{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T19:03:56Z","timestamp":1774465436906,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,4,22]],"date-time":"2013-04-22T00:00:00Z","timestamp":1366588800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Context<\/jats:title><jats:p>Patients with primary adrenal insufficiency (<jats:styled-content style=\"fixed-case\">PAI<\/jats:styled-content>) and patients with congenital adrenal hyperplasia (<jats:styled-content style=\"fixed-case\">CAH<\/jats:styled-content>) receive weight\u2010adapted standard glucocorticoid replacement therapy. Clinically, some patients appear more sensitive to therapeutic administration of glucocorticoids than others. Glucocorticoid sensitivity is at least partially genetically determined by polymorphisms of the glucocorticoid receptor (<jats:styled-content style=\"fixed-case\">GR<\/jats:styled-content>) and might influence bone mineral density (<jats:styled-content style=\"fixed-case\">BMD<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To determine if bone turnover markers and <jats:styled-content style=\"fixed-case\">BMD<\/jats:styled-content> are associated with the <jats:styled-content style=\"fixed-case\">GR<\/jats:styled-content> gene polymorphism <jats:italic>Bcl<\/jats:italic>I in patients with <jats:styled-content style=\"fixed-case\">PAI<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CAH<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design and Patients<\/jats:title><jats:p>A prospective, cross\u2010sectional study including 74 <jats:styled-content style=\"fixed-case\">PAI<\/jats:styled-content> and 38 <jats:styled-content style=\"fixed-case\">CAH<\/jats:styled-content> patients. <jats:styled-content style=\"fixed-case\">BMD<\/jats:styled-content> was evaluated by <jats:styled-content style=\"fixed-case\">DXA<\/jats:styled-content>. Serum levels of bone turnover markers, minerals, vitamins and hormones, and urinary crosslinks were measured.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients carrying the homozygous <jats:italic>Bcl<\/jats:italic>I polymorphism (<jats:styled-content style=\"fixed-case\">GG<\/jats:styled-content>) had significantly higher serum \u03b2\u2010CrossLaps (0\u00b737\u00a0\u00b1\u00a00\u00b734\u00a0\u03bcg\/l; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b705) and urinary collagen crosslinks (<jats:styled-content style=\"fixed-case\">NTX<\/jats:styled-content>, 68\u00b71\u00a0\u00b1\u00a032\u00b74\u00a0nmol\/g; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b7005) despite receiving the lowest average daily hydrocortisone dose of 9\u00b79\u00a0\u00b1\u00a03\u00b77\u00a0mg\/m<jats:sup>2<\/jats:sup> (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b705). The <jats:styled-content style=\"fixed-case\">GG<\/jats:styled-content> genotype occurred significantly more frequently in patients with increased <jats:styled-content style=\"fixed-case\">NTX<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>=6\u00b77, 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>\u00a0=\u00a01\u00b778\u201325\u00b738) than in patients with normal <jats:styled-content style=\"fixed-case\">NTX<\/jats:styled-content>. However, <jats:styled-content style=\"fixed-case\">BMD<\/jats:styled-content> was not significantly different between different allelic variants. No significant differences in associations of the genotypes with outcomes (or in clinical characteristics) were found between the sexes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Although the sample sizes were relatively small and the results should be interpreted with caution, this study suggests that the homozygous (<jats:styled-content style=\"fixed-case\">GG<\/jats:styled-content>) genotype may be associated with higher bone resorption in adult <jats:styled-content style=\"fixed-case\">PAI<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CAH<\/jats:styled-content> patients. <jats:styled-content style=\"fixed-case\">GG<\/jats:styled-content>\u2010carriers needed a lower hydrocortisone dose on average supporting the concept that this <jats:styled-content style=\"fixed-case\">GR<\/jats:styled-content> variant is associated with increased cortisol sensitivity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.12096","type":"journal-article","created":{"date-parts":[[2012,11,8]],"date-time":"2012-11-08T08:41:43Z","timestamp":1352364103000},"page":"831-837","source":"Crossref","is-referenced-by-count":24,"title":["<i>Bcl<\/i>I polymorphism of the glucocorticoid receptor gene is associated with increased bone resorption in patients on glucocorticoid replacement therapy"],"prefix":"10.1111","volume":"78","author":[{"given":"Kathrin R.","family":"Koetz","sequence":"first","affiliation":[{"name":"Department of Clinical Endocrinology Charit\u00e9 Campus Mitte Charit\u00e9 University Medicine Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth F. 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