Pro- and anti-inflammatory cytokines and osteoclastogenesis-related factors in peri-implant diseases: systematic review and meta-analysis.

BACKGROUND: Pro- and anti-inflammatory cytokines are acknowledged, during inflammatory bone destruction, as key regulators of osteoclast and osteoblast differentiation and activity. However, evidence regarding the exact role of pro- and anti-inflammatory cytokines and osteoclastogenesis-related factors in peri-implant diseases is unclear. We aimed to execute a systematic review and meta-analysis about the pro- and anti-inflammatory cytokines and osteoclastogenesis-related factors levels in peri-implant diseases. METHODS: The focused question was elaborated to summarize the levels of pro-and anti-inflammatory cytokines and osteoclastogenesis-related factors in tissue samples (mRNA) and biofluids (protein levels) of patients with/without peri-implant diseases. Electronic searches of the PubMed, Cochrane Controlled Trials Registry, Web of Science, EMBASE, Scopus and Google scholar databases were conducted for publications up to March 2023. Meta-analysis evaluating the mediator´s levels (protein levels by ELISA) in peri-implant crevicular fluid (PICF) were made. The effect size was estimated and reported as the mean difference. The 95% confidence interval was estimated for each mediator, and the pooled effect was determined significant if two-sided p-values < 0.05 were obtained. RESULTS: Twenty-two publications were included in the systematic review (qualitative analysis), with nine of these subjected to meta-analyses (quantitative analysis). In the qualitative analysis, higher pro-inflammatory cytokines [Interleukin (IL)-1ß, IL-6] and pro-osteoclastogenic mediator [Receptor Activator of Nuclear Factor-Kappa B ligand (RANKL)] levels were observed in PICF of individuals with peri-implant diseases in comparison to healthy individuals. Higher RANKL/osteoprotegerin (OPG) ratios were observed in PICF from individuals with peri-implant diseases in comparison to healthy individuals. Meta-analysis showed higher RANKL levels in diseased groups compared to controls. CONCLUSIONS: The results showed that the levels of IL-1ß, IL-6, IL-10, and RANKL/OPG are not balanced in peri-implant disease, suggesting that these mediators are involved in the host osteo-immunoinflammatory response related to peri-implantitis.

Photobiomodulation of gingival lesions resulting from autoimmune diseases: systematic review and meta-analysis.

OBJECTIVES: To evaluate the effects of photobiomodulation (PBM) in gingival lesions resulting from autoimmune diseases; to compare PBM and topical corticosteroid (CS) treatment; and to assess PBM outcome over time of follow-up. MATERIALS AND METHODS: A comprehensive electronic search was performed in four electronic databases. Treatment effects were measured through visual analog scale of pain (VAS) and clinical evolution of lesion (Thongprasom scale for oral lichen planus (OLP)). Meta-analysis was performed to compare PBM with topical corticosteroid treatment and to evaluate PBM effect over time of follow-up. RESULTS: Seventeen studies were included in this review, of which six were used for the meta-analysis. Meta-analysis results showed no significant differences between PBM and topical CS in pain reduction at baseline (MD = 0.20, 95% CI = - 0.92, 1.32, p = 0.72) and 60-day follow-up (MD = 0.63, 95% CI = - 3.93, 5.19, p = 0.79); however, VAS showed significant pain reduction when compared before and after PBM at 30-day (MD = - 3.52, 95% CI = - 5.40, - 1.64, p = 0.0002) and 60-day (MD = - 5.04, 95% CI = - 5.86, - 4.22, p < 0.00001) follow-up. Thongprasom clinical scale for OLP also showed significant improvement at 30-day follow-up (MD = - 2.50, 95% CI = - 2.92, - 2.08, p < 0.00001) after PBM. CONCLUSION: PBM led to significant reduction of pain and clinical scores of the lesions, not having shown significant differences when compared to topical CS. CLINICAL RELEVANCE: PBM has been used in the treatment of autoimmune gingival lesions, but so far there is little strong evidence to support its use.

Systematic review of ratios between disease /health periodontitis modulators and meta-analysis of their levels in gingival tissue and biological fluids.

OBJECTIVE: The ratio between molecules which acts towards the diseased or healthy phenotype determine whether the periodontitis lesions will progress or stabilize. Considering gingival tissue and biofluids, we aimed to present a systematic review (qualitative analysis) on the ratios between disease/health periodontitis modulators, and a meta-analysis (quantitative analysis) of their levels in individuals with periodontitis compared to controls. DESIGN: Electronic searches of the PubMed, Scopus, EMBASE and Web of Science databases were conducted for publications up to May 2020. RESULTS: A total of 53 publications were included in the systematic review, being 22 of them focusing on the ratios between Interleukin [IL]-1/IL-10, IL-6/IL-10, IL-1/IL-1RA and RANKL/OPG. Twenty-one publications were eligible for meta-analyses. The ratios of IL-1, IL-6 and RANKL mRNA levels were significantly higher in diseased gingival tissue, as well as their protein levels in gingival crevicular fluid (GCF) of periodontitis individuals. Considering the saliva levels, the RANKL/OPG ratio was higher in periodontitis subjects in comparison to controls. Meta-analyses showed higher IL-1ß, IL-1α, IL-6 and IL-10 gene expressions in gingival tissue and protein levels in GCF, while RANKL was higher in GCF of periodontitis individuals in comparison to controls. CONCLUSIONS: Both the ratios and meta-analyses showed higher levels of modulators in gingival tissue and GCF of diseased individuals.