**4. Discussion**

Periodontitis is one of the most prevalent illnesses in humans [93]. One of the main challenges faced by the periodontics field is to improve the methods for diagnostic and prognostic of periodontitis [94]. Biomarkers, previously described, can be useful in monitoring the current state of the disease, the effectiveness of the treatment, and possibly predict the progression. However, currently the single ideal biomarker displaying high specificity and sensitivity for discriminating and monitoring this disease has not been determined. Thus, the combination of different biomarkers could be more advantageous than single biomarkers [93]. This would provide a more accurate panorama of the state of periodontal disease.

Classic methods for periodontitis diagnosis as the inspection and the palpation by the specialist can be relatively inaccurate. Additionally, the use of periodontal probes, and radiography could only provide information about previous periodontal damage rather than the current state [93]. Thus, biomarkers have been proposed as complementary methods to defeat the mentioned limitations monitoring the clinical response to an intervention and future risk [95].

Desirable's characteristics in test using biomarkers in periodontitis are easy to perform, rapid, and low cost, which could allow clinicians to perform early diagnosis and more effective personalized treatment.

Different factors are involved in the development of periodontitis, and a complex interaction between bacteria and immune system is observed. Additionally, periodontitis has been linked to at least 43 systemic diseases [96]. Thus, it is important to be careful when interpreting the results of biomarker tests because different factors could have a confounding impact on potential biomarkers [97]. Additionally, further large-scale studies are needed to prove specificity and sensitivity of the biomarkers analyzed in periodontitis and for utilization in routine clinical practice in the future.
