A 55-year-old Caucasian woman on peritoneal dialysis for the last three years due to lupus nephritis was seen in the dialysis clinic for a routine follow-up. Her medical problems included hypertension, secondary hyperparathyroidism, and documented osteoporosis on DEXA scan (Dual energy X-ray absorptiometry) with left femoral neck BMD at 0.637 g/cm2; 2.9 standard deviation below peak BMD. Her medications included Amlodipine 5mg, Cinacalcet 60 mg, and Epoetin weekly injections.\nShe complained of fatigue, muscle cramps, and paresthesias of the hands and feet for the past week. Vital signs were stable. Physical exam was unremarkable with negative Chvostek's and Trousseau's signs. Laboratory work-up showed profound hypocalcemia with a total calcium level of 6.4 mg/dL with corrected calcium level of 6.9mg/dL (serum albumin level of 3.4 g/dL) and markedly increased serum intact PTH level (iPTH) of 2601 pg/mL (). Serum phosphate and serum alkaline phosphatase level was within normal reference range at 3.1 mg/dl and 84 U/L, respectively. Upon history taking, she was found to have received a new medication, denosumab 60mg subcutaneously, prescribed by her rheumatologist 10 days prior to the current presentation.\nBefore the administration of denosumab, the patient had normal serum values of calcium (9.5 mg/dL), phosphorus (3.8 mg/dL), alkaline phosphatases (96 U/L), and 25 vitamin D with slightly elevated iPTH level at 442 pg/mL. The patient was supplemented with 3,000 mg/dL of oral calcium along with oral Calcitriol 0.5mcg daily and Cinacalcet was held. The peritoneal dialysis solution was also changed from low calcium to regular calcium. All these measures resolved her symptoms with serum calcium normalizing (corrected calcium, 8.7 mg/dL) 5 days later whereas iPTH took almost 4 weeks to come back to baseline level (). Subsequently, she was managed as an out-patient with close monitoring of calcium homeostasis.
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. ).