Epileptic seizures associated with denosumab

Denosumab is a fully human monoclonal antibody that targets the receptor activator of nuclear factor κB ligand (RANKL). By specifically binding to RANKL, it inhibits osteoclast formation, activation, and survival, thereby reducing bone resorption and increasing bone mineral density. Clinically, it is primarily used for the treatment of osteoporosis (OP) in patients at high risk of fracture and for preventing skeletal-related events in patients with bone metastases. Notably, RANK is also expressed in neurons, microglia, and astrocytes. Accumulating evidence indicates that the RANKL/RANK/NF-κB signaling pathway modulates neuroinflammation, neurotrophic support, and cognitive processes. We describe the first case of epileptic seizures following subcutaneous denosumab administration in a patient with OP. The Naranjo score was 7, indicating a probable causal relationship. This report aims to alert clinicians to this rare yet potentially severe neurological adverse reaction and to contribute to medication safety.