Identification of High-Risk Individuals for Osteoporosis and Fragility Fractures in Cushing’s Syndrome: A Promising Predictive Approach

<b>Background</b>: Cushing's syndrome (CS) causes excessive cortisol exposure, leading to significant skeletal complications. However, there is no validated, CS-specific model to predict osteoporosis and fracture risk. This study aimed to identify independent predictors and develop a practical clinical scoring system. <b>Methods</b>: A retrospective study was conducted on 139 patients with CS diagnosed between 2014 and 2025. Demographic, clinical, and biochemical data were analyzed. Osteoporosis was defined using dual-energy X-Ray absorptiometry criteria. Logistic regression analyses identified independent predictors, and the Cushing-Related Osteoporosis Risk Estimation (CORE) Score was constructed from normalized beta coefficients of significant variables. <b>Results</b>: Osteoporosis was present in 35.9% and fragility fractures in 13.4% of patients. Independent predictors included age ≥ 51 years, symptom duration ≥ 13.5 months, diabetes mellitus, late-night salivary cortisol ≥ 0.42 μg/dL, and midnight serum cortisol ≥ 10.25 μg/dL (all <i>p</i> < 0.05). The CORE Score (0-6 points) showed strong diagnostic performance for osteoporosis (AUC 0.827; sensitivity 88%, specificity 72%) and fractures (AUC 0.866; sensitivity 84%, specificity 78%). Each one-point increase in the CORE Score elevates the risk of osteoporotic fracture by 3.13 times (<i>p</i> < 0.001). <b>Conclusions</b>: The CORE Score represents a promising disease-specific tool for early identification of CS patients at increased risk of osteoporosis and fragility fractures, enabling more personalized management and follow-up strategies, such as prioritizing bone-protective interventions and closer skeletal monitoring. Early identification of high-risk individuals may also facilitate timely therapeutic interventions, potentially reducing future fracture risk.