Bernd-Michael Kleber

Obesity, Inflammation, and Periodontal Disease

The prevalence of obesity has increased substantially over the past decades in most industrialized countries. Obesity is a systemic disease that predisposes to a variety of co-morbidities and complications that affect overall health. Cross-sectional studies suggest that obesity is also associated with oral diseases, particularly periodontal disease, and prospective studies suggest that periodontitis may be related to cardiovascular disease. The possible causal relationship between obesity and periodontitis and potential underlying biological mechanisms remain to be established; however, the adipose tissue actively secretes a variety of cytokines and hormones that are involved in inflammatory processes, pointing toward similar pathways involved in the pathophysiology of obesity, periodontitis, and related inflammatory diseases. We provide an overview of the definition and assessment of obesity and of related chronic diseases and complications that may be important in the periodontist’s office. Studies that have examined the association between obesity and periodontitis are reviewed, and adipose-tissue-derived hormones and cytokines that are involved in inflammatory processes and their relationship to periodontitis are discussed. Our aim is to raise the periodontist’s awareness when treating obese individuals.

Ridge augmentation and maxillary sinus grafting with a biphasic calcium phosphate: histologic and histomorphometric observations

OBJECTIVES This retrospective study reports on histologic and histomorphometric observations performed on human biopsies harvested from sites augmented exclusively by biphasic calcium phosphate [BCP: hydroxyapatite (HA)/ tricalcium phosphate (TCP) 60/40] and healed for a minimum of 6 months. MATERIALS AND METHODS Five patients benefited from three augmentation regimens (i.e.: one-stage lateral augmentation; two-stage lateral augmentation; and two-stage sinus grafting). In all patients, a degradable collagen membrane served as a cell-occlusive barrier. Core biopsies were obtained from lateral as from crestal aspects 6-10 months after augmentation surgeries. For histologic and histomorphometric evaluations, the non-decalcified tissue processing was performed. RESULTS The histological examination of 11 biopsies showed graft particles frequently being bridged by the new bone, and a close contact between the graft particles and newly formed bone was seen in all samples. The mean percentages of newly formed bone, soft tissue compartment, and graft material were 38.8% (+/-5.89%), 41.75% (+/-6.08%), and 19.63% (+/-4.85%), respectively. Regarding bone-to-graft contact values, the percentage of bone coverage of graft particles for all biopsies ranged from 27.83% to 80.17%. The mean percentage of bone coverage was 55.39% (+/-13.03%). CONCLUSIONS Data from the present study demonstrated osteoconductivity scores for the BCP material (HA/TCP 60/40) in patients resembling those previously shown for grafting materials of xenogenic and alloplastic origin.

Effects of Porphyromonas gingivalis on cell cycle progression and apoptosis of primary human chondrocytes

Background: It has been suggested that bacterial infections have a role in the pathogenesis of rheumatoid arthritis (RA). P gingivalis, a Gram-negative, anaerobic rod, is one of the major pathogens associated with periodontal disease. Objective: To examine P gingivalis infection and its effects on cell cycle progression and apoptosis of human articular chondrocytes. Methods: Primary human chondrocytes cultured in monolayers were challenged with P gingivalis. Infection and invasion of P gingivalis into chondrocytes was analysed by scanning electron microscopy, double immunofluorescence and by antibiotic protection and invasion assay. Cell cycle progression of infected chondrocytes was evaluated by flow cytometry. Also, cell apoptosis was visualised by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) of DNA strand breaks and by western blot analysis. Results: Data showed that P gingivalis could adhere and infect primary human chondrocytes. After chondrocyte infection, intracellular localisation of P gingivalis was noted. Flow cytometry analyses demonstrated affected cell cycle progression, with an increase of the G1 phase and a significant decrease of the G2 phase after infection. In addition, increased apoptosis of P gingivalis-infected chondrocytes was visualised by TUNEL assay and by upregulation of caspase-3 protein expression. Conclusion: These data demonstrate that P gingivalis infects primary human chondrocytes and affects cellular responses, which might contribute to the tissue damage seen in the pathogenesis of rheumatoid arthritis.

Periodontal disease in patients with ankylosing spondylitis

Objective: Ankylosing spondylitis (AS) and periodontal disease (PD) are characterised by dysregulation of the host inflammatory response, resulting in soft and hard connective tissue destruction. AS has been related to other inflammatory diseases, however, there is a paucity of data on whether AS is associated with inflammatory PD. Methods: The association between AS and PD was examined in 48 patients with AS and 48 healthy controls, matched for age and gender. AS was diagnosed according to the modified New York criteria. Periodontal examination included probing pocket depth (PPD), clinical attachment loss (CAL), plaque index (PI) and bleeding on probing (BOP). Potential risk factors of PD such as smoking, low education, alcohol consumption, body mass index (BMI), as well as chronic diseases associated with PD and AS were assessed through questionnaires. Results: In stepwise logistic regression, including AS status, age, gender, education, smoking, alcohol consumption and BMI, only AS status, age and education remained significant predictors of PD. Patients with AS had significant 6.81-fold increased odds (95% CI 1.96 to 23.67) of PD (defined as mean attachment loss >3 mm) compared to controls. The strength of the association was attenuated but remained statistically significant after further adjustment for plaque accumulation (odds ratio (OR) 5.48, 95% CI 1.37 to 22.00). Conclusions: The present study shows that patients with AS have a significantly higher risk of PD, strongly suggesting the need for close collaboration between rheumatologists, periodontists and dental hygienists when treating patients with AS.

Randomized controlled trial on lateral augmentation using two collagen membranes: morphometric results on mineralized tissue compound

BACKGROUND Guided bone regeneration is considered an effective tool for gaining mineralized tissue either at exposed implant surface or in deficient alveolar ridge areas before implant placement. MATERIAL AND METHODS Customized casts obtained following impression taking at surgery and re-entry allowed for morphometric assessment of alveolar ridge alterations 6 months after one-stage augmentation of bone dehiscences. In a randomized pilot study using biphasic calcium phosphate tests (n=17) received treatment with ribose cross-linked collagen membranes (RCLM), whereas controls (n=20) received non-cross-linked membranes. The primary endpoint was to quantify the effect of membrane type on dimensional changes in bone margins at crestal level of endosseous implants. RESULTS Soft tissue dehiscencies occurred at 70.5% and 55% frequency for tests and controls, respectively. Gain in clinically hard newly mineralized tissue at the crestal level was significantly higher in test group in lateral (1.8 versus 0.7 mm; p=.046) and in vertical dimensions (1.1 versus 0.2 mm; p=.035) compared with controls. Second measurement obtained at the border of reflected flap revealed no significant difference between groups (3.0 versus 2.1 mm; p=0.57) for lateral dimension. CONCLUSIONS Both collagen devices were effective in bone augmentation. RCLMs supported mineralization process and remodelling even in sites showing compromised healing as indicated by morphometric outcome.

Calprotectin levels in gingival crevicular fluid predict disease activity in patients treated for generalized aggressive periodontitis.

BACKGROUND AND OBJECTIVE Clinical parameters such as probing depth and bleeding on probing are commonly used for monitoring after periodontal treatment. However, these parameters have poor prognostic utility. The biomarker calprotectin is used to monitor conditions such as inflammatory bowel disease because of its ability to predict disease activity. Levels of calprotectin in gingival crevicular fluid correlate with periodontal disease severity and treatment outcome. The validity of calprotectin as predictor for future periodontal disease activity has not yet been investigated. MATERIAL AND METHODS Thirty-six subjects with generalized aggressive periodontitis were treated with scaling and root planing (SRP), and with adjunctive antimicrobial medications. Probing depth, clinical attachment level and bleeding on probing were assessed at baseline, and 3 and 6mo after SRP. A gingival crevicular fluid sample was collected from the initially deepest site in each patient 3mo after SRP and analysed for calprotectin levels. Activity was defined as a probing depth increase of >0.5mm between 3 and 6mo at the sample site. The ability of individual parameters to predict activity was analysed by construction of receiver operating characteristic curves. RESULTS Nine active sites were identified. Clinical attachment level, probing depth, bleeding on probing and gingival crevicular fluid volume showed no predictive utility [area under the curve (AUC) <0.6, p>0.05]. However, calprotectin concentration (AUC=0.793, p=0.01) and the total amount/sample of calprotectin (AUC=0.776, p=0.02) significantly predicted activity. Patients with calprotectin levels above calculated cut-off values had significantly more active sites than patients with negative results. CONCLUSION Calprotectin levels were predictors of disease activity at both site and subject levels. The calculated cut-off values provide a dichotomous basis for prospective evaluation of calprotectin as a diagnostic marker for monitoring periodontal treatment.

Receptor activator of NF-kappaB ligand (RANKL) and CD 31 expressions in chronic periodontitis patients before and after surgery

Aim of the study The present study investigated the hypothesis that upregulation of receptor activator of NF-kappaB ligand (RANKL) expression may be associated with upregulation of endothelial cell activitiy, which is common for periods of periodontal bone loss in chronic periodontitis. Material and methods RANKL expression of activated cells in soft tissue biopsies with CD 31 activity and the presence of RANKL and osteoprotegerin (OPG) in gingival crevicular fluid (GCF) were assessed in chronic periodontitis patients. Biopsies from 17 patients and 10 healthy subjects were immunohistochemically analyzed. Clinical measurements [plaque index (PI), the gingival index (GI), probing pocket depth (PPD), clinical attachment level (CAL) and gingival bleeding index (GBI)] and GCF samples were obtained before and after periodontal therapy. Results CD31 staining did not support the assumption that endothelium-like cells were predominantly associated with RANKL expression. Conclusions RANKL-positive cells were widely distributed in periodontitis patients giving only partial support to the hypothesis that RANKL expression is restricted to T- and B-cell activation.