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Original Article

Methodological bias and study design influence the reported link between Vitamin-D deficiency and postoperative hypocalcemia

Published online: March 21, 2026

Departamento de Cirugía, Universidad de Antioquia, Medellín, Colombia

Received: 8 December 2025   • Revised: 23 December 2025   • Accepted: 30 January 2026
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Background
Post-thyroidectomy hypocalcemia is the most frequent complication after total thyroidectomy. Preoperative vitamin D deficiency has been suggested as a potential risk factor, but inconsistencies exist in the literature, possibly related to methodological differences. To evaluate whether study design and risk of bias influence the association between preoperative vitamin D deficiency and postoperative hypocalcemia in patients undergoing total thyroidectomy.
Methods
This is a secondary analysis of a previously conducted systematic review. We included observational studies evaluating the association between preoperative vitamin D levels and postoperative hypocalcemia. Methodological quality was assessed using the QUIPS tool. Subgroup analyses were performed based on study design (prospective vs. retrospective) and overall risk of bias (high vs. low/moderate).
Results
Twenty-eight studies comprising 4994 patients were included. Nineteen studies had a prospective design. Both prospective and retrospective studies showed an association between vitamin D deficiency and hypocalcemia; however, the effect size was lower in prospective studies (OR 1.95; 95% CI 1.28-2.97) compared to retrospective ones (OR 2.18; 95% CI 1.02-4.7). Studies with high risk of bias showed a significant association (OR 2.55; 95% CI 1.4-3.6), while those with low/moderate risk did not (OR 1.71; 95% CI 0.96-3.06).
Conclusion
Study design and methodological quality influence the reported association between vitamin D deficiency and postoperative hypocalcemia. These findings suggest caution when recommending preoperative vitamin D supplementation based solely on observational data.

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