To evaluate the efficacy of a slow release doxycycline gel (SRD) adjunctively administered to non-surgical therapy in subjects with recurrent or persistent periodontitis but acceptable oral hygiene during supportive periodontal care.
In this single blind, parallel group, multicenter study, 202 out of 203 recruited periodontal maintenance subjects with recurrent or persistent periodontitis were randomly assigned to subgingival ultrasonic/sonic instrumentation (USI) with (test) or without (control) subsequent administration of SRD in all residual periodontal pockets ≥ 4mm. Intergroup differences in probing depth, BOP reductions, treatment time, probing attachment levels were evaluated at 3, 6 and 12 months. The primary outcome was the inter-group difference in absolute change of probing pocket depth (PPD) 3, 6 and 12 months after intervention.
At baseline, the two groups were comparable. At 3 months, the test group showed a significantly higher decrease in mean probing depth than the control group at 3 months (mean difference = 0.11 mm, 95% CI 0.03 to 0.19 mm, P=0.003). Administration of SRD resulted in significantly greater odds of transition of bleeding pockets ≥ 5 mm to a category of non bleeding sites with PPD ≤ 4 mm at 3 and 6 months (O.R. =1.4, 95% CI 1.2-1.8 at 3 months). At 6 months, SRD benefit was observed only in the deeper pockets. 7.5% of subjects (no significant difference between test and control) showed disease progression (attachment loss ≥ 2 mm) and were exited from the study. No difference in the incidence of adverse events was observed between groups.
The trial results show that topically administered SRD may provide short-term benefit in controlling inflammation and deep pockets in treated periodontal patients participating in a secondary prevention programme and able to maintain a satisfactory level of oral hygiene.
© 2012 John Wiley & Sons A/S
Although a previous study reported that recombinant human growth/differentiation factor-5 (rhGDF-5) coated onto a β-tricalciumphosphate (β-TCP) significantly enhanced periodontal regeneration, the long-term stability/maturation of the regenerated tissues has not been demonstrated. The objective of this study was to evaluate periodontal regeneration/maturation following application of rhGDF-5/β-TCP using an established periodontal defect model and a 24-week healing interval.
Unilateral, surgically created, 4 x 4 x 5 mm (length x width x height), one-wall, critical-size, intrabony periodontal defects at the mandibular 2nd and 4th premolar teeth in 5 young adult Beagle dogs received rhGDF-5/β-TCP. Bilateral sites at the 4th premolar in the other 4 dogs served as pristine controls receiving mucogingival flap surgery without defect induction. The animals were euthanized at 24 weeks for histological analysis. Unpublished data from the previous 8-week study was used to compare tissue maturation between 8 and 24 weeks.
Linear histometric observations of cementum and alveolar regeneration showed no significant differences between the 8- and 24-week observation intervals. However, parameters of periodontal tissue maturation showed significant differences between the observation intervals including increased fraction mineralized tissue and lamellar bone (p<0.05) and decreased osteocyte counts (p<0.05) at 24 compared with 8 weeks. Although the count inserting Sharpey's fiber did not significantly change, regenerated cementum remote from the intact periodontal ligament appeared more highly mineralized and thicker at 24 compared with 8 weeks, and compared with the pristine cementum. Minimal β-TCP remained.
These 24-week observations suggest that regenerated periodontal tissues in sites receiving rhGDF-5/ß-TCP undergo progressive maturation without debilitating aberrant tissue reactions.
© 2012 John Wiley & Sons A/S
Comparison of regenerative therapy of infrabony defects with and without administration of postsurgical systemic doxycycline.
In each of 61 patients one infrabony defect was treated with enamel matrix derivative [EMD], EMD plus filler or membrane at 2 centres. By random assignment patients received either 200 mg doxycycline per day (DOXY) or placebo (PLAC) for 7 days after surgery. Prior to and 6 months after surgery probing depths (PPD) and vertical attachment level (PAL-V) were obtained.
54 patients (DOXY: 27; PLAC: 27) were re-examined after 6 months and had been treated exclusively with EMD. Seven to 8 days after surgery 81% of defects in both groups showed complete flap closure. In both groups significant (p < 0.001) PPD reduction (DOXY: 3.87±1.20 mm; PLAC: 3.67±1.30 mm) and PAL-V gain (DOXY: 3.11±1.23 mm; PLAC: 3.32±1.83 mm) were observed. However, the differences failed to be statistically significant (PPD: 0.20; p = 0.588; PAL-V: 0.21; p = 0.657).
200 mg systemic doxycycline administered for 7 days after therapy of infrabony defects with EMD failed to result in better PPD reduction and PAL-V gain compared to placebo which may be due to low power (50%) and, thus, random chance.
© 2012 John Wiley & Sons A/S
This study aimed to evaluate, histomorphometrically, the use of periodontal ligament cells (PDL cells) in the treatment of class III furcation defects.
PDL cells were obtained from the mandibular tooth extracted from each dog (7), cultured in vitro and phenotypically characterized. Bilateral class III furcation defects were created at mandibular 3th and 4th premolars and were randomly assigned to: Control Group: coronally positioned flap, GTR Group: GTR, Sponge Group: carrier + GTR, Cell Group: carrier + PDL cells + GTR.
After three months of healing, data analysis demonstrated that the Cell Group presented a superior length of new cementum (4.82 ± 0.61 mm; 3.66 ± 0.95 mm; 2.87 ± 0.74 mm and 1.70 ± 0.60 mm, p<0.001), a greater extension of periodontal regeneration (3.43 ± 1.44 mm; 2.33 ± 0.95 mm; 1.52 ± 0.39 mm and 0.69 ± 0.59 mm, p=0.001) and a larger area of new bone (5.45 ± 1.58 mm2; 3.94 ± 1.52 mm2; 2.91 ± 0.56 mm2 and 1.89 ± 0.95 mm2, p=0.0012), when compared with Sponge, GTR and Control Group, respectively.
PDL cells in association with GTR may significantly promote periodontal regeneration in class III furcation defects surgically created in dogs.
© 2012 John Wiley & Sons A/S
To assess clinical and microbiological outcomes of an Er:YAG laser in comparison with sonic debridement in the treatment of persistent periodontal pockets in a prospective randomized controlled multicenter study design.
A total of 78 patients in supportive periodontal therapy with two residual pockets were included, 58 were available for the whole follow-up period. Root surfaces were instrumented either with a sonic scaler (Sonicflex® 2003 L) or with an Er:YAG laser (KEY Laser® 3). Clinical attachment levels (CAL), probing depths (PD), plaque (PCR) and bleeding on probing (BOP) were assessed at baseline, 13 and 26 weeks after treatment. Additionally, microbiological analysis was performed employing a DNA diagnostic test kit (micro-IDent® Plus).
PD and CAL were significantly reduced in both groups over time (p<0.05), without significant differences between the groups (p>0.05). BOP frequency values decreased significantly within both groups (p<0.05), with no difference between the laser and the sonic treatment (p>0.05). Plaque (PCR) frequency values did not change during the observation period (p>0.05). Microbiological analysis failed to expose any significant difference based on treatment group or period.
Employing both sonic and laser treatment procedures during supportive periodontal care, similar clinical and microbiological outcomes can be expected.
© 2012 John Wiley & Sons A/S
Although it is established that peri-implantitis is a bacterially induced disease, little is known about the bacterial profile of peri-implant communities in health and disease. The purpose of the present investigation was to examine the microbial signatures of the peri-implant microbiome in health and disease.
Subgingival and submucosal plaque samples were collected from forty subjects with periodontitis, peri-implantitis, periodontal and peri-implant health and analyzed using 16S pyrosequencing.
Peri-implant biofilms demonstrated significantly lower diversity than subgingival biofilms in both health and disease, however, several species, including previously unsuspected and unknown organisms, were unique to this niche. The predominant species in peri-implant communities belonged to the genera Butyrivibrio, Campylobacter, Eubacterium, Prevotella, Selenomonas, Streptococcus, Actinomyces, Leptotrichia, Propionibacterium, Peptococcus, Lactococcus and Treponema. Peri-implant disease was associated with lower levels of Prevotella and Leptotrichia and higher levels of Actinomyces, Peptococcus, Campylobacter, non-mutans Streptococcus, Butyrivibrio, and Streptococcus mutans than healthy implants. These communities also demonstrated lower levels of Prevotella, non-mutans Streptococcus, Lactobacillus, Selenomonas, Leptotrichia, Actinomyces and higher levels of Peptococcus, Mycoplasma, Eubacterium, Campylobacter, Butyrivibrio, Streptococcus mutans, and Treponema when compared to periodontitis-associated biofilms.
The peri-implant microbiome differs significantly from the periodontal community in both health and disease. Peri-implantitis is a microbially heterogeneous infection with predominantly gram-negative species, and is less complex than periodontitis
© 2012 John Wiley & Sons A/S
This study evaluated the effects of surgical (SD) and non-surgical (NSD) debridements, associated with systemic antimicrobials, on clinical and immunological outcomes of residual pockets [RP; probing depth (PD) ≥5 mm with bleeding on probing] in type 2 diabetics.
A split-mouth, randomized controlled trial was conducted in 21 subjects presenting at least two RP per contralateral quadrant. Subjects received metronidazole plus amoxicillin for 10 days and, contralateral quadrants were assigned to receive SD or NSD. Clinical parameters and local levels of interferon-γ, interleukin (IL)-17, IL-23 and IL-4 were assessed at baseline, 3 and 6 months post-therapies.
Overall, the mean number, PD and clinical attachment level (CAL) of RP improved significantly after therapies (p < 0.05), without differences between groups at any time-point (p > 0.05). At quadrant level, only SD produced significant reductions in the mean CAL. Also, SD promoted higher reduction in PD from baseline to 6 months than NSD (p < 0.05). Levels of all cytokines were increased after SD compared with NSD (p < 0.05).
SD and NSD associated with systemic antimicrobials did not differ in terms of clinical benefits for RP in diabetics up to 6 months post-therapies. RP treated by SD presented increased levels of cytokines.
To investigate the association between the use of oral bisphosphonate therapy and dental implant failure.
The case–control study involved 337 female patients, aged 40 years and older, who had 1181 implants placed at the Department of Periodontology and Implant Dentistry at New York University College of Dentistry between January 1997 and December 2004. Cases, defined as women with one or more implant failures, were identified from the departmental database. Controls were then randomly selected for each case. Adjusted odds ratios were estimated using logistic regression models fitted through generalized estimating equations.
After adjusting for selected covariates, the odds of oral bisphosphonate use was 2.69 (95% confidence interval [CI], 1.49–4.86) times higher in women for whom implants failed compared with those for whom implants did not fail. Although no significant interaction was observed (p = 0.41), the stratified analyses suggest that the association between oral bisphosphonate use and dental implant failure was stronger in the maxilla (Odds Ratio [OR] = 2.60; 95% CI, 1.36–4.96) than in the mandible (OR = 1.38; 95% CI, 0.51–3.73).
Findings from this study suggest that dental practitioners should be aware of the increased risk of implant failure associated with oral bisphosphonate use in the population.
Current literature on chronic periodontitis genetics encompasses numerous single nucleotide polymorphisms-focused case–control studies with inconsistent and controversial results, which typically disregards the exposure concept embraced by case–control definition. Herein, we propose a case–control design reappraisal by clear phenotype selection, where chronic gingivitis represents a genetically resistant phenotype/genotype opposing the susceptible cohort.
The hypothesis was tested in healthy, chronic periodontitis and gingivitis groups through Real-time PCR-based allelic discrimination of classic variants IL1B-3954, IL6-174, TNFA-308, IL10-592 and TLR4-299.
Observed allele/genotype frequencies characterize the healthy group with an intermediate genetic profile between periodontitis and gingivitis cohorts. When comparing genotype/allele frequencies in periodontitis versus healthy and periodontitis versus gingivitis scenarios, the number of positive associations (2–4) and the degree of association (p and odds ratio values) were significantly increased by the new approach proposed (periodontitis versus gingivitis), suggesting the association of IL1B-3954, TNFA-308, IL10-592 and TLR4-299 with periodontitis risk. Power study was also significantly improved by the new study design proposed when compared to the traditional approach.
The data presented herein support the use of new case–control study design based on the case–control definition and clear resistance/susceptibility phenotypes selection, which can significantly impact the study power and odds of identification of genetic factors involved in PD.
Treatment regimens, which predictably support re-osseointegration of implants with peri-implantitis, are needed. Increased wettability may be an important factor for re-osseointegration. In this study, a cold atmospheric pressure gas-discharge plasma was applied to reduce water contact angles on titanium discs with different surface topography and to improve the spreading of osteoblastic cells.
An argon plasma jet with different oxygen admixtures was used to treat titanium discs with different topologies, i.e. machined, SLA®, SLActive®, diamond bur-treated or Airflow®-treated. Water contact angles were measured before and after plasma treatment. The spreading behaviour of human osteoblastic cells was investigated.
Contact angle of titanium discs (baseline values: 68°–117°) were significantly reduced close to 0° irrespective of surface topography after the application of argon plasma with 1.0% oxygen admixture for 60 s or 120 s. The cell size of osteoblastic cells grown on argon-oxygen-plasma-treated titanium discs was significantly larger than on non-treated surfaces (p < 0.001) irrespective of surface topography.
Plasma treatment reduced contact angle and supported spreading of osteoblastic cells. The application of cold plasma may be supportive in the treatment of peri-implant lesions and may improve the process of re-osseointegration.
To characterize the histologic and cellular response to A. actinomycetemcomitans (Aa) infection.
Wistar rats infected with Aa were evaluated for antibody response, oral Aa colonization, loss of attachment, PMN recruitment, TNF-α in the junctional epithelium and connective tissue, osteoclasts and adaptive immune response in local lymph nodes at baseline and 4, 5 or 6 weeks after infection. Some groups were given antibacterial treatment at 4 weeks.
An antibody response against Aa occurred within 4 weeks of infection, and 78% of inoculated rats had detectable Aa in the oral cavity (p < 0.05). Aa infection significantly increased loss of attachment that was reversed by antibacterial treatment (p < 0.05). TNF-α expression in the junctional epithelium followed the same pattern. Aa stimulated high osteoclast formation and TNF-α expression in the connective tissue (p < 0.05). PMN recruitment significantly increased after Aa infection (p < 0.05). Aa also increased the number of CD8+T cells (p < 0.05), but not CD4+T cells or regulatory T cells (Tregs) (p > 0.05).
Aa infection stimulated a local response that increased numbers of PMNs and TNF-α expression in the junctional epithelium and loss of attachment. Both TNF-α expression in JE and loss of attachment was reversed by antibiotic treatment. Aa infection also increased TNF-α in the connective tissue, osteoclast numbers and CD8+T cells in lymph nodes. The results link Aa infection with important characteristics of periodontal destruction.
This study was undertaken to investigate the existence of a periodontopathic bacterium, Fusobacterium nucleatum, in chorionic tissues of pregnant women, and the effects of F. nucleatum on human chorion-derived cells.
Oral and chorionic tissue samples were collected from 24 high-risk pregnant women and 15 normal pregnant women. The presence of F. nucleatum in the samples was detected using polymerase chain reaction. Chorion-derived cells and Toll-like receptor (TLR)-2 or TLR-4 gene-silenced chorion-derived cells were stimulated with F. nucleatum lipopolysaccharide (LPS). Interleukin (IL)-6 and corticotrophin-releasing hormone (CRH) levels in the culture supernatants were measured using ELISA.
F. nucleatum was detected in all oral samples and seven chorionic tissues from the high-risk pregnant women, but was not detected in chorionic tissues from the normal pregnant women. F. nucleatum LPS significantly increased IL-6 and CRH secretion by chorion-derived cells. The F. nucleatum LPS-induced IL-6 and CRH levels were significantly reduced in TLR-2 or TLR-4 gene-silenced chorion-derived cells.
We suggest that F. nucleatum is detected in chorionic tissues of high-risk pregnant women, but not in chorionic tissues of normal pregnant women, and that F. nucleatum induces IL-6 and CRH production via both TLR-2 and TLR-4 in chorion-derived cells.
The aim of this randomized controlled clinical study was to compare the use of an acellular dermal matrix graft (ADMG) with or without the enamel matrix derivative (EMD) in smokers to evaluate which procedure would provide better root coverage.
Nineteen smokers with bilateral Miller Class I or II gingival recessions ≥3 mm were selected. The test group was treated with an association of ADMG and EMD, and the control group with ADMG alone. Probing depth, relative clinical attachment level, gingival recession height, gingival recession width, keratinized tissue width and keratinized tissue thickness were evaluated before the surgeries and after 6 months. Wilcoxon test was used for the statistical analysis at significance level of 5%.
No significant differences were found between groups in all parameters at baseline. The mean gain recession height between baseline and 6 months and the complete root coverage favored the test group (p = 0.042, p = 0.019 respectively).
Smoking may negatively affect the results achieved through periodontal plastic procedures; however, the association of ADMG and EMD is beneficial in the root coverage of gingival recessions in smokers, 6 months after the surgery.
To evaluate the associations of serum 25-Hydroxyvitamin D [25(OH)D] levels with periodontal health and chronic obstructive pulmonary disease (COPD).
We conducted a case–control study of 193 COPD patients and 181 controls. Their periodontal status and lung function were examined, and serum 25(OH)D levels were measured.
Mean serum 25(OH)D concentrations were significantly lower in the COPD group than in the controls (32.1 versus 35.8 nmol/l; p = 0.002). Serum 25(OH)D concentrations were positively correlated with lung function among non-smokers and negatively correlated with plaque index (PLI) among former smokers. After adjustment for age, gender, body mass index, season and smoking status, periodontal indexes were significantly associated with serum 25(OH)D concentrations (number of remaining teeth among all groups; probing depth, clinical attachment level, bleeding index, PLI and alveolar bone loss among COPD group). Lower serum 25(OH)D concentrations were significantly associated with an increased risk of COPD among former smokers (Odd ratio 4.11; 95% confidence interval 1.47–11.5; p = 0.007) after adjustment for periodontal indexes and other variables.
Lower serum 25(OH)D concentrations were significantly associated with poor periodontal health and an increased risk of COPD.
To evaluate the impact of herpesvirus type-1 and -2 on the clinical outcomes of periodontal regenerative procedures in isolated deep intrabony pockets, in an experimental population with no detectable periodontal pathogens.
Seventeen periodontal intraosseous defects in 17 moderate-to-advanced periodontitis patients were treated with regenerative therapy and amelogenins. Microbiological evaluation was performed at baseline (after the completion of initial therapy) and at 1 year to exclude the presence of periodontal pathogens. Herpesviruses-1 and -2 DNA were quantified in the pocket tissues associated to the intrabony defect using molecular assays. Clinical attachment level (CAL), probing pocket depth (PPD) and gingival recession (REC) were recorded at baseline and at 1 year.
After 1 year, the 17 defects resulted in significant CAL gain, PPD reduction and REC increase. HSV-1 was detected in five patients. Herpesvirus-2 was never found. The two subpopulations positive or negative to herpesvirus-1 were homogeneous at baseline. At 1 year, the five herpesvirus-1 positive patients resulted in lower amounts of CAL-gain and PPD reduction and greater amount of REC with respect to the 12 herpesvirus-1 negative patients.
The presence of herpesvirus-1 at baseline is associated with poor clinical outcomes following regenerative therapy.
Periodontal disease is highly prevalent and severe in diabetic patients, and is considered one of the diabetic complications. To elucidate how periodontitis progresses in diabetes, we examined an animal model of periodontitis in diabetic rats.
Two weeks after the induction of diabetes by streptozotocin, surgical nylon thread was ligated around the cervical portion of the unilateral maxillary second molar to induce periodontitis. Periodontitis was evaluated 2 weeks after the ligation by gingival blood flow, mRNA expressions, Western blot analysis, histological examination and micro CT.
Ligation-induced severe periodontitis in the diabetic rats, which was apparently shown by the increase of TNF-α and iNOS mRNA expressions and inflammatory cell infiltration in the gingiva and alveolar bone loss. The number of nitrotyrosine, a footprint of nitrosative stress, -positive cells was significantly higher in the periodontitis of the diabetic rats compared with that in the normal rats. Western blot analysis confirmed that the nitrotyrosine was increased in the periodontitis of the diabetic rats.
This is the first study to confirm increased nitrosative stress due to periodontitis in diabetic rats. Nitrosative stress may play a crucial role in the exacerbation of periodontitis in diabetic patients.
Involvement of TLR2 in the pathophysiology of periodontitis has widely been discussed, but hitherto, no validated genetic associations were reported. Previous association studies lacked sufficient statistical power and adequate haplotype information to draw unambiguous conclusions. The aim of this study was to comprehensively investigate TLR2 linkage disequilibrium (LD) regions for their potential associations with periodontitis in two large analysis populations of aggressive (AgP) and chronic periodontitis (CP) of North West European descent.
The study population comprised 598 AgP patients, 914 CP patients and 1804 healthy controls. Analysis of TLR2 LD regions was performed with haplotype tagging SNPs (tagSNPs) using SNPlex and TaqMan genotyping assays. Genotypic, dominant, multiplicative, and recessive genetic models were tested. The genotypes were adjusted for the covariates smoking, diabetes, and gender. Resequencing was performed by Sanger technology.
Upon covariate adjustment and correction for multiple testing, no tagSNPs showed significant associations with AgP or CP. Targeted resequencing of exon 3 in 47 AgP cases identified carriership of two common and three rare variants.
Common LD regions of TLR2 do not show genetic associations with periodontitis in the North West European population. Resequencing of exon 3 could not identify disease-associated rare variants in TLR2.
To identify possible novel biomarkers in gingival crevicular fluid (GCF) samples from chronic periodontitis (CP) and periodontally healthy individuals using high-throughput proteomic analysis.
Gingival crevicular fluid samples were collected from 12 CP and 12 periodontally healthy subjects. Samples were trypically digested with trypsin, eluted using high-performance liquid chromatography, and fragmented using tandem mass spectrometry (MS/MS). MS/MS spectra were analysed using PILOT_PROTEIN to identify all unmodified proteins within the samples.
Using the database derived from Homo sapiens taxonomy and all bacterial taxonomies, 432 human (120 new) and 30 bacterial proteins were identified. The human proteins, angiotensinogen, clusterin and thymidine phosphorylase were identified as biomarker candidates based on their high-scoring only in samples from periodontal health. Similarly, neutrophil defensin-1, carbonic anhydrase-1 and elongation factor-1 gamma were associated with CP. Candidate bacterial biomarkers include 33 kDa chaperonin, iron uptake protein A2 and phosphoenolpyruvate carboxylase (health-associated) and ribulose biphosphate carboxylase, a probable succinyl-CoA:3-ketoacid-coenzyme A transferase, or DNA-directed RNA polymerase subunit beta (CP-associated). Most of these human and bacterial proteins have not been previously evaluated as biomarkers of periodontal conditions and require further investigation.
The proposed methods for large-scale comprehensive proteomic analysis may lead to the identification of novel biomarkers of periodontal health or disease.
The aim of this study was to investigate the robustness of the observations on the influence of oral hygiene, gingival and periodontal status on the development of bacteraemia from everyday oral activities (B-EOA), analysing its prevalence, duration, magnitude and bacterial diversity.
This systematic review/meta-analysis complies with PRISMA reporting guidelines. MEDLINE-PubMed, the Cochrane Library and Embase were explored for detecting studies on B-EOA.
There were 290 potentially eligible articles, of which 12 article on B-EOA fulfilled the inclusion criteria and were processed for data extraction (seven on toothbrushing, one on dental flossing and four on chewing). Evaluating the influence of plaque and gingival indices on the prevalence of bacteraemia following toothbrushing, the pooled odds ratios were 2.61 [95% confidence interval (CI) = 1.45–4.69] and 2.77 (95% CI = 1.50–5.11), respectively. None of five studies on bacteraemia following dental flossing and chewing revealed a statistically significant association between oral hygiene, gingival or periodontal status and the development of bacteraemia.
Meta-analysis showed that plaque accumulation and gingival inflammation scores significantly increased the prevalence of bacteraemia following toothbrushing. However, systematic review showed no relationship between oral hygiene, gingival and periodontal status and the development of B-chewing, and there is no evidence that gingival and periodontal health status affects B-flossing.
To determine whether periodontitis and three prominent members of the periodontal flora are associated with the development of preeclampsia (hypertension plus proteinuria)
The samples were composed of 127 systemically healthy women. Within 5 days after labour, clinical periodontal parameters and Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia in subgingival plaque were evaluated. Maternal serum IgG antibody specific for each bacteria was determined by enzyme-linked immunosorbent assay. Multivariate logistic regression analysis was used to control for confounders (maternal age, body mass index before pregnancy, parity, and smoking).
Eighteen women were affected with preeclampsia. The number of A.actinomycetemcomitans was shown to be significantly associated with preeclampsia in the logistic regression model (odds ratio; 1.7, 95% confidence interval; 1.1–2.7). There were statistically significant differences between the preeclamptic and control groups in body mass index before pregnancy, pre-term birth and low birthweight (respectively, p = 0.014, p = 0.010 and p < 0.0001). We found no statistically significant association between preeclampsia and periodontal clinical parameters or the presence of periodontitis.
In systemically healthy pregnant women, our findings suggested that the levels of maternal subgingival A. actinomycetemcomitans DNA were elevated in preeclamptic women.
The receptor activator of NF-κB ligand-osteoprotegerin (RANKL-OPG) bi-molecular system is the “bottle-neck” regulator of osteoclastogenesis and bone resorption, both in physiological and pathological conditions. This review aims to elaborate the current knowledge on RANKL and OPG in periodontal disease, and to evaluate their diagnostic and prognostic potential as biomarkers of the disease.
To pursue this aim, electronic and manual searches were performed for identifying clinical and in vivo studies on RANKL and OPG in gingival tissue, gingival crevicular fluid, saliva and blood. Smoking and diabetes mellitus were also considered for their potential effects.
Papers fulfilling the inclusion criteria demonstrate that RANKL is up-regulated, whereas OPG is down-regulated in periodontitis, compared to periodontal health, resulting in an increased RANKL/OPG ratio. This ratio is further up-regulated in smokers and diabetics, and is not affected by conventional periodontal treatment.
The increased RANKL/OPG ratio may serve as a biomarker that denotes the occurrence of periodontitis, but may not necessarily predict on-going disease activity. Its steadily elevated levels post treatment may indicate that the molecular mechanisms of bone resorption are still active, holding an imminent risk for relapse of the disease. Additional adjunct treatment modalities that would “switch-off” the RANKL/OPG ratio may therefore be required.
Although it is known that periodontal matrix metalloproteinase-8 (MMP-8) expression is associated with periodontal disease, the information concerning the periodontal MMP-8 expression in diabetic patients with periodontal disease is insufficient.
Periodontal tissue specimens were collected from seven patients without periodontal disease and diabetes (Group 1), 15 patients with periodontal disease alone (Group 2) and 10 patients with both periodontal disease and diabetes (Group 3). The frozen sections were prepared and MMP-8 protein expression was detected using immunohistochemistry and quantified. For in vitro study, human U937 mononuclear cells were pre-exposed to normal or high glucose and then treated with lipopolysaccharide (LPS).
The nonparametric Kruskal–Wallis test showed that the difference in MMP-8 protein levels among the three groups were statistically significant (p = 0.003). Nonparametric analysis using Jonckheere–Terpstra test showed a tendency of increase in periodontal MMP-8 levels across Group 1 to Group 2 to Group 3 (p = 0.0002). In vitro studies showed that high glucose and LPS had a synergistic effect on MMP-8 expression.
Our current study showed an increasing trend in MMP-8 protein expression levels across patients without both periodontal disease and diabetes, patients with periodontal disease alone and patients with both diseases.
We investigated in subjects with and without periodontitis, the levels of certain salivary proteins and matrix metalloproteinase-8 (MMP-8) in gingival crevicular fluid (GCF), in relation to the presence of specific periodontal pathogens.
Clinical parameters were recorded at baseline, in 1985 and in 2009 from 99 subjects; 56 with and 43 without periodontitis (mean age 59.2 ± SD 2.9). Saliva samples collected in 2009 were analysed for salivary albumin, total protein and immunoglobulins A, G and M. GCF was collected for analysis of MMP-8 levels and for the PCR-analysis of the microorganisms Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Treponema denticola and Tannerella forsythia.
Periodontitis patients were more often infected by P. gingivalis (p < 0.05), P. intermedia and T. denticola (p = 0.01) than controls. Salivary albumin and protein concentrations were significantly higher in subjects with T. denticola (p < 0.05). MMP-8 levels were significantly higher in subjects with T. denticola (p < 0.001) and T. forsythia (p < 0.01). No corresponding results were found in salivary immunoglobulin concentrations.
The presence of T. denticola seemed to increase salivary albumin and total protein concentrations, and GCF levels of MMP-8. Both T. denticola and T. forsythia seemed to induce a cascade of host response with increased MMP-8 in GCF.
Nutrition may be a potential modifying factor in periodontal conditions. The present study investigated this phenomenon for dietary induced hyperparathyroidism (dHPT) by revealing the histopathological and histomorphometrical profiles of healthy and diseased periodontia in dHPT.
Dietary induced hyperparathyroidism was induced in 12 rats by dietary calcium/phosphorous imbalance and 12 rats were fed standard diet (SD). Periodontitis was induced on the right mandibular molar teeth (mmt) of these rats by injecting an endotoxin + saline solution whereas injecting pure saline to the left mmt. Thus, four study groups were created: dHPT + saline (group 1), dHPT + endotoxin (group 2), SD + endotoxin (group 3) and SD + saline (group 4). Histological sections were obtained from the second mmt and examined using light microscope.
Group 1 demonstrated inflammatory and degenerative alterations in periodontium without pocket formation. Periodontitis was evident in groups 2 and 3. Group 2 revealed the highest amounts of gingival inflammatory cell and vessel counts (group 2 > group 3 > group 1 > group 4), attachment and bone losses (group 2 > group 3 > groups 1 > group 4) and osteoclast count (group 2 > group 3 > group 1 > group 4) (p < 0.05).
These results propose that dHPT may impair the health status of periodontium and may worsen the pathobiology of periodontal diseases.
To identify predictor variables involved in exacerbated gingival inflammation associated with pregnancy.
In this cohort study, 48 pregnant and 28 non-pregnant women without periodontitis were included. The pregnant women were evaluated in the first, second and third trimester and at 3 months postpartum, whilst the non-pregnant women were evaluated twice, with a 6-month interval. At each visit, clinical [plaque index (PlI) and gingival index (GI)], hormonal (salivary progesterone and estradiol), immunological [gingival crevicular fluid interleukin-1β, interleukin-6, tumour necrosis factor-α (TNF-α) and prostaglandin-E2] and microbiological (periodontal pathogens culture) evaluations were performed. Statistical analysis was undertaken using exhaustive chi-square automatic interaction detection (exhaustive CHAID) to analyse the predictive value of the independent outcomes to develop pregnancy GI.
PlI was the strongest predictor implicated in the GI throughout pregnancy and after delivery. During the second and third trimesters the presence of Porphyromonas gingivalis significantly contributed to the worsening of gingival inflammation. When compared with the non-pregnant group, significant differences were found in TNF-α amounts and concentrations and in the third trimester site-specific GI.
Bacterial challenge to the gingival tissues, both quantitatively (PlI) and qualitatively (harbouring P. gingivalis) appears to affect the level of gingival inflammation observed during pregnancy.
The present investigation aimed to analyse clinical and microbiological effects of systemic administration of metronidazole and amoxicillin combined with the One-Stage-Full-Mouth-Disinfection protocol (OSFMD) in generalized aggressive periodontitis patients (G-AgP).
Thirty-nine systemically healthy patients with G-AgP were consecutively included. The test group (n = 19) received amoxicillin-metronidazole combination (500 mg of each, three times a day for 7 days) and the OSFMD, the control group (n = 20) received the OSFMD and a placebo. In addition to clinical parameters subgingival plaque samples from moderate (4–5 mm) and deep (≥6 mm) pocket sites were analysed for the presence of Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola using polymerase chain reaction.
Both therapies led to a statistically significant decrease in clinical and microbiological parameters compared to baseline (p < 0.001). The most beneficial changes were observed in the test group which showed significantly greater improvements in probing depth and clinical attachment level and a lower prevalence of Aggregatibacter actinomycetemcomitans, Treponema denticola, and Tannerella forsythia compared to the control one (p < 0.05).
Systemic administration of metronidazole and amoxicillin as an adjunct to OSFMD therapy significantly improved clinical and microbiological outcomes in patients with G-AgP over a 6-month period.
To examine changes in levels of gingival crevicular fluid (GCF) cytokines, after periodontal therapy of generalized aggressive periodontitis (GAgP).
Twenty-five periodontally healthy and 24 GAgP subjects had periodontal clinical parameters measured and gingival crevicular fluid (GCF) samples collected from up to 14 sites/subject. GCF samples were analysed using multiplex bead immunoassay for: GM-CSF, IFN-γ, IL-10, IL-1β, IL-2, IL-6 and TNF-α. Aggressive periodontitis subjects were randomly assigned to either scaling and root planing (SRP) alone or SRP plus systemic amoxicillin (500 mg) and metronidazole (400 mg) 3 times a day for 14 days. Clinical parameters and GCF cytokines were re-measured 6 months after treatment. Differences over time were analysed using the Wilcoxon test and between groups using the Mann-Whitney test.
Significant reductions in GCF GM-CSF, IL-1β and the ratio IL-1β/IL-10 and increases in GCF IL-6 were detected after therapy. The mean change in GCF cytokines did not differ significantly between groups.
Periodontal therapy improved GCF cytokine profiles by lowering IL-1β and increasing IL-10 levels. The reduction in GCF GM-CSF after therapy implicates this cytokine in the pathogenesis of GAgP. There was no difference between therapies in changes of GCF cytokines.
Guided tissue regeneration (GTR) and enamel matrix derivatives (EMD) are two popular regenerative treatments for periodontal infrabony lesions. Both have been used in conjunction with other regenerative materials. We conducted a Bayesian network meta-analysis of randomized controlled trials on treatment effects of GTR, EMD and their combination therapies.
A systematic literature search was conducted using the Medline, EMBASE, LILACS and CENTRAL databases up to and including June 2011. Treatment outcomes were changes in probing pocket depth (PPD), clinical attachment level (CAL) and infrabony defect depth. Different types of bone grafts were treated as one group and so were barrier membranes.
A total of 53 studies were included in this review, and we found small differences between regenerative therapies which were non-significant statistically and clinically. GTR and GTR-related combination therapies achieved greater PPD reduction than EMD and EMD-related combination therapies. Combination therapies achieved slightly greater CAL gain than the use of EMD or GTR alone. GTR with BG achieved greatest defect fill.
Combination therapies performed better than single therapies, but the additional benefits were small. Bayesian network meta-analysis is a promising technique to compare multiple treatments. Further analysis of methodological characteristics will be required prior to clinical recommendations.