Severe and refractory hypocalcaemia secondary to osteoblastic bone metastases in bladder signet ring carcinoma: A case report and literature review

Symptomatic hypocalcaemia is uncommon, occurring in <2% of patients with malignancy. Osteoblastic bone metastasis as a cause of hypocalcaemia is rare and not reported in bladder cancer.We report a case of refractory hypocalcaemia in a patient with bladder cancer with extensive osteoblastic bone metastases. A 64-year-old male with a history of signet ring bladder carcinoma with osteoblastic bone metastases presented with severe hypocalcaemia with corrected calcium of 1.64 (2.09-2.46) mmol/L as well as hypomagnesemia and hypophosphatemia. He was previously treated with chemotherapy and immunotherapy. Denosumab was also initiated for the prevention of skeletal-related events.Additional investigations showed significantly elevated bone formation markers N-terminal propeptide of type I procollagen and alkaline phosphatase. Chest radiography and computed tomography scan also demonstrated extensive areas of sclerotic bone lesions suggestive of osteoblastic bone metastases. He was diagnosed with severe hypocalcaemia secondary to osteoblastic bone metastases and partly to denosumab, vitamin D deficiency, and hypomagnesemia.He was treated aggressively with calcium and vitamin D replacement.Despite prolonged intravenous calcium replacement and high doses of oral calcium, cholecalciferol, and calcitriol replacement, he had persistent hypocalcaemia with calcium levels ranging from 1.8 to 1.9 mmol/L. He died 4 months after his admission.Osteoblastic bone metastases lead to an increased influx of calcium and phosphate into the bone leading to hypocalcaemia and should be considered as a differential in severe and refractory hypocalcaemia. It is rare and has not been described in bladder cancer. Precaution should be taken upon the initiation of antiresorptive in patients with osteoblastic bone metastases.