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