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Background and objectives Vitamin D has been studied primarily for its involvement in calcium and phosphate absorption and bone metabolism. The active form of vitamin D-1,25(OH)2 D-has also been investigated for its immune modulatory properties. We explored associations between serum levels of 25(OH)D and 1,25(OH)2 D and periodontal health. Subjects and methods This case-control study included 55 subjects with chronic periodontitis (cases) and 30 periodontally healthy subjects (controls). Their serum levels of 25(OH)D, 1,25(OH)2 D, ultrasensitive C-reactive protein and high-density lipoprotein cholesterol were determined. Associations between vitamin D and periodontal health status were studied using logistic regression analysis. Results A statistically significant association was found between serum 1,25(OH)2 D level and periodontal health status; in that subjects with a low 1,25(OH)2 D were more likely to belong to the periodontitis group (OR = 0.97, 95% CI = 0.95-1.00). There was practically no association between 25(OH)D level and periodontal health status. Conclusion In this case-control study low serum 1,25(OH)2 D level appeared to be associated with periodontitis, which was in line with the previously reported associations between serum 1,25(OH)2 D levels and other inflammatory diseases. Whether this association is causal in nature, remains to be confirmed in future studies.

The aim of the present study was to investigate associations between serum concentrations of vitamin D metabolites, 25-hydroxyvitamin D [25(OH)D], and its active form, 1,25-dihydroxyvitamin D [1,25(OH)D], and the severity of chronic periodontitis.Presence of dental plaque, probing pocket depth (PD), and attachment level in 80 type 1 diabetes mellitus subjects were recorded. The serum levels of 25(OH)D, 1,25(OH)D, ultrasensitive C-reactive protein, IL-6, TNF-α, high-density lipoprotein cholesterol, and glycosylated hemoglobin (percentage) were determined. Multivariate regression models were used to explore the associations between serum 25(OH)D (nanomoles per liter) and 1,25(OH)D (picomoles per liter) levels and periodontal health status.Antiinfective periodontal therapies were delivered and the clinical examination and laboratory analyses were repeated 8 weeks after the therapies.A statistically significant association was found between the serum level of 1,25(OH)D (odds ratio 1.06, 95% confidence interval 1.02-1.11) and periodontal health at the baseline; subjects with a high level were more likely to belong to the group of no or mild periodontitis. The serum level of 1,25(OH)D showed a statistically significant increase after antiinfective periodontal therapy in both no or mild (P = .001) and moderate or severe periodontitis (P.001) subjects. The association between serum 25(OH)D level and periodontal health was negligible.This study has shown a significant positive association between the serum 1,25(OH)D level and periodontal health status. To what extent this association is causal in nature remains to be confirmed.

Aim High-density lipoprotein (HDL) cholesterol is known for its anti-inflammatory and antioxidant activities in protection against cardiovascular diseases. We investigated whether a protective association also exists between serum HDL and periodontal inflammation in type 1 diabetic subjects (T1DM). Methods Plaque and periodontal inflammation (bleeding and PD ≥ 4 mm) were examined in 80 subjects with T1DM. The serum levels of glycosylated haemoglobin (HbA1c, %) and HDL (mmol/l) were determined. Adjusted associations between inflammation and serum HDL were analysed using linear regression analysis. To study the linearity of the association, the subjects were categorized into HDL tertiles (I-III). Results A statistically significant negative association was observed between serum HDL level and the extent of bleeding and PD ≥ 4 mm. Subjects in HDL tertiles II and III (high HDL) presented significantly fewer inflamed sites when compared with the subjects in tertile I (low HDL), whereas no significant difference in the number of inflamed sites was observed between tertiles II and III. Conclusions Based on the finding of a negative association between serum HDL and periodontal inflammation, HDL may be considered a marker of susceptibility to periodontal inflammation. A longitudinal study is needed to verify possible causal relationship between serum HDL and inflammation.

Passoja A, Knuuttila M, Hiltunen L, Karttunen R, Niemela O, Raunio T, Vainio O, Hedberg P, Tervonen T. Serum IL-6 may modulate periodontal inflammation in type 1 diabetic subjects. J Clin Periodontol 2011; 38: 687–693. doi: 10.1111/j.1600-051X.2011.01731.x. Abstract Aims: To evaluate the associations between serum inflammatory biomarkers and periodontal inflammation in subjects with type 1 diabetes mellitus (T1DM). Our hypothesis was that local host responses may be modulated by the serum inflammatory mediators. Material and methods: Plaque, bleeding on probing and probing pocket depth (PD) were examined in 80 T1DM subjects at the baseline and in 58 subjects 8 weeks after periodontal therapy. The levels of glycosylated haemoglobin, serum interleukin (IL)-6, ultrasensitive C-reactive protein and the lipid profile were measured at the baseline and after therapy. Stratification of the sample separately by smoking and body mass index (BMI) was performed. Adjusted associations between the levels of systemic biomarkers and periodontal parameters were studied using multiple regression models. Results: The level of serum IL-6 was associated with the extent of bleeding and PD4 mm at the baseline in non-smokers and in subjects with BMI26 kg/m2. These associations were also evident after periodontal therapy. Subjects with a high after-therapy IL-6 level presented poorer periodontal healing than those with a low level. Conclusions: The observed associations may be considered to be suggestive of a modulatory effect of IL-6 on host responses in T1DM subjects.

Passoja A, Puijola I, Knuuttila M, Niemela O, Karttunen R, Raunio T, Tervonen T. Serum levels of interleukin-10 and tumour necrosis factor-α in chronic periodontitis. J Clin Periodontol 2010; 37: 881–887. doi: 10.1111/j.1600-051X.2010.01602.x Abstract Aims: To investigate, using a cross-sectional study design, whether the extent of periodontal inflammation associates with the serum levels of cytokine interleukin (IL)-10 and tumour necrosis factor (TNF)-α and their ratio. Material and Methods: The study group consisted of 61 subjects with chronic periodontitis and 30 control subjects with minimally inflamed periodontal tissues. Probing pocket depth (PD), bleeding on probing (BOP) and periodontal attachment level (AL) were measured. The serum IL-10 (pg/ml) and TNF-α (U/l) levels were analysed using enzyme-linked immunosorbent assays. After categorization of the subjects, associations between serum IL-10 and TNF-α levels and the extent of periodontal inflammation were studied using linear regression models adjusted for age, gender, body mass index and smoking. Results: A negative, partly dose-dependent association existed between the extent of BOP, PD4 mm and AL4 mm and serum IL-10 level. The subjects in the periodontitis group presented significantly higher serum TNF-α levels and their TNF-α/IL-10 ratio was approximately threefold when compared with the ratio in the control group. Conclusions: The significantly higher serum TNF-α/IL-10 ratio in the subjects with chronic periodontitis when compared with the ratio in the controls is indicative of a stronger systemic pro-inflammatory state in chronic periodontitis.

Aim The aim of this study was to investigate whether genetic polymorphism in certain cytokine and receptor molecule genes and diabetic status associate with the extent of periodontal disease in type 1 diabetes mellitus (DM). Material and methods Eighty patients with type 1 DM participated. Visible plaque, bleeding on probing (BOP), probing pocket depth (PD) and attachment level (AL) were examined clinically and glycosylated haemoglobin (HbA1c) levels were used to assess the glycemic control of DM. CD-14, IL-6, TNF-alpha, IL-10, IL-1alpha, IL-1beta and TLR-4 gene polymorphisms were studied using the polymerase chain reaction (PCR). Results The 3-year HbA1c was good ( 8.5%) in 48% of the subjects. IL-6(-174) genotype and 3-year GHbA1c associated significantly with BOP and PD>or=4 mm, subjects with the GG genotype of the IL-6(-174) exhibiting more severe periodontal disease than those with the GC/CC genotype. After stratification by IL-6 genotype, associations between the extent of periodontal disease and 3-year HbA1c levels remained significant in subjects carrying the GC/CC but not the GG genotype. Conclusions In addition to the HbA1c level, the IL-6(-174) genotype is a significant susceptibility factor for periodontal disease among type 1 diabetics.

Objective: The aim of this study was to analyse the association between matrix metalloproteinase-8 (MMP-8) concentration in shallow, mostly non-bleeding gingival crevices, and the extent of periodontal disease. Material and Methods: Plaque, bleeding on probing (BOP), probing pocket depth (PPD) and attachment level (AL) were assessed clinically in 48 patients with chronic periodontitis. MMP-8 concentrations in gingival crevicular fluid (GCF) from four shallow (PPD3 mm), and four diseased sites and in serum, were measured by enzyme-linked immunosorbent assay. Results: The mean concentration of MMP-8 in GCF from shallow crevices was 11.8 ± 12.8 ng/ml and from diseased sites was 150.1 ± 91.8 ng/ml. In subjects with moderate to high plaque scores, a statistically significant association was found between MMP-8 concentration from shallow crevices and the extent of AL4 mm (p=0.028) and AL6 mm (p

Aim: To compare the frequencies of cytokine and receptor molecule genotypes in patients with chronic periodontitis with the corresponding frequencies in a reference population and to study the relationship between periodontal disease severity and polymorphisms in the studied genes. Subjects and methods: CD14, IL-6, TNF-α, IL-10, IL-1α, IL-1β, and TLR-4 polymorphisms of 51 periodontitis patients were studied using polymerase chain reaction. The genotype frequencies in the periodontitis patients and a reference population (n=178) were compared. Probing pocket depth (PD), periodontal attachment level (AL), and alveolar bone level (BL) were related to the genotypes. Results: No statistically significant differences could be found between the frequencies of the cytokine genotypes in the periodontitis patients and in the reference group. The extent of periodontal disease was higher in subjects with the T-containing genotype of CD14−260 and the GG genotype of IL-6−174 when compared with the extent in the rest of the group. Subjects carrying the composite genotype of the above two were most severely affected by periodontal disease. Conclusion: According to the present results, an evident association exists between the carriage of the T-containing genotype of CD14−260 and the GG genotype of IL-6−174 and the extent periodontal disease.

Objectives To study the association between periodontitis and serum parathyroid hormone (PTH) and the response of PTH to periodontal therapy in type 1 diabetic patients (T1DM). We also investigated the PTH-1,25(OH)2 D axis in the T1DM group. Methods Periodontal health status was recorded in 54 periodontitis patients and 30 periodontally healthy controls (case-control data). Data were also collected from patients with type 1 diabetes mellitus at the baseline (n = 76) and after periodontal therapy (intervention data) (n = 53). Results Periodontitis was not associated with serum PTH in the case-control data or at the baseline of the intervention data. A post-therapy increase in serum PTH was found in 61% of the T1DM patients; in patients with moderate or severe periodontitis (n = 26) the average increase was 0.6 pmol/l (p = 0.016) and in patients with no or mild periodontitis (n = 27) 0.2 pmol/l (p = 0.250). In 47% of the T1DM patients, an increase in PTH was associated with an increase in serum 1,25(OH)2 D. Conclusion An association between serum PTH and periodontal infection was found only after periodontal therapy in T1DM patients. This post-treatment response in serum PTH may partly explain the previously reported increase in serum 1,25(OH)2 D.

Aim Besides their role in bone metabolism, receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) are also known to be associated with inflammation. We explored associations between the extent/severity of periodontitis and circulating levels of sRANKL and OPG and their ratio using a cross-sectional study design. Subjects & methods The extent of periodontal inflammation and tissue destruction and the serum levels of sRANKL (pg/ml) and OPG (pg/ml) were determined in 80 subjects with type 1 diabetes mellitus (T1DM). Plaque-, age-, gender-, smoking-, HbA1c- and body mass index-adjusted associations between periodontal parameters and serum sRANKL, OPG and their ratio were studied using multiple linear regression analysis. Results Adjusted regression analyses of all the subjects indicated a significant positive association between AL ≥ 4 mm and severity of periodontitis and the level of serum OPG. A major drop in the strength and statistical significance of the above association was observed when the analyses included only non-smokers. Serum sRANKL level and sRANKL/OPG ratio were not associated with periodontitis. Conclusion Our observations suggest that serum OPG may be an indicator of periodontal tissue destruction in T1DM.

To evaluate the associations between serum inflammatory biomarkers and periodontal inflammation in subjects with type 1 diabetes mellitus (T1DM). Our hypothesis was that local host responses may be modulated by the serum inflammatory mediators.Plaque, bleeding on probing and probing pocket depth (PD) were examined in 80 T1DM subjects at the baseline and in 58 subjects 8 weeks after periodontal therapy. The levels of glycosylated haemoglobin, serum interleukin (IL)-6, ultrasensitive C-reactive protein and the lipid profile were measured at the baseline and after therapy. Stratification of the sample separately by smoking and body mass index (BMI) was performed. Adjusted associations between the levels of systemic biomarkers and periodontal parameters were studied using multiple regression models.The level of serum IL-6 was associated with the extent of bleeding and PD≥4 mm at the baseline in non-smokers and in subjects with BMI≤26 kg/m(2). These associations were also evident after periodontal therapy. Subjects with a high after-therapy IL-6 level presented poorer periodontal healing than those with a low level.The observed associations may be considered to be suggestive of a modulatory effect of IL-6 on host responses in T1DM subjects.

To investigate, using a cross-sectional study design, whether the extent of periodontal inflammation associates with the serum levels of cytokine interleukin (IL)-10 and tumour necrosis factor (TNF)-α and their ratio.The study group consisted of 61 subjects with chronic periodontitis and 30 control subjects with minimally inflamed periodontal tissues. Probing pocket depth (PD), bleeding on probing (BOP) and periodontal attachment level (AL) were measured. The serum IL-10 (pg/ml) and TNF-α (U/l) levels were analysed using enzyme-linked immunosorbent assays. After categorization of the subjects, associations between serum IL-10 and TNF-α levels and the extent of periodontal inflammation were studied using linear regression models adjusted for age, gender, body mass index and smoking.A negative, partly dose-dependent association existed between the extent of BOP, PD ≥ 4 mm and AL ≥ 4 mm and serum IL-10 level. The subjects in the periodontitis group presented significantly higher serum TNF-α levels and their TNF-α/IL-10 ratio was approximately threefold when compared with the ratio in the control group.The significantly higher serum TNF-α/IL-10 ratio in the subjects with chronic periodontitis when compared with the ratio in the controls is indicative of a stronger systemic pro-inflammatory state in chronic periodontitis.

Objective: The aim of this study was to find out if periodontal therapy has any effect on glycemic control of type 1 diabetes mellitus (DM). Subjects and Methods: The periodontal health status of 65 type 1 diabetic subjects was assessed at the baseline and 8 weeks after completion of periodontal therapy. Glycemic control was assessed on both visits by measuring the percentage of glycosylated haemoglobin (GHbA1c). The change in HbA1c (ΔHbA1c) was assessed by using both a positive or negative change 0.5% and any change in HbA1c. Results: The mean HbA1c level (±SD) of the whole study group was 8.6% (±1.5) at the baseline and 8.5% (±1.5) after treatment. Glycemic control improved during the study period in 23 subjects (35%) and worsened in 18 subjects (28%). Approximately 78% of the bleeding sites and 87% of the sites with probing depth 4 mm presented healing. ΔHbA1c associated significantly with baseline HbA1c but not with baseline periodontal health status or periodontal healing. Conclusion: Regardless of a significant resolution of periodontal infection, a great majority of the subjects did not present any improvement in their glycemic control.

AIM: To study the extent of periodontal disease and the IL-6(-174) genotype as determinants of serum and mouthwash IL-6 concentration in subjects with moderate to severe periodontal disease. MATERIAL AND METHODS: Fifty-two generally healthy subjects volunteered to participate. Probing pocket depth (PD) and periodontal attachment level (AL) were clinically examined and alveolar bone level (BL) was measured on orthopantomographs. IL-6 concentrations in mouthwash, collected by rinsing with 3 ml saline for 30 s and in serum, obtained by venipuncture, were measured using ELISA. IL-6(-174) polymorphism was studied using a polymerase chain reaction. RESULTS: Eleven subjects carried the GG genotype, and 41 subjects, carried the CG/CC genotype. The mean (+/- SD) concentration of IL-6 in serum was 1.6 (+/- 1.5) pg/ml and, 2.8 (+/- 5.04) pg/ml in mouthwash. The serum concentration of IL-6 was higher in subjects with the GG genotype than with the CG/CC genotype. In regression analyses the percentages of sites with PD> or =6 mm, AL> or =6 mm and BL> or =8 mm, the IL-6(-174) genotype, body mass index and gender associated significantly with serum IL-6 concentration. CONCLUSIONS: The extent of moderate to severe periodontal disease and the IL-6(-174) genotype contribute significantly to serum IL-6 concentration.