A Double Dip: Concurrent Hypocalcemia and Hypophosphatemia After Denosumab in a Patient with CKD

Introduction: Hypocalcemia is a commonly reported adverse event following denosumab infusion, especially among patients with chronic kidney disease (CKD). Hypophosphatemia is a lesser reported but equally important risk following denosumab. We report a case of severe hypophosphatemia and hypocalcemia after the administration of denosumab in a patient with CKD. Case Description: A 71-year-old woman with history of bilateral lung transplant, hypertension, and CKD stage 4 due to biopsy proven calcineurin inhibitor toxicity presented for routine follow up and was found to have calcium 7.7 mg/dL and phosphorus 1.1 mg/dL. Ten days prior to the visit she had received a denosumab infusion and had recently stopped her daily calcium supplement. Additional evaluation revealed creatinine within baseline range at 2.0 mg/dl, increase in PTH from 38 pg/ml 2 months prior to 572 pg/ml, normal 25-hydroxy vitamin D of 31 mg/mL, and elevated 1,25-dihydroxy vitamin D of 115 pg/ml. Urine studies confirmed urinary phosphorus wasting with urine phosphorus to creatinine ratio of 534 mg/g and fractional excretion of phosphorus of 49%. As she was asymptomatic, she declined hospital admission for IV phosphorus infusion. She was prescribed oral phosphorus and calcium supplementation with frequent outpatient labs until her calcium and phosphorus normalized while tapering her supplements. Subsequently, her serum calcium and phosphorus levels remained stable within normal limits off supplementation and PTH improved to 109 pg/ml. Discussion: Hypocalcemia is frequently reported after denosumab infusion, especially among patients with CKD, but hypophosphatemia is rarely reported. A small proportion of patients with CKD were included in the initial trials studying denosumab and hypocalcemia was not a statistically significant adverse event in those trials, though this has since been described in multiple case reports. There are fewer case reports of hypophosphatemia after denosumab infusion, but this represents an important adverse event. The proposed mechanism involves reduction in serum calcium (due to decreased osteoclast activity) leading to hyperparathyroidism and subsequent urinary phosphorus wasting. We recommend clinicians proactively supplement calcium and vitamin D in patients with CKD receiving denosumab and monitor serum calcium and phosphorus levels around 10-14 days after denosumab administration.