{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T15:31:15Z","timestamp":1777476675607,"version":"3.51.4"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T00:00:00Z","timestamp":1694390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Conventional glucocorticoids (C-GC) replacement regimens have a detrimental effect on skeletal health in patients with adrenal insufficiency (AI), ultimately leading to an increased fracture risk. The novel dual-release hydrocortisone (DR-HC) formulations are characterized by a more favourable safety profile on various clinical endpoints. Data comparing the impact of C-GC and DR-HC on bone, however, are scarce.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty-seven patients with autoimmune primary AI (PAI; 13 treated with C-GC and 14 treated with DR-HC) were evaluated to compare bone-related parameters between the two treatment groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>No significant differences between the two treatments groups were observed with respect to bone turnover markers. Patients treated with C-GC showed a lower bone mineral density (BMD) at lumbar spine (LS; 0.791 \u00b1 0.195 vs. 0.942 \u00b1 0.124 g\/cm<jats:sup>2<\/jats:sup>, p=0.025) and at femoral neck (FN; 0.633 \u00b1 0.114 vs. 0.716 \u00b1 0.088 g\/cm<jats:sup>2<\/jats:sup>, p=0.045). Moreover, they were characterized by a lower trabecular bone score (TBS; 1.236 \u00b1 0.035 vs. 1.383 \u00b1 0.030, p=0.004) and by a higher mean number of vertebral fractures per patient (0.75 vs. 0 fractures, p=0.002). TBS was the best predictor of fracture risk, with a pseudo-R<jats:sup>2<\/jats:sup> of 0.593; moreover, at mediation analysis, it was able to fully explain the observed detrimental effect of C-GC, compared to DR-HC, on fracture risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results suggest that DR-HC is associated with less bone-related complications compared to C-GC in patients with PAI. Moreover, TBS seems to play a pivotal role in the mediation of the relationship between glucocorticoid treatment regimens and fracture risk.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1234237","type":"journal-article","created":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T11:27:26Z","timestamp":1694431646000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Bone safety of dual-release hydrocortisone in patients with autoimmune primary adrenal 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