Effect of locally delivered minocycline microspheres on markers of bone resorption.

BACKGROUND: Gingival crevicular fluid (GCF) biomarkers associated with bone resorption may be useful to determine periodontal disease status and response to therapy. The pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), a bone-specific degradation product, and interleukin 1-beta (IL-1), a potent bone-resorptive cytokine, have both been associated with periodontal disease activity. Minocycline is a tetracycline derivative possessing antimicrobial effects on periodontal pathogens and inhibitory properties on matrix metalloproteinases (MMPs) associated with tissue destruction. The aim of this study was to evaluate the effect of periodontal treatment in the form of scaling and root planing (SRP) and locally administered minocycline microspheres on the GCF levels of ICTP and IL-1. METHODS: Forty-eight chronic periodontitis patients were randomly assigned to 2 groups (SRP plus subgingival application of vehicle control [SRP + V], or SRP plus subgingival application of minocycline microspheres [SRP + M]) and monitored at 8 sites per subject at baseline and 1, 3, and 6 months. Four shallow (PD < or = 3 mm) and 4 deep (PD > or = 5 mm) sites were evaluated for both marker levels and for probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP). Eight periodontally healthy control subjects with no probing depths >3 mm and no loss of attachment were also monitored at the same time intervals. GCF levels of ICTP and IL-1 were determined using radioimmunoassay and enzyme-linked immunosorbent assay techniques, respectively. RESULTS: Significant differences (P<0.001) in GCF levels of ICTP and IL-1 were found between deep and shallow sites at all time points in both treatment groups. In addition, healthy subjects demonstrated significantly reduced levels of both markers compared to both shallow and deep sites in periodontitis patients (P <0.001). Only the SRP + M treated patients exhibited significant reductions (P <0.05) in both ICTP and IL-1 levels 1 month after treatment. Furthermore, the SRP + M group demonstrated significantly lower IL-1 levels (P <0.02) at 1 month compared to the SRP + V group. CONCLUSIONS: Results of this study indicate that GCF levels of ICTP and IL-1 correlate with clinical measures of periodontal disease and may aid in assessing disease status and response to periodontal therapy. Furthermore, local administration of minocycline microspheres led to a potent short-term reduction in GCF IL-1 levels. Additional studies are needed to address whether repeated administration of scaling and root planing along with minocycline microspheres will achieve long-term reductions in GCF ICTP and IL-1 levels.

Effect of non-surgical periodontal therapy on C-telopeptide pyridinoline cross-links (ICTP) and interleukin-1 levels.

BACKGROUND: Biochemical markers harvested from gingival crevicular fluid (GCF) may be useful to identify and predict periodontal disease progression and to monitor the response to treatment. C-telopeptide pyridinoline cross-links (ICTP), a host-derived breakdown product specific for bone, and interleukin-1beta (IL-1), a potent bone-resorptive cytokine, have been associated with periodontal tissue destruction. The aim of this study was to examine the effect of non-surgical periodontal therapy on GCF levels of ICTP and IL-1. METHODS: Twenty-five chronic periodontitis subjects were monitored at 8 sites per subject at baseline prior to scaling and root planing and 1, 3, and 6 months after therapy. Four shallow (probing depths < 4 mm) and 4 deep (probing depths > or = 5 mm) sites were monitored for both marker levels and clinical parameters. GCF was collected for 30 seconds on paper strips, and levels of ICTP and IL-1 were determined using radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) techniques, respectively. Clinical measurements included probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP). RESULTS: Deep sites exhibited significantly (P<0.001) higher ICTP and IL-1 levels compared to shallow sites at all time intervals. ICTP demonstrated a stronger association to clinical parameters than IL-1 including a modest correlation (r = 0.40, P<0.001) between ICTP and attachment loss. Significant improvements in PD, CAL, and BOP were observed at 1, 3, and 6 months in all sites (P<0.01). However, non-surgical mechanical therapy did not significantly reduce ICTP and IL-1 levels over the 6-month period. Further examination of subjects based on smoking status revealed that ICTP levels were significantly reduced at 3 and 6 months and IL-1 levels reduced at 3 months among non-smokers only. CONCLUSIONS: A single episode of non-surgical mechanical therapy did not significantly reduce biochemical markers associated with bone resorption in patients exhibiting chronic periodontitis. Future longitudinal studies are warranted to specifically evaluate the relationship between C-telopeptide pyridinoline cross-links and periodontal disease progression.

Relationship between crevicular aspartate aminotransferase levels and periodontal disease progression.

BACKGROUND: Aspartate aminotransferase (AST), an enzyme released from necrotic cells, has been identified in gingival crevicular fluid (GCF), and elevated levels are associated with periodontal tissue destruction. The aim of this study was to examine the relationship between elevated GCF levels of AST and periodontal disease progression. METHODS: Over a 12-month period, 8 to 10 interproximal sites in 41 periodontitis subjects (PS) and 15 healthy subjects (HS) were monitored. Clinical measurements included relative attachment level (RAL), probing depth, and bleeding on probing (BOP). Semiquantitative levels of GCF AST (< 800 microIU, > or = 800 microIU, and > or = 1,200 microIU) were determined using a chairside assay. At the 6- and 12-month visits, scaling and root planing and prophylaxis were performed in the PS and HS, respectively. Sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) were calculated for 2 diagnostic criteria (AST > or = 800 microIU, AST > or = 1,200 microIU) utilizing 4 thresholds of disease progression as determined by 2 methods (absolute change in relative attachment level and cumulative sum [CUSUM]). RESULTS: The percentage of sites exhibiting AST > or = 800 microIU, AST > or = 1,200 microIU, and BOP in the PS was significantly (P<0.02) lower at 6 and 12 months compared to baseline. The use of crevicular AST activity to monitor periodontal disease progression was associated with many false-positive results. Overall, low specificities, PPV, and odds ratios were demonstrated by the assay when using 2 diagnostic criteria and 4 thresholds of disease progression. The high NPV suggest that a negative AST test result was indicative of a periodontally stable site. CONCLUSIONS: These results demonstrate that elevated levels of AST were present at sites that did not subsequently exhibit disease progression. The high prevalence of AST-positive sites due to gingival inflammation diminished the test's ability to discriminate between progressive and stable, but inflamed, sites.

Treatment of periodontitis by local administration of minocycline microspheres: a controlled trial.

BACKGROUND: Periodontitis is an inflammatory condition of tooth-supporting tissues that is usually treated by mechanical removal of plaque and microorganisms that adhere to teeth. This treatment, known as scaling and root planing, is not optimally effective. Adjunctive therapy with locally delivered antimicrobials has resulted in improved clinical outcomes such as probing depth reduction. This article reports on the efficacy and safety of locally administered microencapsulated minocycline. METHODS: Seven hundred forty-eight (748) patients with moderate to advanced periodontitis were enrolled in a multi-center trial and randomized to 1 of 3 treatment arms: 1) scaling and root planing (SRP) alone; 2) SRP plus vehicle; or 3) SRP plus minocycline microspheres. The primary outcome measure was probing depth reduction at 9 months. Clinical assessments were performed at baseline and 1, 3, 6, and 9 months. RESULTS: Minocycline microspheres plus scaling and root planing provided substantially more probing depth reduction than either SRP alone or SRP plus vehicle. The difference reached statistical significance after the first month and was maintained throughout the trial. The improved outcome was observed to be independent of patients' smoking status, age, gender, or baseline disease level. There was no difference in the incidence of adverse effects among treatment groups. CONCLUSIONS: Scaling and root planing plus minocycline microspheres is more effective than scaling and root planing alone in reducing probing depths in periodontitis patients.

Correlation of peri-implant health and aspartate aminotransferase levels: a cross-sectional clinical study.

At present, there are no diagnostic tools that permit early detection of peri-implantitis. The purpose of this cross-sectional study was to evaluate the correlation of aspartate aminotransferase (AST) levels with traditional periodontal clinical parameters around dental implants, since AST has been associated with destruction of cardiac, hepatic, and periodontal tissues. Twenty healthy volunteers with 59 implants were recruited from the Harvard School of Dental Medicine clinics. Clinical parameters evaluated included: AST level, probing depth (mm), Gingival Index (0, 1, 2, or 3), and bleeding on probing (0 or 1). Utilizing the site or implant as the unit of measure, the authors found a statistically significant association of increased AST activity with positive bleeding on probing, increased probing depth, and increased Gingival Index. No statistical correlations were found between clinical indices and increased AST levels when the results were examined on an individual patient basis. This cross-sectional study was able to demonstrate a statistical correlation between diseased clinical periodontal parameters and elevated AST levels.

Human histologic evaluation of bioactive ceramic in the treatment of periodontal osseous defects.

This study examined the healing of intrabony defects around 5 teeth treated with bioactive glass ceramic (PerioGlas). Healing was evaluated by clinical measurements, radiographic observation, and histologic analysis. The protocol included a presurgical phase of scaling and root planing therapy, with measurements obtained immediately prior to the surgical procedures and after 6 months of healing. Following therapy there was a mean of 2.7 mm of probing depth reduction, 2.2 mm of clinical attachment gain, and 0.5 mm of recession. The histologic analysis revealed healing by a long junctional epithelium with minimal new connective tissue attachment to the teeth, except in one case where the intrabony region demonstrated new cementum formation and new connective tissue attachment. Graft particles were found to be biocompatible, as evidenced by being embedded in a stroma of dense connective tissue with minimal inflammatory infiltrate. There was minimal new bone formation limited to the most apical borders of the defects. No signs of periodontal regeneration as defined by new cementum, periodontal ligament, and bone formation on a previously diseased root surface were observed. Although the clinical results are encouraging and radiographs evidenced radiopacities within the defects, histologic analysis revealed that as a periodontal grafting material, bioactive glass ceramic has only limited regenerative properties.

Assessment and management of periodontal infections: a medical-surgical approach.

Over the last 30 years, significant advances have been achieved in elucidating the etiology, pathogenesis, and treatment of periodontal diseases. A new paradigm has emerged that includes the initiation of disease by specific bacteria within a biofilm that stimulate an immunoinflammatory host response, resulting in host tissue destruction. Disease modifiers, which may be of genetic, environmental, or acquired origin, have been recognized as major determinants of disease severity and progression. Current treatment protocols include an assessment of risk factors to identify an individual's degree of susceptibility and therapeutic responsiveness. Basic and clinical research has resulted in the development of several strategies to identify specific bacteria and host-derived markers associated with disease progression. Preventive and therapeutic antimicrobial therapies, which use various delivery systems, have been devised to target drug placement to the infection site. More recently, host modulatory therapies have been created that inhibit disease progression through the reduction of inflammatory mediators. Finally, biological mediators, including growth and differentiation factors, have been used to enhance an individual's healing potential to achieve periodontal and bone regeneration. A combined medical-surgical approach is indicated for these new methods of diagnosis, prevention, and treatment of periodontal diseases, which will allow for earlier treatment interventions and improved patient outcomes.

Current periodontal plastic procedures around teeth and dental implants.

Periodontal plastic procedures are performed to prevent or correct anatomical, developmental, traumatic or plaque-induced defects of the gingiva, alveolar mucosa or bone. The majority of these procedures are performed in combination with restorative and/or orthodontic therapy, with the primary goal of enhancing esthetics. In this review, some of the more prominent techniques currently available to address mucogingival deficiencies, including pedicle grafts, free soft tissue grafts and combination grafts, are illustrated. In addition, potential complications associated with periodontal plastic procedures will be discussed.

Periodontal cosmetic surgery.

Periodontal plastic procedures are performed to prevent or correct anatomical, developmental, traumatic, or plaque induced defects of the gingiva, alveolar mucosa, or bone. The majority of these procedures are performed in combination with restorative and/or orthodontic therapy with the primary goal of enhancing aesthetics. In this review some of the more prominent techniques currently available to address mucogingival deficiencies including pedicle grafts, free soft tissue grafts, and combination grafts are illustrated. In addition, potential complications associated with periodontal plastic procedures are discussed.

The effect of different diagnostic thresholds on incidence of disease progression.

Detection of periodontal disease progression occurs when a predetermined threshold of attachment loss is exceeded during longitudinal monitoring. The incidence of disease progression in a population may be dependent on the method and threshold utilized to identify significant changes in attachment level measurements. The aim of this study was to investigate the effect of utilizing different methods and thresholds on the incidence of disease progression in an untreated periodontitis population. The relationship between baseline clinical parameters and disease progression was also examined. A total of 411 interproximal sites in 46 individuals were monitored monthly over a 6-month period. Disease progression was determined by the cumulative sum (CUSUM) method and by the absolute change in relative attachment level between months 0 and 6 utilizing 3 different thresholds for attachment level change (0.58 mm, 1.16 mm, and 1.74 mm) based upon examiner repeatability using an automated probe. Utilizing the CUSUM method, 49 of 411 sites (11.9%) demonstrated attachment loss over the 6-month observation period. When attachment level changes > or = 0.58 mm, > or = 1.16 mm, and > or = 1.74 mm were used to identify disease progression, the percentage of sites exhibiting deterioration were 19.5%, 8.8%, and 2.9%, respectively. These results demonstrate that the apparent incidence of disease progression was dependent on the method and threshold utilized to detect progressive sites. When utilizing the CUSUM and 0.58 mm thresholds a significant (P < 0.05), but weak relationship (r = -0.26) was observed between baseline relative attachment level measurements and sites exhibiting disease progression. This finding suggests that sites with significant but relatively less attachment loss may be more likely to experience further breakdown compared to sites with a history of greater periodontal destruction.

C-telopeptide pyridinoline cross-links (ICTP) and periodontal pathogens associated with endosseous oral implants.

Detection of periodontal or peri-implant sites exhibiting progressing disease or those at risk of deterioration has proven difficult. Pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), a marker specific for bone degradation found in gingival crevicular fluid (GCF), has been associated with both bone and attachment loss in periodontitis and may be useful for predicting disease activity. The aim of this cross-sectional study was to examine the relationship between ICTP levels and subgingival species around implants and teeth from 20 partially and 2 fully edentulous patients. GCF and plaque samples were collected from the mesiobuccal site of each implant and tooth. Radioimmunoassay techniques were utilized to determine GCF ICTP levels. Plaque samples were analyzed utilizing checkerboard DNA-DNA hybridization. Traditional clinical parameters were assessed. Seventy-one implants and 370 teeth from 22 subjects were examined. ICTP levels and subgingival plaque composition were not significantly different between implants and teeth. Implant sites colonized by Prevotella intermedia, Capnocytophaga gingivalis, Fusobacterium nucleatum ss vincentii, and Streptococcus gordonii exhibited odds ratios of 12.4, 9.3, 8.1, and 6.7, respectively of detecting ICTP. These results suggest a relationship between elevated ICTP levels at implant sites and some species associated with disease progression. Longitudinal studies are necessary to determine whether elevated ICTP levels may predict the development of peri-implant bone loss.

Enantiospecific inhibition of ligature-induced periodontitis in beagles with topical (S)-ketoprofen.

Systemic and topical administration of non-steroidal anti-inflammatory drugs (NSAIDs) has been shown to reduce periodontal disease progression in both animal models and human subjects. Our present research focuses on single enantiomers of these agents to examine whether enantiospecific therapy will be efficacious in slowing periodontitis. The purpose of this study was to evaluate the inhibitory effects of (S)-ketoprofen on experimentally induced alveolar bone loss in beagle dogs. 16, 18-month-old, female beagles were brought to optimal periodontal health over a 2-week pretreatment period. Experimental periodontitis was then induced by placing silk ligatures around premolar and molar teeth and by instituting a soft, plaque-promoting diet. At baseline, animals were randomized to 1 of 4 groups, consisting of 2x daily administration of (1) placebo dentifrice, (2) 0.3% (S)-ketoprofen dentifrice, (3) 3.0% (S)-ketoprofen dentifrice, or (4) 10.0 mg (S)-ketoprofen capsules (p.o.) over a 60 day treatment period. Standardized, periapical radiographs exposed at days 1 and 60 were analyzed by computer-assisted digital radiography in order to assess the rate of alveolar bone loss. Secondary outcomes included technetium 99m-tin-diphosphonate (99mTc-Sn-MDP) uptake and the gingival index. At baseline, no differences were observed among the groups for linear bone height or 99mTc-Sn-MDP uptake ratios. From days 1 to 60, cohorts differed significantly in terms of bone loss rates (p < 0.001). In particular, beagles treated with systemic or topical (S)-ketoprofen (0.3% or 3.0% dentifrices) exhibited significantly lower mean rates of bone loss compared to placebo treated beagles (p < 0.05). Group differences in mean radiopharmaceutical uptake ratio changes approached significance (ANOVA, p = 0.07), where animals treated with topical 0.3% (S)-ketoprofen demonstrated a reduction and other groups demonstrated elevations over the 60-day dosing period. Treatment cohorts did differ significantly with respect to changes in mean gingival indices (p < 0.05). Animals treated with 0.3% or 3.0% (S)-ketoprofen dentifrice exhibited significantly reduced elevations in gingival index scores as compared to placebo treated animals. These data provide evidence that enantiospecific therapy with (S)-ketoprofen, topically or systemically delivered, may alter the progression of periodontal disease in the beagle dog model.

Comparison of manual and automated probing in an untreated periodontitis population.

Diagnosis of periodontal disease progression involves recording two probing attachment level measurements over an adequate time interval. A diagnostic instrument which exhibits less measurement variability allows for increased sensitivity and earlier disease detection. Traditionally, a manual probe with an occlusal stent of the cementoenamel junction (CEJ) as a reference landmark has been the method of choice. Automated probes that use an occlusal disk as the reference landmark have been developed as an alternative means of measure. The aim of this study was to compare the variability of these two probing methods. Four hundred eleven (411) interproximal sites in 46 untreated periodontitis patients were monitored by a single examiner over a 6-month period. Each site was measured on a monthly basis, first with an automated probe (AP) followed by a manual probe (MP) in combination with a custom-fabricated acrylic stent. Measurement variability of the two probing methods was also compared over a 7-day interval. The AP measurements were significantly more variable than the MP measurements (P < 0.001) when considering the variability between two passes at the same visit. Over the 6-month period, the MP measurements demonstrated significantly more variability than the AP measurements (P < 0.001). It was also noted that MP measurements exhibited more variability at sites with frequent bleeding during the 6 months of the study (P = 0.006). The results of this study demonstrate that AP may have less variability of attachment level measurements over a 6-month period and may be less influenced by local inflammatory changes. However, future comparison studies should include multiple examiners to reduce examiner bias and should alternate the probing method to reduce bias created by local tissue changes from multiple probings.