Effectiveness of perioperative calcium and vitamin D supplementation in preventing post-thyroidectomy hypocalcaemia: network meta-analysis of randomized trials.

Abstract

Post-thyroidectomy hypocalcaemia is the most common complication after total thyroidectomy. Although perioperative calcium and vitamin D supplementation is widely used, the comparative effectiveness of different prophylactic strategies remains uncertain. A systematic review and Bayesian network meta-analysis of randomized clinical trials was performed according to PRISMA guidelines. PubMed, Scopus, Web of Science, and the Cochrane Library were searched from inception to 7 May 2026. Adult patients undergoing total or near-total thyroidectomy were included. Three strategies were compared: no routine supplementation, calcium alone, and calcium combined with vitamin D analogues. Primary outcomes were clinical hypocalcaemia, biochemical hypocalcaemia, and need for intravenous calcium supplementation; length of hospital stay was secondary. Random-effects network meta-analysis estimated odds ratios with 95% credible intervals. Risk of bias was assessed using RoB 2. The protocol was registered in PROSPERO (CRD420251068837). Twenty randomized trials including 3669 patients were analysed. Calcium plus vitamin D significantly reduced clinical hypocalcaemia versus no supplementation (odds ratio 0.31, 95% credible interval 0.17 to 0.51) and calcium alone (odds ratio 0.52, 0.25 to 1.04). Combination therapy also reduced biochemical hypocalcaemia compared with no supplementation (odds ratio 0.27, 0.17 to 0.42) and calcium alone (odds ratio 0.44, 0.22 to 0.83), and markedly decreased intravenous calcium requirements (odds ratio 0.15, 0.05 to 0.32). Calcium monotherapy showed no significant benefit. Combination therapy ranked as most effective and was associated with shorter length of hospital stay (mean difference 0.44 days). Perioperative calcium combined with vitamin D is the most effective strategy for preventing post-thyroidectomy hypocalcaemia and reducing intravenous calcium use, supporting routine postoperative implementation despite heterogeneity in supplementation protocols.