Periodontal Disease Augments Cardiovascular Disease Risk Biomarkers in Rheumatoid Arthritis.

Objectives: Periodontal disease (PD) and rheumatoid arthritis (RA) are known chronic conditions with sustained inflammation leading to osteolysis. Cardiovascular diseases (CVD) are frequent comorbidities that may arise from sustained inflammation associated with both PD and RA. In order to determine CVD risk, alterations at the molecular level need to be identified. The objective of this study, therefore, was to assess the relationship of CVD associated biomarkers in RA patients and how it is influenced by PD. Methods: The study consisted of patient (26 RA with PD, 21 RA without PD, 51 patients with PD only) and systemically and periodontally healthy control (n = 20) groups. Periodontal parameters bleeding on probing, probing pocket depth, and marginal bone loss were determined to characterize the patient groups. Proteomic analysis of 92 CVD-related protein biomarkers was performed using a multiplex proximity extension assay. Biomarkers were clustered using the search tool for retrieval of interacting genes (STRING) to determine protein−protein interaction (PPI) networks. Results: RA patients with PD had higher detection levels for 47% of the measured markers (ANGPT1, BOC, CCL17, CCL3, CD4, CD84, CTRC, FGF-21, FGF-23, GLO1, HAOX1, HB-EGF, hOSCAR, HSP 27, IL16, IL-17D, IL18, IL-27, IL6, LEP, LPL, MERTK, MMP12, MMP7, NEMO, PAPPA, PAR-1, PARP-1, PD-L2, PGF, PIgR, PRELP, RAGE, SCF, SLAMF7, SRC, THBS2, THPO, TNFRSF13B, TRAIL-R2, VEGFD, VSIG2, and XCL1) as compared to RA without PD. Furthermore, a strong biological network was identified amongst these proteins (clustering coefficient = 0.52, PPI enrichment p-value < 0.0001). Coefficients for protein clusters involved in CVD (0.59), metabolic (0.53), and skeletal (0.51) diseases were strongest in the PD group. Conclusion: Periodontal disease augments CVD-related biomarkers in RA through shared pathological clusters, concurrently enhancing metabolic and skeletal disease protein interactions, independent of autoimmune status.

Upregulation of circulating inflammatory biomarkers under the influence of periodontal disease in rheumatoid arthritis patients.

OBJECTIVES: Periodontal disease (PD) and rheumatoid arthritis (RA) are chronic immuno-inflammatory conditions with osteolysis being a hallmark feature. The influence of PD on RA's systemic inflammatory status and disease activity remains unclear. The objective of this study was to assess the systemic inflammation and disease activity of RA under the influence of PD. METHODS: In this case-control study, 38 RA patients (19 with PD and 19 without PD) were compared to 38 non-RA patients and 12 healthy controls. Periodontal parameters (bleeding on probing (BOP), probing pocket depth (PPD), PPD Total, PPD Disease and marginal bone loss (MBL) were determined. Serological analyses included quantification of 92 inflammatory biomarkers using a multiplex proximity extension assay, anti-citrullinated protein antibodies (ACPA), rheumatoid factor (IgM-RF) and erythrocyte sedimentation rate (ESR). RA disease activity was determined using Disease Activity Score for 28 joints (DAS28). All RA patients were on medication. RESULTS: IgM-RF was higher in RA patients with PD. PD conditions were more severe in the non-RA group. Inflammatory biomarkers (IL-10RB, IL-18, CSF-1, NT-3, TRAIL, PD-L1, LIF-R, SLAMF1, FGF-19, TRANCE, CST5, STAMPB, SIRT2, TWEAK, CX3CL1, CXCL5, MCP-1) were significantly higher in RA patients with PD than RA without PD. DAS28 associated with twice as many inflammatory biomarkers in RA patients with PD whereas IgM-RF and ACPA associated more frequently with biomarkers in the RA without PD group. IgM-RF correlated inversely with BOP. CONCLUSION: Periodontal disease augments systemic inflammation in RA. A profound influence exists independent of autoimmune status.

Association of Glycated Proteins with Inflammatory Proteins and Periodontal Disease Parameters.

Periodontitis is a chronic inflammatory condition that may contribute to diabetogenesis. The aim was to investigate the levels of glycated proteins and their correlation with periodontal and systemic inflammation. Fifty-one patients with periodontitis and 20 healthy subjects underwent probing pocket depth (PPD) measurements. PPD total and PPD disease with and without tooth adjustment were used as continuous indices. Marginal bone loss (MBL) for mandibular premolars and molars was measured digitally. Body mass index (BMI) and waist circumference (WC) were also analyzed. Glycated hemoglobin (HbA1c) and fructosamine (FrAm) levels were measured in all subjects. A multiplex proximity extension assay (PEA) was used to analyze the serum samples for simultaneous measurement of 92 proteins. Both HbA1c and FrAm inversely correlated with IL-10, FGF-21, MCP-1, and TNF beta amongst 16 proteins. HbA1c correlated directly with OPG. Parameters of disease severity were consistently significant for HbA1c. Adjusted PPD total and number of missing teeth were increased in diabetes whereas levels of RANKL and RANKL to OPG ratio were the highest in nondiabetic periodontitis patients. Hyperglycemic conditions in periodontitis patients are associated with reduced levels of anti-inflammatory proteins as well as dysregulated bone resorption.

Periodontal disease influences osteoclastogenic bone markers in subjects with and without rheumatoid arthritis.

BACKGROUND: Periodontal disease (PD) and rheumatoid arthritis (RA) are bone pathologies mediated through immuno-inflammatory mechanisms. The aim of this study was to investigate the serum markers osteopontin (OPN), tumor necrosis factor receptors 1 (TNFR1) and 2 (TNFR2) receptor activator of nuclear factor-kappa B ligand (RANKL) and RANKL/ osteoprotegerin (OPG) ratio and compare them in PD and RA groups. MATERIALS & METHODS: RA (with PD = 19 and without PD = 19), PD (n = 38) and 14 healthy subjects underwent bleeding on probing (BOP) and probing pocket depth (PPD) measurement. PD was defined as PPD measuring ≥5mm registered in ≥3 sites. Marginal bone loss (MBL) for premolars and molars was measured on digital panoramic radiographs. Serum samples were collected from all subjects. OPN, TNFR1, TNFR2 and RANKL were measured by enzyme-linked immunosorbent assays (ELISAs). OPG was measured as part of a multiplex proximity extension assay (PEA). RESULTS: OPN, TNFR1, TNFR2 and RANKL serum levels were the highest in the RA group with PD, while the RA group without PD were comparable to PD subjects only. The RANKL/OPG ratios were comparable between PD group and both RA groups with (p = 0.051) and without PD (p = 0.37). Serum RANKL levels were associated with MBL (p = 0.008) and PPD ≥ 5mm (p = 0.01). CONCLUSION: Peripheral osteoclastogenesis is a feature of periodontal disease with systemic levels of osteoclastogenic markers comparable to the effects observed in rheumatoid arthritis.

Correlation of serum cytokines, chemokines, growth factors and enzymes with periodontal disease parameters.

BACKGROUND: Periodontal disease (PD) is characterized by inflammatory tissue destruction in tooth supporting apparatus. Many studies indicate that the underlying pathogenesis is in concordance with rheumatoid arthritis (RA) sharing immune-inflammatory events affect both diseases. The aim of this study was to investigate serum cytokines, chemokines, growth factors, enzymes and costimulatory proteins in association with periodontal conditions in PD and RA subjects. MATERIALS & METHODS: Periodontal examination was performed in RA (n = 38), PD (n = 38) and healthy subjects (n = 14). Bleeding on probing (BOP) and probing pocket depth (PPD) were measured. Marginal bone loss (MBL) for premolars and molars was measured on digital panoramic radiographs. PD was defined as present if the PPD was ≥5mm in ≥ 3 different sites. Serum samples were collected from all subjects. A multiplex proximity extension assay (PEA) was used to analyze the samples for simultaneous measurement of 92 cytokines. Cytokines with ≥ 60% quantitative results were included. RESULTS: A significant positive correlation was seen for ST1A1, FGF-19 and NT-3 whereas EN-RAGE, DNER, CX3CL1 and TWEAK associated inversely with BOP, PPD≥ 5mm and MBL but positively with number of teeth. Several CD markers (CD244, CD40, CDCP1, LIF-R, IL-10RA, CD5 and CD6) were found to be associated with BOP, shallow and deep pockets, MBL and number of teeth, either directly or inversely. Most chemokines (CCL8, CX3CL1, CXCL10, CXCL11, CCL11, CCL4, CCL20, CXCL5, CXCL6, and CCL23) were positively associated with number of teeth and some inversely related to MBL (CCL8, CXCL10). Proteins with enzymatic activity (ST1A1, HGF and CASP-8) were directly related to the severity of periodontal conditions and inversely related to number of teeth. Aside from FGF-19, other growth factors were also directly associated with MBL (HGF), number of teeth (VEGF-A, LAP TGF-beta-1) and, inversely to, shallow pockets (LAP TGF-beta-1, TGFA and Beta-NGF). Out of 33 cytokines, 32 associated inversely with shallow pockets, whereas only CD40 associated positively. Associations between cytokines and periodontal parameters in the RA group were comparatively less. Statistical analyses were adjusted for multivariate effects using the Benjamini-Hochberg false discovery rate method. CONCLUSION: Systemic inflammatory burden, via known and novel markers, is associated with periodontal conditions in PD and RA subjects. Shallow pockets are not associated with a higher inflammatory state.

Periodontal conditions, oral Candida albicans and salivary proteins in type 2 diabetic subjects with emphasis on gender.

BACKGROUND: The association between periodontal conditions, oral yeast colonisation and salivary proteins in subjects with type 2 diabetes (T2D) is not yet documented. The present study aimed to assess the relationship between these variables in type 2 diabetic subjects with reference to gender. METHODS: Fifty-eight type 2 diabetic subjects (23 males and 35 females) with random blood glucose level >or= 11.1 mmol/L were investigated. Periodontal conditions (plaque index [PI], bleeding on probing [BOP], probing pocket depth [PD] (4 to 6 mm and >or= 6 mm), oral yeasts, salivary immunoglobulin (Ig) A, IgG and total protein concentrations, and number of present teeth were determined. RESULTS: Periodontal conditions (PI [p < 0.00001], BOP [p < 0.01] and PD of 4 to 6 mm [p < 0.001], salivary IgG (microg)/mg protein (p < 0.001) and salivary total protein concentrations (p < 0.05) were higher in type 2 diabetic females with Candida albicans (C. albicans) colonisation compared to males in the same group. Type 2 diabetic females with C. albicans colonisation had more teeth compared to males in the same group (p < 0.0001). CONCLUSION: Clinical and salivary parameters of periodontal inflammation (BOP and IgG (mug)/mg protein) were higher in type 2 diabetic females with oral C. albicans colonisation compared to males in the same group. Further studies are warranted to evaluate the association of gender with these variables in subjects with T2D.

Effect of diabetes on periodontal status of a population with poor oral health.

OBJECTIVE: Diabetes is a global health problem and its prevalence is increasing worldwide. The objective of the study was to investigate the effect of diabetes on the periodontal status of a Pakistani population with poor oral hygiene. MATERIAL AND METHODS: Eighty-eight individuals with diabetes and 80 non-diabetic individuals were recruited from a disadvantaged district in Karachi, Pakistan. The group with diabetes comprised 50 males and 38 females, and the non-diabetic group 43 males and 37 females. All underwent clinical and radiographic examination. RESULTS: The average numbers of teeth in the diabetes and non-diabetes groups were 24 and 26, respectively. The odds ratio (OR) for missing or fewer teeth was 2.3 times higher for diabetics than for non-diabetics (CI 1.32-4.14; p<0.001). Diabetic patients had more sites with plaque than did non-diabetics (OR 1.96, CI 0.99-3.88; p<0.056). Moderate to severe periodontitis was significantly more prevalent among diabetic patients (p<0.01). CONCLUSION: In this disadvantaged population with poor oral hygiene, diabetes has had a strongly negative influence on oral health: diabetic patients have fewer teeth, more plaque, and a higher prevalence of moderate to severe periodontal disease than non-diabetics.

Periodontal conditions and oral symptoms in gutka-chewers with and without type 2 diabetes.

OBJECTIVE: The aim of the study was to investigate the periodontal conditions and oral symptoms among gutka-chewers in subjects with and without type 2 diabetes (T2D). MATERIAL AND METHODS: Subjects aged between 45 and 64 years were included. "Gutka-chewers" were defined as subjects who had been chewing at least one sachet of gutka daily for at least 12 months. Subjects who reported never to have used tobacco in any form were categorized as "non-chewers". Periodontal conditions (plaque index [PI], bleeding on probing [BOP], and probing depth [PD] [4 mm<6 mm and > or =6 mm]), number of missing teeth, oral symptoms, reasons for gutka use, and random blood glucose levels were recorded. Exclusion criteria were smoking and use of antibiotics, non-steroidal anti-inflammatory drugs, and steroids. RESULTS: Mean durations of gutka use in subjects with and without T2D were 10.5 (range 8.0-15.5 years) and 8.4 (range 6.0-20.2 years) years correspondingly. In subjects with T2D, gutka-chewers (n=29) and non-chewers (n=44) showed no difference in periodontal conditions, missing teeth, and gingival bleeding. In subjects without T2D, gutka-chewers (n=36) had increased PI (p<0.01), BOP (p<0.001), PD (4 mm<6 mm) (p<0.01), number of missing teeth, and gingival bleeding (p<0.01) compared to non-chewers (n=42). Non-chewers in subjects with T2D had poorer periodontal conditions and increased oral symptoms compared to gutka-chewers and non-chewers in subjects without T2D. CONCLUSION: In subjects without T2D, gutka-chewers have severe periodontal conditions and oral symptoms compared to non-chewers. In subjects with T2D, the severity of these variables is related to glycemic levels rather than gutka consumption.

Influence of betel nut chewing, dental care habits and attitudes on perceived oral health among adult Pakistanis.

PURPOSE: To survey an adult population in a deprived district of Karachi, with reference to factors influencing perceived oral health. MATERIALS AND METHODS: Of 1000 questionnaires distributed to households, 994 were returned. The respondents were aged between 30 and 50 years old. Women comprised 49% of the sample. RESULTS: Pan and betel nut chewing had a strong influence on the perceived oral health of the respondents. Pan chewers, 32% of the respondents, had a greater risk of oral problems, odds ratio 3.63. In contrast to other oral problems, dental caries was significantly less frequent among pan chewers (odds ratio 0.63). Betel nut chewing (28%) was less deleterious to oral health: the only significant effects were a higher risk for dental caries, odds ratio 4.51, and more gingival bleeding. While most of the respondents used a toothbrush for oral hygiene, a substantial proportion (27%) used their fingers. The oral hygiene method had no influence on the perceived oral health, nor did consumption of sweets and tea with sugar. Over 80% of the participants seldom or never visited a dentist. Cleaning frequency was significantly associated with oral health: those who cleaned their teeth at least daily had fewer oral problems. Almost all participants considered that eating sweets, smoking, and chewing pan and betel nuts endangered oral health. CONCLUSIONS: In this population, typical of deprived urban areas of Pakistan, betel nut habits and frequency of oral hygiene have a strong influence on perceived oral health, while cleaning method and sugar intake do not.

Comparison of periodontal and socioeconomic status between subjects with type 2 diabetes mellitus and non-diabetic controls.

BACKGROUND: The association among periodontal conditions, socioeconomic status (SES), and diabetes has been reported. However, there is a lack of published data comparing periodontal conditions among individuals with poorly controlled type 2 diabetes mellitus (T2D). The aim of the present study was to compare the periodontal conditions and SES between subjects with T2D and non-diabetic controls. METHODS: A total of 75 (31 males and 44 females) individuals with T2D (62 poorly controlled and 13 well-controlled) and 99 non-diabetic patients (healthy controls; 51 males and 48 females) participated in the study. Plaque index (PI), bleeding on probing (BOP), and probing depth (PD) were investigated. Random blood glucose level was recorded. Premolar and molar marginal bone loss (MBL) was measured digitally on scanned orthopantomograms. RESULTS: Individuals with poorly controlled T2D had increased MBL in molars and maxillary premolars (P<0.05) compared to individuals with well-controlled T2D. PI, BOP, and PD of 4 to <6 mm were increased in individuals with poorly controlled T2D compared to those with well-controlled T2D (P<0.001). There was no difference between the diabetic groups when PD was >or=6 mm. Individuals with poorly controlled T2D had a lower SES compared to patients with well-controlled T2D (P<0.05). Illiteracy and the number of missing teeth were not different between the groups. CONCLUSIONS: Radiologic and clinical indicators of periodontal destruction were increased in individuals with poorly controlled T2D. Low SES aggravated the periodontal condition in individuals with T2D.

Perception of oral health among adults in Karachi.

PURPOSE: To survey an adult population in a deprived district of Karachi, with special reference to perceived oral health. MATERIALS AND METHODS: One thousand questionnaires, covering topics such as socioeconomic status, general health and oral health were distributed to the participants' homes by dental auxiliaries, and 994 were returned. The respondents were adults aged between 30 and 50 years. Women comprised 49% of the sample. RESULTS: Over half the participants (54%) perceived that they had oral problems: esthetic issues predominated (33%), but pain (17%), cavities (15%) and difficulty chewing (8%) were also reported. Most participants (94%) had dentitions of > or = 20 teeth. There was a weak but significant negative correlation between age and number of teeth (r2=0.03, p<0.001). Age and female gender were significantly associated with pain, bleeding gums and periodontitis. Pain was a more frequent complaint among poorly educated subjects than among the better educated. Diabetics comprised 17% of respondents and reported higher frequencies of dental problems, bleeding gums and calculus and fewer teeth. However, after compensation for age, gender, smoking, education and income, no significant associations were disclosed. Smoking was reported by 30% of all subjects and was significantly associated with pain, bleeding gums and periodontitis. CONCLUSION: The survey disclosed that over half the subjects in this sample of underprivileged Pakistani adults suffered from poor oral health, including pain.