*3.3.3 Alkaline phosphatase*

A study was conducted to determine the usefulness of alkaline phosphatase as a biomarker, and this study showed a correlation with the clinical characteristics when mediated in crevicular fluid [80].

## *3.3.4 miRNAs*

According to Mico et al. [81], epigenetic regulation by miRNAs has not yet been studied in periodontal disease using crevicular fluid. They analyzed the possible use as biomarkers of six miRNAs: miR-671, miR-122, miR-1306, miR-27a, miR-223, and miR-1226. Of the six miRNAs analyzed, only miR-1226 can be used as a promising biomarker for periodontal disease since it had statistically significant differences between the healthy group and patients with periodontitis.

### *3.3.5 Oxidative stress*

As previously mentioned, 8-OhdG is a marker of DNA damage and is considered a biomarker to detect oxidative stress [24], that is why it is not surprising that its usefulness as a biomarker of periodontitis was explored. This study was conducted in crevicular fluid, and it could be determined that evaluating this biomarker in crevicular fluid is more effective than in saliva and that it can be useful as a biomarker for determining periodontitis since according to the authors, the severity of the periodontal disease can be revealed [82].

### *3.3.6 Telopeptide*

Telopeptide has also been evaluated as a biomarker in periodontitis in the study by Aruna [83], which suggests that this biomarker could be useful as a specific marker of bone turnover in patients with periodontitis.

#### *3.3.7 Other markers of periodontal disease*

Chondroitin sulfate is a biomarker that, due to its results in patients with chronic periodontitis, suggests that it is important in the diagnosis to evaluate the severity

of alveolar destruction [80]. MUC4 protein was measured in crevicular fluid and according to this study can be considered as a new biomarker to rule out patients with periodontitis from healthy ones (p < 0.01) [79].
