Denosumab-induced Hypocalcemia in Patients with Osteoporosis and Normal Renal Function

Introduction: The reported hypocalcemia was low in denosumab-treated postmenopausal women with osteoporosis (0.05-1.7% to 7.4%). The major prediction factors were Vitamin D and calcium levels and renal function. Aim: To assess the rate of hypocalcemia in patients with osteoporosis treated with denosumab, with normal renal function and Vitamin D. Materials and Methods: A retrospective analysis was conducted using the medical records (2021-2022). We looked for hypocalcemia (albumin-adjusted calcium lower than 2.1 mmol/L). Results: We included 201 women with postmenopausal osteoporosis who received denosumab treatment plus prophylactic Vitamin D3 capsules. The mean age of the patient population was 75.7 +/- 7.0 years (56-91 years). Hypocalcemia was observed in 46 (23%) patients following a single subcutaneous dose of denosumab 60 mg. Median calcium was 2.25 mmol/L (minimum: 0.890 mmol/L, maximum: 2.6 mmol/L). Fourteen (30.4%) patients had severe cases (< 1.8 mmol/L) and required parenteral correction. A comparison between hypocalcemia and patients with normal calcium indicated that the strongest predictors of hypocalcemia were pretreatment parathyroid hormone levels (9.9 +/- 0.5 vs. 7.6 +/- 0.5 pg/L, respectively; p<0.005). Eight patients (3.3%) developed hypophosphatemia. The baseline serum albumin, calcium, and alkaline phosphatase levels were normal. Conclusion: The denosumab-associated hypocalcemia is more prevalent than previously shown in patients with osteoporosis receiving adequate calcium and Vitamin D supplementation. An elevated parathyroid hormone is an important predicting factor in patients with normal calcium and Vitamin D levels.