Treatment of intrabony defects with enamel matrix proteins and guided tissue regeneration. A prospective controlled clinical study. Comparison of infrabony defects treated with enamel matrix derivative versus guided tissue regeneration with a nonresorbable membrane. Treatment of intrabony defects with enamel matrix proteins or barrier membranes: results from a multicenter practice-based clinical trial. Treatment of intrabony defects using guided tissue regeneration or enamel matrix derivative: a 3-year prospective randomized clinical study. Enamel matrix proteins in the treatment of intra-bony defects. A prospective 24-month clinical trial. Enamel matrix proteins and guided tissue regeneration with titanium-reinforced expanded polytetrafluoroethylene membranes in the treatment of infrabony defects: a comparative controlled clinical trial. Enamel matrix derivative in the treatment of human intrabony osseous defects. Enamel matrix proteins in the regenerative therapy of deep intrabony defects. Comparison of treatments of infrabony defects with enamel matrix derivative, guided tissue regeneration with a nonresorbable membrane and Widman modified flap. A pilot study.
Utilisation of enamel matrix proteins (EMD) and application of the guided tissue regeneration principle (GTR) are treatment modalities which both have been shown to result in periodontal regeneration. However, it is yet unknown whether the combination of EMD and GTR may additionally favor the regeneration process.
                The aim of the present controlled study was to evaluate clinically the treatment effect of EMD, GTR, combination of EMD and GTR, and flap surgery (control) on intrabony defects.
                56 patients each of whom displaying one intrabony defect of a depth of at least 6 mm were randomly treated with one of the treatment modalities. Prior to surgery and at one year after, the following parameters were evaluated by a blinded examiner: Plaque index (PlI), gingival index (GI), bleeding on probing (BOP), probing pocket depth (PPD), gingival recession (GR) and clinical attachment level (CAL). No statistical significant differences between the four groups were observed at baseline for any of the investigated parameters.
                At 1 year after therapy, the sites treated with EMD demonstrated a mean PPD reduction of 4.1 +/- 1.7 mm and a mean CAL gain of 3.4 +/- 1.5 mm (p<0.001). The sites treated with GTR showed a mean PPD reduction of 4.2 +/- 1.9 mm and a mean CAL gain of 3.1 +/- 1.5 mm (p<0.001). The sites treated with the combined treatment showed a mean PPD reduction of 4.3 +/- 1.4 mm and a mean CAL gain of 3.4 +/- 1.1 mm (p<0.001). In the control group, the mean PPD reduction was 3.7 +/- 1.4 mm (p<0.001) and the mean CAL gain measured 1.7 +/- 1.5 mm (p<0.01). All 4 treatments led to statistically significant PPD reduction and CAL gain. All three regenerative treatments led to higher CAL gain than the control treatment (p<0.05). No statistical significant differences in PPD reduction and CAL gain were observed between the three regenerative treatments.
                It may be concluded that (a) all 3 regenerative treatment modalities may lead to higher CAL gain than the control one, and (b) the combined treatment does not seem to improve the outcome of the regenerative procedure. The purpose of the present multicenter clinical trial was to compare the efficacy of two different procedures in the treatment of infrabony defects: guided tissue regeneration (GTR) with nonresorbable membranes and enamel matrix derivative (EMD).
                Six centers participated in this study. Ninety-eight patients with an interproximal infrabony defect were selected. All patients were treated with an initial phase of scaling and root planing, and at the study's baseline the selected defects presented a value of probing depth (PD) > or =6 mm with an infrabony component > or =4 mm. Forty-nine patients were treated with GTR procedures (using ePTFE membranes (Gore-Tex W.L. Gore and Associates, Flagstaff, AZ, USA)) and forty-nine with EMDs (Emdogain (U Biora AB Malm, Sweden)). The efficacy of each treatment modality was investigated through covariance analysis.
                The patients were reevaluated at one year postop. Probing attachment level (PAL) gain and PD reduction were analyzed. In the Emdogain group the PAL before surgery (PAL 0) and the PD before surgery (PD 0) were respectively 9.9+/-1.4 and 8.5+/-1.6 mm. The PAL gain and the PD reduction at 1 year postsurgery were respectively 4.1+/-1.8 and 5.3+/-1.9 mm. The group of patients treated with membranes showed that PAL 0 and PD 0 were respectively 8.9+/-1.9 and 8.1+/-1.9. The PAL gain was 4.3+/-1.9 mm and the PD reduction was 5.6+/-1.5 mm. The mean PAL gain expressed by percentage (PAL gain/PAL 0) for the group treated with EMD was 41%, while it was 48% for the group treated with GTR. Results from our analysis suggest that there is no statistically significant difference between GTR and EMD treatments in terms of PAL gain, PD reduction and recession variation. Applying the regression model to a group of patients with a PAL 0 > or =8 mm, we observed a better clinical outcome in terms of PAL gain (difference of 0.3 mm) in patients treated with the GTR procedure compared to those treated with EMD. Covariance analysis showed a strong correlation in both groups of patients between PAL gain and full mouth bleeding score, and between PAL gain and defect morphology and depth. This prospective multicenter, randomized, controlled clinical trial compared the clinical outcomes of enamel matrix proteins (EMD) versus placement of a bioabsorbable membrane in conjunction with guided tissue regeneration (GTR).
                Seventy-five patients with advanced chronic periodontitis were recruited in seven centers in three countries. All patients had at least one intrabony defect of > or = 3 mm. Heavy smokers (> or = 20 cigarettes/day) were excluded. The surgical procedures included access for root instrumentation using the simplified papilla preservation flap and either the application of EMD or the placement of a GTR membrane. At baseline and 1 year following the interventions, clinical attachment levels (CAL), probing depths (PD), recession (REC), full-mouth plaque scores, and full-mouth bleeding scores were assessed. A total of 67 patients completed the study.
                At 1 year, the EMD defects gained 3.1 +/- 1.8 mm of CAL, versus 2.5 +/- 1.9 mm for GTR defects. Probing depth reduction was 3.8 +/- 1.5 mm and 3.3 +/- 1.5 mm, respectively. A multivariate analysis indicated that the differences between EMD and GTR treatments were not significant while a center effect and baseline PD significantly influenced CAL gains. No significant differences in terms of frequency distribution of the outcomes were observed. All cases treated with GTR presented at least one surgical complication, mostly membrane exposure, while only 6% of EMD treated sites displayed complications (P < 0.0001).
                The results of this trial failed to demonstrate superiority of one treatment modality over the other. GTR outcomes in this trial were lower than anticipated based on previous evidence. This was attributed to the high prevalence of post-surgical complications in the GTR group. The aim of this randomized, controlled, prospective clinical study was to compare guided tissue regeneration (GTR) to enamel matrix derivative (EMD) for the treatment of intrabony defects in patients with chronic advanced periodontitis.
                Forty (39 evaluable) 3-wall intrabony defects, each with a depth > or = 4 mm measured from the crest of the bony defect, were treated in 40 subjects with advanced chronic periodontitis. Regeneration of angular bone defects was induced using non-resorbable membranes (GTR group; n = 20) or EMD (EMD group; evaluable n = 19). Clinical parameters, including probing depth (PD), clinical attachment level (CAL), gingival recession, radiographic measurement of the defect depth, plaque index, and bleeding on probing, were measured at baseline and at 12 and 36 months following surgery.
                Twelve months after surgery, sites treated with GTR demonstrated a mean CAL gain of 2.5 +/- 1.2 mm and a mean reduction in PD of 3.5 +/- 1.2 mm compared to baseline. The corresponding outcomes at 36 months were 2.0 +/- 1.1 mm (CAL) and 3.2 +/- 1.1 mm (PD). Sites treated with EMD demonstrated a mean CAL gain of 2.9 +/- 1.4 mm and a mean reduction in PD of 3.5 +/- 1.4 mm at 12 months, with a mean CAL gain of 2.4 +/- 1.2 mm and a mean PD reduction of 3.1 +/- 1.4 mm at 36 months. The differences in PD reduction and CAL gain were statistically significant between the groups and for each time point compared to baseline. Attachment loss was seen in both groups between the 12- and 36-month observations. Measured radiographic bone fill was 57.0% +/- 21% at 12 months and 53.7% +/- 14.3% at 36 months in the GTR group compared to 50.5% +/- 19% at 12 months and 58.8% +/- 14.9% at 36 months in the EMD group.
                The treatment of intrabony defects in patients with chronic advanced periodontitis using GTR or EMD led to significantly improved clinical parameters. Tests of statistical significance demonstrated better results with EMD, although the absolute differences between treatment modalities was small. Further studies with a larger number of treated defects are necessary to verify these findings. A growing flow of recent evidence indicates enamel matrix derivative (EMD, Emdogain) as a useful tool for the regeneration of periodontal tissues. This prospective clinical study aimed to evaluate the efficacy of EMD combined with surgical treatment of periodontal intra-bony defects, as compared with surgery alone, up to 24 months of follow-up.
                Twenty-four intra-bony defects were treated in 24 patients in a single clinical centre. Each defect had intra-bony depth (IBD) > or = 4 mm and probing pocket depth (PPD) > or = 6 mm. Patients were randomly assigned to either test or control group. Plaque index (PI), gingival index (GI), PPD and periodontal attachment level (PAL) were assessed at baseline pre-surgical examination at the site to be treated. Full mouth plaque score (FMPS) and full mouth bleeding score (FMBS) were also evaluated. Twelve patients were treated by simplified papilla preservation flap technique (control group), while 12 patients were treated with the same surgical technique plus EMD after ethylenediamine tetraacetic acid root conditioning (test group). Any probing at the involved sites was avoided in the first year post-surgery. Radiographs were taken at baseline, 12 and 24 months after surgery using customized bite blocks. Intra-bony defect depth (IBD) and angle (IBA) were measured from X-rays by a computer-aided technique. At 12 and 24 months post-surgery, FMPS, FMBS, PI, GI, PPD, PAL and radiographic IBD and IBA were assessed. The difference between each follow-up and baseline, and between groups at each follow-up was evaluated for the above parameters by standard statistical methods.
                In both groups, clinical and radiographic parameters were improved at either 12 or 24 months when compared with baseline. The test group displayed better outcomes when compared with the control group for IBD, PPD, and PAL gain at 12 months, and only for PAL and IBD gain at 24 months. No adverse event related to the use of EMD was reported.
                The surgical procedure used in the present study, aiming for maximum preservation of the regenerative potential of periodontal tissues, showed per se excellent results. The use of EMD as an adjunct to periodontal surgery in the treatment of angular defects possibly enhances periodontal regeneration rate. Several studies have documented the clinical efficacy of guided tissue regeneration (GTR) with non-resorbable expanded polytetrafluoroethylene (ePTFE) membranes and enamel matrix proteins (EMP) in the treatment of infrabony defects. The objective of this controlled clinical study was to compare the clinical outcomes of 3 surgical modalities in the treatment of deep interproximal infrabony defects.
                Ninety (90) defects in 90 healthy subjects affected by chronic periodontitis were assigned to 1 of 3 treatment groups by blocking to prognostic variables. The test group was treated with the application of EMP and the simplified papilla preservation (SPP) technique; the second group was treated with titanium-reinforced ePFTE membranes and the SPP technique; and the third group was treated with the SPP technique used as access flap control procedure. No differences were observed in terms of baseline oral hygiene and defect characteristics among the 3 groups, indicating that the blocking approach was effective. A stringent infection control program was adopted for 1 year.
                The 1-year results indicated that: 1) all treatment modalities resulted in clinically significant improvements in clinical attachment levels (CAL) and reduction in probing depth (PD); 2) a statistically significant treatment effect was demonstrated comparing the EMP test, the membrane control, and the flap control groups in terms of CAL gains; 3) both the EMP test and the membrane control groups showed significant CAL gains compared to the flap control group; 4) a statistically significantly greater amount of CAL gain was demonstrated in GTR-treated compared to EMP-treated patients; 5) deeper residual probing depths but smaller increases in gingival recession were demonstrated following EMP therapy; and 6) smoking habits reduced the clinical outcomes of both regenerative procedures.
                The use of a regenerative procedure is indicated in the treatment of deep vertical bony defects since both the regenerative techniques (GTR and EMD) in the present study resulted in clinically and statistically significant improvements in clinical parameters compared to the access flap procedure. The use of EMP can be helpful in esthetically-sensitive sites and in reducing patient morbidity. There is limited information available from clinical trials regarding the performance of enamel matrix derivative (EMD) in the treatment of periodontal intrabony defects. This randomized, double-blind, placebo-controlled, split-mouth study was designed to compare the clinical and radiographical effects of EMD treatment to that of placebo-controlled treatment for intrabony defects.
                Sixteen patients were included, each of whom had 1 or 2 pairs of intrabony defects located contralaterally in the same arch. Thirty-six intrabony defects were randomly assigned treatment with flap surgery plus EMD or flap surgery plus placebo. At baseline and at the 12-month follow-up evaluation visit, clinical and radiographic measurements were determined. Data were statistically analyzed using the Wilcoxon-signed rank test (alpha = 0.05).
                At the 12-month visit, bleeding on probing for the EMD group was 0.11 +/- 0.32 compared to the placebo group, 0.61 +/- 0.50 (P <0.05). Probing depth reduction was greater in the EMD group (3.00 +/- 0.97 mm) compared to the placebo group (2.22 +/- 0.81 mm) (P <0.05). Mean values for clinical attachment gain in the EMD and the placebo groups were 1.72 +/- 1.07 mm and 0.83 +/- 0.86 mm, respectively (P <0.05). Vertical relative attachment gain was 38.5 +/- 22.6% in the EMD group and 21.4 +/- 25.2% in the placebo group (P<0.05). Radiographic bone density gain was greater in the EMD (20.2 +/- 16.6%) compared to the placebo group (-3.94 +/- 23.3%) (P<0.01).
                Treatment with flap surgery and EMD, compared to flap surgery with placebo, produced a significantly more favorable clinical improvement in intrabony periodontal defects. This prospective multicentre randomized controlled clinical trial was designed to compare the clinical outcomes of papilla preservation flap surgery with or without the application of enamel matrix proteins (EMD).
                172 patients with advanced chronic periodontitis were recruited in 12 centers in 7 countries. All patients had at least one intrabony defect of > or =3mm. Heavy smokers (> or =20 cigarettes/day) were excluded. The surgical procedures included access for root instrumentation using either the simplified or the modified papilla preservation flap in order to obtain optimal tissue adaptation and primary closure. After debridement, roots were conditioned for 2 min with a gel containing 24% EDTA. EMD was applied in the test subjects, and omitted in the controls. Postsurgically, a strict plaque control protocol was followed. At baseline and 1 year following the interventions, clinical attachment levels (CAL), pocket probing depths (PPD), recession (REC), full-mouth plaque scores and full-mouth bleeding scores were assessed. A total of 166 patients were available for the 1-year follow-up.
                At baseline, 86 test and 86 control patients presented with similar subject and defect characteristics. On average, the test defects gained 3.1+/-1.5 mm of CAL, while the control defects yielded a significantly lower CAL gain of 2.5+/-1.5 mm. Pocket reduction was also significantly higher in the test group (3.9+/-1.7 mm) when compared to the controls (3.3+/-1.7 mm). A multivariate analysis indicated that the treatment, the clinical centers, cigarette smoking, baseline PPD, and defect corticalisation significantly influenced CAL gains. A frequency distribution analysis of the studied outcomes indicated that EMD increased the predictability of clinically significant results (CAL gains > or =4 mm) and decreased the probability of obtaining negligible or no gains in CAL (CAL gains <2 mm).
                The results of this trial indicated that regenerative periodontal surgery with EMD offers an additional benefit in terms of CAL gains, PPD reductions and predictability of outcomes with respect to papilla preservation flaps alone. The purpose of the present study was to compare the efficacy of 3 different surgical procedures in the treatment of infrabony defects: guided tissue regeneration (GTR) with non-resorbable membranes, Widman modified flap (WMF) and enamel matrix derivative (EMD).
                30 patients with an infrabony component > or = 4 mm were selected. 10 were treated with expanded polytetrafluorethylene (ePTFE (Gore - Tex W. L. Gore and Associates, Flagstaff, AZ, USA)) membranes, 10 with WMF and 10 with enamel matrix derivatives (Emdogain (U Biora AB Malm, Sweden)). The efficacy of each treatment modality was investigated through regression analysis. Probing attachment level (PAL) gain, probing depth (PD) reduction and gingival recession (REC) variation were analyzed.
                Both Emdogain (enamel matrix derivative) and ePTFE treatment show significant better results as compared to the WMF procedure in which there were no significant changes in PAL gain and PD reduction at baseline and 1 year after surgery.
                Results from our analysis suggest that there is no statistically significant difference in PAL gain between GTR and EMD. The clinical outcomes of this pilot study may be of little significance, considering the small number of patients, but it has provided an important base for a controlled clinical trial (with a larger number of patients) which is currently in progress.
One year after its application, EMD significantly improved PAL levels (1.1 mm) and PPD reduction (0.9 mm) when compared to a placebo or control, however, the high degree of heterogeneity observed among trials suggests that results have to be interpreted with great caution. In addition, a sensitivity analysis indicated that the overall treatment effect might be overestimated. The actual clinical advantages of using EMD are unknown. With the exception of significantly more postoperative complications in the GTR group, there was no evidence of clinically important differences between GTR and EMD. Bone substitutes may be associated with less REC than EMD.