Preoperative Zoledronate Use and Risk of Postoperative Hypocalcemia After Parathyroidectomy for Primary...

Background: Given the limited and conflicting evidence regarding both the role of bisphosphonate (BP) use and the risk factors for postoperative hypocalcemia, as well as ongoing clinical hesitation toward preoperative BP use due to concerns about the occurrence of hypocalcemia, we aimed to investigate their association in patients with primary hyperparathyroidism (PHPT). Materials and Methods: A total of 73 patients undergoing parathyroidectomy were included, with 22 in the BP-positive (zoledronate) group and 51 in the BP-negative group. In BP-treated patients, biochemical values obtained after zoledronate infusion but before surgery were used as the preoperative baseline for perioperative comparisons, whereas pre-infusion calcium values were used only to characterize the clinical indication for treatment. Factors associated with postoperative hypocalcemia were evaluated using hypocalcemia as a dichotomous outcome. Results: Postoperative hypocalcemia was more frequent in BP-treated patients (27.3% vs. 3.9%, p = 0.008). However, in multivariable analysis including alkaline phosphatase (ALP), the association between BP use and hypocalcemia was attenuated and no longer statistically significant (OR 4.81, 95% CI 0.74-31.30; p = 0.100). ALP was independently associated with hypocalcemia (OR 1.016, 95% CI 1.001-1.031; p = 0.040). Additionally, hypocalcemia was associated with a shorter infusion-to-surgery interval (median 10 vs. 72 days, p = 0.0045) among BP-treated patients. Conclusions: Although hypocalcemia was more frequent among patients receiving preoperative zoledronate, this association was attenuated after adjustment for alkaline phosphatase and may reflect underlying disease severity. Alkaline phosphatase was independently associated with postoperative hypocalcemia, supporting the role of increased bone turnover. Given the limited number of events, an independent effect of zoledronate cannot be excluded, and treatment timing may warrant further investigation.