SUN-800 - Effect of Preoperative Bisphosphonate Therapy on Hungry Bone Syndrome and Calcium Requirements after Parathyroidectomy: Systematic Review and Meta-Analysis

Background

The use of preoperative bisphosphonates has long been proposed as a potential resource in the management of the clinical manifestations of the Hungry Bone Syndrome (HBS) post-parathyroidectomy, especially in the reduction of the postoperative requirements for calcium. Nonetheless, the current literature has shifted from the optimistic views in the past to the current uncertainties, with newer studies yielding inconsistent results. The purpose of this meta-analysis is to provide a clear perspective on the relationship between preoperative bisphosphonates and the incidence of HBS post-parathyroidectomy.



Methods:

The analysis was conducted according to a registered PROSPERO protocol (CRD420251272548) and PRISMA standards. The literature search was conducted using PubMed, Embase, Scopus, and Web of Science databases on December 23rd, 2025. The inclusion criteria included comparative adult cohorts after parathyroidectomy for assessing incidence of preoperative bisphosphonate exposure vs. non-bisphosphonate exposure. The inclusion criteria included baseline study characteristics, bisphosphonate exposure variables, and outcome variables for incidence of HBS. For pairs and larger number of comparable studies, a random effects meta-analysis was performed.



Results:

The meta-analysis consisted of four studies (231 participants), 58 in the treatment group and 173 in the control group. The risk ratio (RR) was 0.79, but the 95% confidence interval (CI 0.04-14.50; p = 0.81) was inconclusive. The heterogeneity among studies was high (I2 = 82.8%; τ = 2.51, p = 0.0006), so it cannot be attributed to chance but to real differences among studies. The inequality in this case is due to true differences among studies rather than chance. Sensitivity analyses for missing data were in accordance with an RR of 0.74 in the best-case scenario and an RR of 0.85 in the worst-case scenario; in both cases, it was insignificant. The results of the leave-one-out sensitivity analyses could not find one study that would be enough to alleviate this inequality in relative safety and harm, from meaningful protection to harm.



Conclusions

Clinical and statistical heterogeneity are sufficiently large to preclude definitive inferences on preoperative bisphosphonate therapy. Effect size spanned from protective to harmful in different studies. This raises an important question and underlines again that multicenter randomized clinical trials are required to establish whether, and in whom, bisphosphonates affect postoperative mineral metabolism and HBS risk.

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