Doc! I Have an Urgent Consultation for a Patient with Severe Hypocalcemia and Hypomagnesemia

Multiple myeloma (MM) is known to cause accelerated osteoclastogenic and increased bone resorption through Receptor Activator of Nuclear Factor Kappa-B Ligand pathway (RANKL). Denosumab, which is a RANKL inhibitor is commonly used in treating hypercalcemia in these patients. Incidence of hypocalcemia is 8-14% after the administration of denosumab in such patient population. We present a case of severe hypocalcemia and hypomagnesemia in a patient with multiple myeloma and CKD after treatment with Denosumab.

Case Description:

A 68-year-old African American male admitted with recent onset altered mental status. Family reported him complaining of headache, nausea, vomiting and abdominal discomfort few days prior to this admission. Patient was an elderly appearing frail man, confused at exam. He did not have any motor weakness, tics, tremors. Chvostek and Trousseau’s sign were negative on admission. He was found to be hypocalcemic at 5.3 mg/dL (8.9-10.4), ionized calcium 0.88 mmol/L (1.09-1.30), EKG showing prolonged QTc interval to 541 ms (normal < 450). Other labs were significant for low magnesium 1.1 mg/dL (1.8 -2.5), vitamin D 25 OH 12.8 ng/dL, eGFR 40 ml/min/1.73 m2 and appropriately elevated PTH 208.9 pg/mL (10-65). CT head without contrast showed no acute intracranial abnormality. Non-contrast CT abdomen/pelvis demonstrated cholelithiasis without evidence of acute cholecystitis. Extensive lucent lesions were seen throughout the bony structures. Patient was diagnosed with multiple myeloma a month prior and received first-line treatment with the cyclophosphamide, bortezomib and dexamethasone. On further review, he had received denosumab (60 mg subcutaneously) for severe hypercalcemia of 13.0 mg/dl from underlying MM with lytic bone lesions, two weeks prior to this admission. Patient responded to treatment with intravenous calcium gluconate, calcitriol 0.5mcg oral twice daily, calcium carbonate, vitamin D3 (total elemental calcium 1.8 gm and 1500 mcg Vitamin D3 daily) and magnesium supplements. Calcium levels improved to 7.6 mg/dl, magnesium 1.9, ionized calcium 1.13 mmol/l (1.09-1.30). He was discharged home on the same regimen of calcium, calcitriol and vitamin D3 with close follow up scheduled with our clinic.

Discussion:

Denosumab prevents skeletal-related complications and treats hypercalcemia in patients with bone metastases with underlying multiple myeloma and CKD. Severe hypocalcemia ( <7 meq/dl) or symptomatic hypocalcemia is known with denosumab use in patients with renal dysfunction. Weight-based dose of denosumab (0.3 mg/kg) in advanced CKD (eGFR < 30 ml/min) has been proposed in literature to minimize the risk of hypocalcemia. We suggest caution with use of denosumab in patients with eGFR between 30-45ml/min, with closer follow-up to prevent hypocalcemia. In our patient, hypovitaminosis D and hypomagnesemia could have contributed to this complication.