{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:38:39Z","timestamp":1779237519045,"version":"3.51.4"},"reference-count":59,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T00:00:00Z","timestamp":1710374400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes, Digestive, and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>The body has evolved homeostatic mechanisms to maintain free levels of Ca+2 and 1,25-dihydroxyvitamin D (1,25(OH)2D) within narrow physiological ranges. Clinical guidelines emphasize important contributions of parathyroid hormone (PTH) in maintaining this homeostasis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>This work aimed to investigate mechanisms of homeostatic regulation of vitamin D (VitD) metabolism and to apply mechanistic insights to improve clinical assessment of VitD status.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This crossover clinical trial studied community participants before and after VitD3 supplementation. Participants included 11 otherwise healthy individuals with VitD deficiency (25-hydroxyvitamin D [25(OH)D] \u226420\u2005ng\/mL). VitD3 supplements (50 000\u2005IU once or twice a week depending on body mass index, for 4-6 weeks) were administered to achieve 25(OH)D of 30 ng\/mL or greater.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>VitD3 supplementation significantly increased mean 25(OH)D by 2.7-fold and 24,25-dihydroxyvitamin D (24,25(OH)2D) by 4.3-fold. In contrast, mean levels of PTH, fibroblast growth factor-23, and 1,25(OH)2D did not change. Mathematical modeling suggested that 24-hydroxylase activity was maximal for 25(OH)D 50\u2005ng\/mL or greater and achieved a minimum (\u223c90% suppression) with 25(OH)D less than 10 to 20\u2005ng\/mL. The 1,25(OH)2D\/24,25(OH)2D ratio better predicted modeled 24-hydroxylase activity (h) (\u03c1 = \u22120.85; P = .001) compared to total plasma 25(OH)D (\u03c1 = 0.51; P = .01) and the 24,25(OH)2D\/25(OH)D ratio (\u03c1 = 0.37; P = .3).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Suppression of 24-hydroxylase provides a first line of defense against symptomatic VitD deficiency by decreasing metabolic clearance of 1,25(OH)2D. The 1,25(OH)2D\/24,25(OH)2D ratio provides a useful index of VitD status since it incorporates 24,25(OH)2D levels, and therefore provides insight into 24-hydroxylase activity. When VitD availability is limited, this suppresses 24-hydroxylase activity\u2014thereby decreasing the level of 24,25(OH)2D and increasing the 1,25(OH)2D\/24,25(OH)2D ratio. Thus, an increased 1,25(OH)2D\/24,25(OH)2D ratio signifies triggering of homeostatic regulation, which occurs at early stages of VitD deficiency.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgae156","type":"journal-article","created":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T08:32:00Z","timestamp":1710405120000},"page":"e443-e455","source":"Crossref","is-referenced-by-count":7,"title":["Critical Role for 24-Hydroxylation in Homeostatic Regulation of Vitamin D Metabolism"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1056-4523","authenticated-orcid":false,"given":"Zhinous","family":"Shahidzadeh Yazdi","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine , Baltimore, MD 21201 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth A","family":"Streeten","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine , Baltimore, MD 21201 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hilary B","family":"Whitlatch","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine , Baltimore, MD 21201 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"May E","family":"Montasser","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine , Baltimore, MD 21201 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amber L","family":"Beitelshees","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine , Baltimore, MD 21201 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7500-7854","authenticated-orcid":false,"given":"Simeon I","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine , Baltimore, MD 21201 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2024,3,14]]},"reference":[{"issue":"1-2","key":"2025012110282654600_dgae156-B1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.mce.2011.05.038","article-title":"Vitamin D and intestinal calcium absorption","volume":"347","author":"Christakos","year":"2011","journal-title":"Mol Cell 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