18th Vitamin D Workshop (of March 2016) abstracts – Nov 2016

The Journal of Steroid Biochemistry and Molecular Biology, Volume 164, Pages 1-394 (November 2016)
Note: 19th conf will be in Orlando March 2017

Most of the PDFs cost $35.95 each, only 4 are free (author had to pay?)

International Congress on Vitamin D (VitaminD Workshop) – NY May 2019 has links to many previous workshops

Abstracts are typically available online

Diabetes: Far less if high vitamin D, far more if dark skin (low Vitamin D)

See below: Consistent ethnic specific differences . . . .

 

Histogram of 60,000 patients in one hospital from 136 countries

 Download the PDF via ResearchGate from VitaminDWiki
Here are additional histograms from Australia   and historgrams for multiple races

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Editorial: Highlights from the 18th workshop on vitamin D, Delft, The Netherlands, April 21–24, 2015

Pages 1-3
Paul Lips, JoEllen Welsh, Marie Demay, Roger Bouillon
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Consistent ethnic specific differences in diabetes risk and vitamin D status in the National Health and Nutrition Examination Surveys

Pages 4-10, Monika H.E. Christensen, Robert K. Scragg
(free PDF) graphical Purchase PDF - $35.95 Supplementary content

Associations of vitamin D status and vitamin D-related polymorphisms with sex hormones in older men

Pages 11-17
R. Rafiq, N.M. van Schoor, E. Sohl, M.C. Zillikens, M.M. Oosterwerff, L. Schaap, P. Lips, R.T. de Jongh
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Highlights

• Vitamin D might influence sex hormone and gonadotropin levels.
• We studied relationships between 25(OH)D, gene polymorphisms and sex hormone levels.
• Lower vitamin D status is associated with lower testosterone levels.
• There was no association between gene polymorphisms and sex hormone levels.

Single nucleotide polymorphisms in the vitamin D pathway associating with circulating concentrations of vitamin D metabolites and non-skeletal health outcomes: Review of genetic association studies

Pages 18-29
David A. Jolliffe, Robert T. Walton, Christopher J. Griffiths, Adrian R. Martineau
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Highlights

• We review a total of 120 genetic association studies on vitamin D pathway SNP.
• Significant associations reported for a total of 55 SNP in 11 vitamin D pathway genes.
• 44 studies report 114 findings of SNP which determine metabolite concentration.
• 76 studies report 105 findings of SNP which affect non-skeletal health outcomes.
• Infectious and auto-immune related disease were most frequent to associate with SNP.
• Limited overlap of SNP predicting vitamin D status and SNP affecting disease outcomes.

Environmental and genetic determinants of vitamin D status among older adults in London, UK

Pages 30-35
David A. Jolliffe, Yasmeen Hanifa, Karolina D. Witt, Timothy R. Venton, Marion Rowe, Peter M. Timms, Elina Hypponen, Robert T. Walton, Christopher J. Griffiths, Adrian R. Martineau
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Highlights

• We report that 65% of a cohort of older adults living in sheltered accommodation in London, UK, were vitamin D deficient (serum 25-hydroxyvitamin D concentrations <50 nmol/L).
• Sampling in winter/spring, non-white ethnic origin and lack of vitamin D supplement use were independently associated with lower vitamin D status.
• None of a panel of 15 single nucleotide polymorphisms in DBP, DHCR7, CYP2R1, CYP27B1, CYP24A1 or VDR associated with serum 25-hydroxyvitamin D concentrations in this population.
• Vigorous efforts should be made to improve uptake of vitamin D supplements among older adults in the UK in order to protect them against vitamin D deficiency.

Treatment of vitamin D deficiency in cystic fibrosis

Pages 36-39
Supavit Chesdachai, Vin Tangpricha
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Highlights

• Vitamin D insufficiency is common in patients with cystic fibrosis.
• Vitamin D status is important for bone health, lung and immune function in patients with cystic fibrosis.
• Treatment of vitamin D insufficiency in patients with cystic fibrosis requires high dose cholecalciferol or ergocalciferol.
• Randomized, double blind, placebo controlled, large scale clinical trials are underway to evaluate the role of vitamin D as an adjunctive treatment in patients with cystic fibrosis.

Synthesis, metabolism, and biological activity of 2-3-(tetrazolyl)propyl-1α,25-dihydroxy-19-norvitamin D3

Pages 40-44
Masashi Takano, Kaori Yasuda, Erika Higuchi, Eri Tohyama, Akiko Takeuchi, Toshiyuki Sakaki, Atsushi Kittaka
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Convergent synthesis of double point modified analogs of 1α,25-dihydroxyvitamin D2 for biological evaluation

Pages 45-49
Sharmin Nadkarni, Michal Chodynski, Krzysztof Krajewski, Piotr Cmoch, Ewa Marcinkowska, Geoffrey Brown, Andrzej Kutner
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Synthesis and evaluation of geometric analogs of 1α,25-dihydroxyvitamin D2 as potential therapeutics

Pages 50-55
Narasimha Rao Bolla, Aoife Corcoran, Kaori Yasuda, Michal Chodynski, Krzysztof Krajewski, Piotr Cmoch, Ewa Marcinkowska, Geoffrey Brown, Toshiyuki Sakaki, Andrzej Kutner
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Stereoselective synthesis of 1β,25-Dihydroxyvitamin D3 and its 26,27-hexadeuterated derivative

Pages 56-58
Julian Loureiro, Miguel A. Maestro, Antonio Mourino, Rita Sigueiro
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Novel analogs of 1,25-dihydroxyvitamin D2 combined with a plant polyphenol as highly efficient inducers of differentiation in human acute myeloid leukemia cells

Pages 59-65
Matan Nachliely, Ehud Sharony, Andrzej Kutner, Michael Danilenko
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Highlights

• Novel vitamin D2 analogs are highly efficient differentiation inducers.
• Carnosic acid enhances prodifferentiation effects of vitamin D2 analogs.
• Vitamin D2 analogs are less effective than 1,25(OH)2D3 in activating VDRE.

Biological evaluation of new vitamin D2 analogues (free PDF)

Pages 66-71
Aoife Corcoran, Maria A. Bermudez, Samuel Seoane, Roman Perez-Fernandez, Malgorzata Krupa, Anita Pietraszek, Michal Chodynski, Andrzej Kutner, Geoffrey. Brown, Ewa Marcinkowska
PDF (1108 K)
Highlights

• We examined activity profiles of double-point modified analogues of vitamin D2.
• The analogues were less toxic in vivo than 1,25D.
• Pro-differentiating activities of analogues were stronger than that of 1,25D.
• The analogues upregulated expression of CYP24A1 and CD14 stronger than 1,25D.
• Neither calcemic, nor pro-differentiation effects were correlated to VDR binding.

Enhancement of arabinocytosine (AraC) toxicity to AML cells by a differentiation agent combination

Pages 72-78
Xuening Wang, Jonathan S. Harrison, George P. Studzinski
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Eldecalcitol (ED-71), an analog of 1α,25-dihydroxyvitamin D3 as a potential anti-cancer agent for oral squamous cell carcinomas

Pages 79-84
T. Shintani, S.N.Z. Rosli, F. Takatsu, Y.F. Choon, Y. Hayashido, S. Toratani, E. Usui, T. Okamoto
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Highlights

• ED-71, an analog of 1,25(OH)2D3, was able to inhibit the growth of cancer cell lines in serum-free culture.
• The anti-tumor activity of ED-71 was much higher than that of 1,25(OH)2D3 in both UE and NA cells.
• ED-71 significantly induced expression of CYP24A1 in cancer cell lines and in human gingival fibroblasts.
• ED-71 induced CYP24A1 expression in oral cancer cell lines in a dose-dependent manner.
• ED-71 inhibited growth of A431-derived tumor in athymic mice.

WCRF-AICR continuous update project: Systematic literature review of prospective studies on circulating 25-hydroxyvitamin D and kidney cancer risk

Pages 85-89
Andrea L. Darling, Leila Abar, Teresa Norat
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Highlights

• A systematic review of studies assessing 25(OH)D status and kidney cancer risk.
• Four cohort or nested case-control studies and one Pooling Project were included.
• Subject populations and smoking prevalence may explain between cohort differences.
• An association between low 25(OH)D and kidney cancer risk could not be ruled out.

Identification of vitamin D3 target genes in human breast cancer tissue

Pages 90-97
Lei Sheng, Paul H. Anderson, Andrew G. Turner, Kathleen I. Pishas, Deepak J. Dhatrak, Peter G. Gill, Howard A. Morris, David F. Callen
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Highlights

• 1,25D-mediated target genes and pathways were identified in human breast explants.
• Inhibition of CYP24A1 activity may enhance the antitumor effect of 1,25D.
• Up-regulation of three 1,25D targets predicts prolonged relapse-free survival.
• Our data agree with evidence that high 25D levels improve breast cancer outcome.

Novel vitamin D analogues; cytotoxic and anti-proliferative activity against a diffuse large B-cell lymphoma cell line and B-cells from healthy donors

Pages 98-105
Pawel Kozielewicz, Gillian Grafton, Andrzej Kutner, S. John Curnow, John Gordon, Nicholas M. Barnes
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Highlights

• We have examined the action of 1,25D3 and vitamin D analogues (VDAs) on malignant and healthy B cells.
• 1,25D3 and VDAs displayed moderate cytotoxic and pro-apoptotic actions upon DLBCL cells.
• 1,25D3 and VDAs displayed concentration and time-dependent anti-proliferative actions upon stimulated B-cells from healthy donors.
• VDAs may offer therapeutic potential for the treatment of DLBCL or conditions benefitted by B-cell depletion.

Vitamin D levels and breast cancer characteristics: Findings in patients from Saudi Arabia

Pages 106-109
Omalkhair Abulkhair, Ahmed Saadeddin, Olaa Makram, Ahmed Gasmelseed, Tabrez Pasha, Hussam Shehata, Hana M. Fakhoury
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Highlights

• There is a paucity of research on vitamin D and breast cancer in Saudi Arabia.
• We are the first to study vitamin D and breast cancer characteristics in Saudi Arabia and even in the Middle East.
• In a population where the prevalence of vitamin D deficiency 25 (OH) D level below 50 nmol/L ranges between 68% and 85%, we found that 71% of breast cancer patients were vitamin D deficient.
• Triple negative disease was significantly associated with vitamin D level below 25 nmol/L.

Vitamin D metabolite profiling using liquid chromatography–tandem mass spectrometry (LC–MS/MS)

Pages 110-114
Glenville Jones, Martin Kaufmann
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Highlights

• The 50 year history of vitamin D assays has seen a number of different technologies used from competitive-protein binding assays to radioimmunoassays to high pressure liquid chromatography-based assays.
• Liquid chromatography–tandem mass spectrometry (LC–MS/MS) is emerging as the method of choice for vitamin D metabolite analysis in both research and clinical applications.
• LC–MS/MS offers improved levels of accuracy and reproducibility over traditional methods while also providing the ability to measure multiple vitamin D metabolites simultaneously.
• Evidence is presented that shows LC–MS/MS is superior for measuring 25-OH-D in testing schemes; evidence is presented that the technique can be used successfully on individual mouse samples; evidence is presented to show vitamin D metabolite profiles differ between species.

Developing vitamin D dietary guidelines and the lack of 25-hydroxyvitamin D assay standardization: The ever-present past

Pages 115-119
C.T. Sempos, R.A. Durazo-Arvizu, N. Binkley, J. Jones, J.M. Merkel, G.D. Carter
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Highlights

• 25(OH)D used to define states of vitamin D status, e.g., deficient, and sufficient.
• Unstandardized 25(OH)D data is the fundamental limitation thwarting that effort.
• Vitamin D Standardization Program (VDSP) was developed to correct this problem.
• In all future research, collect only 25(OH)D data standardized using VDSP methods.
• VDSP has developed methodology for standardizing stored serum samples too.
• Standardization of past research key to defining vitamin D status states is essential.

A novel, fully-automated, chemiluminescent assay for the detection of 1,25-dihydroxyvitamin D in biological samples (free PDF)

Pages 120-126
Andre Valcour, Claudia Zierold, Angela L. Podgorski, Gregory T. Olson, John V. Wall, Hector F. DeLuca, Fabrizio Bonelli
Abstract PDF (1303 K)

Determination of human reference values for serum total 1,25-dihydroxyvitamin D using an extensively validated 2D ID-UPLC–MS/MS method

Pages 127-133
Niek F. Dirks, Frans Martens, Dirk Vanderschueren, Jaak Billen, Steven Pauwels, Mariette T. Ackermans, Erik Endert, Martin den Heijer, Marinus A. Blankenstein, Annemieke C. Heijboer
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Highlights

• We have developed a LC–MS/MS method able to measure both 1,25dihydroxyvitamin D3 and D2.
• The method was extensively validated with regard to sensitivity, specificity and robustness and correlated well with another published LC–MS/MS method.
• Human reference values for 1,25-dihydroxyvitamin D3 and D2 were 59–159 pmol/L and <17 pmol/L, respectively.
• Premenopausal women taking oral contraceptive pills show significantly higher 1,25-dihydroxyvitamin D3 values compared to postmenopausal women.

25-Hydroxyvitamin D assays: Potential interference from other circulating vitamin D metabolites

Pages 134-138
G.D. Carter, J.C. Jones, J. Shannon, E.L. Williams, G. Jones, M. Kaufmann, C. Sempos
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Highlights

• Both 3-epi-25-OHD3 and 24,25-dihydroxyvitamin D (24,25(OH)2D) show a strong correlation with 25-OHD3.
• 3-epi-25-hydroxyvitamin D(3-epi-25-OHD) does not cross react in immunoassays for 25-hydroxyvitamin D (25-OHD).
• Some HPLC/UV and LC–MS/MS methods may not resolve 3-epi-25-OHD3 from 25-OHD3.
• Cross reaction of 24,25(OH)2D in 25-OHD immunoassays may contribute to the positive bias of some assays, particularly at high 25-OHD concentrations.
• The use of exogenous 24,25(OH)2D gives misleading results in recovery experiments.

Screening for nutritional rickets in a community

Pages 139-144
John M. Pettifor
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Highlights

• The global prevalence of nutritional rickets appears to be rising.
• Global efforts are required to address this readily preventable condition.
• Screening tools to identify possible rickets need to be developed.
• Active rickets can only be confirmed by the use of radiographs

Prevention and treatment of nutritional rickets

Pages 145-147
N.J Shaw
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Highlights

• Nutritional rickets is due to a variable combination of vitamin D deficiency and dietary calcium deficiency in growing children.
• There is evidence of an increasing incidence of nutritional rickets in several developed countries.
• Prevention of nutritional rickets can be achieved by ensuring that pregnant women and infants receive regular supplements of vitamin D.
• Treatment of nutritional rickets requires a combination of oral vitamin D and adequate dietary calcium intake.
• Vitamin D supplementation of infants should be regarded as having a similar level of importance as immunisation.

Vitamin D supplementation during pregnancy: Updated meta-analysis on maternal outcomes (free PDF)

Pages 148-155
Cristina Palacios, Luz Maria De-Regil, Lia K. Lombardo, Juan Pablo Pena-Rosas
PDF (601 K)
Highlights

• Supplementing pregnant women with vitamin D significantly increases 25(OH)D at term but results were inconsistent.
• It is unknown at this point what is the clinical significance of this finding but there is some indication that vitamin D supplementation, with or without calcium, may reduce the risk of pre-eclampsia.
• More studies are needed to confirm these results and to determine the effects of vitamin D supplementation on the risk of other maternal outcomes, such as gestational diabetes, impaired glucose tolerance, caesarean section, gestational hypertension, other adverse conditions and maternal death.

Note By Henry Lahore @ VitaminDWiki
Study chose to ignore the trials which used more than one dose of vitamin D (so as to account for obesity, etc)
Study ignored the dose levels in the trials which it did accept - treating doses of 200 IU the same as 300,000 IU (loading)
 Download the PDF from VitaminDWiki

Prevention and consequences of vitamin D deficiency in pregnant and lactating women and children: A symposium to prioritise vitamin D on the global agenda

Pages 156-160
Inez Schoenmakers, John M. Pettifor, Juan-Pablo Pena-Rosas, Christel Lamberg-Allardt, Nick Shaw, Kerry S. Jones, Paul Lips, Francis H. Glorieux, Roger Bouillon
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Highlights

• World Health Organization and the Vitamin D Workshop organised a joint symposium.
• Vitamin D deficiency is common in women of child bearing age.
• Causes of nutritional rickets in infants and children include vitamin D and calcium deficiency.
• Diagnostic criteria for nutritional rickets in infants and children were identified.
• Strategies to prioritise research needs and implement nutritional policies were discussed.

Prevalence and predictors of vitamin D deficiency based on maternal mid-gestation and neonatal cord bloods: The Generation R Study

Pages 161-167
Anna A.E. Vinkhuyzen, Darryl W. Eyles, Thomas H. Burne, Laura M.E. Blanken, Claudia J. Kruithof, Frank Verhulst, Vincent W. Jaddoe, Henning Tiemeier, John J. McGrath
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Highlights

• Vitamin D deficiency (defined as less than 25 mol/L) was identified in 26% of pregnant women at midgestation (?20 weeks) in the mothers of the Dutch Generation R Study.
• Vitamin D deficiency was found in 46% of the offspring when assessed in cord blood.
• Based on both midgestation and cord blood sample, 21% of the mother-infant pairs had persistent vitamin D deficiency.
• Persistent vitamin D deficiency in mother-infant pairs was strongly associated with non-European ancestry and spring birth.

Relative importance of summer sun exposure, vitamin D intake, and genes to vitamin D status in Dutch older adults: The B-PROOF study

Pages 168-176
Elske M. Brouwer-Brolsma, Anouk M.M. Vaes, Nikita L. van der Zwaluw, Janneke P. van Wijngaarden, Karin M.A. Swart, Annelies C. Ham, Suzanne C. van Dijk, Anke W. Enneman, Evelien Sohl, Natasja M. van Schoor, Nathalie van der Velde, Andre G. Uitterlinden, Paul Lips, Edith J.M. Feskens, Rosalie A.M. Dhonukshe-Rutten, Lisette C.P.G.M. de Groot
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Highlights

• 45% of this Dutch older population had serum 25(OH)D concentrations <50 nmol/L.
• Only 6% of the participants with a vitamin D deficiency used vitamin D supplements.
• Sun habits are still an important determinant of 25(OH)D status in older adults.
• 35% of the variation in serum 25(OH)D was explained by the determinants under study.

Preferred natural food of breeding Kakapo is a high value source of calcium and vitamin D

Pages 177-179
P.R. von Hurst, R.J. Moorhouse, D. Raubenheimer
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Highlights

• The kakapo is a highly endangered ground-dwelling parrot native to New Zealand.
• The primary food source during breeding is the fruit of a tall podocarp, the Rimu tree.
• Rimu fruit were found to be extremely high in both calcium and vitamin D.
• High concentrations of both D2 and D3 isoforms were identified in rimu fruit.

The vitamin D-dependent transcriptome of human monocytes

Pages 180-187
Antonio Neme, Veijo Nurminen, Sabine Seuter, Carsten Carlberg
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Highlights

• The transcriptome of 1,25(OH)2D3-stimulated THP-1 cells (determined by RNA-seq) is reviewed.
• Primary and secondary vitamin D target genes being up- and down-regulated were related to changes in the epigenome.
• Epigenomic and transcriptomic responses of THP-1 cells to 1,25(OH)2D3 represent a master example of the impact of vitamin D on human physiology.

Dietary nitrogen and calcium modulate bone metabolism in young goats

Pages 188-193
Kristin Elfers, Annette Liesegang, Mirja R. Wilkens, Gerhard Breves, Alexandra S. Muscher-Banse
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Highlights

• A nitrogen (N) reduced diet modulated bone metabolism in young goats.
• N reduced fed goats showed decreased bone mineral density and bone mineral content.
• Increased bone resorption was not mediated by PTH in a classical way.
• Decreased plasma IGF1 is a potential mediator of renal calcitriol synthesis.

Vitamin D status in the Chinese population in the Netherlands: The DRAGON study

Pages 194-198
Ping Wai Man, Wenzhi Lin, Irene M. van der Meer, Annemieke C. Heijboer, Ron Wolterbeek, Mattijs E. Numans, Barend J.C. Middelkoop, Paul Lips
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Highlights

• No data were available on the vitamin D status of the Chinese in the Netherlands.
• More than half of the Chinese in the Netherlands had 25(OH)D levels < 50 nmol/L.
• Use of vitamin D supplements contributed most to an adequate vitamin D status.

Oral intake of 7-dehydrocholesterol increases vitamin D3 concentrations in the liver and kidney

Pages 199-204
Julia Kuhn, Frank Hirche, Stefanie Geissler, Gabriele I. Stangl
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Highlights

• The effect of dietary 7-dehydrocholesterol on vitamin D metabolism was investigated.
• Oral intake of 7-dehydrocholesterol induced a dose-responsive accumulation of vitamin D3 in the liver and kidney.
• 25-hydroxyvitamin D3 in the serum, liver and kidney was not affected by dietary 7-dehydrocholesterol.

Vitamin D3 and calcidiol are not equipotent

Pages 205-208
Cristina Navarro-Valverde, Manuel Sosa-Henriquez, Maria Rosa Alhambra-Exposito, Jose Manuel Quesada-Gomez
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Highlights

• It is recommended, as endorsed by international clinical guides, to use Vitamin D3 to treat vitamin D deficiency.
• In several parts of the world, the use of calcidiol at the same dose than Vitamin D3 is an extended prescription.
• Our data confirm the available evidence stating that they are not equipotent. This may lead to over-dosage.
• Calcifediol is faster and 3–6 times more powerful to obtain adequate serum levels of 25(OH)D in the medium-long term.
• This circumstance must be assessed and included in the therapeutic prescription guides of Osteoporosis.

Vitamin D deficiency: A single centre analysis of patients from 136 countries

Pages 209-213
Afrozul Haq, Jitka Svobodova, Samira Imran, Charles Stanford, Mohammed S. Razzaque
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The frequency distribution of 25(OH)D concentrations are shown as a skewed distribution, and most of the values are less than 50 nmol/L. Skewness right distribution of 25(OH)D concentration of patients with median of 42.25 nmol/L. For variables normality was tested by Anderson-Darling test. The null hypothesis was rejected on significance level of alpha 0.05, that’s why non-parametric test was used. Genders in result value of 25(OH)D were tested by two-tailed Mann-Whitney test. Gender affected the result value of 25(OH)D, with a statistically significant difference between male and female (Sig. = 0.000).

Prevalence and treatment of hypovitaminosis D in the haemodialysis population of Coventry

Pages 214-217
Sharon A. Huish, Simon Fletcher, Janet A. Dunn, Martin Hewison, Rosemary Bland
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Highlights

• Hypovitaminosis D is common in the haemodialysis (HD) population in Coventry.
• There is an absence of clear supplementation guidelines for this population.
• We have developed a local guideline for vitamin D supplementation in HD patients.

Prediction of winter vitamin D status and requirements in the UK population based on 25(OH) vitamin D half-life and dietary intake data (free PDF)

Pages 218-222
Inez Schoenmakers, Petros Gousias, Kerry S. Jones, Ann Prentice
PDF (505 K)
Highlights

• We developed a mathematical model to predict longitudinally the population mean plasma 25(OH)D concentration during winter.
• Predicted values closely matched plasma 25(OH)D concentrations as measured in the UK population.
• Vitamin D intake required to maintain the population mean plasma 25(OH)D concentration at a predetermined concentration can be predicted from this model.

Vitamin D production in UK Caucasian and South Asian women following UVR exposure

Pages 223-229
Ohood A. Hakim, Kathryn Hart, Patrick McCabe, Jacqueline Berry, Robertson Francesca, Lesley E. Rhodes, Nicholas Spyrou, Abdulrahman Alfuraih, Susan Lanham-New
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Highlights

• We investigated ethnic differences in vitamin D production in UK postmenopausal women in response to a defined and controlled UVR exposure.
• All women significantly increased their 25(OH)D. Initial vitamin D level affects the amount of UVB needed to reach a set 25(OH)D concentration.
• The greater response to UVR exposure found amongst the South Asian women reflects their lower baseline level of 25(OH)D.
• No ethnic differences in 25(OH)D synthesis were observed; baseline differences in 25(OH)D and sample size are potential confounders.
• To confirm no effect of ethnicity or skin tone on 25(OH)D synthesis, a larger sample including other groups with highly pigmented skin is required.

Prevalence of Vitamin D deficiency in the North-West region of Russia: A cross-sectional study

Pages 230-234
T. Karonova, A. Andreeva, I. Nikitina, O. Belyaeva, E. Mokhova, O. Galkina, E. Vasilyeva, E. Grineva
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Highlights

• We performed a cross-sectional study in North-West region of Russia to assess vitamin D status.
• Beside laboratory data we also assessed anthropometric parameters and nutritional questionnaire.
• High prevalence of vitamin D deficiency and insufficiency was observed regardless of age and gender.
• Obese subjects had lower serum 25(OH)D level than subjects with normal body mass.

Sun exposure, skin color and vitamin D status in Arab children and adults

Pages 235-238
Nasser M. Al-Daghri, Yousef Al-Saleh, Nasiruddin Khan, Shaun Sabico, Naji Aljohani, Hanan Alfawaz, Maha Alsulaimani, Abdulaziz M. Al-Othman, Majed S. Alokail
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Highlights

• Vitamin D deficiency is common in both Arab children and adults.
• 25-(OH)D concentrations were significantly lower in dark-skinned Arab boys than fair-skinned Arab boys having the same age and same duration of sun exposure of less than 20 min.
• There is no association between skin color and 25(OH)D levels in Arab girls and adult women.

The phenotype and function of murine bone marrow-derived dendritic cells is not affected by the absence of VDR or its ability to bind 1α,25-dihydroxyvitamin D3

Pages 239-245
An-Sofie Vanherwegen, Gabriela Bomfim Ferreira, Elien Smeets, Yoko Yamamoto, Shigeaki Kato, Lut Overbergh, Conny Gysemans, Chantal Mathieu
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Highlights

• A truncated VDR does not interfere with myeloid dendritic cell phenotype or function.
• Rendering VDR unable to bind ligand does not alter the phenotype of bone marrow-derived myeloid dendritic cells.
• An unliganded VDR does not affect the T cell stimulatory capacity of bone marrow-derived myeloid dendritic cells.

Species-specific regulation of innate immunity by vitamin D signaling

Pages 246-253
Vassil Dimitrov, John H. White
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Highlights

• The hormonal form of vitamin D, 1,25-dihydroxy vitamin D, is a key regulator of innate immunity.
• In humans, the activated vitamin D receptor (VDR) is a direct regulator of transcription of genes encoding antimicrobial peptides, pattern recognition receptors, and innate immune cytokines.
• While regulation of VDR target genes implicated in innate immunity in humans appears to be widely conserved in primates, the regulation is not conserved in mice.
• Given the increasing evidence that vitamin D signaling can regulate innate immunity in mice, the combined data indicate that the mechanisms of innate immune regulation by vitamin D are species-specific.

A low vitamin D status at diagnosis is associated with an early conversion to secondary progressive multiple sclerosis

Pages 254-257
Anne-Hilde Muris, Linda Rolf, Kelly Broen, Raymond Hupperts, Jan Damoiseaux, Joost Smolders
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Highlights

• Vitamin D status is lower in SPMS patients than in RRMS patients.
• Vitamin D status in RRMS does not predict a 3-year risk of conversion to SPMS.
• SPMS patients with a short RRMS duration also have low diagnostic 25(OH)D levels.
• A low vitamin D status at diagnosis may be associated with early conversion to SPMS.

Vitamin D and its receptor: molecular mechanisms

Selective regulation of Mmp13 by 1,25(OH)2D3, PTH, and Osterix through distal enhancers
Pages 258-264
Mark B. Meyer, Nancy A. Benkusky, Melda Onal, J. Wesley Pike
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Highlights

• Mmp13 is regulated by coordination of three distinct distal enhancers at ?10, ?20, and ?30 kb.
• PTH utilizes the promoter proximal region for activation of Mmp13.
• Osterix binds to and regulates Mmp13 through the ?30 kb, ?20 kb and promoter proximal regions.
• CRISPR deletion of the ?10 kb enhancer in mice leads to a loss of Mmp13 induction by 1,25(OH)2D3.

The vitamin D receptor functions as a transcription regulator in the absence of 1,25-dihydroxyvitamin D3

Pages 265-270
Seong Min Lee, J. Wesley Pike
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Highlights

• The VDR de-represses PTH secretion in the absence of 1,25(OH)2D3.
• The VDR is involved in bone metabolism in the absence of 1,25(OH)2D3.
• The VDR modulates expression of its target genes in the absence of 1,25(OH)2D3.

Influence of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 on expression of P-glycoprotein and cytochrome P450 3A in sheep

Pages 271-276
M.R. Wilkens, L.M. Mate, N. Schnepel, S. Klinger, A.S. Muscher-Banse, M. Ballent, G. Virkel, A.L. Lifschitz
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Highlights

• In contrast to rodents no induction of renal P-glycoprotein by 1,25-dihydroxyvitamin D in sheep.
• Reduction of ruminal, jejunal and hepatic P-glycoprotein expression by 25-hydroxyvitamin D.
• Induction of cytochrome P450 3A only with 1,25-dihydroxyvitamin D treatment.
• Drug–drug interactions caused by vitamin D metabolites cannot be excluded.

Analysis of SOST expression using large minigenes reveals the MEF2C binding site in the evolutionarily conserved region (ECR5) enhancer mediates forskolin, but not 1,25-dihydroxyvitamin D3 or TGFβ1 responsiveness

Pages 277-280
Hillary C. St. John, Sydney J. Hansen, J. Wesley Pike
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Highlights

• We examined full length and four deletion/mutation SOST BAC clone reporters.
• Response to 1,25(OH)2D3, OSM, Dex, TGFβ1, BMP-2, and forskolin was evaluated.
• ECR5 deletion and ECR5/MEF2 mutation eliminated the forskolin response.
• ECR5 deletion and ECR5/MEF2 mutation did not eliminate the TGBβ1 response.
• 1,25(OH)2D3, OSM, Dex, TGFβ1, and BMP-2 effects were maintained in all reporters.

Tie-2Cre mediated deletion of the vitamin D receptor gene leads to improved skeletal muscle insulin sensitivity and glucose tolerance

Pages 281-286
Wei Ni, Denis J. Glenn, David G. Gardner
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Highlights

• We found improved glucose disposal in Tie-2Cre-mediated endothelial/macrophage VDR KO mice.
• Improvement in glucose disposal is due to increased insulin sensitivity in skeletal muscle not in liver.
• Reduced insulin secretion is likely secondary to improved insulin sensitivity.

Vitamin D metabolism and regulation in pediatric MSCs

Pages 287-291
B. Ruggiero, B.L. Padwa, K.M. Christoph, S. Zhou, J. Glowacki
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Highlights

• Pediatric MSCs showed constitutive expression of CYP27B1 and other vitamin D-related genes.
• There was greater expression of vitamin D-related genes in MSCs from boys than girls.
• Those gender differences had not been seen in MSCs from adults.
• Vitamin D-related genes were upregulated by in vitro treatment with 25(OH)D3 and with 17β-estradiol.
• Expression and regulation of vitamin D-related genes in pediatric hMSCs reinforces an autocrine/paracrine role for vitamin D in hMSCs.

Amplification of lipotoxic cardiomyopathy in the VDR gene knockout mouse

Pages 292-298
Denis J. Glenn, Michelle C. Cardema, David G. Gardner
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Highlights

• Deletion of the vitamin D receptor results in increased hypertrophy and a marked increase in cardiac fibrosis in the setting of cardiac steatosis.
• The increase in fibrosis may result from an increase in TGFβ expression.

Adipose-specific Vdr deletion alters body fat and enhances mammary epithelial density

Pages 299-308
Donald G. Matthews, Joseph D’Angelo, Jordan Drelich, JoEllen Welsh
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Highlights

• Adipose-specific Vdr deletion enhanced weight gain in response to high fat diet.
• Effects of adipose-specific Vdr deletion were gender-specific.
• Ucp1 expression was increased in visceral fat of adipose specific Vdr deleted mice.
• Mammary gland ductal branching was enhanced by adipose-specific Vdr deletion.

Effect of a transcriptional inactive or absent vitamin D receptor on beta-cell function and glucose homeostasis in mice

Pages 309-317
Roman Vangoitsenhoven, Heidi Wolden-Kirk, Katleen Lemaire, Annemieke Verstuyf, Lieve Verlinden, Yoko Yamamoto, Shigeaki Kato, Leentje Van Lommel, Frans Schuit, Bart Van der Schueren, Chantal Mathieu, Lut Overbergh
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Highlights

• Mice with a mutation in the transcriptional activation site of Vdr (VDRΔAF2) were generated.
• VDRΔAF2 mice have normal fur phenotype but lower body weight than wild type (WT) mice.
• In vivo glucose tolerance is similar between adult normocalcemic WT, VDR?/? and VDRΔAF2 mice.
• Ex vivo glucose stimulated insulin secretion is similar in islets from WT, VDR?/? and VDRΔAF2 mice.
• Phosphodiesterase 10a mRNA is upregulated in VDR?/? and VDRΔAF2 islets, as compared to WT mice

The Vitamin D Assessment (ViDA) Study: design of a randomized controlled trial of vitamin D supplementation for the prevention of cardiovascular disease, acute respiratory infection, falls and non-vertebral fractures

Pages 318-325
Robert Scragg, Debbie Waayer, Alistair W. Stewart, Carlene M.M. Lawes, Les Toop, Judy Murphy, Kay-Tee Khaw, Carlos A. Camargo Jr.
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Highlights

• Observational studies show vitamin D status inversely associated with disease risk.
• Vitamin D supplementation trials required to confirm if associations are causal.
• Vitamin D assessment (ViDA) Study recruited 5110 participants aged 50–84 years.
• Participants took monthly oral 100,000 IU vitamin D3 (or placebo) capsules.
• Follow-up completed July 2015 and primary results available in 2016.

Vitamin D—Cellular Ca2+ link to obesity and diabetes

Pages 326-330
Igor N. Sergeev
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Highlights

• The hormone 1,25(OH)2D3 targets Ca2+ signaling pathways in adipocytes and pancreatic β-cells.
• 1,25(OH)2D3 triggers apoptosis in mature adipocytes via induction of the apoptotic Ca2+ signal—a sustained increase in concentration of intracellular Ca2+, followed by activation of Ca2+-dependent apoptotic proteases, calpain and caspase-12.
• 1,25(OH)2D3 induces synchronous Ca2+ oscillations in pancreatic β-cells, which pattern oscillatory insulin release from these cells.
• The role of 1,25(OH)2D3 in Ca2+-mediated apoptosis in adipocytes and insulin secretion from pancreatic β-cells can support the recommendation to maintain optimal vitamin D status as a plausible approach for preventing type 2 diabetes and decreasing adiposity.

Skeletal characterization of an osteoblast-specific vitamin D receptor transgenic (ObVDR-B6) mouse model

Pages 331-336
Rahma Triliana, Nga N. Lam, Rebecca K. Sawyer, Gerald J. Atkins, Howard A. Morris, Paul H. Anderson
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Highlights

• VDR over-expression in osteoblasts of C57Bl6/J mice (ObVDR-B6) increases bone volume and strength.
• ObVDR- B6 mice exhibit increased metaphyseal MAR and reduced bone resorption.
• Changes in ObVDR-B6 bone volume is dependent on skeletal site and gender.

Forkhead box O transcription factors in chondrocytes regulate endochondral bone formation

Pages 337-343
G. Eelen, L. Verlinden, C. Maes, I. Beullens, C. Gysemans, J.-H. Paik, R.A. DePinho, R. Bouillon, G. Carmeliet, A. Verstuyf
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Highlights

• Function of Forkhead Box O (FoxO) transcription factors in growth plate chondrocytes during bone formation is largely unknown.
• Collagen2-Cre;FoxO1lox/lox;FoxO3alox/lox;FoxO4lox/lox mice display growth plate abnormalities.
• Loss of FoxO expression significantly increases the length of the hypertrophic zone of the growth plate.

Long-term vitamin D deficiency in older adult C57BL/6 mice does not affect bone structure, remodeling and mineralization
Pages 344-352
K. van der Meijden, J. Buskermolen, H.W. van Essen, T. Schuurman, W.T Steegenga, E.M. Brouwer-Brolsma, G.E.J. Langenbach, L.J. van Ruijven, M. den Heijer, P. Lips, N. Bravenboer
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Evidence for altered osteoclastogenesis in splenocyte cultures from Cyp27b1 knockout mice

Pages 353-360
Daniel C. Reinke, Masakazu Kogawa, Kate R. Barratt, Howard A. Morris, Paul H. Anderson, Gerald J. Atkins
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Highlights

• Osteoclast differentiation in mice with global deletion of Cyp27b1 (Cyp27b1 KO) was studied.
• Cyp27b1 KO splenocytes gave rise to fewer osteoclasts in response to recombinant RANKL/M-CSF.
• Cyp27b1 KO derived osteoclasts had enhanced resorptive capacity.

Sex-related differences in the skeletal phenotype of aged vitamin D receptor global knockout mice

Pages 361-368
Jackson W. Ryan, Yolandi Starczak, Helen Tsangari, Rebecca K. Sawyer, Rachel A. Davey, Gerald J. Atkins, Howard A. Morris, Paul H. Anderson
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Highlights

• Adult male Vdr?/? mice exhibit bone loss despite being fed the rescue diet.
• Female Vdr?/? mice exhibit vertebral bone loss and yet increased femoral bone volume.
• Rescue diet fed to Vdr?/? mice does not normalise bone volume.
• In addition to the intestine, VDR may be required to directly regulate bone homeostasis.

Early response of the human SOST gene to stimulation by 1α,25-dihydroxyvitamin D3

Pages 369-373
Asiri R. Wijenayaka, Matthew Prideaux, Dongqing Yang, Howard A. Morris, David M. Findlay, Paul H. Anderson, Gerald J. Atkins
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Highlights

• We examined SOST mRNA and sclerostin protein levels in differentiated SaOS2 cultures.
• SOST expression was induced by 1,25D after 3 h at the mRNA level.
• Sclerostin protein levels increased by 12 h in response to 1,25D.

Comparison of the biological effects of exogenous and endogenous 1,25-dihydroxyvitamin D3 on the mature osteoblast cell line MLO-A5

Pages 374-378
Dongqing Yang, Paul H. Anderson, Andrew G. Turner, Howard A. Morris, Gerald J. Atkins
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Highlights

• Both endogenous and exogenous 1,25D display anabolic effects on MLO-A5 cells.
• Endogenous and exogenous 1,25D display distinct pharmacodynamics for induction of Cyp24a1 mRNA.
• mRNA of some genes are induced by lower endogenous 1,25D levels compared to exogenous 1,25D

Vitamin D and calcium regulation of epidermal wound healing

Pages 379-385
Yuko Oda, Chia-Ling Tu, Alicia Menendez, Thai Nguyen, Daniel D. Bikle
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Highlights

• Deleting the vitamin D receptor (VDR) from keratinocytes (epiVDRKO) in combination with a low calcium diet delays skin wound healing.
• The delay in wound healing is accompanied by a reduction in β-catenin signaling.
• Proliferation and migration of the keratinocytes at the edge of the wound are reduced in the epiVDRKO as is the expression of axin 2, indicating the role of β-catenin signaling in the epidermal response to wounding and its dependence on the VDR.

Vitamin D, PTH and the risk of overall and disease-specific mortality: Results of the Longitudinal Aging Study Amsterdam

Pages 386-394
Jamila El Hilali, Elisa J. de Koning, Adriana J. van Ballegooijen, Paul Lips, Evelien Sohl, Harm W.J. van Marwijk, Marjolein Visser, Natasja M. van Schoor
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Highlights

• Low 25(OH)D levels were associated with a higher risk of overall mortality.
• Men with high PTH levels had a higher risk of overall and cardiovascular mortality.
• No associations of 25(OH)D or PTH with cancer mortality were observed.
• The association of 25(OH)D with overall mortality was (partly) mediated by PTH.
• Serum 25(OH)D and PTH should be regarded as important health markers.