Hungry bone syndrome-like state following denosumab in a patient with multiple myeloma

Denosumab-induced hypocalcemia is a well-recognized entity, especially in patients with renal impairment or vitamin D deficiency. Hungry bone syndrome (HBS), characterized by prolonged hypocalcemia and hypophosphatemia due to rapid skeletal remineralization, is classically seen post-parathyroidectomy and is rare in purely osteolytic malignancies such as multiple myeloma (MM). A 76-year-old man with newly diagnosed MM (extensive osteolytic skeletal involvement) developed severe, prolonged hypocalcemia following two doses of denosumab administered one month apart. Pre-denosumab evaluation showed elevated creatinine and calcium, sufficient vitamin D, and suppressed parathyroid hormone. One week after the second dose, he was found to have profound hypocalcemia, hypophosphatemia, hypomagnesemia, and QT interval prolongation. Despite aggressive oral calcium, calcitriol, and magnesium supplementation, hypocalcemia, hypophosphatemia, and hypomagnesemia persisted. Subsequent evaluation revealed secondary hyperparathyroidism and persistently elevated bone turnover markers (both formation and resorption). Low urinary calcium excretion supported the presence of a skeletal mineral sink. This case highlights an HBS-like state after denosumab-induced osteoclast inhibition in high-turnover osteolytic lesions of MM. Renal impairment and extensive skeletal involvement were predisposing factors. Persistence of elevated resorption marker suggests incomplete suppression of bone resorption due to secondary hyperparathyroidism and renal impairment. Close monitoring and anticipatory mineral supplementation are essential after denosumab in high-risk individuals.