Case Presentation: A 67-year-old woman with a history of osteoporosis, GERD, diverticulitis, and osteoarthritis presented to the emergency department with altered mental status and a witnessed tonic-clonic seizure one day after receiving zoledronic acid (ZA) for treatment of osteoporosis. The seizure was refractory to medical management and she required intubation for airway protection. Labs were notable for hyponatremia (120 mg/dL), hypocalcemia (7.9 mg/dL), hypokalemia (3.3 mEq/L), and later hypomagnesemia and hypophosphatemia during admission. CT and MRI head, EEG, and lumbar puncture were normal. Chart review revealed the patient had normal labs four days prior to ZA infusion (Na 140 mg/dL, Ca 9.7 mg/dL).The patient’s acute hyponatremia was corrected with hypertonic saline, followed by normal saline. Hypocalcemia was managed with calcitriol and calcium carbonate, and magnesium and phosphorus were aggressively repleted. Other causes of hyponatremia, specifically SIADH, were ruled out with 24-hour urine studies, morning cortisol, and other studies. Previous reports show acquired Fanconi syndrome following ZA use, which would have explained the patient’s hypophosphatemia, but 24-hour urine electrolytes were inconsistent and additional diagnostic criteria were not met. On hospital day 3, the patient developed rhabdomyolysis with peak creatinine kinase (CPK) of 19,875 U/L; this was attributed to electrolyte abnormalities rather than her seizure as the CPK rose suddenly three days later. She was resuscitated with fluids to prevent kidney injury. At discharge (hospital day 7), the patient’s electrolytes were within normal range, and CPK was trending down. She was alert and oriented with no neurologic abnormalities.
Discussion: ZA is an aminobisphosphonate that accumulates at sites of high bone turnover where it is internalized by osteoclasts and decreases bone resorption by inhibiting farnesyl pyrophosphate synthase and preventing protein prenylation. ZA is a common treatment for osteoporosis, bone metastases from solid tumors, and hypercalcemia of malignancy; infusions are typically well-tolerated. The most common side effects are pyrexia, myalgias, influenza like symptoms, headache, and arthralgias with a peak onset after 1 day and average duration of 3 days. Other reported adverse events include renal failure, atrial fibrillation, osteonecrosis of the jaw, and hypocalcemia. There is one case report of a patient who experienced diarrhea and hyponatremia after ZA; the hyponatremia in this case was attributed to gastrointestinal fluid losses. According to the World Health Organization’s Causality Scale, ZA was the likely cause of this patient’s electrolyte abnormalities given the temporal relationship of the infusion and patient’s presentation. This was further supported by ruling out other common causes of hyponatremia. However, the direct mechanism by which the ZA infusion caused the hyponatremia remains unclear.
Conclusions: We present the case of a patient with acute, symptomatic hyponatremia caused by ZA through an unclear mechanism which has not been previously described in the literature. This case illustrates the importance of taking a thorough history at the time of hospital admission including a careful review of all medications, including recent outpatient infusions. It also highlights the side effect profile of a medication that hospitalists may prescribe, particularly to treat hypercalcemia of malignancy.