Denosumab Induced Severe Hypocalcemia in a Patient With Metastatic Prostate Cancer

Abstract

Background: Denosumab can lead to severe hypocalcemia in patients with underlying risk factors such as vitamin D deficiency, low PTH, hypomagnesemia, and CKD. Denosumab is a monoclonal antibody against RANKL, reducing the activity of osteoclasts and thus reducing the release of calcium in the bloodstream causing hypocalcemia. Hypocalcemia can range from mild to severe symptoms requiring prolonged hospitalization. Medications such as zoledronic acid and Denosumab are known to reduce the occurrence of Skeletal related events (pathological fracture, spinal cord compression, and radiation to bone). For metastatic prostate cancer, about 90% can develop bone metastasis with significant morbidity and mortality [1]. Our patient presented with severe hypocalcemia after denosumab use without any above risk factors. Clinical Case: A 66-year-old male with a medical history of Prostate cancer with Metastasis to chest and bone presented to ER with syncope. Patient-reported poor oral intake, nausea, and vomiting for the last few days. In the ER, the patient was found afebrile, bp 116/76, HR 92, saturating 100% on room air. On examination, the patient was found lethargic, malnourished, foley in place due to chronic urinary retention. The abdomen was soft and non-tender. Laboratory findings were significant for Hb 9.1, Na 133, K3.6, bicarb 21, total calcium (Ca) 4.2, ionized Ca 0.63 and corrected Ca 5.4, magnesium 1.6, phosphorus 2.1, albumin 3.3, ALT 218, AST 229, ALP 1607. Lipase 82, Total bilirubin 1.5, direct bilirubin 0.8. Spot Urinary Ca 0.7, Vitamin D 25 OH 36.9, serum PTH 225 pg/mL. Serum cortisol AM 20.9, BUN 16, and serum Creatinine 1.0. The patient was started on 11g calcium gluconate in 1L dextrose @ 50c/hr and calcitriol 0.25mcg twice daily. Serum Ca level was monitored every 6 hours and reached 6.7. Later was started on Ca carbonate 1250 TID with meals. Finally, after electrolyte correction, the patient clinically improved and was discharged with the plan to follow Calcium at the outpatient clinic. On review of previous labs at the oncology clinic, the patient received Denosumab at his oncologist’s clinic 10 days before this hospital admission, last Ca level from 6 months ago 8.6, the patient was not any vitamin D or Ca supplement. Conclusion: Many case reports have been published on severe hypocalcemia after denosumab usage. Several patients had underlying risk factors such as vitamin D deficiency, osteoblastic lesion, and AKI leading to an additional cause of hypocalcemia. We emphasize careful monitoring of serum Ca levels particularly in the first few weeks of treatment even without significant risk factors for hypocalcemia. References: [1] Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Bubendorf L, Schöpfer A, Wagner U, Sauter G, Moch H, Willi N, Gasser TC, Mihatsch MJ. . Hum Pathol. 2000 May; 31(5):578–83