Is periodontitis associated with the risk of immune-mediated systemic conditions?

Abstract

This study evaluates the long-term risk of immune-mediated systemic conditions in individuals with periodontitis compared to those without. A structured online search was conducted in Medline, Cochrane library, and EMBASE using MeSH terms. All the databases were explored from initiation to June 2022. Reference lists of the eligible studies were hand searched as well. Peer-reviewed longitudinal retrospective/prospective cohorts and randomized controlled trials comparing incident metabolic/autoimmune/inflammatory diseases in periodontitis to healthy individuals were deemed eligible. Only studies with a minimum follow-up of one year were included. The authors checked demographics, data source, exclusion/inclusion criteria, total follow-up duration, disease outcome, and limitations to determine the eligible studies. After assessing the risk of bias for the included studies using the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool, the authors used the following measures to quantify the disease outcome: relative risk (RR), odds ratio (OR), and hazard ratio (HR). Systemic conditions were categorized as immune-mediated via disrupted metabolic networks (diabetes, kidney disease, liver disease, metabolic syndrome) or chronic inflammation (inflammatory bowel disease, osteoporosis, RA, psoriasis, Sjogren's syndrome), hence recognized as metabolic or autoimmune/inflammatory diseases, respectively. A random effect meta-analysis was used to synthesize the risk of developing each disease. The authors performed subgroup analysis for periodontitis diagnosis type (self-report/clinically diagnosed) and severity. They also conducted a sensitivity analysis to assess the effect of removing studies that did not adjust for smoking status. From 3354 studies, 166 full texts were screened. Finally, 30 studies were deemed eligible for the systematic review, of which 27 made it to the meta-analysis. The risks of diabetes, rheumatoid arthritis (RA) and osteoporosis were increased in individuals with periodontitis compared to those without periodontitis (diabetes-relative risk [RR]: 1.22, 95% CI: 1.13-1.33; RA-RR: 1.27, 95% CI: 1.07-1.52; osteoporosis-RR: 1.40, 95% CI: 1.12-1.75). The risk of diabetes showed a gradient increase by periodontitis severity (moderate-RR = 1.20, 95% CI = 1.11-1.31; severe-RR = 1.34, 95% CI = 1.10-1.63). People with moderate-to-severe periodontitis have the highest risk of developing diabetes. In contrast, the effect of periodontal severity on the risk of other immune-mediated systemic conditions requires further investigation. More homologous evidence is needed to assess the periodontitis-multimorbidity association further.