Chronic kidney disease and denosumab in metastatic bone disease: A multicenter Turkish cohort study on severe hypocalcemia, skeletal events, and survival
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background: Denosumab, a monoclonal antibody against receptor activator of nuclear factor kappa-B ligand (RANKL), is widely used to prevent skeletal-related events (SREs) in patients with bone metastases from solid tumours. However, its safety in individuals with advanced chronic kidney disease (CKD), particularly regarding severe hypocalcaemia and skeletal complications, is not well defined. Methods: We conducted a retrospective, multicentre study within the Turkish Oncology Group including patients with breast, prostate, or lung cancer who received denosumab between January 2011 and December 2022. Demographic and clinical data, CKD stage, prior fractures, serum calcium levels, episodes of hypocalcaemia, concomitant medications, and adverse events were recorded. Primary endpoints were the incidences of grade ≥ 3 hypocalcaemia and other grade ≥ 3 toxicities; secondary endpoints included skeletal-related events and overall survival. Results: We analysed 264 patients from 17 oncology centres. Overall, 18 patients (6.8 %) experienced grade ≥ 3 toxicity, including 16 cases of severe hypocalcaemia and two of renal function decline. Among 42 patients with baseline estimated glomerular filtration rate (eGFR) < 60 mL/min, 13 (31.0 %) developed grade ≥ 3 toxicity (11 hypocalcaemia, two renal decline), representing a significantly higher risk than in patients with eGFR ≥ 60 mL/min (p < 0.01). Pathological fractures occurred in 21 patients, six with eGFR < 60 mL/min (p = 0.035). Eight patients required surgery for skeletal-related events, four with eGFR < 60 mL/min (p = 0.012). Conclusion: Cancer patients with CKD receiving denosumab have an increased risk of severe hypocalcaemia and skeletal complications. Close monitoring of calcium and renal function is essential, and clinicians should carefully balance the benefits of denosumab against these risks in this vulnerable population.
Source: Journal of bone oncology
Authors: Halil İbrahim Ellez, Hüseyin Salih Semiz, Ferhat Ekinci, Atike Pınar Erdoğan, Fatih Kuş, Fatih Karataş, Ertuğrul Bayram, Kubilay Karaboyun, Havva Yeşil Çınkır, Nilgün Yıldırım, Melek Karakurt Eryılmaz, Esma Türkmen Bekmez, Özkan Alan, Melike Özçelik, Yakup Düzköprü, Teoman Şakalar, Naziye Ak, Yusuf İlhan, Tuğba Yavuzşen, Nazım Serdar Turhal
Institutions: Şanlıurfa Mehmet Akif İnan Eğitim ve Araştırma Hastanesi, Sağlık Bilimleri Üniversitesi, Dokuz Eylül University, Manisa Celal Bayar University, Hacettepe University, Karabük University, Cukurova University, Ağrı Eğitim ve Araştırma Hastanesi, Gaziantep University, Fırat University, Necmettin Erbakan University, Health Sciences University Derince Training and Research Hospital, Koç University, Ümraniye Eğitim ve Araştırma Hastanesi, Aksaray University, Kahramanmaraş Sütçü İmam University, Istanbul University, Antalya Şehi̇r Hastanesi̇
Language: English
Topic: Bone health and treatments
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,990
OpenAlex ID: W4416528244