Lack of keratinized mucosa increases peri-implantitis risk
Authors: Afrashtehfar Kelvin I. , Oh Kyung Chul , Jurado Carlos A. , Lee Hyeonjong 
Published: August 2023

Abstract
Design
A systematic appraisal and statistical aggregation of primary studies in humans.

Data sources
The researchers utilized PubMed (Medline) and Scopus databases as the primary data sources for this study. They performed a comprehensive literature search based on free keywords and Medical Subject Heading (MeSH) terms to enhance the search accuracy. The database search was concluded on November 13, 2022. Furthermore, a meticulous examination of the references cited in the selected studies was conducted to identify additional relevant articles that could be incorporated into the analysis.

Study selection
The systematic review focused on partially or fully edentulous patients receiving dental implants and aimed to determine if the lack of keratinized mucosa at the implant site increased the risk of peri-implantitis compared to patients with adequate keratinized mucosa. Human studies with a minimum of 100 implants, cross-sectional, cohort, or case-control designs, and a follow-up period of at least one year were included. Studies lacking a clear case definition or information on peri-implantitis and those that did not investigate keratinized mucosa as a risk indicator were excluded.

Data extraction and synthesis
Two reviewers independently utilized a systematic review screening website (Rayyan, Qatar Computing Research Institute, Qatar Foundation) to select potential articles, and conflicts were resolved through discussion or consultation with a third reviewer. The data extraction process involved recording information from the included articles, such as study design, patient and implant numbers, prosthesis type (fixed or removable), follow-up duration, peri-implantitis case definition, prevalence at patient and implant levels, keratinized mucosa cutoff value, odds ratio (OR) of peri-implantitis considering keratinized mucosa, and conclusions on the potential effect of keratinized mucosa from each study. The Newcastle Ottawa scale (NOS) and a modified version of NOS were used, respectively, to assess the quality of cohort and cross-sectional studies. Studies scoring below 6 out of 9 points were classified as low quality. For the meta-analysis, the relationship between peri-implantitis and keratinized mucosa was evaluated using the odds ratio (OR) and standard error (SE). Heterogeneity was assessed through the Chi2 test and I2 index, determining whether a random-effects or fixed-effects model should be applied. Subgroup and cluster analyses were conducted based on specific criteria, and forest plots and funnel plots were generated to visualize results and identify potential study bias. Sensitivity analysis was performed to verify the robustness of the meta-analysis, with statistical significance set at p < 0.05. The Review Manager (RevMan) software facilitated data analysis.
The GRADE rating system was used to determine the level of evidence, considering factors such as bias risk, imprecision, inconsistency, indirectness, and publication bias. The certainty of the evidence was evaluated based on the overall outcomes of analyzed subgroups.

Results
Twenty-two primary studies were identified, and a meta-analysis was conducted on 16 cross-sectional studies. The prevalence of peri-implantitis ranged from 6.68% to 62.3% at the patient level and from 4.5% to 58.1% at the implant level. The overall analysis revealed a significant association between the lack of keratinized mucosa and a higher prevalence of peri-implantitis (OR = 2.78, 95% CI 2.07–3.74, p < 0.00001). Subgroup analyses with a consistent case definition of peri-implantitis (MBL ≥ 2 mm) showed similar results (OR = 1.96, 95% CI 1.41–2.73, p < 0.0001). Studies focusing on fixed prostheses only demonstrated that the lack of keratinized mucosa was associated with an increased prevalence of peri-implantitis (OR = 2.82, 95% CI 1.85–4.28, p < 0.00001). Among patients under regular implant maintenance, the absence of keratinized mucosa significantly raised the occurrence of peri-implantitis (OR = 2.08, 95% CI 1.41–3.08, p = 0.0002). Studies adjusting for other variables also confirmed a higher risk of peri-implantitis with inadequate keratinized mucosa (OR = 3.68, 95% CI 2.32–5.82, p = 0.007). Although some publication bias was observed, the certainty of evidence based on the GRADE system was judged to be "moderate."

Conclusions
The lack of keratinized mucosa increased the risk of peri-implantitis, emphasizing the need to consider it during dental implant placement. Inadequate data on patient-specific factors and the predominance of cross-sectional studies influenced the evidence quality (i.e., moderate). Future studies with consistent methodologies shall confirm these findings and identify additional risk indicators to improve implant dentistry practices.