A 43-year-old female patient with chronic kidney disease stage 5 received a single subcutaneous dose of 60 mg of denosumab for osteoporosis. Prior to treatment, her calcium level was 2.25 mmol·L^-1. After 13 days, she experienced numbness in her limbs and mouth corners, as well as muscle spasms. Her blood calcium dropped to 1.12 mmol·L^-1, and an electrocardiogram revealed a prolonged QT interval. Symptoms improved with intravenous and oral calcium plus active vitamin D treatment, raising her blood calcium to 2.23 mmol·L^-1. Following discharge from the hospital, the patient continued oral calcium supplementation. However, during the six-month follow-up period, it was observed that the patient still experienced recurrent hypocalcemia. The Naranjo’s assessment scale indicated that severe and refractory hypocalcemia was very likely associated with denosumab. This case highlights the importance of vigilance for hypocalcemia in chronic kidney disease patients following denosumab administration, emphasizing the need for thorough pre-medication assessment and post-medication monitoring to ensure patient safety.

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