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 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 .