Table 3.

Evidence-based Compilation of Biomarkers in External Apical Root Resorption.

Biomarker Category Biomarkers Studied References to Related Studies Specified Relative Risk Characteristics Outcomes Related to Characteristics
Dentinal proteins DSPP, DSP, DPP, DMP1 2, 5, 7, 13, 16, 23, 25, 29, 30 RR severity PP and DSP in severe RR (>2 mm) greater than mild root resorption (≤2 mm)7
DSP in coronal RR greater than apical RR (NS)5
Physiologic relative risk DPP in primary resorbing molar greater than orthodontically treated tooth13
DSP levels in physiologic RR greater than non-resorbing teeth5
Comparison with controls undergoing no orthodontic Tx or no relative risk DPP in orthodontically treated teeth (1–3 mm of resorption) greater than in controls (Sig. diff)13
DMP1, PP, DSP in RR greater than in control groups (Sig. diff)7
Time-related changes DSP levels increased in GCF in 12 months of orthodontic treatment5
DSPP levels increased significantly in GCF in 2 months of intrusion compared to baseline25
ELISA method for detection DSPP detection with ELISA using spectrophotometry and electrochemistry possible but NS. Lower end of detection is 10 times greater in spectrophotometry (5 pg/mL) than in electrochemical detection (0.5 pg/mL), hence latter method more sensitive2
Modified micro-bead approach is more reliable than standard ELISA for DSP23
Cytokines and growth factors IL (1β, 2, 4, 5, 6, 8, 10, 12, 13), TNF-α, IL-1RA, IFN-γ, OPG, OPN, RANKL, GM-CSF, salivary cytokine profile 9, 12, 16, 19, 26, 29 Severity of relative risk RANKL/OPG ratio in severe (>2 mm) RR greater than in controls (Sig. diff)19
Higher GM-CSF levels in low vs high RR26
DSPP levels lower in controls vs orthodontic patients, and least in pediatric patients; Sig. diff between IL-1RA and DSPP, IL-1RA cut-off for OIRR (≤432.6 pg/mL) and DSPP (≥7.33 pg/mL); reliability of DSPP (100%) vs IL-1RA (80%)
Variation with orthodontic force levels TNF-α in GCF significantly increased in teeth receiving 225 g of controlled buccal tipping force, as early as 3 h and at 28 days when compared with contralateral control teeth26
Comparison to controls with no orthodontic Tx or no relative risk OPN (66 kDa), OPG (30 kDa) detected in RR; proteins detected in controls19
RANKL in root resorption greater than controls19
GCF IL-6 levels in female subjects with severe RR (>⅓ root) higher than without RR9
Moderate to severe RR shows significantly increased IL-7, IL-10, IL-12p70, and IFN-γ vs no resorption12
Moderate to severe RR shows significantly decreased IL-4 vs no RR12
In blood, RR has higher osteocalcin and P1NP vs no RR12
Physiologic resorption IL-1RA significantly downregulated in physiologic RR vs no RR16
IL-1RA levels greater in controls than in physiologic RR group29
Early detection of biomarkers Detection of TNF-α as early as 3 h in GCF in RR26
Enzymes ALP, AST, TRAP, MMP-8 15, 16, 31 Variation with orthodontic force levels/type ALP shows higher levels in 1 week upon application of continuous 150 g force compared to 100 g force and faster canine movement with no RR15
Significant increase in TRAP from baseline to 3–5 weeks in 100 g force while AST increased in 5 weeks upon application of 150 g force; 100 g force as effective as 150 g force22
Early detection of biomarkers ALP detected as early as 1 week after 150 g force application in RR patients15
Resorption proteins and metabolites Protein profile in GCF and saliva 20, 21, 24, 27, 28 Comparison to controls with no orthodontic Tx or no relative risk Higher protein bands in mild to moderate RR as compared to controls20
187 salivary metabolites identified in female RR patients compared to controls27
Physiologic resorption 37 RR proteins upregulated and 59 RR proteins downregulated in primary molar physiologic RR compared to teeth with no RR21
Influence of age on relative risk and protein levels In moderate-to-severe young RR group, 244 salivary proteins significantly increased and 97 decreased24
In moderate-to-severe adult RR group, 58 salivary proteins significantly increased and 198 significantly decreased24
In young mild RR group, 318 salivary proteins significantly increased and 78 decreased24
In adult mild RR group, 102 salivary proteins increased, and 153 significantly decreased24
Potential biomarker candidates Fetuin-A and p21-ARC24
Early detection of biomarkers Early increase of 16 proteins in GCF in mild RR patients after 1 month of orthodontic force application28

ALP, alkaline phosphatase; AST, aspartate aminotransferase; DMP1, dentin matrix protein 1; DPP, dentin phosphophoryn; DSP, dentin sialoprotein; DSPP, dentin sialophosphoprotein; ELISA, enzyme-linked immunosorbent assay; GCF, gingival crevicular fluid; GM-CSF, granulocyte-macrophage colony-stimulating factor; h, hours; IFN-γ, interferon gamma; IL, interleukin; IL-1RA, interleukin-1 receptor antagonist; MMP-8, matrix metalloproteinase-8; NS, not significant; OIRR, orthodontically induced root resorption; OPG, osteoprotegerin; OPN, osteopontin; P1NP, procollagen type I N-terminal propeptide; p21-ARC, cyclin-dependent kinase inhibitor p21; PP, dentin phosphophoryn (alternate abbreviation in the literature); RANKL, receptor activator of nuclear kappa B ligand; RR, root resorption; Sig. diff, significant difference; Tx, treatment; TNF-α, tumor necrosis factor-α; TRAP, tartrate-resistant acid phosphatase.

RMMJ Rambam Maimonides Medical Journal Rambam Health Care Campus 2022; 13(4): e0027. ISSN: 2076-9172
Published online 2022 October 27. doi: 10.5041/RMMJ.10482