## 10 Future Directions for Primary Studies  
The current literature assessing the relationship between OSA and PD reveals significant limitations that hinder a definitive understanding of their association. Most primary studies vary significantly in their methodologies, including differences in participant selection, diagnostic criteria for OSA and periodontitis, and assessment tools used to measure outcomes. Many studies are limited by small or region-specific populations, which restricts the generalizability of findings. Studies with larger cohorts are necessary to validate exist  
Figure 2: AMSTAR-2 response rates by item. Y = yes, PY = partial yes, N = no, NMC = no meta-analysis conducted.  
ing associations. Studies examining the role of oral microbiota in the association between OSA and periodontitis often employ different sampling methods and analytical techniques, leading to inconsistent findings on microbiome composition and its potential mechanistic link to both conditions. Several studies fail to adequately control for shared risk factors, such as smoking, diabetes, and obesity, which are independently associated with both conditions. This raises concerns about whether the observed associations are truly causal or mediated by these confounders.  
To advance our understanding of the relationship between OSA and PD, future primary studies must address current methodological shortcomings to maximize clinical relevance. Although OSA and PD are associated, whether this association is causative is uncertain. Thus, longitudinal and interventional study designs should be prioritized to establish causality and clarify the temporal interplay between OSA severity and PD progression. Incorporating extended follow-up periods is critical to evaluate long-term outcomes and their systemic implications. Standardizing diagnostic criteria and definitions for both OSA and PD is an essential step to mitigate inconsistencies that currently limit comparability and reproducibility across studies.  
Future research should employ an integrative approach, combining clinical assessments, microbiological analyses, and biomarker investigations. Particular attention should be given to salivary biomarkers, alterations in the oral microbiome, and systemic inflammatory mediators to unravel the mechanisms by which intermittent hypoxia in OSA accelerates periodontal tissue damage. Studies focusing on dose-response relationships between OSA severity--quantified by AHI--and periodontal outcomes, including CAL and PPD, are especially needed to refine our understanding of these associations.  
Accounting for patient variability is equally important. Stratifying analyses based on demographic, behavioral, and health-related factors such as age, smoking, and comorbidities will enhance precision and relevance. Transparent reporting of funding sources is critical to minimize bias and bolster the credibility of findings. Furthermore, randomized controlled trials exploring the potential of periodontal therapy to alleviate OSA symptoms and reduce systemic inflammation should be a key area of focus. Such trials will provide robust evidence on the bidirectional impact of treating one condition on the other. Collaborative efforts between dental and sleep medicine specialists will be essential to guide these investigations, fostering an integrated care model that improves both oral and systemic health outcomes.