{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T19:35:40Z","timestamp":1770406540094,"version":"3.49.0"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T00:00:00Z","timestamp":1760745600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Elsbeth-Bonhoff-Foundation"},{"DOI":"10.13039\/501100001659","name":"DFG","doi-asserted-by":"publisher","award":["TZ 74\/4-1"],"award-info":[{"award-number":["TZ 74\/4-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"DFG","doi-asserted-by":"publisher","award":["SI 493\/7-1"],"award-info":[{"award-number":["SI 493\/7-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Exogenous glucocorticoids (GCs) like prednisone are used to treat inflammatory diseases in nearly 10% of older patients. This increases osteoporosis and the risk of fractures. Until now, the negative effect on bone is thought to be a direct effect mediated exclusively by the GC receptor. However, GC effects are also locally regulated at a prereceptor level by 11\u03b2-hydroxysteroid dehydrogenase type 1 (11\u03b2-HSD1). Here, we investigated the role of 11\u03b2-HSD1 in the metabolism of exogenous GC in both human mesenchymal-progenitor-cell models and in patients undergoing GC treatment. We performed experiments focusing on regulation, activity, and effects of 11\u03b2-HSD1 on the conversion of prednisone to prednisolone and back. Subsequently, GC metabolites were analyzed in combination with adipogenic and osteogenic differentiation. We also analyzed 216 patients treated with prednisolone or methylprednisolone for different inflammatory diseases. Bone mineral density, fractures, and history of falls were investigated in combination with genotyping for single nucleotide polymorphisms of HSD11B1 as parameter of 11\u03b2-HSD1 activity. Our in vitro experiments prove that not only the activation of prednisone to prednisolone but also the reverse step of inactivation is catalyzed by 11\u03b2-HSD1 with corresponding influence on cell differentiation. In fact, in patients the inactivation of prednisolone seems to be the dominant effect influencing bone mineral density. Our results change the understanding of GC responsiveness in patient treatment and further highlight the significance of prereceptor GC regulation by 11\u03b2-HSD1.<\/jats:p>","DOI":"10.1093\/pnasnexus\/pgaf315","type":"journal-article","created":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T05:41:41Z","timestamp":1760766101000},"source":"Crossref","is-referenced-by-count":0,"title":["The local inactivation of glucocorticoid as regulator for the development of glucocorticoid-induced osteoporosis"],"prefix":"10.1093","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5016-2591","authenticated-orcid":false,"given":"Martina","family":"Blaschke","sequence":"first","affiliation":[{"name":"Clinic of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center , 37075 G\u00f6ttingen ,","place":["Germany"]},{"name":"Medical Care Center (MVZ) Endokrinologikum G\u00f6ttingen , 37075 G\u00f6ttingen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ina","family":"Dressel","sequence":"additional","affiliation":[{"name":"Clinic of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center , 37075 G\u00f6ttingen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regine","family":"K\u00f6pp","sequence":"additional","affiliation":[{"name":"Clinic of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center , 37075 G\u00f6ttingen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriele","family":"Armbrecht","sequence":"additional","affiliation":[{"name":"Center for Muscle and Bone Research, Charit\u00e9 , 12203 Berlin ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Sehmisch","sequence":"additional","affiliation":[{"name":"Clinic for Trauma Surgery, Orthopedics and Reconstructive Surgery, University Medical Center , 37075 G\u00f6ttingen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mladen V","family":"Tzvetkov","sequence":"additional","affiliation":[{"name":"Department of General Pharmacology, University Medicine Greifswald , 17487 Greifswald ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3030-5388","authenticated-orcid":false,"given":"Frank","family":"Streit","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, University Medical Center , 37075 G\u00f6ttingen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4647-057X","authenticated-orcid":false,"given":"Holger M","family":"Reichardt","sequence":"additional","affiliation":[{"name":"Institute for Cellular and Molecular Immunology, University Medical Center , 37075 G\u00f6ttingen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claus-C","family":"Gl\u00fcer","sequence":"additional","affiliation":[{"name":"Biomedical Imaging Section, Department of Radiology and Neuroradiology, MOINCC , 24118 Kiel ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8366-8625","authenticated-orcid":false,"given":"Heide","family":"Siggelkow","sequence":"additional","affiliation":[{"name":"Clinic of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center , 37075 G\u00f6ttingen ,","place":["Germany"]},{"name":"Medical Care Center (MVZ) Endokrinologikum G\u00f6ttingen , 37075 G\u00f6ttingen ,","place":["Germany"]},{"name":"Clinic for Trauma Surgery, Orthopedics and Reconstructive Surgery, University Medical Center , 37075 G\u00f6ttingen 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