Aggressive Periodontitis: Antibiotics or PDT as an Adjunct?
The results of the present study revealed that in patients with AgP the use of amoxicillin and metronidazole resulted in a statistically significant reduction of MMP-8 GCF levels at 3 and 6 months after treatment. Treatment with SRP + PDT yielded a reduction in MMP-8 GCF level, but this change was not statistically significant. Compared to the application of PDT, the systemic administration of amoxicillin and metronidazole has led at both evaluation time points to statistically significantly higher reductions of MMP-8 CGF levels compared to the application of PDT. These findings are in line with the clinical results, which have demonstrated statistically and clinically significantly higher clinical improvements in amoxicillin plus metronidazole group compared to the PDT one (i.e. at six months following therapy the total number of pockets ≥ 7 mm was reduced from 141 to 3 in the antibiotic group, while the corresponding values were 137 and 45, respectively in the PDT one). Comparable findings were also reported by Goncalves et al. who found dramatic decrease in MMP-8 and-9 levels after SRP and systemic use of Amoxicillin + Metronidazole. Thus, the present changes of GCF MMP-8 levels reflect the clinical improvements and provide additional evidence for the efficacy of amoxicillin and metronidazole in the treatment of patients with AgP.
The fact that the application of PDT in conjunction with SRP has failed to result in statistically significant reduction of MMP-8 CGF level compared to baseline appears to indicate that in patients with AgP, the application of PDT additionally to SRP leads to a more moderate healing response compared to the systemic administration of amoxicillin and metronidazole. These findings might be explained by the capacity of certain periodontopathic bacteria such as A.a. and P.g. to adhere to cells and to invade cells even in deeper soft tissues layers surrounding periodontally diseased teeth.
Since it has been demonstrated that the cytotoxic product which results following PDT, e.g. O2, cannot migrate at a deeper distance than 0.02 μm after its formation, it may be anticipated that PDT is more suitable for local application without reaching distant molecules, cells or organs. Hence, it appears that the systemic administration of an adequate dose of specifically selected antibiotics may have a substantially higher potential to reach the cells harboring periodontopathic bacteria than the application of PDT.
On the other hand, it has to be kept in mind that despite the fact that the clinical improvements obtained in the antibiotic group were significantly higher compared to those obtained with PDT, the use of PDT has also led to statistically significant improvements compared to baseline. These results corroborate, at least in part, very recent findings in patients with AgP evaluating the adjunctive use of PDT to SRP. At 90 days, in deep periodontal pockets ≥ 7 mm at baseline, the adjunctive application of PDT yielded statistically significantly higher decrease in PD and clinical attachment gain compared to treatment with SRP. The SRP + PDT group also demonstrated significantly less periodontal pathogens of red and orange complexes and a lower ratio IL-1β/IL-10 than the SRP Group. However, when comparing the aforementioned results to our findings, it has to be kept in mind, that differences in the frequency of PDT application after SRP (i.e. 2× versus 4×) may have also influenced the outcomes. Taken together, the available data appear to suggest a potential role of PDT in modulating periodontal inflammation.
In the present study, the MMP-9 levels were reduced in both groups. Despite the fact that the reduction of MMP-9 levels was greater in the antibiotic group, the differences between the examinations periods and among the groups did not reach statistical significance. This finding is somewhat in contradiction with those reported data by Gocalves et al. who have reported statistically significant reductions in MMP-1, MMP-8, MMP-9, MMP-12, and MMP-13 levels up to 6 months, comparable to healthy sites. Significant correlations were noted between MMP-2, MMP-3, MMP-8, MMP-9, MMP-12, and MMP-13 levels and percentage of sites with PD >4 mm. Other authors have also reported a reduction of multiple inflammatory biomarkers including MMP-9 levels after different modalities of periodontal therapy, but the responses were inconsistent among the subjects while the changes of inflammatory markers correlated poorly with clinical parameters. Moreover, GCF MMP-8 and MMP-9 data showed very high standard deviations, which may be related with individual variability. Obviously, these very high standard deviations prevented detection of statistically significant differences between different time points and between the study groups at the same time points.
These inconsistent findings are also in line with the conclusions of a sytematic review which indicated that at present, no single or combination of markers exists that can reveal periodontal destruction adequately and further studies are needed to provide an objective demonstration of the use of such markers to monitor periodontal destruction.
When interpreting the present results, it should be mentioned that from a scientific point of view a third group of AgP patients, treated with SRP alone, would have been of interest to evaluate and compare the additive effects of antibiotics and PDT. On the other hand, substantial data from the literature has provided clear evidence indicating that the use of systemic antibiotics represents today's state of the art in the treatment of AgP. Therefore, for obvious ethical reasons, the inclusion of a third treatment arm using SRP alone was not feasible.
Discussion
The results of the present study revealed that in patients with AgP the use of amoxicillin and metronidazole resulted in a statistically significant reduction of MMP-8 GCF levels at 3 and 6 months after treatment. Treatment with SRP + PDT yielded a reduction in MMP-8 GCF level, but this change was not statistically significant. Compared to the application of PDT, the systemic administration of amoxicillin and metronidazole has led at both evaluation time points to statistically significantly higher reductions of MMP-8 CGF levels compared to the application of PDT. These findings are in line with the clinical results, which have demonstrated statistically and clinically significantly higher clinical improvements in amoxicillin plus metronidazole group compared to the PDT one (i.e. at six months following therapy the total number of pockets ≥ 7 mm was reduced from 141 to 3 in the antibiotic group, while the corresponding values were 137 and 45, respectively in the PDT one). Comparable findings were also reported by Goncalves et al. who found dramatic decrease in MMP-8 and-9 levels after SRP and systemic use of Amoxicillin + Metronidazole. Thus, the present changes of GCF MMP-8 levels reflect the clinical improvements and provide additional evidence for the efficacy of amoxicillin and metronidazole in the treatment of patients with AgP.
The fact that the application of PDT in conjunction with SRP has failed to result in statistically significant reduction of MMP-8 CGF level compared to baseline appears to indicate that in patients with AgP, the application of PDT additionally to SRP leads to a more moderate healing response compared to the systemic administration of amoxicillin and metronidazole. These findings might be explained by the capacity of certain periodontopathic bacteria such as A.a. and P.g. to adhere to cells and to invade cells even in deeper soft tissues layers surrounding periodontally diseased teeth.
Since it has been demonstrated that the cytotoxic product which results following PDT, e.g. O2, cannot migrate at a deeper distance than 0.02 μm after its formation, it may be anticipated that PDT is more suitable for local application without reaching distant molecules, cells or organs. Hence, it appears that the systemic administration of an adequate dose of specifically selected antibiotics may have a substantially higher potential to reach the cells harboring periodontopathic bacteria than the application of PDT.
On the other hand, it has to be kept in mind that despite the fact that the clinical improvements obtained in the antibiotic group were significantly higher compared to those obtained with PDT, the use of PDT has also led to statistically significant improvements compared to baseline. These results corroborate, at least in part, very recent findings in patients with AgP evaluating the adjunctive use of PDT to SRP. At 90 days, in deep periodontal pockets ≥ 7 mm at baseline, the adjunctive application of PDT yielded statistically significantly higher decrease in PD and clinical attachment gain compared to treatment with SRP. The SRP + PDT group also demonstrated significantly less periodontal pathogens of red and orange complexes and a lower ratio IL-1β/IL-10 than the SRP Group. However, when comparing the aforementioned results to our findings, it has to be kept in mind, that differences in the frequency of PDT application after SRP (i.e. 2× versus 4×) may have also influenced the outcomes. Taken together, the available data appear to suggest a potential role of PDT in modulating periodontal inflammation.
In the present study, the MMP-9 levels were reduced in both groups. Despite the fact that the reduction of MMP-9 levels was greater in the antibiotic group, the differences between the examinations periods and among the groups did not reach statistical significance. This finding is somewhat in contradiction with those reported data by Gocalves et al. who have reported statistically significant reductions in MMP-1, MMP-8, MMP-9, MMP-12, and MMP-13 levels up to 6 months, comparable to healthy sites. Significant correlations were noted between MMP-2, MMP-3, MMP-8, MMP-9, MMP-12, and MMP-13 levels and percentage of sites with PD >4 mm. Other authors have also reported a reduction of multiple inflammatory biomarkers including MMP-9 levels after different modalities of periodontal therapy, but the responses were inconsistent among the subjects while the changes of inflammatory markers correlated poorly with clinical parameters. Moreover, GCF MMP-8 and MMP-9 data showed very high standard deviations, which may be related with individual variability. Obviously, these very high standard deviations prevented detection of statistically significant differences between different time points and between the study groups at the same time points.
These inconsistent findings are also in line with the conclusions of a sytematic review which indicated that at present, no single or combination of markers exists that can reveal periodontal destruction adequately and further studies are needed to provide an objective demonstration of the use of such markers to monitor periodontal destruction.
When interpreting the present results, it should be mentioned that from a scientific point of view a third group of AgP patients, treated with SRP alone, would have been of interest to evaluate and compare the additive effects of antibiotics and PDT. On the other hand, substantial data from the literature has provided clear evidence indicating that the use of systemic antibiotics represents today's state of the art in the treatment of AgP. Therefore, for obvious ethical reasons, the inclusion of a third treatment arm using SRP alone was not feasible.
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