Identification of the risk factors associated with hypocalcemia induced by denosumab

Area of Science:

• Oncology
• Pharmacology
• Nephrology

Background:

• Denosumab, a monoclonal antibody, inhibits osteoclast activation and bone resorption.
• Hypocalcemia is a serious adverse effect of denosumab, particularly in advanced cancer patients.
• Risk factors for denosumab-induced hypocalcemia remain largely unreported, hindering predictive monitoring.

Purpose of the Study:

• To identify and characterize the independent risk factors for hypocalcemia following denosumab administration.
• To establish predictive criteria for denosumab-induced hypocalcemia in clinical practice.

Main Methods:

• Retrospective review of 53 patients who received denosumab at Tokushima University Hospital (April 2012 - May 2013).
• Univariate and multivariate logistic regression analyses were employed to identify risk factors.
• Receiver-operator characteristic (ROC) curve analysis determined the optimal creatinine clearance (CCr) cutoff value.

Main Results:

• Eleven out of 53 patients (20.8%) developed hypocalcemia post-denosumab administration.
• Univariate analysis indicated that prior zoledronic acid non-administration and lower CCr were associated with higher hypocalcemia risk.
• Multivariate analysis identified non-administration of zoledronic acid (OR 10.43) and CCr < 50.0 mL/min (OR 5.90) as independent risk factors.

Conclusions:

• Non-administration of zoledronic acid and creatinine clearance below 50.0 mL/min are significant independent risk factors for denosumab-induced hypocalcemia.
• These findings are crucial for proactive monitoring and management of hypocalcemia in patients receiving denosumab.
• Further research may refine patient selection and monitoring protocols for denosumab therapy.