Preventive strategies for postoperative hypocalcemia and hungry bone syndrome following parathyroidectomy: a systematic review and pairwise meta-analysis

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Background: Postoperative hypocalcemia and hungry bone syndrome (HBS) remain clinically important after parathyroidectomy, particularly in renal hyperparathyroidism. Preventive drug regimens, calcium-infusion protocols, dialysis-related measures, and bundled pathways are used, but direct head-to-head comparisons between active strategies are largely absent. We therefore mapped the available strategies and determined which clinically comparable direct comparisons could support pairwise meta-analysis. Methods: The review was registered in PROSPERO (CRD420261373430). PubMed/MEDLINE, Embase, Web of Science Core Collection, Cochrane CENTRAL, and Wanfang Data were searched from January 1990 through 21 April 2026. Comparative studies of adults undergoing parathyroidectomy were selected using prespecified population, intervention, comparator, outcome, and study-design criteria. Strict HBS, biochemical hypocalcemia, early serum calcium, and postoperative intravenous-calcium requirement were analyzed as distinct outcomes. Studies reporting random allocation were assessed with Risk of Bias 2 (RoB 2) and non-randomized studies with Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I). Clinically compatible direct comparisons were synthesized using random-effects restricted maximum likelihood models, and certainty was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Network meta-analysis was not performed because transitivity was not defensible. Results: The searches yielded 10,640 records; 15 studies with 1,322 participants were included. These evaluated vitamin D (3 studies), intravenous bisphosphonates (3 studies), cinacalcet (4 studies), preventive intravenous calcium (2 studies), active vitamin D (1 study), high-calcium dialysate (1 study), and an enhanced-recovery bundle (1 study). All 3 studies reporting random allocation had some concerns under RoB 2, and all 12 non-randomized studies had serious ROBINS-I risk. In 2 non-randomized secondary-hyperparathyroidism studies (396 participants), preventive intravenous calcium was associated with less severe postoperative hypocalcemia [adjusted odds ratio (OR) 0.12, 95% confidence interval (CI): 0.06–0.22; I 2 =0%]. Four non-randomized studies (325 participants) did not show that preoperative cinacalcet reduced postoperative intravenous-calcium requirement [risk ratio (RR) 1.08, 95% CI: 0.48–2.41; I 2 =64.2%]. Strict HBS data were not poolable; certainty was very low. Conclusions: Preventive intravenous calcium may reduce short-term biochemical hypocalcemia in selected secondary-hyperparathyroidism pathways, but serious confounding prevents a causal claim and the result does not establish prevention of strict HBS. Evidence did not support a clear benefit of cinacalcet or any comparative treatment ranking. Standardized randomized studies are needed.