Fan Yang, Shuai Zheng, Wei Tang, Yu Duan, Xiaoping Huang, Wei He, and Tao Yang, Volume 2014 (2014), Article ID 631819, 6 pages

See also VitaminDWiki

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