Osteoporosis International · Oct 22, 2026

Hip fracture risk in patients with Cushing's syndrome: a population-based cohort study

By Masri-Iraqi H, Rudman Y, Shochat T et al.

UNLABELLED: Cushing's syndrome causes bone loss, yet the risk of hip fractures remains poorly defined. In this nationwide cohort, patients showed a modestly increased risk of hip fracture, particularly soon after diagnosis. These results underscore the importance of early osteoporosis screening and timely fracture prevention strategies. BACKGROUND: Glucocorticoid-induced osteoporosis is a common complication of Cushing's syndrome (CS). While the increased risk for vertebral fractures is well-established, evidence regarding hip fracture risk is limited. This study investigates the association between endogenous CS and hip fracture risk and examines the effect of remission on this risk. METHODS: A nationwide retrospective matched-cohort study was conducted using the Clalit Health Services database in Israel, including patients diagnosed with endogenous CS between 2000 and 2023. Patients with CS were matched 1:5 to controls based on age, sex, socioeconomic status, and body mass index. The primary outcome was the first diagnosis of hip fractures following the diagnosis of CS. Patients with a history of hip fractures prior to CS diagnosis were excluded. RESULTS: The study included 606 patients with CS and 2,988 matched controls, with a mean age at diagnosis of 47.8 ± 17.1 years; 65.3% were female. Follow-up durations were 14.0 ± 6.5 years for patients with CS and 14.5 ± 6.5 years for controls. Hip fractures occurred in 3.9% of patients with CS and 2.5% of matched controls, corresponding to a modest association in competing risk analysis (HR 1.57, 95% CI 1.0-2.5; p = 0.05). The risk was higher among patients with Cushing's disease (CD) (HR 2.2, 95% CI 1.07-4.75; p = 0.03) but not in those with an adrenal source (HR 1.3, 95% CI 0.6-2.8). Analysis by remission status showed that hip fractures occurred in 4.3% of patients without remission and 3.6% of those in remission, with no significant difference between groups (HR 1.14, 95% CI 0.4-3.0). In multivariate analysis, older age at CS diagnosis and pre-existing osteoporosis were independently associated with an increased risk of hip fracture. CONCLUSION: Endogenous Cushing's syndrome may be associated with an increased hip fracture risk, particularly in CD, driven mainly by older age at diagnosis and pre-existing osteoporosis, with no significant risk reduction after remission. These findings underscore the need for early fracture risk assessment and targeted osteoporosis management in patients with CS.

doi.org/10.1007/s00198-026-08230-zPubMed 42911249Populations