Diagnostic Accuracy of Oral Fluids Biomarker Profile to Determine the Current and Future Status of Periodontal and Peri-Implant Diseases

Abstract

Severe periodontitis is ranked as the sixth most prevalent disease affecting humankind, with an estimated 740 million people affected worldwide. The diagnosis of periodontal diseases mainly relies upon assessment of conventional clinical parameters. However, these parameters reflect past, rather than current, clinical status or future disease progression and, likely, outcome of periodontal treatment. Specific and sensitive biomarkers for periodontal diseases have been examined widely to address these issues and some biomarkers have been translated as point-of-care (PoC) tests. The aim of this review was to provide an update on PoC tests for use in the diagnosis and management of periodontal diseases. Among the PoC tests developed so far, active matrix metalloproteinase-8 has shown promising results in terms of diagnostic and prognostic values. However, further studies are required to increase the sensitivity and specificity via combining more than one biomarker and merging these test kits with periodontal risk assessment tools. Furthermore, the validity of these test kits needs to be investigated by applying the results in further independent studies and the impact on these test kits', together with the results of risk factors for periodontal diseases, such as diabetes and smoking, also needs to be examined.

Keywords: MMP8; biomarkers; diagnostic; periodontal diseases; point-of-care test; prognostic.

Figure 1

Number of studies examined biomarkers for periodontal diseases from 1974 to 2020 (PubMed).

Figure 2

Criteria for the ideal biomarker.

Figure 3

Sources of matrix metalloproteinase (MMP) 8 in oral fluids. Polymorphonuclear leukocytes (PMN) cells represent the main source for MMP8 following their degranulation. MMP8 then released into gingival crevicular fluid (GCF), peri-implant sulcular fluid (PISF), saliva, and mouthrinse samples. MMP8 is also released to a lesser extent from other immune and non-immune cells together with other cytokines, including interleukin (IL) 8, IL1β, tumor necrosis factor (TNF)-α, receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), and prostaglandin E2 (PGE2).

Figure 4

Cut off point of aMMP8 to differentiate periodontal/peri-implant health and disease. The cut off value of aMMP8 that differentiates from health (green dotted line) and gingivitis/peri-mucositis (blue continuous line) is equal to 6.46 ng/mL. While aMMP8 levels ≥20 ng/mL represent the cut off value distinguishing gingivitis/peri-mucositis from periodontitis/peri-implantitis. The latter two conditions could respond favorably to periodontal therapy which is reflected by downregulation of aMMP8 expression in oral fluids (black continuous line) or the destruction of periodontal tissues further progress if neglected (orange continuous line). aMMP8 levels exceeding 60 ng/mL potentially predict poor prognosis of periodontitis/peri-implantitis to periodontal treatment.