Role of lactoferrin in periodontal disease: A meta‑analytical assessment of its reliability as a biomarker

The present systematic review and meta-analysis assessed the clinical utility of lactoferrin as a biomarker for periodontitis by evaluating its association with established periodontal parameters, including probing pocket depth (PPD), clinical attachment loss (CAL) and gingival index (GI). The PICOS question was: 'Are lactoferrin levels different between individuals with periodontitis and periodontally healthy controls, and are these levels associated with disease severity and established clinical periodontal indicators, supporting their role as diagnostic or prognostic biomarkers for periodontitis?'. The present meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was formally registered in PROSPERO (CRD420251003457). A total of 384 articles were initially identified through various databases, from which 15 studies were selected. A random-effects model was applied to analyse lactoferrin concentration in saliva, serum and gingival crevicular fluid in relation to periodontitis and its periodontal parameters, using standardized mean differences (SMDs) with 95% confidence intervals (CIs). Heterogeneity and potential publication bias were examined through statistical methods, including funnel plots, forest plots, Egger's regression analysis, and Begg's rank correlation test. From the initial pool of 384 studies, 15 satisfied the inclusion criteria for the present meta-analysis, comprising a total of 798 participants (496 patients with periodontitis and 302 healthy controls). The combined SMD was 2.630 (P=<0.010; 95% CI: 1.140-11.180), demonstrating a significant link between elevated lactoferrin levels and periodontitis compared with the controls. Egger's regression test produced a t-statistic of -0.646 (P=0.529), reflecting a lack of significant evidence for publication bias. In addition, there was a significant association between lactoferrin concentration and periodontal indicators such as PPD, CAL and GI. In conclusion, lactoferrin showed potential as a biomarker for periodontal disease, with elevated levels consistently linked to its presence and disease severity. However, significant variability in reported levels across studies and a lack of methodological standardization currently limit its diagnostic reliability.