Diagnostic accuracy of bone-related biomarkers on peri-implantitis: potential of A-proliferation-inducing ligand

Abstract

Objective: To study the biomarker profile in peri-implant crevicular fluid (PICF) of A proliferation-inducing ligand (APRIL), receptor activator of nuclear factor κβ (RANKL) and interleukin (IL)-23, in healthy, periimplant mucositis and peri-implantitis sites, and to explore their diagnostic accuracy on periimplantitis (PI) diagnosis.

Materials and methods: An exploratory cross-sectional study was conducted. Sociodemographic and clinical were recorded. Implant diagnosis was made based on the latest classification consensus. PICF samples were collected with paper strips from healthy, mucositis and PI implants. The biomarkers were analyzed by Luminex assay. The diagnostic accuracy was determined through sensitivity, specificity, predictive values (PV), and receiver operating characteristic (ROC) curves.

Results: Overall, 54 patients were recruited; 17 were healthy implants, 19 with mucositis and 18 have PI. RANKL and APRIL levels in PICF were significantly increased in PI implants compared to healthy implants (p < 0.001 and p = 0.005). IL-23 did not present differences between groups (p > 0.05). Positive correlations between PICF-RANKL levels and clinical attachment loss, plaque index score and bleeding on probing were observed (rho = 0.33; rho = 0.35; rho = 0.33; p < 0.05, respectively). Additionally, PICF-IL-23 and APRIL were correlated with the plaque index score and peri-implant probing depth (rho = 0.28; rho = 0.28, p < 0.05). PICF-APRIL concentrations and plaque index score were associated with PI (OR:3.01; 95%CI [1.08-8.38], p = 0.035, and OR:11.24; 95% CI [2.63-48.16], p = 0.001, respectively). The regression model, which included PICF-APRIL and plaque index, showed an AUC-ROC of 0.95, a sensitivity of 94.4%, 83.3% specificity, a positive PV of 73.9%, and a negative PV of 96.8%.

Conclusions: Implants with PI have higher levels of APRIL and RANKL in PICF compared to healthy implants. The model that includes the levels of APRIL in PICF combined with the plaque index score leads to an enhanced accuracy of PI diagnosis.

Clinical relevance: Clinical diagnosis of peri-implant disease can be improved with molecular tools, in this case, APRIL demonstrated high accuracy for the diagnosis of PI.

Keywords: Biomarkers; Molecular diagnosis; Peri-implant crevicular fluid; Peri-implantitis.

Fig. 1

Peri-implant crevicular fluid concentrations of IL-23, APRIL, RANKL, and plaque index score description by implant diagnosis. *Kruskal Wallis and Dunn´s test

Fig. 2

Heatplot of correlations between the concentrations of IL-23, APRIL, and RANKL in peri-implant crevicular fluid with periodontal and peri-implant clinical parameters. Abbreviations: CAL, Clinical attachment loss; PPD, Periodontal probing depth; PIPD, Peri-implant probing depth; PIx, Plaque index score; BOP, Bleeding on probing. Spearman correlation coefficient. *: significantly p-value < 0.05

Fig. 3

Area under the AUC-ROC curve for the studied biomarkers in peri-implant crevicular fluid and plaque index score, and the proposed model which combined peri implant fluid levels of APRIL with the plaque index score for the peri-implantitis diagnosis discrimination