J Bone Metab.  2025 Feb;32(1):38-48. 10.11005/jbm.24.803.

Incidence of Hypercalcemia and Vertebral Fractures Following Denosumab Withdrawal in Lung Cancer Patients: A Longitudinal Cohort Study

• Villanova M
• Chou SH
• Min L

• KMID: 2565577
• DOI: http://doi.org/10.11005/jbm.24.803

Abstract

Background
Bone-target agents (BTAs), including denosumab (DMAb), are one of the bone metastasis treatments that should continue indefinitely. However, BTAs may be interrupted in some cases. In osteoporosis, DMAb withdrawal causes a rebound effect characterized by an increased bone turnover with spine fractures and hypercalcemia; evidence of the DMAb withdrawal effect in oncology is lacking.
Methods
This study aimed to identify the DMAb withdrawal effect amongst lung cancer patients treated with DMAb for bone metastases between January 2020 and December 2021. Patients who discontinued DMAb were included. Encounter notes, radiological and laboratory findings were comprehensively reviewed.
Results
Thirty patients were included with a median follow-up of 21 months (interquartile range [IQR], 10-30) after DMAb discontinuation. Bisphosphonates were administered before starting DMAb in 7 patients (23.3%) and after DMAb withdrawal in 4 cases (13.3%). Three cases of DMAb withdrawal-related hypercalcemia and 3 cases of spine fractures following DMAb cessation were identified in 5 patients (16.7%), all of them were females and the median age was 65 years old (IQR, 65-70). No statistical difference in DMAb duration or number of injections was found in patients developing DMAb withdrawal-related spine fractures or hypercalcemia compared with others (binary logistic regression, p=0.688 and p=0.938, respectively).
Conclusions
Patients with bony-metastatic lung cancer, especially post-menopausal women, are at risk of fractures and calcium abnormalities after DMAb discontinuation, suggesting that DMAb withdrawal effect may also be present in the oncological setting. A close follow-up and careful monitoring during and after discontinuation of DMAb is necessary.

Keyword

Denosumab · Hypercalcemia · Osteoporosis · Risk assessment · Spinal fratures