MON-767 - A Silent Drop; Denosumab and Calcium Paradox in ESRD Patient.

Introduction:
Patients receiving dialysis are at markedly increased risk for osteoporosis and fractures; however, therapeutic decisions are complicated by chronic kidney disease–mineral and bone disorder (CKD-MBD). Denosumab is often considered an attractive option in advanced CKD because it is not renally cleared, yet its potent antiresorptive effect can precipitate clinically significant hypocalcemia. This case highlights a severe and prolonged hypocalcemia following denosumab administration in a peritoneal dialysis patient with secondary hyperparathyroidism.

Case presentation:
A 57-year-old woman with a past medical history of ESRD on peritoneal dialysis, coronary artery disease, chronic CHF, hypertension, hyperlipidemia, history of DVT/PE, type 1 diabetes mellitus, hypothyroidism, osteoporosis, chronic pancreatitis, restless leg syndrome presented to the hospital with fatigue and muscle cramps in bilateral upper and lower extremities. Labs were pertinent for hypocalcemia of 5 mg/dl. She had received denosumab for the treatment of osteoporosis 5 days prior and also skipped calcitriol after having received denosumab. She underwent peritoneal dialysis upon admission and received IV calcium gluconate, and calcitriol. Following that, her calcium levels gradually increased to 6.2 mg/dl. Calcium carbonate and vitamin D were added. She was also treated for pneumonia during this hospitalization. She was discharged home on calcitriol, and vitamin D. Subsequently, she returned with similar symptoms of exhaustion and brain fog with concern for medication non-compliance. Labs again were significant for hypocalcemia of 5.5. She was managed with IV calcium gluconate, calcium carbonate, vitamin D, and calcitriol. After her calcium level stabilized to 8.7 mg/dl, she was discharged home.

Conclusion:
Denosumab suppresses osteoclast-mediated bone resorption by inhibiting RANKL, thereby reducing skeletal calcium efflux. In patients with preserved renal function, compensatory mechanisms—particularly parathyroid hormone–mediated calcium mobilization—limit the severity of hypocalcemia. In contrast, dialysis patients frequently have impaired calcitriol synthesis, elevated fibroblast growth factor-23, and high bone turnover due to secondary hyperparathyroidism, creating a “calcium sink” when bone resorption is abruptly inhibited. This pathophysiology likely explains the profound hypocalcemia observed in this patient despite vitamin D optimization.
Although denosumab-associated hypocalcemia has been reported in CKD, severe symptomatic cases in peritoneal dialysis patients remain uncommon. Observational data suggest that lower baseline serum calcium, reduced kidney function, and higher bone turnover states increase risk. Notably, hypocalcemia may occur after any dose and may be delayed, underscoring the importance of longitudinal monitoring.

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