Diabetes, periodontitis, and the subgingival microbiota

Both type 1 and type 2 diabetes have been associated with increased severity of periodontal disease for many years. More recently, the impact of periodontal disease on glycaemic control has been investigated. The role of the oral microbiota in this two-way relationship is at this stage unknown. Further studies, of a longitudinal nature and investigating a wider array of bacterial species, are required in order to conclusively determine if there is a difference in the oral microbiota of diabetics and non-diabetics and whether this difference accounts, on the one hand, for the increased severity of periodontal disease and on the other for the poorer glycaemic control seen in diabetics

Ante-dependence modeling in a longitudinal study of periodontal disease: the effect of age, gender, and smoking status

Background: It is generally accepted that periodontal disease progresses by a series of bursts that are interspersed by periods of stability or even gain of attachment. In order to analyze longitudinal data on a patient's disease experience, it is necessary to use models which accommodate serial dependence. Ante-dependence between the results of a series of periodontal examinations over time can be modeled using a Markov chain. This model describes temporal changes in patients' levels of disease in terms of transition probabilities, which allow for both regression and progression of the disease. The aim of the present study was to demonstrate the use of a Markov chain model to analyze data from a longitudinal study investigating the progression of periodontal disease in an adult population. Methods: The study population consisted of 504 volunteers; however, only 456 were included in the analysis because the remaining 48 subjects did not give consecutive data. Subjects were examined at baseline, 6 months, and 1, 2, and 3 years. Probing depths (PD) were recorded using an automated probe. Disease was defined as four or more sites with PD greater than or equal to 4 mm. Markov chain modeling was used to determine the effect of age, gender, and smoking on the natural progression and regression (healing) of periodontal disease. Results: Smoking and increasing age had no effect on the progression of disease in this population, but did have a significant effect (P values less than or equal to 0.05) in reducing the regression of disease; i.e., their effect on disease appears to be inhibition of the natural healing process. Gender had no significant effects. Conclusions: These results demonstrate how ante-dependence modeling of longitudinal data can reveal effects that may not be immediately apparent from the data, with smoking and increasing age being seen to inhibit the healing process rather than promote disease progression

Effects of zoledronic acid and geranylgeraniol on angiogenic gene expression in primary human osteoclasts

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious complication associated with bisphosphonate treatment. Zoledronic acid (ZA) is a commonly used bisphosphonate due to its effectiveness in increasing bone density and reducing skeletal events, with evidence that it alters angiogenesis. Replacement of the mevalonate pathway using geranylgeraniol (GGOH) was studied to determine the effects of ZA on angiogenic gene expression in primary human osteoclasts. Osteoclast cultures were generated from peripheral blood mononuclear cells of three patients using the peripheral blood mononuclear cell isolation. These cells were phenotyped by phase-contrast microscopy, tartrate-resistant acid phosphatase staining, and pit assays. Primary osteoclasts were found to express a number of key angiogenic molecules at very high levels. Gene expression levels for 84 human angiogenic factors were determined using PCR arrays. Three genes with significant fold regulation (FR) in response to ZA were as follows: tumor necrosis factor (FR = +2.57, P = 0.050), CXCL9 (FR = +39.48, P = 0.028), and CXCL10 (FR = +18.52, P = 0.0009). The co-addition of geranylgeraniol with ZA resulted in the significant down-regulation of these three genes along with CCL2, TGFBR1, ENG, and CXCL1. GGOH reversed the gene changes induced by ZA and may offer a promising treatment for BRONJ

Improvement in Periodontal Health and Antibody Response to Heat-Shock Proteins

There is evidence that periodontal disease may be associated with atherosclerosis due to cross-reactivity of bacterial GroEL immunity with human heat shock protein 60 (hHSP60). Objective: To examine changes in serum antibody responses to Porphyromonas gingivalis, hHSP60, and P. gingivalis GroEL following improvement in periodontal health in patients with cardiovascular disease (CVD) and in patients with high cardiovascular (CV) risk and low CV risk. Methods: Patients were selected from two large longitudinal studies and had undergone yearly periodontal examinations and peripheral blood collections. CVD patients (n=15) selected from one study had experienced a significant CV event while patients derived from the other study had not experienced a CV event. These latter patients were further classified according to CV risk (≥6 classical risk factors=high CV risk n=13; ≤1 classical risk factor=low CV risk n=14). Patients demonstrating a quantifiable improvement in periodontal health (≥62% reduction in number of sites with probing depth≥4mm) from the baseline visit were selected. Serum IgG antibody levels to P.gingivalis, hHSP60, and P.gingivalis GroEL were measured using ELISA. Results: Median reductions, after improvement in periodontal health, in antibody levels to P.gingivalis GroEL differed significantly across the three groups (Kruskal-Wallis