Anna Maria Heikkinen

Smoking affects diagnostic salivary periodontal disease biomarker levels in adolescents.

BACKGROUND The effects of smoking on periodontal biomarkers in adolescents are unknown. This study investigates matrix metalloproteinase (MMP)-8 and polymorphonuclear leukocyte elastase levels in saliva together with periodontal health indices accounting for body mass index and smoking in a birth cohort from Finland. METHODS The oral health of boys (n = 258) and girls (n = 243) aged 15 to 16 years was examined clinically. Health habits were assessed by questionnaire. Saliva samples were collected and analyzed by immunofluorometric and peptide assays for MMP-8 levels and polymorphonuclear leukocyte elastase activities, and investigated statistically with the background factors. RESULTS Median MMP-8 values of male smokers were 112.03 microg/l compared to 176.89 microg/l of non-smokers (P = 0.05). For female smokers corresponding values were 170.88 microg/l versus 177.92 microg/l in non-smokers (not statistically significant). Elastase values in male smokers were 5.88 x 10(-3) Delta OD(405)/h versus 11.0 x 10(-3) Delta OD(405)/h in non-smokers (P = 0.02), and in female smokers 9.16 x 10(-3) Delta OD(405)/h versus 10.88 x 10(-3) Delta OD(405)/h in non-smokers (P = 0.72). The effect was strengthened by high pack-years of smoking (MMP-8, P = 0.04; elastase, P = 0.01). Both biomarkers increased with gingival bleeding. However, statistically significant associations were observed with bleeding on probing and MMP-8 (P = 0.04); MMP-8 was suggestively associated with probing depth (P = 0.09) in non-smoking boys. In smokers with calculus, MMP-8 increased after adjusting with body mass index (P = 0.03). No corresponding differences were seen in girls. CONCLUSIONS Smoking significantly decreased both biomarkers studied. Compared to girls, boys seem to have enhanced susceptibility for periodontitis as reflected in salivary MMP-8 values.

Pilot Study on Oral Health Status as Assessed by an Active Matrix Metalloproteinase-8 Chairside Mouthrinse Test in Adolescents

BACKGROUND Matrix metalloproteinase (MMP)-8 is a major destructive collagenase involved in periodontitis and can be regarded as a periodontitis biomarker. A neutrophil collagenase 2 (active MMP-8 [aMMP-8]) oral fluid immunoassay has recently been demonstrated to be a periodontitis risk indicator among adults. The aim of this study is to investigate whether a point-of-care mouthrinse test based on an aMMP-8 immunoassay could identify patients with oral inflammatory burden (periodontitis and caries) among adolescents with early pathologic findings. METHODS This cross-sectional study was carried out at the Kotka Health Center, Finland. First, the aMMP-8 chairside mouthrinse test was performed on enrolled individuals (adolescents aged 15 to 17 years, n = 47), and the results were read based on a color change within 5 minutes. Then, full-mouth clinical parameters of oral health were assessed, including periodontal, oral mucosal, and caries status. RESULTS The sensitivity and specificity of the test for bleeding on probing were 71.8% and 77.5%, respectively (P = 0.05); for ≥1 site with probing depth (PD) ≥4 mm, 48.3% and 100% (P <0.001); for ≥2 sites with PD ≥4 mm, 63.6% and 100% (P <0.001); and for >2 sites with PD ≥4 mm, 76.5% and 96.7% (P <0.01). Regarding periodontitis (≥1 site with PD ≥4 mm), hardly any false-positive results were identified. The sensitivity of the immunoassay for ≥1 caries lesions was 76.5%, and the specificity was 96.7% (P <0.01). CONCLUSIONS In 5 minutes, the aMMP-8 chairside test showed promising results, recognizing oral inflammatory burden in adolescents with early initial signs of periodontitis. Caries lesions could also be detected, but less efficiently.

Salivary Diagnostics—Point-of-Care diagnostics of MMP-8 in dentistry and medicine

Human saliva is an easily accessible biological fluid and contains a variety of disease-related biomarkers, which makes it a potential diagnostic medium. The clinical use of salivary/oral fluid biomarkers to identify oral and systemic conditions requires the development of non-invasive screening and diagnostic technologies, and is among the main goals of oral fluid researchers. The analysis of the disease-specific oral and systemic biomarkers in saliva and oral fluids (i.e., mouth-rinse, gingival crevicular fluid (GCF) and peri-implantitis sulcular fluid (PISF)) is demanding. Several factors influence their expression and release; these factors include the intracellular location, the molecular size and the flow characteristics of the biological fluid. The type of saliva/oral fluid utilized for the diagnostics affects the analysis. High sensitivity together with sophisticated methods and techniques are essential to get a useful outcome. We describe here a recently developed mouth-rinse that is practical, convenient and inexpensive, as well as PISF chair-side/point of care (PoC) lateral-flow active matrix metalloproteinase (aMMP-8) immunoassays to detect, predict and monitor the course and treatment of periodontitis and peri-implantitis.

Pilot Study on the Genetic Background of an Active Matrix Metalloproteinase-8 Test in Finnish Adolescents

BACKGROUND In periodontitis, genetics and smoking play important roles in host immune system response. The aim of this study is to determine whether the genetic background of initial periodontitis and caries could be detected using an active matrix metalloproteinase (aMMP)-8 chairside test in Finnish adolescents. METHODS Forty-seven participants gave approval for analysis of both oral fluid collection and DNA. An aMMP-8 chairside test was performed on participants (adolescents aged 15 to 17 years), and full-mouth clinical parameters of oral health were assessed including periodontal, oral mucosal, and caries status in Eastern Finland from 2014 to 2015. DNA was extracted from oral fluid samples and genotyped for 71 polymorphisms in 29 candidate genes for periodontitis. Results were analyzed using a logistic regression model. P values were corrected for multiple testing using false discovery rate (<0.05). RESULTS aMMP-8 chairside test positivity and three or more ≥4 mm pockets were associated with vitamin D receptor (VDR) (rs2228570, P = 0.002, q = 0.04) and MMP3 (rs520540, rs639752, rs679620, P = 0.0009, 0.003, 0.003, q = 0.04, respectively). None of the other single-nucleotide polymorphisms studied showed a significant association with the aMMP-8 chairside test and at least one caries lesion positivity. CONCLUSION Genetic polymorphisms of MMP3 and VDR are linked to initial periodontitis in Finnish adolescents, and the aMMP-8 chairside test can eventually detect initial periodontitis in young patients with predisposing genetic background.

Effect of teenage smoking on the prevalence of periodontal bacteria

The aim of our study was to investigate how teenage smoking affects the prevalence of periodontal bacteria and periodontal health with the hypothesis that smoking increases the prevalence of the bacteria. Oral health of 264 adolescents (15- to 16-year-olds) was clinically examined, and their smoking history was recorded. The participants also filled in a structured questionnaire recording their general health and health habits. Pooled subgingival plaque samples were taken for polymerase chain reaction analysis of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia, Prevotella nigrescens, and Treponema denticola. The prevalence of P. intermedia (21% vs. 4%, p = 0.01) and T. forsythia and T. denticola (23% vs. 8%, p < 0.05, for both) was higher among female smokers than among non-smokers. T. forsythia and T. denticola were more often associated with bleeding on probing (29% vs. 12%; 25% vs. 10%, respectively) and deep pockets (25% vs. 15%; 23% vs. 10%, respectively) with smokers than non-smokers. Among the girls, a significant association was found between pack-years and the prevalence of P. nigrescens (p < 0.007). In both genders, A. actinomycetemcomitans and P. gingivalis were rare in this study. To conclude, periodontal bacteria were associated with higher periodontal index scores among all teenage smokers. Smoking girls harbored more frequently certain periodontal bacteria than non-smokers, but this was not seen in boys. Hence, our study hypothesis was only partly confirmed.

Periodontitis in early and chronic rheumatoid arthritis: a prospective follow-up study in Finnish population

Objectives To investigate the association between rheumatoid arthritis (RA) and periodontitis with special emphasis on the role of antirheumatic drugs in periodontal health. Design Prospective follow-up study. Patients with early untreated RA and chronic active RA were examined at baseline and 16 months later. Controls were examined once. Settings and participants The study was conducted in Finland from September 2005 to May 2014 at the Helsinki University Hospital. Overall, 124 participants were recruited for dental and medical examinations: 53 were patients with early disease-modifying antirheumatic drug (DMARD) naїve RA (ERA), 28 were patients with chronic RA (CRA) with insufficient response to conventional DMARDs. After baseline examination, patients with ERA started treatment with synthetic DMARDs and patients with CRA with biological DMARDs. Controls were 43 age-matched, gender-matched and community-matched participants. Outcome measures Degree of periodontitis (defined according to the Center for Disease Control and Prevention and the American Academy of Periodontology). Prevalence of periodontal bacteria (analysed from plaque samples), clinical rheumatological status by Disease Activity Score, 28-joint count (DAS28), function by Health Assessment Questionnaire (HAQ) and treatment response by European League Against Rheumatism (EULAR) criteria. Results Moderate periodontitis was present in 67.3% of patients with ERA, 64.3% of patients with CRA and 39.5% of control participants (p=0.001). Further, patients with RA had significantly more periodontal findings compared with controls, recorded with common periodontal indexes. In the re-examination, patients with RA still showed poor periodontal health in spite of treatment with DMARDs after baseline examination. The prevalence of Porphyromonas gingivalis was higher in patients with ERA with periodontal probing depth ≥4 mm compared with patients with CRA and controls. Antirheumatic medication did not seem to affect the results. Conclusions Moderate periodontitis was more frequent in patients with RA than in controls. Patients with ERA and CRA exhibited poorer periodontal health parameters when compared with controls. There was no association between antirheumatic treatment and periodontal parameters.

Oral Health and Mortality in Patients With Chronic Kidney Disease.

BACKGROUND Factors related to mortality of patients with chronic kidney disease (CKD) were investigated to find out whether oral disease inflammatory burden or different etiology (diabetes nephropathy vs. other etiologies) of CKD could be associated with mortality. METHODS This prospective cohort study comprised 144 adults at the predialysis stage. Clinical oral and radiologic examination was made from 2000 to 2005. Patients were followed up until August 2015 (complete follow-up time: 157 months). Cause of death could be verified from 62 of 65 patients. Clinical health data were combined with mortality records obtained from the Finland national statistics database. Number of teeth, total dental index (TDI), and periodontal inflammatory burden index were calculated to describe degree of oral inflammation. RESULTS Primary causes of death were cardiovascular diseases, infection, and cancer. There was a statistically significant difference in survival between diabetic nephropathy (23.8%) and other patients with CKD (59.9%; log-rank test P <0.001). A Cox regression model showed fewer teeth, higher age, and diabetes mellitus were statistically significant independent risk factors for death. Deceased patients had fewer teeth (P <0.001) and higher TDI (P <0.05). CONCLUSIONS Risk of death was higher among patients with diabetic nephropathy. The deceased had fewer teeth and more oral infections. However, indices used failed to show independent association with survival.

Periodontal Inflammatory Burden and Salivary Matrix Metalloproteinase-8 Concentration Among Patients With Chronic Kidney Disease at the Predialysis Stage

BACKGROUND The aim of the present study is to compare periodontal inflammatory burden related to the salivary matrix metalloproteinase (MMP)-8 concentration among patients with chronic kidney disease (CKD) at the predialysis stage. METHODS Salivary samples from 118 predialysis patients were assayed for MMP-8 by immunofluorometric assay. Of the patients, 43 (36%) had diabetic nephropathy, whereas 75 (64%) had other kidney disease. Clinical and radiographic oral health examination was made at Helsinki University Hospital. Oral and general health data including laboratory findings were recorded from hospital records, and the periodontal inflammatory burden index (PIBI) and the total dental index (TDI) were calculated. Results were analyzed with cross tabulation, Pearson χ(2) test, and Mann-Whitney U test. RESULTS Results included elevated PIBI, increased TDI, and two or more sites with ≥ 6 mm or deeper periodontal pocket, associated with elevated salivary MMP-8 concentrations (P < 0.05 in all associations). The diabetic nephropathy group and patients with high hemoglobin A1c (HbA1c) values (≥ 6.5%, ≥ 48 mmol/mol) exerted slightly elevated median salivary MMP-8 values compared with the other CKD group or regarding patients with HbA1c values < 6.5%, but these differences were not statistically significant. CONCLUSIONS Elevated salivary MMP-8 associated significantly with more severe oral/periodontal inflammatory burden among patients with CKD at the predialysis stage. Thus, salivary MMP-8 analysis could give adjunctive information regarding oral health.

Inflammatory mediator polymorphisms associate with initial periodontitis in adolescents

Several studies have addressed cytokine gene polymorphisms and their possible associations with periodontitis. We examined the association between salivary anti‐ and pro‐inflammatory mediator polymorphisms and initial periodontitis in Finnish adolescents, taking into account the effect of smoking. Salivary samples of 93 clinically examined adolescents from Eastern Finland were analyzed. Their oral health and smoking habits were recorded. Periodontal probing depth (PPD), and bleeding on probing (BOP) at four sites per tooth, root calculus (RC), and visible plaque index (VPI) were recorded from the index teeth. Salivary MMP‐8 median values were assessed. The sites with ≥4 mm PD were categorized as follows: PPD1 = one or more ≥4 mm pocket, PPD2 = two or more ≥4 mm pockets, and PPD3 = three or more ≥4 mm pockets. Genomic DNA was extracted from 300 μl of the saliva samples by genomic QIAamp® DNA Blood Mini Kit and genotyped for polymorphisms. Genetic variants for genotyping were selected from the following genes of interest: S100A8, FCGR2A, FCGR2B, IL10, MMP8, MMP3, MMP13, VDR, TLR4, MMP2, MPO, ELANE, IL1A, IL1B, IL1RN, CD28, MMP9, DDX39B, NFKBIL1, LTA, TNF, SOD2, IL6, TLR4, TIMP1, and SYN1. After false discovery rate control (FDR), polymorphisms in MMP3 (rs679620, rs520540, rs639752), CD28 (rs3116496), and VDR (rs2228570) associated (FDR q < 0.05) with deepened periodontal pockets. Smoking did not affect the results. Genetic polymorphisms of pro‐inflammatory mediators MMP3, CD28, and VDR seem to link to initial periodontitis.

High percentage of oral lichen planus and lichenoid lesion in oral squamous cell carcinomas

Abstract Objective: Oral lichen planus (OLP) and lichenoid lesions (OLL) are regarded as precursor lesions of oral squamous cell carcinoma (OSCC) with potential for malignant transformation. This potential is not clear due to difficulties in diagnosis of OLP and OLL. Our aim was therefore to evaluate previously identified OLP and OLL as precursor lesions in OSCC and to identify cancer related etiological factors such as smoking and alcohol consumption. Material and methods: We retrospectively reviewed all cases (total 323, comprising 164 females and 159 males) with OSCC treated at the Department of Oral and Maxillofacial Diseases and Surgery, Helsinki University Hospital during 2015. Confirmed by histopathological biopsy, 58 (17.9%) had OLP and 13 had OLL (4.0%) as precursor lesion. Results: Patients with OLP were slightly older than those without it. OLP was more common in females than in males (p < .0001). TN class 1 tumors were more prevalent among patients with OLP or OLL (p = .006) and cancer relapses less common (p = .005). Smoking was less frequent in patients with OLP and OLL (p < .0001). Also alcohol abuse was less frequent among these patients (p < .001). Conclusion: Our findings confirm the importance of active follow-up of all patients with OLP and OLL even in patients who do not fit a traditional high-risk category for OSCC.