Bone safety of dual-release hydrocortisone in patients with autoimmune primary adrenal insufficiency

BACKGROUND: 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. METHODS: 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. RESULTS: 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 ± 0.195 vs. 0.942 ± 0.124 g/cm(2), p=0.025) and at femoral neck (FN; 0.633 ± 0.114 vs. 0.716 ± 0.088 g/cm(2), p=0.045). Moreover, they were characterized by a lower trabecular bone score (TBS; 1.236 ± 0.035 vs. 1.383 ± 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(2) 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. CONCLUSIONS: 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.