Patient 1 is an 80-year-old woman with stage 3B chronic kidney disease (CKD) who received an inadvertent dose of denosumab 1 month after her regularly scheduled dose. Eighteen days following the second dose, the patient presented to the emergency department with severe weakness that prevented her from getting out of bed. She denied seizures, syncope, chest pain, or palpitations. Neurological exam revealed 4/5 strength in all extremities. Chvostek sign was absent. Chemistries revealed a serum total calcium of 4.2 mg/dL, magnesium 1.2 mg/dL, phosphorous 2.4 mg/dL, ionized calcium 0.56 mmol/L (normal 1.11–1.3 mmol/L), 25-hydroxy vitamin D 11.0 ng/mL (normal 30–100 ng/mL), and intact PTH was >3,639 pg/mL (normal 14–60 pg/mL). Her eGFR on admission was 31 mL/min/1.72m2, and her serum creatinine was 1.9 mg/dL (baseline between 1.5 and 2 mg/dL). Two months prior to admission she had a serum calcium of 9.2 mg/dL. ECG revealed prolonged QT interval of 479 ms and prominent T waves. These two changes caused the automated interpretation of the ECG to indicate a heart rate 133/min, while her clinicians interpreted the heart rate to be 75 (Fig. ).
Patient 2 is a 66-year-old woman with a history of Crohn's disease and an ileostomy. She presented to the emergency department with profound, debilitating weakness 22 days following her regularly scheduled dose of denosumab. She had received biannual treatments for 5 years at this point. Neurological exam revealed 5-/5 strength in all extremities. She exhibited mild psychomotor slowing. Chvostek sign was absent. Serum chemistries demonstrated a serum total calcium of 4.5 mg/dL, magnesium 1.6 mg/dL, phosphorous of <1.0 mg/dL, ionized calcium 0.89 mmol/L and intact PTH 2,356 pg/mL. 25-hydroxy vitamin D was 4 ng/mL. The last prior vitamin D measurement in our records was 2 years prior and measured <4.0 ng/mL. This measurement was drawn 2 weeks after a dose of denosumab was administered, and the importance of supplementation was reinforced to the patient at that time. This patient had no evidence of CKD with an eGFR of 101 mL/min/1.72m2 and a serum creatinine of 0.7 mg/dL. It should be noted that patient 2 had a history of mild, asymptomatic hypocalcemia (with values ranging from 6.0 to 10.4 mg/dL) in the year prior to admission with an intact PTH ranging between 300 and 500 pg/mL and mildly low serum phosphorous levels. Vitamin D deficiency limiting intestinal phosphorous absorption and denosumab-induced elevated PTH levels causing phosphaturia would account for hypophosphatemia. Patients with vitamin D deficiency in the absence of denosumab treatment typically have mildly elevated PTH levels, though generally no higher than 110 pg/mL []. The laboratory findings upon admission of both patients are presented in Table .