Temporal dynamics of human biomarkers of orthodontically-induced root resorption: A systematic review

Clinical Snapshot

Key Findings

• P Value: Not reported at review level; individual study p-values not summarised in abstract

• Effect Size: Not quantified; narrative synthesis only. Directional associations reported: higher baseline salivary secretory IgA and anti-dentin humoral responses associated with greater OIRR severity; lower baseline mineralised-tissue regulators associated with greater OIRR severity

• Primary Outcome: Time-related biomarker changes across OIRR stages: early rise in pro-inflammatory cytokines following force application, subsequent signals of osteoclastic activity and regulation, and later detection of root hard tissue degradation products correlating with OIRR volume

• Nnt Or Sensitivity: Not applicable; no diagnostic accuracy metrics, NNT, or hazard ratios reported. No biomarker sensitivity/specificity thresholds established for OIRR prediction or monitoring

• Confidence Interval: Not reported; meta-analysis was not performed due to study heterogeneity

Clinical Application

Currently limited. Biomarker assays (primarily ELISA) are not routinely available in clinical orthodontic settings. Gingival crevicular fluid and saliva collection are non-invasive and feasible in principle, but standardised collection protocols, validated reference ranges, and point-of-care assay platforms do not yet exist for OIRR monitoring. Translation to clinical practice requires prospective validation in larger cohorts with standardised protocols before implementation. In Australia, OIRR is a recognised complication of orthodontic treatment and is addressed within RACGP-adjacent dental specialist guidelines. No TGA-approved biomarker test for OIRR monitoring currently exists, and no PBS-listed diagnostic pathway incorporates salivary or GCF biomarkers for this indication. Australian orthodontic practice currently relies on periapical radiography (with CBCT reserved for high-risk cases per ARPANSA radiation guidelines) for OIRR monitoring. This review's findings are hypothesis-generating and could inform future Australian research priorities, but do not yet support changes to current RACGP or Australian Society of Orthodontists monitoring recommendations. Any future clinical translation would require TGA regulatory consideration for diagnostic biomarker assays. Patients undergoing fixed orthodontic treatment, particularly those at elevated risk of OIRR (e.g., patients with pre-existing short roots, history of trauma, prolonged treatment duration, or high-force mechanics). The findings are most relevant to orthodontists seeking early monitoring strategies for OIRR during active treatment.

Abstract

OBJECTIVE: To summarize time-related biomarker changes in orthodontically-induced root resorption (OIRR), classify biomarkers by function, and examine trajectories across OIRR stages. MATERIALS AND METHODS: PubMed/MEDLINE, Embase, Scopus, Web of Science, CENTRAL, CINAHL and grey literature, were searched from inception to October 1, 2025. Reference lists were manually searched. The risk of bias was assessed using the Cochrane RoB 2 for RCTs and ROBINS-I for non-RCTs. The certainty of evidence was evaluated via GRADE. Because of heterogeneity, findings were synthesized narratively. RESULTS: From 11,434 records, 14 studies (225 participants) were included. Gingival crevicular fluid, saliva and serum were analyzed, mainly using enzyme-linked immunosorbent assay. RoB was 'moderate'- 'serious' (non-RCTs) or 'some concerns' (RCTs). Studies reported a rise of pro-inflammatory cytokines right after force application. Subsequent force application phases showed signals of osteoclastic activity and regulation, followed by detection of root hard tissue degradation products that correlated with OIRR volume. Higher baseline salivary secretory IgA and anti-dentin humoral responses and lower baseline mineralized-tissue regulators were associated with greater OIRR severity. CONCLUSION: Evidence suggests time-related changes involving early inflammatory activation and later matrix degradation, which may be shaped by interaction between orthodontic force and patients' biological responses. Standardized multicenter prospective cohorts are needed for validation. CLINICAL RELEVANCE: Early cytokines changes and later signals of osteoclast regulation and root hard tissue degradation may help define candidate monitoring method for OIRR during treatment. Baseline immune profiles could inform future risk stratification, while bone turnover biomarkers may reflect tooth movement rather than resorption.

References

1. 1.Feng, W., Van Orshoven, L., Bostanci, N., Nilsen, B. W., & Cadenas de Llano Perula, M. (2026). Temporal dynamics of human biomarkers of orthodontically-induced root resorption: A systematic review. Clinical Oral Investigations. https://doi.org/10.1186/s40510-017-0191-z