{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:50:38Z","timestamp":1789537838518,"version":"build-2803163510"},"reference-count":28,"publisher":"The Endocrine Society","issue":"7","license":[{"start":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T00:00:00Z","timestamp":1646956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/K015176\/2"],"award-info":[{"award-number":["MR\/K015176\/2"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["20090506"],"award-info":[{"award-number":["20090506"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"NIHR","doi-asserted-by":"publisher","award":["CRF-2016-1002"],"award-info":[{"award-number":["CRF-2016-1002"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"NIHR","doi-asserted-by":"publisher","award":["CRF 20"],"award-info":[{"award-number":["CRF 20"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>The causative link between circulating glucocorticoid excess and osteoporosis is well-established. The enzyme 11\u03b2-hydroxysteroid dehydrogenase type 1 (11\u03b2-HSD1), which increases local cortisol production, is expressed in human osteoblasts and its activity increases with age.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We hypothesized that local 11\u03b2-HSD1 might mediate an age-related decrease in bone formation and that selective 11\u03b2-HSD1 inhibition may enhance bone formation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A dual-center, phase II, randomized, double-blind, placebo-controlled trial of 90 days\u2019 treatment with AZD4017 (a selective 11\u03b2-HSD1 inhibitor) was conducted in 55 postmenopausal women with osteopenia. Participants received 400 mg oral AZD4017 twice daily vs matched placebo over 90 days. The primary outcome measure was the impact on the bone formation marker osteocalcin. Secondary objectives included correlation with 11\u03b2-HSD1 activity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>At 90 days, osteocalcin levels did not differ between treatment groups: active (mean 22.3 [SD 8.6] ng\/mL, n\u2005=\u200522) and placebo (21.7 [SD 9.2] ng\/mL, n\u2005=\u200524), with a baseline-adjusted treatment effect of 0.95 (95% CI: \u22122.69, 4.60). The results from the urinary [THF\u2005+\u2005alloTHF]\/THE ratio (index of 11\u03b2-HSD1 activity) and the urinary cortisol\/cortisone ratio (index of 11\u03b2-HSD2 activity) confirmed a &amp;gt; 90% inhibition of 11\u03b2-HSD1 but no change in activity of 11\u03b2-HSD2.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>This trial demonstrates that AZD4017 selectively inhibits 11\u03b2-HSD1 activity in vivo in a safe and reversible manner. Following 90 days of treatment, there is no effect on bone formation, indicating that the relative impairment of bone mineral density in postmenopausal women is not mediated by local intracellular production of cortisol under normal physiological concentrations.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgac100","type":"journal-article","created":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T15:20:17Z","timestamp":1647012017000},"page":"2026-2035","source":"Crossref","is-referenced-by-count":11,"title":["Effect of AZD4017, a Selective 11\u03b2-HSD1 Inhibitor, on Bone Turnover Markers in Postmenopausal Osteopenia"],"prefix":"10.1210","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2497-6887","authenticated-orcid":false,"given":"Afroze","family":"Abbas","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Health, University of Leeds, and Leeds Teaching Hospitals NHS Trust , Leeds LS9 7TF , 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UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel K","family":"Crowley","sequence":"additional","affiliation":[{"name":"School of Medicine and Medical Science, University College Dublin , Dublin , Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S","family":"Cooper","sequence":"additional","affiliation":[{"name":"Concord Clinical School, Faculty of Medicine & Health, University of Sydney, NSW 2139 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca J","family":"Fairclough","sequence":"additional","affiliation":[{"name":"Emerging Innovations Unit, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca , Cambridge , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0323-3366","authenticated-orcid":false,"given":"Richard","family":"Eastell","sequence":"additional","affiliation":[{"name":"Academic Unit of Bone Metabolism, University of Sheffield , Sheffield S5 7AU , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M","family":"Stewart","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health, University of Leeds, and Leeds Teaching Hospitals NHS Trust , Leeds LS9 7TF , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2022,3,11]]},"reference":[{"issue":"1","key":"2022061616031851300_CIT0001","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s11657-020-0706-y","article-title":"Fragility fractures in Europe: burden, management and opportunities","volume":"15","author":"Borgstr\u00f6m","year":"2020","journal-title":"Arch Osteoporos."},{"issue":"10","key":"2022061616031851300_CIT0002","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1007\/s001980200108","article-title":"The epidemiology of corticosteroid-induced osteoporosis: a 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