Severe Hypocalcemia Induced by a Single Dose of Denosumab in a Patient with Osteomalacia Secondary to Long Standing Vitamin D Deficiency

Objective: Denosumab is a human monoclonal antibody that inhibits osteoclastic bone resorption via inhibition of RANKL. Hypocalcemia is a known risk of denosumab, but it can be very severe and resistant to treat when administered without adequate replacement of calcium and vitamin D. Methods: 32-year-old lady with history of rickets secondary to vitamin D deficiency was diagnosed with osteoporosis on DEXA scan and prescribed denosumab. She presented to ER within 24 hours with carpo-pedal spasms and was found to be severely hypocalcemic with ionized calcium of 2.2mg/dL (4.7- 5.3 mg/dl) and total calcium of 4.7 mg/dL (8.5-10.5 mg/dl). Her vitamin D levels and magnesium levels were also low. Her hypocalcemia was very resistant to treatment and required aggressive replacement of calcium and magnesium along with vitamin D and calcitriol. Results: We hereby report a case of life threatening hypocalcemia in a patient with vitamin D deficiency that occurred after administration of denosumab. Treatment required 130 grams of calcium, 48 grams of magnesium and 500,000 units of vitamin D with 10 mcg of calcitriol over a period of 10 days. Conclusion: Thorough evaluation for secondary causes of low bone density should be done prior to administering antiresorptive therapy in subjects suspected to have osteoporosis. We also emphasize that hypocalcemia can be extremely resistant to treatment when there is concomitant magnesium deficiency and if present should be replaced aggressively in subjects with hypocalcemia.