Diederik Hentenaar

43 Biomarkers in crevicular peri-implant fluid As part of the RANK/sRANKL/OPG system, the markers OPG and sRANKL play a pivotal role in bone biology (i.e., regulation of osteoblast and osteoclast activities). OPG protects the bone from excessive resorption by binding to sRANKL. Hereby, sRANKL is prevented from binding to RANK (a receptor bound to osteoclasts) which in turn prevents activation of osteoclast cells (Rakic et al. 2013). It therefore seems likely that both markers are involved in alveolar bone destruction in peri-implantitis (Arikan et al. 2011). However, to date, conflicting results regarding both markers have been reported in the literature. In a study Monov et al. (2006), subjects with increased peri- implant bone loss and clinical signs of inflammation did not show increased levels of sRANKL. Additionally, significantly lower sRANKL concentrations, OPG total amounts and OPG concentrations in peri-implantitis implants were reported by Arikan et al. (2011) when compared to healthy implants. Our study seems in line with the results on OPG reporting no difference in levels between both groups. On the other hand, significantly higher levels were found in peri-implantitis sites by Rakic et al. (2013), but without a difference in OPG/RANKL ratio. Therefore, although it seems reasonable to believe that both markers are important in peri-implant sites with bone loss, as of yet, the literature does not seem to support this thought. At last, a biomarker which previously not seemed to be evaluated in peri-implant fluid is G-CSF (Panopoulos & Watowich 2008). This cytokine is known as a type of growth factor that stimulates bone marrow to produce white blood cells (e.g., neutrophil granulocytes). Although relatively few of the samples in this study (in both groups) had G-CSF levels above the level of detection, we believe with our study to be the first to show no difference in G-CSF between healthy and diseased implants. Considering that a recent study, which focused on a close relative of G-CSF (i.e., macrophage-CSF) in the PICF of peri-implantitis patients, found higher levels of macrophage-CSF when compared to peri-implant mucositis patients (Lira-Junior et al. 2020) interpretation of our outcomes should be done cautiously. However, one might suggest that colony stimulating factors might play a role in the pathogenesis of peri-implant disease. Altogether, the research effort spent thus far on markers around implants with and without signs of inflammation has identified one potential biomarker (IL-1β) which could reliably be used in PICF diagnostics, to flank clinical and radiographical examination in differentiating between both groups. In addition, our study shows a promising role for the association between the expression of MMP-8 and the pathophysiology of peri- implantitis. However, this needs to be rigorously confirmed in future studies together with data on other potential markers (e.g., TNF-α, MCP-1 and G-CSF). 2