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Showing papers in "Journal of Periodontology in 2008"


Journal ArticleDOI
TL;DR: It seems that the reduction of inflammation and attenuation of the host's immune reaction to the microbial plaque, eventually leading to a decreases in the ratio of RANKL/OPG and a decrease in associated bone loss, are the actual and desired outcomes of periodontal therapy.
Abstract: Inflammation and bone loss are hallmarks of periodontal disease (PD). The question is how the former leads to the latter. Accumulated evidence demonstrates that PD involves bacterially derived factors and antigens that stimulate a local inflammatory reaction and activation of the innate immune system. Proinflammatory molecules and cytokine networks play essential roles in this process. Interleukin-1 and tumor necrosis factor-alpha seem to be primary molecules that, in turn, influence cells in the lesion. Antigen-stimulated lymphocytes (B and T cells) also seem to be important. Eventually, a cascade of events leads to osteoclastogenesis and subsequent bone loss via the receptor activator of nuclear factor-kappa B (RANK)-RANK ligand (RANKL)-osteoprotegerin (OPG) axis. This axis and its regulation are not unique to PD but rather are critical for pathologic lesions involving chronic inflammation. Multiple lines of evidence in models of PD clearly indicate that increases in RANKL mRNA expression and protein production increase the RANKL/OPG ratio and stimulate the differentiation of macrophage precursor cells into osteoclasts. They also stimulate the maturation and survival of the osteoclast, leading to bone loss. OPG mRNA expression and protein production do not generally seem to be increased in the periodontitis lesion. Studies of RANKL and OPG transgenic and knockout animals provide further support for the involvement of these molecules in the tissue loss observed in PD. Ironically, periodontal practitioners have focused on the bacterial etiology of PD and believed that plaque removal was aimed at eliminating specific bacteria or bacterial complexes. However, it seems that the reduction of inflammation and attenuation of the host's immune reaction to the microbial plaque, eventually leading to a decrease in the ratio of RANKL/OPG and a decrease in associated bone loss, are the actual and desired outcomes of periodontal therapy. Future therapeutic options are likely to have regulation of the RANK-RANKL-OPG axis as their goal.

624 citations


Journal ArticleDOI
TL;DR: Although the precise role of inflammation in the development of diabetic microvascular diseases is still unclear, it is likely that inflammation induced by diabetes and insulin resistance can accelerate atherosclerosis in patients with diabetes.
Abstract: The prevalence of diabetes worldwide is increasing rapidly in association with the increase in obesity. Complications are a major fear of patients with diabetes. Complications of diabetes affect many tissues and organs, causing retinopathy, nephropathy, neuropathy, cardiovascular diseases, peripheral vascular diseases, stroke, and periodontal pathologies. Immunologic abnormalities are associated with type 1 and type 2 diabetes and diabetic complications. T cell abnormalities are believed to be the major cause of autoimmune disease in type 1 diabetes, leading to the destruction of pancreatic islets. In type 2 diabetes, inflammation and activation of monocytes are postulated to be important for enhancing insulin resistance and may contribute to the loss of insulin secretory function by islet cells. Many factors can enhance insulin resistance, including genetics, a sedentary lifestyle, obesity, and other conditions, such as chronic inflammation or infection. Increases in inflammation, such as activation of monocytes and increased levels of inflammatory markers, e.g., C-reactive protein, plasminogen activator inhibitor-1, and other cytokines, were reported in insulin-resistant states without diabetes. One possible mechanism is that abnormal levels of metabolites, such as lipids, fatty acids, and various cytokines from the adipose tissue, activate monocytes and increase the secretion of inflammatory cytokines, enhancing insulin resistance. According to this model, obesity activates monocytes and enhances insulin resistance, increasing the risk for type 2 diabetes. Abnormalities in innate immunity might also participate in the development of diabetic complications. In general, hyperglycemia is the main initiator of diabetic retinopathy, nephropathy, and neuropathy, and it participates in the development of diabetic cardiovascular diseases. Although the precise role of inflammation in the development of diabetic microvascular diseases is still unclear, it is likely that inflammation induced by diabetes and insulin resistance can accelerate atherosclerosis in patients with diabetes. Also, it was shown that conditions with an inflammatory basis, such as obesity and type 2 diabetes, can contribute to periodontal disease, suggesting that periodontal abnormalities may be partly influenced by inflammatory changes. Further research is required to confirm the role of inflammation and the onset of diabetes, microvascular diseases, and periodontal pathologies.

577 citations


Journal ArticleDOI
Dana T. Graves1
TL;DR: Key findings are summarized that attempt to delineate the mechanisms by which immune factors can lead to the loss of connective tissue attachment and alveolar bone in periodontal disease.
Abstract: Although periodontal diseases are initiated by bacteria that colonize the tooth surface and gingival sulcus, the host response is believed to play an essential role in the breakdown of connective tissue and bone, key features of the disease process. An intermediate mechanism that lies between bacterial stimulation and tissue destruction is the production of cytokines, which stimulates inflammatory events that activate effector mechanisms. These cytokines can be organized as chemokines, innate immune cytokines, and acquired immune cytokines. Although they were historically identified as leukocyte products, many are also produced by a number of cell types, including keratinocytes, resident mesenchymal cells (such as fibroblasts and osteoblasts) or their precursors, dendritic cells, and endothelial cells. Chemokines are chemotactic cytokines that play an important role in leukocyte recruitment and may directly or indirectly modulate osteoclast formation. This article focuses on aspects of osteoimmunology that affect periodontal diseases by examining the role of cytokines, chemokines, and immune cell mediators. It summarizes some of the key findings that attempt to delineate the mechanisms by which immune factors can lead to the loss of connective tissue attachment and alveolar bone. In addition, a discussion is presented on the importance of clarifying the process of uncoupling, a process whereby insufficient bone formation occurs following resorption, which is likely to contribute to net bone loss in periodontal disease.

569 citations


Journal ArticleDOI
TL;DR: It is hoped that improved conceptual models of pathogenesis will assist in focusing new research and speed the translation of new data into practical applications.
Abstract: Chronic adult periodontitis is a bacterially induced chronic inflammatory disease that destroys the connective tissue and bone that support teeth. Concepts of the specific mechanisms involved in the disease have evolved with new technologies and knowledge. Histopathologic observations of diseased human tissues were used previously to speculate on the causes of periodontitis and to describe models of pathogenesis. Experimental evidence later emerged to implicate bacterial plaque deposits as the primary factor initiating periodontitis. At the same time, specific bacteria and immunoinflammatory mechanisms were differentially implicated in the disease. In the mid-1990s, early insights about complex diseases, such as periodontitis, led to new conceptual models of the pathogenesis of periodontitis. Those models included the bacterial activation of immunoinflammatory mechanisms, some of which targeted control of the bacterial challenge and others that had adverse effects on bone and connective tissue remodeling. Such models also acknowledged that different environmental and genetic factors modified the clinical phenotype of periodontal disease. However, the models did not capture the dynamic nature of the biochemical processes, i.e., that innate differences among individuals and changes in environmental factors may accelerate biochemical changes or dampen that shift. With emerging genomic, proteomic, and metabolomic data and systems biology tools for interpreting data, it is now possible to begin describing the basic elements of a new model of pathogenesis. Such a model incorporates gene, protein, and metabolite data into dynamic biologic networks that include disease-initiating and -resolving mechanisms. This type of model has a multilevel framework in which the biochemical networks that are regulated by innate and environmental factors can be described and the interrelatedness of networks can be captured. New models in the next few years will be merely frameworks for integrating key knowledge as it becomes available from the "-omics" technologies. However, it is possible to describe some of the key elements of the new models and discuss distinctions between the new and older models. It is hoped that improved conceptual models of pathogenesis will assist in focusing new research and speed the translation of new data into practical applications.

471 citations


Journal ArticleDOI
TL;DR: Only RA status and age remained significant predictors of periodontal disease in a stepwise logistic regression, including RA status, age, gender, education, smoking, alcohol consumption, and BMI.
Abstract: Background: A limited number of studies suggest a higher prevalence of periodontal disease among individuals with rheumatoid arthritis (RA); however, results have been inconsistent. Further, it is unclear to what extent poor oral hygiene among patients with RA may account for this association.Methods: The association between RA and periodontitis was examined in 57 subjects with RA and 52 healthy controls, matched by age and gender. Oral examination included plaque index (PI), gingival index (GI), probing depth (PD), and clinical attachment loss (CAL). Potential risk factors for periodontal disease, such as smoking, education, alcohol consumption, and body mass index (BMI), as well as chronic diseases associated with RA and periodontal disease were assessed through questionnaires.Results: In a stepwise logistic regression, including RA status, age, gender, education, smoking, alcohol consumption, and BMI, only RA status and age remained significant predictors of periodontal disease. Subjects with RA had a ...

323 citations


Journal ArticleDOI
TL;DR: The ridge-preservation approach using porcine bone in combination with collagen membrane significantly limited the resorption of hard tissue ridge after tooth extraction compared to extraction alone.
Abstract: Background: The preservation of bone volume immediately after tooth removal might be necessary to optimize the success of implant placement in terms of esthetics and function. The objectives of this randomized clinical trial were two-fold: 1) to compare the bone dimensional changes following tooth extraction with extraction plus ridge preservation using corticocancellous porcine bone and a collagen membrane; and 2) to analyze and compare histologic and histomorphometric aspects of the extraction-alone sites to the grafted sites. Methods: Forty subjects who required tooth extraction and implant placement were enrolled in this study. Using a computer-generated randomization list, the subjects were randomly assigned to the control group (EXT; extraction alone) or to the test group (RP; ridge-preservation procedure with corticocancellous porcine bone and collagen membrane). The following parameters were assessed immediately after extraction and 7 months prior to implant placement: plaque index, gingival index, bleeding on probing, horizontal ridge width, and vertical ridge changes. A bone biopsy was taken from the control and test sites 7 months after the surgical treatment. Histologic and histomorphometric analyses were also performed. Results: A significantly greater horizontal reabsorption was observed at EXT sites (4.3 – 0.8 mm) compared to RP sites (2.5 – 1.2 mm). The ridge height reduction at the buccal side was 3.6 – 1.5 mm for the extraction-alone group, whereas it was 0.7 – 1.4 mm for the ridge-preservation group. Moreover, the vertical change at the lingual sites was 0.4 mm in the ridge-preservation group and 3 mm in the extraction-alone group. Forty biopsies were harvested from the experimental sites (test and control sites). The biopsies harvested from the grafted sites revealed the presence of trabecular bone, which was highly mineralized and well structured. Particles of the grafted material could be identified in all samples. The bone formed in the control sites was also well structured with a minor percentage of mineralized bone. The amount of connective tissue was significantly higher in the extraction-alone group than in the ridge-preservation group. Conclusions: The ridge-preservation approach using porcine bone in combination with collagen membrane significantly limited the resorption of hard tissue ridge after tooth extraction compared to extraction alone. Furthermore, the histologic analysis showed a significantly higher percentage of trabecular bone and total mineralized tissue in ridge-preservation sites compared to extraction-alone sites 7 months after tooth removal. J Periodontol 2008;79:1370-1377.

278 citations


Journal ArticleDOI
TL;DR: It is proposed that the determination and integration of subject-level factors, microbial composition, systemic immune response, and gingival tissue inflammatory mediator responses will better reflect the biology of the biofilm-gingival interface in a specific patient and may provide insights on clinical management.
Abstract: Clinical signs and symptoms, as well as medical and dental history, are all considered in the clinical determination of gingival inflammation and periodontal disease severity. However, the "biologic systems model" highlights that the clinical presentation of periodontal disease is closely tied to the underlying biologic phenotype. We propose that the determination and integration of subject-level factors, microbial composition, systemic immune response, and gingival tissue inflammatory mediator responses will better reflect the biology of the biofilm-gingival interface in a specific patient and may provide insights on clinical management. Disease classifications and multivariable models further refine the biologic basis for the increasing severity of periodontal disease expression. As such, new classifications may better identify disease-susceptible and treatment-non-responsive individuals than current classifications that are heavily influenced by probing and attachment level measurements alone. New data also suggest that the clinical characteristics of some complex diseases, such as periodontal disease, are influenced by the genetic and epigenetic contributions to clinical phenotype. Although the genetic basis for periodontal disease is considered imperative for setting an inflammatory capacity for an individual and, thus, a threshold for severity, there is evidence to suggest an epigenetic component is involved as well. Many factors long associated with periodontitis, including bacterial accumulations, smoking, and diabetes, are known to produce strong epigenetic changes in tissue behavior. We propose that we are now able to rethink periodontal disease in terms of a biologic systems model that may help to establish more homogeneous diagnostic categories and can provide insight into the expected response to treatment.

252 citations


Journal ArticleDOI
TL;DR: Data supporting a role for inflammation in cardiovascular disease is summarized and the possibility that other disorders characterized by inflammation, such as periodontal disease, may have an indirect role by influencing the risk, manifestation, and progression of vascular events is offered.
Abstract: Atherothrombosis of the coronary and cerebral vessels is understood to be a disorder of inflammation and innate immunity, as well as a disorder of lipid accumulation. From a vascular biology perspective, the processes of cellular adhesion, monocyte and macrophage attachment, and transmigration of immune cells across the endothelium are crucial steps in early atherogenesis and in the later stages of mature plaque rupture, particularly the transition of unstable plaque at the time of acute thrombosis. There is abundant clinical evidence demonstrating that many biomarkers of inflammation are elevated years in advance of first ever myocardial infarction (MI) or thrombotic stroke and that these same biomarkers are highly predictive of recurrent MI, recurrent stroke, diabetes, and cardiovascular death. In daily practice, the inflammatory biomarker in widest use is high-sensitivity C-reactive protein (hsCRP); when interpreted within the context of usual risk factors, levels of hsCRP 3 mg/l denote lower, average, and higher relative risk for future vascular events. Risk-prediction models that incorporate hsCRP, such as the Reynolds Risk Score, have been developed that improve risk classification and the accuracy for global risk prediction, particularly for those deemed at "intermediate risk" by usual algorithms, such as the Framingham Risk Score. With regard to cerebral vessels, increased biomarkers of inflammation, including hsCRP, have been associated with increased stroke risk as well as an increased rate of atherosclerosis progression in the carotid vessels. Although the proportion of variation in hsCRP explained by genetic factors may be as large as 20% to 40%, diet, exercise, and smoking cessation remain critical tools for risk reduction and CRP reduction. Statin therapy reduces hsCRP in a largely low-density lipoprotein (LDL)-independent manner, and the "anti-inflammatory" properties of these agents have been suggested as a potential mechanism beyond LDL reduction for the efficacy of these agents. The ongoing multinational Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial of 17,802 initially healthy men and women with low levels of LDL cholesterol but increased levels of hsCRP will help to define whether vascular protection can be achieved with statin therapy, even in the absence of hyperlipidemia. Targeted anti-inflammatory therapies are being developed that may provide a direct method of translating the biology of inflammation into new clinical treatments across multiple vascular beds. This article summarizes data supporting a role for inflammation in cardiovascular disease and offers the possibility that other disorders characterized by inflammation, such as periodontal disease, may have an indirect role by influencing the risk, manifestation, and progression of vascular events.

251 citations


Journal ArticleDOI
TL;DR: The additional application of a single episode of PDT to scaling and root planing failed to result in an additional improvement in terms of PD reduction and CAL gain, but it resulted in a significantly higher reduction in bleeding scores compared to scaled andRoot planing alone.
Abstract: Background: Recent preclinical and clinical data have suggested a potential benefit of photodynamic therapy (PDT) in the treatment of periodontitis. However, there are very limited data from controlled clinical trials evaluating the effect of PDT in the treatment of periodontitis. The aim of this study was to evaluate the clinical and microbiologic effects of the adjunctive use of PDT to non-surgical periodontal treatment. Methods: Twenty-four subjects with chronic periodontitis were randomly treated with scaling and root planing followed by a single episode of PDT (test) or scaling and root planing alone (control). Full-mouth plaque score (FMPS), full-mouth bleeding score (FMBS), probing depth (PD), gingival recession, and clinical attachment level (CAL) were measured at baseline and 3 and 6 months after therapy. Primary outcome variables were changes in PD and CAL. Microbiologic evaluation of Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia (previously T. forsythensis), Treponema denticola, Parvimonas micra (previously Peptostreptococcus micros or Micromonas micros), Fusobacterium nucleatum, Campylobacter rectus, Eubacterium nodatum, Eikenella corrodens, and Capnocytophaga spp. was performed at baseline and 3 and 6 months following therapy by using a commercially available polymerase chain reaction test. Results: At 3 and 6 months after treatment, there were no statistically significant differences between the groups with regard to CAL, PD, FMPS, or microbiologic changes. At 3 and 6 months, a statistically significantly greater improvement in FMBS was found in the test group. Conclusion: The additional application of a single episode of PDT to scaling and root planing failed to result in an additional improvement in terms of PD reduction and CAL gain, but it resulted in a significantly higher reduction in bleeding scores compared to scaling and root planing alone. J Periodontol 2008;79:1638-1644.

218 citations


Journal ArticleDOI
TL;DR: New evidence suggests a key role for epigenetics in human pathologies, including in inflammatory and neoplastic disorders, and differences in methylation status of CpG sites, monoallelic silencing, and other epigenetic regulatory mechanisms have been observed in key inflammatory response genes.
Abstract: Epigenetics can be defined as all the meiotically and mitotically inherited changes in gene expression that are not encoded in the DNA sequence itself. Epigenetic modifications of chromatin and DNA have been recognized as important permissive and suppressive factors in controlling the expressed genome via gene transcription. Two major epigenetic mechanisms are the posttranslational modification of histone proteins in chromatin and the methylation of DNA itself, which areregulatedbydistinct, butcoupled,pathways.Itisclear that the epigenetic state is a central regulator of cellular development and activation. Emerging evidence suggests a key role for epigenetics in human pathologies, including in inflammatory and neoplastic disorders. The epigenome is influenced by environmental factors throughout life. Nutritional factors can have profound effects on the expression of specific genes by epigenetic modification, and these may be passed on to subsequent generations with potentially detrimental effects. Many cancers are associated with altered epigenetic profiles, leadingtoalteredexpressionofthegenesinvolvedincellgrowth or differentiation. Autoimmune and neoplastic diseases increase in frequency with increasing age, with epigenetic dysregulation proposed as a potential explanation. In support of this hypothesis, studies in monozygotic twins revealed increasing epigenetic differences with age. Differences in methylation status of CpG sites, monoallelic silencing, and other epigenetic regulatory mechanisms have been observed in key inflammatory response genes. The importance of the epigenome in the pathogenesis of common human diseases is likely to be as significant as that of traditional genetic mutations. With advances in technology, our understanding of this area of biology is likely to increase rapidly in the near future. J Periodontol 2008;79:1514-1519.

213 citations


Journal ArticleDOI
TL;DR: Work in animal models of periodontitis has revealed the potential of this therapeutic approach for its prevention and treatment and forced the reconsideration of the understanding of the pathogenesis of human periodontal diseases.
Abstract: It has become clear in recent years that periodontitis is an inflammatory disease initiated by oral microbial biofilm. This distinction implies that it is the host response to the biofilm that destroys the periodontium in the pathogenesis of the disease. As our understanding of pathways of inflammation has matured, a better understanding of the molecular basis of resolution of inflammation has emerged. Resolution of inflammation is an active, agonist-mediated, well-orchestrated return of tissue homeostasis. There is an important distinction between anti-inflammation and resolution; anti-inflammation is pharmacologic intervention in inflammatory pathways, whereas resolution is biologic pathways restoring homeostasis. A growing body of research suggests that chronic inflammatory periodontal disease involves a failure of resolution pathways to restore homeostasis. This article reviews the resolution of inflammation in the context of periodontal disease and the potential for the modification of resolution pathways for the prevention and treatment of periodontal diseases. Proof-of-concept studies in the 1980s demonstrated that pharmacologic anti-inflammation prevented and slowed the progression of periodontal diseases in animals and man. However, the side-effect profile of such therapies precluded the use of non-steroidal anti-inflammatory drugs or other enzyme inhibitors or receptor antagonists in periodontal therapy. The isolation and characterization of resolving agonist molecules has opened a new area of research using endogenous lipid mediators of resolution as potential therapeutic agents for the management of inflammatory periodontitis. Work in animal models of periodontitis has revealed the potential of this therapeutic approach for its prevention and treatment and forced the reconsideration of our understanding of the pathogenesis of human periodontal diseases.

Journal ArticleDOI
TL;DR: The alveolar response to corticotomy as a function of time and proximity to the surgical injury in a rat model is investigated to investigate periodontally accelerated osteogenic orthodontics.
Abstract: Background: Modifying the balance between resorption and apposition through selectively injuring the cortical plate of the alveolus has been an approach to speed tooth movement and is referred to as periodontally accelerated osteogenic orthodontics. The aim of this study was to investigate the alveolar response to corticotomy as a function of time and proximity to the surgical injury in a rat model.Methods: Maxillary buccal and lingual cortical plates were injured in 36 healthy adult rats adjacent to the upper left first molars. Twenty-four animals were euthanized at 3, 7, or 11 weeks. In one group, the maxillae were removed and stripped of soft tissues, and histomorphometric analysis was performed to study alveolar spongiosa and periodontal ligament (PDL) modeling dynamics. Catabolic activity was analyzed with tartrate-resistant acid phosphatase–positive osteoclasts and preosteoclasts. Anabolic actions were measured using a fluorescent vital bone stain series followed by sacrifice at 30 and 51 days. To f...

Journal ArticleDOI
TL;DR: To evaluate the match between the positions and axes of the planned and placed implants using stereolithographic (SLA) surgical guides, ninety-four implants were placed using SLA surgical guides generated from computed tomography (CT) between 2005 and 2006.
Abstract: Background: Dental implant placement requires precise planning with regard to anatomic limitations and restorative goals. The aim of this study was to evaluate the match between the positions and axes of the planned and placed implants using stereolithographic (SLA) surgical guides.Methods: Ninety-four implants were placed using SLA surgical guides generated from computed tomography (CT) between 2005 and 2006. Radiographic templates were used for all subjects during CT imaging. After obtaining three-dimensional CT images, each implant was virtually placed on the CT images. SLA surgical guides, fabricated using an SLA machine with a laser beam to polymerize the liquid photo-polymerized resin, were used during implant placement. A new CT scan was taken for each subject following implant placement. Special software was used to fuse the images of the planned and placed implants, and the locations and axes were compared.Results: Compared to the planned implants, the placed implants showed angular deviation of ...

Journal ArticleDOI
TL;DR: The role of periostin in maintaining the functional integrity of the periodontium was determined using a murine PDL cell line and real-time reverse transcription-polymerase chain reaction was used to quantify mRNA levels of peruostin and TGF-β.
Abstract: Background: The ability of the periodontal ligament (PDL) to absorb and distribute forces is necessary for periodontal homeostasis. This adaptive response may be determined, in part, by a key molecule, periostin, which maintains the integrity of the PDL during occlusal function and inflammation. Periostin is primarily expressed in the PDL and is highly homologous to βig-H3 (transforming growth factor-beta [TGF-β] inducible gene). Cementum, alveolar bone, and the PDL of periostin-null mice dramatically deteriorate following tooth eruption. The purpose of this study was to determine the role of periostin in maintaining the functional integrity of the periodontium.Methods: The periodontia from periostin-null mice were characterized followed by unloading the incisors. The effect of substrate stretching on periostin expression was evaluated using a murine PDL cell line. Real-time reverse transcription-polymerase chain reaction was used to quantify mRNA levels of periostin and TGF-β. TGF-β1 neutralizing antibod...

Journal ArticleDOI
TL;DR: The effects of periodontal therapy (scaling and root planing [SRP]) on the serum levels of glycated hemoglobin (HbA1c) and on inflammatory biomarkers were evaluated and a significant reduction in interleukin (IL)-6 and interferon-inducible protein 10 levels were verified.
Abstract: Background: Periodontitis, a complication of diabetes mellitus (DM), can induce or perpetuate systemic conditions. This double-masked, placebo-controlled study evaluated the effects of periodontal therapy (scaling and root planing [SRP]) on the serum levels of glycated hemoglobin (HbA1c) and on inflammatory biomarkers.Methods: Thirty subjects with type 2 DM and periodontitis were treated with SRP + placebo (SRP; N = 15) or with SRP + doxycycline (SRP+Doxy; N = 15), 100 mg/day, for 14 days. Clinical and laboratory data were recorded at baseline and at 3 months after treatment.Results: After 3 months, the reduction in probing depth was 0.8 mm for the SRP group (P <0.01) and 1.1 mm for the SRP+Doxy group (P <0.01) followed by a 0.9% (SRP; P = 0.17) and 1.5% (SRP+Doxy; P <0.01) reduction in HbA1c levels. A significant reduction in interleukin (IL)-6; interferon-inducible protein 10; soluble fas ligand; granulocyte colony-stimulating factor; RANTES; and IL-12 p70 serum levels were also verified (N = 30). To ou...

Journal ArticleDOI
TL;DR: The use of rapid, chair-side tests of MMP activity, in particular for MMP-8 and bone collagen fragments, show strong potential as non-invasive measures of tissue health or disease and the application of these bone-preservation strategies to periodontal management and treatment are discussed in the context of high-risk patients susceptible to disease reactivation or disease complications.
Abstract: Periodontal diseases are initiated by Gram-negative tooth-associated microbial biofilms that elicit a host response, with resultant osseous and soft tissue destruction. In response to endotoxins derived from periodontal pathogens, several osteoclast-related mediators target the destruction of alveolar bone and supporting connective tissues. Major drivers of this aggressive tissue destruction are matrix metalloproteinases (MMPs), cathepsins, and other osteoclast-derived enzymes. This article focuses on the downstream factors of the osteoclast responsible for the degradation of bone and soft tissues around teeth and oral implants. Furthermore, therapeutic approaches that target MMP-2, -8, and -9 inhibition, such as MMP inhibitors, chemically modified tetracyclines, and subantimicrobial formulations of tetracycline analogues, are discussed. The use of rapid, chair-side tests of MMP activity, in particular for MMP-8 and bone collagen fragments, show strong potential as non-invasive measures of tissue health or disease. In addition, studies using other agents for the preservation of bone mass, such as bisphosphonates that inhibit osteoclast recruitment, are highlighted. The application of these bone-preservation strategies to periodontal management and treatment are discussed in the context of high-risk patients susceptible to disease reactivation or disease complications.

Journal ArticleDOI
TL;DR: A comparison of gene expression signatures between healthy and diseased gingival tissues would provide novel insights in the pathobiology of periodontitis and would inform the design of future studies.
Abstract: Background: Clinical and radiographic measures are gold standards for diagnosing periodontitis but offer little information regarding the pathogenesis of the disease. We hypothesized that a comparison of gene expression signatures between healthy and diseased gingival tissues would provide novel insights in the pathobiology of periodontitis and would inform the design of future studies.Methods: Ninety systemically healthy non-smokers with moderate to advanced periodontitis (63 with chronic periodontitis and 27 with aggressive periodontitis) each contributed at least two diseased interproximal papillae (with bleeding on probing [BOP], probing depth [PD] ≥4 mm, and attachment loss [AL] ≥3 mm) and a healthy papilla, if available (no BOP, PD ≤4 mm, and AL ≤2 mm). RNA was extracted, amplified, reverse-transcribed, labeled, and hybridized with whole genome microarrays. Differential expression was assayed in 247 individual tissue samples (183 from diseased sites and 64 from healthy sites) using a standard mixed-...

Journal ArticleDOI
TL;DR: The use of a repeated local antibiotic as an adjunct to the mechanical treatment of peri-implantitis lesions demonstrated improvements in probing depths that were significantly different from controls and were sustained for 6 months.
Abstract: BACKGROUND: Peri-implantitis is an inflammatory process caused by microorganisms affecting the tissues around an osseointegrated implant in function, resulting in a loss of supporting bone. Limited data exist regarding the treatment of peri-implantitis. The aim of this study was to assess the clinical and microbiologic outcome of repeated local administration of minocycline microspheres, 1 mg, in cases of peri-implantitis. METHODS: Thirty-two subjects with at least one implant with a probing depth > or =4 mm combined with bleeding and/or exudate on probing and the presence of putative pathogenic bacteria were included in the study. At baseline, subjects were randomly assigned to receive local minocycline microspheres (17 subjects and 57 implants) or chlorhexidine gel (15 subjects and 38 implants) following debridement. Treatments were performed on three occasions: baseline and days 30 and 90. Follow-up examinations were conducted at 10 days and at 1, 3, 6, 9, and 12 months. RESULTS: The use of minocycline resulted in significant improvements in probing depths compared to chlorhexidine at days 30, 90, and 180 (P = 0.5, P = 0.01, and P = 0.04, respectively). For the deepest sites of the minocycline-treated implants, the mean probing depth reduction was 0.6 mm at 12 months. Regarding bleeding on probing, significant differences between groups, based on all four sites at the implants, were found at days 30, 90, 180, 270, and 360. Both treatments resulted in a marked reduction in the indicator bacteria. CONCLUSIONS: The use of a repeated local antibiotic as an adjunct to the mechanical treatment of peri-implantitis lesions demonstrated improvements in probing depths that were significantly different from controls and were sustained for 6 months. The adjunctive use of minocycline microspheres is beneficial in the treatment of peri-implant lesions, but the treatment may have to be repeated.

Journal ArticleDOI
TL;DR: This article addresses some surgical complications associated with dental implant placement and discusses how to avoid and manage them when they occur.
Abstract: Proposing to place endosseous implants is an integral facet of dental treatment plans. Their insertion is usually associated with a low incidence of untoward events. However, despite careful planning, surgical complications can arise: infection, intraoral hemorrhage, wound dehiscence, postoperative pain, lack of primary implant stability, inadvertent penetration into the maxillary sinus or nasal fossa, sinus lift sequelae, neurosensory disturbances, injuries to adjacent teeth, tissue emphysema, and aspiration, or ingestion of surgical instruments. This article addresses some surgical complications associated with dental implant placement and discusses how to avoid and manage them when they occur.

Journal ArticleDOI
TL;DR: Compared patient-based outcomes for CTGs and FGGs: proportion of subjects reporting pain in the palate at 3 days was significantly greater for FGG (P <0.05) and there were no significant intergroup differences at 3 weeks.
Abstract: Background: Subepithelial connective tissue grafts (CTGs) and free gingival grafts (FGGs) are common periodontal procedures with similar indications; however, they may differ regarding patient outcomes. Reports on postoperative periodontal patient outcomes are limited. The aim of this observational trial was to compare patient-based outcomes for CTGs and FGGs.Methods: Patients who received CTG or FGG completed postoperative questionnaires at 3 days and 3 weeks to assess pain, number of analgesic pills taken, and number of days pills were taken. Postoperative pain was assessed using a visual analog scale (VAS).Results: Twenty-three subjects (12 CTGs and 11 FGGs) completed the study. Differences between CTG and FGG groups in VAS pain scores at 3 days did not reach statistical significance. The proportion of subjects reporting pain in the palate at 3 days was significantly greater for FGG (P <0.05). There were no significant intergroup differences at 3 weeks. For the FGG group, 3-week VAS pain scores were le...

Journal ArticleDOI
TL;DR: Two-dimensional finite element imaging was used to create a cross-sectional model of an implant placed in the premolar region of the mandible and stress patterns in bone, especially in the crestal region were analyzed, finding microthreads increased crestal stress upon loading.
Abstract: Background: The aims of this study were to investigate the effects of implant microthreads on crestal bone stress compared to a standard smooth implant collar and to analyze how different abutment diameters influenced the crestal bone stress level. Methods: Two-dimensional finite element imaging was used to create a cross-sectional model of an implant (5-mm platform and 13 mm in length) placed in the premolar region of the mandible. The two tapered implant models consisted of one with microthreads at the crestal portion and the other with a smooth neck. The implant model was reverse-engineered to resemble a commercially available microthread implant. Abutments of different diameters (4.0 mm: 20% platform switching; 4.5 mm: 10% platform switching; and 5.0 mm: standard) were loaded with a force of 100 N at 90� vertical and 15� oblique angles. Finite element analysis was used to analyze the stress patterns in bone, especially in the crestal region. Results: Upon loading, the microthread implant model had 29% greater stress (31.61 MPa in oblique and 9.31 MPa in vertical) at the crestal bone adjacent to the implant than the smooth-neck implant (24.51 and 7.20 MPa, respectively). When the abutment diameter decreased from 5.0 to 4.5 mm and then to 4.0 mm, the microthread model showed a reduction of stress at the crestal bone level from 6.3% to 5.4% after vertical loading and from 4.2% to 3.3% after oblique loading. The smooth-neck model showed a reduction of stress from 5.6% to 4.9% after vertical loading and from 3.7% to 2.9% after oblique loading. Conclusions: Microthreads increased crestal stress upon loading. Reduced abutment diameter (i.e., platform switching) resulted in less stress translated to the crestal bone in the microthread and smooth-neck groups. J Periodontol 2008;79:2166-2172.

Journal ArticleDOI
TL;DR: The surgical, prosthetic, and anatomic factors involved in the management of peri-implant tissues, including presence/absence of the interproximal papilla, interimplant–tooth distance, distance from the base of the contact point to the interdental bone, and soft tissue biotype were analyzed.
Abstract: Background: Gingival esthetics around dental implants have become a main focus for clinicians. This study analyzed the surgical, prosthetic, and anatomic factors involved in the management of peri-implant tissues.Methods: Forty-eight subjects with one tooth scheduled for tooth extraction and immediate implant placement were included in the study. After healing, the implants were restored with single-crown fixed prostheses. The following parameters were assessed after 12 months: presence/absence of the interproximal papilla, interimplant–tooth distance (ITD), distance from the base of the contact point to the interdental bone (CPB), and soft tissue biotype. ITD and CPB values were derived from computer analysis of periapical radiographs. A statistical analysis determined the effect of ITD and CPB on the presence of the interproximal papilla.Results: Papilla was significantly present (P <0.05) for ITD of 2.5 to 4 mm in anterior and posterior areas and for CPB ≤7 mm in posterior areas. Thick biotype was sign...

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TL;DR: Infliximab tended to aggravateGingival inflammation as indicated by differences in the modified gingival and papillary bleeding indices between subjects in groups I and II with coexisting periodontitis before and after treatment.
Abstract: Background Because periodontitis presents many similarities with rheumatoid arthritis (RA) with regard to tumor necrosis factor-alpha (TNF-alpha)-induced bone resorption, the benefits of TNF-alpha blockade in RA prompted us to determine its efficacy in treating coexisting periodontitis. Methods Periodontal status was evaluated in 40 subjects with RA who were divided into two groups: Group I contained 20 subjects who had received infliximab every 6 weeks for > or =22 months at the time of periodontal evaluation. The 20 subjects in group II were evaluated before their first infusion with infliximab. Nine subjects in group II had periodontitis. These subjects were reevaluated after they received nine infusions of infliximab. Results Infliximab tended to aggravate gingival inflammation as indicated by differences in the modified gingival and papillary bleeding indices between subjects in groups I and II with coexisting periodontitis before and after treatment. Methotrexate had no effect on periodontal status. Although the plaque index revealed that bacterial infection persisted, the probing depth was equal in groups I and II and equivalent before and after treatment in subjects with periodontitis, whereas attachment loss was decreased after infliximab treatment. Conclusions Inflammation and destruction constitute two interrelated yet separate components of periodontitis in patients with RA. Therefore, TNF-alpha blockade could be beneficial in the treatment of periodontitis.

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TL;DR: The mid-term follow-up of 2 to 4 years showed that the risk for mucosal recession was low with this treatment concept and Prospective clinical studies are required to confirm these encouraging results.
Abstract: BACKGROUND: The concept of early implant placement is a treatment option in postextraction sites of single teeth in the anterior maxilla. Implant placement is performed after a soft tissue healing period of 4 to 8 weeks. Implant placement in a correct three-dimensional position is combined with a simultaneous guided bone regeneration procedure to rebuild esthetic facial hard and soft tissue contours. METHODS: In this retrospective, cross-sectional study, 45 patients with an implant-borne single crown in function for 2 to 4 years were recalled for examination. Clinical and radiologic parameters, routinely used in implant studies, were assessed. RESULTS: All 45 implants were clinically successful according to strict success criteria. The implants demonstrated ankylotic stability without signs of a peri-implant infection. The peri-implant soft tissues were clinically healthy as indicated by low mean plaque (0.42) and sulcus bleeding index (0.51) values. None of the implants revealed a mucosal recession on the facial aspect as confirmed by a clearly submucosal position of all implant shoulders. The mean distance from the mucosal margin to the implant shoulder was -1.93 mm on the facial aspect. The periapical radiographs showed stable peri-implant bone levels, with a mean distance between the implant shoulder and the first bone-implant contact of 2.18 mm. CONCLUSIONS: This retrospective study demonstrated successful treatment outcomes for all 45 implants examined. The mid-term follow-up of 2 to 4 years also showed that the risk for mucosal recession was low with this treatment concept. Prospective clinical studies are required to confirm these encouraging results.

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TL;DR: Findings suggest that defective resolution mechanisms may underlie the inflammatory phenotypes that are believed to characterize many common human diseases.
Abstract: A well-integrated host inflammatory response is essential in maintaining health and fighting disease. It is important to achieve a complete understanding of the cellular and molecular events that govern the resolution of acute inflammation. Because novel lipid-derived mediators, called resolvins and protectins in animal models, control the duration and magnitude of inflammation, the mapping of these resolution circuits may provide new ways of understanding the molecular basis of many inflammatory diseases. This article provides an overview of recent studies on resolvin and protectin biosynthesis and of advances in understanding the actions of these novel anti-inflammatory and proresolving lipid mediators. These new families of lipid-derived mediators were originally isolated from experimental murine models of acute inflammation identified during the natural spontaneous resolution phase. They are biosynthesized from omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) and possess potent ant...

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TL;DR: Evaluated radiographic crestal bone changes around experimental dental implants with non-matching implant-abutment diameters revealed very little bone loss and a slight increase in bone level for implants placed at the level of the crest or 1 mm above; however, it was a small amount.
Abstract: BACKGROUND: It has been shown that different implant designs and different vertical implant positions have an influence on crestal bone levels. The aim of the present study was to evaluate radiographic crestal bone changes around experimental dental implants with non-matching implant-abutment diameters placed submucosally or transmucosally at three different levels relative to the alveolar crest. METHODS: Sixty two-piece dental implants with non-matching implant-abutment diameters were placed in edentulous spaces bilaterally in five foxhounds. The implants were placed submucosally or transmucosally in the left or the right side of the mandible. Within each side, six implants were randomly placed at three distinct levels relative to the alveolar crest. After 12 weeks, 60 crowns were cemented. Radiographs were obtained from all implant sites following implant placement, after crown insertion, and monthly for 6 months after loading. RESULTS: Radiographic analysis revealed very little bone loss and a slight increase in bone level for implants placed at the level of the crest or 1 mm above. The greatest bone loss occurred at implants placed 1 mm below the bone crest. No clinically significant differences regarding marginal bone loss and the level of the bone-to-implant contact were detected between implants with a submucosal or a transmucosal healing. CONCLUSIONS: Implants with non-matching implant-abutment diameters demonstrated some bone loss; however, it was a small amount. There was no clinically significant difference between submucosal and transmucosal approaches.

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TL;DR: The antibacterial effect of suspended miswak pieces suggests the presence of volatile active antibacterial compounds in the region of periodontitis and caries.
Abstract: BACKGROUND: The chewing stick (miswak) is used for oral hygiene in many parts of the world. In addition to the mechanical removal of plaque, an antibacterial effect has been postulated; however, tests of miswak extract from Salvadora persica (Arak) disclosed only low to moderate antibacterial effects. This may be attributable to the extraction process. Our aim was to test in vitro the antibacterial effect of miswak pieces, without extraction, on bacteria implicated in the etiology of periodontitis and caries. METHODS: Miswak pieces were standardized by size and weight (0.07 and 0.14 g) and tested against Streptococcus mutans, Lactobacillus acidophilus, Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), Porphyromonas gingivalis, and, as a reference, Haemophilus influenzae. The miswak pieces were tested in two ways: embedded in the agar plate or suspended above the agar plate. RESULTS: The inhibitory effect was most pronounced on P. gingivalis, A. actinomycetemcomitans, and H. influenzae, less on S. mutans, and least on L. acidophilus. Suspended miswak had comparable or stronger effects than miswak embedded in agar. The 0.14-g suspended miswak exhibited significantly greater inhibition on A. actinomycetemcomitans and H. influenzae than the 0.14-g miswak embedded in agar (P<0.01 and P<0.001, respectively). CONCLUSIONS: Miswak embedded in agar or suspended above the agar plate had strong antibacterial effects against all bacteria tested. The antibacterial effect of suspended miswak pieces suggests the presence of volatile active antibacterial compounds.

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TL;DR: Salivary levels of TNF-α, C-telopeptide pyridinoline cross-links of type I collagen, and receptor activator of nuclear factor-kappa B ligand have been associated with bone remodeling and periodontal tissue destruction and were significantly higher in individuals withperiodontal disease than in controls.
Abstract: Background: Tumor necrosis factor-alpha (TNF-α), C-telopeptide pyridinoline cross-links of type I collagen (ICTP), and receptor activator of nuclear factor-kappa B ligand (RANKL) have been associated with bone remodeling and periodontal tissue destruction. This study evaluated the level of these biomarkers in saliva with respect to periodontal disease status.Methods: Levels of TNF-α in unstimulated whole saliva of 74 adults (35 subjects with moderate to severe periodontal disease and 39 healthy controls) and salivary levels of RANKL and ICTP of a subset of 21 subjects and 21 matched controls were examined using enzyme immunosorbent assays in a case-control clinical study.Results: Salivary levels of TNF-α were detected in all subjects, whereas levels of ICTP and RANKL were detected in only a minority of subjects. Mean salivary levels of TNF-α were significantly higher in individuals with periodontal disease (mean: 4.33 pg/ml) than in controls (mean: 2.03 pg/ml; P = 0.02), with a maximum level (27.96 pg/ml)...

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TL;DR: This study aimed to examine quantitative relationships between P. gingivalis, T. denticola, and T. forsythia in subgingival biofilms and the relationship between the quantity and prevalence of these three bacteria and site-specific periodontal health.
Abstract: Background: Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia (previously T. forsythensis), which are regarded as the principal periodontopathogenic bacteria, exist as a consortium in subgingival biofilms. We aimed to examine quantitative relationships between P. gingivalis, T. denticola, and T. forsythia in subgingival biofilms and the relationship between the quantity and prevalence of these three bacteria and site-specific periodontal health.Methods: This study was cross-sectional. The study population consisted of 35 adult subjects who visited the Kyushu Dental College Hospital. Plaque samples were collected from 105 periodontal pocket sites. Quantitative analyses of each of the three periodontopathogenic bacteria were performed using real-time polymerase chain reaction with species-specific primers and hybridization probes.Results: The plaque samples were divided into four groups based on the presence or absence of a periodontal pocket (probing depth [PD] ≥4 mm) and bleeding on ...

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TL;DR: Compared to baseline, the 12-month results indicated that both treatment modalities resulted in significant changes in all clinical parameters and radiographic parameters and however, the test group exhibited statist...
Abstract: Background: The aim of the present randomized, double-masked, clinical trial was to compare platelet-rich plasma (PRP) combined with a demineralized freeze-dried bone allograft (DFDBA) to DFDBA mixed with a saline solution in the treatment of human intrabony defects.Methods: Sixty interproximal intrabony osseous defects in 60 healthy, non-smoking subjects diagnosed with chronic periodontitis were treated in this study. Thirty subjects each were randomly assigned to the test group (PRP + DFDBA) or the control group (DFDBA + saline). Clinical and radiographic measurements were made at baseline and at the 12-month evaluation.Results: Compared to baseline, the 12-month results indicated that both treatment modalities resulted in significant changes in all clinical parameters (gingival index, bleeding on probing, probing depth, clinical attachment level, and gingival recession; P <0.001) and radiographic parameters (hard tissue fill and bone depth reduction; P <0.001). However, the test group exhibited statist...