Clinical application of genetics to guide prevention and treatment of oral diseases.

Dental care costs in the United States exceed $100 billion annually. Personalized medicine efforts in dentistry are driven by potentially compelling clinical utility and cost-effectiveness prospects in the major diseases of periodontitis, caries, and oral cancers. This review discusses progress and challenges identifying genetic markers and showing clinical utility in dentistry. Genome-wide association studies (GWAS) of chronic periodontitis (CP) identified no significant variants, but CDKN2BAS variants on chromosome 9 were significantly associated with aggressive periodontitis. Stratifying patients by interleukin (IL)-1 gene variants, smoking and diabetes differentiated CP prevention outcomes. Dental caries' GWAS identified significant signals in LYZL2, AJAp1, and KPNA4; and efforts are ongoing to identify genetic factors for multiple caries phenotypes. Trials of molecularly targeted therapies are in progress for oral, head, and neck squamous cell carcinomas (OHNSCC) and results have been promising but limited in their effectiveness. Current opportunities and challenges for molecular targeting for OHNSCC are discussed.

IL-1 receptor antagonist gene as a predictive biomarker of progression of knee osteoarthritis in a population cohort.

OBJECTIVE: Within the interleukin-1 (IL-1) cytokine family, IL-1 receptor antagonist (IL1RN) gene variants have been associated with radiological severity of knee osteoarthritis (OA) in cross-sectional studies. The present study tested the relation between IL1RN gene variants and progression of knee OA assessed radiographically by change in Kellgren-Lawrence (KL) score over time. DESIGN: 1153 Caucasian adults (age range: 44-89) from the Johnson County Osteoarthritis Project were evaluated for unequivocal radiographic evidence of knee OA at baseline, defined as KL score ≥2, and were re-examined after 4-11 years for radiographic changes typical of OA progression. IL1RN gene variants were tested for association with OA progression and for potential interaction with body mass index (BMI). Other IL-1 gene variations were tested for association with OA progression as a secondary objective. RESULTS: Of 154 subjects with OA at baseline, 88 showed progression at follow-up. Seven IL1RN single nucleotide polymorphisms (SNPs) and one IL-1 receptor SNP were associated with progression. Four IL1RN haplotypes, each occurring in >5% of this population, showed different relationships with progression, including one (rs315931/rs4251961/rs2637988/rs3181052/rs1794066/rs419598/rs380092/rs579543/rs315952/rs9005/rs315943/rs1374281; ACAGATACTGCC) associated with increased progression [odds ratio (OR) 1.91 (95%CI 1.16-3.15); P = 0.012]. Haplotypes associated with progression by KL score were also associated with categorical change in joint space narrowing. BMI was associated with OA progression in subjects carrying a specific IL1RN haplotype, but not in subjects without that haplotype. CONCLUSION: A significantly greater likelihood of radiological progression of knee OA was associated with a commonly occurring IL1RN haplotype that could be tagged by three IL1RN SNPs (rs419598, rs9005, rs315943). Interactions were also observed between IL1RN gene variants and BMI relative to OA progression. This suggests that IL1RN gene markers may be useful in stratifying patients for medical management and drug development.

Implantation of Bacteroides gingivalis in nonhuman primates initiates progression of periodontitis.

Although periodontitis is a bacterial disease, its multidimensional nature and its bacterial complexity have made it difficult to definitively prove that specific microorganisms initiate the disease process. The successful implantation of a rifampin-resistant strain of the putative periodontal pathogen Bacteroides gingivalis into the periodontal microbiota of monkeys (Macaca fascicularis) resulted in an increase in the systemic levels of antibody to the microorganism and rapid and significant bone loss.

The effect of supragingival plaque control on the composition of the subgingival microbial flora in ligature-induced periodontitis in the monkey.

The influence of supragingival plaque control on the subgingival microflora and clinical parameters of ligature-induced periodontitis in the Cynomolgus monkey was investigated. No clinical changes were observed during the six-week experimental period. The total cultivable flora and the proportions of total black-pigmented Bacteroides (BPB) and asaccharolytic black-pigmented Bacteroides decreased significantly in the cleaned test sites as compared to those in the non-cleaned controls. The study suggests that six wk of supragingival plaque control in the presence of periodontal disease may alter the periodontitis-associated microflora in the monkey, but not sufficiently to alter clinical signs of disease in this time period.

Controlled-release local delivery antimicrobials in periodontics: prospects for the future.

New knowledge about the microbial etiology of periodontal diseases emerged in the 1970s and 1980s and led to widespread interest in the use of antimicrobial agents to treat periodontitis. The controlled-release delivery of antimicrobials directly into the periodontal pocket has received great interest and appears to hold some promise in periodontal therapy. Some techniques for applying antimicrobials subgingivally, such as subgingival irrigation, involve local delivery but not controlled-release. Controlled-release local delivery systems, in which the antimicrobial is available at therapeutic levels for several days, have been evaluated in several forms and using different antimicrobials. Although most studies with such systems have focused on drug delivery kinetics and "proof of principle" evaluations, some controlled clinical trials have recently been reported. The most widely tested system, monolithic tetracycline-containing fibers, has shown significant clinical benefit when used alone as compared to no subgingival therapy. Similarly, controlled trials involving chlorhexidine strips used subgingivally every 3 months in place of routine supportive periodontal therapy have shown significant clinical benefit for up to 2 years. Although these data are now emerging, many questions concerning the optimal use and role of this therapy in clinical practice remain. This review attempts to summarize and interpret current data and to outline key remaining questions that must be addressed as this technology is transferred into clinical practice.

The effect of long-term low-dose tetracycline therapy on the subgingival microflora in refractory adult periodontitis.

Twenty patients were selected for antibiotic treatment due to poor response to conventional therapy. Ten patients were evaluated after taking 250 mg/day of tetracycline for 2 to 7 years. Ten other patients who had been on tetracycline for at least 2 years were evaluated 6 months to 2 years after stopping the antibiotic. Subgingival plaque was cultured anaerobically on nonselective media (ETSA) and ETSA with 1 microgram/ml of tetracycline HCl. Pocket depth, plaque and gingivitis were scored. Those patients on tetracycline had no bleeding on probing despite residual pockets ranging from 3 to 7 mm. Gram-negative anaerobic rods made up to 49.8% of the microflora of these patients, with Fusobacterium nucleatum dominating. B. melaninogenicus, and B. gingivalis were not detected in the samples. Five of ten patients off tetracycline bled on probing and had pocket depths in the same range as those on tetracycline. The microflora of tetracycline-off sites was predominately Gram-negative rods (63.1% with B. gingivalis and F. nucleatum 7.3% and 3.1% of the flora respectively). In tetracycline-on samples 76.6% of the isolates were resistant to 1 microgram/ml of tetracycline compared to 25.9% in the patients off tetracycline and 7.1% resistant organisms in 14 untreated control samples from periodontitis patients not exposed to any long-term tetracycline therapy. Long-term, low-dose tetracycline was associated with a healthy clinical condition and diverse Gram-negative anaerobic flora resistant to the antibiotic. After discontinuing tetracycline the clinical and bacterial status was more characteristic of disease.

Clinical and microbiological evaluation of therapy for juvenile periodontitis.

Eight patients (mean age 15.6 yrs) with severe molar-incisor bone loss and pocket formation characteristic of juvenile periodontitis were entered into a clinical protocol of three sequential stages: scaling and root planing (S/RP); S/RP concurrent with systemic tetracycline therapy (1 gm/day for 28 days); periodontal surgery concurrent with systemic tetracycline therapy. Clinical and microbiological examinations were scheduled at baseline, at 1 to 2 months after Stage I, at 1 to 2 months after completion of tetracycline therapy in Stages II and III, and during recall. A decision to progress to the next stage or to place the patient on a 3-month recall was based solely on clinical findings (suppuration, bleeding upon probing and pocket depth) at the deepest site in each patient. Paperpoint subgingival plaque samples from representative affected sites were analyzed for percentage of total cultivable microflora composed of black-pigmented Bacteroides species (BPB), surface translocating bacteria (STB) and Actinobacillus actinomycetemcomitans (Aa). At baseline, all sites bled to probing, seven of eight sites showed suppuration, and deepest pocket depths averaged 8.0 mm. STB were detected in one and BPB in four sites, respectively, and all sites demonstrated Aa, which constituted approximately 40% of the total cultivable flora. S/RP alone had essentially no effect on either clinical or microbiological findings, and all patients progressed to Stage II. Five went on to Stage III. S/RP with tetracycline was clinically and microbiologically more effective at sites in which Aa was predominant. Surgery was required in all sites containing high levels of both BPB and Aa. These results suggest that microbiological diagnosis may be useful in selecting and monitoring treatment for juvenile periodontitis.

Association of clinical risk factors with treatment outcomes.

A patient's decision to accept treatment recommended by his dental health care provider will be strongly influenced by the quality of the information he is given. Estimates of prognosis and treatment predictability must be based on the evidence available from the literature and the practitioners' own experience. Thorough, accurate, and relevant clinical and adjunctive diagnostic data will be a major influence in the development of the patient's individualized treatment strategy. Some clinical findings such as severity of disease for age, deepening pockets accompanied by loss of clinical attachment, frequent bleeding on probing, and bone loss can be considered as risk and prognosis factors. "Hard" data implicating specific clinical or diagnostic findings as risk factors or markers are difficult to find because there are few randomized longitudinal trials available. A new approach which attempts to focus on reducing the risk of undesirable outcomes while improving the probability of successful outcomes following treatment has been referred to as the Treatment Predictability Model. A key feature of this approach is the focus on individual patient circumstances and preferences through the use of decision analysis techniques. A large scale, long-term project utilizing a practice-based research network (PBRN) provided some descriptive information about factors that could distinguish between responders and nonresponder patients undergoing treatment for advanced periodontitis. Bacterial colonization, level of post-treatment plaque control, and smoking were major predictive variables in this group of periodontitis patients. The predictive treatment approach may be one way to develop evidence that will improve the predictability of outcomes for individual patients.

Non-human primates used in studies of periodontal disease pathogenesis: a review of the literature.

The inability to examine initiation and progression of periodontal disease and to assess certain therapies in humans has led to a great interest in the use of animal models in periodontal research. Some of the most prominent animals used are non-human primates. This article reviews the characteristics of non-human primate models in periodontal health, in the transition from health to gingivitis to periodontitis, and in experimental gingivitis and periodontitis. Where possible, the results of these studies are compared with results from human studies. Only a few studies have compared in detail the anatomy, physiology, immunology, and tissue interactions in monkeys with those of humans. With the exceptions of differences and variations in size of the dentition, the number of each tooth type as well as larger canines, presence of diastemata between anterior teeth, and an edge-to-edge relationship of the incisors, the dental and periodontal anatomy of non-human primates seem quite similar to that of humans. Clinically healthy gingiva can be established and maintained in non-human primates, and gingivitis as well as periodontitis occur in these animals. It is possible to induce experimental periodontitis by placement of peri-dental silk ligatures or orthodontic elastics as well as by surgical removal of alveolar bone. Although the most appropriate model for studies of periodontal disease pathogenesis in non-human primates appears to involve the application of silk ligatures, some difficulties may occur in establishing periodontal break-down by using this model. Many clinical, histological, microbiological, and immunological characteristics of spontaneous and experimental marginal inflammation in most non-human primates are similar to those in humans. The most significant differences between small non-human primates and humans are the very limited number of lymphocytes and plasma cells in the inflammatory infiltrate of squirrel monkeys (Saimiri sciureus) and marmosets. Therefore, the use of squirrel monkeys and marmosets may not be appropriate in many studies of periodontal disease pathogenesis. The most significant microbial differences between macaque species and humans are a lower proportion of Actinomyces species, the presence of a catalase-producing Prevotella melaninogenica strain, and the high carrier rate for Actinobacillus actinomycetemcomitans in subgingival plaque of macaque species. The significance of these differences is presently unknown. It is concluded that the use of many non-human primate species due to the apparent close anatomic and biologic similarities to humans is appropriate in experimental studies of periodontal disease, provided the use of laboratory animals is requisite and lower species are not applicable.(ABSTRACT TRUNCATED AT 400 WORDS)

Changes of subgingival total colony forming units and black pigmented bacteroides after a single irrigation of periodontal pockets with 1.64% SnF2.

Periodontal pockets of 11 subjects were irrigated once with either 1.64% SnF2 or saline applied by syringe. Changes on the total anaerobic colony forming units (CFU) and black pigmented bacteroides (BPBs) of the irrigated pockets were assessed for 31 days. The results showed little change of the CFUs by either single application of SnF2 or saline. However, SnF2 irrigation produced a decrease in the BPBs for 1 week with the greatest effect (1/2 log reduction) being seen at 3 days after the irrigation. Some subjects had more impressive reductions in BPBs, yet four of the 11 subjects showed no reductions in BPBs in those sites irrigated with SnF2. Further studies with frequent irrigation intervals are necessary to evaluate the potential usefulness of SnF2 for subgingival irrigation.

A 6-month multi-center evaluation of adjunctive tetracycline fiber therapy used in conjunction with scaling and root planing in maintenance patients: clinical results.

The purpose of this study was to compare the efficacy of scaling and root planing (S and RP) alone versus tetracycline fiber therapy used adjunctively with S and RP in the treatment of localized recurrent periodontitis sites in maintenance patients. A total of 113 patients receiving regular supportive periodontal therapy (SPT) were treated with whole mouth S and RP. Two non-adjacent sites in separate quadrants were selected in each patient for monitoring based on criteria that the sites were 5 to 8 mm deep and had a history of bleeding on probing. The chosen sites were randomly assigned to one of the two treatment groups. Probing depth (PD), bleeding on probing (BOP), and clinical attachment level (CAL) were measured at baseline and 1, 3, and 6 months. At 1, 3 and 6 months, adjunctive fiber therapy was significantly better in reducing PD (P < 0.05) and reducing BOP (P < 0.05) than S and RP alone. At 6 months, fiber therapy was significantly better in promoting clinical attachment gain (P < 0.05) than S and RP alone. Overall, these results indicate that fiber therapy significantly enhanced the effectiveness of S and RP in the management of localized recurrent periodontitis sites, in patients receiving regular supportive periodontal treatment.

Field testing as clinical trial methodology in periodontics.

In the early 1950s the randomized control trial (RCT) was introduced and became widely accepted as the definitive proof of efficacy of a specific medical treatment. In fact, the acceptance and application of this methodology were instrumental in converting medicine from an unpredictable art to a science. At present no other methodologies exist that allow the evaluation of therapeutic efficacy with confidence comparable to that achieved with randomized controlled trials. In recent years researchers have applied new experimental designs and data analysis techniques to clinical trials conducted in a field trial environment to facilitate the understanding of proper use of new therapeutic agents and procedures. Since many of the new methodologies are still evolving or have only recently been introduced, this review considers some of the major trends and developments, as well as experiences of the authors, in field trial methodology. This manuscript addresses the following questions: 1) are there current clinical trial needs that are not met by RCT? 2) If so, what considerations are necessary for new approaches to have scientific usefulness? and 3) What are the strengths and weaknesses of the field trial's setting relative to an institutional environment?

The effect of intensive antibacterial therapy on the sulcular environment in monkeys. Part I. Changes in the bacteriology of the gingival sulcus.

The changes induced in the bacteriology of the gingival sulcus were evaluated as part of a study considering the keratinizing potential of the sulcular epithelium when bacterial plaque was essentially eliminated. Two Rhesus monkeys were scaled and placed on a daily therapeutic regimen which included a prophylaxis, systemic tetracycline, and topical chlorhexidine. Over the 40 day experimental period and 74 days post-therapy, subgingival plaque samples were taken periodically. The plaque samples were cultured anaerobically and aerobically to determine the predominant bacterial flora. The total cultivable bacterial flora decreased from initial levels by greater than 99.9% with the antibacterial therapy. The flora shifted with therapy from one dominated by anaerobic organisms, including Bacteroides melaninogenicus (18%) and Fusobacterium species (13.9%), to a flora dominated by organisms growing aerobically. During treatment B. melaninogenicus and Fusobacterium species were not detected in any sample. After cessation of all therapy the anaerobes increased to dominance again, but B. melaninogenicus remained undetectable through 74 days post-therapy.

Clinical and microbiological effects of controlled-release locally delivered minocycline in periodontitis.

The clinical efficacy of minocycline in a subgingival local delivery system was evaluated alone (M) or as an adjunct to scaling and root planing (M + SRP), in comparison to scaling and root planing (SRP) or to no subgingival treatment (NoTx) in adult periodontitis. Fifty-one adult patients with > or = 7 mm periodontal pockets demonstrating the presence by culture of Porphyromonas gingivalis (Pg), Prevotella intermedia (P(i)), or Actinobacillus actinomycetemcomitans (Aa) were randomized into one of the above 4 treatment groups. All sites > or = 5 mm in the most diseased quadrant in each patient received the therapy. Other quadrants were not treated. All patients received standardized oral hygiene instructions at the beginning of the study. At 0, 1, 3 and 6 months following therapy the 7 mm experimental sites were evaluated for selected periodontal pathogens by DNA probe analysis. At these same time points, the plaque index, gingival index, and bleeding on probing were evaluated as well as probing depth and relative clinical attachment level which were assessed by means of an automated probe. Probing depth reduction with M + SRP was significantly greater than all other groups at one month and significantly greater than NoTx and SRP at 3 months. There were no differences in probing depth reduction among groups at 6 months. At 6 months the gain in clinical attachment level was significantly greater for SRP than for either the NoTx or M groups. The prevalence of Pg decreased significantly in the M and M + SRP groups at one month.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of supragingival plaque control on clinical and microbial outcomes following the use of antibiotics for the treatment of periodontitis.

Although supragingival plaque control is essential to successful periodontal therapy, the role of plaque control following systemic antibiotic use in periodontal disease has not been well defined. This study evaluated, following antibiotic use, which clinical and microbial parameters appeared to be influenced primarily by the antibiotics, independent of plaque control, and which outcomes appeared to be dependent on plaque control. Two hundred thirty-six patients (236) with moderate to severe periodontitis were clinically evaluated and microbial samples were taken by their private-practice periodontists. All patients were treated with scaling and root planing and a variety of systemic antibiotics, which were selected based on the microbial and clinical profile of the patient. Three months after therapy, patients were reevaluated and grouped by post-treatment plaque control, as either having very good oral hygiene (LoPl: N = 143; < or = 10% plaque-covered surfaces) or poor oral hygiene (HiPl: N = 93; > or = 25% plaque-covered surfaces). The two groups had different plaque and bleeding scores initially, but similar numbers of pockets probing > 5 mm and similar microbial patterns. Although the LoPl group had a significantly greater reduction in plaque than the HiPl group, bleeding scores and probing depths changed comparably in both groups after antibiotic therapy. Plaque control influenced outcomes significantly, but in a complex manner. The LoPl group exhibited a significantly greater reduction in certain bacteria, for example P. gingivalis. Interactions between plaque control and specific microbial parameters significantly affected clinical outcomes, although neither alone was sufficient to predict outcomes following antibiotic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

The relationship between probing attachment loss and computerized radiographic analysis in monitoring progression of periodontitis.

This study attempted to evaluate quantitative changes in radiographic density as an indicator of progression of periodontitis. Twenty-one subjects with a history of periodontitis were monitored at baseline, 3, 6, and 9 months using duplicate probing attachment level (PAL) measurements from stents and computer assisted densitometric image analysis (CADIA) of standardized radiographs. Results indicate that the majority of sites exhibited no PAL change during the 9-month period; however, the percentage of sites with loss increased with time. A mean of 6.1% of the sites/patient exhibited probing attachment loss during the study, as compared to a mean of 38.3% of the sites/patient that exhibited a loss of radiographic density. Due to the two dimensional nature of radiographs, density analysis was calculated in terms of radiographic "complexes" of multiple probing sites. There was significantly more density loss at complexes with greater than or equal to 2 mm of attachment loss than at sites with no change in PAL at 9 months; there was no such difference noted at 3 and 6 months. Also, density loss tended to increase as more sites within each complex experienced PAL. Although there was a significant correlation between mean density and PAL changes during the same time interval, there were wide variations at individual sites. This study suggests that there is a complex relationship between density change on radiographs and PAL change. The difficulties inherent in comparing highly sensitive new technologies to relatively imprecise clinical measurements of the attachment level are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

Ligature-induced marginal inflammation around osseointegrated implants and ankylosed teeth: stereologic and histologic observations in cynomolgus monkeys (Macaca fascicularis).

The aim of the investigation was to provide quantitative and qualitative histologic data on marginal inflammation around osseointegrated implants. The significance of the lack of a periodontal ligament in the initial breakdown phase of supporting tissues in implants was examined by comparing stereologic and histologic manifestations of ligature-induced marginal inflammation around osseointegrated implants with those around ankylosed and normal control teeth in 8 cynomolgus monkeys (Macaca fascicularis). Clinical and radiographic findings have been reported elsewhere. The marginal connective tissue around ligated implants was infiltrated by a significantly increased total number of lymphocytes, plasma cells, and neutrophils compared to non-ligated implants and teeth. The total number of lymphocytes around ligated implants was significantly higher than around ligated ankylosed and normal control teeth. There were, however, no significant differences in the total number of plasma cells and neutrophils within the ligated group. Osteoclasts were exclusively observed around ligated implants and ankylosed teeth. Although variations in microbiota and susceptibility of different jaw positions to periodontal break-down may influence the results of the present study, the results seem to substantiate the theory that marginal inflammation around implants and ankylosed teeth may have more serious implications than does marginal inflammation around teeth with a periodontal ligament. Since presence of osteoclasts was not related to the absence of cervical cementum with inserting gingival fibers around ligated ankylosed teeth, the increased susceptibility of bone loss of implants is probably not caused by the absence of these tissue components. In contrast, the histologic observations seem to support that the increased susceptibility for bone loss around implants may be related to the absence of a periodontal ligament.

Effects of a bisphosphonate on experimental periodontitis in monkeys.

Bisphosphonates have been shown to increase bone mass in estrogen-deficient patients by inhibiting osteoclast activity. The purpose of this study was to measure clinical and radiographic effects of a bisphosphonate on periodontitis development in monkeys. Twenty-seven (27) adult cynomolgus monkeys were studied. After quarantine, baseline data were obtained including plaque index, gingival index, clinical probing depth measurements, and intraoral radiographs. Standardized radiographs were analyzed for quantitative changes in bone density using a computer assisted densitometric (CADIA) system. Animals were divided into 3 groups to receive 1 of the 3 treatment agents; these agents consisted of two levels of the test drug (alendronate) and a saline placebo. Agents were injected in the saphenous vein of the lower leg every 2 weeks for 16 weeks. One week after the initiation of treatment agent injections, mandibular right molars and premolars were ligated with 3-0 silk sutures to induce periodontitis. Ligated teeth were also inoculated with Porphyromonas gingivalis to insure a significant etiologic challenge. Nonligated homologous teeth served as controls. Clinical measurements and radiographs were repeated at 8 and 16 weeks after ligation. The bisphosphonate at a concentration of 0.05 mg/kg significantly retarded the progression of periodontitis as measured by bone density changes. The higher level dose of the test drug did not differ from placebo with respect to loss of bone density. Clinical indices were not affected significantly by the test drugs. Drugs that alter bone metabolism may offer a new approach to the treatment of periodontal disease.

Clinical and microbiological patterns of adults with periodontitis.

Although current data suggest that periodontitis may actually be multiple diseases each with varying responses to therapy, little evidence exists to support this theory in adult patients. This report describes the design and initial findings of a longitudinal field trial involving the diagnosis and treatment of adult and refractory periodontitis patients in private practice. Adult patients (N = 221) who met specific clinical criteria were selected from the private practices of 22 periodontists. Clinical characteristics were recorded and subgingival plaque samples were sent to microbiology laboratories at either UCLA or The University of Texas Health Science Center at San Antonio (UTHSCSA). Samples were processed according to protocols standardized between the 2 centers. Five different combinations of the initial clinical and microbial findings were evaluated for patterns in the data by means of cluster analysis. Plaque, bleeding on probing, bone loss scores, probing depth distributions, and microbial findings produced multiple cluster solutions. Solutions involving 6 clusters explained 39.4% to 76.4% of the variation between patients and produced ratios for variation between clusters to variation within clusters of 5.2 to 15.3. The optimal cluster solution incorporated both clinical and microbial findings, with some clusters characterized by high plaque and moderate bleeding on probing and bone loss, whereas others had low plaque but high bleeding on probing and bone loss. Microbial findings of each cluster exhibited distinct patterns with some clusters having a high prevalence (83% to 100%) of specific target bacterial species while other clusters had an absence of these species.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of irrigation effects on gingivitis.

Although gingivitis is initiated by plaque and plaque removal controls gingivitis, gingival irrigation with water has been shown to reduce gingivitis without reducing plaque. This study attempted to explore possible mechanisms involved in the treatment of gingivitis by water irrigation. Patients (n = 125) with more than 20 teeth, less than 4 sites with probing depth (PD) deeper than 6 mm, bleeding on probing (BOP) frequency of 30% or higher, and no systemic disease were randomized to one of four treatment groups: toothbrushing alone (brush), toothbrushing plus chlorhexidine 0.12% rinse 2x/day (CHX), toothbrushing plus water irrigation 1x/day (irr+H2O), or toothbrushing plus chlorhexidine 0.04% irrigation 1x/day (irr+CHX). Six sites/tooth were examined at baseline, and at 3 and 6 months for BOP and PD using an automated probe, and for gingival index (GI) and plaque index (PI) by standard means. A prophylaxis and oral hygiene instructions were provided after baseline and 6 month measurements. Subgingival microbial samples and crevicular fluid (GCF) were collected from 2 teeth/subject at each time point. Microbial samples were processed for anaerobic culture and the predominant cultivable flora was determined. CHX and irr+CHX had a 30 to 35% decrease in mean PI, while brush and irr+H2O had only a 12 to 16% decrease. BOP was reduced by 14% in the brush group and 23 to 24% in the other groups. GI was significantly correlated with PI in the brush, CHX, and irr+CHX groups, but not in the irr+H2O group. Prevotella intermedia was significantly reduced in both irrigation groups, but not CHX or brush groups.(ABSTRACT TRUNCATED AT 250 WORDS)