Context: Patients with endogenous Cushing syndrome (CS), in addition to significant cardiovascular morbidity, are burdened by a high prevalence of fragility fractures. Bone mineral density (BMD) alone poorly predicts the risk of fracture, and the implementation of trabecular bone score (TBS) is supported only by scant evidence. Indeed, reliable predictors of fractures in endogenous CS are still lacking.
Objective: This work aimed to analyze the prevalence and the potential predictors of fragility fractures in our patients with CS.
Methods: A monocentric, retrospective, cross-sectional study. A total of 51 patients with overt CS were enrolled. Main outcome measures included biochemical evaluation, BMD measurement, TBS evaluation, fracture presence, body composition evaluation, and arterial intima-media thickness (IMT) assessment.
Results: Fragility fractures were found in 62.7% of patients at diagnosis. Fractured patients exhibited lower spine T-score (P = .03), longer disease duration (P = .025), higher waist circumference (P = .006), and predominantly male sex (P = .008). Increased serum uric acid levels (P = .001), greater IMT (P = .017), and higher prevalence of venous thromboembolism events (31.3% vs 5.3%, P = .037) and atherosclerotic plaques (47% vs 5.3%, P = .002) were described in the fracture group.Multivariable logistic regression identified the presence of atherosclerosis (OR 13.35; 95% CI 1.154-154.34, P = .038) and osteoporosis (OR 11.30; 95% CI 1.55-82.56, P = .017) as independent predictors. TBS values were inversely correlated with body mass index, fat and lean mass, and serum uric acid, and positively correlated with high-density lipoprotein cholesterol.
Conclusion: CS patients with higher overall burden of cardiovascular morbidity are more prone to experience fragility fractures.
Keywords: Cushing syndrome; TBS; cardiovascular morbidity; fragility fractures.
© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society.