Bisphosphonate-induced Severe Hypocalcemia - A Case Report -
A 78-year-old female patient who had loss of appetite, lethargy, disorientation, and speech disturbance for several days came to our hospital in emergency room due to mental deterioration. About a month before the hospital visit, the patient had femur neck fracture caused by hitting on a table and then received hip arthroplasty under spinal anesthesia. At the time of the visit, blood pressure, body temperature, pulse rate, and respiratory rate were 120/70 mmHg, 36.5℃, 70 times/minute, and 20 times/minute, respectively, and the patient responded to pains but couldn't communicate. Brain magnetic resonance imaging (MRI) was carried out in order to check the occurrence of cerebrovascular event but acute lesion was not observed. Laboratory test showed the result of leukocyte count 6,530/µL, hemoglobin 11.3 g/dL, platelet count 197,000/µL, blood urea nitrogen 36.9 mg/dL (8-23), serum creatinine 3.67 mg/dL (0.6-1.2), fractional excretion of sodium (FENa) 5.9%, serum albumin 3.3 g/dL (3.2-4.5), sodium 143.4 mEq/L (136-142), potassium 3.3 mEq/L (3.8-5.0), corrected calcium concentration 3.96 mg/dL (9-11), phosphorus 2.5 mg/dL (2.3-4.7), parathyroid hormone (PTH) 486.6 pg/mL (12-88), ionized calcium 1.8 mg/dL (4-4.8), and magnesium 1.4 mg/dL (1.3-2.1). The corrected calcium concentration was calculated utilizing equation of 'total calcium concentration in serum (mg/dL) + (0.8 × (4.0 - serum albumin concentration [g/dL])'. On electrocardiography, corrected QT interval (519 msec) was prolonged, but Trousseau's phenomenon or Chvostek's sign was not exhibited. In the past medical history, no special diseases such as hypertension and diabetes were present and the patient was a non-smoker and a non-drinker. When the patient had femur neck fracture about a month ago, bone mineral density (BMD) was measured utilizing dual-energy X-ray absorptiometry (DXA; Hologic QDR-4500W; Hologic, Inc., Bedford, MA, USA). In result, osteoporosis was considered with T-scores of -3.9 and -3.4 in lumbar spine (L1-4) and hip, respectively (). Therefore, 5 mg of zoledronate (Aclasta®) was injected intravenously for 15 minutes on the day after the surgery and then calcium supplements were continuously being given until visiting the emergency room. In the blood test at the time of injecting zoledronate intravenously, serum creatinine concentration was 2.83 mg/dL and corrected calcium concentration was 8.4 mg/dL.\nThe patient was diagnosed intravenous zoledronate-induced hypocalcemia and then 20 mL of calcium gluconate (diluted in 100 mL of normal saline) and 1 µg/day of vitamin D (calcitriol, Bonky®) were started to inject intravenously. From the day after the intravenous injection of calcium, the patient showed gradual improvement in consciousness as well as lethargy and fatigue. However, in spite of continuous supplying of oral calcium carbonate, 3 g/day, and oral vitamin D, 0.5 µg/day, serum calcium concentration was not improved as much with 4.68 mg/dL of corrected calcium concentration in 2 weeks after the hospital visit. In the follow up examination performed in out-patient clinic after discharging from the hospital, serum creatinine concentration was 3.14 mg/dL and calcium concentration was 7.2 mg/dL (4 weeks after the symptom occurrence) and 9.3 mg/dL (4 months after the symptom occurrence) ().