BACKGROUND: The presence of a polymicrobial dysbiotic film in direct and constant contact with periodontal tissues initiates the host immune response. Interleukin 18 (IL-18) triggers up-regulates the production of other proinflammatory cytokines (TNF-α, IL-1β, IL-6), creating a vicious cycle that expands the inflammatory and destructive process in the periodontal tissue. A systematic review and meta-analysis was carried out with the main propose to investigate IL-18 expression in different biological samples from subjects with chronic periodontitis.
METHODS: The protocol followed PRISMA guidelines and was registered in Open Science Framework (OSF): https://doi.org/10.17605/OSF.IO/BS9GM . A digital search was conducted in the databases PubMed, ScienceDirect, Google Scholar, Web of Science and Dentistry & Oral Sciences Source databases were consulted from March 15th, 2005 to February 10th, 2023. Study quality was assessed using the JBI tool for cross-sectional studies and clinical trials. A meta-analysis was performed using a random/fixed effects model to evaluate the concentration of IL-18 in serum, plasma, saliva, gingival tissue and GCF of exposure group compared to control group.
RESULTS: The search strategy provided a total of 3,156 articles, of which 18 investigations met the inclusion criteria and 15 articles were quantitatively analyzed. The total number of patients studied was 1,275 (682 cases and 593 controls). The meta-analysis revealed significantly elevated IL-18 levels of serum, saliva and GCF of subjects with chronic periodontitis compared to healthy subjects (Serum: SMD = 62.73, 95%CI: 25.43-100.03, Z = 3.29, p = 0.001*; Saliva: SMD = 243.63, 95%CI: 8.68-478.59, Z = 2.03, p = 0.042*; GCF: SMD = 150.26, 95%CI: 56.86-243.66, Z = 3.15, p = 0.02*).
CONCLUSIONS: IL-18 levels in serum, saliva and GCF could have the potential to be used as complementary diagnostic tools to the clinical and radiographic parameters in subjects with periodontitis.

Periodontitis is a preventable and treatable multifactorial chronic inflammatory disease that can lead to irreversible periodontal destruction and tooth loss. Wnt signaling and its regulators play an important role in periodontal inflammation, destruction, regeneration, and reconstruction. This systematic review aimed at investigating the involvement of Wnt signaling agonists and antagonists in periodontitis and healthy subjects, before and after periodontal treatment. Electronic searches were carried out using MEDLINE/PubMed, EMBASE, and Cochrane Library databases in addition to hand searches. Studies having different designs assessing the levels of Wnt signaling antagonist and agonist levels in gingival crevicular fluid, serum, and tissue in patients diagnosed with periodontitis or gingivitis, compared with healthy individuals were included. In addition, studies compared these levels in periodontitis patients before and after non-surgical periodontal therapy were also eligible. Sixteen studies met the eligibility criteria. Sclerostin (SOST) has been mainly investigated in the literature (8 publications). Sclerostin (5 studies), Wnt-5a (2 studies), secreted frizzled-related protein 1 (SFRP1) (3 studies), and β-catenin (3 studies) show increased levels in periodontitis compared with periodontal health. Strong correlations between marker levels and periodontal clinical parameters were identified for SOST (5 studies), SFRP1 (2 studies), and β-catenin (2 studies). SOST (3 studies) and SFRP1 (1 study) levels significantly decrease following non-surgical periodontal treatment. The present systematic review demonstrated an association between Wnt signaling agonist and antagonist levels and periodontitis. Wnt agonists and antagonists may serve as valuable diagnostic and prognostic markers for periodontitis onset and progression. Further case-control and longitudinal studies should be conducted for different Wnt signaling agonists and antagonists.

OBJECTIVE: Two focused questions were addressed within this systematic review. Q1) What is the effect of alveolar ridge preservation on linear and volumetric alveolar site dimensions, keratinised measurements, histological characteristics and patient-based outcomes when compared to unassisted socket healing. Q2) What is the size effect of these outcomes in three different types of intervention (guided bone regeneration, socket grafting and socket seal).
METHODS: An electronic search (MEDLINE, EMBASE, Cochrane Central Register LILACS, Web of Science) and hand-search was conducted up to June 2015. Randomised controlled trials (RCT) and controlled clinical trials (CCT); with unassisted socket healing as controls: were eligible in the analysis for Q1. RCTs, CCTs and large prospective case series with or without an unassisted socket healing as control group were eligible in the analysis for Q2.
RESULTS: Nine papers (8 RCTs and 1 CCTs) were included in the analysis for Q1 and 37 papers (29 RCTs, 7 CCTs and 1 case series) for Q2. The risk for bias was unclear or high in most of the studies. Q1: the standardised mean difference (SMD) in vertical mid-buccal bone height between ARP and a non-treated site was 0.739 mm (95% CI: 0.332 to 1.147). The SMD when proximal vertical bone height and horizontal bone width was compared was 0.796mm (95% CI: -1.228 to 0.364) and 1.198 mm (95% CI: -0.0374 to 2.433). Examination of ARP sites revealed significant variation in vital and trabecular bone percentages and keratinised tissue width and thickness. Adverse events were routinely reported, with three papers reporting a high level of complications in the test and control groups and two papers reporting greater risks associated with ARP. No studies reported on variables associated with the patient experience in either the test or the control group. Q2: A pooled effect reduction (PER) in mid-buccal alveolar ridge height of -0.467 mm (95% CI: -0.866 to -0.069) was recorded for GBR procedures and -0.157 mm (95% CI: -0.554 to 0.239) for socket grafting. A proximal vertical bone height reduction of -0.356 mm (95% CI: -0.490 to -0.222) was recorded for GBR, with a horizontal dimensional reduction of -1.45 mm (95% CI: -1.892 to -1.008) measured following GBR and -1.613 mm (95% CI: -1.989 to -1.238) for socket grafting procedures. Five papers reported on histological findings after ARP. Two papers indicated an increase in the width of the keratinised tissue following GBR, with two papers reporting a reduction in the thickness of the keratinised tissue following GBR. Histological examination revealed extensive variations in the treatment protocols and biomaterials materials used to evaluate extraction socket healing. GBR studies reported a variation in total bone formation of 47.9 ± 9.1% to 24.67 ± 15.92%. Post-operative complications were reported by 29 papers, with the most common findings soft tissue inflammation and infection.
CONCLUSIONS: ARP results in a significant reduction in the vertical bone dimensional change following tooth extraction when compared to unassisted socket healing. The reduction in horizontal alveolar bone dimensional change was found to be variable. No evidence was identified to clearly indicate the superior impact of a type of ARP intervention (GBR, socket filler and socket seal) on bone dimensional preservation, bone formation, keratinised tissue dimensions and patient complications.