Adjunctive efficacy of systemic metronidazole in the surgical treatment of periodontitis: a double-blind parallel randomized clinical trial.

OBJECTIVES: The purpose of this study was to evaluate the clinical and microbiological impact of adjunctive metronidazole to periodontal surgery. MATERIALS AND METHODS: Systemically healthy patients, with stages III-IV, grades B-C periodontitis, were randomly assigned to receive metronidazole or placebo adjunctive to periodontal surgery, after subgingival instrumentation. Clinical variables were recorded at the initial visit, 6 weeks after subgingival instrumentation, and 3, 6, and 12 months after surgery. Microbiological samples were taken at initial and final visits and analyzed by quantitative polymerase chain reaction. RESULTS: Our results showed no statistically significant differences in the reduction of probing depth between the initial and final (1 year) visits in the two treatment groups. Additionally, no statistically significant differences were observed between study groups when comparing the post-subgingival instrumentation and final visits. However, 3 months after surgery, probing depth (mean difference, MD = 0.31 mm, 95% confidence interval, CI [0.13; 0.49]; p = 0.001) and clinical attachment level (MD = 0.64 mm, 95% CI [0.02; 1.27]; p = 0.044) were significantly lower in the test group. CONCLUSIONS: The adjunctive use of systemic metronidazole to periodontal surgery has a limited clinical and microbiological impact in the present study, and therefore, its use is not recommended. CLINICAL RELEVANCE: There are no studies that have evaluated the clinical and microbiological impact of the adjunctive use of systemic metronidazole to periodontal surgery (step 3 of periodontal therapy). The results of the present study do not support the adjunctive use of systemic metronidazole to periodontal surgery.

Treatment of intrabony periodontal defects in controlled diabetic patients with an enamel matrix derivative: a split-mouth randomized clinical trial.

OBJECTIVE: This split-mouth randomized controlled trial aimed to evaluate the effect of enamel matrix derivative (EMD) associated with a simplified papilla preservation flap (SPPF) compared to SPPF alone in the surgical treatment of intrabony defects (ID) in type 2 diabetic mellitus (T2DM) patients. MATERIAL AND METHODS: Thirteen patients with controlled T2DM presenting with ID in at least two quadrants were included. In each patient, the test site (TS) was treated with SPPF plus EMD, whereas the control site (CS) was treated only with SPPF. Prior to surgery and at 6 months after intervention, the following parameters were evaluated: clinical attachment level (CAL), probing pocket depth (PPD), and gingival recession (GR). RESULTS: The TS and CS demonstrated a mean CAL gain of 3.31 ± 0.96 mm and 1.61 ± 1.12 mm, and a PPD reduction from 8.15 ± 0.98 to 3.00 ± 0.57 mm and 7.53 ± 0.96 to 4.69 ± 0.63 mm after 6 months, respectively. In both sites, the mean CAL gain and PPD reduction improved significantly after 6 months compared to baseline; however, the improvement was higher in the TS (p < 0.001). CONCLUSIONS: Both surgical procedures presented with clinical improvements in controlled T2DM patients. However, the additional use of EMD showed enhanced clinical results after 6 months with regard to CAL gain and PPD reduction. CLINICAL RELEVANCE: This study showed a better PPD reduction and CAL gain when an EMD was applied in addition to SPPF. Therefore, EMD may be used to enhance clinical outcomes in periodontal ID of controlled T2DM patients.

An Umbrella Review Exploring the Effect of Periodontal Treatment in Pregnant Women on the Frequency of Adverse Obstetric Outcomes.

OBJECTIVE: In the recent years, efforts have been made to reduce epidemiologic indicators of periodontal disease in pregnant women. This umbrella review aims to analyze the systematic reviews/meta-analyses investigating the effect of periodontal therapy in pregnant women on the frequency of obstetric complications (low birth weight, preterm delivery, and preeclampsia) and to identify the gaps in the scientific literature. METHODS: A systematic review of systematic reviews with and without meta-analysis of intervention studies was conducted. Quality evaluation and qualitative analysis of the reviews were performed. RESULTS: A total of 223 articles were obtained, and 18 of them were included in the analysis, 13 articles included meta-analysis, where 11 were of high quality and 7 of medium quality according to the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) guide. These systematic reviews/meta-analyses included a total of 19 studies (17 randomized clinical trials). Descriptive systematic reviews showed that periodontal therapy has positive effects on reducing the frequency of adverse pregnancy outcomes. In systematic reviews with meta-analysis, overall effect estimators were not significant, although a reduction in the incidence of obstetric complications was observed. Subgroup analysis resulted in significant effects, depending on sociodemographic conditions. CONCLUSIONS: Differential findings are not enough to demonstrate that there is a significant reduction in the frequency of adverse pregnancy outcomes in pregnant women receiving periodontal therapy. Possible explanations are related to factors such as the type of studies analyzed, indicator of obstetric complication considered, and specific variables included in the analysis. Many systematic reviews did not address publication bias and did identify gaps in knowledge that require further clarification.

Evaluation of DNA methylation of inflammatory genes following treatment of chronic periodontitis: A pilot case-control study.

OBJECTIVE: To evaluate the influence of periodontal therapy on DNA methylation in patients with chronic periodontitis as compared to healthy individuals. MATERIAL AND METHODS: Twenty patients were enrolled into two groups: (i) 10 diagnosed as clinically healthy; and (ii) 10 diagnosed with chronic periodontitis. Clinical measures were recorded and gingival biopsies were harvested at baseline (both patient groups) and at 2 and 8 weeks post-baseline for diseased individuals. Molecular DNA methylation analysis was performed by pyrosequencing for the putative inflammation-associated genes LINE-1, COX-2, IFN-γ and TNF-α. Random-intercept linear regression models were applied to evaluate methylation levels across groups at baseline and the methylation changes over time in the diseased and normal tissues. RESULTS: Periodontal therapy did not influence gene expression methylation of TNF-α, IFN-γ and LINE-1 levels at normal and periodontitis sites over time. However, it significantly reduced COX-2 methylation levels comparable to healthy individuals at both 2 and 8 weeks post-treatment (p < .05). CONCLUSIONS: Periodontal therapy resets the DNA methylation status of inflammatory gene for COX-2 in patients with periodontal disease. DNA methylation levels of TNF-α, IFN-γ and LINE-1 were sustained in periodontitis sites despite therapy. Future studies should consider an expanded panel of inflammatory genes over time. (ClinicalTrials.gov NCT02835898).

The Effect of Periodontal Treatment on Clinical and Biological Indicators, Quality of Life, and Oral Health in Rheumatoid Arthritis Patients: A Quasi-Experimental Study.

Non-surgical periodontal therapy (NSPT) has been shown to have systemic effects. It has been suggested that, similar to rheumatoid arthritis (RA), periodontitis (PD) has an impact on general health, in terms of psychological, physical, and social aspects. This study determines the effect of periodontal treatment in RA activity, health-related quality of life, and oral health self-perception before and after periodontal treatment in RA patients. A quasi-experimental, prospective, non-randomized study was conducted, and 52 patients were included in the study. Periodontal parameters and the instruments disease activity score-28 (DAS-28), SF-36, and OHIP-14 were measured at baseline and at 3 months after NSPT. All differences were statistically assessed. The study protocol was registered in Clinical Trials (NCT04658615). No statistically significant differences were found in the scores of DAS-28 before and after the intervention in the group with PD and reduced periodontium. When the effect of periodontal treatment was analyzed in the group of 29 patients who were followed up, it was found that there were statistically significant differences before and after in variables such as psychological distress, emotional role, and mental health, which indicates an improvement in the scores of these variables. NSPT influenced the health-related quality of life measured with SF-36 and OHIP-14 in patients with RA. In conclusion, NSPT has an effect on self-reported quality of life and health indicators more than the RA activity as measured with DAS-28. However, the clinical effect of periodontal treatment in RA patients provides important data to support periodontal care in patients.

Regenerative Medicine Technologies to Treat Dental, Oral, and Craniofacial Defects.

Additive manufacturing (AM) is the automated production of three-dimensional (3D) structures through successive layer-by-layer deposition of materials directed by computer-aided-design (CAD) software. While current clinical procedures that aim to reconstruct hard and soft tissue defects resulting from periodontal disease, congenital or acquired pathology, and maxillofacial trauma often utilize mass-produced biomaterials created for a variety of surgical indications, AM represents a paradigm shift in manufacturing at the individual patient level. Computer-aided systems employ algorithms to design customized, image-based scaffolds with high external shape complexity and spatial patterning of internal architecture guided by topology optimization. 3D bioprinting and surface modification techniques further enhance scaffold functionalization and osteogenic potential through the incorporation of viable cells, bioactive molecules, biomimetic materials and vectors for transgene expression within the layered architecture. These computational design features enable fabrication of tissue engineering constructs with highly tailored mechanical, structural, and biochemical properties for bone. This review examines key properties of scaffold design, bioresorbable bone scaffolds produced by AM processes, and clinical applications of these regenerative technologies. AM is transforming the field of personalized dental medicine and has great potential to improve regenerative outcomes in patient care.

Supracrestal Non-Surgical Therapy in Periodontal Diseases.

Periodontal diseases are the complex disease with a dynamic relationship between biofilm and the host immunoinflammatory response. The goal of periodontal therapy is to preserve the natural dentition and increase their longevity by creation of a favorable environment around the teeth. The mainstay to achieve this is by the non-surgical periodontal therapy, followed by surgical and other recent treatment modalities. However, there seems no sure indication to choose amongst them that are clinically significant and offer long term predictability. We report here two cases that had supracrestal defects and were treated with less invasive instrumentation and repeated full mouth scaling and root planing. This avoided a surgical intervention and was more cost-effective in treating moderate to severe young chronic periodontitis patients. The decision for the type of treatment needs to be critically assessed with a better understanding of the outcome, morphology of the defects, and type of teeth involved. Fundamentals like positive reinforcements, compliance and self-performed plaque control will always remain an integral component regardless of nonsurgical or surgical periodontal therapy.

Comparative evaluation of bovine porous bone mineral.

BACKGROUND: The aim of the present clinical study was to compare the efficacy of bovine porous bone mineral (BPBM) with and without platelet-rich plasma (PRP) for the treatment of periodontal intrabony defects. MATERIALS AND METHODS: Twenty eight identical bilateral periodontal intrabony defects were selected from 14 chronic periodontitis patients. The subjects were randomly assigned to test group (BPBM+PRP) or the control group (BPBM). The clinical, radiographic, and intrasurgical (re-entry) measurements were made at baseline and at 9 months postoperatively. RESULTS: Both treatment modalities resulted in significant reduction in probing depth and gain in clinical attachment level as compared to baseline values. The probing depth reduction was 6.20±1.40 mm in BPBM and 6.60±1.43 mm for the BPBM/PRP-treated sites. The gain in clinical attachment level observed was 4.16±1.05 mm for BPBM and 4.70±0.76 mm for the BPBM/PRP group. Radiographically, there was a significant defect fill (3.83±1.01 mm) for the BPBM group and (4.04±1.77 mm) in the BPBM/PRP group. Similar trend was observed between the two groups in relation to intrasurgical parameters. CONCLUSIONS: The combination therapy (BPBM+PRP) showed more favorable clinical outcome in the treatment of intrabony defects than the BPBM alone group, although the mean difference between the two groups was statistically nonsignificant.

Methods for Evaluation of Regenerative Procedures.

A multitude of new procedures and materials are being tested for their ability to promote periodontal wound healing. This review provides an overview of the most wellaccepted methods for evaluating periodontal wound healing procedures/materials. Topics discussed include appropriate patient selection, general principles in non-surgical and surgical therapy as they relate to wound healing trials, clinical soft and hard tissue measurements which are generally obtained, an overview of radiographic assessments, and a discussion of the methods and role of histological evaluations in clinical trials. The advantages and disadvantages of the various methodologies are presented. The review concludes with the potential endpoints which can be used in periodontal wound healing studies. J Periodontol 1992; 63:1085-1092.

Radiographic Methods in the Evaluation of Periodontal Therapy.

Radiographic methods are commonly utilized to assess periodontal bone changes in clinical trials. Radiographs are unique as a data source in that they provide a permanent visual record of the bone support and allow for linear, area, and volume measurements of periodontal lesions. The major limiting factors in the use of radiographic outcomes measures are geometric distortion and radiographic processing errors. The use of standardized methods and computer algorithms has reduced the effect of these errors on data from radiographs. Radiographic analysis in clinical trials is largely done in digital format by indirect digitizing film with a video camera. Direct digital detectors are now available for intra-oral use. The use of a direct detector eliminates the need for film processing and allows for dose reduction. The detectors currently available are limited in size and resolution. Subtraction radiography allows for area and volume estimates of bone gain or loss. The subtraction methods are highly precise, but are also technically exacting and labor intensive. The clinical trial hypothesis, size, length, and accuracy required should be the final consideration in choosing a radiographic method. J Periodontol 1992; 63:1078-1084.

Isolation of Periodontal Species After Guided Tissue Regeneration.

One advanced localized periodontal lesion in each of 10 patients was treated using the guided tissue regeneration procedure. Six weeks after placement of expanded polytetrafluoroethylene (ePTFE) membranes, microbial samples were taken from each treated site and the membranes were removed. Six weeks later the cases were re-evaluated. They had all healed successfully with varying amounts of gain of clinical attachment. Gram-negative, anaerobic rods were found in all samples and made up 31% of all organisms cultivated. In 1 patient, Porphyromonas gingivalis was found in a proportion of 17.5%. Six of the other 9 patients harbored Prevotella intermedia (mean proportion 21.3%) and 6 Prevotella melaninogenica (6.8%). Fusobacterium and Capnocytophaga were also frequently found. The results demonstrate that ePTFE membranes are frequently colonized by periodontal microorganisms. The importance of bacterial colonization on clinical success is presently not known. Further studies are needed to determine the effect of the presence or absence of putative pathogens during guided tissue regeneration. J Periodontol 1993; 64:1171-1175.

Guided Tissue Regeneration Using Bioresorbable and Non-Resorbable Devices: Initial Healing and Long-Term Results.

Studies on periodontal wound healing have resulted in the development of the treatment modality known as "guided tissue regeneration" (GTR) based on a principle of guiding the proliferation of the various periodontal tissue components during healing following periodontal surgery. The first report of a human tooth treated according to the principle of GTR was presented 10 years ago by Nyman et al. Since then numerous clinical studies and animal experiments have been performed bringing the concept of GTR to a clinical reality. We also know that the results obtained through GTR therapy can be maintained on a long-term basis. The first generation of GTR devices has been non-resorbable, which calls for a second surgical procedure. This is avoided when bioresorbable devices become available. This paper suggests some demands regarding safety and efficacy criteria for both non-resorbable and bioresorbable devices. Results from recent animal experiments and clinical studies following the use of a bioresorbable device in GTR therapy are presented. J Periodontol 1993; 64:1157-1165.

The Role of Infection and Anti-Infection Treatment in Regenerative Therapy.

Infection associated with regenerative therapy is becoming an increasingly important consideration as the frequency and numbers of regenerative procedures increase. Specific recommendations for antimicrobial treatment associated with membranes, grafts, and implants are presented in the context of establishing general principles of infection management. J Periodontol 1993; 64:1166-1170.

Periodontal Therapy: Prospects for the Future.

Prior to the 1950s, periodontitis was treated mostly by tooth exfoliation or extraction, and that is still the predominant treatment for most of the world's populations today. Debridement of the root surface by scaling and root planing came into relatively common use in the first half of the present century and has become the central feature held in common by all currently-used forms of periodontal therapy. Until the 1980s, the most commonly-used treatment consisted of scaling and root planing, followed by resective surgery aimed at achieving zero pocket depth. During the 1980s, data were obtained demonstrating that the thoroughness of root debridement and subgingival infection control, not the presence or absence or periodontal pockets, is the major determinant of successful periodontal therapy, and non-surgical therapy became a commonlyused treatment. Neither resective surgery nor non-surgical therapy results in significant regeneration of periodontal attachment. With the realization that periodontitis is an infectious process, the use of antibiotics and other anti-infective agents came into common use as adjuncts to other standard therapies. An understanding of the pathways by which the soft and calcified tissues of the periodontium are destroyed has led to the likelihood of widespread future use of the non-steroidal, anti-inflammatory family of drugs to suppress alveolar bone destruction by blocking prostaglandin production, and to the use of chemically-modified tetracyclines that chelate divalent cations and thereby block tissue destruction by the metalloproteinases. Recent data clearly show that regeneration of the previously-destroyed periodontal attachment tissues is biologically possible, and regeneration has become the goal of therapy for the 1990s. Use of osteoconductive and osteoinductive graft materials can, under favorable conditions, induce roughly 60% to 70% regeneration of bone lesion height or volume with concomitant improvement in the clinical conditions. Regeneration by grafting may be further enhanced by use of barrier membranes that exclude gingival fibroblasts and epithelium from the healing site. Still further enhancement seems to be possible by local application of various growth factors, although studies in this important area are now only in their infancy. The future of periodontal therapy is exceedingly bright. It seems likely that we may be able to achieve nearly complete regeneration of periodontal attachment at many, although not all, sites through the use of root debridement and anti-infective and anti-inflammatory drugs and agents that inhibit metalloproteinases to arrest progress of disease and resolve the inflammatory process, followed by the combined use of graft material, barrier membranes, and growth factors to induce regeneration of periodontal attachment tissues. J Periodontol 1993; 64:744-753.

Microbiological Testing in the Diagnosis of Periodontal Disease.

The oral microbiota plays a primary role in the initiation and progression of the most common forms of periodontal disease. Because of the multiplicity of factors that control the establishment and long-term evolution of the oral microbiota, a great deal of heterogeneity exists in the composition of the periodontal microbiota among individual subjects. Despite these individual differences and the complex interactions between bacteria and the host and among bacteria, an association has been demonstrated between certain species and various forms of periodontal disease. However, the predictive value of either positive or negative tests for selected bacterial species has not proved to be high enough for routine use in clinical practice. Nevertheless, bacteriological tests have been of value in the management of patients with juvenile Periodontitis and refractory forms of periodontal disease. The increasing availability of diagnostic laboratory services and diagnostic kits for office use will make it easier for the practitioner to select appropriate antimicrobial treatments and monitor patients undergoing antimicrobial therapy. J Periodontol 1992; 63:332-337.

Parameter on Aggressive Periodontitis.

The American Academy of Periodontology has developed the following parameter on the treatment of aggressive periodontitis. Patients should be informed of the disease process, therapeutic alternatives, potential complications, expected results, and their responsibility in treatment. Consequences of no treatment should be explained. Failure to treat aggressive periodontitis appropriately can result in progressive and often rapid loss of periodontal supporting tissues. This may have an adverse effect upon prognosis and could result in tooth loss. Given this information, patients (or their parents or guardians, as appropriate) should then be able to make informed decisions regarding their periodontal therapy. J Periodontol 2000;71:867-869.

Parameter on Periodontal Maintenance.

The American Academy of Periodontology has developed the following parameter on Periodontal Maintenance. Periodontal maintenance is an integral part of periodontal therapy for patients with a history of inflammatory periodontal diseases. Patients should be informed of the disease process, therapeutic alternatives, potential complications, expected results, and their responsibility in treatment. Consequences of no treatment should be explained. Failure to comply with a periodontal maintenance program may result in recurrence or progression of the disease process. Given this information, patients should then be able to make informed decisions regarding their periodontal therapy. J Periodontol 2000;71:849-850.

Retrospective Evaluation of the Influence the Interleukin-1 Genotype on Radiographic Bone Levels in Treated Periodontal Patients Over 10 Years.

BACKGROUND: A difference in genetic susceptibility to plaque accumulation has been advocated to explain different responses to periodontal therapy. The purpose of this study is to assess the role of the interleukin-1(IL-1) polymorphism on the rate of bone and tooth loss in non-smoking periodontally treated patients during maintenance. METHODS: Sixty consecutive non-smoking patients (mean age 46.8 ± 5.0) with moderate to severe periodontitis, treated and maintained for over 10 years were selected. At baseline (T0), radiographic evaluation (cementoenamel junction [CEJ]-root apex, CEJ-bottom of defect mesial and distal, CEJ-bone crest mesial and distal, crown-root ratio) was performed. All patients received scaling and root planing; 36 patients then underwent surgical therapy. Subsequently, all patients were enrolled in a periodontal maintenance program with recall visits every 3.4 ± 1.0 months for at least 10 years. At the latest recall visit (T2) the same radiographic measurements evaluated at baseline were taken and a DNA sample for IL-1 genetic susceptibility testing was collected and sent for analysis. RESULTS: Twenty-three of the 60 patients (38.3%) were IL-1 genotype positive. A total of 52 teeth (3.3%) out of 1,566 were lost due to periodontitis between T0 and T2; 28 of 957 (2.9%) in the IL-1 genotype negative group and 24 of 609 (3.9%) in IL-1 genotype positive group. The mean variation in bone defect level (ΔBD) averaged -0.04 mm in IL-1 genotype negative patients and 0.01 mm in IL-1 genotype positive patients. The mean variation in bone crest level (ΔBC) averaged -0.24 mm in IL-1 genotype negative patients and -0.28 mm in IL-1 genotype positive patients. However, a few patients showed significant differences in response to therapy based on initial bone levels and genotype. IL-1 negative patients who showed minimal initial bone loss responded to the therapy better than the IL-1 positive patients. IL-1 positive patients with severe initial bone loss showed a better response to the therapy than IL-1 negative patients. CONCLUSIONS: On average, there were no significant differences related to IL-1 genotype in tooth loss after 10 years in a non-smoking, well-maintained periodontal population. On an individual patient basis, the IL-1 genotype, in combination with the initial bone level, seems useful at the beginning of therapy for predicting bone level variation. J Periodontol 2001;72:767-773.

Clinical and Radiographic Evaluation Periodontal Intrabony Defects Treated With Guided Tissue Regeneration. A Pilot Study.

BACKGROUND: The aim of this clinical and radiographic study was to evaluate the effect of guided tissue regeneration using a bioabsorbable barrier in the treatment of intrabony defects in humans. METHODS: Intrabony osseous defects (2 or 3 walls) around mandibular canines and premolars were treated in 10 systemically healthy patients with ages ranging from 35 to 56 years. Prior to the surgical phase, patients were enrolled in a strict maintenance program including oral hygiene instructions and scaling and root planing (presurgical PI and GI <10%). Patients were seen for professional prophylaxis during the duration of the study. Clinical measurements were performed with an electronic probe at baseline and at reentry 8 months following surgical therapy. Measurements included clinical attachment levels (CAL), gingival margin levels (GML), probing depths (PD), bone defect levels (BDL), and alveolar crest level (ACL). A split mouth design was used. Quadrants were randomly assigned for treatment by GTR (experimental) or open flap debridement alone control). Standardized radiographs were taken at baseline and at reentry. Digital images were analyzed by subtraction to assess changes in area (A) and optical density (OD). Data were evaluated using paired t test. RESULTS: Statistically significant differences were found in both groups when comparing baseline and post-treatment values for CAL, GML, PD, and BDL (P <0.01). Greater reductions in BDL and gain in A and OD were observed in the GTR group when compared to control (P <0.01). Both therapies were effective in improving the clinical parameters assessed. CONCLUSION: Clinical and radiographic findings from this study demonstrated more bone fill in sites treated with GTR. J Periodontol 2002;73:353-359.

Response to Periodontal Therapy in Diabetics and Smokers.

Diabetics and smokers are two patient groups at high risk for periodontal disease who also exhibit impaired wound healing and, therefore, constitute two different groups in whom the relationship between host-parasite interaction, outcome of periodontal therapy, and systemic factors is best represented. The results of two independent clinical trials involving treatment of periodontal disease in diabetics and smokers are presented. A new treatment regimen-for the management of periodontal disease associated with diabetes mellitus is proposed. This treatment approach incorporates both antimicrobial agents and pharmacological modulation of the host response. Elimination of periodontal infection and reduction of periodontal inflammation in diabetic patients resulted in a significant short-term reduction in the concentration of glycosylated hemoglobin (HbA1c ). Control of chronic infections and modulation of the host response offer a new therapeutic approach in the management of patients with both diabetes and periodontal disease. The effect of smoking on periodontal healing is also discussed. The clinical and microbiological response of smokers to non-surgical periodontal therapy is compared to non-smokers. In addition, possible mechanisms whereby diabetes mellitus and cigarette smoking increase the severity of periodontal disease are discussed. J Periodontol 1996;67:1094-1102.