{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:55:28Z","timestamp":1789559728180,"version":"build-2803163510"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,11,14]],"date-time":"2020-11-14T00:00:00Z","timestamp":1605312000000},"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\/100000062","name":"National Institute of Diabetes, Digestive, and Kidney Diseases","doi-asserted-by":"crossref","award":["K23DK118197"],"award-info":[{"award-number":["K23DK118197"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Loan Repayment Program","award":["R01DK101720"],"award-info":[{"award-number":["R01DK101720"]}]},{"name":"Loan Repayment Program","award":["K24 DK110427"],"award-info":[{"award-number":["K24 DK110427"]}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["5R01AG027002"],"award-info":[{"award-number":["5R01AG027002"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["R01AG033087"],"award-info":[{"award-number":["R01AG033087"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University of Washington Nutrition and Obesity Research Center","award":["P30DK035816"],"award-info":[{"award-number":["P30DK035816"]}]},{"name":"Established Investigator Award from the American Heart Association","award":["14EIA18560026"],"award-info":[{"award-number":["14EIA18560026"]}]},{"name":"National Institute on Aging (NIA","award":["N01-AG-6-2101"],"award-info":[{"award-number":["N01-AG-6-2101"]}]},{"name":"National Institute on Aging (NIA","award":["N01-AG-6-2103"],"award-info":[{"award-number":["N01-AG-6-2103"]}]},{"name":"National Institute on Aging (NIA","award":["N01-AG-6-2106"],"award-info":[{"award-number":["N01-AG-6-2106"]}]},{"name":"National Institute on Aging (NIA","award":["R01-AG028050"],"award-info":[{"award-number":["R01-AG028050"]}]},{"name":"National Institute on Aging (NIA","award":["R01-NR012459"],"award-info":[{"award-number":["R01-NR012459"]}]},{"name":"Intramural Research Program of the NIH"},{"name":"National Institute on Aging. A.N. Hoofnagle"},{"name":"Waters, Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>25-Hydroxyvitamin D [25(OH)D] may be a poor marker of vitamin D status as it reflects differences in vitamin D binding protein (VDBP) between individuals. The vitamin D metabolite ratio [VMR, ratio of 24,25(OH)2D3 to 25(OH)D3] is a marker of vitamin D status that has been hypothesized to be independent of variability in VDBP. This hypothesis has not been directly evaluated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We measured 25(OH)D3, 24,25(OH)2D3, 1,25(OH)2D3, and VDBP in 377 community-dwelling older adults that participated in the Health Aging and Body Composition Study. 24,25(OH)2D3 and 25(OH)D3 were used to calculate the VMR. We used linear regression to assess the relationship between VDBP with the VMR, 24,25(OH)2D3, 25(OH)D3, and 1,25(OH)2D3.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Participants had mean age 75\u2009\u00b1\u20093\u2009years, 52% were female, 40% were black, and 24% had chronic kidney disease. VDBP concentrations were associated with sex, serum albumin, and VDBP phenotype in multivariable models. In fully adjusted models, each 1% higher VDBP was associated with a 0.92%[95% CI(0.37,1.49%)], 0.76% (0.39, 1.13%), and 0.57% (0.29, 0.85%), higher 24,25(OH)2D3, 25(OH)D3, and 1,25(OH)2D3. The VMR was independent of VDBP concentration, [0.16%(-0.11, 0.44) higher VMR per 1% higher VDBP, P\u2009=\u2009.25].<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The VMR was independent of VDBP concentration, whereas VDBP was strongly directly associated with the individual vitamin D metabolite concentrations. Prior studies evaluating only 25(OH)D3 may have been confounded by absence of data on VDBP status. The VMR may serve as an important biomarker of vitamin D status and clinical outcomes that can be utilized in populations with a large spectrum of VDBP concentrations.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/clinchem\/hvaa238","type":"journal-article","created":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T19:24:11Z","timestamp":1602617051000},"page":"385-393","source":"Crossref","is-referenced-by-count":37,"title":["The Vitamin D Metabolite Ratio Is Independent of Vitamin D Binding Protein Concentration"],"prefix":"10.1093","volume":"67","author":[{"given":"Charles","family":"Ginsberg","sequence":"first","affiliation":[{"name":"Division of Nephrology-Hypertension, University of California, San Diego, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew N","family":"Hoofnagle","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and the Kidney Research Institute, University of Washington, Seattle, WA"},{"name":"Department of Medicine and the Kidney Research Institute, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronit","family":"Katz","sequence":"additional","affiliation":[{"name":"Kidney Research Institute, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica O","family":"Becker","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and the Kidney Research Institute, University of Washington, Seattle, WA"},{"name":"Department of Medicine and the Kidney Research Institute, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen B","family":"Kritchevsky","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G","family":"Shlipak","sequence":"additional","affiliation":[{"name":"Kidney Health Research Collaborative, Veterans Affairs Medical Center, San Francisco, CA"},{"name":"University of California, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J","family":"Sarnak","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology, Tufts Medical Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim H","family":"Ix","sequence":"additional","affiliation":[{"name":"Division of Nephrology-Hypertension, University of California, San Diego, San Diego, CA"},{"name":"Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,11,14]]},"reference":[{"key":"2021020107553325200_hvaa238-B1","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.amjmed.2003.12.029","article-title":"Positive association between 25-hydroxy vitamin D levels and bone mineral density: a population-based study of younger and older adults","volume":"116","author":"Bischoff-Ferrari","year":"2004","journal-title":"Am J Med"},{"key":"2021020107553325200_hvaa238-B2","doi-asserted-by":"crossref","first-page":"2448","DOI":"10.1001\/jama.2017.4392","article-title":"Trends in use of high-dose vitamin D supplements exceeding 1000 or 4000 international units daily, 1999-2014","volume":"317","author":"Rooney","year":"2017","journal-title":"JAMA"},{"key":"2021020107553325200_hvaa238-B3","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1359\/jbmr.090728","article-title":"Bone mineralization defects and vitamin D deficiency: histomorphometric analysis of iliac crest bone biopsies and circulating 25-hydroxyvitamin D in 675 patients","volume":"25","author":"Priemel","year":"2010","journal-title":"J Bone Miner Res"},{"key":"2021020107553325200_hvaa238-B4","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.bone.2017.11.011","article-title":"The 24,25 to 25-hydroxyvitamin D ratio and fracture risk in older adults: the Cardiovascular Health Study","volume":"107","author":"Ginsberg","year":"2018","journal-title":"Bone"},{"key":"2021020107553325200_hvaa238-B5","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1053\/j.ajkd.2018.03.026","article-title":"Serum calcitriol concentrations and kidney function decline, heart failure, and mortality in elderly community-living adults persons: the Health Aging and Body Composition Study","volume":"72","author":"Selamet","year":"2018","journal-title":"Am J Kidney Dis"},{"key":"2021020107553325200_hvaa238-B6","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1016\/j.ekir.2019.08.014","article-title":"Vitamin D metabolic ratio and risks of death and CKD progression","volume":"4","author":"Bansal","year":"2019","journal-title":"Kidney Int Rep"},{"key":"2021020107553325200_hvaa238-B7","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"},{"key":"2021020107553325200_hvaa238-B8","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/ki.2012.193","article-title":"The serum 24,25-dihydroxyvitamin D concentration, a marker of vitamin D catabolism, is reduced in chronic kidney disease","volume":"82","author":"Bosworth","year":"2012","journal-title":"Kidney Int"},{"key":"2021020107553325200_hvaa238-B9","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","author":"Chun","year":"2014","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2021020107553325200_hvaa238-B10","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1056\/NEJMc1502602","article-title":"Vitamin D-binding protein concentrations quantified by mass spectrometry","volume":"373","author":"Hoofnagle","year":"2015","journal-title":"N Engl J Med"},{"key":"2021020107553325200_hvaa238-B11","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.1210\/jc.2013-4388","article-title":"Clinical utility of simultaneous quantitation of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D by LC-MS\/MS involving derivatization with DMEQ-TA","volume":"99","author":"Kaufman","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"key":"2021020107553325200_hvaa238-B12","doi-asserted-by":"crossref","first-page":"582S","DOI":"10.1093\/ajcn\/88.2.582S","article-title":"Pharmacokinetics of vitamin D toxicity","volume":"88","author":"Jones","year":"2008","journal-title":"Am J Clin Nutr"},{"key":"2021020107553325200_hvaa238-B13","doi-asserted-by":"crossref","first-page":"507S","DOI":"10.1093\/ajcn\/88.2.507S","article-title":"Measuring 25-hydroxyvitamin D in a clinical environment: challenges and needs","volume":"88","author":"Hollis","year":"2008","journal-title":"Am J Clin Nutr"},{"key":"2021020107553325200_hvaa238-B14","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1373\/clinchem.2015.244541","article-title":"Measurement by a novel LC-MS\/MS methodology reveals similar serum concentrations of vitamin D-binding protein in Blacks and Whites","volume":"62","author":"Henderson","year":"2016","journal-title":"Clin Chem"},{"key":"2021020107553325200_hvaa238-B15","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1373\/clinchem.2016.261461","article-title":"Short-term variability of vitamin D-related biomarkers","volume":"62","author":"Lutsey","year":"2016","journal-title":"Clin Chem"},{"key":"2021020107553325200_hvaa238-B16","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1056\/NEJMoa1114248","article-title":"CKD-EPI Investigators. Estimating glomerular filtration rate from serum creatinine and cystatin C","volume":"367","author":"Inker","year":"2012","journal-title":"N Engl J Med"},{"key":"2021020107553325200_hvaa238-B17","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1373\/clinchem.2015.240051","article-title":"24,25-Dihydroxyvitamin D3 and vitamin D status of community-dwelling black and white Americans","volume":"61","author":"Berg","year":"2015","journal-title":"Clin Chem"},{"key":"2021020107553325200_hvaa238-B18","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1515\/cclm-2019-0996","article-title":"Simultaneous measurement of 25(OH)-vitamin D and 24,25(OH)2-vitamin D to define cut-offs for CYP24A1 mutation and vitamin D deficiency in a population of 1200 young subjects","volume":"58","author":"Cavalier","year":"2020","journal-title":"Clin Chem Lab Med"},{"key":"2021020107553325200_hvaa238-B19","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":"2021020107553325200_hvaa238-B20","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1359\/JBMR.041007","article-title":"Osteoporosis and fracture risk in women of different ethnic groups","volume":"20","author":"Barrett-Connor","year":"2004","journal-title":"J Bone Miner Res"}],"container-title":["Clinical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/clinchem\/article-pdf\/67\/2\/385\/36156836\/hvaa238.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/clinchem\/article-pdf\/67\/2\/385\/36156836\/hvaa238.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T07:59:39Z","timestamp":1612166379000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/clinchem\/article\/67\/2\/385\/5981919"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,14]]},"references-count":20,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,11,14]]},"published-print":{"date-parts":[[2021,1,30]]}},"URL":"https:\/\/doi.org\/10.1093\/clinchem\/hvaa238","relation":{},"ISSN":["0009-9147","1530-8561"],"issn-type":[{"value":"0009-9147","type":"print"},{"value":"1530-8561","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,2,1]]},"published":{"date-parts":[[2020,11,14]]}}}