Prevalence and Incidence of Fractures in Patients With Nonfunctional Adrenal Tumors

Abstract

Importance: It is unclear whether nonfunctional adrenal tumors (NFATs) are associated with fractures. Objective: To analyze fracture frequencies in individuals with NFATs. Design, Setting, and Participants: A national retrospective cohort study was conducted in patients with NFATs diagnosed in Sweden between January 1, 2005, and December 31, 2019, and control participants without adrenal tumors followed up until death or the end of 2019. Individuals with a diagnosis of adrenal hormonal excess or previous malignant tumors were excluded. Sensitivity analyses were performed in subgroups of individuals with a combination of gallbladder, biliary tract, and pancreas diseases (for whom it was assumed that controls would also have undergone computed tomography) and 3- and 12-month survival free of malignant tumors after the NFAT diagnosis. The data were analyzed from September to November 2023. Exposures: Diagnosis of NFATs. Main Outcomes and Measures: Main study outcomes were prevalence and incidence of fractures after adjustment for sex, age, and comorbidities. Secondary outcomes were fragility fractures, fractures with fall on the same level, and fracture locations (distal arm and vertebral and hip fractures). Fracture incidence after adrenalectomy was also studied. Results: Among 20390 patients, 12120 (59.4%) were women, and the median (IQR) age was 66 (57-73) years; among 125392 controls, 69994 (55.8%) were women, and the median (IQR) age was 66 (57-73) years. Previous fractures were more common in patients diagnosed with NFATs compared with controls (4310 of 20390 [21.1%] vs 20323 of 125392 [16.2%]; odds ratio [OR], 1.39; 95% CI, 1.34-1.45; adjusted OR [AOR], 1.27; 95% CI, 1.23-1.33). During the follow-up period (median [IQR], 4.9 [2.2-8.2] years), incident fractures were more common in patients with NFATs (3127 of 20390 [15.3%] vs 16086 of 125392 [12.8%]; hazard ratio [HR], 1.40; 95% CI, 1.34-1.45; adjusted HR [AHR], 1.27; 95% CI, 1.22-1.33). An association between NFATs and vertebral fractures was found (AOR, 1.51; 95% CI, 1.33-1.72; AHR, 1.83; 95% CI, 1.60-2.09). In men younger than 50 years, NFATs were associated with fractures (AOR, 1.45; 95% CI, 1.21-1.74; AHR, 1.48; 95% CI, 1.20-1.82). There was no association among individuals who had undergone adrenalectomy (AHR, 1.12; 95% CI, 0.90-1.38). The association between NFATs and fractures remained significant and of similar magnitude in all sensitivity analyses. Conclusions and Relevance: In this cohort study, NFATs were associated with fractures, particularly among younger men; thus, patients with NFATs should have bone health evaluation with appropriate treatment and monitoring, especially in younger men.