Disclosure(s): No relevant financial relationship(s) to disclose.
Introduction: This is a case of denosumab-induced hypocalcemia in a female patient with metastatic breast cancer, with baseline chronic kidney disease stage IIIc, and gastroesophageal reflux disease on proton pump inhibitors (PPI). Denosumab, which is a bone antiresorptive therapy, can cause hypocalcemia, particularly in patients with renal impairment, vitamin D deficiency, or those using PPIs. The patient's condition required ICU admission due to the severity of the hypocalcemia.
Description: 79-year-old female presented with perioral numbness, muscle cramping and shortness of breath for 2 days. She recently received denosumab for metastatic breast cancer to the bone. Physical examination was significant for tachypnea, carpopedal spasm on blood pressure measurement. EKG showed QTc of 513. Labs showed calcium of 5.8mg/dl, albumin 3.7 mg/dl, and magnesium of 0.4 mg/dl. Patient was admitted to the ICU for closer monitoring given the concern for respiratory compromise, seizures, and more vigilant electrolytes monitoring. Patient underwent aggressive electrolyte repletion. Later labs showed low-normal Vitamin D 25-OH levels, as well as PTH of 111 pg/dl (normal 15-65 pg/dl). Patient was subsequently downgraded. The patient was discharged on oral magnesium 800 mg twice daily, calcium carbonate 1000 mg twice daily with close follow-up to repeat calcium and magnesium level within 5 days. Her pantoprazole was switched to famotidine.
Discussion: While severe hypocalcemia from denosumab use is relatively rare, the presence of additional risk factors can significantly increase its likelihood, most notably, CKD, PPI usage, vitamin D deficiency, and low-normal calcium level at baseline, as each of these conditions impair either absorption or regulation of calcium, compounding the effect of denosumab. Usually calcium levels are checked two weeks post injection. There are no current guidelines recommending earlier checks even in potentially higher risk patient population. This case highlight the importance of risk factors optimization includes vitamin D and calcium supplementation if needed and thorough medication reconciliation.
