Changes in the levels of salivary biomarkers of bone remodelling during orthodontic tooth movement – a systematic review and meta-analysis

Objective To systematically review studies assessing the variations in levels of different biomarkers in saliva involved in bone remodelling during Orthodontic tooth movement (OTM).Search Methods A comprehensive search of databases for studies from January 2003 up to April 2025 and a revised search for studies from January 2001 to June 2025, including PubMed, Web of Science, Scopus, and Google Scholar, was conducted, limited to the English language.Selection Criteria Observational studies aligning with the PECO question were included, and their risk of bias was assessed using the Revised JBI tool for cohort studies.Data Collection and Analysis Data were collected using Covidence software, and a meta-analysis was conducted with a random-effects model and Standardized Mean Difference (SMD) by STATA 19.5 software. The primary outcome was changes in the levels of salivary biomarkers during different phases of OTM.Results Twenty-five studies were reviewed, and fourteen were included in the meta-analysis. Although many studies had a low overall risk of bias, concerns remained regarding confounding factors, classification of exposure and statistical analysis. Timepoints were grouped into baseline, initial phase, lag phase and post-lag phase to standardize comparisons. The certainty of evidence from these results is very low. IL-1β, TNF-α and PGE2 showed an early transient rise, peaking during the initial phase before declining, with inconsistent long-term changes. Bone remodelling markers showed phase-specific changes during OTM with considerable clinical and methodological heterogeneity.Conclusions MMP-8, MMP-9 and Myeloperoxidase showed statistically significant increases between baseline and initial phase, but the certainty of evidence is very low, with limited clinical applicability of these findings.PROSPERO CRD420251012590