Prevalence, risk factors and management of bone complications in Cushing`s syndrome across Europe. Data from the European Registry on Cushing’s syndrome (ERCUSYN) - 04/02/26

Doi : 10.1016/j.ando.2026.102490

Aleksandra Zdrojowy-Wełna ^1,⁎ , Claudia Amaral ², Marta Araujo-Castro ³, Nienke Biermasz ⁴, Marek Bolanowski ¹, Jens Bollerslev ⁵, Thierry Brue ⁶, Davide Carvalho ⁷, Frederic Castinetti ⁸, Filippo Ceccato ⁹, Justine Cristante ¹⁰, Daniela Dadej ¹¹, Mario Detomas ¹², Timo Deutschbein ^12,¹³, Emanuele Ferrante ¹⁴, Atanaska Elenkova ¹⁵, Joan Gil ^16,¹⁷, Ezio Ghigo ¹⁸, Aleksandra Gilis-Januszewska ¹⁹, Roberta Giordano ²⁰, Miklos Goth ²¹, Cecile Greaud ²², Yona Greenman ²³, Daniela Guelho ²⁴, Irena Ilovayskaya ²⁵, Sonia Kaniuka-Jakubowska ²⁶, Darko Kastelan ²⁷, Tomaz Kocjan ^28,²⁹, Irina Komerdus ²⁵, Michal Krsek ³⁰, Dominique Maiter ³¹, Olga Moros ³², Katarina Mlekuš Kozamernik ²⁸, Eleni Papakokkinou ³³, Giuseppe Reimondo ³⁴, Oskar Ragnarsson ³³, Martin Reincke ³⁵, Helga Sigurjonsdottir ³⁶, Christian J. Strasburger ³⁷, Antoine Tabarin ³⁸, Miklós Tóth ³⁹, Greisa Vila ⁴⁰, Birute Zilaitiene ⁴¹, Alicia Santos ¹⁷, Susan M Webb ¹⁷, Elena Valassi ^16,⁴²

ERCUSYN Study Group

¹ Department of Endocrinology and Internal Diseases, Wroclaw Medical University, Wroclaw, Poland

² Centro Hospitalar Universitário de Santo António, Porto, Portugal

³ Department of Endocrinology & Nutrition. Ramón y Cajal University Hospital, Madrid, Spain

⁴ Leiden University Medical Center, Leiden, The Netherlands

⁵ Faculty of Medicine, University, Oslo, Norway

⁶ Aix Marseille Univ, INSERM, UMR1251, Marseille Medical Genetics, Institut MarMaRa and Department of Endocrinology, La Conception Hospital, APHM, Marseille, France

⁷ Hospital de Sao João, Faculty of Medicine, Universidade do Porto, Porto, Portugal

⁸ Aix Marseille Université, Marseilles, France

⁹ Endocrinology Unit, University-Hospital of Padova, Padova, Italy

¹⁰ Centre Hospitalier Universitaire de Grenoble, Grenoble, France

¹¹ Poznan University of Medical Sciences, Poznań, Poland

¹² Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, Germany

¹³ Medicover Oldenburg MVZ, Oldenburg, Germany

¹⁴ Endocrinology Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy

¹⁵ Expert Center for Rare Endocrine Diseases - Sofia; Department of Endocrinology, Medical University, Sofia, Bulgaria

¹⁶ Germans Trias i Pujol Hospital and Research Institute, Badalona, Spain

¹⁷ IR SANT PAU, Hospital de la Santa Creu i Sant Pau, EndoERN and CIBERER U747, ISCIII, Univ Autònoma Barcelona, Barcelona, Spain

¹⁸ Division of Endocrinology, Diabetology and Metabolism, University of Turin, Turin, Italy

¹⁹ Department of Endocrinology, Jagiellonian University, Medical College, Krakow, Poland

²⁰ Department of Biological Science; University of Turin, Turin, Italy

²¹ Div. of Endocrinology, 2nd Dept. of Internal Medicine, Central Hospital Northern Pest – Military Hospital, Budapest, Hungary

²² Bicêtre Hospital, Paris, France

²³ Institute of Endocrinology, Diabetes, Metabolism and Hypertension, Tel Aviv-Sourasky Medical Center and Tel Aviv University, Tel Aviv, Israel

²⁴ CHUC - Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal

²⁵ Department of Neuroendocrine Diseases, Moscow Regional Research and Clinical Institute, Moscow, Russia

²⁶ Department of Endocrinology and Internal Medicine, Medical University of Gdansk, Gdansk, Poland

²⁷ Department of Endocrinology, University Hospital Zagreb, Zagreb, Croatia

²⁸ Department of Endocrinology, Diabetes and Metabolism, University Medical Centre Ljubljana, Ljubljana, Slovenia

²⁹ Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

³⁰ 3rd Department of Medicine – Department of Endocrinology and Metabolism, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republik

³¹ Department of Endocrinology, UCLouvain Cliniques Saint Luc, Brussels, Belgium

³² Zentrum für Endokrinologie, Diabetologie, Rheumatologie, Dortmund, Germany

³³ Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden

³⁴ Department of Clinical and Biological Sciences, AOU San Luigi, University of Turin, Turin, Italy

³⁵ Medical Department IV, University Hospital, LMU Munich, Munich, Germany

³⁶ Dept of Medicine, Landspitali University Hospital and School of Medicine, University of Iceland, Reykjavik, Iceland

³⁷ Dept of Endocrinology and Metabolism, Charitè Universitätsmedizin Berlin, Berlin, Germany

³⁸ Endocrinologie - Diabète et Nutrition du CHU de Bordeaux, Bordeaux, France

³⁹ Department of Internal Medicine and Oncology, Semmelweis University, Budapest, Hungary

⁴⁰ Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Austria

⁴¹ Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania

⁴² School of Medicine, Universitat Internacional de Catalunya (UIC), Barcelona, Spain

^⁎ Corresponding author: Department of Endocrinology and Internal Diseases, Wroclaw Medical University, Wyb. Pasteura 4, 50-367 Wroclaw, Poland Department of Endocrinology and Internal Diseases, Wroclaw Medical University Wyb. Pasteura 4 Wroclaw 50-367 Poland

Sous presse. Manuscrit accepté. Disponible en ligne depuis le Wednesday 04 February 2026

Abstract

Objective: The aim of the study was to investigate bone comorbidities and their management in patients included in the European Register on Cushing`s syndrome (ERCUSYN).

Design: A retrospective multicentric cohort study and on-line survey.

Methods: We analyzed the prevalence of osteoporosis (OP) and fractures among 1682 patients with Cushing`s syndrome (CS), at initial evaluation and during follow-up. All the ERCUSYN partners received a survey addressing bone disease management in CS.

Results: Seven hundred and sixty-six patients (45%) had DXA examination at baseline, of whom 157 (21%) presented OP at spine and 103 (13%) at hip. Risk factors for OP were older age (p=0.038) and lower BMI (p=0.022). An X-ray was performed in 492 (29%) patients and fracture was detected in 87 (18%). Risk factors for fractures at baseline were male sex (p<0.001), muscle weakness (p=0.026) and bone mineral density (BMD) at hip indicating OP (p=0.026). During follow-up, spine BMD deterioration was more common in older patients (p=0.005) and in those with diabetes mellitus (p=0.024), while worsening of hip BMD was more frequent in patients with hypopituitarism (p=0.021), diabetes mellitus (p=0.034), on levothyroxine substitution (p=0.008) and those less often treated with anti-osteoporotic agents (p=0.022). The survey evidenced significant heterogeneity in terms of timing of bone evaluation and treatment initiation.

Conclusions: A significant number of patients with CS experienced OP and fractures. Clinical factors may help to select patients at the highest risk. There are currently no standards of care for the management of bone complications in CS across Europe.

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Key words : osteoporosis, bone fractures, Cushing`s syndrome, hypercortisolism, ERCUSYN

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Prevalence, risk factors and management of bone complications in Cushing`s syndrome across Europe. Data from the European Registry on Cushing’s syndrome (ERCUSYN) - 04/02/26

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