Preoperative Zoledronic Acid for the Prevention of Hungry Bone Syndrome After Parathyroidectomy in Primary Hyperparathyroidism: A Randomized Placebo-Controlled Trial

Objective To determine whether preoperative zoledronic acid (ZA) reduces the incidence of hungry bone syndrome (HBS) after curative parathyroidectomy in patients with primary hyperparathyroidism (PHPT).Methods In this single-blind, randomized, placebo-controlled trial, adults with PHPT and albumin-corrected serum calcium ≥11 mg/dL were randomized in a 1:1 ratio to receive either ZA 5 mg or placebo within 2 weeks before surgery. Following parathyroidectomy, participants underwent daily inpatient biochemical monitoring until discharge and were subsequently assessed during three prespecified outpatient windows over 12 months. HBS was identified using postoperative calcium, phosphorus, alkaline phosphatase, clinical findings, and postoperative parathyroid hormone where available.Results HBS occurred in 6 of 22 patients in the ZA group and 6 of 23 patients in the placebo group. Preoperative ZA did not reduce the odds of HBS compared with placebo, OR 1.06, 95% CI 0.28-3.98; P=0.928. BMD increased after parathyroidectomy in both groups; however, ZA did not provide a statistically significant additional benefit in lumbar spine or femoral neck BMD gain. CTX suppression was more consistently pronounced in the ZA group, reflecting greater inhibition of bone resorption. Adverse events were more frequent in the ZA group, largely driven by a higher frequency of paresthesias.Conclusion In patients with PHPT undergoing curative parathyroidectomy, a single preoperative infusion of ZA did not prevent HBS. These findings do not support routine use of ZA solely for prevention of HBS, although it may still be considered selectively for preoperative control of hypercalcemia or as a bridge to surgery.