## 4 Discussion
However, [PERSON] and [PERSON] [31] found that the salivary levels of CRP are not as reliable and do not strongly correlate with serum levels. This may be due to the presence of local oral inflammation, such as gingivitis, contributing to its increased local production. In our study, saliva showed higher levels of hs-CRP compared to serum but in both saliva and serum; the hs-CRP levels decreased at 1-year post-treatment follow-up compared to their respective baseline. Levels of hs-CRP have been shown to be an indicator of systemic inflammation when tested in the gingival crevicular fluid (GCF) rather than the result of local production by gingival cells [32]. As hs-CRP is only produced by the liver, it has been found that it enters saliva through passive diffusion or filtration from other oral fluids, such as GCF, resulting in raised levels in saliva [33]. Studies have shown that salivary levels of CRP are strongly correlated with serum levels in adults. Specifically, elevated salivary levels of CRP were correlated with serum directly after acute myocardial infarction. Therefore, salivary hs-CRP may be a viable option for the detection of acute myocardial infarction in adults [34]. However, this correlation would depend upon the level of oral inflammation. Several studies have investigated the correlation of salivary and serum biomarkers. For example, [PERSON], et al. [35] found a medium correlation between salivary and serum samples for the detection of CRP, TNF-\(\alpha\) and IL-10 [35]. Furthermore, [PERSON], et al. [36] found a correlation in the levels of IL-6 in both serum and saliva. In our study, a positive correlation was found between the salivary and serum levels of FGF-23, ICAM-1, E-Selectin and TNF-\(\alpha\), indicating the possible use of saliva as an inflammatory indicator as a substitute to serum. FGF-23 is a hormone produced by osteocytes and osteoblasts and, therefore, any bone alteration caused by inflammation could indirectly affect the production of FGF-23 [37; 38]. Increased levels of FGF-23 were found to impact the kidney and the heart by increasing the sodium absorption, renin-angiotensin activation and affecting the heart and blood vessels, which subsequently may lead to hypertension, subclinical atherosclerosis and cardiovascular events [39; 40]. Furthermore, FGF-23 is produced in lower concentrations in salivary glands, stomach, skeletal muscles, brain, liver and heart [41]. Salivary levels of FGF-23 were reduced after 2 years when compared to 1-year follow-up, and a positive correlation was seen between pre-operative salivary levels of FGF-23 and the post-operative size of the radiolucency. It has been found that excess levels of FGF-23 can negatively impact bone mineralization [42]. When analysed in serum, FGF-23 was the only marker that was reduced in all review appointments, indicating its potential use as a treatment outcome predictor [16]. Finally, soluble adhesion molecules including ICAM-1 and VCAM-1 were found to have an impact in the progression of atherosclerosis and CVDs [43]. ICAM-1 is a glycoprotein interfering with the adhesion-dependent cell-to-cell interaction. Both ICAM-1 and VCAM are activated by cytokines including TNF-\(\alpha\), reactive oxygen species and high glucose concentration [44]. In our study, the levels of VCAM-1 were positively correlated with the pre-operative size of radiolucency. In addition, at 1-year post-treatment follow-up, it was positively correlated with the treatment outcome (i.e., the better the outcome, the lower the levels of VCAM-1). When correlating the serum and salivary inflammatory markers' levels, ICAM-1 levels of saliva were positively correlation to serum levels. This was in line with the study done by [PERSON], et al. [45] in patients with periodontitis, indicating that the presence of local inflammation, such as apical periodontitis, may have systemic effect and increase systemic burden [45].