Increased risk of osteoporotic fractures and osteoporosis in patients with Addison's disease in Sweden: A nationwide population‐based cohort study

Abstract Background The risk of major osteoporotic fractures (MOFs) and osteoporosis in patients with autoimmune Addison's disease (AAD) is unclear. Objective To investigate the risk of MOF in patients with AAD and the possible correlation with adrenal hormone replacement doses. Methods Swedish national health registers were used to identify 1869 subjects with AAD and 16,844 matched controls. The primary outcome was MOF, and the secondary outcome was treatment with osteoporosis medications. Marginal Cox models were used to compare time‐to‐event outcomes. The study period spanned from 1 July 2005 until 31 December 2020. Individuals at risk were followed from inclusion until censored or the end of the study period. Results A total of 77 patients with AAD (7.1/1000 person‐years [PY]), and 387 matched controls (3.9/1000 PY) were diagnosed with MOF. The risk of MOF was higher in patients with AAD compared to matched controls, with an adjusted hazard ratio (aHR) of 1.82 (95% confidence interval [CI], 1.41–2.35) and increased in both male and female patients, with aHR of 2.51 (95% CI, 1.56–4.02) and 1.65 (95% CI, 1.22–2.24), respectively. Patients with AAD had an increased risk of treatment with osteoporosis medications: aHR 3.25 (95% CI, 2.71–3.99), compared to controls. No significant differences in MOF rates were observed between patients treated with intermediate or high doses of glucocorticoids compared to low doses ( p = 0.967 and p = 0.580, respectively). Similarly, stratification by mineralocorticoid dose (<0.10 vs. ≥0.10 mg/day) showed no significant association regarding MOF ( p = 0.915). Conclusions The risk of MOF is increased in patients with AAD without any apparent correlation to adrenal hormone replacement doses.