{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T09:52:29Z","timestamp":1780480349432,"version":"3.54.1"},"reference-count":32,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2019,11,27]],"date-time":"2019-11-27T00:00:00Z","timestamp":1574812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100005627","name":"Thrasher Research Fund","doi-asserted-by":"publisher","award":["02829-4"],"award-info":[{"award-number":["02829-4"]}],"id":[{"id":"10.13039\/100005627","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["5RC1HD063562"],"award-info":[{"award-number":["5RC1HD063562"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013043","name":"Yale Center for Clinical Investigation","doi-asserted-by":"publisher","award":["UL1 RR024139"],"award-info":[{"award-number":["UL1 RR024139"]}],"id":[{"id":"10.13039\/100013043","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Vitamin D status is usually assessed by serum total 25-hydroxyvitamin D (t25-OHD). Whether free 25-hydroxyvitamin D measures better correlate with various clinical outcomes is unclear.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To identify correlations between t25-OHD, calculated and direct measures of free 25-OHD, and to identify associations of these measures with other outcomes in children, across the 6 common GC haplotypes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Healthy urban-dwelling children underwent measurement of relevant variables.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>Academic medical center.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Participants<\/jats:title>\n                  <jats:p>The study included 203 healthy, urban-dwelling children, aged 6 months to 10 years, predominantly of Hispanic background and representative of all common GC haplotypes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Intervention<\/jats:title>\n                  <jats:p>None.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main Outcome Measures<\/jats:title>\n                  <jats:p>Total and free 25-OHD and 1,25(OH)2D, calcium, phosphate, parathyroid hormone (PTH), glucose, insulin, aldosterone, and renin.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Mean t25-OHD [26.3\u2005\u00b1\u20056.7ng\/ml; 65.8\u2005\u00b1\u200516.8nmol\/L] were lowest in the GC2 genotype. Mean t1,25(OH)2D [57.6\u2005\u00b1\u200516.5pg\/ml; 143.9\u2005\u00b1\u200541.3pmol\/L], were lowest in GC1f\/1f, GC1f\/2, and GC2\/2 groups. T25-OHD correlated strongly with calculated free 25-OHD (cf25-OHD) (r\u2005=\u20050.89) and moderately with directly measured free 25-OHD (dmf25-OHD) (r\u2005=\u20050.69). Cf25-OHD correlated with dmf25-OHD (r\u2005=\u20050.69) (P\u2005&amp;lt;\u20050.001 for all). t25-OHD inversely correlated with body mass index (BMI) (r=-0.191; P\u2005=\u20050.006), skin reflectometry, and systolic blood pressure. T25-OHD correlated with fasting insulin and the homeostatic model assessment for insulin resistance (HOMA-IR), however significance for these correlations was not evident after adjustment for BMI. PTH inversely correlated with all measures of 25-OHD, but most strongly with t25-OHD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Measures of circulating total and free 25-OHD are comparable measures of vitamin D status in heathy children. Correlations are similar with other outcome variables, however t25-OHD remains the strongest correlate of circulating PTH and other variables. These data argue against routine refinement of the t25-OHD measure using currently available assessments of free 25-OHD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trial Information<\/jats:title>\n                  <jats:p>Clinicaltrials.gov registration no: NCT01050387 (January 15, 2010).<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgz230","type":"journal-article","created":{"date-parts":[[2019,11,27]],"date-time":"2019-11-27T11:00:30Z","timestamp":1574852430000},"page":"e1631-e1640","source":"Crossref","is-referenced-by-count":9,"title":["Relationship of Total and Free 25-Hydroxyvitamin D to Biomarkers and Metabolic Indices in Healthy Children"],"prefix":"10.1210","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7887-5577","authenticated-orcid":false,"given":"Christine A","family":"Simpson","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Yale University School of Medicine, New Haven, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane H","family":"Zhang","sequence":"additional","affiliation":[{"name":"Veterans Administration Cooperative Studies Program Coordinating Center, VA Connecticut Healthcare System, West Haven, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Vanderschueren","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Ageing, Katholieke Universiteit Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresita C","family":"Pennestri","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (Endocrinology Section), Yale University School of Medicine, New Haven, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6446-3763","authenticated-orcid":false,"given":"Roger","family":"Bouillon","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Ageing, Katholieke Universiteit Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E C","family":"Cole","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario"},{"name":"Department of Medicine, University of Toronto, Toronto, Ontario"},{"name":"Department of Genetics, University of Toronto, Toronto, Ontario"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1328-6768","authenticated-orcid":false,"given":"Thomas O","family":"Carpenter","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (Endocrinology Section), Yale University School of Medicine, New Haven, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2019,11,27]]},"reference":[{"issue":"24","key":"2021122210031014800_CIT0001","first-page":"4315","article-title":"Vitamin D and overall cancer risk and cancer mortality: a Mendelian randomization study","volume":"27","author":"Ong","year":"2018","journal-title":"Hum Mol Genet."},{"key":"2021122210031014800_CIT0002","first-page":"CD008422","article-title":"Vitamin D for the management of multiple sclerosis","volume":"9","author":"Jagannath","year":"2018","journal-title":"Cochrane Database Syst Rev."},{"issue":"2","key":"2021122210031014800_CIT0003","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1111\/obr.12793","article-title":"Vitamin D and cardiometabolic disorders: a review of current evidence, genetic determinants and pathomechanisms","volume":"20","author":"Marquina","year":"2019","journal-title":"Obes Rev."},{"issue":"4","key":"2021122210031014800_CIT0004","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1210\/er.2018-00126","article-title":"Skeletal and extra-skeletal actions of vitamin D: current evidence and outstanding questions","volume":"40","author":"Bouillon","year":"2019","journal-title":"Endocr Rev."},{"key":"2021122210031014800_CIT0005","first-page":"97","article-title":"The vitamin D-binding protein","volume-title":"Vitamin D (4th Edition).","author":"Bouillon","year":"2018"},{"key":"2021122210031014800_CIT0006","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jsbmb.2017.01.007","article-title":"Vitamin D metabolites in captivity? Should we measure free or total 25(OH)D to assess vitamin D status?","volume":"173","author":"Bikle","year":"2017","journal-title":"J Steroid Biochem Mol Biol."},{"issue":"7","key":"2021122210031014800_CIT0007","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1002\/jbmr.387","article-title":"Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship","volume":"26","author":"Powe","year":"2011","journal-title":"J Bone Miner Res."},{"issue":"10","key":"2021122210031014800_CIT0008","doi-asserted-by":"crossref","first-page":"3666","DOI":"10.1210\/jcem.84.10.6079","article-title":"A critical evaluation of simple methods for the estimation of free testosterone in serum","volume":"84","author":"Vermeulen","year":"1999","journal-title":"J Clin Endocrinol Metab."},{"issue":"3","key":"2021122210031014800_CIT0009","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1097\/MOU.0000000000000384","article-title":"The role of prostate cancer biomarkers in undiagnosed men","volume":"27","author":"Dani","year":"2017","journal-title":"Curr Opin Urol."},{"issue":"4","key":"2021122210031014800_CIT0010","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.ecl.2017.07.013","article-title":"Current controversies: Are free vitamin metabolite levels a more accurate assessment of vitamin D status than total levels?","volume":"46","author":"Bikle","year":"2017","journal-title":"Endocrinol Metab Clin North Am."},{"key":"2021122210031014800_CIT0011","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.jsbmb.2013.09.012","article-title":"Vitamin D and DBP: the free hormone hypothesis revisited","volume":"144 Pt A","author":"Chun","year":"2014","journal-title":"J Steroid Biochem Mol Biol."},{"issue":"1","key":"2021122210031014800_CIT0012","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1002\/jbmr.1735","article-title":"Vitamin D binding protein is a key determinant of 25-hydroxyvitamin D levels in infants and toddlers","volume":"28","author":"Carpenter","year":"2013","journal-title":"J Bone Miner Res."},{"issue":"1","key":"2021122210031014800_CIT0013","doi-asserted-by":"crossref","first-page":"e30773","DOI":"10.1371\/journal.pone.0030773","article-title":"Vitamin D binding protein and monocyte response to 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D: analysis by mathematical modeling","volume":"7","author":"Chun","year":"2012","journal-title":"PLoS One."},{"issue":"9","key":"2021122210031014800_CIT0014","doi-asserted-by":"crossref","first-page":"3278","DOI":"10.1210\/jc.2018-00295","article-title":"Determination of free 25(OH)D concentrations and their relationships to total 25(OH)D in multiple clinical populations","volume":"103","author":"Schwartz","year":"2018","journal-title":"J Clin Endocrinol Metab."},{"issue":"1","key":"2021122210031014800_CIT0015","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/nyas.13219","article-title":"Extraskeletal actions of vitamin D","volume":"1376","author":"Bikle","year":"2016","journal-title":"Ann N Y Acad Sci."},{"issue":"1","key":"2021122210031014800_CIT0016","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/(SICI)1096-8644(200005)112:1<17::AID-AJPA3>3.0.CO;2-D","article-title":"Comparison of narrow-band reflectance spectroscopy and tristimulus colorimetry for measurements of skin and hair color in persons of different biological ancestry","volume":"112","author":"Shriver","year":"2000","journal-title":"Am J Phys Anthropol."},{"issue":"3","key":"2021122210031014800_CIT0017","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.jocd.2006.03.013","article-title":"Quantitative ultrasound in the evaluation of bone status in premature and full-term infants","volume":"9","author":"Teitelbaum","year":"2006","journal-title":"J Clin Densitom."},{"issue":"12","key":"2021122210031014800_CIT0018","doi-asserted-by":"crossref","first-page":"4615","DOI":"10.1210\/jc.2007-1279","article-title":"Serum 25-hydroxyvitamin D measurement in a large population survey with statistical harmonization of assay variation to an international standard","volume":"92","author":"Hypp\u00f6nen","year":"2007","journal-title":"J Clin Endocrinol Metab."},{"key":"2021122210031014800_CIT0019","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1385\/0-89603-204-3:201","article-title":"Rocket immunoelectrophoresis technique or electroimmunodiffusion","volume-title":"Immunochemical Protocols","author":"Laine","year":"1992"},{"issue":"2","key":"2021122210031014800_CIT0020","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/S0022-3476(05)82883-5","article-title":"Vitamin D metabolism in chronic childhood hypoparathyroidism: evidence for a direct regulatory effect of calcium","volume":"116","author":"Carpenter","year":"1990","journal-title":"J Pediatr."},{"issue":"4","key":"2021122210031014800_CIT0021","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1210\/jcem-60-4-736","article-title":"Osteocalcin in human serum: a circadian rhythm","volume":"60","author":"Gundberg","year":"1985","journal-title":"J Clin Endocrinol Metab."},{"issue":"2","key":"2021122210031014800_CIT0022","doi-asserted-by":"crossref","first-page":"314","DOI":"10.2337\/diacare.27.2.314","article-title":"Indexes of insulin resistance and secretion in obese children and adolescents: a validation study","volume":"27","author":"Conwell","year":"2004","journal-title":"Diabetes Care."},{"issue":"6","key":"2021122210031014800_CIT0023","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1097\/MED.0000000000000371","article-title":"Vitamin D in obesity","volume":"24","author":"Walsh","year":"2017","journal-title":"Curr Opin Endocrinol Diabetes Obes."},{"key":"2021122210031014800_CIT0024","article-title":"Data from: relationship of total and free 25-hydroxyvitamin D to biomarkers and metabolic indices in healthy children. Dryad, Dataset","author":"Simpson"},{"issue":"5","key":"2021122210031014800_CIT0025","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.1021\/ac9026862","article-title":"Development of a candidate reference measurement procedure for the determination of 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 in human serum using isotope-dilution liquid chromatography-tandem mass spectrometry","volume":"82","author":"Tai","year":"2010","journal-title":"Anal Chem."},{"issue":"12","key":"2021122210031014800_CIT0026","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1056\/NEJMoa1807841","article-title":"Vitamin D-binding protein deficiency and homozygous deletion of the GC gene","volume":"380","author":"Henderson","year":"2019","journal-title":"N Engl J Med."},{"issue":"2","key":"2021122210031014800_CIT0027","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1172\/JCI5244","article-title":"Osteopathy and resistance to vitamin D toxicity in mice null for vitamin D binding protein","volume":"103","author":"Safadi","year":"1999","journal-title":"J Clin Invest."},{"key":"2021122210031014800_CIT0028","first-page":"e3686","article-title":"Obesity decreases hepatic 25-hydroxylase activity causing low serum 25-hydroxyvitamin D","author":"Roizen","year":"2019","journal-title":"J Bone Miner Res."},{"key":"2021122210031014800_CIT0029","doi-asserted-by":"crossref","first-page":"5015417","DOI":"10.1155\/2018\/5015417","article-title":"Effects of vitamin D supplementation on renin and aldosterone concentrations in patients with advanced heart failure: the EVITA trial","volume":"2018","author":"Zittermann","year":"2018","journal-title":"Int J Endocrinol."},{"key":"2021122210031014800_CIT0030","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.neulet.2015.01.013","article-title":"Administration of exogenous 1,25(OH)2D3 normalizes overactivation of the central renin-angiotensin system in 1\u03b1(OH)ase knockout mice","volume":"588","author":"Zhang","year":"2015","journal-title":"Neurosci Lett."},{"issue":"2","key":"2021122210031014800_CIT0031","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/ki.2008.101","article-title":"Calcium-independent and 1,25(OH)2D3-dependent regulation of the renin-angiotensin system in 1alpha-hydroxylase knockout mice","volume":"74","author":"Zhou","year":"2008","journal-title":"Kidney Int."},{"issue":"4","key":"2021122210031014800_CIT0032","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.4049\/jimmunol.179.4.2060","article-title":"Cutting edge: vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin","volume":"179","author":"Liu","year":"2007","journal-title":"J Immunol."}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgz230\/31143574\/dgz230.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/105\/4\/e1631\/41860759\/jcem_105_4_e1631.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/105\/4\/e1631\/41860759\/jcem_105_4_e1631.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T18:09:14Z","timestamp":1640196554000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/105\/4\/e1631\/5644233"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,27]]},"references-count":32,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,11,27]]},"published-print":{"date-parts":[[2020,4,1]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgz230","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,4]]},"published":{"date-parts":[[2019,11,27]]}}}