Preoperative Zoledronic Acid for the Prevention of Hungry Bone Syndrome After Parathyroidectomy in Primary Hyperparathyroidism: A Randomized Placebo-Controlled Trial
In brief
Zoledronic acid leaves hungry bone syndrome rates unchanged after surgery
Hungry bone syndrome developed in 6 of 22 patients given preoperative zoledronic acid and 6 of 23 given placebo, with no prevention benefit in this randomized trial. The drug also did not significantly improve bone density gains and caused more adverse events, mostly tingling; the small trial leaves uncertainty about selective use for other reasons.
- Journal
- Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists (Q1)
- Published
- 30 September 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Akanksha Gautam, Vivek Jha, Prabhat Rijal, Rahul Gupta, Divya Dahiya, Tulika Singh, et al.
- PMID
- 42815726
- DOI
- 10.1016/j.eprac.2026.07.020
Why clinicians should know about it
- Picked for Breast and Endocrine Surgery (top studies of the week, 4 October 2026): Preop zoledronic acid does not prevent hungry bone syndrome
Abstract
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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.