Efficacy and Safety of Intravenous Pamidronate for Parathyroid Hormone-dependent Hypercalcemia in Hospitalized Patients

Context: Bisphosphonates are effective for hypercalcemia of malignancy (HOM). Efficacy and safety data for bisphosphonates in parathyroid hormone-related hypercalcemia (PTHRH) are rare, including pamidronate (Pam), which is not indicated for this condition. Objective: This work aims to evaluate the efficacy and safety of Pam for moderate-to-severe PTHRH. Methods: This retrospective case-control study was conducted at a tertiary care medical center. Patients included adults hospitalized with serum calcium levels greater than 12 mg/dL, from October 29, 2013 to December 17, 2019. Etiology was categorized as PTHRH or PTH-independent. Clinical and laboratory data of PTHRH patients treated with Pam (PTHRH-Pam+) were compared to Pam-untreated counterparts (PTHRH-Pam-). Results: Thirty-four patients with 37 hospitalizations for PTHRH (Pam-treated and -untreated) met the inclusion criteria. Pam was given in 24 of 37 cases (64.8%). Admission serum calcium levels for the PTHRH-Pam+ group were higher than for PTHRH-Pam- group (14.4 mg/dL vs 13.0 mg/dL, P=.005). Median total Pam dose was 60 mg (range, 30-180 mg) in the treated group. Serum calcium decreased 3.5 mg/dL for PTHRH-Pam+ vs 1.6 mg/dL for PTHRH-Pam- (P=.003). No PTHRH-Pam+ patients developed hypocalcemia or acute kidney injury. Nadir serum phosphorus levels were lower in the PTHRH-Pam+ vs PTHRH-Pam- group (1.7 mg/dL vs 2.4 mg/dL, respectively, P=.004). Three PTHRH-Pam+ patients developed severe hypophosphatemia; all resolved with intravenous and oral supplementation. Seventeen patients underwent parathyroidectomy, of whom 10 received Pam within 28 days preoperatively. Postoperatively, 4 developed hypocalcemia and 3 hypophosphatemia. Conclusion: This study demonstrates that Pam is effective and safe for treating PTHRH, while ensuring close laboratory monitoring of calcium and phosphorus metabolism. Larger, prospective studies are needed to establish the role of Pam and other potent bisphosphonates in moderate-to-severe PTHRH.