41
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      Vitamin D assays and the definition of hypovitaminosis D: results from the First International Conference on Controversies in Vitamin D : Vitamin D assays and defining hypovitaminosis D

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          <p class="first" id="d391853e578">The First International Conference on Controversies in Vitamin D was held in Pisa, Italy, 14–16 June 2017. The meeting's purpose was to address controversies in vitamin D research, review the data available, to help resolve them, and suggest a research agenda to clarify areas of uncertainty. The serum 25‐hydroxyvitamin D [25(OH)D] concentration [i.e. the sum of 25(OH)D <sub>3</sub> and 25(OH)D <sub>2</sub>] remains the critical measurement for defining vitamin D status. Assay variation for 25(OH)D has contributed to the current chaos surrounding efforts to define hypovitaminosis D. An essential requirement to develop a consensus on vitamin D status is that measurement of 25(OH)D and, in the future, other potential vitamin D biomarkers [e.g. 1α,25(OH) <sub>2</sub>D <sub>3</sub>, 3‐epi‐25(OH)D, 24,25(OH) <sub>2</sub>D <sub>3,</sub> vitamin D‐binding protein, free/bioavailable 25(OH)D and parathyroid hormone] be standardized/harmonized, to allow pooling of research data. Vitamin D Standardization Program tools are described and recommended for standardizing 25(OH)D measurement in research. In the future, similar methodology, based on National Institute for Standards and Technology standard reference materials, must be developed for other candidate markers of vitamin D status. Failure to standardize/harmonize vitamin D metabolite measurements is destined to promulgate continued chaos. At this time, 25(OH)D values below 12 ng ml <sup>–1</sup> (30 nmol l <sup>–1</sup>) should be considered to be associated with an increased risk of rickets/osteomalacia, whereas 25(OH)D concentrations between 20 ng ml <sup>–1</sup> and 50 ng ml <sup>–1</sup> (50–125 nmol l <sup>–1</sup>) appear to be safe and sufficient in the general population for skeletal health. In an effort to bridge knowledge gaps in defining hypovitaminosis D, an international study on rickets as a multifactorial disease is proposed. </p>

          Related collections

          Most cited references75

          • Record: found
          • Abstract: found
          • Article: not found

          Comparative analysis of nutritional guidelines for vitamin D

          Governments and scientific societies regularly update recommendations for intake of vitamin D, especially for those individuals who have limited exposure to sunlight — the main source of vitamin D. Here, Roger Bouillon presents an overview of these guidelines, highlighting common ground and areas of discord.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Vitamin D-Mediated Hypercalcemia: Mechanisms, Diagnosis, and Treatment.

            Hypercalcemia occurs in up to 4% of the population in association with malignancy, primary hyperparathyroidism, ingestion of excessive calcium and/or vitamin D, ectopic production of 1,25-dihydroxyvitamin D [1,25(OH)2D], and impaired degradation of 1,25(OH)2D. The ingestion of excessive amounts of vitamin D3 (or vitamin D2) results in hypercalcemia and hypercalciuria due to the formation of supraphysiological amounts of 25-hydroxyvitamin D [25(OH)D] that bind to the vitamin D receptor, albeit with lower affinity than the active form of the vitamin, 1,25(OH)2D, and the formation of 5,6-trans 25(OH)D, which binds to the vitamin D receptor more tightly than 25(OH)D. In patients with granulomatous disease such as sarcoidosis or tuberculosis and tumors such as lymphomas, hypercalcemia occurs as a result of the activity of ectopic 25(OH)D-1-hydroxylase (CYP27B1) expressed in macrophages or tumor cells and the formation of excessive amounts of 1,25(OH)2D. Recent work has identified a novel cause of non-PTH-mediated hypercalcemia that occurs when the degradation of 1,25(OH)2D is impaired as a result of mutations of the 1,25(OH)2D-24-hydroxylase cytochrome P450 (CYP24A1). Patients with biallelic and, in some instances, monoallelic mutations of the CYP24A1 gene have elevated serum calcium concentrations associated with elevated serum 1,25(OH)2D, suppressed PTH concentrations, hypercalciuria, nephrocalcinosis, nephrolithiasis, and on occasion, reduced bone density. Of interest, first-time calcium renal stone formers have elevated 1,25(OH)2D and evidence of impaired 24-hydroxylase-mediated 1,25(OH)2D degradation. We will describe the biochemical processes associated with the synthesis and degradation of various vitamin D metabolites, the clinical features of the vitamin D-mediated hypercalcemia, their biochemical diagnosis, and treatment.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Affinity differences for vitamin D metabolites associated with the genetic isoforms of the human serum carrier protein (DBP).

              Human vitamin D binding protein (DBP) displays considerable polymorphism with 120 described alleles. Among these, three alleles are frequently observed, Gc 1F (pI 4.94-4.84), Gc 1S (pI 4.95-4.85) and Gc 2 (pI 5.1). Differences between these genetic forms of the protein in affinity for vitamin D metabolites have been detected by electrophoretic methods. The constant affinity (Ka) values determined in this study confirm these differences. The affinities of six rare variants were also examine. Those of the DBP genetic forms to the vitamin D derivatives 25-OH-D3 and 1,25-(OH)2-D3 seem to be related to the isoelectric point of the proteins: a high affinity corresponding to a low isoelectric point. The Gc 1A9 and 1A11 mutants were associated with higher affinity for the vitamin D derivatives and the Gc 1C1 and 1C21 mutants were deficient.
                Bookmark

                Author and article information

                Journal
                British Journal of Clinical Pharmacology
                Br J Clin Pharmacol
                Wiley
                03065251
                October 2018
                October 2018
                July 17 2018
                : 84
                : 10
                : 2194-2207
                Affiliations
                [1 ]Vitamin D Standardization Program; Havre de Grace MD USA
                [2 ]Endocrine Laboratory, Department of Clinical Chemistry; VU University Medical Center; Amsterdam The Netherlands
                [3 ]Laboratory of Endocrinology; Academic Medical Center; Amsterdam The Netherlands
                [4 ]San Francisco, San Francisco Department of Veterans Affairs Medical Center, Endocrine Research Unit; University of California; San Francisco CA USA
                [5 ]Section of Specialized Endocrinology, Department of Endocrinology; Oslo University Hospital, Rikshospitalet; Oslo Norway
                [6 ]Faculty of Medicine; University of Oslo; Oslo Norway
                [7 ]Department of Chronic Diseases, Metabolism and Ageing; Laboratory of Clinical and Experimental Endocrinology; KU Leuven Belgium
                [8 ]Division of Nutritional Sciences; Cornell University; Ithaca NY USA
                [9 ]Department of Biochemistry; University of Wisconsin-Madison; Madison WI USA
                [10 ]Department of Biomedical and Molecular Sciences; Queen's University; Kingston ON Canada
                [11 ]Institute of Endocrinology and Diabetes; The Children's Hospital at Westmead; Sydney NSW Australia
                [12 ]Department of Medicine, Endocrinology Division, College of Physicians and Surgeons; Columbia University; New York NY USA
                [13 ]Division of Endocrinology; San Raffaele University Hospital; Milan Italy
                [14 ]Osteoporosis Clinical Research Program and Institute on Aging; University of Wisconsin-Madison; Madison WI USA
                Article
                10.1111/bcp.13652
                6138489
                29851137
                8f82674f-8068-43a8-b063-76a9cdc83335
                © 2018

                http://doi.wiley.com/10.1002/tdm_license_1.1

                http://onlinelibrary.wiley.com/termsAndConditions#vor

                History

                Comments

                Comment on this article