Adjunctive Treatment For Periodontitis Research Articles

Local Application of a New Chalconic Derivative (Chalcone T4) Reduces Inflammation and Oxidative Stress in a Periodontitis Model in Rats.

Chalcones are phenolic compounds with biological properties. This study had the aim to evaluate the effects of topical administration of a new synthetic chalcone, Chalcone T4, in an animal model of periodontitis induced by ligature. Forty rats were distributed in the following experimental groups: negative control (without periodontitis and topical application of distilled water), positive control (periodontitis and topical application of distilled water), chalcone I and II (periodontitis and topical application of 0.6 mg/mL and 1.8 mg/mL, respectively). Chalcone or distilled water was administered into the gingival sulcus of the first molars daily for 10 days, starting with the ligature installation. The following outcomes were evaluated: alveolar bone loss (µCT and methylene blue dye staining), quantification of osteoclasts (histomorphometry), cell infiltrate and collagen content (stereometry), gene expression of mediators (Nfact11, Tnf-α, Mmp-13, iNos, Sod and Nrf2) by (RT-qPCR); expression of BCL-2 and Caspase-1 (immunohistochemistry). Chalcone T4 inhibited bone resorption and prevented collagen matrix degradation. Reduction in the expression of inflammatory markers (Nfact11, Tnf-α, Mmp-13, and Caspase-1), attenuation of oxidative stress (iNOS reduction, and increase in Sod), and pro-apoptotic effect of the compound (BCL-2 reduction), were associated its effects on periodontal tissues. Topical application of Chalcone T4 prevented bone resorption and inflammation, demonstrating potential in the adjunctive treatment of periodontitis.

Airflowing as an adjunctive treatment for periodontitis: A randomized controlled trial.

The aim of this randomized controlled trial was to assess clinical and patient-reported outcomes of subgingival instrumentation (SI) with adjunctive use of erythritol airflowing (EAF)compared toSI alone in the treatmentofperiodontitis. Twenty-six participants with Stage III/IV periodontitis requiring nonsurgical periodontal treatment were randomly allocated into two treatment groups: SI with EAF or SI alone. Clinical parameters of percentage of probing pocket depths (PPDs) of ≥5mm, full mouth bleeding and plaque scores (FMBS and FMPS), and PPD values were recorded at baseline, and at 3 and 6 months posttreatment.A visual analogue scale was used to evaluatepostoperative participants' perception of pain, swelling, bleeding, bruising, and root sensitivity.The impact of periodontal treatment onquality of lifewas assessed using the General Oral Health Assessment Index (GOHAI) at six months. A total of 26 participants with Stage III/IV periodontitis completed the 6-month follow-up. SI with or without EAF resulted in a statistically significant reductions in the FMBS, FMPS, PPDs, and percentage of PPDs of ≥5mm at the 3- and 6-month follow-up visits. There was no statistically significant difference between the two treatment groups for any time interval. Participants receiving SI/EAF exhibited a higher reduction in FMBS compared to those in SI alone group at 3 (SI/EAF: 19.4±11.9, SI alone:30.1±20.5; P=0.12) and 6 months (SI/EAF: 14.3±9.6, SI alone: 24.5±18.2; P=0.09). A lower percentage of sites with deep PPDs (≥5mm) was also noted amongst participants in the SI/EAF group compared to SI alone at 3 months (SI/EAF: 14.3±14.1, SI alone:19.2±20.3; P=0.48) and 6 months (SI/EAF: 8.3±10.0, SI alone: 15.4±17.4; P=0.22). Patient-reported outcomes showed no significant differences between the two treatment groups, except in the psychosocial domain of the GOHAI at 6 months favoring the SI/EAF group (P=0.03). Within the limitations of the study, the adjunctive use of EAF in addition to SI in the treatment of Stage III/IVperiodontitisdid not result in a significant improvement in clinical parameters. Limited improvement in the QoL with EAF could be achieved.

Diode laser as an adjunctive treatment for periodontitis: Arandomized controlled trial.

The aim of this randomized controlled trial was to assess clinical and patient reported outcomes of subgingival instrumentation (SI) with adjunctive use of diode laser (DL) versus SI alone in the treatment of periodontitis. Participants requiring non-surgical periodontal treatment were randomly allocated into two treatment groups: SI with DL or SI alone. Clinical parameters [full mouth bleeding and plaque scores (FMBS and FMPS), probing pocket depth and clinical attachment level] were recorded at baseline, three and 6 months post-treatment. Visual analogue scale was used to evaluate postoperative participants' perception of pain, swelling, bleeding, bruising and root sensitivity. The impact of periodontal treatment on quality of life was assessed using the General Oral Health Assessment Index (GOHAI) at 6 months. A total of 22 participants with stage III/IV periodontitis completed the 6-month follow-up. SI with or without DL resulted in statistically significant reduction in FMBS, FMPS, PPDs, and percentage of PPDs of ≥5 mm at 3- and 6-month follow-up visits (p = 0.001 to <0.001). The participants in SI/DL group had a greater reduction in the percentage of deep PPDs (≥5 mm) compared to those receiving SI alone, but statistically significant differences between the two groups were not observed (16.40 ± 9.57 vs. 32.50 ± 38.76 at 3 months and 7.20 ± 6.86 vs. 19.50 ± 35.06 at 6 months). The difference in the mean total GOHAI scores was not statistically significant at 6 months with total GOHAI scores of 7.25 ± 2.45 and 5.40 ± 3.06 for SI and SI/DL groups, respectively. Within the limitations of this study, the use of DL as an adjunct to SI in the treatment of stage III/IV periodontitis did not produce significant additional improvement in clinical parameters or patient reported outcomes in the 6-month observation period.

Oxygen Availability on the Application of Antimicrobial Photodynamic Therapy against Multi-Species Biofilms.

Methylene blue (MB)- or Curcumin (Cur)-based photodynamic therapy (PDT) has been used as an adjunctive treatment for periodontitis. Its actual clinical efficacy is still in question because the lack of oxygen in a deep periodontal pocket might reduce the PDT efficacy. We aim to investigate the effect of oxygen on PDT efficacy and to examine if the addition of hydrogen peroxide (HP) could improve PDT performance anaerobically. To this end, we cultured 48 h saliva-derived multi-species biofilms and treated the biofilms with 25 µM MB or 40 µM Cur, HP (0.001%, 0.01% and 0.1%), light (L-450 nm or L-660 nm), or combinations thereof under ambient air or strictly anaerobic conditions. MB- and Cur-PDTs significantly reduced biofilm viability in air but not under anaerobic conditions. HP at 0.1% significantly enhanced the killing efficacies of both MB- and Cur-PDTs anaerobically. The killing efficacy of Cur-PDT combined with 0.1% HP was higher anaerobically than in air. However, this was not the case for MB-PDT combined with 0.1% HP. In conclusion, this study demonstrated that the biofilm killing efficacies of MB- and Cur-PDTs diminished when there was no oxygen. HP at 0.1% can enhance the efficacy of PDT performed anaerobically, but the level of enhancement is photosensitizer-dependent.

Effects of Antibiotics Versus Repeated Applications of Photodynamic Therapy as an Adjunctive Treatment for Periodontitis: A Systematic Review and Meta-Analysis

Objective: Although multiple applications of antimicrobial photodynamic therapy (aPDT) and antibiotics (AB) have been proved to have a biomodulatory effect, no systematic review has exclusively compared the effectiveness as an adjunct to scaling and root planning (SRP). This study sought to systematically compare the clinical efficacy of repeated antimicrobial photodynamic therapy (RaPDT) with that of the systemic administered AB as an alternative approach to SRP in treating periodontitis. Methods: In this systematic review, two independent reviewers searched PubMed, Embase, and CENTRAL databases. The primary outcomes assessed were bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment level (CAL). Results: Five randomized clinical trials were included after screening 457 records. Results revealed that when patients from all studies were categorized based on their baseline CAL, AB demonstrated significant benefits over RaPDT in the improvement of PPD [weighted mean differences (WMD) = -0.36, 95% confidence interval (CI) = -0.71 to -0.02, p < 0.05] in the patients with severe periodontitis (CAL baseline ≥5 mm) 3-month postoperatively, and CAL (WMD = -0.57, 95% CI = -1.11 to -0.04, p < 0.05) at 6-month observation. Nevertheless, AB failed to show significant benefits over RaPDT, when CAL baseline <5 mm in terms of clinical parameters. Conclusions: RaPDT may represent an alternative approach to SRP in treating slight-to-moderate periodontitis cases (CAL <5 mm), whereas AB remain a main therapy for treating severe periodontitis (CAL ≥5 mm).

Melanin pigmented gingival tissue impairs red-light lateral scattering for antimicrobial photodynamic therapy.

Gingival melanin pigmentation is present in many African and Oriental descendant people and its occurrence in patients may interfere with the absorption and scattering of therapeutic doses of light. Antimicrobial photodynamic therapy (aPDT) is used as an adjunctive treatment for periodontitis and light irradiation may be impaired by tissue size and its melanin content. The aim of this clinical study was to measure the red-light attenuation in gingival tissue naturally pigmented with melanin. Ten patients with melanized gingival tissue were selected and irradiated by 100 mW red laser. The patients were photographed in frontal and incisal regions with a T2i camera (Canon, Japan) with 100 mm macro lens, 35 mm focal length, aperture f22, 1/100 shutter speed and ISO 200. Three randomly selected sites of each patient were used for evaluations and the irradiation values were assessed in the IMAGEJ software (NIH, Wayne Rasband, USA). Intensity in pixels was quantified in relation to the distance from the light incident point. Data were normalized and the results were presented as relative light intensity as a function of distance. The results demonstrated that red laser light is exponentially attenuated as a function of lateral distance and loses approximately 50 % of its intensity by 2.23 mm. On the other hand, the light travels 3 mm in depth to decay 50 %. In conclusion, our data suggest that melanin presence decreases optical pathway and irradiation protocols for antimicrobial photodynamic therapy in gingival tissue should consider light attenuation and depth of periodontal pockets so that efficient illumination of the target tissue occurs. Periodontal pockets bigger than 6 mm should be irradiated with more than one point.

Effects of Calendula Officinalis and Hypericum Perforatum on Antioxidant, Anti-Inflammatory, and Histopathology Indices of Induced Periodontitis in Male Rats.

Statement of the Problem: Periodontitis is one of the most common bacterial infections of the oral cavity. It is important to find adjunctive methods for chemical treatment of periodontitis with less complications and proven therapeutic properties. Purpose: The aim of this study was to compare the effects of Calendula officinalis and Hypericum perforatum on antioxidant, anti-inflammatory and histopathologic indices of induced periodontitis in male rats.Materials and Method: In this experimental animal study, forty adult male Sprague-Dawley rats were randomly divided into 4 groups (n=10) and then experimental periodontitis was induced by 3-0 nylon non-absorbable ligature. Each group was treated for 10 days as follows: 1) H. perforatum hydroalcoholic extract, 1000 mg/kg/daily, orally; 2) C. officinalis hydroalcoholic extract, 1000 mg/kg/daily, orally; 3) a mix of the two plants, 1000 mg/kg/ daily, orally, 4) normal saline solution. At the end of study, blood sample were obtained via cardiocentesis, the rats were euthanized, and their maxillae were removed. The samples were analyzed for histopathological scores and total antioxidant capacity and IL-1β were measured. Results: Mixed hydroalchoholic extract of H. perforatum and C. officinalis decreased IL-1β (4.3020±0.63), and increased the antioxidant parameter in comparison to the control group (3.1192±0.43) (p< 0.001). There were significant histopathological differences between the treatment groups and the control group.Conclusion: Mixed hydroalchoholic extract of H. perforatum and C. officinalis might be considered as an adjunctive treatment for periodontitis.

Microbial Composition of Oral Biofilms after Visible Light and Water-Filtered Infrared a Radiation (VIS+wIRA) in Combination with Indocyanine Green (ICG) as Photosensitizer.

In view of increasing antibiotic resistance, antimicrobial photodynamic therapy (aPDT) is an alternative treatment method used to eradicate the microbial community of oral biofilms that can be responsible for different oral infections. In order to investigate changes in the microbial composition after application of aPDT with visible light and water-filtered infrared A (VIS+wIRA) in combination with indocyanine green (ICG), oral microorganisms of the initial and mature biofilm were evaluated by mass spectrometry (MALDI-TOF-MS). To determine surviving microorganisms using MALDI-TOF-MS, an in situ biofilm was irradiated with VIS+wIRA for five minutes in the presence of ICG (300 and 450 µg/mL, respectively). Treatment with chlorhexidine (0.2%) served as positive control. Identified microorganisms of the initial biofilm treated with ICG showed a clear reduction in diversity. The microbial composition of the mature oral biofilm also showed changes after the implementation of aPDT, which mainly resulted in a shift in the percentage of bacterial species. The resulting destruction of the microbial balance within the oral biofilm by aPDT using VIS+wIRA and ICG can be seen as an advantageous supplementary approach in the adjunctive treatment of periodontitis and peri-implantitis.

The sialidase inhibitor, DANA, reduces Porphyromonas gingivalis pathogenicity and exerts anti-inflammatory effects: An in vitro and in vivo experiment.

Sialidase has an important role in the pathogenesis of periodontitis and Porphyromonas gingivalis is a sialidase-producing organism implicated in periodontitis development. The aim of this study was to evaluate the anti-virulence and anti-inflammatory properties of the sialidase inhibitor, 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (DANA), in vitro and in vivo. The effects of DANA on P. gingivalis sialidase and cell viability were determined, and the effects of DANA on P. gingivalis virulence were evaluated by assessment of growth curves, cell morphology, biofilm formation, fimbriae gene expression, and gingipains and lipopolysaccharide (LPS) activity. Anti-inflammatory effects of DANA on LPS-induced macrophages were assessed by measurement of tumor necrosis factor-alpha (TNF-α), interleukin (IL-1β), inducible nitric oxide synthase (iNOS) secretions. The effect of DANA on P. gingivalis-induced periodontitis in rats was analyzed by radiography, stereoscopic microscopy, histopathology, and immunohistochemistry. Sialidase inhibition rate of 1mM DANA was 72.01%. Compared with untreated controls, treatment with DANA inhibited P. gingivalis growth and biofilm formation, and significantly decreased expression of the fimA, fimR, and fimS genes, as well as gingipains activity. DANA did not influence macrophage viability, but significantly inhibited TNF-α, IL-1β, and iNOS production in LPS-stimulated macrophages. In the periodontitis rat model, DANA prevented alveolar bone absorption and inhibited TNF-α and IL-1β production. DANA can reduce the growth, the biofilm formation and the virulence of P. gingivalis and exhibits anti-inflammatory effects, as well as effects against rat periodontitis, suggesting that DANA should be considered for development as a new adjunctive treatment for periodontitis.

Synergistic effects of LFchimera and antibiotic against planktonic and biofilm form of Aggregatibacter actinomycetemcomitans.

Adjunctive use of antibiotics in periodontal treatment have limitations and disadvantages including bacterial resistance. Antimicrobial peptides (AMPs) are potential new agents that can combat bacterial infection. In this study, antimicrobial activity of different concentrations of conventional antibiotics minocycline (MH), doxycycline (DOX), and antimicrobial peptides LL-37, LL-31, Lactoferrin chimera (LFchimera) and Innate Defense Regulator Peptide 1018 (IDR-1018) against Aggregatibacter actinomycetemcomitans ATCC 43718 were determined using colony culturing assay. Subsequently, in vitro activity of the most effective drug and peptide combination was evaluated by checkerboard technique. Impact of the drug and peptide co-administration on biofilm at different stages, i.e., during adhesion and 1-day old biofilm was compared to each of the agents used alone. Results revealed that the killing effects of all AMPs range from 13–100%. In contrast, MH and DOX at 1 and 5 μM showed no killing activity and instead stimulated growth of bacteria. DOX has better killing activity than MH. LFchimera displayed the strongest killing amongst the peptides. Checkerboard technique revealed that combining DOX and LFchimera yielded synergism. Confocal laser scanning microscopy further showed that the combination of DOX and LFchimera caused significant reduction of bacterial adhesion and reduction of biomass, average biofilm thickness and substratum biofilm coverage of 1-day old biofilm compared to DOX and LFchimera alone. In conclusion, LFchimera alone and in combination with DOX exhibited strong antibacterial and anti-biofilm property against A. actinomycetemcomitans. The findings suggest that LFchimera should be considered for development as a new potential therapeutic agent that may be used as an adjunctive treatment for periodontitis.

Effect of Metronidazole Loaded Nanoparticles on Treatment of Induced Periodontal Defects in Dogs

Objective: The aim of the present study was to compare between 25% metronidazole gel and 25% metronidazole loaded nanoparticle gel formulation on healing of experimentally induced periodontal defects in dogs.Materials and Methods: Periodontal defects were induced by ligatures placement in 10 beagle dogs in both lower sites. The defects were randomly and equally allocated in a split-mouth design to either Metronidazole gel nanoparticles gel (25%) (Experimental site group I) or Metronidazole gel (25 %) (Control site group II) The animals were sacrificed with an overdose of anesthesia at 8 weeks and block sections of the defects were collected for histological and histometric analysis.Results: The results showed improved outcomes in terms of bone as well as new cementum and functionally oriented periodontal ligament formation. However, sites treated with metronidazole loaded nanoparticles (25%) gel formula (experimental group I) showed significantly greater regenerative potential of the attachment apparatus in terms of newly formed cementum and bone compared to conventional metronidazole gel treated group.Conclusion: This, in turn, proves that 25% metronidazole loaded nanoparticle gel is more efficient compared to conventional metronidazole gel in treatment of periodontal defects. Clinical Relevance: Scientific Rationale for Study: Evaluating the effect of metronidazole loaded nanoparticles on the treatment of induced periodontal defects in dogs. Principal Findings: Findings from this animal study of 10 beagle dogs supported the potential of metronidazole loaded nanoparticles gel, as compared to 25% metronidazole gel, for providing a safe, inexpensive, and effective therapy for induced periodontitis by regenerating new bone as well as new cementum and forming functionally oriented periodontal ligaments. Practical Implications: Metronidazole loaded nanoparticles gel can be used as adjunctive treatment of periodontitis.

Regulation of matrix metalloproteinase secretion by green tea catechins in a three-dimensional co-culture model of macrophages and gingival fibroblasts

ObjectivesElevated levels of matrix metalloproteinases (MMPs) have been associated with the active phases of tissue and bone destruction in periodontitis, an inflammatory disease characterized by a significant breakdown of tooth support. In the present study, we used a three-dimensional (3D) co-culture model of macrophages and gingival fibroblasts to investigate the ability of a green tea extract and its major constituent epigallocatechin-3-gallate (EGCG) to regulate the secretion of MMP-3, -8, and -9. MethodsThe 3D co-culture model was composed of gingival fibroblasts embedded in a type I collagen matrix overlaid with macrophages. Two arbitrary ratios were tested. The ratio composed of 1 macrophage to 10 fibroblasts was used to mimic a slightly inflamed periodontal site while the ratio composed of 10 macrophages to 1 fibroblast was used to mimic a severely inflamed periodontal site. The 3D co-culture model was pre-treated for 2h with either the green tea extract or EGCG. It was then stimulated with Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS). The model was also first stimulated with LPS for 2h and then incubated with the green tea extract or EGCG. The concentrations of secreted MMP-3, -8, and -9 were quantified by enzyme-linked immunoassays. ResultsWhen the 3D co-culture model was stimulated with A. actinomycetemcomitans LPS, the 10:1 ratio of macrophages to gingival fibroblasts was associated with a highest secretion of MMP-3 and -9 and, to a lesser extent, MMP-8, than the 1:10 ratio. Non-cytotoxic concentrations of the green tea extract or EGCG reduced the basal secretion levels of all three MMPs. A 2-h treatment with the green tea extract or EGCG prior to the stimulation with LPS resulted in a dose-dependent decrease in MMP secretion, with MMP-9 showing the most significant decrease. A decrease in MMP secretion was also observed when the green tea extract or EGCG was added following a 2-h stimulation with LPS. ConclusionsOur results suggested that green tea catechins, and more specifically EGCG, offer promising prospects for the development of a novel adjunctive treatment for periodontitis because of their ability to decrease the secretion of MMPs, which are important tissue-destructive enzymes produced by mucosal and immune cells.

Effects of low-dose doxycycline on cytokine secretion in human monocytes stimulated with Aggregatibacter actinomycetemcomitans

Doxycycline is an antibiotic used in the treatment of a variety of inflammatory conditions, including periodontitis. Apart from its antimicrobial properties, this drug also has independent anti-inflammatory effects at sub-antimicrobial doses. The present study aimed to investigate the effects of low-doses of doxycycline (LDD) on cytokine production by human monocytic cells challenged with the periodontal pathogen Aggregatibacter actinomycetemcomitans, for up to 6h. The simultaneous regulation of 12 cytokines were measured by a Human Cytokine Array Kit. To validate the array findings, selected cytokines were also measured by enzyme-linked immunosorbant assay (ELISA). A. actinomycetemcomitans stimulated the production of tumor necrosis factor (TNF)-α, interleukin (IL)-1α, IL-1β, IL-6 and IL-8 by the cells after 6h of challenge, and doxycycline significantly inhibited this effect. The kinetics of this regulation demonstrated an early (within 2h) and significant (P<0.05) inhibition of pro-inflammatory cytokines, with a mild (0.5-fold) up-regulation of the anti-inflammatory cytokine IL-10. The results indicate that LDD acts as an anti-inflammatory agent in human monocytic cells stimulated with A. actinomycetemcomitans. This model provides clear evidence that some of the clinically proven benefits of LDD may be related to its ability to regulate inflammatory mediator release by monocytic cells. This property may contribute to the clinically proven benefits of this antibiotic as an adjunctive treatment for periodontitis.

Cranberry components inhibit interleukin‐6, interleukin‐8, and prostaglandin E2 production by lipopolysaccharide‐activated gingival fibroblasts

Periodontitis is a chronic inflammatory disease that affects the tooth supporting tissues. Gingival fibroblasts are the most abundant cells in periodontal tissues and participate actively in the host inflammatory response to periodontopathogens, which is known to mediate local tissue destruction in periodontitis. The aim of this study was to investigate the effect of a proanthocyanidin-enriched cranberry fraction, prepared from cranberry juice concentrate, on inflammatory mediator production by gingival fibroblasts stimulated by the lipopolysaccharide (LPS) of Aggregatibacter actinomycetemcomitans. Interleukin (IL)-6, IL-8, and prostaglandin E(2) (PGE(2)) production by fibroblasts treated with the cranberry fraction and stimulated by A. actinomycetemcomitans LPS was evaluated by enzyme-linked immunosorbent assay. Changes induced by A. actinomycetemcomitans LPS and the cranberry fraction in the expression and phosphorylation state of fibroblast intracellular signaling proteins were characterized by antibody microarrays. The LPS-induced IL-6, IL-8, and PGE(2) responses of gingival fibroblasts were inhibited by treatment with the cranberry fraction. This fraction was found to inhibit fibroblast intracellular signaling proteins, a phenomenon that may lead to a down-regulation of activating protein-1 activity. Cranberry components also reduced cyclooxygenase 2 expression. This study suggests that cranberry juice contains molecules with interesting properties for the development of new host-modulating therapeutic strategies in the adjunctive treatment of periodontitis.

Measurement of total antioxidant capacity in gingival crevicular fluid and serum in dogs with periodontal disease

To determine whether gingival crevicular fluid (GCF) and serum total antioxidant capacities (TACs) correlate with the degree of severity of periodontal disease in dogs. 41 Toy and Miniature Poodles. After assessment of the degree of severity of naturally occurring periodontitis, GCF samples from both maxillary fourth premolars and a blood sample were collected from each dog. The condition of the periodontium of the entire dentition and at each site of GCF collection was recorded. Clinical parameters assessed included plaque index, gingival index, and probing depth. Radiographic analysis of alveolar bone level was also performed. Total antioxidant capacity was measured in GCF and serum samples by use of a commercial kit. Dogs with gingivitis and minimal periodontitis had significantly higher TAC in GCF than dogs with advanced periodontitis. Bivariate regression analysis revealed significant negative correlations between TAC in GCF and clinical parameters and age. The TAC in serum was significantly negatively correlated with the degree of gingival inflammation but was not significantly correlated with age. TAC in GCF is related to the degree of severity of periodontal disease in dogs. This is likely the result of release of reactive oxygen species by activated phagocytes and fibroblasts in the inflamed periodontal tissues. The results of our study suggest that the local delivery of antioxidants may be a useful adjunctive treatment for periodontitis in dogs.

Subantimicrobial dose doxycycline as adjunctive treatment for periodontitis. A review.

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. 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. 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. 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.