Table 1.

Data extracted from the included studies. C-C: a case-control study, CS: cross-section study. pro-Matrix MetalloPeptidase 9, MMP-8: Matrix MetalloPeptidase 8, TIMP-1: MetalloProteinase Inhibitor 1 Precursor, NE: Neutrophil elastase, MPO: Myeloperoxidase, proMMP-2 pro-Matrix MetalloPeptidase 2, NGAL: Neutrophil Gelatinase-Associated Lipocalin, MMP-9: Matrix MetalloPeptidase 9, IL-1β: Interleukin-1β, GCF: Gingival Crevicular Fluid, hs-CRP: high sensibility-C Reactive Protein, CFU: colony-forming units, IL-6: Interleukin-6, TNF-α: Tumor Necrosis Factor-α, sRANKL: Soluble receptor activator of nuclear factor (NF)-κB ligand, OPG: Osteoprotegerin, SBD: Sleep-related Breathing Disorder, IL-33: Interleukin-33, IL-21: Interleukin-21, PTX-3: pentraxin-3, ODI: Oxygen Desaturation Index, MMPS: Matrix MetalloPeptidases, SpO₂: oxygen saturation.

Author	Type of Study	Sample Size	Middle Age	OSAS Diagnosis Method	AHI	Periodontal Parameters	Results	Risk of Bias	Authors’ Conclusions
Keller et al. 2013	C-C	29,284 (18,232 M; 11,052 F)	47.6 (±15.4)	PSG	<5 >5	PD (6 sites/each tooth), ABL	Prevalence of periodontitis: in cases 33.8% vs. 22.6% in controls OR of prior periodontitis for cases was 1.75 (95% CI = 1.68–1.88) times greater than that of controls OR = 1.78 of OSAS in patients with previous periodontitis excluding those who received treatment	5 high	There is an association between OSAS and a previous diagnosis of periodontitis
Nizam et al. 2015	C-C	50 (20 F; 30 M)		PSG	<5 5–30 >30	CAL, PD, BoP, PI (all 6 sites/each tooth)	Serum levels of proMMP-9 significantly lower in the severe OSAS group than in the control. No difference between the control group and the mild-moderate OSAS group. No significant difference between the study groups in serum levels of MMP-8, TIMP-1, NE, MPO, proMMP-2, or MMP-8/TIMP-1 ratio. Significantly lower salivary NE concentration in the OSAS groups compared to the control group. No significant difference between groups in the salivary concentration of MMP-8, TIMP-1, MPO, NGAL, or MMP-8/TIMP-1 ratio. The salivary concentration of proMMP-2 significantly lower in the OSAS groups than in the control group. Degree of activation of salivary MMP-9 significantly lower in the severe OSAS group than in the control group. Negative correlation between ODI and serum levels of proMMP-2 and between AHI and serum concentration of NE and proMMP-2. Negative correlation between AHI and salivary proMMP-9 and -2	5 high	There is no pathophysiological link between the severity of OSAS and the periodontal clinical status mediated by the products of neutrophils and MMPs. Periodontal clinical parameters were higher in the severe OSAS group but the difference between the study groups was not statistically significant.
Nizam et al. 2016	C-C	52 (32 M; 20 F)		PSG	<5 5–30 >30	CAL, PD, salivary cytokines BoP, PI (6 sites/each tooth)	The total of the equivalent CFU averages increases according to the severity of the OSAS. Marked increase in Gram—in plaque samples from patients with severe OSAS and periodontal disease. Salivary levels of IL-6 significantly higher in the OSAS group than in the non-OSAS group. Significantly higher salivary apelin levels in the severe OSAS group than in the control group. Salivary levels of TNF-α, sRANKL, OPG, and OPG/sRANKL similar in all study groups. Highest serum IL-6 and apelin concentration in the OSAS group. Salivary IL-6 is significantly related to the severity of OSAS. CAL-related number of apnea episodes	6 medium	There is a marked change in the presence of particular oral and periodontal microorganisms in the subgingival plaque; these data suggest that OSAS has a connection with the development of periodontal inflammation. Increased salivary IL-6 concentration could both cause and impact periodontal disease in patients with OSAS
Nizam et al. 2014	C-C	52 (32 M; 20 F)	46.60	PSG	<5, 5–30 >30	CAL, PI, PD, and BoP (6 sites/each tooth), salivary cytokines	The concentration of IL-6 significantly lower in the control group than in the group with OSAS IL-33 significantly higher in the OSAS group than in the non-OSAS group No statistically significant difference in IL-1β, IL-21, and PTX-3 concentration between OSAS and non-OSAS Significant correlation between CAL and IL-21 PD and CAL significantly correlated with OSAS severity indicators such as AHI, ODI, SpO2	5 high	OSAS does not affect the salivary levels of IL-1β, IL-21, and PTX-33 The levels of IL-6 and IL-33 increase in the patients. OSAS regardless of the severity of the OSAS The increased concentration of these cytokines could play a role in the pathogenesis of periodontal disease in patients with OSAS
Gamsiz-Isik et al. 2017	C-C	163 (122 M; 41 F)	45	PSG	<5 5–15 >15	CAL, PD, PI by Silness and Loe, GI (all 6 sites/each tooth), and BoP	PI, GI, PD, CAL, BoP, PD ≥ 4 mm, and PD ≥ 4 mm% significantly higher in the OSAS group. Periodontitis prevalence 96.4% OSAS group compared to 75% non-OSAS. Prevalence of severe periodontitis in the OSAS group 48.2%. Levels of IL-1β in GCF and hs-CRP in serum significantly higher in the OSAS group. Significant correlation between IL-1β in GCF and PI, GI, CAL, PD, BoP, and PD ≥ 4 mm% CAL and PD significantly associated with hs-CRP levels in serum and GCF in the OSAS group	6 medium	Periodontitis prevalence is higher in OSAS groups compared to the control group. OSAS associated with periodontal indices and local inflammation parameters such as higher IL-1β
Latorre et al. 2018	CS	199 (107 F; 92 M)	49.9	PSG	<5 5–15 15–30 >30	CAL, PD (6 sites/each tooth)	Prevalence of periodontitis 62.3% Statistically significant association between mild OSAS and periodontitis OR = 1.37	7 medium	Statistically significant association between mild OSAS and periodontitis. This association is more frequent in women with hypertension or hypertensive cardiomyopathy. Periodontitis associated with severe OSAS in men with hypertension or hypertensive cardiomyopathy
Loke et al. 2015	CS	100 (91 M; 9 F)	52.6	PSG	<5 5–15 15–30 >30	CAL, PD, REC (all 6 sites/each tooth), PI (4 sites/each tooth) and BoP	Prevalence of periodontitis in the sample population 73%. If AHI is expressed as a continuous variable, there is no correlation between AHI and the severity of periodontal disease. Significant relationship between AHI class and % of plaque. No significant relationship between AHI class and % BoP or sites with CAL ≥ 3	7 medium	A statistically significant association was not found between OSAS and the prevalence of moderate/severe periodontitis; no association was found between the severity of OSAS and the periodontal state
Gunaratnam et al. 2009	CS	66 (54 M; 12 F)	54.9	PSG	>5	CAL, PD, BoP, PI by Silness and Loë, REC, GI (modified by Lobene)	Periodontitis prevalence in the OSAS group 77–79%. Significant association between CAL and total sleep time	6 medium	Higher prevalence of periodontitis in OSAS patients than in non-OSAS
Sanders et al. 2015	CS	12,469 (7473 F; 4996 M)		ARES	0 0–5 5–15 >15	CAL, PD, and REC (6 sites/each tooth)	Greater prevalence of periodontitis as the severity of OSAS increases. The association between periodontitis and OSAS is stronger in the 18–34 age group. No apparent relationship between OSAS and the prevalence of severe periodontitis in subjects aged ≥55 years. OR = 1.4 of severe periodontitis in patients with subclinical SDB; in patients with mild SDB OR = 1.6; with moderate/severe SDB OR = 1.5	8 low	Severe periodontitis is positively associated with OSAS, in particular mild. This association is more pronounced in young adults. There is an independent association between severe periodontitis and OSAS. Blood levels of hs-CRP do not explain this relationship.
Seo et al. 2013	CS	687 (460 M; 227 F)	55.85 (±6.63)	PSG	>5	CAL, PD, BoP, PI by Silness and Loë, REC, GI	Prevalence of periodontitis in the whole sample population 17.5%. 60% of subjects with periodontitis had OSAS. OSAS associated with periodontitis OR = 1.84. OSAS associated with periodontitis in the age group ≥55 years OR = 2.51. Dose-response relationship between periodontitis and OSAS severity	8 low	There is a significant association between OSAS and periodontal disease. OSAS positively associated with periodontitis, PD, and CAL in a dose-response manner.