Surgical treatment of aggressive periodontitis
The diagnosis of aggressive periodontitis is often made at an advanced stage of the disease, which means that clinicians will have to treat severely compromised teeth. Consequently, after initial nonsurgical therapy, residual pockets will remain, and these may require surgical treatment. Surgery provides the practitioner with direct access to root surfaces and furcation areas, thus permitting a more thorough debridement. It has also been suggested that because A. actinomycetemcomitans can invade the pocket epithelium, placing itself out of reach of scaling and root planing, the removal of pocket epithelium can help in controlling the disease. Furthermore, intrabony defects can be addressed by either bone-recontouring or regenerative techniques. Although few studies have specifically addressed surgery in aggressive periodontitis, those that have often report positive results. If risk factors, such as smoking, can be controlled, the level of maintenance therapy is high and the patient is compliant, the outcome of periodontal surgery in aggressive periodontitis can be comparable with that in chronic periodontitis. Different surgical techniques are possible in patients with aggressive periodontitis.
The effectiveness of a modified Widman flap procedure in reducing probing pocket depths is shown in several small-sample-size studies. Christersson et al.  treated 25 deep periodontal lesions in seven patients with localized aggressive periodontitis using one of three treatments: scaling and root planing alone; scaling and root planing with additional soft-tissue curettage; or modified Widman flap surgery. Microbiological and clinical effects were monitored up to 16 weeks after treatment. The results showed that scaling and root planing alone did not effectively suppress A. actinomycetemcomitans in periodontal pockets, whereas scaling and root planing combined with soft-tissue curettage and modified Widman flap surgery did. Furthermore, the clinical response to treatment was significantly better for scaling and root planing combined with soft-tissue curettage and for modified Widman flap surgery . Lindhe & Liljenberg  treated 16 patients with localized aggressive periodontitis by means of tetracycline administration, scaling and root planing and modified Widman flap surgery, after which the patients were enrolled in a maintenance program for 5 years. Lesions at first molars and incisors in a group of patients with chronic periodontitis were treated in an identical manner and served as controls. The treatment resulted in the resolution of gingival inflammation, gain of clinical attachment and bone refill in angular bony defects. The healing of the lesions in the patients with aggressive periodontitis was similar to the healing observed in patients with chronic periodontitis . In another study, performed by Mandell & Socransky , eight patients with localized aggressive periodontitis were treated using modified Widman surgery and a doxycycline regimen. Twelve months after surgery the treatment had been effective in eliminating A. actinomycetemcomitans from the pockets and obtaining mean probing pocket-depth reductions of approximately 3.6 mm, as well as a mean attachment gain of 1.3 mm . Aside from these aforementioned studies there are many case reports in which modified Widman surgery helped to accomplish a stable periodontium [75, 80]. Buchman et al.  enrolled 13 patients with aggressive periodontitis in a prospective case series and reported gains in clinical attachment for up to 5 years after initial treatment. Treatment consisted of a combination of scaling and root planing, together with access surgery, without osseous recontouring for pockets deeper than 6 mm. All patients received amoxicillin combined with metronidazole systemically. A significant 2.3-mm gain in clinical attachment was recorded 3 months after therapy. These improvements were maintained for up to 5 years after treatment during which the patients were enrolled in a supportive periodontal-therapy program. In this study, periodontal-disease progression was successfully arrested in 95% of the initially compromised lesions, whilst 2–5% experienced discrete or recurrent episodes of loss of periodontal support .
An alternative to access surgery to resolve residual periodontal pockets is the use of regenerative techniques in an attempt to resolve intrabony defects. Many different techniques (such as bone grafting, guided tissue regeneration using membranes, the use of biologic modifiers and combinations of the above) have been developed over the years to regenerate vertical bone defects. These techniques were designed for the regeneration of steep vertical defects and have very specific indications, and their effectiveness is dependent on the defect morphology, tooth mobility and furcation involvement. Poor results are expected in the treatment of horizontal bone loss, furcation defects and increased tooth mobility .
Bone grafting can lead to regeneration by providing a scaffold for the ingrowth of bone. There are different types of grafts. Autografts are grafts that are harvested from the patient's own body and as such do not cause much tissue reaction during healing. Theoretically, the autograft contains viable bone cells, giving it osteogenic qualities aside from osteoconductive qualities. However, it has been shown that few bone cells survive the harvesting procedure. The autograft is the graft of choice when available, but there are limitations in obtaining it. Alternatives are allografts (e.g. freeze-dried bone allograft), xenografts (bovine or corral derived) and alloplastic materials (e.g. bioactive glass, hydroxyapatite and beta-tricalcium phosphate). Although case reports have been published on their utility in patients with aggressive periodontitis [22, 28, 95], very few controlled studies have been conducted using adequate numbers of patients or in which treatments were compared. Using freeze-dried bone allografts, Yukna & Sepe  reported an average defect fill of 80% in 12 patients with localized aggressive periodontitis at re-entry after 12 months. In addition to this study, using a split-mouth approach, Mabry et al.  demonstrated significantly greater bone fill (mean = 2.8 mm) and resolution of osseous defects (mean = 72.7%) in allogeneic freeze-dried bone-grafted osseous bone defects in 16 patients with localized aggressive periodontitis when compared with defects that were treated with debridement only. The best results were obtained when adjunctive systemic tetracycline was administered using the surgical procedure. Evans et al.  evaluated a 4:1 (volume by volume) ratio combination of beta-tricalcium phosphate/tetracycline, hydroxyapatite/tetracycline or freeze-dried bone allograft/tetracycline in a split-mouth study of 10 patients with localized aggressive periodontitis. At re-entry, significant decreases in defect depth and pocket depth were detected for each graft material. No significant differences between the different grafting materials were found in terms of hard-tissue or soft-tissue changes. However, a greater percentage of defect fill was demonstrated for hydroxyapatite/tetracycline compared with beta-tricalcium phosphate/tetracycline. The results of these studies show that the use of these grafting materials in combination with tetracycline can result in additional bone fill and resolution of the residual osseous defects in patients with localized aggressive periodontitis.
Guided tissue regeneration using membranes
Membranes are used to influence the ingrowth of different tissues into intrabony defects. By holding off the ingrowth of epithelium and connective tissue, cells from the periodontal ligament are allowed to grow into the defect, resulting in regeneration of the periodontal attachment. There are nonresorbable and resorbable membranes. Nonresorbable membranes provide a marginally greater attachment gain, but a second procedure is necessary for removing them. Resorbable membranes are biodegradable and do not require a second procedure to remove them; however, they do cause a greater inflammatory response. The use of nonresorbable expanded polytetrafluoroethylene membranes has been shown to be effective for regenerating intrabony defects in aggressive periodontitis in case reports [25, 61, 89, 109].
Using a split-mouth approach, Sirirat et al.  compared the effect of a polytetrafluoroethylene membrane with osseous surgery in six patients with aggressive periodontitis. Whilst both treatments were effective 1 year following surgery, probing depth reduction and clinical attachment gain were significantly greater in the polytetrafluoroethylene membrane-treated defects than in the osseous surgery-treated defects, reaching a mean probing pocket-depth reduction of 2.6 mm and a gain in clinical attachment of 2.2 mm. The base of the polytetrafluoroethylene membrane-treated defects showed a significant increase in bone fill. Zucchelli et al.  treated similar intrabony defects in 10 patients with localized aggressive periodontits and in 10 patients with chronic periodontitis using titanium-reinforced polytetrafluoroethylene membranes. After 1 year there were no significant differences in the amount of clinical attachment gain, reduction of probing pocket depth or increase in gingival recession between chronic periodontitis and localized aggressive periodontitis groups. DiBattista et al.  treated seven patients with intrabony defects on first molars using surgical debridement, polytetrafluoroethylene membrane, polytetrafluoroethylene membrane with root conditioning or polytetrafluoroethylene membrane plus root conditioning and composite graft, consisting of calcium-sulfate, freeze-dried bone allograft and doxycycline. A significant gain in attachment and bone fill was observed for all techniques. There were no significant differences in results between the techniques. The average gain in attachment for all sites combined was 3.2 mm. The number of patients in relation to the number of tested treatments in this study is low and does not permit reasonable conclusions to be made on the effect of the separate techniques. Mengel et al.  performed a comparative study on the regeneration of one- to three-wall bony defects in 12 patients with generalized aggressive periodontitis using a bioresorbable membrane or with bioactive glass. They treated 22 defects using a membrane and 20 defects using the alloplastic graft. Both treatment modalities resulted in significant changes in probing pocket depth and in clinical attachment gain of about 4 mm and 3 mm, respectively. No significant differences between the two treatments were found.
The use of enamel matrix proteins (amelogenin) attempts to recreate the physiological environment for the development of the periodontal ligament. This allows the regeneration of new cementum and the formation of new attachment in periodontal defects. The use of enamel matrix protein results in more attachment gain than open-flap debridement in patients with chronic periodontitis . There is, however, little evidence for an advantage in patients with aggressive periodontitis. Most published articles on the use of enamel matrix protein in patients with aggressive periodontitis are case reports [9, 42]. In this regard, Vandana et al.  published a case series involving four patients with chronic periodontitis and four patients with aggressive periodontitis. Sixteen intrabony defects were surgically treated with either enamel matrix proteins or surgical debridement alone using a split-mouth design. The mean pocket-depth reduction and amount of defect fill were significant in both treatments, 9 months postsurgery, in both groups of patients. No significant differences in mean pocket-depth reduction, clinical attachment level gain, amount of defect fill or defect resolution were detected between the two treatments, in both groups of patients. This study failed to demonstrate an advantage of using enamel matrix proteins compared with surgical debridement alone.
Growth factors and differentiation factors also play an import role in tissue development and healing and are therefore used as tools for gaining attachment. Mediators such as platelet-derived growth factor, insulin-like growth factor, fibroblast growth factor, bone morphogenetic protein and transforming growth factor-beta have shown promising results in animal studies and in vitro [71, 79, 97]. Platelet-rich plasma has been shown to improve clinical and radiographic parameters for compromised teeth . Their disadvantages are the low tissue specificity and unknown systemic effects. At present, their effectiveness in patients with aggressive periodontitis is unknown [23, 80]. There is, however, a case series published by Mauro et al.  on the regenerative surgery of intrabony defects with platelet gel. Three patients, who had shown a refractory response to previous treatments, were treated and followed for 15 months. The operated sites showed a reduction of pocket depth and a gain in attachment. Moreover, the effect remained stable during the 15-month follow up, whereas previous treatments had not been as effective .
Once treatment has resulted in a stable and healthy periodontium, the patient should enter a maintenance program. The purpose of this supportive periodontal therapy is to ensure that periodontal health is maintained after active therapy , so that no additional teeth are lost and disease recurrence is prevented. Supportive periodontal therapy should therefore be directed towards risk factors for disease recurrence and tooth loss. Several factors (such as smoking, diabetes mellitus, age, irregular supportive periodontal therapy and ineffective plaque control) have been shown to increase the risk for tooth loss during supportive periodontal therapy in patients with chronic periodontitis [13-15, 48, 59]. A higher risk for disease recurrence and tooth loss after active periodontal therapy can be anticipated in patients with aggressive periodontitis than in patients with chronic periodontitis because of a higher susceptibility for disease progression in patients in the former group. However, the risk factors for tooth loss and/or recurrence of periodontitis in patients with aggressive periodontitis have only recently been investigated. Few studies have assessed the mean tooth loss in patients with aggressive periodontitis during supportive periodontal therapy [8, 35, 85]. The mean annual tooth loss for these patients seems to range from 0.11  to 0.29  teeth, although in the latter study also untreated patients were included. In the recent retrospective study of Baumer et al. , tooth loss of 0.13 teeth/year was calculated in patients with aggressive periodontitis. Interestingly, when the authors differentiated between the different types of aggressive periodontitis, patients with generalized aggressive periodontitis exhibited a higher tooth loss, of 0.14 teeth/year, whereas patients with localized aggressive periodontitis only lost 0.02 teeth/year. An additional analysis showed that patients with aggressive periodontitis who followed the supportive periodontal care regularly had a tooth loss of 0.075 teeth/year, whereas patients with irregular periodontal care had a tooth loss of 0.15 teeth/year, stressing the importance of regular periodontal supportive therapy. Age, low educational status and absence of the interleukin-1 composite genotype were significantly correlated with tooth loss and could be defined as risk factors. Nearly significant correlations could be found for smoking, type of aggressive periodontitis, irregular supportive periodontal therapy and the plaque-control record. In terms of risk factors for disease recurrence (defined as the occurrence of probing pocket depths of 5 mm or more at 30% or more of the teeth), Baumer et al.  also identified smoking as the main significant risk factor, thereby confirming the data from Kamma & Baehni . In the latter study, the authors also identified stress as a significant predictive factor for future clinical attachment loss. The type of aggressive periodontitis was a nearly significant risk factor for which patients with generalized aggressive periodontitis showed an odds ratio of 35.2 for recurrence and which confirms the results of studies showing long-term stability of the disease in patients with localized aggressive periodontitis [35, 65]. Additionally, an elevated gingival bleeding index and a high plaque-control record showed odds ratios of 31.1 and 63.8, respectively, for disease recurrence. No statistical analysis could be performed for supportive periodontal treatment as a risk factor for disease recurrence because none of the patients receiving regular supportive periodontal therapy experienced recurrence of the disease. However, this stresses the effectiveness of this risk factor. In summary, age, educational status, generalized aggressive periodontitis (vs. localized aggressive periodontitis), absence of the interleukin-1 composite genotype, irregular supportive periodontal therapy, smoking, high mean gingival bleeding index and high plaque-control records are important risk factors for disease recurrence or tooth loss in patients with aggressive periodontitis. Of these, maintenance of supportive periodontal therapy, smoking, high mean gingival bleeding index and high plaque-control records are modifiable risk factors, and the latter two are correlated with the patient's oral hygiene. Therefore, it seems tempting to support the daily oral hygiene of aggressive periodontitis patients with antiseptics as part of the supportive periodontal therapy. To date, only one trial, performed by Guarnelli et al.  in 18 patients, has evaluated the effect of an amine fluoride/stannous fluoride-containing mouthrinse in patients with aggressive periodontitis. In a crossover clinical trial this mouthrinse was effective for reducing the amount of supragingival plaque deposits. However, there was no significant difference compared with the placebo mouthwash on the gingivitis index. The impact of these results on disease progression and tooth loss has not been determined.
Regular supportive periodontal therapy has been shown to be effective in controlling the progression of aggressive periodontitis. Maintenance therapy is considered to be a lifelong requirement, but the frequency of recall visits is unclear. The use of many different protocols is being reported in the literature. Deas & Mealey  stated that monthly intervals are advisable during the first 6 months of maintenance. Some studies have reported an effective control of disease progression using three to four recall visits per year. To date there are no studies comparing the effect of different follow-up intervals in patients with aggressive periodontitis. In order to define such intervals for patients with chronic periodontitis, the periodontal risk assessment, which estimates the patient's risk profile for the progression of periodontitis, based on six risk factors, was created . Meyer-Baumer et al.  recently attempted to confirm the prognostic value of the model in aggressive periodontitis. When the interleukin-1 composite genotype was not taken into account, the impact of this model could be shown to be statistically significant and allowed patients with aggressive periodontitis to be characterized into different risk groups.
Finally, needless to say, each visit for supportive periodontal treatment should consist of a thorough medical review, an inquiry into recent periodontal problems, an extensive oral examination, a renewal of oral-hygiene instructions, debridement of residual pockets and prophylaxis. Also, the need to control modifiable risk factors, such as smoking, must be stressed to the patient.