Short-term effects of an anti-inflammatory treatment on clinical parameters and serum levels of C-reactive protein and proinflammatory cytokines in subjects with periodontitis.

BACKGROUND: Periodontal disease is the most common multifactorial disease, afflicting a very large proportion of the adult population. Periodontal disease secondarily causes increases in the serum levels of C-reactive protein (CRP) and other markers of inflammation. An increased level of CRP reflects an increased risk for cardiovascular disease. The aim of the current randomized clinical trial was to evaluate the short-term effect of a combination of dipyridamole and prednisolone (CRx-102) on the levels of high-sensitivity (hs)-CRP, proinflammatory markers in blood, and clinical signs of periodontal disease. METHODS: Fifty-seven patients with >/=10 pockets with probing depths >/=5 mm were randomized into two groups in this masked single-center placebo-controlled study: CRx-102 (n = 28) and placebo (n = 29). hs-CRP levels, inflammatory markers (interleukin [IL]-6, -1beta, -8, and -12, tumor necrosis factor-alpha, and interferon-gamma [IFN-gamma]), bleeding on probing (BOP), and changes in probing depths were evaluated. The subjects received mechanical non-surgical therapy after 42 days, and the study was completed after 49 days. RESULTS: At day 42, the differences in the hs-CRP, IFN-gamma, and IL-6 levels between the two groups were statistically significant (P <0.05), whereas no difference was found for the other inflammatory markers. There was no change in probing depth or BOP between the two groups. CONCLUSION: The administration of CRx-102 resulted in significant decreases in hs-CRP, IFN-gamma, and IL-6, but it did not significantly change BOP or probing depths.

Mechanical and repeated antimicrobial therapy using a local drug delivery system in the treatment of peri-implantitis: a randomized clinical trial.

BACKGROUND: Peri-implantitis is an inflammatory process caused by microorganisms affecting the tissues around an osseointegrated implant in function, resulting in a loss of supporting bone. Limited data exist regarding the treatment of peri-implantitis. The aim of this study was to assess the clinical and microbiologic outcome of repeated local administration of minocycline microspheres, 1 mg, in cases of peri-implantitis. METHODS: Thirty-two subjects with at least one implant with a probing depth > or =4 mm combined with bleeding and/or exudate on probing and the presence of putative pathogenic bacteria were included in the study. At baseline, subjects were randomly assigned to receive local minocycline microspheres (17 subjects and 57 implants) or chlorhexidine gel (15 subjects and 38 implants) following debridement. Treatments were performed on three occasions: baseline and days 30 and 90. Follow-up examinations were conducted at 10 days and at 1, 3, 6, 9, and 12 months. RESULTS: The use of minocycline resulted in significant improvements in probing depths compared to chlorhexidine at days 30, 90, and 180 (P = 0.5, P = 0.01, and P = 0.04, respectively). For the deepest sites of the minocycline-treated implants, the mean probing depth reduction was 0.6 mm at 12 months. Regarding bleeding on probing, significant differences between groups, based on all four sites at the implants, were found at days 30, 90, 180, 270, and 360. Both treatments resulted in a marked reduction in the indicator bacteria. CONCLUSIONS: The use of a repeated local antibiotic as an adjunct to the mechanical treatment of peri-implantitis lesions demonstrated improvements in probing depths that were significantly different from controls and were sustained for 6 months. The adjunctive use of minocycline microspheres is beneficial in the treatment of peri-implant lesions, but the treatment may have to be repeated.

Periodontal infections cause changes in traditional and novel cardiovascular risk factors: results from a randomized controlled clinical trial.

BACKGROUND: Chronic infections, such as periodontitis, are associated with increased risk of systemic diseases driven by a persistent low-grade systemic inflammation and metabolic changes. Severity of periodontitis has also been associated with increased systolic blood pressure (BP). However, the issue remains poorly investigated. We aimed to estimate the effect of periodontal therapy on traditional and novel cardiovascular risk factors in systemically healthy individuals who have periodontitis. METHODS: We enrolled 40 otherwise healthy patients with severe chronic generalized periodontitis in a 6-month pilot intervention trial. Individuals were randomized either to a standard course of periodontal therapy (subgingival scaling and root planing) or an intensive one (including the adjunctive use of a locally delivered antimicrobial, IPT). RESULTS: Compared to control, IPT produced significant reductions in a cluster of inflammatory markers at 1 (P = .0406) and 2 (P = .0060) months together with an improvement in lipid markers at 2 (P = .0320) and 6 (P = .0432) months after therapy. Intensive periodontal therapy produced greater reductions in IL-6 at 1 (0.4 +/- 0.2 ng/L difference, 95% CI 0.03-0.9, P = .0284) and 2 months (0.3 +/- 0.2 ng/L difference, 95% CI 0.1-0.8, P = .0284), together with decreases in C-reactive protein (0.4 +/- 0.2 mg/L difference, 95% CI 0.01-0.8, P = .0438) and total cholesterol (0.3 +/- 0.1 mmol/L difference, 95% CI 0.04-0.6, P = .0254). Moreover, a 7 +/- 3-mm Hg decrease in systolic BP was observed at 2 months in the IPT group (95% CI 1-12, P = .0211), and this difference was greater in current smokers (14 +/- 5 mm Hg 95% CI 3-25, P = 0.0124). Intensive periodontal therapy subjects exhibited a 1.53% +/- 1.20% (95% CI 1.05-2.24, P = .0290) and 2.00% +/- 1.42% (95% CI 0.98-4.09, P = .0568) decreases in cardiovascular risk scores (Framingham) at 2 and 6 months, respectively, when compared to those in the standard group. CONCLUSIONS: Our findings suggest that intensive periodontal treatment reduces systemic inflammatory markers and systolic BP, and improves lipid profiles with subsequent changes in cardiovascular risk when compared to standard therapy.

Periodontitis in cardiology--a clinical perspective.

The association between ischemic cardiovascular disease and infectious disease is very dubious, and evidence points in several directions. Chronic periodontitis has been proposed as a potential risk factor based on many studies. A review of these studies demonstrates that the majority of them are retrospective epidemiological studies and therefore of little value in determining a possible association. New data seems to indicate an association between atherosclerosis and alveolar bone loss, thus indicating that a long-standing burden of infection is related to the slow process of atherosclerosis plaque buildup. Future secondary prevention studies will have to be performed to determine if periodontal therapy intervention results in decreased cardiovascular mortality or morbidity, proving a strong association between the two diseases.

A post-marketing study of 2805 patients treated for periodontal disease with Arestin.

Recent studies have demonstrated the effectiveness of locally delivered antibiotics adjunctive with scaling and root planing (SRP) in patients with chronic periodontitis. Specifically, several studies have demonstrated the efficacy of minocycline microspheres (Arestin). The objective of the current study was to evaluate the use of Arestin in a study using private practices all over the United States and adopting a predefined protocol. Eight hundred ninety-five dentists and 2805 patients participated in the largest reported trial in chronic periodontal disease in private practice. The protocol outlined that patients were to have SRP at baseline with one application of Arestin in all pockets > or = 5 mm, a recall visit three months later that included a second application of Arestin, and a final assessment after 6 months. One thousand ninety five patients were treated in accordance with the protocol, and 1710 patients returned for a second assessment but only received one therapeutic intervention. Mean pocket depth reduction from baseline in the 1710 patients was 1.82 mm (p < 0.0001) and for the 1095 patients at 6 months it was 1.94 mm (p < 0.0001). Similar results were obtained in smokers, diabetes patients and patients with a history of cardiovascular disease. After 1 treatment 62% of sites had decreased to less than 5 mm and after two treatments the corresponding number was 67%. There were no serious adverse events in the study. This study demonstrated that a large study could be conducted in a private practice setting, that Arestin and SRP were effective in reducing pocket depth, and that adherence to the protocol yielded additional benefits.

Treatment of incipient peri-implant infections using topical minocycline microspheres versus topical chlorhexidine gel as an adjunct to mechanical debridement.

This report presents the clinical results three months after application of minocycline microspheres as an adjunct to mechanical treatment of incipient peri-implant infections compared to adjunctive treatment employing 1% chlorhexidine gel application. Sixteen patients in the minocycline group and 14 in the chlorhexidine group completed the study. Each patient had one or more implants with probing depth > or = 4 mm combined with bleeding and/or exudate on probing and presence of putative pathogenic bacteria. At baseline, patients were randomly assigned to minocycline or chlorhexidine treatment. Follow-up examinations were carried out after 10, 30, 60 and 90 days. The combined mechanical/antimicrobial treatment for the chlorhexidine group did not result in any reduction in probing depth and only limited reduction of bleeding scores. The adjunctive use of minocycline microspheres, on the other hand, resulted in improvements in both probing depths and bleeding scores. For the deepest sites of the treated implants, mean probing depth was reduced from 5.0 mm to 4.1 mm. The reductions in bleeding scores, although greater than for the chlorhexidine group, were modest. Thus, the question as to what extent the combined mechanical/minocycline treatment could be considered adequate for the treated lesions remains to be answered. The present short-term findings, however, encourage further studies with longer observation intervals on adjunctive use of minocycline microspheres in the treatment of periimplant lesions.

Enhancing the value of scaling and root-planing: Arestin clinical trial results.

Locally delivered antibiotics are used to treat periodontitis and these agents are found to be effective in improving the treatment result. Microencapsulated minocycline hydrochloride (Arestin) has been tested and reported to provide significantly greater probing depth reduction in conjunction with scaling and root-planing than scaling and root-planing alone. Thus, it was suggested that the use of locally delivered antimicrobial agents should be incorporated as part of an optimal non-surgical therapeutic regimen. This paper evaluates the efficacy of the minocycline microspheres in patients with moderate to severe periodontitis in a model, which is a randomised, evaluator-blinded study with an open-label; four arm parallel design. The patients were selected based upon 'active' disease, as determined by at least two teeth having one site each with pocket depth (PD) > or = 6 mm and with prostaglandin E2 (PGE2) levels > 66.2 ng/ml in gingival crevicular fluid. The trial was of 6 months duration and used a formulation of minocycline microspheres containing 1 mg minocycline. Responses of groups receiving SRP followed by one dose per pocket of the minocycline microspheres (SRP + MPTS) were compared to SRP alone, MPTS alone or no treatment. There were substantially greater reductions in PD and gains in clinical attachment level (CAL) at each post-treatment time point in the SRP + MPTS group compared to the other treatment groups. PD reduction and gain in CAL at month 3 in the SRP + MPTS group vs. SRP alone was statistically significant. These data further support the adjunctive use of minocycline in a slow release vehicle for the treatment of periodontitis with SRP.

The challenge of treating periodontal patients who smoke--the efficacy of Arestin.

Smoking is considered a risk factor for periodontitis and an impediment to treatment. The current studies evaluated the efficacy of the local administration of 1 mg minocycline hydrochloride encapsulated in a bioresorbable polymer in periodontal pockets of > or = 5 mm in all three studies. Two hundred and seventy one patients who smoked were enrolled in the two single blind controlled studies (data pooled) with efficacy compared to scaling and root planing (SRP) and 71 smokers were enrolled in an open label study. In the three studies SRP was performed at baseline and the unit dose minocycline administered at baseline, three and six months. Efficacy and safety were measured at one, three, six, and nine months. Adjunctive treatment resulted in statistically significant pocket depth reduction in both studies in these smokers. In the controlled studies the difference in probing depth reduction between the adjunctive therapy group and the SRP alone group was statistically significant at one, three, six, and nine months. No serious adverse events were recorded in any of the studies.

Periodontal treatment by Arestin and its effects on glycemic control in type 1 diabetes patients.

Studies indicate that a dual pathway between diabetes mellitus and periodontal disease exists. Elimination of periodontal infection by using systemic antibiotics in conjunction with scaling and root planing (SRP) improved metabolic control in diabetic patients, as defined by reduction in glycated haemoglobin or reduction in insulin requirements (Grossi and Genco, 1998). The aim of this randomised pilot clinical trial was to determine if type 1 diabetes patients with periodontitis will experience a reduction in HbA1c levels when treated with locally delivered minocycline microspheres (Arestin) as an adjunct to scaling and root planing. Twenty adult patients with poorly controlled diabetes (HbA1c 7.5%) and adult periodontitis, as determined by the presence of four teeth with 5 mm periodontal pockets, two of which had 6-9 mm pockets and bleeding on probing, were included in the study. All patients received full mouth SRP at baseline. Arestin was administered to all pockets > or => or = 5 mm at baseline and again at 12 weeks in the test group. Probing depth (PD), clinical attachment level (CAL), plaque index (PI), gingival index (GI), and HbA1c were evaluated at baseline and at weeks 6, 12, 18 and 24. The results demonstrated that local administration of Arestin as an adjunct to scaling and root planing is significantly more effective in reducing probing depths and providing a gain in clinical attachment levels than scaling and root planing alone in type 1 diabetic patients. Hb1Ac was reduced in all patients; however the difference between the test and control groups was not significant.

Are cardiac transplant patients more likely to have periodontitis? A case record study.

In several large epidemiological studies chronic periodontitis has been implicated as an additional risk factor, independent of other risk factors, for the development of ischaemic heart disease. The underlying mechanism is thought to be a localised infection giving rise to an inflammatory host response, and some experimental data agree with this hypothesis. Recently, however, some studies have questioned the post dated relationship between the two diseases. The current case-record study was undertaken to evaluate the prevalence of chronic periodontitis and the severity of such periodontal disease in a heart transplant population, assuming the latter represented a relatively severely compromised cardiovascular patient population. The study demonstrated that 76% of the patients had various degrees of periodontal disease prior to undergoing a heart transplant. Thus, it is possible that a relationship between cardiovascular disease and periodontal disease exists, but further, large intervention studies will be needed to confirm such a conclusion.

Topically applied minocycline microspheres: why it works.

This article presents the results of a single-arm, open-label, multicenter clinical trial of the topical use of sustained-release minocycline hydrochloride (HCl) microspheres as an adjunct to scaling and root planing. The objective of this study was to evaluate the long-term safety and efficacy of the subgingival application of resorbable minocycline microspheres as an adjunct to scaling and root planing in the treatment of chronic periodontitis. The primary outcome measures were the reduction in probing pocket depth at 9- and 12-month evaluations, and the percent of bleeding upon probing. A total of 173 patients with moderate-to-severe chronic periodontitis were enrolled in this multicenter clinical trial. All patients received full-mouth scaling and root planing plus minocycline microspheres in all periodontal pockets that probed > or = 5 mm. All sites treated at baseline and any new sites > or = 5 mm again received minocycline microspheres at 3- and 6-month follow-up appointments with no further scaling and root planing. Significant improvements in all clinical parameters measured were found at all time points (1, 3, 6, 9 and 12 months). The product was found to be well-tolerated by patients, safe, and easy to deliver. Scaling and root planing with the topical application of minocycline microspheres appeared to give better results than would have been expected with scaling and root planing alone.

Dermagraft: Use in the Treatment of Chronic Wounds.

PROBLEM: Lower limb ulceration is a common problem in clinical practice. A variety of metabolic and physical causes can lead to a diversity of chronic ulcer types, including diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs). SOLUTION: A wide variety of technologies have been developed to treat chronic wounds, with varying levels of success. Depending upon the type and severity of the wound being treated, treatments may include systemic or local antibiotic therapy, application of fillers such as collagen sponges, use of negative wound pressure, hyperbaric oxygen therapy, application of select growth factors, advanced wound dressings, and more recently, the use of cell-based tissue-engineered products. NEW TECHNOLOGY: Dermagraft® is a sterile, cryopreserved, human fibroblast-derived dermal substitute generated by the culture of neonatal dermal fibroblasts onto a bioabsorbable polyglactin mesh scaffold. During the product-manufacturing process, the human fibroblasts proliferate to fill the interstices of this scaffold and secrete collagen, other extracellular matrix proteins, growth factors, and cytokines, creating a three-dimensional human tissue containing metabolically active living cells. INDICATIONS FOR USE: Dermagraft has been approved for marketing in the United States for the treatment of DFUs. In addition, the product is in active development for the treatment of VLUs and has been clinically used in a variety of other indications to stimulate wound healing. CAUTION: When treating DFUs, Dermagraft should be used in conjunction with standard wound care regimens and in patients who have adequate blood supply to the involved foot.

Topical minocycline microspheres versus topical chlorhexidine gel as an adjunct to mechanical debridement of incipient peri-implant infections: a randomized clinical trial.

AIM: This randomized clinical trial presents a 12-month follow-up of the clinical and microbiological results after application of minocycline microspheres as an adjunct to mechanical treatment of incipient peri-implant infections compared with an adjunctive treatment using 1% chlorhexidine gel application. MATERIAL AND METHODS: Thirty-two subjects with probing depth > or =4 mm, combined with bleeding and/or exudate on probing and presence of putative pathogenic bacteria were given oral hygiene instructions and mechanical treatment of infected areas adjacent to implants. The subjects were then randomly assigned adjunctive subgingival antimicrobial treatment using either chlorhexidine gel or minocycline microspheres. Sixteen patients in the minocycline group and 14 in the chlorhexidine group completed the study. Follow-up examinations were carried out after 10 days, 1, 2, 3, 6, 9 and 12 months. RESULTS: The adjunctive use of minocycline microspheres resulted in improvements of probing depths and bleeding scores, whereas the adjunctive use of chlorhexidine only resulted in limited reduction of bleeding scores. For the deepest sites of the treated implants in the minocycline group, the mean probing depth was reduced from 5.0 to 4.4 mm at 12 months. This study could not show any significant difference in the levels of bacterial species or groups at any time point between the two antimicrobial agents tested. The present findings encourage further studies on adjunctive use of minocycline microspheres in the treatment of peri-implant lesions. CONCLUSIONS: The use of a local antibiotic as an adjunct to mechanical treatment of incipient peri-implantitis lesions demonstrated improvements in probing depths that were sustained over 12 months.

Locally delivered minocycline microspheres for the treatment of periodontitis in smokers.

AIM: The aim of the present analysis of a larger phase 3 clinical trial was to evaluate the efficacy of 1 mg minocycline hydrochloride microencapsulated in 3 mg of resorbable polymer, subgingivally administered as an adjunct to scaling and root planing (SRP) in smokers with chronic periodontitis. MATERIAL AND METHODS: Two hundred and seventy-one patients who smoked were randomized to one of three treatment groups: (1) SRP alone, (2) SRP plus vehicle (polymer without minocycline) or (3) SRP plus minocycline microspheres. Full mouth SRP was performed for all groups at baseline, and vehicle or minocycline microspheres were administered to the appropriate patients at all periodontal pockets > or =5 mm at baseline, 3 and 6 months. Efficacy was evaluated over 9 months. RESULTS: Significantly greater pocket depth reductions with SRP plus adjunctive minocycline microsphere treatment were observed at 1, 6 and 9 months (p<0.05) versus control treatments. At 9 months, smokers treated with SRP plus minocycline microspheres exhibited a pocket depth reduction of 1.19 mm from baseline, as compared to 0.90 mm for smokers treated with SRP alone. The efficacy of adjunctive minocycline microspheres was consistent among all tested smoking subcohorts, including those based on gender, age and smoking exposures. CONCLUSION: These data indicate that treatment with SRP plus locally delivered minocycline microspheres is more effective than SRP alone in reducing pocket depths in smokers with periodontitis.