Prevalence and treatment of osteoporosis and bone fractures in Cushing's syndrome across Europe

Abstract

Introduction Real-world data on management of bone alterations in Cushing’s syndrome (CS) are scanty. The aim of our study was to assess the prevalence of osteoporosis (OP) and bone fractures (BF) in CS patients included in the European Registry on Cushing’s Syndrome (ERCUSYN), and to describe the diagnostic and therapeutic strategies adopted across Europe to address these comorbidities. Patients and methods In this retrospective, observational cohort study, we evaluated the prevalence of OP and BF in 1684 patients (81% females; mean age 44 (G14.1) years) of whom 1234 (73%) had a pituitary-dependent (PIT-CS) and 450 (27%) an adrenal-dependent (ADR-CS) CS from 60 European centers in 26 countries. In addition, we created a survey to collect real-life data on bone disease management in CS. Results A dual-energy X-ray absorptiometry (DXA) was performed in 766 (51%) patients at diagnosis. Lumbar and hip OP were found in 21% and 13% of patients, respectively. After treatment, lumbar and hip OP were found in 18% and 11% of patients respectively, after a median follow-up of 24 (36) months, with a similar prevalence between patients in remission (78%) and those with persistent disease (22%). Fractures were present in 17% of patients at diagnosis, most in the spine (30%). Patients with BF at the time of diagnosis were older than patients without [mean (G S.D.) age 48.3G13.1 vs 43.4G14.2 years; P!0.001] and were more often males (P!0.001). Median delay to diagnosis was longer in patients with BF as compared with those without [3 (3.5) vs 2 (2) years, PZ0.02] at diagnosis. Most of the survey responders (87%) evaluate bone health using DXA in all newly diagnosed patients, whereas the remaining only assess it in high-risk patients. Forty-six percent of responders perform X-ray only in patients with fracture symptoms. Seventy-six percent of the centers start specific treatment in all patients with OP at diagnosis, 21% only treat patients with fractures. After successful treatment, 59% of the responders re-check bone status within two years,whereas the remaining individualize control based on fracture risk stratification. The most widely used medications to treat OP and/or BF are vitamin D with calcium (74%), zolendronate (72%), alendronate (59%), denosumab (49%), risendronate (25%) and teriparatide (25%). Conclusions There is a need to optimize the management of bone impairment across Europe. In the ERCUSYN cohort, older age, male sex and longer delay to diagnosis were associated with increased rate of fractures at the time of diagnosis.