Treatment with subantimicrobial dose doxycycline improves the efficacy of scaling and root planing in patients with adult periodontitis

BACKGROUND: In a previous study, subantimicrobial dose doxycycline (SDD) significantly improved clinical parameters associated with periodontal health in patients with adult periodontitis (AP) when used as an adjunct to a maintenance schedule of supragingival scaling and dental prophylaxis. In this double-blind, placebo-controlled, parallel-group, multicenter study, the efficacy and safety of SDD were evaluated in conjunction with scaling and root planing (SRP) in patients with AP. METHODS: Patients (n = 190) received SRP at the baseline visit and were randomized to receive either SDD 20 mg bid or placebo bid for 9 months. Efficacy parameters included the per-patient mean changes in clinical attachment level (CAL) and probing depth (PD) from baseline, the per-patient percentages of tooth sites with attachment loss (AL) > or = 2 mm and > or = 3 mm from baseline, and the per-patient percentage of tooth sites with bleeding on probing. Prior to analysis, tooth sites were stratified by the degree of disease severity evident at baseline RESULTS: In tooth sites with mild to moderate disease and severe disease (n = 183, intent-to-treat population), improvements in CAL and PD were significantly greater with adjunctive SDD than with adjunctive placebo at 3, 6, and 9 months (all P <0.05). In tooth sites with severe disease, the per-patient percentage of sites with AL > or = 2 mm from baseline to month 9 was significantly lower with adjunctive SDD than with adjunctive placebo (P<0.05). Improvements in clinical outcomes occurred without detrimental shifts in the normal periodontal flora or the acquisition of doxycycline resistance or multiantibiotic resistance. SDD was well tolerated, with a low incidence of discontinuations due to adverse events. CONCLUSIONS: The adjunctive use of SDD with SRP is more effective than SRP alone and may represent a new approach in the long-term management of AP.     

Subantimicrobial dose doxycycline enhances the efficacy of scaling and root planing in chronic periodontitis: a multicenter trial

BACKGROUND: Previous studies have shown that subantimicrobial dose doxycycline (SDD) is of clinical benefit in the treatment of chronic periodontitis (CP). The aim of this study was to further assess the role of SDD as an adjunct to scaling and root planing (SRP) in the treatment of CP. METHODS: A double-blind, randomized, placebo-controlled, multicenter clinical study was conducted to test the efficacy of SDD (20 mg doxycycline B.I.D.) in combination with SRP in subjects with moderate to severe CP. Two-hundred ten subjects were treated with a standardized episode of SRP and randomized to receive either adjunctive SDD or placebo for 9 months. Efficacy parameters included per-subject mean changes in clinical attachment level (CAL) and probing depth (PD) from baseline, and the total number of sites with attachment gains and probing depth reductions > or = 2 mm and > or = 3 mm from baseline. RESULTS: In periodontal sites with PD 4 to 6 mm and > or = 7 mm (N = 209, intent-to-treat population), mean improvements in CAL and PD were greater following SRP with adjunctive SDD than SRP with placebo, achieving statistical significance in all baseline disease categories at month 9 (P < 0.05). At month 9, 42.3% of sites in the SDD group demonstrated CAL gain > or = 2 mm compared to 32.0% of sites in the placebo group (P < 0.01). CAL gain > or = 3 mm was seen in 15.4% of sites in the SDD group compared to 10.6% of sites in the placebo group (P < 0.05). When considering the same thresholds of change in PD, 42.9% of sites in the SDD group compared to 31.1% of sites in the placebo group demonstrated PD reduction > or = 2 mm (P < 0.01), and 15.4% of sites in the SDD group compared to 9.1% of sites in the placebo group demonstrated PD reduction > or = 3 mm (P < 0.01). CONCLUSION: Adjunctive subantimicrobial dose doxycycline enhances scaling and root planing. It results in statistically significant attachment gains and probing depth reductions over and above those achieved by scaling and root planing with placebo.     

Effects of sub-antimicrobial dose doxycycline therapy on crevicular fluid MMP-8, and gingival tissue MMP-9, TIMP-1 and IL-6 levels in chronic periodontitis

OBJECTIVE: To investigate whether sub-antimicrobial dose doxycycline (SDD) therapy for 120 d in chronic adult periodontitis patients had significant effects on gingival crevicular fluid (GCF) matrix metalloproteinase-8 (MMP-8) levels, and on gingival tissue MMP-9, tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) and interleukin-6 (IL-6) levels. BACKGROUND: Tetracycline can significantly inhibit MMP activity in GCF and in gingival tissue, even in much lower dosage then a traditional antimicrobial dosage used in conventional therapy. Sub-antimicrobial dose doxycycline (SDD) therapy has been shown to reduce periodontal disease activity to control MMP and pro-inflammatory cytokines. METHODS: A total of 32 patients with incipient to moderate (probing pocket depth approximately 4-7 mm) chronic adult periodontitis were included in the study. Subjects were randomly assigned to two groups. After scaling and root planning (SRP), the SRP + SDD group received SDD, 20 mg bid, whereas the SRP + placebo group received placebo, 20 mg bid. In the follow-up, efficacy measures included the change in probing pocket depth (PD), clinical attachment level (CAL), bleeding on probing (BOP) and gingival crevicular fluid MMP-8 levels, gingival tissue MMP-9, TIMP-1 and IL-6 levels from baseline to 120 d. RESULTS: After 120 d, PD and CAL improved significantly in the SRP + SDD group. Initial MMP-8 levels for the SRP + SDD group and the SRP + placebo group were 407.13 +/- 114.45 ng/ml and 378.71 +/- 189.39 ng/ml, respectively, with no statistical difference between the two groups. MMP-8 levels for the SRP + SDD group and the SRP + placebo group were: 235.35 +/- 134.58 ng/ml and 364.04 +/- 219.27 ng/ml at 30 d; 157.50 +/- 95.95 ng/ml and 236.60 +/- 186.16 ng/ml at 60 d; 102.70 +/- 67.64 ng/ml and 208.56 +/- 124.54 ng/ml at 90 d; and 63.77 +/- 53.33 ng/ml and 229.13 +/- 168.09 ng/ml at 120 d, respectively. The amount of decrease in MMP-8 levels for the SRP + SDD group was statistically significant compared to that for the SRP + placebo group, especially apparent at 120 d (p < 0.05). TIMP-1 levels in both groups increased from the baseline to 120 d with statistical significance (p-value < 0.05), but there was no significant difference between the two groups. Changes in MMP-9 and IL-6 levels were not statistically significant. CONCLUSION: Adjunctive SDD therapy can improve the clinical parameters and this clinical improvement is reflected by controlled level of MMP-8 in chronic adult periodontitis after the therapy.     

Adjunctive subantimicrobial dose doxycycline: effect on clinical parameters and gingival crevicular fluid transforming growth factor-beta levels in severe, generalized chronic periodontitis

BACKGROUND: At present there is limited data concerning the efficacy of non-surgical periodontal therapy supplemented with subantimicrobial dose doxycycline (SDD) in the treatment of severe, generalized periodontitis. The purpose of the present study was to evaluate the effect of adjunctive SDD therapy on clinical periodontal parameters and gingival crevicular fluid (GCF) transforming growth factor-beta1 (TGF-beta1) levels in patients with severe, generalized chronic periodontitis over a 6-month period. METHODS: Thirty-five patients with severe, generalized periodontitis and 11 periodontally healthy subjects were included in the present study. Patients received full-mouth supragingival debridment at baseline and randomized to take either SDD b.i.d. or placebo b.i.d. for 3 months. Patients received root planing and oral hygiene instruction once a week for four consecutive weeks. Clinical measurements including probing depth (PD), clinical attachment level, papilla bleeding index and plaque index and GCF sampling were performed at baseline, 3 and 6 months. The GCF TGF-beta1 levels were analysed by enzyme-linked immunosorbent assay. RESULTS: Thirteen patients in both study groups completed the 6-month trial. Following scaling and root planing (SRP) plus SDD and SRP plus placebo therapy significant improvements in clinical periodontal parameters of both groups were observed (p<0.025). In the SDD group a significantly higher percentage (%73.4) of deep pockets resolved (PD reduction > or =3 mm from baseline) when compared with placebo group (%49.7) at 6 months (p<0.05). At baseline there were no significant differences in GCF TGF-beta1 levels between three groups. Both total amount and concentration of GCF TGF-beta1 in SDD and placebo groups increased when compared with baseline at 3 months. However, only GCF TGF-beta1 levels of SDD group was significantly higher than baseline (p<0.025) and placebo group (p<0.017) at 3 months. At 6 months GCF TGF-beta1 levels of both groups were similar to baseline levels (p<0.025). CONCLUSIONS: These data indicate that combination of SDD with non-surgical therapy improves clinical parameters of periodontal disease and increases GCF TGF-beta1 levels together with a decrease in prevalence of residual pockets in patients with severe, generalized chronic periodontitis. Increased GCF TGF-beta1 levels following SDD therapy might suggest a novell pleiotrophic mechanism for tetracyclines to inhibit connective tissue breakdown.     

Subantimicrobial dose doxycycline as an adjunct to scaling and root planing: post-treatment effects

BACKGROUND/OBJECTIVE: Subantimicrobial dose doxycycline (SDD 20 mg bid) plus scaling and root planing (SRP) significantly improved clinical attachment level (CAL) and reduced probing depth (PD) compared with placebo plus SRP in a double-blind, placebo-controlled, multicenter study of patients with adult periodontitis (AP). In a study conducted as a follow-up, the post-treatment effects of SDD were assessed in patients who completed the SRP study. METHODS: The SRP study was a 9-month, active-treatment study and the follow-up was a 3-month, no-treatment study. In the SRP study, tooth sites in qualifying quadrants were scaled and root planed and patients were randomized to receive twice daily SDD 20 mg or placebo. In the follow-up, patients received no study drug; investigators and patients remained blinded to the previous treatment group assignments. Efficacy measures included the change in CAL and PD from baseline values determined at the start of the SRP study in tooth sites stratified by baseline PD (i.e., 0-3 mm, 4-6 mm, > or =7 mm). Safety was evaluated using adverse event data and the results of clinical laboratory tests, oral pathology examinations, and microbiological assessments. RESULTS: Within each disease stratum, the incremental improvements in PD and CAL demonstrated in the SDD group over 9 months of active treatment were maintained through 3 additional months of no treatment. Treatment cessation did not result in an accelerated regression of periodontal health. No differences in the incidence of adverse events (including those related to infection) or laboratory or microbiological parameters were noted between the SDD group and the placebo group. CONCLUSIONS: The administration of SDD 20 mg bid for a period of up to 9 months is not associated with rebound effects or delayed or negative after-effects for a 3-month period after cessation of therapy.     

Efficacy of short-term adjunctive subantimicrobial dose doxycycline in diabetic patients - randomized study

Oral Diseases (2012) 18 , 763–770 Objective: To investigate the effectiveness of short‐term adjunctive subantimicrobial dose doxycycline (SDD) treatment in patients with diabetes mellitus type 2 and chronic periodontitis (CP). Methods: Thirty‐four patients with CP and type 2 diabetes mellitus were included in the placebo‐controlled, double‐blind study. After scaling and root planing (SRP), patients were randomly assigned to two groups, receiving either SDD or placebo bid for 3 months. The probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), approximal plaque index, glycated hemoglobin (HbA1c) level were recorded and gingival crevicular fluid (GCF) samples were collected at baseline and after 3‐month therapy for the estimation of matrix metalloproteinase‐8 levels. Results: Clinical attachment level, PD, and BOP improved significantly in both groups after therapy (P < 0.05). The statistically significant difference between the two groups after the therapy was observed only in PD in tooth sites with initial PD ≥ 4 mm (SRP + placebo: 3.41 ± 0.6 mm vs SRP + SDD: 2.92 ± 0.5 mm, P < 0.05). GCF matrix metalloproteinase‐8 levels were significantly reduced only in SRP + SDD group (P < 0.01). There were no changes in HbA1c levels after therapy. Conclusion: The short‐term administration of SDD gives significant benefit at tooth sites with moderate disease (PD ≥ 4 mm) when compared to SRP alone in patients with diabetes and CP.     

Adjunctive subantimicrobial dose doxycycline in smokers and non-smokers with chronic periodontitis

OBJECTIVES: Previous studies have demonstrated the clinical benefits of sub-antimicrobial dose doxycycline (SDD) in the treatment of chronic periodontitis (CP). The aim of this study was to retrospectively evaluate the role of SDD as an adjunct to scaling and root planing (SRP) in the treatment of smokers and non-smokers with CP. MATERIAL AND METHODS: A meta-analysis of two previously reported clinical studies was undertaken. Both were 9-month, double-blind, randomized, placebo-controlled, multi-centre clinical trials that investigated the efficacy of SDD (20 mg doxycycline twice daily) in combination with SRP in subjects with moderate-severe CP. 36.9% of the combined study population were smokers. Three hundred and ninety-two subjects were included in the meta-analysis, which evaluated per-subject mean changes in clinical attachment level (CAL) and probing depth (PD) from baseline and the total number of sites with attachment gains and PD reductions > or =2 and > or =3 mm from baseline in four subgroups: smokers/SDD; smokers/placebo; non-smokers/SDD; non-smokers/placebo. RESULTS: A hierarchical treatment response was observed, with non-smokers who received SDD demonstrating the greatest CAL gains and PD reductions. Smokers who received placebo demonstrated the smallest clinical improvements following treatment. Smokers who received SDD demonstrated an intermediate treatment response that was broadly equivalent to that seen in non-smokers who received placebo. In sites with baseline PD 4-6 mm, month 9 CAL gains were 19-45% better in non-smokers who received SDD compared with all other subgroups (p<0.05), and were 21% greater in smokers who received SDD compared with smokers who received placebo (p<0.05). Furthermore, month 9 PD reductions were 21-53% greater in non-smokers who received SDD compared with all other subgroups (p<0.01), and were 26% greater in smokers who received SDD compared with smokers who received placebo (p<0.05). CONCLUSION: Adjunctive SDD enhances therapeutic outcomes compared with SRP alone, resulting in clinical benefit in both smokers and non-smokers with CP.     

Effects of scaling and root planing and sub-antimicrobial dose doxycycline on oral and systemic biomarkers of disease in patients with both chronic periodontitis and coronary artery disease

OBJECTIVES: This study evaluated the effects of scaling and root planing (SRP) +/- sub-antimicrobial dose doxycycline (SDD) on gingival crevicular fluid (GCF) levels of matrix metalloproteinase (MMP) -1, -8, -13 and on serum levels of high-sensitivity C-reactive protein (HsCRP) and lipid fractions in patients with both chronic periodontitis (CP) and coronary artery disease (CAD). MATERIAL AND METHODS: Thirty-six patients were randomly distributed into two groups (Placebo or SDD; 6 weeks) and both received two regimens of SRP. At baseline and 6 weeks, GCF and blood were collected and clinical indices were recorded. MMPs, HsCRP and lipid fractions were assayed. RESULTS: There were statistically significant improvements for all clinical parameters, GCF volumes, GCF MMPs and serum levels of HsCRP, apolipoprotein-A (APO-A), high-density lipoprotein (HDL) and lipoprotein-a between pre- and post-treatment in both groups. Between groups, there were statistically significant greater improvements in pocket depth (PD), gingival index (GI), APO-A and HDL, favouring the group receiving SDD adjunctive to SRP (p < 0.05). CONCLUSION: Greater improvement was detected for PD and GI, and for serum levels of APO-A and HDL cholesterol when using SRP+SDD compared with SRP+placebo in this study. An investigation with larger numbers of patients and a longer duration of drug treatment is needed to confirm these preliminary findings.     

Modified-release subantimicrobial dose doxycycline enhances scaling and root planing in subjects with periodontal disease

BACKGROUND: Previous studies showed that adjunctive subantimicrobial dose doxycycline (SDD; 20 mg, twice daily) provides significant clinical benefits to scaling and root planing (SRP). A modified-release SDD formulation containing 40 mg doxycycline (SDD-40) to be taken once daily has been developed. The aim of this study was to investigate the efficacy of SDD-40 when used as an adjunct to SRP for the treatment of periodontitis. METHODS: A 9-month, double-masked, randomized, placebo-controlled, multicenter study was conducted to test the efficacy of adjunctive SDD-40 in 266 subjects with periodontitis. Subjects were treated by SRP and randomized to receive SDD-40 or placebo for 9 months with evaluations at 3, 6, and 9 months. RESULTS: Adjunctive SDD-40 provided significantly greater clinical benefits than placebo at all time points. At month 9, at sites with baseline probing depths (PD) > or =6 mm, 72% to 76% of sites in the SDD-40 group demonstrated clinically significant PD reductions and clinical attachment level (CAL) gains > or =2 mm compared to 56% to 58% of sites in the placebo group (P <0.0001); 48% to 52% of sites in the SDD-40 group demonstrated PD reductions and CAL gains > or =3 mm compared to 32% of sites in the placebo group (P <0.0001). In moderate sites (baseline PD 4 to 6 mm), adjunctive SDD-40 provided significant clinical benefits compared to placebo for mean CAL (all time points: P <0.05), PD (3 months: P = 0.002; 6 and 9 months: P = 0.001), and bleeding on probing (BOP) (3 months: P <0.01; 6 months: P <0.02; 9 months: P <0.05). In deep sites (baseline PD > or =7 mm), SDD-40 provided significant benefits over control for mean CAL (3 months: P <0.05; 6 and 9 months: P <0.01), PD (all time points: P <0.001), and BOP (3 months: P <0.05; 6 months: not statistically significant; 9 months: P <0.05). Compliance with study medication was high (>92%) with no significant differences in adverse events between groups and no evidence of microbiologically significant changes or development of antibiotic resistance in the subgingival flora in either group. CONCLUSION: SDD-40 used as an adjunct to SRP resulted in significantly greater clinical benefits than SRP alone in the treatment of periodontitis.     

Post-treatment effects of subantimicrobial dose doxycycline on clinical parameters and gingival crevicular fluid transforming growth factor-beta1 in severe, generalized chronic periodontitis

Abstract: Objective: Present study aimed to evaluate the effect of 3‐month adjunctive subantimicrobial dose doxycycline (SDD) on clinical parameters and gingival crevicular fluid (GCF) transforming growth factor‐beta1 (TGF‐β₁) levels in chronic periodontitis patients over 12 months. Methods: Thirty‐five patients with severe, generalized periodontitis participated in the present randomized, placebo‐controlled study. Patients received scaling and root planing (SRP) plus 3 months adjunctive SDD or placebo. Clinical measurements and GCF sampling were performed at baseline, 3, 6, 9 and 12 months. Eleven periodontally healthy subjects served as controls for GCF TGF‐β₁ analysis. Results: Clinical parameters of both SDD and placebo groups significantly improved during the study (P < 0.0125). SDD group exhibited significantly higher PD reduction at deep sites (baseline PD ≥7 mm) compared with placebo group at 6 months (P < 0.05). In SDD group significantly higher percentage of deep pockets resolved (PD reduction ≥3 mm from baseline) when compared with placebo group at 6 and 9 months (73.4% versus 49.7%; 79.9% versus 50.6%, respectively, P < 0.05). PD reduction ≥4 mm for deep pockets from baseline was also greater in SDD group than placebo at 6 months (53.4% versus 36.3%, P < 0.05). GCF TGF‐β₁ levels of SDD group was significantly higher than baseline (P < 0.0125) and placebo group (P < 0.017) at 3 months. Conclusions: These results ensure further data for beneficial effects of adjunctive SDD therapy in the management of severe chronic periodontitis.     

The effect of adjunctive subantimicrobial dose doxycycline therapy on GCF EMMPRIN levels in chronic periodontitis

BACKGROUND: The aim of the present randomized, double-masked, placebo-controlled, parallel-arm study was to examine the effectiveness of a 3-month regimen of subantimicrobial dose doxycycline (SDD) in combination with scaling and root planing compared to scaling and root planing alone on levels of gingival crevicular fluid (GCF) extracellular matrix metalloproteinase inducer (EMMPRIN) in patients with chronic periodontitis. METHODS: GCF samples were collected, and clinical parameters, including probing depth (PD), clinical attachment level, gingival index (GI), and plaque index, were recorded. Thirty chronic periodontitis subjects were randomized to receive SDD or placebo. The SDD group received SDD (20 mg, twice a day) for 3 months plus scaling and root planing, whereas the placebo group took placebo capsules twice a day for 3 months and received scaling and root planing. The subjects were reevaluated at 3 and 6 months. At each visit, all clinical parameters were measured and GCF was sampled. GCF EMMPRIN levels were determined by Western immunoblotting assay. Intragroup comparisons were tested by the Friedman test followed by the Wilcoxon signed-rank test to analyze the significance of changes over time. The Mann-Whitney test was used to determine differences between the SDD and placebo groups. RESULTS: Significant improvements were observed in all clinical parameters in the SDD group over the 6-month study period (P <0.025). The SDD group showed a significantly greater reduction in mean PD scores at 6 months and in mean GI scores at 3 and 6 months than the placebo group (P <0.05). From baseline to 6 months, the GCF EMMPRIN levels were reduced significantly in the SDD group (P <0.025). The GCF EMMPRIN level in the SDD group was significantly lower than that of the placebo group at 3 and 6 months (P <0.05). CONCLUSIONS: SDD therapy in combination with scaling and root planing reduced GCF EMMPRIN levels and improved clinical periodontal parameters in subjects with chronic periodontitis. The ability of SDD to downregulate, in vivo, the GCF levels of EMMPRIN, a unique upregulator of matrix metalloproteinase expression, is one of its beneficial host-modulatory properties. These results expand the usefulness of SDD therapy as an adjunct to scaling and root planing in the long-term management of periodontal disease.     

The effect of adjunctive low-dose doxycycline therapy on clinical parameters and gingival crevicular fluid matrix metalloproteinase-8 levels in chronic periodontitis

BACKGROUND: Low-dose doxycycline (LDD) is recognized to have non-antimicrobial properties that can therapeutically modulate the host response. The aim of the present randomized, double-blind, placebo-controlled, parallel-arm study was to examine the effectiveness of LDD in combination with non-surgical periodontal therapy, compared to non-surgical periodontal therapy alone, on gingival crevicular fluid (GCF) matrix metalloproteinase-8 (MMP-8) levels and clinical parameters over a 12-month period in patients with chronic periodontitis. METHODS: GCF samples were collected, and clinical parameters including probing depth (PD), clinical attachment level, gingival index (GI), and plaque index were recorded. Thirty chronic periodontitis patients were randomized either to a low-dose doxycycline (LDD) or placebo group. The LDD group received low-dose doxycycline (20 mg) b.i.d. for 3 months plus scaling and root planing (SRP), while the placebo group was given placebo capsules b.i.d. for 3 months plus SRP. The patients were evaluated every 3 months during the 12-month study period. At each visit, all clinical measurements and GCF sampling were repeated. GCF MMP-8 levels were determined by a time-resolved immunofluorescence assay. Intragroup comparisons were tested by the Friedman test followed by Wilcoxon signed-rank test to analyze significance of changes over time. The Mann-Whitney test was used to determine differences between the LDD and placebo groups. RESULTS: Significant improvements were observed in all clinical parameters in both groups over the 12-month period (P < 0.0125). The LDD group showed a significantly greater reduction in mean PD scores at 9 and 12 months and in mean GI scores at all time points than the placebo group (P < 0.05). From baseline to 12 months, GCF MMP-8 levels were significantly reduced in both groups (P < 0.0125). The GCF MMP-8 level in the LDD group was significantly lower than that of the placebo group at 6 months (P < 0.05). CONCLUSIONS: The present results indicate that low-dose doxycycline therapy in combination with scaling and root planing can reduce GCF MMP-8 levels and improve clinical periodontal parameters in patients with chronic periodontitis. These results provide additional information about the usefulness of low-dose doxycycline therapy as an adjunct to non-surgical periodontal therapy in the long-term management of periodontal disease. The effectiveness and course of low-dose doxycycline therapy can be monitored conveniently by assessing GCF MMP-8 levels.     

The effect of subgingival controlled-release delivery of chlorhexidine chip on clinical parameters and matrix metalloproteinase-8 levels in gingival crevicular fluid

BACKGROUND: The present study evaluated the efficacy of controlled-release delivery of chlorhexidine gluconate (CHX) on clinical parameters and on gingival crevicular fluid (GCF) matrix metalloproteinase (MMP)-8 levels in chronic periodontitis patients. METHODS: Twenty patients with chronic periodontitis were screened for 6 months. Two interproximal sites were selected from mesial surfaces of anterior teeth with probing depths of 6 to 8 mm that bled on probing in each patient. There were at least 2 teeth between the selected sites. CHX chip was inserted into a randomly selected site following scaling and root planing (SRP+CHX), while the other selected site received only SRP in each patient. Probing depth (PD), clinical attachment level (CAL), plaque index (PI), and papilla bleeding index (PBI) were recorded at baseline and at 1, 3, and 6 months. GCF MMP-8 levels were analyzed at baseline; 2 and 10 days; and at 1, 3, and 6 months by immunofluorometric assay (IFMA). RESULTS: At baseline, there were no statistically significant differences in the mean PD, CAL, PBI, and PI scores between SRP+CHX and SRP alone groups. At 1, 3, and 6 months, all clinical parameters in each group significantly decreased (P <0.0167) when compared to baseline. The reduction of PD and improvement in CAL were higher in the SRP+CHX group compared to SRP alone at 3 and 6 months. However, the differences between the 2 groups were not statistically significant. PBI and PI scores were not significantly different between SRP+CHX and SRP alone groups at any visit. GCF MMP-8 levels were similar in both groups at baseline. Intragroup analysis showed significant decreases in the GCF MMP-8 level for the SRP+CHX group between baseline and 1, 3, and 6 months (P<0.01). Intergroup analysis demonstrated significantly lower mean levels of GCF MMP-8 at 1 month in the SRP+CHX group compared to the SRP alone group (P <0.05). CONCLUSIONS: These data suggest that CHX chip application following SRP is beneficial in improving periodontal parameters and reducing GCF MMP-8 levels for 6 months' duration. The use of a chairside MMP-8 dipstick periodontitis test might be a useful adjunctive diagnostic tool when monitoring the course of CHX chip treatment.     

Long-term treatment with subantimicrobial dose doxycycline exerts no antibacterial effect on the subgingival microflora associated with adult periodontitis

BACKGROUND: The purpose of this study was to determine whether treatment with subantimicrobial dose doxycycline (SDD), 20 mg bid, exerted an antimicrobial effect on the microflora associated with adult periodontitis. METHODS: Following the approval of the protocol and informed consent forms by the respective IRBs at the University of Florida and West Virginia University, 76 subjects with adult periodontitis were entered and randomly assigned to receive SDD or placebo. A split-mouth design was utilized, with each subject receiving subgingival scaling and root planing (SRP) in two quadrants immediately following baseline data collection, while the remaining two quadrants were left unscaled (non-SRP). Microbial samples were collected prior to treatment, after 3, 6, and 9 months of treatment, and after 3 months of no treatment. The samples were examined by microscopy and by enumeration on selective and non-selective media. RESULTS: All treatments resulted in statistically significant decreases in the proportions of spirochetes and motile rods (P <0.05) and in an increase in the proportion of coccoid forms (P <0.0001) relative to baseline. No between-treatment differences were detected between the SDD and placebo treatments in either the SRP or non-SRP design, with the exception of the small and large spirochetal groups. The spirochetal proportions present in the SDD group were significantly lower (P<0.05) than the paired placebo group during the 9-month treatment and was preceded by a significant decrease (P<0.01) in the proportion of microbiologic sample sites that bled on probing. No between- treatment differences were detected in any of the other microbial parameters. CONCLUSION: The microbial differences observed were attributed to the anticollagenase and anti-inflammatory properties of SDD and not to an antimicrobial effect.     

Effectiveness of adjunctive low-dose doxycycline therapy on clinical parameters and gingival crevicular fluid laminin-5 gamma2 chain levels in chronic periodontitis

BACKGROUND: Laminin-5 (Ln-5) is involved in the apical migration of epithelial cells during the development of periodontal pockets. Low-dose doxycycline (LDD) can therapeutically modulate the host response with its non-antimicrobial properties. In the present randomized, double-blind, placebo-controlled, parallel arm study, the effectiveness of LDD in combination with non-surgical periodontal therapy on gingival crevicular fluid (GCF) Ln-5 gamma2 chain fragment levels and clinical parameters in patients with chronic periodontitis was examined over a 12-month period. METHODS: GCF samples were collected and clinical parameters including probing depth (PD), clinical attachment level, gingival index (GI), and plaque index were recorded. Thirty chronic periodontitis patients were randomized either to low-dose doxcycline or placebo groups. LDD group received doxycycline (20 mg, b.i.d.) for 3 months plus scaling and root planing (SRP), while placebo group was given placebo capsules b.i.d. for 3 months plus SRP. The patients were evaluated every 3 months during the 12-month study period. All clinical parameters and GCF sampling were repeated at each visit. GCF Ln-5 gamma2 chain fragment levels were determined by Western immunoblotting using specific antibody and quantitated by computerized image analysis. Friedman test was used for intragroup comparisons followed by Wilcoxon signed rank test to analyze significance of changes over time. The Mann-Whitney test was used to determine differences between both LDD and placebo groups. RESULTS: Both groups revealed significant improvements in all clinical parameters over the 12-month period (P < 0.0125). LDD group showed a significantly greater reduction in the mean PD scores at 9 and 12 months and in the mean GI scores at all time points than the placebo group (P < 0.05). In the LDD group, GCF Ln-5 gamma2 chain fragment levels were significantly reduced at 3 months (P < 0.0125) and then slightly increased during the rest of the study period. In the placebo group, GCF 45 and 70 kDa Ln-5 gamma2 chain fragments tended to decrease at 3 months compared to baseline, but did not reach significance; these levels continued to increase throughout the remainder of the study period. GCF Ln-5 gamma2 chain fragment levels in LDD group were significantly lower than those of the placebo group during the study period (P < 0.05). CONCLUSIONS: The present data indicate that LDD therapy in combination with SRP therapy can reduce GCF Ln-5 gamma2 chain fragment levels and improve clinical periodontal parameters in patients with chronic periodontitis. Since matrix metalloproteinases (MMP)-mediated fragmentation of laminin-5 can contribute to pocket formation by stimulating epithelial cell migration, the reduction of Ln-5 gamma2 chain fragment levels could provide a new mechanism by which LDD, adjunctive to SRP, inhibits periodontal disease more effectively than SRP alone. Thus, these results provide extended and additional information about the effectiveness of the LDD therapy as an adjunct to non-surgical periodontal therapy in the long-term management of periodontal disease.     

Efficacy of 1% Metformin Gel in Patients With Moderate and Severe Chronic Periodontitis: A Randomized Controlled Clinical Trial

Background: The aim of this study is to investigate efficacy of metformin (MF) 1% gel as an adjunct to scaling and root planing (SRP) in the treatment of moderate and severe chronic periodontitis (CP). Methods: Seventy patients were categorized into two treatment groups: 1) SRP plus 1% MF and 2) SRP plus placebo. Clinical parameters were recorded at baseline and 3, 6, and 9 months. They included plaque index (PI), modified sulcus bleeding index (mSBI), probing depth (PD), and clinical attachment level (CAL). Radiologic assessment of intrabony defects (IBDs) and percentage defect depth reduction (DDR%) was done at baseline and 6‐ and 9‐month intervals using computer‐aided software. PD, CAL, and DDR% were evaluated in two subgroups in both the placebo and MF group: 1) initial PD of 5 to 7 mm and 2) initial PD of >7 mm. Results: Mean PD reduction and mean CAL gain was found to be greater in the MF group than the placebo group at all visits. Clinical parameters (PD, CAL) in both subgroups, with initial PDs of 5 to 7 and >7 mm, showed significant improvement in the 1% MF group compared with the placebo group. A significantly greater mean DDR% was found in the MF group than the placebo group at 6 and 9 months in both subgroups, 5 to 7 and >7 mm of initial PD. Conclusion: There was a greater decrease in PD and more CAL gain with significant IBD depth reduction at sites treated with SRP plus locally delivered MF in patients with CP in both initial PD = 5 to 7 and >7 mm subgroups compared with placebo.     

GCF MMP-8 levels in smokers and non-smokers with chronic periodontitis following scaling and root planing accompanied by systemic use of flurbiprofen

BACKGROUND: Cigarette smoking has been identified as an important risk factor for the initiation and progression of chronic periodontitis (CP). The aim of this study was to investigate the effects of phase I periodontal therapy and adjunctive flurbiprofen administration on matrix metalloproteinase (MMP)-8 levels in gingival crevicular fluid (GCF) samples from smoking and non-smoking patients with CP. METHODS: Twenty-nine non-smoking and 29 smoking patients with CP were divided into four groups according to periodontal treatment modalities. Group 1 (non-smokers with CP) and group 3 (smokers with CP) patients received daily 100-mg flurbiprofen tablets in a 2 x 1 regimen for 10 days together with scaling and root planing (SRP). Patients in group 2 (non-smokers with CP) and group 4 (smokers with CP) received placebo tablets in a 2 x 1 regimen for 10 days together with SRP. Plaque index (PI), gingival index (GI), probing depth (PD), and clinical attachment level (CAL) measurements were recorded; GCF samples were collected from each sampling area at baseline and after the 10-day period of drug intake by a single examiner who was unaware of the treatment modality. Assays for GCF MMP-8 were carried out by an enzyme-linked immunosorbent assay. RESULTS: All groups showed statistically significant reductions in PI and GI scores following the phase I periodontal treatment (P < 0.05), but no statistical differences were observed in PD and CAL scores after therapy. In all groups, the reduction of GCF MMP-8 levels after therapy was statistically significant compared to baseline levels (P < 0.001). When groups 1 and 3 and 2 and 4 were compared according to GCF MMP-8 levels after the therapy, no statistically significant differences were observed (P = 0.117 and P = 0.485, respectively). CONCLUSION: Flurbiprofen administration had no additional inhibitory effect over SRP alone on GCF levels of MMP-8 in smokers compared to non-smokers with CP.     

Adjunctive Non‐Surgical Therapy of Inflamed Periodontal Pockets During Maintenance Therapy Using Diode Laser: A Randomized Clinical Trial

Background: Numerous studies have documented the clinical outcomes of laser therapy for untreated periodontitis, but very few have reported on lasers treating inflamed pockets during maintenance therapy. The aim of this study is to compare the effectiveness of scaling and root planing (SRP) plus the adjunctive use of diode laser therapy to SRP alone on changes in the clinical parameters of disease and on the gingival crevicular fluid (GCF) inflammatory mediator interleukin‐1β (IL‐1β) in patients receiving regular periodontal maintenance therapy. Methods: This single‐masked and randomized, controlled, prospective study includes 22 patients receiving regular periodontal maintenance therapy who had one or more periodontal sites with a probing depth (PD) ≥5 mm with bleeding on probing (BOP). Fifty‐six sites were treated with SRP and adjunctive laser therapy (SRP + L). Fifty‐eight sites were treated with SRP alone. Clinical parameters, including PD, clinical attachment level (CAL), and BOP, and GCF IL‐1β levels were measured immediately before treatment (baseline) and 3 months after treatment. Results: Sites treated with SRP + L and SRP alone resulted in statistically significant reductions in PD and BOP and gains in CAL. These changes were not significantly different between the two therapies. Similarly, differences in GCF IL‐1β levels between SRP + L and SRP alone were not statistically significant. Conclusion: In periodontal maintenance patients, SRP + L did not enhance clinical outcomes compared to SRP alone in the treatment of inflamed sites with ≥5 mm PD.     

Subantimicrobial dose doxycycline as adjunctive treatment for periodontitis. A review

BACKGROUND: Subantimicrobial dose doxycycline (SDD--20 mg doxycycline twice daily) is indicated as an adjunctive treatment for periodontitis. Doxycycline downregulates the activity of matrix metalloproteinases (MMPs), key destructive enzymes in periodontal disease. Current understanding of periodontal pathogenesis suggests that MMPs play a major role in the destruction of periodontal tissues, leading to the clinical signs of periodontitis. Research supports that downregulation of MMPs by SDD confers benefit to patients with periodontitis. METHOD: We review the clinical, microbiological and safety data relating to the use of SDD in patients with periodontitis, and consider the historical events that led to the development of adjunctive SDD as a treatment for periodontitis. RESULTS: Studies have shown that SDD, when prescribed as an adjunct to scaling and root planing (SRP), results in statistically and clinically significant gains in clinical attachment levels and reductions in probing depths over and above those that are achieved by SRP alone. SRP must be thorough and performed to the highest standard to maximise the benefits of adjunctive SDD. SDD does not result in antibacterial effects, or lead to the development of resistant strains or the acquisition of multiantibiotic resistance. The frequency of adverse events is low, and does not differ significantly from placebo. CONCLUSIONS: Adjunctive SDD confers clinical benefit to patients with periodontitis. A comprehensive treatment strategy is suggested, involving patient education and motivation, reduction of the bacterial burden by SRP, host response modulation with SDD, and periodontal risk factor modification.     

Systemic MMP inhibition for periodontal wound repair: results of a multi-centre randomized-controlled clinical trial

Aim: This multi-centre, prospective, controlled trial was designed to examine the biological response of the matrix metalloproteinase(MMP) inhibitor subantimicrobial dose doxycycline (SDD) combined with access flap surgery on periodontal wound repair in patients with chronic severe periodontitis.
Material and Methods: Seventy subjects were enrolled into a 12-month, randomized, placebo-controlled, double-masked trial to evaluate disease response to 6 months therapy and "wash-out" of either placebo+surgery or SDD (20 mg b.i.d.)+surgery. Primary outcome measure included clinical attachment levels (CAL) and secondary outcomes included probing depth (PD), bleeding on probing (BOP), as well as gingival crevicular fluid bone marker assessment [collagen telopeptides (ICTP)]. These measurements were taken at baseline through 12 months post-surgery and drug administration.
Results: Patients treated with SDD and surgery demonstrated stronger reductions in PD in surgically-treated sites of 7 mm as well as gains in CAL ( p <0.004). Furthermore, SDD+surgery resulted in short-term reductions in ICTP levels compared with placebo. Rebounds in ICTP levels and clinical parameters occurred when SDD was withdrawn.
Conclusions: The results from this multi-centre study suggests that SDD in combination with surgery improves the short-term response of periodontal therapy by reducing PD, increasing CAL gain and inhibiting early stage bone resorption.