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      Consensus statement from 2 nd International Conference on Controversies in Vitamin D

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          Abstract

          The 2 nd International Conference on Controversies in Vitamin D was held in Monteriggioni (Siena), Italy, September 11-14, 2018. The aim of this meeting was to address ongoing controversies and timely topics in vitamin D research, to review available data related to these topics and controversies, to promote discussion to help resolve lingering issues and ultimately to suggest a research agenda to clarify areas of uncertainty. Several issues from the first conference, held in 2017, were revisited, such as assays used to determine serum 25-hydroxyvitamin D [25(OH)D] concentration, which remains a critical and controversial issue for defining vitamin D status. Definitions of vitamin D nutritional status (i.e. sufficiency, insufficiency and deficiency) were also revisited. New areas were reviewed, including vitamin D threshold values and how they should be defined in the context of specific diseases, sources of vitamin D and risk factors associated with vitamin D deficiency. Non-skeletal aspects related to vitamin D were also discussed, including the reproductive system, neurology, chronic kidney disease and falls. The therapeutic role of vitamin D and findings from recent clinical trials were also addressed. The topics were considered by 3 focus groups and divided into three main areas: 1) “Laboratory”: assays and threshold values to define vitamin D status; 2) “Clinical”: sources of vitamin D and risk factors and role of vitamin D in non-skeletal disease and 3) “Therapeutics”: controversial issues on observational studies and recent randomized controlled trials. In this report, we present a summary of our findings.

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          Vitamin D receptor-mediated stromal reprogramming suppresses pancreatitis and enhances pancreatic cancer therapy.

          The poor clinical outcome in pancreatic ductal adenocarcinoma (PDA) is attributed to intrinsic chemoresistance and a growth-permissive tumor microenvironment. Conversion of quiescent to activated pancreatic stellate cells (PSCs) drives the severe stromal reaction that characterizes PDA. Here, we reveal that the vitamin D receptor (VDR) is expressed in stroma from human pancreatic tumors and that treatment with the VDR ligand calcipotriol markedly reduced markers of inflammation and fibrosis in pancreatitis and human tumor stroma. We show that VDR acts as a master transcriptional regulator of PSCs to reprise the quiescent state, resulting in induced stromal remodeling, increased intratumoral gemcitabine, reduced tumor volume, and a 57% increase in survival compared to chemotherapy alone. This work describes a molecular strategy through which transcriptional reprogramming of tumor stroma enables chemotherapeutic response and suggests vitamin D priming as an adjunct in PDA therapy. PAPERFLICK: Copyright © 2014 Elsevier Inc. All rights reserved.
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            Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial.

            Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures; however, adherence to daily supplementation is typically poor. To determine whether a single annual dose of 500,000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture. A double-blind, placebo-controlled trial of 2256 community-dwelling women, aged 70 years or older, considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were randomly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years. The study concluded in 2008. 500,000 IU of cholecalciferol or placebo. Falls and fractures were ascertained using monthly calendars; details were confirmed by telephone interview. Fractures were radiologically confirmed. In a substudy, 137 randomly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels. Women in the cholecalciferol (vitamin D) group had 171 fractures vs 135 in the placebo group; 837 women in the vitamin D group fell 2892 times (rate, 83.4 per 100 person-years) while 769 women in the placebo group fell 2512 times (rate, 72.7 per 100 person-years; incidence rate ratio [RR], 1.15; 95% confidence interval [CI], 1.02-1.30; P = .03). The incidence RR for fracture in the vitamin D group was 1.26 (95% CI, 1.00-1.59; P = .047) vs the placebo group (rates per 100 person-years, 4.9 vitamin D vs 3.9 placebo). A temporal pattern was observed in a post hoc analysis of falls. The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months (test for homogeneity; P = .02). In the substudy, the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3% of the substudy participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group, 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L, were approximately 90 nmol/L at 3 months, and remained higher than the placebo group 12 months after dosing. Among older community-dwelling women, annual oral administration of high-dose cholecalciferol resulted in an increased risk of falls and fractures. anzctr.org.au Identifier: ACTRN12605000658617; isrctn.org Identifier: ISRCTN83409867.
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              New evidence pyramid

              A pyramid has expressed the idea of hierarchy of medical evidence for so long, that not all evidence is the same. Systematic reviews and meta-analyses have been placed at the top of this pyramid for several good reasons. However, there are several counterarguments to this placement. We suggest another way of looking at the evidence-based medicine pyramid and explain how systematic reviews and meta-analyses are tools for consuming evidence—that is, appraising, synthesising and applying evidence.
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                Author and article information

                Contributors
                boneboss@aol.com
                Journal
                Rev Endocr Metab Disord
                Rev Endocr Metab Disord
                Reviews in Endocrine & Metabolic Disorders
                Springer US (New York )
                1389-9155
                1573-2606
                17 March 2020
                17 March 2020
                2020
                : 21
                : 1
                : 89-116
                Affiliations
                [1 ]GRID grid.15496.3f, Chair of Endocrinology, School of Medicine, , Vita-Salute San Raffaele University, ; Milan, Italy
                [2 ]GRID grid.18887.3e, ISNI 0000000417581884, Division of Endocrinology, , IRCCS San Raffaele Scientific Institute, ; Milan, Italy
                [3 ]GRID grid.224260.0, ISNI 0000 0004 0458 8737, McGuire Veterans Affairs Medical Center and Virginia Commonwealth University School of Medicine, ; Richmond, VA USA
                [4 ]GRID grid.14003.36, ISNI 0000 0001 2167 3675, Osteoporosis Clinical Research Program and Institute on Aging, , University of Wisconsin-Madison, ; Madison, WI USA
                [5 ]GRID grid.55325.34, ISNI 0000 0004 0389 8485, Section of Specialized Endocrinology, Department of Endocrinology, , Oslo University Hospital, ; Rikshospitalet, Oslo, Norway
                [6 ]GRID grid.5510.1, ISNI 0000 0004 1936 8921, Faculty of Medicine, , University of Oslo, ; Oslo, Norway
                [7 ]Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Ageing, Leuven, KU Belgium
                [8 ]GRID grid.429997.8, ISNI 0000 0004 1936 7531, Jean Mayer USDA Human Nutrition Research Center on Aging, , Tufts University, ; Boston, MA USA
                [9 ]GRID grid.1002.3, ISNI 0000 0004 1936 7857, Department of Medicine, School of Clinical Sciences, , Monash University, ; Clayton, VIC Australia
                [10 ]GRID grid.168010.e, ISNI 0000000419368956, Department of Medicine, , Endocrinology Division, Stanford University School of Medicine, ; Stanford, CA USA
                [11 ]GRID grid.411249.b, ISNI 0000 0001 0514 7202, Division of Endocrinology, , Escola Paulista de Medicina – Universidade Federal de Sao Paulo (EPM-UNIFESP), ; Sao Paulo, Brazil
                [12 ]GRID grid.5395.a, ISNI 0000 0004 1757 3729, Department of Clinical and Experimental Medicine, , University of Pisa, ; Pisa, Italy
                [13 ]GRID grid.150338.c, ISNI 0000 0001 0721 9812, Divison of Bone Diseases, , Geneva University Hospitals and Faculty of Medicine, ; Geneva, Switzerland
                [14 ]Vitamin D Standardization Program LLC, Havre de Grace, MD USA
                [15 ]GRID grid.21729.3f, ISNI 0000000419368729, Department of Medicine, Endocrinology Division, College of Physicians and Surgeons, , Columbia University, ; New York, NY USA
                Article
                9532
                10.1007/s11154-019-09532-w
                7113202
                32180081
                da7016b0-f357-4f7c-890e-cbd7263f150d
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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                © Springer Science+Business Media, LLC, part of Springer Nature 2020

                Endocrinology & Diabetes
                vitamin d,osteoporosis,fractures,extra-skeletal effects,food,skin
                Endocrinology & Diabetes
                vitamin d, osteoporosis, fractures, extra-skeletal effects, food, skin

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