SUN-768 - From Hypercalcemia to Hypocalcemia: A Prolonged Calcium Shift after Zoledronic Acid

Introduction:
Zoledronic acid, a potent intravenous bisphosphonate used in osteoporosis and malignancy-associated bone disease, inhibits osteoclastic bone resorption and may precipitate hypocalcemia. While mild, transient hypocalcemia is relatively common, severe or refractory cases are uncommon and are typically linked to vitamin D deficiency, impaired parathyroid reserve, renal dysfunction, hypomagnesemia, malabsorption, or high bone turnover. Prompt recognition is essential, as prolonged hypocalcemia can cause significant neuromuscular and cardiac complications and may require aggressive calcium and calcitriol repletion.

Case:
A 67-year-old female with plasma cell dyscrasia complicated by multiple lytic spinal lesions was receiving monthly zoledronic acid for malignancy-related hypercalcemia. She was admitted after routine outpatient labs revealed hypocalcemia, 10 days following her most recent zoledronic acid infusion. Laboratory evaluation showed low total calcium and ionized calcium (0.96 mmol/L) with albumin 3.5 g/dL, creatinine 0.66 mg/dL, vitamin D 31 ng/mL, markedly elevated PTH 365 pg/mL (15–65 pg/mL), and undetectable PTHrP ( < 2.0 pmol/L), consistent with bisphosphonate-associated hypocalcemia. She was treated with IV calcium gluconate boluses followed by continuous infusion and magnesium repletion. Despite 24 hours of therapy, ionized calcium remained low at 1.01 mmol/L. Oral calcium citrate was initiated due to concurrent proton pump inhibitor use limiting calcium carbonate absorption. Given persistently low calcium, calcitriol 0.25 mcg twice daily was started and increased to 0.5 mcg twice daily. Calcium recovery was gradual, and by hospital day 15 ionized calcium stabilized above 1.1 mmol/L, allowing transition to high-dose oral calcium plus calcitriol with a taper plan and close outpatient monitoring.

Discussion:
Zoledronic acid can unmask limited calcium homeostatic reserve by abruptly reducing calcium efflux from bone. Most patients compensate via increased PTH secretion, enhanced renal calcium reabsorption, and increased 1,25-dihydroxyvitamin D production; refractory hypocalcemia occurs when these mechanisms are impaired. In this patient, markedly elevated PTH supported intact parathyroid reserve and suggested ongoing skeletal calcium sequestration and/or impaired effective calcium absorption. Management includes symptom assessment with ECG monitoring, prompt IV calcium for severe hypocalcemia or QT prolongation, early magnesium correction, and sustained repletion with high-dose oral calcium and calcitriol given the prolonged bisphosphonate effect. Prevention remains critical: assessing and correcting calcium and vitamin D before infusion, reviewing renal function and medications affecting absorption, and reinforcing adherence to supplementation.

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